bluuebunny/crossref_metadata_2025 huggingface dataset:
Nimodipine Transfer into Human Breast Milk and Cerebrospinal Fluid
Authors: Carcas Antonio J , Abad-Santos Francisco , de Rosendo Jesús M , Frias Jesús
Published: January 2017

OBJECTIVE:

To report nimodipine concentrations in breast milk and cerebrospinal fluid (CSF) of a lactating woman who was given the drug to prevent a vascular spasm secondary to angiographic examination.

METHODS:

A 36-year-old woman received a total dose of nimodipine 46 mg iv over 24 hours. She extracted milk when she noted mammary tightness, and blood samples were taken simultaneously by venipuncture in the arm contralateral to that of the nimodipine infusion. A CSF sample also was taken in a diagnostic lumbar puncture.

RESULTS:

Nimodipine concentration in milk was much lower than that in serum, with a milk/serum ratio of 0.06–0.15. The CSF/serum ratio was 0.01. We estimate that the infant would have received between 0.008% and 0.092% of the weight-adjusted dose that was administered to the mother if the baby had been nursed.

CONCLUSIONS:

Nimodipine is transferred to human milk in a lower proportion than are other calcium-channel blockers. These results suggest that treating the mother with nimodipine would entail no risk to the nursing infant.
Serum Concentrations of Salicylic Acid following Topically Applied Salicylate Derivatives
Authors: Morra Pina , Bartle William R , Walker Scott E , Lee S Nicole , Bowles Susan K , Reeves Richard A
Published: January 2017

OBJECTIVE:

To compare the rate and extent of systemic salicylate absorption following single and multiple applications of two topically applied analgesics, one containing methyl salicylate and the other containing trolamine salicylate.

DESIGN:

Two-period, two-treatment, randomized, crossover, multiple-dose study in healthy men and women volunteers.

PARTICIPANTS:

Six men and six women volunteers, 21–14 years of age.

INTERVENTIONS:

Subjects applied 5 g of an ointment containing 12.5% methyl salicylate twice daily for 4 days (8 doses) or a cream containing trolamine 10% twice daily for two doses, to a 10-cm2 area on the thigh. Treatment order and leg (right or left) were assigned randomly. Subjects were crossed over to the alternate treatment on the other leg after a minimum washout period of 7 days.

MAIN OUTCOME MEASURES:

The total amount of salicylate recovered in the urine during two dosing intervals (24 hours) on each study day, relative to the applied dose, was used to calculate the bioavailability of each product. Mean standard pharmacokinetic parameters including area under the curve, maximum concentration (Cmax), time to maximum concentration, and minimum concentrations at steady-state were determined from serum concentrations. Serum concentrations were fit to three pharmacokinetic models and the suitability of each model was evaluated. Estimates of absorption rate constant, clearance, volume, and fraction absorbed on day 1 were estimated by using the best-fitting model.

RESULTS:

Salicylic acid could not be detected in serum after trolamine application. However, concentrations between 0.31 and 0.91 mg/L were detected within 1 hour of the first application of methyl salicylate and Cmax, between 2 and 6 mg/L were observed following the seventh application on day 4. Both the extent and rate of absorption changed after the first 24 hours. The absorption rate constant increased significantly from the first to the seventh dose (first dose absorption rate constant: 0.16 h−1; seventh dose: 0.28 h−1; p < 0.035). Urinary recovery of total salicylate (salicylic acid and principal metabolites of salicylic acid) during the first 24 hours of the methyl salicylate phase averaged 175.2 mg, exceeding the 6.9 mg (p < 0.05) recovered during the trolamine phase. The recovery of salicylate in the urine in the first 24 hours after application of methyl salicylate was significantly greater than the 1.4% recovered after application of trolamine (p < 0.05). Furthermore, the fraction of methyl salicylate recovered in the urine increased significantly from 15.5% on day 1 to approximately 22% on the second, third, and fourth days.

CONCLUSIONS:

A considerable amount of salicylic acid may be absorbed through the skin after topical application of methyl salicylate products and this may increase with multiple applications. Caution is warranted in patients for whom systemic salicylate may be hazardous or problematic.
Azathioprine and Allopurinol: The Price of an Avoidable Drug Interaction
Authors: Kennedy Daniel T , Hayney Mary S , Lake Kathleen D
Published: January 2017

OBJECTIVE:

To report the price of a drug interaction between azathioprine and allopurinol that resulted in pancytopenia in a patient who had undergone a heart transplant.

CASE SUMMARY:

A 63-year-old white man who received an orthotopic heart transplant in 1987 was hospitalized in June 1991 with a diagnosis of pancytopenia. His immunosuppressive medications on admission included cyclosporine 125 mg bid, azathioprine (AZA) 200 mg/d, and prednisone 2.5 mg/5 mg every other day. Six weeks prior to admission, the patient's local physician prescribed allopurinol for left wrist pain suspected to be gout. It was determined that the pancytopenia was caused by the drug interaction between AZA and allopurinol, both of which were withheld on admission. During hospitalization, the patient's white blood cell count dropped to 1.1 × 103/mm3 with an absolute neutrophil count of less than 0.5 × 103/mm3, a platelet count of less than 20 × 103/mm3, and a hemoglobin of 3.7 g/dL. Four units of packed red blood cells were transfused and regramostim (GM-CSF) therapy was begun on hospital day 3 to speed the marrow recovery process. The patient was discharged on hospital day 8 and AZA, which had been withheld since admission, was restarted. The dosage was titrated to 200 mg/d over the following 2 weeks. The price of this patient's hospital stay was $13 042.

DISCUSSION:

Not included in this price was the effect this drug interaction had on the patient's quality of life. Even after discharge from the hospital, it was estimated that it would take up to 3 months for the patient to fully recover his previous level of strength and functional capability. This interaction between AZA and allopurinol could easily have been avoided. Both the physician and the pharmacist missed this well-documented and potentially life-threatening drug interaction. Also, the patient failed to notify the transplant team when allopurinol was prescribed by his local physician. The importance of patient responsibility for medication therapy must be stressed to help avoid unnecessary drug interactions.

CONCLUSIONS:

Undetected drug interactions can be life-threatening to patients as well as costly to the healthcare system. Drug interactions also can have a profound negative effect on the patients' quality of life, the price of which cannot be measured in dollars alone. It is vital that the physician, pharmacist, and patient work together to optimize therapeutic outcomes and avoid unnecessary drug interactions.
Pharmacologic Considerations for Antiviral Drug Development
Authors: Fletcher Courtney V
Published: January 2017

OBJECTIVE:

To discuss pharmacologic considerations for the development of antiviral agents.

DATA SOURCES:

English-language literature pertaining to the development and clinical evaluation of antiviral compounds, primarily agents targeted against herpes group viruses and HIV.

STUDY SELECTION AND DATA EXTRACTION:

Pertinent information, as judged by the author, was selected for discussion.

DATA SYNTHESIS:

Drug development of antiviral agents presents unique problems compared with that of antimicrobial and other agents. Understanding the mechanism of action and both pharmacokinetic and pharmacodynamic considerations is critical to developing a rational dosing strategy and safe, effective use. The lack of standardized methods for antiviral susceptibility testing and the influence of factors such as strain of virus, host cell type, culture medium, inoculum size, end point, and method of measurement on the results obtained illustrate factors that complicate preclinical pharmacologic analysis of antiviral agents. Acyclovir offers a model for clinical drug development. Its mechanism of action, pharmacokinetics, and pharmacodynamics have been studied extensively. Rational guidelines for usage are available, including guidelines in special patient populations such as kidney transplant recipients and neonates. A pregnancy registry has allowed evaluation of the incidence of birth defects in fetuses exposed to systemic acyclovir. Several pitfalls in antiviral drug development are associated with inadequate pharmacologic information. The development of dextran sulfate and fialuridine provides two examples. Integration of pharmacokinetic and pharmacodynamic analyses using modern sampling and analysis techniques may facilitate more rapid development of antiviral agents and more informed dosage regimens to achieve the highest probability of therapeutic success.

CONCLUSIONS:

Insufficient knowledge of the pharmacokinetic and pharmacodynamic characteristics of an antiviral agent is a barrier to efficient drug development. Application and early integration of pharmacologic information into clinical investigations hold promise as a means to shorten the development process and, more importantly, to arrive at informative dosing regimens that optimize therapeutic success.
Placebo Response in Anxiety Disorders
Authors: Piercy Marlena A , Sramek John J , Kurtz Neil M , Cutler Neal R
Published: January 2017

OBJECTIVE:

To review literature on placebo response in anxiety, to discuss sources and levels of placebo response in various anxiety disorders, and to suggest methods to prevent high placebo response rates in clinical research trials.

DATA SOURCE:

Data from scientific literature were identified using a MEDLINE search, and were extracted and summarized for this review.

STUDY SELECTION:

Representative findings were selected from clinical and epidemiologic studies, review articles, letters to the editor, book chapters, and proceedings.

DATA EXTRACTION:

Data from English-language reports of studies on humans were included. Only the most representative conclusions drawn from review articles were used.

DATA SYNTHESIS:

Anxiety disorders in general are thought to be extremely susceptible to a variety of influences, including patient characteristics and environmental variables. Reported placebo response levels in clinical studies of anxiolytics for generalized anxiety disorder and panic disorder vary widely, with a tendency to be rather high, although studies in social phobia and obsessive-compulsive disorder appear to have consistently low placebo response rates. Comparisons of anxiety studies with studies of other indications, such as depression, show similar overall placebo response rates. To determine efficacy, drug response rates and placebo response rates must be clearly differentiated.

CONCLUSIONS:

Examination of the literature suggests that placebo response rates in studies of anxiolytics are influenced by a number of factors, including both endogenous and exogenous variables. High placebo response rates may mask true drug response rates and may result from poor study design or lack of procedural standardization. The use of certain design methods may help to prevent high placebo response rates in anxiolytic clinical trials.
Hypnotic Drug Use in Spain: A Cross-Sectional Study Based on a Network of Community Pharmacies
Authors: Rayón Pilar , Serrano-Castro Mariantonia , Barrio Horacio del , Alvarez Carmen , Montero Dolores , Madurga Mariano , Palop Ramón , De Abajo Francisco J.
Published: January 2017

OBJECTIVE:

To investigate how hypnotic drugs are used in Spain, specifically, (1) to characterize the user population in some simple demographic (e.g., sex, age) and clinical (e.g., type of insomnia, type of physician who prescribed the drug) variables; (2) to estimate the proportion of long-term users (>3 mo); (3) to determine the frequency of different administration schedules; (4) to determine whether the kind of hypnotic drug prescribed according to the duration of its effect correlates with the type of sleep disorder or patient age; and (5) to compare the dosage used by the elderly with that used by adults.

DESIGN:

Cross-sectional pharmacy-based study.

SETTING:

A network of 318 community pharmacies throughout Spain.

SUBJECTS:

Patients (n = 5324) requesting a hypnotic drug for insomnia who agreed to take part in the study.

MAIN OUTCOME MEASURES:

Distribution of the use of hypnotic drugs by age, sex, type of insomnia, type of physician, specific hypnotic drug, daily dosage, treatment schedule, and duration of treatment.

RESULTS:

Women (67%) and the elderly (58%) constituted the largest subgroups in the sample. Difficulties in sleep onset and in sleep maintenance as single disorders were reported by 38% and 37% of users, respectively. Prescriptions were written by general practitioners in 80% of cases. Daily use was reported by 88% and long-term use (>3 mo) by 72% of the users. Long-term treatment was two- to threefold more frequent in the elderly than in middle-aged subjects. Intermediate-action hypnotic drugs were used by 59% of subjects, short-action drugs by 24%, and long-action drugs by 17%. The type of hypnotic drug prescribed was not related to the kind of sleep disorder or the age of patients. Specialists prescribed long-action hypnotic drugs more often than did general practitioners. No relevant differences were observed between dosages used by the elderly and those used by adults. In both groups the dosage taken by most patients, regardless of the drug, corresponded to the available strength. Substitution drugs for triazolam belonged to the intermediate-action class in 53% of the cases.

CONCLUSIONS:

Recommendations on hypnotic drug use are largely not followed in Spain. Most patients are taking hypnotic drugs daily, over long time periods, and without an adequate dosage titration according to age. Measures should be taken to correct this situation.
Dirithromycin: A New Macrolide
Authors: Wintermeyer Susan M. , Abdel-Rahman Susan M. , Nahata Milap C.
Published: January 2017

OBJECTIVE:

To review the clinical microbiology and therapeutic use of dirithromycin, emphasizing comparative data between dirithromycin and the standard macrolide erythromycin, as well as clarithromycin and azithromycin.

DATA SOURCES:

A MEDLINE search of English-language literature during the years 1966–1996, and an extensive review of journals were conducted to prepare this article.

DATA EXTRACTION:

The data on pharmacokinetics, adverse effects, and drug interactions were obtained from open and controlled studies. Controlled single- or double-blind studies were evaluated to assess the efficacy of dirithromycin in the treatment of various upper and lower respiratory tract infections, as well as skin and soft tissue infections.

DATA SYNTHESIS:

The spectrum of activity of dirithromycin is similar to that of erythromycin, clarithromycin, or azithromycin, with some notable exceptions. Dirithromycin was more active in vitro against Campylobacter jejuni and Borrelia burgdorferi than was erythromycin or clarithromycin, but in general demonstrated less activity than erythromycin, clarithromycin, or azithromycin against a majority of microorganisms. The pharmacokinetic profile of dirithromycin offers the advantages of once-daily dosing and high and prolonged tissue concentrations; dosing adjustments are not needed in the elderly or in patients with renal or mild hepatic impairment. Clinical efficacy and bacteriologic eradication rates with dirithromycin and erythromycin are comparable for the treatment of respiratory and skin and soft tissue infections due to susceptible pathogens. Dirithromycin appears to have adverse effect profiles similar to those of the other macrolides, with reported problems most often related to the gastrointestinal tract. Dirithromycin does not seem to cause clinically important interactions with drugs such as theophylline, oral contraceptives, cyclosporine, or terfenadine.

CONCLUSIONS:

Dirithromycin offers some attractive pharmacokinetic properties. The long elimination half-life of dirithromycin allows once-daily dosing and higher and more prolonged tissue concentrations than are achievable with erythromycin. The spectrum of activity, adverse effect profile, clinical efficacy, and bacteriologic eradication rate of dirithromycin may be similar to those of erythromycin. No significant drug interactions with dirithromycin have been reported. Based on available data, dirithromycin may not offer any unique clinical advantage over clarithromycin or azithromycin. Future clinical trials may reveal a special role for dirithromycin in patient care.
Topical Antimicrobial Prophylaxis in Minor Wounds
Authors: Langford Jane H , Artemi Phillip , Benrimoj Shalom I
Published: January 2017

OBJECTIVE:

To evaluate the ability of a novel topical antimicrobial gel containing cetrimide, bacitracin, and polymyxin B sulfate to prevent infections of minor wounds.

DESIGN:

A clinical trial compared the test preparation with placebo and a povidone iodine antiseptic cream.

SETTING:

Five primary schools in Sydney, Australia, participated in the study over a 6-week spring/summer school term.

SUBJECTS:

Children aged 5–12 years with parental consent were eligible for study participation. Accidental injuries occurring at school were treated in a standardized manner by nurses at each site.

OUTCOME MEASURES:

Wounds were evaluated by the medical practitioner after 3 days of topical treatment. The clinical outcome was classified as resolution or suspected infection. If a clinical infection was suspected, the injury was swabbed for microbiologic evaluation. Growth of a dominant microorganism was classified as a microbiologic infection.

RESULTS:

Of the 177 injuries treated, there were nine clinical infections. A comparison of these showed a significant difference among treatment groups (p < 0.05). This difference was associated with the test preparation and placebo; the test preparation reduced the incidence of clinical infection from 12.5% to 1.6% (p < 0.05; 95% CI, 0.011 to 0.207). A comparison of microbiologic infections showed no significant differences among treatment groups (p > 0.05).

CONCLUSIONS:

The novel gel preparation containing cetrimide, bacitracin, and polymyxin B sulfate showed therapeutic action and reduced the incidence of clinical infections in minor accidental wounds. It may be a suitable product for first aid prophylaxis.
Nitroprusside Treatment of Erythromelalgia in an Adolescent Female
Authors: Stone Jonathan D , Rivey Michael P , Allington Douglas R
Published: January 2017

OBJECTIVE:

TO report a case of erythromelalgia in an adolescent patient successfully treated with nitroprusside.

CASE SUMMARY:

A 15-year-old girl with erythromelalgia resistant to aspirin therapy received an infusion of nitroprusside. The response of the erythromelalgia to nitroprusside was dramatic, with complete pain resolution within 17 hours after the start of therapy. No relapse of erythromelalgia was seen when nitroprusside was discontinued and the patient remained well after 6 months.

DISCUSSION:

This case adds to existing literature substantiating the benefit of nitroprusside for the treatment of erythromelalgia in pediatric patients. Erythromelalgia in children may represent a different disease entity than that seen in adults, which is commonly responsive to aspirin therapy. The pathogenesis of erythromelalgia is unclear and precludes formulating a proposed mechanism by which nitroprusside has benefit in children.

CONCLUSIONS:

Nitroprusside is valuable for erythromelalgia resistant to aspirin therapy in pediatric patients. Because of unanswered questions regarding the disease, aspirin remains the agent of first choice in all patients with this rare disease.
Acute Asthma Associated with Sustained-Release Verapamil
Authors: Ben-Noun Liubov
Published: January 2017

OBJECTIVE:

TO describe a patient with asymptomatic bronchial asthma and hypertension who developed an acute asthma attack after receiving sustained-release verapamil.

CASE SUMMARY:

A 66-year-old white woman with a 10-year history of hypertension and bronchial asthma was switched from immediate-release verapamil hydrocloride 40 mg tid to sustained-release verapamil 240 mg/d po for better hypertension control. After taking the first tablet, she developed dyspnea, cough, and wheezing. Antiasthmatic medications were prescribed, but the asthma symptoms did not improve. She continued taking verapamil for 6 months, then, on her own, stopped all medications including the sustained-release verapamil, and her asthma symptoms disappeared. On rechallenge she developed severe dyspnea, cough, and wheezing 20 minutes after administration. The asthma resolved within 24 hours following three albuterol inhalations. The next day similar symptoms developed with rechallenge of the same brand of sustained-release verapamil in a 120-mg formulation, and verapamil was discontinued. Six months later she was again prescribed sustained-release verapamil 240 mg in another clinic where the physician was unaware of her previous reaction. Once again, severe dyspnea, cough, and wheezing developed.

DISCUSSION:

On four separate occasions the patient was challenged, advertently or inadvertently, with sustained-release verapamil. Similar symptoms developed after each challenge and resolved after discontinuing this preparation. Although dyspnea associated with verapamil administration has been reported, this is the first report of an elderly asymptomatic asthmatic patient with hypertension who developed an acute asthma attack following sustained-release verapamil administration.

CONCLUSIONS:

Sustained-release verapamil is thought to be the cause of the asthma attack in this patient because she was not taking any other preparations; the symptoms started with the administration of sustained-release verapamil and were relieved after its discontinuation.
Consensus Guidelines for Coordinated Outpatient Oral Anticoagulation Therapy Management
Authors: Ansell Jack E , Buttaro Marissa L , Thomas Orsula Voltis , Knowlton Calvin H ,   Anticoagulation Guidelines Task Force
Published: January 2017

OBJECTIVE:

TO provide primary and referring healthcare practitioners with guidelines for the provision of safe and effective anticoagulation management in any venue to standardize and improve quality of care and to permit negotiation for reimbursement from third-party payers.

DATA EXTRACTION AND SYNTHESIS:

Data on the current practice of anticoagulation providers and outcomes related to anticoagulation clinic care were obtained through the literature, interviews with anticoagulation providers, and a focus group meeting of anticoagulation clinic stakeholders. This information collation process revealed that an anticoagulation service consists of three separate areas for which guidelines should be developed. Based on the consensus opinions of the committee members, the literature review, and the current practice of anticoagulation services providers, a draft guideline was developed and reviewed by an independent multidisciplinary panel of anticoagulation services providers whose comments were incorporated into the final guideline.

CONCLUSIONS:

Systematic outpatient anticoagulation services are systems of care designed to coordinate and optimize the delivery of anticoagulation therapy by (1) evaluating patient-specific risks and benefits to determine the appropriateness of therapy; (2) facilitating the management of anticoagulation dosages and prescription pick up or delivery; (3) providing ongoing education of the patient and other caregivers about warfarin and the importance of self-care behavior leading to optimal outcomes; (4) providing continuous systematic monitoring of patients, international normalized ratio results, diet, concomitant drug therapy, and disease states; and (5) communicating with other healthcare practitioners involved in the care of the patient. To create a reproducible framework for the provision of these services, guidelines for structure, process, and outcomes of coordinated outpatient anticoagulation management services were developed. Guidelines for organization and management include (1) qualifications for personnel, (2) supervision, (3) care management and coordination, (4) communication and documentation, and (5) laboratory monitoring. Guidelines for the process of patient care include (6) patient selection and assessment, (7) initiation of therapy, (8) maintenance and management of therapy, (9) patient education, and (10) management and triage of therapy-related and unrelated problems. Guidelines for the evaluation of patient outcomes include (11) organizational components and (12) patient outcomes. The impact of these 12 guidelines on patient care and reimbursement procurement will depend on their implementation and the perceived value of their use.
Zolpidem: Distinct from Triazolam?
Authors: Lobo Bob L , Greene William L
Published: January 2017

OBJECTIVE:

TO review the literature that compares Zolpidem with triazolam, with an emphasis on efficacy and safety in humans.

DATA SOURCES:

Information was retrieved from a MEDLINE search (1983–1996) of the English-language literature using the terms triazolam and zolpidem.

STUDY SELECTION:

Reports of clinical trials comparing the safety and efficacy of zolpidem and triazolam were included in this review.

DATA EXTRACTION:

Data were evaluated according to study design, efficacy, and adverse effects. Pertinent information was selected and the data synthesized into a review format.

DATA SYNTHESIS:

Zolpidem and triazolam have similar pharmacokinetic and pharmacodynamic effects in humans. Clinical trials have shown that usually recommended, equipotent dosages of zolpidem and triazolam do not differ with respect to pharmacokinetics, efficacy, tolerability, residual effects, memory impairment, rebound insomnia, abuse potential, or other adverse effects.

CONCLUSIONS:

Zolpidem offers no distinct therapeutic advantage over triazolam for the treatment of insomnia.
The Effect of ICU Sedation Guidelines and Pharmacist Interventions on Clinical Outcomes and Drug Cost
Authors: Devlin John W , Holbrook Anne M , Fuller Hugh D
Published: January 2017

OBJECTIVE:

To measure the effect of evidence-based intensive care unit (ICU) sedation guidelines and interventions by a pharmacist to promote these guidelines on the weaning time from mechanical ventilation and sedation drug cost.

DESIGN:

Before-after study.

SETTING:

A 15-bed medical-surgical ICU at a tertiary-care teaching hospital.

PATIENTS:

100 patients (2 groups of 50 consecutive patients) on mechanical ventilation (assist or pressure control mode for ≥6 h) who were successfully discharged from the ICU.

METHODS:

ICU sedation guidelines were developed through physician, nursing, and pharmacy consensus using a physician survey and literature overview as points of reference and were implemented into practice. Prospectively, data on the time required to wean patients from mechanical ventilation (successful trial of T-piece, pressure support, or intermittent mandatory ventilation leading to extubation) and total drug costs for sedation were measured and compared between groups. All prospective ICU pharmacist interventions pertaining to sedation were documented.

RESULTS:

New sedation guidelines promoted lorazepam use in preference to midazolam and suggested propofol for patients not successfully sedated with high-dose lorazepam, haloperidol, or morphine. Over the 2-month collection periods, there was no difference in the median weaning time between the pre- (16 h, range 2–607) and post- (18 h, range 1–284) guideline groups. Total sedation drug costs decreased from $4515 to $1152 ($US) (p = 0.081). Median sedation drug costs decreased from $ 11.27 (range $0–1340) to $3.55 (range $0–250), with the amount (mg) of midazolam and propofol used decreasing by 86% and 100%, respectively. The ICU pharmacist successfully recommended a change from midazolam to lorazepam in 12 of 50 patients, 5 of whom had received midazolam for more than 24 hours.

CONCLUSIONS:

High compliance with ICU sedation guidelines promoting lorazepam rather than midazolam or propofol in mechanically ventilated patients led to a 75% decrease in sedation drug costs and did not adversely affect the clinicians' ability to wean patients from mechanical ventilation.
Pancreatic Insufficiency Due to Antituberculous Therapy
Authors: Liu Barbara A , Knowles Sandra R , Cohen Lawrence B , Werb Marsha R , Shear Neil H
Published: January 2017

OBJECTIVE:

To describe a case of chronic pancreatic insufficiency related to antituberculous therapy.

CASE SUMMARY:

A 57-year-old man developed rash, fever, and hepatitis (aspartate aminotransferase 369 IU/L, alanine aminotransferase 506 IU/L), 6 weeks after starting isoniazid, rifampin, ethambutol, and pyrazinamide. He also developed severe metabolic acidosis secondary to diabetic ketoacidosis and lactic acidosis (serum bicarbonate 7 mEq/L, glucose 1778 mg/dL, and lactate 4.0 mEq/L). Acute pancreatitis was diagnosed on the basis of a mildly elevated amylase concentration (392 U/L) and radiologic evidence of pancreatic inflammation. He developed pancreatic insufficiency with steatorrhea and an abnormal secretin test. He continues to require pancreatic enzyme replacement and insulin therapy. Rechallenge was not performed.

DISCUSSION:

Hypersensitivity syndromes have been reported for various drug therapies, including antituberculous agents. Hypersensitivity syndrome reactions are characterized by fever, rash, and internal organ involvement. Rifampin has been reported to cause acute pancreatitis in up to 2.7% of patients. Drug-induced chronic pancreatitis, however, is reported to be extremely rare. This is the first reported case of chronic pancreatic insufficiency occurring in the setting of a hypersensitivity syndrome reaction to antituberculous drugs.

CONCLUSIONS:

Chronic pancreatic insufficiency should be considered as a possible long-term sequelae of a hypersensitivity syndrome reaction to antituberculous therapy.
Gentamicin and Tobramycin Pharmacokinetics in Pediatric Bone Marrow Transplant Patients
Authors: Jacobson Pamala A , West Nina J , Price Jessica , Hutchinson Raymond J
Published: January 2017

OBJECTIVE:

To describe the pharmacokinetic parameters of gentamicin and tobramycin in pediatric bone marrow transplant patients.

DESIGN:

Retrospective medical record review. Setting: Pediatric bone marrow transplant unit in a university teaching hospital.

MAIN OUTCOME MEASURES:

Pharmacokinetic parameters (apparent volume of distribution [Vd] in L/kg, half-life [t1/2] in h, elimination rate constant [ke] in h−1, clearance [Cl] in mL/min/1.73 m2 and mL/min/kg) calculated from serum concentrations.

PATIENTS:

Thirty-three patients aged 15 years or less who underwent bone marrow transplant and received gentamicin or tobramycin.

RESULTS:

Mean pharmacokinetic parameters were Vd 0.32 ± 0.07 L/kg, t1/2 2.32 ± 0.65 h, Cl 1.71 ± 0.53 mL/min/kg, and Cl 86.2 ± 24.5 mL/min/1.73 m2. Factors such as disease state, type of marrow graft, gender, or exposure to cyclosporine had no significant effect on pharmacokinetic parameters. Linear regression indicated a weak relationship between serum creatinine (SCr) and Cl in mL/min/kg (r = 0.59), but no relationship was found between SCr and Cl in mL/min/1.73 m2, between age and apparent Vd, or between SCr and apparent Vd. Models for estimating Cl and ke developed by multiple regression were somewhat predictive (r = 0.7). Required calculated maintenance dosages to obtain therapeutic concentrations were 8, 7, and 6 mg/kg/d in children 6 or younger, 7–12, and 13–15 years, respectively.

CONCLUSIONS:

The mean Cl and apparent Vd for all ages are similar to those reported in pediatric oncology patients who had not undergone marrow transplantation. Children 6 years or younger had lower than expected Cls and larger apparent Vds than did the older children. Dosages estimated to be necessary to achieve therapeutic concentrations were 6–8 mg/kg/d.
Cost-Effectiveness Comparison of Sequential Ofloxacin versus Standard Switch Therapy
Authors: Partsch Deborah J , Paladino Joseph A
Published: January 2017

OBJECTIVE:

To compare the cost-effectiveness of sequential intravenous-to-oral ofloxacin versus intravenous-to-oral standard switch therapy for the treatment of patients with sepsis who are hospitalized with bacterial infections.

DESIGN:

Cost-effectiveness analysis from a provider perspective, including resources important to an integrated healthcare network, of a randomized, open-label, controlled, clinical trial.

SETTING:

Millard Fillmore Health System, Buffalo, NY.

PATIENTS:

Hospitalized adults requiring parenteral antibiotics for a complicated urinary tract infection, lower respiratory tract infection, or skin and soft tissue infection.

INTERVENTIONS:

Sequential intravenous-to-oral ofloxacin or standard intravenous-to-oral switch antibiotics.

OUTCOME MEASURES:

Clinical outcomes and direct costs associated with hospitalization, primary physician services, specialist physician services, and outpatient care.

RESULTS:

Eighty-two of 89 patients randomized into the two treatment groups were evaluable. Standard switch therapy failed with 12 patients versus 10 patients receiving ofloxacin. Complete economic data were available for 74 patients. Sequential ofloxacin therapy resulted in a 1-day-shorter antibiotic-related hospitalization without evidence of recurrent infection during the posttherapy follow-up evaluations. An average cost savings of $399 per patient was achieved in the sequential ofloxacin group. Although this difference did not attain statistical significance (probably due to the large variance), it is an economically significant finding. The cost-effectiveness ratios were $5735 per successful outcome for the standard switch therapy group versus $5126 per successful outcome in the sequential ofloxacin group.

CONCLUSIONS:

Sequential ofloxacin was as effective as and consistently less expensive than standard switch antibiotics in the initial evaluation and in the sensitivity analysis of room cost and drug acquisition cost. Standard switch therapy would have to be greater than 25% more effective than sequential ofloxacin therapy to change the economic decision.
Indinavir Sulfate Renal Toxicity in a Pediatric Hemophiliac with HIV Infection
Authors: Ascher David P , Lucy Mitchell D
Published: January 2017

OBJECTIVE:

To report a case of renal toxicity associated with administration of indinavir sulfate in a pediatric hemophiliac with HIV infection.

CASE SUMMARY:

A 16-year-old white hemophiliac boy with HIV infection secondary to tainted coagulation factor VIII was treated with indinavir sulfate. The patient developed gross hematuria, proteinuria, pyuria, abdominal pain, increased bilirubin, an elevated serum creatinine (SCr) of 1.2 mg/dL (baseline 0.9–1.0), and symptoms of renal colic within 1 month of starting indinavir sulfate therapy. Approximately 2 months later the patient developed a low-grade fever with a further increase in SCr. He was prescribed a 10-day course of cefpodoxime proxetil for a possible urinary tract infection. One week later, the patient developed fever, chills, nausea, vomiting, decreased appetite, sterile pyuria, nasal congestion, and an elevated SCr of 1.3–1.7 mg/dL. Indinavir sulfate and cefpodoxime proxetil were discontinued and the patient was suspected of having tubulointerstitial nephritis secondary to indinavir sulfate. The patient's nephritis resolved and the SCr decreased to 1.1 mg/dL within 1 month of discontinuing indinavir sulfate.

CONCLUSIONS:

This case demonstrates the potential for renal toxicity with the use of indinavir sulfate in HIV-infected hemophiliacs.
New Pharmacotherapy for Parkinson's Disease
Authors: Gottwald Mildred D , Bainbridge Jacquelyn L , Dowling Glenna A , Aminoff Michael J , Alldredge Brian K
Published: January 2017

OBJECTIVE:

To summarize the development, pharmacology, pharmacokinetics, efficacy, and safety of five investigational antiparkinsonian drugs that are in or have recently completed Phase III trials: three dopamine agonists, pramipexole, ropinirole, and cabergoline; and two catechol- O-methyltransferase (COMT) inhibitors, entacapone and tolcapone. The pathophysiology and the role of dopamine in Parkinson's disease are also reviewed.

DATA SOURCES:

A MEDLINE search of relevant English-language literature, clinical studies, abstracts, and review articles pertaining to Parkinson's disease was conducted. Manual searches of 1996/1997 meeting abstracts published by the American Academy of Neurology and the Movement Disorders Society were also performed. Manufacturers provided unpublished Phase III trial efficacy and pharmacokinetic data.

STUDY SELECTION AND DATA EXTRACTION:

Clinical trial investigations selected for inclusion were limited to human subjects. Interim analyses after 6 months for long-term clinical trial studies in progress were included. Pharmacokinetic data from animals were cited if human data were unavailable. Statistical analyses for all studies were evaluated.

DATA SYNTHESIS:

By selectively targeting D2 receptors, the newer dopamine agonists (i.e., cabergoline, pramipexole, ropinirole) may delay the introduction of levodopa and thus the occurrence of levodopa-induced dyskinesias. In addition, they are efficacious as adjunctive therapies in patients with advanced Parkinson's disease. Unlike the currently available dopamine agonists, pramipexole and ropinirole are non-ergot derivatives and do not cause skin inflammation, paresthesias, pulmonary infiltrates, or pleural effusion. The COMT inhibitors, tolcapone and entacapone, improve the pharmacokinetics of levodopa by preventing its peripheral catabolism and increasing the concentration of brain dopamine; thus, these agents may reduce the incidence of “wearing-off ' effects associated with the short half-life of levodopa and the progression of Parkinson's disease.

CONCLUSIONS:

Interim 6-month analyses of pramipexole, ropinirole, and cabergoline for symptomatic treatment of early Parkinson's disease have shown these drugs to be efficacious and relatively well-tolerated when used as monotherapy. Their role in delaying the development of motor fluctuations and delaying the addition of levodopa is the subject of long-term clinical studies. In advanced stages of Parkinson's disease, these medications were also efficacious; however, the main adverse effects included dyskinesias, somnolence, and hallucinations. The COMT inhibitors, entacapone and tolcapone, have also demonstrated efficacy in improving on-time in patients with stable disease. Tolcapone has also demonstrated efficacy in patients with motor fluctuations. Both drugs are relatively well-tolerated, with the exception of dyskinesias that require reduction of the levodopa dosage and occasional diarrhea.
Melatonin: Therapeutic Use in Sleep Disorders
Authors: Chase Jennifer E , Gidal Barry E
Published: January 2017

OBJECTIVE:

To review the use of melatonin in sleep disorders, including jet lag, shift work disorder, insomnia, and sleep cycle disorders in neurologically impaired patients.

DATA SOURCE:

A MEDLINE search (1966 to April 1996) was performed that included clinical studies and reviews on melatonin in the English language. References used in those articles were also screened for additional information.

STUDY SELECTION:

All published trials were considered for inclusion in this review, with an emphasis placed on more recently published studies (last 5 years).

DATA SYNTHESIS:

There is significant evidence that links the hormone melatonin to circadian sleep cycles in humans. It has been suggested that in situations where the endogenous melatonin concentration is reduced (advancing age) or the normal circadian cycle is disrupted (jet lag, shift work, blind patients), supplementation with exogenous melatonin may improve both sleep duration and quality. Limited data from generally short-term trials and anecdotal reports suggest that melatonin may be effective in several of these sleep disorders. Melatonin use in jet lag appears to decrease jet lag symptoms and hasten the return to normal energy levels. Melatonin may be helpful in rotating shift schedules to improve sleep quality and maintain normal circadian rhythm. In some patients with insomnia, melatonin appears to induce sleep onset. The optimal dosage and timing of drug administration is still unclear.

CONCLUSIONS:

Although there is some evidence that melatonin may have modest efficacy, especially in insomnia, jet lag, and sleep disorders in neurologically impaired patients, adequate long-term studies examining both efficacy and toxicity are lacking. In addition, further studies evaluating dose-response relationships and drug interactions are warranted.
Reevaluation of a Weight-Based Heparin Dosing Nomogram: Is Institution-Specific Modification Necessary?
Authors: Schlicht John R , Sunyecz Lisa , Weber Robert J , Tabas Gary H , Smith Roy E
Published: January 2017

OBJECTIVE:

To compare a heparin dosing nomogram using an initial infusion rate of 18 units/kg/h with physician-directed heparin prescribing and with a modified version of the nomogram adjusted for institution-specific data.

METHODS:

During consecutive phases of this cohort study, patients' intravenous heparin therapies were initiated and adjusted by using one of the following three methods: (1) physician-directed dosing, (2) a body weight—based dosing nomogram with an initial infusion rate of 18 units/kg/h, and (3) a body weight—based dosing nomogram with an initial infusion rate determined by the median dose of heparin (in units/kg/h) required to achieve therapeutic activated partial thromboplastin times (aPTTs) during the first two phases. The time required to achieve therapeutic aPTTs as well as the percentage of initial aPTTs in the therapeutic range were compared for the three phases.

RESULTS:

The heparin dosing nomogram in which the initial infusion rate was adjusted for our individual institution resulted in a statistically shorter median time until aPTTs were in the therapeutic range than did either the physician-directed dosing or unmodified nomogram groups (6.1 h in the modified nomogram group, 10.5 h in the physician-directed group, 21.5 h in the unmodified nomogram group; p < 0.05 for all differences). Use of the institution-specific nomogram resulted in the greatest percentage of initial aPTTs in the therapeutic range (84% in the 13 units/kg/h nomogram group vs. 47% in the physician-directed group and 18% in the 18 units/kg/h nomogram group; p < 0.05 for all differences).

CONCLUSIONS:

Use of a heparin dosing nomogram with an initial infusion rate of 18 units/kg/h resulted in prolongation of the time to reach therapeutic aPTTs. By modifying the nomogram for use at an individual institution, we reduced the time to achieve therapeutic range of aPTTs while still reducing the likelihood of excessive anticoagulation of patients.
Fluoxetine-Associated Stomatitis
Authors: Palop Vicente , Sancho Asunción , Morales-Olivas Francisco J , Martínez-Mir Inocencia
Published: January 2017

OBJECTIVE:

To describe two cases of stomatitis related to fluoxetine given for the treatment of depression that were detected in the hospital emergency department.

DATA SYNTHESIS:

Two women developed stomatitis after the intake of fluoxetine for the treatment of depression. One of the patients had six recurrent episodes of stomatitis without suspecting an association with fluoxetine. No other drugs were administered during these episodes. The second patient was treated concurrently with fluoxetine and bentazepam. In both patients the lesion improved upon discontinuation of fluoxetine, even though the second patient continued to take a different benzodiazepine.

DISCUSSION:

Stomatitis related to fluoxetine has not been previously reported in clinical trials or in the literature. According to the causal algorithm used by the Spanish Drug Surveillance Schemes, the first case constituted a defined adverse reaction and the second was probable.

CONCLUSIONS:

Our observations suggest that fluoxetine may be considered as a probable cause of stomatitis. The reporting of isolated cases of adverse drug reactions (ADRs) makes it possible to define the toxicity profile of recently marketed drugs such as selective serotonin-reuptake inhibitors, including fluoxetine. Emphasis is placed on the potential role played by emergency departments in detecting ADRs.
Overview of the Hospital Formulary Systems in Hong Kong: Princess Margaret Hospital as a Baseline
Authors: Chang Sophie , Wong Joyee WS , Wong Chloe WY , Chiu Harry CC , Raymond Kenneth
Published: January 2017

OBJECTIVE:

To investigate the popularity of formulary systems in all Hong Kong hospitals and to compare these with the newly introduced formulary system in a major government hospital, the Princess Margaret Hospital (PMH), as the baseline.

DESIGN:

Questionnaire and selected interviews by pharmacy students.

SETTING:

All hospital pharmacies in Hong Kong.

PARTICIPANTS:

Department managers (directors of pharmacy services) of hospital pharmacies.

MAIN OUTCOME MEASURE:

The popularity of the hospitals' formulary systems and their formulary decision-making strategies. Calculations of cost savings of the new formulary system in PMH and a comparison of the PMH system with the US standards were also made.

RESULTS:

Among 38 responding hospitals, 35 (92%) had a formulary handbook and 21 (55.3%) claimed to have a formulary system. The evaluation processes and formulary decision-making procedures were found to be inadequate because basic components in drug evaluation (e.g., standardized criteria for drug evaluation) were not used regularly. However, the formulary system in PMH was found to be comparable with the US standards. Substantial cost savings were made through rejection of less cost-effective drugs by the Formulary Subcommittee in PMH.

CONCLUSIONS:

In general, comprehensive formulary systems are still not popular in Hong Kong. This may be due to insufficient staffing and lack of administrative and physicians' support. The new formulary system in PMH can be used as a model to develop a successful formulary system in which hospital pharmacists can prove their expertise for the benefit of both hospitals and patients in Hong Kong.
Subtalar Pronation — Relationship to the Medial Longitudinal Arch Loading in the Normal Foot
Authors: Arangio George A. , Phillippy Douglas C. , Xiao Dayan , Gu Wei-Kai , Salathe Eric P.
Published: January 2017

A three-dimensional biomechanical model was used to calculate the mechanical response of the foot to a load of 683 Newtons with the subtalar joint in the neutral position, at five degrees of pronation, and at five degrees of supination. Pronation causes the forefoot to evert, increasing the load borne by the first metatarsal. This results in a 47% increase in the moment about the talonavicular joint and a 58% increase in the moment about the navicular-medial cuneiform joint. Subtalar joint supination causes the forefoot to invert and results in a 55% increase in the moment about the calcaneal-cuboid joint.
The Plantar Loading Variations to Uphill and Downhill Gradients During Treadmill Walking
Authors: Grampp John , Willson John , Kernozek Thomas
Published: January 2017

The purpose of the study was to examine the plantar loading changes during 5 gradient conditions on a treadmill (−15%, −8.5%, Level, 8.5%, 15%) for 20 participants using the Pedar® in-shoe pressure measurement system. The measurement system uses EMED insoles, each consisting of 99 capacitive sensors, sampled at 50 Hz. Data was collected from the last 20 seconds at each gradient condition while participants walked. As the treadmill gradient increased, loading (peak pressure [PP] and peak force [PF]) increased in the hallux and 1st metatarsal regions and decreased in the heel region. With negative gradients, loading (PP and PF) increased in the heel region and decreased in the 4th and 5th metatarsal regions.