bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antithymocyte Immunoglobulin in Severe Aplastic Anemia and Bone Marrow Transplantation
Authors: Colby Christine , Stoukides Cheryl A. , Spitzer Thomas R. 
Published: January 2017

OBJECTIVE: To review antithymocyte immunoglobulin (ATG) and its current role in the treatment of severe aplastic anemia (SAA), focusing on ATG in immunosuppressive therapy compared with bone marrow transplantation (BMT). DATA SOURCES: A MEDLINE search (1966 to 1996) of English-language literature and human subjects pertaining to ATG and BMT therapy in SAA was performed. Additional literature was obtained from reference lists of pertinent articles identified through the search. 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: The hallmark of SAA is pancytopenia and bone marrow hypoplasia. Although the etiology in a majority of cases remains unknown, current data implicate an immune-mediated destruction of stem cells. ATG is a potent immunosuppressive agent and has emerged as an important therapy for patients with SAA. The exact mechanism of immunosuppressive action is not fully understood, although ATG appears to disrupt cell-mediated immune responses resulting in inhibition or altered T-cell function. Numerous trials have evaluated the use of ATG both as monotherapy and in combination with other immunosuppressive agents. Treatment with ATG in SAA has demonstrated a 40–70% response rate. Data suggest that intensive immunosuppressive therapy with ATG in combination with cyclosporine may provide the optimal immunosuppressive treatment. Questions still remain concerning complications and long-term survival of the patients. Although more than a 2-year follow-up shows a decline in mortality, a plateau in the survival curve was not achieved. BMT is a potential treatment for SAA. Although there is a high initial mortality due to treatment-related toxicities, successful marrow engraftment provides a cure for SAA. Many patients (75–90%) experience long-term survival after allogenic BMT. Age, donor availability, and severity of disease limit the number of eligible patients. CONCLUSIONS: Due to excellent results with BMT, it has become the therapy of choice for selected patients with SAA. For patients who are not eligible for BMT, intensive immunosuppressive therapy with ATG and cyclosporine is recommended. Further study to better understand the pathogenesis of SAA and prevent treatment-related complications is essential to provide the best care to all patients.
Conscientious Objection to Assisted Death: Can Pharmacy Address This in a Systematic Fashion?
Authors: Mullan Kenneth , Allen William L. , Brushwood David B. 
Published: January 2017

OBJECTIVE: To describe a legal structure for the accommodation of pharmacists' rights of conscience in the dispensing of drugs for pharmaceutically assisted death. BACKGROUND: Pharmacists have indicated that there is disagreement in the profession regarding the appropriateness of a practice known as “pharmaceutically assisted death”, in which lethal medications are prescribed for terminally ill patients who want to end their lives. Pharmacists who object to pharmaceutically assisted death may be asserting a conscientious objection that threatens to create a conflict with their employers. In addition, pharmacists who support pharmaceutically assisted death, but whose employers forbid the dispensing of medications for this purpose, may face a similar conflict. Current laws and principles of professional ethics fail to adequately address the resolution of either of these conflicts. DISCUSSION: We propose a system within which the pharmacy profession could accommodate the right to conscientious objection without sacrificing the quality of patient care. At the heart of our proposal is the understanding that employers must respect an employee's right to beliefs that differ from those of the employer and, correspondingly, the understanding that employees must respect the employer's duty to provide products and services to those who seek them from the employer. CONCLUSIONS: Pharmacy associations can adopt policies for conscientious objection and have those policies become law through action of the state legislature or the state board of pharmacy. This approach could lead to the development of a clear policy and procedure for resolving the issue of conscientious objection within the pharmacy community, making it far less likely that institutions outside pharmacy would be required to develop a solution for pharmacy.
Stability of Fosphenytoin Sodium with Intravenous Solutions in Glass Bottles, Polyvinyl Chloride Bags, and Polypropylene Syringes
Authors: Fischer James H , Cwik Michael J , Luer Mark S , Sibley Carolyn B , Deyo Kelly L 
Published: January 2017

OBJECTIVE: To determine the stability of fosphenytoin sodium admixtures with NaCl 0.9% injection and dextrose 5% (D5W) injection when stored in glass or polyvinyl chloride (PVC) containers, to evaluate the compatibility of fosphenytoin with 11 other intravenous solutions, and to determine the stability of fosphenytoin repackaged in polypropylene syringes. METHODS: Dilutions of fosphenytoin sodium 1, 8, and 20 mg phenytoin sodium equivalents (PE)/mL were prepared in NaCl 0.9%, D5W, and 11 other intravenous fluids. Aliquots of each solution in NaCL 0.9% or D5W were transferred to three glass bottles for storage at 25 °C and 21 PVC bags for storage at 25, 4, or −20 °C Aliquots of each admixture with the other intravenous fluids were transferred to three PVC bags and stored at 25 °C for 7 days. In addition, 63 syringes were filled with fosphenytoin sodium 50 mg PE/mL (undiluted) and stored at 25, 4, or −20 °C. Samples of each solution from the three containers were analyzed for visual compatibility, pH, and fosphenytoin concentration initially and at 0.5, 1, 2, 3, 7, 14, and 30 days during storage at 25 and 4 °C and at 1, 7, 14, and 30 days during storage at–20 °C. Following removal of containers from the freezer, additional samples were obtained after 7 days at 4 or 25 °C, and 7 days at 25 °C, and then 7 days at −20 °C. RESULTS: No visible precipitation or change in color or clarity was observed in any of the fosphenytoin solutions during the study. The concentration of fosphenytoin at each sampling time remained within 97–104% of initial concentration, regardless of container, concentration, intravenous admixture, or storage temperature. CONCLUSIONS: Fosphenytoin sodium, either undiluted in polypropylene syringes or diluted with NaCl 0.9% or D5W in PVC bags, remains stable for at least 30 days at room temperature, under refrigeration, or frozen. After removal from the freezer, fosphenytoin can be thawed, kept at 4 or 25 °C for 7 days, and then returned to the freezer for another 7 days. Admixtures of fosphenytoin sodium in various other intravenous fluids are stable for at least 7 days at room temperature.
Cost-Effectiveness of Thrombolytic Therapy for Acute Myocardial Infarction
Authors: Castillo Paul A , Palmer Cynthia S , Halpern Michael T , Hatziandreu Evi J , Gersh Bemard J 
Published: January 2017

OBJECTIVE: TO estimate the cost-effectiveness of thrombolytic therapy versus no thrombolytic therapy for patients following acute myocardial infarction, focusing on the impact of time to treatment on outcome. METHODS: A decision model was developed to assess the benefits, risks, and costs associated with thrombolytic therapy for treatment of acute myocardial infarction compared with standard nonthrombolytic therapy. The model used pooled data from a recent study of nine large randomized, controlled clinical trials and 12-month outcome data from a recently published meta-analysis of thrombolytic therapy trial data. Outcomes were expressed in terms of survival to hospital discharge and survival to 1 year after discharge. The risks of treatment that led to death, morbidity, or added costs were estimated. The model determined excess and marginal costs per death averted to hospital discharge and at 1 year. Results were also estimated in terms of cost per year of life saved. Sensitivity analyses included variations in time to treatment and drug cost. RESULTS: The marginal cost of thrombolytic therapy per death averted at 1 year was $222 344, or $14 438 per year of life saved. For patients treated within 6 hours of acute myocardial infarction, the marginal cost per death averted was $181 536 at 1 year, or $11 788 per year of life saved. CONCLUSIONS: Thrombolytic therapy is significantly more cost-effective than many other cardiovascular interventions and compares favorably with other forms of medical therapy. Results suggest that shortening the time to treatment has a critical impact on the cost-effectiveness of thrombolytic therapy.
Short-Term Comparison of Once- versus Twice-Daily Administration of Glimepiride in Patients with Non-Insulin-Dependent Diabetes Mellitus
Authors: Sonnenberg Gabriele E , Garg Dyal C , Weidler Donald J , Dixon Russell M , Jaber Linda A , Bowen Angela J , DeChemey G Stephen , Mullican William S , Stonesifer Larry D 
Published: January 2017

OBJECTIVE: To investigate the metabolic effects and frequency of adverse events with 6 mg of glimepiride, a new oral sulfonylurea, given both in once- and twice-daily dosages to patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: This 15-week study involved 161 subjects with NIDDM. Subjects were randomized into two groups. For 4 weeks, group 1 received glimepiride 3 mg twice daily, and group 2 received glimepiride 6 mg once daily. After a 3-week placebo-washout period, twice- and once-daily regimens were crossed over for a second 4-week treatment period. Subjects were hospitalized at the end of each placebo or active-treatment phase. Their glucose concentrations were recorded at 20 time points over a 24-hour period, and their insulin and C-peptide concentrations were recorded at 16 time points over the same period. Parameters that were calculated included fasting, 24-hour, and postprandial concentrations of glucose, insulin, and C-peptide. RESULTS: One hundred six patients were randomized to receive treatment; 94 completed the entire study. Existing physiologic mechanisms of glucose control were apparently unimpaired by glimepiride treatment. Insulin concentrations increased more during the postprandial glucose peaks than when subjects were fasting. Both twice- and once-daily regimens proved equally effective in reducing concentrations of fasting, postbreakfast, postlunch, and postdinner plasma glucose. Twenty-four-hour mean glucose concentrations showed a slightly greater decrease from baseline for the twice-daily regimen; the difference between the regimens was statistically significant but not clinically meaningful. The incidence of adverse events with glimepiride approximated that obtained with placebo, with both groups reporting only one adverse event, headache, in more than 5% of the subjects. CONCLUSIONS: Glimepiride is equally effective whether administered once or twice daily. Glimepiride seems to stimulate insulin production primarily after meals, when plasma glucose concentrations are highest, but controls blood glucose throughout the day.
Riluzole: A New Agent for Amyotrophic Lateral Sclerosis
Authors: Wagner Mary L , Landis Barbara E 
Published: January 2017

OBJECTIVE: To provide a comprehensive review of riluzole, including its mechanism of action, pharmacokinetics, adverse drug reactions, drug interactions, efficacy, and administration. A brief review of amyotrophic lateral sclerosis (ALS) is also included. DATA SOURCES: A computerized search of the MEDLINE database in May 1996 was used to identify publications regarding ALS, riluzole, and metabolism by CYP1A2. Manufacturer's information on riluzole was used when there was no primary literature. DATA SYNTHESIS: Riluzole is approximately 90% absorbed following an oral dose. Its bioavailability is 60%. Peak concentrations occur within 1–1.5 hours of administration. Riluzole extensively binds to lipoproteins and albumin. This agent primarily undergoes CYP1A2 hydroxylation and glucuronidation, after which it is eliminated by the kidneys. Clearance is reduced in native Japanese healthy subjects and may be reduced in patients with hepatic impairment. Two trials with a total of 1114 patients addressed the efficacy of riluzole in ALS. Riluzole extended the time to tracheostomy or death, and the effect was greatest with dosages of 100 mg/d or greater. No effect on patients' symptoms or global assessment was detected at 18 or 21 months. Several flaws in these trials have led to questions concerning the validity of these results. The most commonly reported adverse effects of riluzole have been transient elevation of liver enzyme concentrations (2–5 times the upper limit of normal), worsening of asthenia, nausea, vomiting, diarrhea, anorexia, dizziness, vertigo, somnolence, and mouth paresthesia. Not as commonly reported, but still very serious, is neutropenia, which occurred in 3 of 4000 patients. CONCLUSIONS: Although the benefits of riluzole are questionable and it is expensive, this agent may extend the time to tracheostomy or death in patients with ALS. At present, this is the only agent approved for the treatment of ALS and should be made available for these patients.
Automated Peritoneal Dialysis: New Implications for Pharmacists
Authors: Brophy Donald F , Mueller Bruce A 
Published: January 2017

OBJECTIVE: To review the new automated peritoneal dialysis (APD) modalities that are available to patients with end-stage renal disease (ESRD), and to examine their potential pharmacokinetic and drug dosing consequences. DATA SOURCES: A MEDLINE search (from January 1966 to June 1996) of English-language literature pertaining to peritoneal dialysis was performed. Additional references were obtained by reviewing the references of pertinent articles identified through the search. Tertiary sources were also used. DATA EXTRACTION: Data regarding peritoneal dialysis techniques and pharmacokinetics were extracted from the literature. Data were evaluated according to the study design, population, results, and conclusions. DATA SYNTHESIS: ESRD is the result of progressive chronic renal insufficiency and requires renal replacement therapy. APD is the fastest growing renal replacement therapy by percentage in the US and provides dialysis exchanges via a machine while the patient sleeps, thereby improving patient convenience, peritoneal dialysis compliance rates, and decreasing peritonitis rates. Well-designed pharmacokinetic studies involving APD have not been conducted. Consequently, no formal drug dosing recommendations are available for APD, and pharmacists must rely on established dosing guidelines for continuous ambulatory peritoneal dialysis (CAPD) when recommending dosing regimens. This article describes the new APD treatment modalities available and the potential pharmacokinetic differences between CAPD and APD. CONCLUSIONS: Well-designed studies are needed to fully characterize the pharmacokinetic parameters of drugs in APD. Until then, pharmacists should recommend that intraperitoneally administered drugs be given during the longest peritoneal dialysate dwell of the day and that serum concentrations of drugs with narrow therapeutic indices be monitored closely.
Minocycline-Induced Lupus
Authors: Farver Debra K 
Published: January 2017

OBJECTIVE: To report a case of drug-induced lupus occurring 5 months after the initiation of minocycline therapy for acne. DATA SOURCE: Case report information was obtained from the physician, patient's family, and the medical record. MEDLINE and Index Medicus were searched to obtain relevant published literature from 1966 to 1996. CASE SUMMARY: A 14-year-old white girl developed symptoms of myalgias, arthralgias, polyarthritis, and flushed face. The antinuclear antibody test was positive. Minocycline was discontinued and the patient's condition dramatically improved within 7 days. CONCLUSIONS: Healthcare providers should recognize early common and unusual symptoms of minocycline-induced lupus in adolescents being treated for acne.
Topiramate: A New Antiepileptic Drug
Authors: Privitera Michael D 
Published: January 2017

OBJECTIVE: To review proposed mechanisms of action, clinical pharmacology, efficacy, safety, and tolerability of the antiepileptic drug (AED) topiramate. METHODS: All available data from the clinical development program — Published and unpublished data (provided by investigators or the RW Johnson Pharmaceutical Research Institute) — Were analyzed, with emphasis on the results of double-blind, placebo-controlled trials. Data from open-label studies provided information about long-term efficacy and tolerability. FINDINGS: Topiramate is highly effective in the control of previously therapy-resistant partial seizures, with or without secondary generalization. In the refractory adult patient population enrolled in controlled clinical trials, seizures were reduced by 50% or more in 27–47% of patients compared with 0–18% in placebo-treated patients and by 75% or more in 9–36% of the patients compared with 0–9% of those receiving placebo. The most common adverse effects involve the central nervous system and are mild to moderate in nature. Adverse effects include somnolence, fatigue, psychomotor slowing, and concentration problems. The currently recommended dosing is lower and titration slower than schedules used in the clinical trials; this may improve the tolerability of topiramate. Topiramate has few interactions with currently available AEDs, but phenytoin concentrations increased in some patients. Topiramate can be used initially as adjunctive therapy. Plasma topiramate concentrations are reduced substantially when used with enzyme-inducing AEDs. Open-label data and a single double-blind trial suggest that topiramate monotherapy may be effective. Open-label data also indicate that topiramate may be effective in generalized seizures of nonfocal origin, including those associated with Lennox-Gastaut syndrome. CONCLUSIONS: The robust clinical effects of topiramate expand the therapeutic options for patients with epilepsy. Controlled clinical trials are needed to verify initial observations that topiramate may be effective against a broad spectrum of seizure types and to directly compare efficacy and tolerability with other new and standard AEDs.
Advanced HIV Infection Treated with Zidovudine Monotherapy: Lifetime Values of Absolute Cost—Effectiveness as a Pharmacoeconomic Reference for Future Studies Evaluating Antiretroviral Combination Treatments
Authors: Messori Andrea , Becagli Paola , Berto Valeria , Trippoli Sabrina , Font Maria , Tosolini Francesca , Venturini Francesca , Martini Nello ,   The Osservatorio SIFO sui Farmaci
Published: January 2017

OBJECTIVE: This study was undertaken to evaluate the cost and the effectiveness of zidovudine monotherapy in patients with advanced HIV infection and to derive preliminary data on the cost—effectiveness of the triple treatment with saquinavir plus zalcitabine plus zidovudine compared with zidovudine alone. DESIGN: We used a combined method of survival analysis utilizing both the quality-adjusted time without symptoms or toxicity (Q-TWIST) method and the Gompertz approach. This combined method was applied to assess the absolute cost-effectiveness and cost—utility ratios of zidovudine monotherapy and to perform a preliminary incremental cost—effectiveness comparison of saquinavir plus zalcitabine plus zidovudine versus zidovudine alone. The clinical material used in our study was derived from two reports on the treatment of advanced HIV infection. Data of lifetime costs of HIV infection were obtained from published information. RESULTS: In patients with advanced HIV infection treated with zidovudine monotherapy, lifetime survival was 252.1 discounted person-years per 100 patients. Using an average lifetime cost of $93 000 (discounted) per individual, the absolute ratio of cost—effectiveness for zidovudine monotherapy was $36 980 per life-year, while the absolute cost—utility ratio was $47 112 per quality-adjusted life-year. In the comparative analysis of saquinavir plus zalcitabine plus zidovudine versus zidovudine alone, our calculations showed that the administration of the triple treatment can have an “average” cost—effectiveness, provided that mean lifetime survival per patient (discounted) is improved to at least 3.68 years (with an average survival gain of at least 14 mo per patient). CONCLUSIONS: The values of absolute cost—effectiveness and cost—utility ratios for zidovudine monotherapy are a useful reference point for further pharmacoeconomic studies in the area of antiretroviral drugs.
Interdigital Neuroma: Intermuscular Neuroma Transposition Compared with Resection
Authors: Colgrove Robert C. , Huang Emily Y. , Barth Alan H. , Greene Marie A. 
Published: January 2017

This prospective, randomized study compares the treatment of an interdigital neuroma (IDN) by the standard resection operation with a technique in which the IDN is transposed into the inter-muscular space between the adductor hallucis and the interossei muscles after division of the digital nerves distal to the IDN. The resection group contained 22 patients and 22 neuromas and the transposition group contained 22 patients and 23 neuromas. An interviewer, blinded as to the operative technique used, telephoned each patient preoperatively, and at 1 month, 3 months, 6 months, 12 months, and 36–48 months postoperatively. The interviewer recorded the patient's reported pain level on a numerical rating scale of 0 to 100. In the resection group the average pain level was slightly lower through the first 6 month period, but at the 12 month review the resection group had a slightly higher average pain level. At the 36–48 month survey the resection group again reported a greater average pain level and fewer asymptomatic patients. It was concluded that it is unnecessary to excise the IDN to obtain excellent relief of pain. It was also concluded that transposition of the IDN into an intermuscular position between the adductor hallucis and the interossei muscles produced significantly better long term results than did the standard resection operation.
Precise Anatomic Configuration Changes in the First Ray of the Hallux Valgus Foot
Authors: Tanaka Yasuhito , Takakura Yoshinori , Sugimoto Kazuya , Kumai Tsukasa , Sakamoto Tatsuya , Kadono Kunihiko 
Published: January 2017

To detect precise anatomical configuration of the first ray in feet with hallux valgus, a two-dimensional coordinate system was devised for evaluation of a weight-bearing dorsoplantar radiograph. The radiographs, taken from 229 feet of 114 patients with symptomatic hallux valgus and 94 normal feet, were investigated. A comparative study showed the first metatarsal head of a foot with hallux valgus was located on the medial side of that of the normal foot and the base of the proximal phalanx of the hallux valgus foot was located on the same point of that of the normal foot. Lateral translation of the base of the proximal phalanx occurred only in cases with overlap toes. Our study shows that subluxation of the metatarsophalangeal joint in hallux valgus is primarily caused by metatarsus primus varus. This study indicated that first metatarsal osteotomies should be given the first priority in consideration for bunion surgery, because these procedures could move the first metatarsal heads laterally in a more normal position.