bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insulin Aspart: A New Rapid-Acting Insulin Analog
Authors: Setter Stephen M , Corbett Cynthia F , Campbell R Keith , White John R 
Published: June 2003

OBJECTIVE: To examine the pharmacology, therapeutics, pharmacokinetics, dosing guidelines, adverse effects, and drug interactions of insulin aspart, and summarize the clinical trials of efficacy and safety in patients with type 1 or type 2 diabetes mellitus. DATA SOURCES: A MEDLINE database search (1985–May 2000) was performed to identify all applicable published articles and abstracts; in some cases, Novo Nordisk unpublished information was also obtained. Review articles on insulin analogs were also identified, as well as review chapters in medical textbooks. STUDY SELECTION: The majority of the studies identified were in abstract form. These studies reported information on the pharmacokinetics of insulin aspart in healthy volunteers and in those with diabetes, as well as the therapeutic utility, safety, and clinical efficacy in patients with diabetes. A limited number of randomized studies were reported as articles in the medical literature. DATA EXTRACTION: All published clinical studies were reviewed. DATA SYNTHESIS: Insulin aspart, the second Food and Drug Administration—approved rapid-acting insulin analog, is produced by recombinant technology that replaces the proline at position 28 on the B chain of insulin with negatively charged aspartic acid. Insulin aspart exists as hexamers that rapidly dissociate into monomers and dimers on subcutaneous injection. When administered immediately prior to a meal, insulin aspart is at least as effective as regular human insulin in control of postprandial blood glucose concentrations. Insulin aspart achieves higher peak insulin concentrations in less time and with a shorter duration of action than regular human insulin. CONCLUSIONS: Insulin aspart is a convenient premeal insulin for use by patients requiring mealtime insulin. Furthermore, due to favorable pharmacokinetics, insulin aspart controls postprandial blood glucose concentrations at least as well as regular human insulin and contributes to improved quality of life.
Hormone Replacement Therapy in a Postmenopausal Woman with Epilepsy
Authors: Peebles Carolyn T , McAuley James W , Moore J Layne , Malone Helen J , Reeves Andrew L 
Published: June 2003

OBJECTIVE: To prospectively evaluate the effects of hormone replacement therapy (HRT) on seizure activity in a postmenopausal woman with epilepsy. BACKGROUND: Postmenopausal women are at an increased risk for cardiovascular disease and osteoporosis secondary to a lack of estrogen's protective effects. As a result, women without known contraindications often take HRT to counteract this risk. Postmenopausal women with epilepsy are at a greater risk for osteoporosis because of the negative effects that certain antiepileptic drugs have on bone density. Clinical studies and experience have shown that hormonal variances across a woman's lifetime play a significant role in seizure activity, but the effects of HRT in postmenopausal women with epilepsy are unknown. CASE SUMMARY: We report the case of a 51-year-old postmenopausal white woman with epilepsy who presented with frequent vasomotor flushing. To determine individual effects of HRT on seizure activity, therapy was initiated in two three-month phases, with monthly evaluation. A weekly transdermal patch of estradiol 0.1 mg/d was initiated for the first three months. During the second three months, the regimen was expanded to include oral medroxyprogesterone acetate 2.5 mg once daily. Antiepileptic medications and their dosages remained constant. HRT was associated with a decreased incidence of seizures, cessation of vasomotor flushing, improved sleep, and a positive impact on the lipid profile. CONCLUSIONS: This case report describing the prospective addition of HRT in a postmenopausal woman with epilepsy suggests that HRT can be initiated in certain women to achieve therapeutic benefits without adversely affecting seizure activity.
Gabapentin Treatment for Bipolar Disorders
Authors: Maidment Ian D 
Published: June 2003

OBJECTIVE: To review the effectiveness data on the use of gabapentin in bipolar disorders. DATA SOURCES: Clinical literature was accessed through MEDLINE (January 1985–November 2000). Key search terms included gabapentin, mood stabilizer, and bipolar disorder. DATA SYNTHESIS: Bipolar disorder is a complex condition that can be difficult to treat effectively. Mood stabilizers are increasingly being used to manage bipolar disorder. Studies that used gabapentin in bipolar disorders are evaluated. CONCLUSIONS: From the data presented, gabapentin cannot be recommended for treatment of bipolar disorder. Further studies are required to determine whether gabapentin has any role in the management of bipolar disorder.
Meta-Analysis of Proton Pump Inhibitors in Treatment of Bleeding Peptic Ulcers
Authors: Zed Peter J , Loewen Peter S , Slavik Richard S , Marra Carlo A 
Published: June 2003

OBJECTIVE: To evaluate the efficacy of proton pump inhibitors (PPIs) compared with placebo and histamine receptor antagonists (H2RAs) for reducing the incidence of rebleeding, surgery, and death in acute gastrointestinal bleeding (GIB) associated with peptic ulcer disease. DATA SOURCES: A systematic search of the English-language literature was performed using MEDLINE, EMBASE, and Pre-MEDLINE (from 1966 to September 2000) and a manual search of references. STUDY SELECTION: Randomized, controlled trials evaluating any PPI for acute GIB in adults with the end points of rebleeding, surgery or death. DATA SYNTHESIS: Nine trials (1829 pts.) were included. The relative odds of rebleeding indicated a 50% reduction in the PPI-treated group (OR 0.50, 95% CI 0.33 to 0.77; p = 0.002, NNTB 9; 95% CI NNTB 6 to 13). The relative odds of surgery indicated a 53% reduction in the PPI-treated group (OR 0.47, 95% CI 0.29 to 0.77; p = 0.003; NNTB 17, 95% CI 12 to 35). The relative odds for mortality indicated a nonsignificant 8% decrease in the odds of death in the PPI-treated group (OR 0.92, 95% CI 0.46 to 1.83, p = 0.81; NNTB 323, 95% CI NNTB 47 to ∞ to NNTH 33). CONCLUSIONS: PPIs are superior to H2RAs and placebo in preventing rebleeding and the need for surgery in patients with GIB, although they do not appear to reduce mortality.
Infrastructure of Pharmaceutical Research and Development in Japan
Authors: Ono Shunsuke , Kodama Yasuo , Nagao Taku 
Published: June 2003

OBJECTIVE: To examine the roles of different types of hospitals in implementation of multicenter Phase II/III trials in Japan, specifically focusing on two dichotomies: public versus private, and academic versus nonacademic. Possible explanation was sought as to why a hospital of one category was more likely to participate in specific types of trials in the Japanese medical environment. METHODS: A database containing attributes of published clinical trials (n = 217) was established from four journals featuring reports of clinical trial results. The preferences of public and academic hospitals for specific types of trials were estimated by applying a linear regression model. The trial compositions of these institutions were also estimated, taking the actual prevalence of trials in 1995 into consideration. RESULTS: Public sector hospitals, which were established for particular policy purposes in the national healthcare system, were more likely to accept trials in some fields (e.g., cardiovascular diseases, anesthesiology, antineoplastics, pediatrics) and of some kinds (e.g., Phase II rather than Phase III trials, trials supervised by the principal investigator in the public sector). Academic hospitals also showed preferences for some types of trials (e.g., cardiovascular diseases, dermatology; Phase II rather than Phase III trials). The analysis focusing on public hospitals suggested that policy purposes were achieved at least in some fields such as antineoplastics and anesthesiology. CONCLUSIONS: Japanese clinical trials were unevenly distributed between public and private sectors, and also between academic and nonacademic sectors. These data provide fundamental information about the clinical research environment for future pharmaceutical research and development strategies and policies.
Candida Lusitaniae Catheter-Related Sepsis
Authors: Pietrucha-Dilanchian Paula , Lewis Russell E , Ahmad Hussain , Lechin Alex E 
Published: June 2003

OBJECTIVE: To present a case describing Candida lusitaniae candidemia in an immunocompetent patient successfully treated with fluconazole antifungal therapy. Time—kill studies of the C. lusitaniae isolate using amphotericin B, and an extensive review of the literature are also presented. CASE SUMMARY: A 52-year-old immunocompetent Latin-American woman was admitted to the special care unit with severe sepsis. Her recent medical history included an exploratory laparotomy for gallstone pancreatitis, requiring cholecystectomy, segmental sigmoid colectomy, drainage of peritoneal abscesses, and a colostomy. In addition, the patient required a central venous catheter (CVC) placement for prolonged broad-spectrum antibiotic therapy and total parenteral nutrition therapy. Yeast was isolated from the abdominal abscess and blood cultures obtained on day 1, and from the catheter tip on day 5. The woman received initial empiric antifungal therapy with fluconazole, which was later changed to amphotericin B. After the yeast was identified as C. lusitaniae on day 8, this was changed to fluconazole for the duration of therapy. C. lusitaniae was not present in blood cultures taken two weeks after the CVC was removed, and the cultures remained negative thereafter. After a prolonged hospitalization, the patient was discharged home. DISCUSSION: Disseminated infections with C. lusitaniae usually occur in immunocompromised patients, although isolated reports of C. lusitaniae infections in immunocompetent patients have been described. Therapeutic challenges of C. lusitaniae treatment include its primary resistance to amphotericin B and species misidentification. Isolates recovered from our patient were submitted for fungus time—kill studies that suggested unique susceptibility patterns to amphotericin B, indicating a trend toward resistance. CONCLUSIONS: Based on variable susceptibility patterns of C. lusitaniae to amphotercin B and flucytosine, fluconazole is an appropriate choice as first-line therapy for C. lusitaniae candidemia.
Misoprostol in the Prevention of Postpartum Hemorrhage
Authors: Mategrano Vanessa A , Gabay Michael P 
Published: June 2003

OBJECTIVE: To evaluate the data regarding the use of misoprostol in the prevention of postpartum hemorrhage. DATA SOURCES: Pertinent literature was identified through a MEDLINE search (1966–January 2001) and through other secondary literature databases and/or bibliographies of pertinent articles. DATA SYNTHESIS: New strategies in the prevention of postpartum hemorrhage are being evaluated due to the obstacles surrounding conventional therapies. One therapeutic option is the use of misoprostol. This literature review evaluates the published clinical data involving misoprostol in the prevention of postpartum hemorrhage. Current data suggest that the use of misoprostol for the prevention of postpartum hemorrhage reduces mean estimated blood loss compared with placebo. However, no clinical trials have detected a statistically significant decrease in the incidence of postpartum hemorrhage in misoprostol-treated subjects. There is conflicting evidence regarding the efficacy of misoprostol compared with conventional uterotonics, such as oxytocin or Syntometrine. CONCLUSIONS: In situations where conventional oxytocics are not readily available, storage requirements for oxytocics cannot be met, or the equipment for parenteral administration is not obtainable, misoprostol may be an acceptable prophylactic option.
Intracerebral Hemorrhage following Possible Interaction between Celecoxib and Clopidogrel
Authors: Fisher Alex A , Le Couteur David G 
Published: June 2003

OBJECTIVE: To report a case of intracerebral hemorrhage following short-term, concomitant use of celecoxib and clopidogrel. CASE SUMMARY: An 86-year-old white woman with a medical history of paroxysmal atrial fibrillation, heart failure, osteoarthritis, peptic ulcer disease, chronic airway limitation, and surgery for carcinoma of the bowel and breast began clopidogrel therapy following a syncopal episode. She also began taking celecoxib for osteoarthritis at the same time. Three weeks later, she presented with headaches and left hemiparesis. Computed tomography scan revealed intracerebral hemorrhage that had not been previously detected. Celecoxib and clopidogrel were discontinued, and she recovered fully. DISCUSSION: This is the first case describing a possible interaction between celecoxib and clopidogrel. A pharmacokinetic interaction mediated by CYP2C9 is possible. However, the hemorrhage may have been secondary to the effects of either drug alone or concomitant disease. CONCLUSIONS: Celecoxib and clopidogrel have favorable risk profiles and, therefore, are prescribed widely among older people. However, clinicians should recognize that there may be an interaction between celecoxib and clopidogrel that increases the risk of hemorrhage in older people.
Cerivastatin and Gemfibrozil—Associated Rhabdomyolysis
Authors: Bruno-Joyce Jeanne , Dugas Jane M , MacCausland Owen E 
Published: June 2003

OBJECTIVE: To report a case of rhabdomyolysis resulting from concurrent use of cerivastatin and gemfibrozil. CASE SUMMARY: An 82-year-old white man presented to the emergency department with severe muscle weakness and inability to walk approximately one month after starting cerivastatin. He had been taking gemfibrozil for several years without any known adverse effects. Both medications were discontinued and the patient recovered. He was discharged with a diagnosis of rhabdomyolysis secondary to his medications. DISCUSSION: Four previous reports describing rhabdomyolysis in patients on concomitant cerivastatin and gemfibrozil have been cited. Although monotherapy with cerivastatin is well tolerated and has a low frequency of adverse events, the combination with nicotinic acid (i.e., niacin) or a fibric-acid derivative (i.e., gemfibrozil, fenofibrate) may result in severe skeletal muscle toxicity and rhabdomyolysis. CONCLUSIONS: According to the Naranjo scale, a probable relationship exists between the concomitant use of gemfibrozil and cerivastatin with the resulting development of rhabdomyolysis. Concurrent use of gemfibrozil and cerivastatin is therefore contraindicated.
Sedation Assessment in Critically Ill Adults
Authors: Devlin John W , Fraser Gilles L , Kanji Salmaan , Riker Richard R 
Published: June 2003

OBJECTIVE: To review methods for assessing sedation in critically ill adults, discuss their impact on patient outcomes, and provide recommendations for implementing these methods into clinical practice in the intensive care unit (ICU). DATA SOURCES: A computerized search of MEDLINE from 1980 through June 2000 and a manual search of abstracts presented at recent critical care meetings were performed. STUDY SELECTION AND DATA EXTRACTION: Sedation assessment tools that have been used to titrate therapy in adult, critically ill patients were identified. Special emphasis was placed on sedation assessment instruments that have been prospectively validated. Objective methods that have been used to assess sedation therapy were also identified. DATA SYNTHESIS: Twenty-three adult sedation assessment instruments were identified. Few scales have been prospectively evaluated for validity (n = 6) or reliability (n = 7). Other methods of sedation assessment were identified (e.g., bispectral index monitor); however, most of these methods have only been studied in small subsets of critically ill patients. CONCLUSIONS: Incorporation of sedation assessment into ICU clinical practice may improve patient care. These sedation assessment instruments must be further evaluated to determine their impact on quality of care and ICU length of stay.
Citalopram-Induced Bradycardia and Presyncope
Authors: Isbister Geoffrey K , Prior Felicity H , Foy Aidan 
Published: June 2003

OBJECTIVE: To report a case of symptomatic bradycardia and hypotension that resulted from the therapeutic use of citalopram and to review any previous reports in the literature, from the manufacturer, and the Australian Drug Reaction Advisory Committee (ADRAC). CASE SUMMARY: A 60-year-old white woman who had been taking citalopram 20 mg/d for two weeks presented to the hospital with a heart rate of 39 beats/min, mild hypotension (systolic BP 105 mm Hg), and a normal electrocardiogram (QTc <440 msec), following a presyncopal episode. The patient was admitted for cardiac monitoring, and citalopram was discontinued. The bradycardia and hypotension resolved in the 48-hour period following cessation of citalopram. No other medical or pharmacologic cause was found for the adverse drug reaction. DISCUSSION: Bradycardia has been reported rarely with citalopram in therapeutic doses, but this is the first detailed case with a dose of only 20 mg. The manufacturer reports bradycardia as an infrequent adverse effect (0.1–1%) of citalopram. There have been no reports to ADRAC or to the manufacturer in postmarketing surveillance. There is a case report of asymptomatic bradycardia in a patient whose dose was increased to 40 mg. In the case reported here, there was no QTc prolongation consistent with previous reports. The sinus bradycardia reported more often with therapeutic doses would appear to be distinct to QT abnormalities seen with citalopram overdose. CONCLUSIONS: Citalopram should be used with care in the elderly and in persons with a history of heart disease. Heart rate and blood pressure should be monitored in the first week of therapy and when doses are modified.
Burning Mouth Syndrome after Taking Clonazepam
Authors: Culhane Nicole S , Hodle Audrey D 
Published: June 2003

OBJECTIVE: To report the first published case of clonazepam-induced burning mouth syndrome (BMS). CASE SUMMARY: A 52-year-old white woman presented to the clinic with burning mouth symptoms. The patient was previously maintained on alprazolam therapy for anxiety, but was switched to clonazepam because of increased anxiety and panic. Clonazepam significantly relieved her symptoms, but after four weeks of therapy, she reported a constant, mild, oral burning sensation. An oral examination was negative for mucosal abnormalities, and laboratory tests were unremarkable. The clonazepam dose was reduced, and the symptoms decreased, but remained intolerable. Clonazepam was discontinued, and the burning mouth symptoms completely resolved. Since no other medications relieved the anxiety and panic symptoms, the patient requested clonazepam to be reinitiated, but she again developed intolerable burning mouth symptoms. As clonazepam was discontinued, the symptoms resolved. DISCUSSION: The clinical presentation of BMS includes burning and painful sensations of the mouth in the absence of mucosal abnormalities. Candidiasis, anemia, menopause, diabetes mellitus, medications, anxiety, and depression are some causes of this syndrome. Paradoxically, clonazepam has been studied for the treatment of BMS and has demonstrated mild to moderate improvement. In this patient, underlying causes of BMS were eliminated when possible. The association between clonazepam and BMS was highly probable according to the Naranjo probability scale. CONCLUSIONS: This is the first published report describing BMS with a benzodiazepine. Although uncommon, clinicians should be aware of this potential adverse effect due to the widespread use of benzodiazepines.
Concurrent Tissue and Circulating Tumor DNA Molecular Profiling to Detect Guideline-Based Targeted Mutations in a Multicancer Cohort
Authors: Iams Wade T. , Mackay Matthew , Ben-Shachar Rotem , Drews Joshua , Manghnani Kabir , Hockenberry Adam J. , Cristofanilli Massimo , Nimeiri Halla , Guinney Justin , Benson Al B. 
Published: January 2024

ImportanceTissue-based next-generation sequencing (NGS) of solid tumors is the criterion standard for identifying somatic mutations that can be treated with National Comprehensive Cancer Network guideline–recommended targeted therapies. Sequencing of circulating tumor DNA (ctDNA) can also identify tumor-derived mutations, and there is increasing clinical evidence supporting ctDNA testing as a diagnostic tool. The clinical value of concurrent tissue and ctDNA profiling has not been formally assessed in a large, multicancer cohort from heterogeneous clinical settings.ObjectiveTo evaluate whether patients concurrently tested with both tissue and ctDNA NGS testing have a higher rate of detection of guideline-based targeted mutations compared with tissue testing alone.Design, Setting, and ParticipantsThis cohort study comprised 3209 patients who underwent sequencing between May 2020, and December 2022, within the deidentified, Tempus multimodal database, consisting of linked molecular and clinical data. Included patients had stage IV disease (non–small cell lung cancer, breast cancer, prostate cancer, or colorectal cancer) with sufficient tissue and blood sample quantities for analysis.ExposuresReceived results from tissue and plasma ctDNA genomic profiling, with biopsies and blood draws occurring within 30 days of one another.Main Outcomes and MeasuresDetection rates of guideline-based variants found uniquely by ctDNA and tissue profiling.ResultsThe cohort of 3209 patients (median age at diagnosis of stage IV disease, 65.3 years [2.5%-97.5% range, 43.3-83.3 years]) who underwent concurrent tissue and ctDNA testing included 1693 women (52.8%). Overall, 1448 patients (45.1%) had a guideline-based variant detected. Of these patients, 9.3% (135 of 1448) had variants uniquely detected by ctDNA profiling, and 24.2% (351 of 1448) had variants uniquely detected by solid-tissue testing. Although largely concordant with one another, differences in the identification of actionable variants by either assay varied according to cancer type, gene, variant, and ctDNA burden. Of 352 patients with breast cancer, 20.2% (71 of 352) with actionable variants had unique findings in ctDNA profiling results. Most of these unique, actionable variants (55.0% [55 of 100]) were found in ESR1, resulting in a 24.7% increase (23 of 93) in the identification of patients harboring an ESR1 mutation relative to tissue testing alone.Conclusions and RelevanceThis study suggests that unique actionable biomarkers are detected by both concurrent tissue and ctDNA testing, with higher ctDNA identification among patients with breast cancer. Integration of concurrent NGS testing into the routine management of advanced solid cancers may expand the delivery of molecularly guided therapy and improve patient outcomes.