bluuebunny/crossref_metadata_2025 huggingface dataset:
Ceftriaxone Distribution and Protein Binding between Maternal Blood and Milk Postpartum
Authors: Bourget Philippe , Quinquis-Desmaris Valérie , Fernandez Hervé
Published: January 2017

OBJECTIVE:

To study postpartum distribution and protein binding of ceftriaxone (CTX) between maternal blood and milk and to discuss risk factors and possible impact for the neonate.

DATA SOURCES:

Reference articles and books are identified in the text.

DATA SYNTHESIS:

CTX distribution and protein binding between maternal blood and milk postpartum were studied in a patient at term presenting with acute pyelonephritis caused by Escherichia coli. The antibiotic therapy prescribed pending bacteriology results consisted of CTX 2 g/d, ornidazole 1 g/d, and tobramycin 3 mg/kg/d. Pharmacokinetics of total CTX were studied after the first 2-g infusion. At plateau (i.e., two days after delivery; seventh infusion), pharmacokinetics and milk distribution of total and free CTX also were studied. No accumulation of CTX was noted in the plasma at plateau. When high dosages of CTX are used (∼2g), its penetration into the milk is important (i.e., protein binding capacity is overwhelmed). No notable adverse reactions occurred in mother or child. Thus, an important diffusion into the milk (4.4 percent of the dose) appears not to be clinically important. Our knowledge of both metabolism and milk distribution of drugs with high protein binding (≥95 percent) and an acid characteristic should be expanded to better understand their use during both the pregnancy and postpartum periods. Finally, the child of the patient described here has normal initial growth and development at the present time.

CONCLUSIONS:

Caution should be taken when drugs such as CTX, which have both high protein binding (≥95 percent) and an acid characteristic are administered to breastfeeding women. Drugs of this type should be systematically investigated to better understand their use during pregnancy and postpartum.
Excretion of Bupropion in Breast Milk
Authors: Briggs Gerald G. , Samson John H. , Ambrose Peter J. , Schroeder David H.
Published: January 2017

OBJECTIVE:

To measure the excretion of bupropion and its metabolites in breast milk. A secondary objective was to determine whether the drug accumulated in the nursing infant.

CASE SUMMARY:

Milk and plasma samples were collected from a woman taking bupropion 300 mg/d in divided doses who was breastfeeding her 14-month-old son. A single plasma sample was collected from the infant.

RESULTS:

After a 100-mg dose, the peak bupropion breast milk concentration measured at two hours was 0.189 (μg/mL. Milk-to-plasma ratios ranged from 2.51 to 8.58 over a six-hour interval. Two of three metabolites also were measured in milk. Bupropion and its metabolites were not detected in the single plasma sample obtained from the infant.

CONCLUSIONS:

Bupropion accumulates in human breast milk in concentrations much higher than in maternal plasma. Two metabolites are also excreted into the milk. Neither bupropion nor its metabolites were detected in the infant's plasma, indicating that accumulation did not occur in this infant.
Hepatotoxicity Associated with Cisplatin Chemotherapy
Authors: Cersosimo Robert J.
Published: January 2017

OBJECTIVE:

To report a case of possible cisplatin-associated hepatotoxicity.

CASE SUMMARY:

A 69-year-old man received three cycles of cisplatin (100 mg/m2) and fluorouracil (1000 mg/m2/d for five days) for management of squamous cell carcinoma of the head and neck. Liver enzyme concentrations were within normal limits prior to each cycle of therapy but the aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase concentrations increased on the second day of each cycle. The concentrations began to decline on day 3 of each course, despite continued fluorouracil administration, and returned to normal by day 10. The patient's antiemetic therapy included metoclopramide in cycle 1 and ondansetron in cycles 2 and 3, which may have contributed to the enzyme elevations.

DISCUSSION:

Case reports of cisplatin-associated hepatotoxicity are reviewed. An association between cisplatin administration and hepatotoxicity is proposed in this patient.

CONCLUSIONS:

This patient may have experienced cisplatin-induced liver damage. Metoclopramide and ondansetron may have contributed to this effect.
Reversible Seizures and Mental Status Changes in a Dialysis Patient on Isoniazid Preventive Therapy
Authors: Asnis Deborah S. , Bhat J. Ganesh , Melchert Alex F.
Published: January 2017

OBJECTIVE:

To report a case of reversible seizures and mental status changes in a dialysis patient given preventive isoniazid therapy.

CASE SUMMARY:

A 66-year-old woman on continuous ambulatory peritoneal dialysis (CAPD) was given isoniazid prophylaxis following a purified protein derivative (PPD) reaction greater than 20 mm induration. Oral administration of isoniazid 300 mg/d was started and four days later she was admitted to the hospital for confusion, lethargy, and focal seizures that began 24 hours after initiation of therapy. All medications were discontinued with the exception of oral pyridoxine 50 mg/d. Dialysis was withheld to determine if the seizures were medication induced rather than uremia related. Seizures and mental status changes were reversed with pyridoxine. Dialysis was restarted after the symptoms resolved.

CONCLUSIONS:

Preventive therapy against tuberculosis with isoniazid should be stressed throughout the medical community. Isoniazid has adverse effects including hepatitis and peripheral neuropathy (common) and convulsions (rare). Our experience suggests that additional supplementation with pyridoxine 50 mg/d should be given routinely to prevent adverse reactions in uremic patients.
Stroke Prophylaxis: Hypertension Management and Antithrombotic Therapy
Authors: Tortorice Kathryn L. , Carter Barry L.
Published: January 2017

OBJECTIVE:

To review trials involving risk factor management and pharmacologic therapy for the prevention of stroke.

DATA SOURCES:

English-language literature published between 1966 and 1992 was analyzed; pertinent literature is reviewed.

STUDY SELECTION:

Studies that evaluated the impact of risk factor management on prevention of vascular events were selected. In addition, trials assessing the safety and efficacy of pharmacologic intervention in primary and secondary stroke prevention were evaluated.

DATA EXTRACTION:

Trials were evaluated for their ability to demonstrate a decrease in stroke occurrence.

DATA SYNTHESIS:

Various trials were analyzed in several categories. Studies evaluating risk factor management of hypertension and cardiogenic cerebral emboli were reviewed and recommendations made based on a consensus of these trials. The use of antiplatelet agents in stroke prevention was addressed by a review of pertinent trials and meta-analyses.

CONCLUSIONS:

The control of risk factors and the use of antiplatelet agents significantly reduces the risk of vascular events. Benefit from different therapies may be specific to certain patient populations and recommendations are made for these patients.
Potential Interaction between Carbamazepine and Loxapine: Case Report and Retrospective Review
Authors: Collins D. Michael , Gidal Barry E. , Pitterle Michael E.
Published: January 2017

OBJECTIVE:

To report a potential interaction between carbamazepine (CBZ), an anticonvulsant medication, and loxapine, an antipsychotic. CBZ is being increasingly used to treat a variety of psychiatric disorders. Because of this, the potential for multiple-drug therapy and subsequent drug interactions is increased.

METHODS:

We prospectively monitored plasma CBZ and carbamazepine epoxide (CBZE) concentrations in a single patient during and after withdrawal of loxapine comedication. Additionally, we retrospectively evaluated four patients who had received concomitant therapy with CBZ and loxapine.

RESULTS:

Plasma CBZE/CBZ ratios decreased from 0.76 to 0.18 following discontinuation of loxapine. Absolute CBZE plasma concentrations also decreased from 1.7 to 0.6 μg/mL after loxapine therapy was stopped. Retrospectively screened patients who were receiving concomitant loxapine-CBZ therapy all had unusually elevated CBZE/CBZ plasma concentration ratios (0.75–1.91).

CONCLUSIONS:

These cases suggest that an interaction occurs between loxapine and CBZ. Possible mechanisms include either induction of CBZ metabolism to its epoxide metabolite, or inhibition of the enzymatic metabolism of CBZE (epoxide hydrolase).
Treatment of Aspergillosis with Itraconazole
Authors: Jennings Timothy S. , Hardin Thomas C.
Published: January 2017

OBJECTIVE:

To review the role of itraconazole as oral therapy for the major infections caused by Aspergillus spp.: allergic bronchopulmonary aspergillosis, aspergilloma, and invasive aspergillosis.

DATA SOURCES:

A MEDLINE search of articles published in the English language between 1986 and 1993 was used to identify relevant citations, including review articles. In addition, a search of the published abstracts of the past two Interscience Conferences on Antimicrobial Agents and Chemotherapy (ICAAC) was performed.

STUDY SELECTION:

Clinical trials that evaluated itraconazole therapy in either allergic bronchopulmonary aspergillosis, aspergilloma, or invasive aspergillosis were critically reviewed. Trials were evaluated based upon entry criteria for the diagnosis of each type of aspergillosis, risk factors for the development of aspergillosis (neutropenia, transplant recipient, hematologic malignancy), prior antifungal chemotherapy, and dose and duration of itraconazole therapy.

DATA SYNTHESIS:

Overall, the clinical trials of itraconazole therapy for aspergillosis are limited and of variable quality. In the treatment of allergic bronchopulmonary aspergillosis, itraconazole has been reported to prompt a reduction in corticosteroid dosage in selected patients. There have been no controlled trials of itraconazole as treatment for aspergilloma, but data from several open-label trials suggest that this agent may be of clinical benefit in aspergilloma, primarily as an alternative to surgery. The use of itraconazole for invasive aspergillosis has been evaluated in several trials, most often in patients who were intolerant to amphotericin B treatment. Response to oral itraconazole has generally been promising.

CONCLUSIONS:

Although itraconazole offers promise for oral therapy against infections caused by Aspergillus spp., it should not presently be regarded as primary therapy for any of these diseases. Amphotericin B, in doses ranging from 1 to 1.5 mg/kg to a total dose of 1.5–4.0 g, should remain the treatment of choice in both aspergilloma and invasive aspergillosis. Itraconazole use should be restricted to patients who experience severe toxicity with amphotericin B therapy. Corticosteroids continue to be first-line therapy for allergic bronchopulmonary aspergillosis, with the use of itraconazole reserved for those patients who would benefit from a reduction in corticosteroid dose.
Paroxetine: A Selective Serotonin Reuptake Inhibiting Antidepressant
Authors: Caley Charles F. , Weber Stanley S.
Published: January 2017

OBJECTIVE:

To review the pharmacology, pharmacokinetics, clinical investigations, adverse effects, and dosing strategies of paroxetine as a treatment of major depression.

DATA SOURCES:

Specific paroxetine information was selected from a MEDLINE search using paroxetine as the search term. Other sources included manual searches of pertinent journal article references, meeting abstracts, and the manufacturer.

STUDY SELECTION:

Clinical investigations with a blind, controlled (placebo and/or active), randomized design were selected. With the exception of treatment-resistant depression, no short-term, open investigations were selected.

DATA EXTRACTION:

Clinical investigations were evaluated for design, sample size, diagnosis, duration, definition of response, and outcome. Data from all investigations were selected by one author and reviewed by both authors.

DATA SYNTHESIS:

Paroxetine is a selective serotonin reuptake inhibitor (SSRI) recently approved for the treatment of major depression. It is a potent and selective inhibitor of serotonin reuptake and has weak or no activity on the other monoamines; it is also weakly anticholinergic. Although pharmacokinetic parameters are variable, paroxetine is generally well absorbed, highly protein bound, hepatically cleared, and has no active metabolites. Clinical investigations support paroxetine's effectiveness as an antidepressant in an outpatient population with moderately severe depression. Its effectiveness is superior to that of placebo and is comparable to that of active controls. The majority of investigations have been six weeks in duration. Additional data are required to support paroxetine's promise for longer treatment periods (i.e., ≥1 y), in the elderly, and for treatment-resistant depression. Adverse effects appear to be similar to those caused by the other SSRIs; some of the most common are nausea, diarrhea, insomnia, dry mouth, and nervousness. Significant drug interactions may occur with the monoamine oxidase inhibitors, phenobarbital, and phenytoin.

CONCLUSIONS:

Paroxetine is safe and effective for treatment of outpatients with moderately severe depression. Further clinical data and experience are necessary to determine this agent's place in the long-term treatment of major depression.
Pharmacoepidemiology of Clozapine in 202 Inpatients with Schizophrenia
Authors: Zito Julie Magno , Volavka Jan , Craig Thomas J. , Czobor Pal , Banks Steve , Vitrai Jozsef
Published: January 2017

OBJECTIVE:

To evaluate clozapine in a field trial for hospitalized patients with treatment-resistant schizophrenia.

METHOD:

The setting consisted of a large, state-operated, public psychiatric system. The protocol called for the treating psychiatrist to provide symptom- and adverse-effect ratings at four times following the start of drug therapy. The outcome criteria included the Sandoz study outcome measure of symptom improvement as well as discharge status for one year of follow-up. To assess the validity of the ratings, several measures of internal consistency were determined. Clozapine therapy was started in 227 patients, and symptom data are available for 202.

RESULTS:

Overall, 33 percent (n=66) of the patients were improved at the end of one year of treatment; 12 percent (n=24) maintained symptom improvement at all three evaluation times. Modest, statistically significant improvement after 12 weeks compared with baseline Brief Psychiatric Rating Scale (BPRS) total scores was observed for the patients continuing medication (n=152); the emergence of a previously unimproved group (n=26) explains this modest improvement. However, in the analysis of all patients (n=202), (including dropouts), there was no significant symptom improvement after 12 weeks. Lower baseline BPRS scores predicted significant symptom improvement after 12 weeks of treatment. Among those medicated for one year, the pattern of symptom improvement showed that the probability of late improvement was 0.26 for those previously unimproved, and the probability of a 12-week responder losing improvement was 0.23, resulting in a net group gain of 3 cases in 100. By the end of one year, 8 percent (n=17) of the cohort was discharged, and 3 percent (n=7) was transferred to another facility while continuing to receive clozapine. Of the 227 original patients started on clozapine therapy, medication was discontinued for adverse effects in 11 percent (n=25): white blood cell count (WBC) decrease (but no agranulocytosis) in 5 percent (n=12), seizures in 1 percent (n=3), one patient with seizures and decreased WBC count, and other events (e.g., cardiovascular changes, fever, or possible neuroleptic malignant syndrome) in 4 percent (n=9). Patient refusal was reported for 6 percent (n=13) of those starting treatment.

CONCLUSIONS:

Although only 19 percent of the patients exhibited improvement at 6 weeks, the response rate at 12 weeks (29 percent) for this naturalistic study cohort was similar to that in the major, double-blind, six-week, controlled, clinical trial of clozapine. The impersistence of response as symptoms were followed for up to one year is a finding that deserves rigorous evaluation.
Abnormal Bone Mineral Metabolism after Long-Term Anticonvulsant Treatment
Authors: Alderman Christopher P. , Hill Catherine L.
Published: January 2017

OBJECTIVE:

To present a case of anticonvulsant-induced disturbances of bone mineral metabolism associated with long-term phenytoin treatment.

CASE SUMMARY:

An 87-year-old woman was hospitalized with generalized acroparesthesia. Her medical history was significant for grand mal epilepsy, which had been treated with phenytoin for more than ten years. On admission she was found to be hypocalcemic, and her alkaline phosphatase concentration was markedly elevated.

DISCUSSION:

Further investigations revealed that the patient's serum concentration of 25-hydroxycalciferol was well below the expected range. Phenytoin treatment was withdrawn, and calcitriol supplementation commenced. Ten weeks later she was normocalcemic, and the calcitriol dosage was reduced. Radiologic investigations at this time revealed an ununited hip fracture, as well as widespread evidence of bone demineralization.

CONCLUSIONS:

Minor elevations of liver enzymes observed in association with anticonvulsant treatment may reflect hepatic microsomal enzyme induction. Marked elevation of serum alkaline phosphatase, particularly when seen in concert with hypocalcemia, may be markers of anticonvulsant-induced bone disease. Under these circumstances, further radiologic investigations and measurement of the vitamin D serum concentration should be undertaken.
Comparison of Prescription and Medical Records in Reflecting Patient Antihypertensive Drug Therapy
Authors: Christensen Dale B. , Williams Barbara , Goldberg Harold I. , Martin Diane P. , Engelberg Ruth , LoGerfo James P.
Published: January 2017

OBJECTIVE:

To determine the completeness of prescription records, and the extent to which they agreed with medical record drug entries for antihypertensive medications.

SETTING:

Three clinics affiliated with two staff model health maintenance organizations (HMOs).

PARTICIPANTS:

Randomly selected HMO enrollees (n=982) with diagnosed hypertension.

METHODS:

Computer-based prescription records for antihypertensive medications were reviewed at each location using an algorithm to convert the directions-for-use codes into an amount to be consumed per day (prescribed daily dosage). The medical record was analyzed similarly for the presence of drug notations and directions for use.

RESULTS:

There was a high level of agreement between the medical record and prescription file with respect to identifying the drug prescribed by drug name. Between 5 and 14 percent of medical record drug entries did not have corresponding prescription records, probably reflecting patient decisions not to have prescriptions filled at HMO-affiliated pharmacies or at all. Further, 5–8 percent of dispensed prescription records did not have corresponding medical record drug entry notations, probably reflecting incomplete recording of drug information on the medical record. The percentage of agreement of medical records on dosage ranged from 68 to 70 percent across two sites. Approximately 14 percent of drug records at one location and 21 percent of records at the other had nonmatching dosage information, probably reflecting dosage changes noted on the medical record but not reflected on pharmacy records.

CONCLUSIONS:

In the sites studied, dispensed prescription records reasonably reflect chart drug entries for drug name, but not necessarily dosage.
Safety of Combination Aspirin and Anticoagulation in Acute Ischemic Stroke
Authors: Fagan Susan C. , Kertland Heather R. , Tietjen Gretchen E.
Published: January 2017

OBJECTIVE:

To assess the risk of bleeding complications in patients treated with combination aspirin and heparin for cerebral ischemia.

DESIGN:

A retrospective, cohort study.

SETTING:

A large urban teaching hospital.

PATIENTS:

One hundred charts of stroke patients who had received anticoagulation with or without aspirin therapy were identified from the Stroke Data Bank. Bleeding rates were compared between the two groups.

RESULTS:

Forty-two patients who had received heparin and/or warfarin in combination with aspirin were compared with 33 patients who had received anticoagulation alone. The mean duration of anticoagulant therapy was 8.0 and 8.4 days, respectively. Bleeding rates were not different between the two groups: 23.8 percent (10/42) (p=0.78) and 24.2 percent (8/33), respectively. Although the bleeding rate was substantial, there was only one major bleed (severe epistaxis) occurring in a patient receiving anticoagulation only. No patient had an intracerebral hemorrhage.

CONCLUSIONS:

Our data suggest that combination antithrombotic therapy is safe in a controlled, inpatient setting.
Potential Pharmacokinetic Interaction between Felbamate and Phenobarbital
Authors: Gidal Barry E. , Zupanc Mary L.
Published: January 2017

OBJECTIVE:

TO REPORT A CASE OF A POTENTIAL PHARMACOKINETIC INTERACTION BETWEEN FELBAMATE AND PHENOBARBITAL IN A PATIENT WITH EPILEPSY.

CASE SUMMARY:

A patient with a history of a mixed seizure disorder and static encephalopathy who was receiving sodium valproate 750 mg/d and phenobarbital 230 mg/d was initiated on felbamate (as part of a compassionate use program). Upon instituting felbamate, valproate dosage was reduced to 500 mg/d and phenobarbital to 200 mg/d. Felbamate dosage was titrated to approximately 50 mg/kg/d over three weeks. In this patient, plasma phenobarbital concentrations increased from 48 μg/mL, to 68 μg/mL, at which point the patient was hospitalized because of clinically significant neurotoxicity. Phenobarbital dosage was subsequently reduced to 150 mg/d; this resulted in phenobarbital trough concentrations of 60 μg/mL.

CONCLUSIONS:

Felbamate has been shown previously to interact with multiple other anticonvulsant medications, including valproate, phenytoin, and carbamazepine. Felbamate appears to decrease the clearance of valproate, phenytoin, and carbamazepine epoxide to a significant extent, an effect that may be the result of inhibition of the metabolism of these compounds. Carbamazepine plasma concentrations have been demonstrated to decrease following administration of felbamate, suggesting metabolic induction. It is reasonable to suggest that based on these findings and the observations in our patient, felbamate comedication may result in clinically significant increases in plasma phenobarbital concentrations. It would seem prudent, therefore, when initiating or adjusting felbamate therapy in patients receiving this drug combination, to monitor phenobarbital plasma concentrations.
Agranulocytosis Associated with Etodolac
Authors: Cramer Richard L. , Aboko-Cole Vivian C. , Gualtieri Richard J.
Published: January 2017

OBJECTIVE:

To report a case of probable etodolac-induced agranulocytosis.

CASE SUMMARY:

A 72-year-old woman who had been taking etodolac 300 mg bid for approximately six weeks presented to the emergency department with symptoms of urosepsis. She was found to be profoundly granulocytopenic. Etodolac was discontinued and broad-spectrum intravenous antibiotic therapy was administered for the next 17 days. Results of bone marrow biopsy revealed marked hypocellularity consistent with drug-induced agranulocytosis. Following etodolac withdrawal, the total white blood cell count reached a low value of 0.9 × 109L and then returned to a preetodolac baseline after 15 days. Her hemoglobin concentration also decreased significantly during hospitalization.

DISCUSSION:

Agranulocytosis has rarely been reported in association with nonsteroidal antiinflammatory drugs (NSAIDs), and there are no literature reports associating etodolac with agranulocytosis. This case involving etodolac is consistent with the pattern described with other NSAIDs. Factors correlating etodolac as the causative agent are identified. Details of patient history, treatment, follow-up, and assessment are discussed.

CONCLUSIONS:

Detailed case assessment demonstrated probable etodolac-induced agranulocytosis in our patient. Clinicians should be aware that etodolac, like other NSAIDs, has potential to cause agranulocytosis.
Suicide Attempt by Means of Aspirin Enema
Authors: Watson Jerry E. , Tagupa Eumar T.
Published: January 2017

OBJECTIVE:

To report a suicide attempt with an aspirin enema.

CASE SUMMARY:

A patient presented to the emergency room after self-administering, in enema form, approximately 700 aspirin tablets dissolved in water. Over the next 12hours the patient became progressively acidemic with eventual cardiac arrest and subsequent chronic hypoxic encephalopathy.

DISCUSSION:

This patient's poor outcome was the result of retained aspirin products in the rectal vault combined with the failure to recognize the delayed absorption properties of rectally administered aspirin.

CONCLUSIONS:

In rectal aspirin overdoses, aspirin absorption from the rectum may occur over a long period of time. It is important to remove as much aspirin from the rectum as possible and to closely monitor these patients so that appropriate therapy may be started quickly. Activated charcoal given both in enema and oral form may help decrease aspirin absorption. Hemodialysis should be available and performed without delay should the patient require it.
Tacrolimus, a New Immunosuppressant—A Review of the Literature
Authors: Hooks Michael A.
Published: January 2017

OBJECTIVE:

To review the clinical pharmacology, pharmacokinetics, adverse effects, therapeutic uses, and current status of tacrolimus.

DATA SOURCES:

Data from scientific literature were identified by a MEDLINE search. The data were extracted, evaluated, and summarized for presentation. Experiences from studies evaluating tacrolimus in the form of articles, abstracts, letters to the editor, or proceedings were considered for inclusion.

STUDY SELECTION:

Open and controlled clinical and animal trials were reviewed in evaluating the pharmacology, pharmacokinetics, and adverse effects of tacrolimus.

DATA EXTRACTION:

Data from animal and human studies published in the English literature were evaluated.

DATA SYNTHESIS:

Tacrolimus is an 822-kDa macrolide antibiotic that has potent immunosuppressive properties. The mechanism of action is similar to that of cyclosporine in that it ultimately blocks the production of interleukin 2, thereby inhibiting further T-lymphocyte proliferation. Tacrolimus is metabolized solely in the liver and the metabolites are primarily excreted in the bile. The elimination halflife of tacrolimus is approximately 8.5 h, and is prolonged in hepatic dysfunction. Tacrolimus has shown efficacy in the prophylaxis of allograft rejection in both animals and human clinical trials, and has been used effectively to rescue patients who have exhibited refractory rejection failing cyclosporine prophylaxis. Adverse effects requiring tacrolimus dosage adjustment include nephrotoxicity, neurotoxicity, alterations in glucose metabolism, and infection or susceptibility to malignancy.

CONCLUSIONS:

To date, trials comparing tacrolimus with cyclosporine are not available in the literature; however, tacrolimus appears to be useful in rescuing grafts, particularly liver grafts that fail cyclosporine-based immunosuppression. Direct comparisons with cyclosporine are needed to define the role of tacrolimus as primary transplant therapy.
Risk Factors for Acute Renal Insufficiency in Patients with Suspected or Documented Bacterial Pneumonia
Authors: Welage Lynda S. , Walawander Cynthia A. , Timm Edward G. , Grasela Thaddeus H.
Published: January 2017

OBJECTIVE:

To describe the incidence of acute renal insufficiency and identify potential risk factors associated with this adverse medical event.

DESIGN:

A cohort analytic study of patients with documentedor suspected bacterial pneumonia.

SETTING:

Nationwide survey of 74 acute care hospitals across the US.

INCLUSION AND EXCLUSION CRITERIA:

A total of 1822 adult patients with documented or suspected bacterial pneumonia who were receiving a cephalosporin, penicillin, or an aminoglycoside were enrolled. Patients were excluded if the duration of antimicrobial therapy was <3 days or if the pneumoniawas judged to be nonbacterial.

DATA COLLECTION:

Clinical pharmacists completed standardized data collection forms on all patients enrolled in the study. Information regarding patient demographics, concurrent illnesses and medications, antibiotic administration, representative laboratory data, and the occurrenceof any adverse clinical event was specifically captured. Information regardingthe development of acute renal insufficiency was targetedas an event to be captured.

MAIN OUT COME MEASURES:

Univariateand multivariate analyseswere performed to identify significant risk factors for acute renal insufficiency. A subset analysis was similar lyperformed to identify risk factors associated with aminoglycoside-related acute renal insufficiency.

RESULTS:

Of the patients enrolled in this study, 8.2 percent developed acute renal insufficiency. Risk factors for acute renal insufficiency included renal disease, aminoglycoside therapy, nosocomial pneumonia, elevated estimated creatinine clearance prior to study entry, cardiac arrest/shock, congestive heart failure, total duration of antibiotics >7 days, clindamycin therapy, liver disease, and first-generation cephalosporin usage. Risk factors for aminoglycoside-related acute renal insufficiency identified via multiple logistic regression included amphotericin B, congestive heart failure, aminoglycoside trough concentration >1.5 mg/L, and clindamycin therapy.

CONCLUSIONS:

The risk factors identified for acute renal insufficiency suggest that severity of illness strongly influences the development of renal insufficiency. Theoretically, the results of this study could serve as a framework for developing risk prevention programs within individual hospitals. Specific risk factors could be identified for a patient population and risk factors that could be modified could then be targeted for intervention. This type of information can also assist cliniciansin predictingthe probability of the adverseevent for a particular patient and subsequently minimizing this risk by initiating intense monitoring or modifying the drug regimen.
Adult Height in Girls with Turner Syndrome Treated with Low-Dose Estrogens and Androgens
Authors: Lin Tsu H. , Kirkland Rebecca T. , Kirkland John L.
Published: January 2017

OBJECTIVE:

To determine if low dosages of estrogens and androgens administered to girls with Turner syndrome adversely affected their adult height.

DESIGN:

A nonrandomized control trial of nine girls.

SETTING:

The endocrine clinic at Texas Children's Hospital in Houston, Texas, an academic referral center.

PARTICIPANTS:

Participants had chromosomal defects consistent with Turner syndrome. Informed consent was obtained in accordance with institutional review board procedures. Eligibility criteria included an absence of previous hormone treatment. No one withdrew from this study because of adverse effects.

INTERVENTIONS:

Hormonal replacement therapy was initiated with conjugated estrogen 0.15 mg and tluoxymesterone 1 mg administered daily.

MAIN OUTCOME MEASURES:

Outcome measurements were a comparison of the final heights following treatment versus the predicted adult heights prior 10 treatment.

RESULTS:

The predicted adult height in these children prior to treatment was 140.0 ± 4.4 cm (mean ± SD); the actual adult height was 139.63 ± 4.1 cm. The difference was 0.37 ± 3.54 cm, which was not statistically significant by Wilcoxon signed-rank test (p=0.23). The 95% confidence interval on this difference ranged from −3.1 to 2.3 cm, which indicates a true mean height loss of no more than 3.1 cm or a true mean gain of no more than 2.3 cm.

CONCLUSIONS:

Our results indicate that hormone replacement therapy with low dosages of conjugated estrogens and androgens starting at 10–11 years of age in children with Turner syndrome does not adversely affect actual adult height.
Update on Childhood Immunizations
Authors: de Clavijo Irene V. , Weart C. Wayne
Published: January 2017

OBJECTIVE:

To provide an overview of childhood immunizations with emphasis in new recommendations, as well as recent vaccine developments and special populations.

DATA SOURCES:

English language literature identified via a MEDLINE search. Additional references were obtained from cited references.

STUDY SELECTION AND DATA EXTRACTION:

Original articles, reviews, and official publications were used to obtain the most accurate data on safety and efficacy of available pediatric vaccines, as well as current recommendations for their use.

DATA SYNTHESIS:

Immunizations have been an area of vigorous research for several years. New vaccines have been developed by improving older products to maximize immunogenicity and minimize adverse effects. Some of these novel vaccines, like the Haemophilus influenzae type b conjugate vaccines (HibCV), have already contributed significantly to the prevention of diseases in childhood. New recommendations have been issued to help speed this process. Adverse effects of routine immunizations are generally mild and transient.

CONCLUSIONS:

The development of new effective and safe vaccines for children is an important step in the global eradication of contagious diseases. A new generation of combination vaccines has started with the combination of the diphtheria-tetanus-pertussis vaccine and HibCV. Some other combined products are yet to come that would eventually make immunization schedules more costeffective and improve compliance rates. Our colleagues in the community and in the ambulatory care setting must actively participate in the implementation of vaccination programs and provide education to parents regarding all aspects of the immunization process.
Vancomycin-Induced Neutropenia during Treatment of Endocarditis in a Pediatric Patient
Authors: Shinohara Y. Todd , Colbert James
Published: January 2017

OBJECTIVE:

To report a case of reversible vancomycin-associated neutropenia occurring during long-term therapy with vancomycin using weight and age-adjusted dosing.

CASE SUMMARY:

A 2-year-old boy was started on vancomycin therapy for presumed endocarditis resulting from his ventriculoseptal defect. After 18 days of treatment, neutropenia with an absolute neutrophil count (ANC) of 990 × 106 cells/L was noted. The neutropenia progressed over the next 3 days and reached a nadir concentration of 459 × 106 cells/L. Vancomycin therapy was discontinued after 17 days (antibiotic day 20). A rise in the ANC occurred within 2 days of discontinuation. An improved ANC of 1672 × 106 cells/L occurred within 5 days. Vancomycin serum concentrations remained within an acceptable range: a peak of 30 μg/mL and a trough of 9 μg/mL.

DISCUSSION:

Case reports in the literature of vancomycin-associated neutropenia in adults were briefly reviewed and compared. The onset and resolution and mechanism of vancomycin-induced neutropenia were studied. The potential relationship between vancomycin, weight-, and age-adjusted dosing and the occurrence of neutropenia in our pediatric patient was postulated.

CONCLUSIONS:

Vancomycin is identified as a possible cause of drug-induced neutropenia. More data are needed that clearly indicate vancomycin as the offending agent in children. The vancomycin-induced neutropenia is believed to be immunologically based and independent of drug concentrations.
Once-Daily Administration of Aminoglycosides
Authors: Bates Richard D. , Nahata Milap C.
Published: January 2017

OBJECTIVE:

To provide an overview of the efficacy and adverse effects associated with once-daily administration of aminoglycosides.

DATA SOURCES:

An extensive MEDLINE search and review of journals was conducted to identify information for this review.

DATA SYNTHESIS:

Aminoglycosides alone or in combination with beta-lactams are commonly used for their activity against gram-negative microorganisms. Numerous studies have been performed comparing efficacy and toxicity of once-daily administration of aminoglycosides with multiple-daily dosing. Two studies have found a significant difference in clinical efficacy between once-daily and multiple-daily dosing of aminoglycosides. Several studies have observed a lower incidence of toxicity with once-daily than multiple-daily dosing, but others have found no difference.

CONCLUSIONS:

Review of the literature suggests that once-daily administration of aminoglycosides may be as safe and effective as multiple-daily dosing regimens for the treatment of certain infections caused by gram-negative bacteria.
Gabapentin: A New Agent for the Management of Epilepsy
Authors: Andrews Carlota O. , Fischer James H.
Published: January 2017

OBJECTIVE:

To review the pharmacology, pharmacokinetics, efficacy, and safety of gabapentin, a new antiepileptic drug (AED). Gabapentin's potential role in the treatment of epilepsy also was assessed.

DATA SOURCE:

A MEDLINE search was performed to identify all published literature (manuscripts and abstracts). Abstracts presented at the American Epilepsy Society, International Epilepsy Congress, and American Academy of Neurology meetings from 1991 to 1993 also were reviewed. A copy of the proceedings from the Food and Drug Administration Peripheral and Central Nervous System Advisory Committee meeting and package insert were obtained from Parke Davis.

STUDY SELECTION:

All pertinent literature was reviewed. Emphasis was placed on published information, particularly placebo-controlled clinical trials.

DATA SYNTHESIS:

Gabapentin is effective as adjunctive treatment for patients with partial seizures with or without secondary generalization refractory to the standard AEDs. It has a unique pharmacokinetic profile for an AED, including no binding to plasma proteins, primary elimination by the kidney, and dose-dependent oral absorption at high dosages. No drug interactions occur with the other AEDs. The most frequent adverse reactions noted in patients receiving gabapentin have been mild and transient central nervous system effects. No serious hypersensitivity or systemic reactions have been observed.

CONCLUSIONS:

Gabapentin appears to be a useful new AED. Further studies evaluating its use as monotherapy, in higher dosages, and in pediatric and elderly patients are required to better delineate its therapeutic role relative to that of other AEDs.
Pharmacokinetics of Once-Dally Dosing of Gentamicin in Surgical Intensive Care Unitpatients with Openfractures
Authors: Sangha Kiranpal S. , Miyagawa Clyde I. , Healy Daniel P. , Bjornson H. Stephen
Published: January 2017

Objective:

To compare the first-dose pharmacokinetic parameters of gentamicin 6 mg/kg and 2 mg/kg in stable, nonobese surgical intensive care unit patients with open extremity fractures receiving gentamicin prophylactically.

Methods:

Serial blood samples were obtained over 8 or 24 hours following the first dose of gentamicin. Serum concentrations of gentamicin were measured using fluorescence polarization immunoassay and analyzed by noncompartmental means.

Results:

Eleven patients were enrolled, 7 in the 6 mg/kg group and 4 in the 2 mg/kg group. The median (6 vs. 2 mg/kg) age was 29 versus 28 years; serum creatinine 80 versus 88 μmol/L; and APACHE H score 13 versus 10. The mean ± SD (μg/mL) of concentration at the end of the 30-minute infusion (Cmax), concentration 30 minutes after the end of the infusion (Cpk), and concentration at the end of the dosing interval for 6 versus 2 mg/kg were: 35.0 ± 19.0 versus 10.1 ± 1.77; 17.0 ± 2.7 versus 5.4 ± 0.4, and 0.45 ± 0.31 versus 0.69 ± 0.11, respectively. Area under the curves0-∞ (AUC0-∞), apparent volume of distribution, and half-life were: 89.0 ± 28.9 versus 26.1 ± 1.2 mg·h/L, 0.40 ± 0.10 versus 0.47 ± 0.14 L/kg, and 4.0 ± 1.1 versus 4.3 ± 1.5 h, respectively.

Conclusions:

The first-dose pharmacokinetics of gentamicin 6 mg/kg resulted in a proportional rise in Cmax, Cpk, and AUC0-∞, compared with gentamicin 2 mg/kg in patients with open fractures, but with greater variability.
Ifosfamtoe-Induced Fanconi Syndrome
Authors: Garcia Agustin A
Published: January 2017

Objective:

To report a case of possible ifosfamide-induced Fanconi syndrome in an adult with cancer.

Case Summary:

A 20-year-old man was treated for an osteosarcoma with a chemotherapy regimen that included ifosfamide, methotrexate, and doxorubicin. Three months after completing therapy he developed polyuria, polydypsia, and bilateral ankle pain. Laboratory findings showed decreased serum concentrations of phosphorus, uric acid, calcium, potassium, and bicarbonate; elevated blood urea nitrogen and creatinine; and increased urinary excretion of phosphorus, potassium, calcium, citrate, and protein. The patient was diagnosed with Fanconi syndrome and osteomalacia. Treatment with oral supplements of potassium, sodium, citric acid, calcium, and calcitriol corrected the electrolyte abnormalities.

Discussion:

The adverse effect most frequently associated with ifosfamide is hemorrhagic cystitis. The incidence of hemorrhagic cystitis is decreased with the concomitant administration of the uroprotective agent mesna. The development of Fanconi syndrome after ifosfamide therapy has been described previously, although it occurs more frequently in children than adults. The mechanism by which ifosfamide causes renal tubular damage is not well understood, but it appears to involve metabolites of the drug.

Conclusions:

The development of renal tubular defects and renal failure should be considered in patients receiving ifosfamide. Although this complication appears more frequently in children, adults also can be affected. Renal function should be monitored closely to detect the appearance of this adverse effect. Renal tubular dysfunction can, as this case illustrates, develop months after completing chemotherapy.
Interactions Between Antipsychotic and Antihypertensive Drugs
Authors: Markowitz John S , Wells Barbara G , Carson William H
Published: January 2017

Objective:

To provide a comprehensive review of the pharmacokinetic and pharmacodynamic interactions between antipsychotics and antihypertensives and to provide recommendations for the selection of antihypertensives in patients receiving antipsychotic therapy.

Data Sources:

A MEDLINE search of the English-language literature was used to identify pertinent human and animal studies, reviews, and case reports.

Study Selection:

All available sources were reviewed.

Data Extraction:

Background information was obtained from comprehensive reviews. Individual case reports were assimilated, and pertinent data were extracted.

Data Synthesis:

Because hypertension is common in patients with psychiatric illness and antihypertensive agents are used for a multiplicity of indications, significant numbers of patients receive concurrent therapy with antihypertensives and antipsychotics. Many antipsychotics may block the antihypertensive efficacy of guanethidine and related drugs. The interaction between Clonidine and antipsychotics is defined less clearly. Limited data suggest possible additive hypotensive effects when chlorpromazine and methyldopa are given in combination. Increased plasma concentrations of thioridazine with a resultant increase in adverse effects have been reported when propranolol or pindolol are added to the regimen. A similar increase in chlorpromazine concentrations has been reported when propranolol was added. Although there are no reports documenting an interaction between a calcium-channel antagonist and an antipsychotic, the possible inhibition of oxidative metabolism of antipsychotics, additive calcium-blocking activity, and additive pharmacodynamic effects are theorized. Hypotension and postural syncope were reported in a patient given therapeutic dosages of chlorpromazine and Captopril, and in 2 patients when clozapine was added to enalapril therapy.

Conclusions:

No antipsychotic-antihypertensive combination is absolutely contraindicated, but no combination should be considered to be completely without risk. Antihypertensives with no centrally acting activity, such as diuretics, may be the least likely to result in adverse reactions. The combination of the beta-antagonists propranolol or pindolol with thioridazine or chlorpromazine should be avoided if possible. Scrupulous patient monitoring for attenuated or enhanced activity of either agent is essential whenever antipsychotics and antihypertensives are given concurrently.
Thrombosis and the Pharmacology of Antithrombotic Agents
Authors: Haines Stuart T , Bussey Henry I
Published: January 2017

Objective:

To provide an overview of the current state of knowledge regarding the physiology of hemostasis, the pathophysiology of thrombosis, and the pharmacology of antithrombotic agents.

Data Sources:

A MEDLINE search was conducted to identify pertinent literature published since 1984. Recently published textbooks devoted to the subjects of hematology, hemostasis, and thrombosis also were reviewed, particularly their bibliographies. The bibliographies of selected review articles also were reviewed.

Study Selection:

As the amount of literature was vast, only the most significant and noteworthy published studies were reviewed. Review articles and book chapters authored by researchers of international reputation also were reviewed.

Data Extraction:

Identified studies from the primary literature and selected reviews were analyzed carefully. Information regarding hemostasis, thrombosis, and antithrombotic drugs was extracted. Particular attention was given to data regarding drugs currently available or soon to be available on the US market.

Data Synthesis:

Knowledge regarding the regulation of blood coagulation has expanded substantially in recent years. Hemostasis involves the dynamic interplay of numerous intravascular constituents, including the vessel wall, circulating procoagulants and anticoagulants, platelets, and fibrinolytic proteins. Thrombosis is the abnormal formation of a clot within the vascular system. When sufficiently large, thrombi can prevent the flow of blood and nutrients to vital tissues. Thrombosis is associated with many common diseases and is among the leading causes of death in developed countries. Many drugs are now available to prevent the formation and propagation of thrombi. These agents work by different pharmacologic mechanisms and are useful in different clinical situations.

Conclusions:

Thrombosis research has increased our understanding of the pharmacology of antithrombotic drugs and promoted the discovery of new agents targeted more specifically toward the critical steps in pathologic clot formation. New agents have the potential for greater efficacy and fewer adverse effects. An increased understanding of hemostasis, thrombosis, and the pharmacology of antithrombotic drugs should enable the clinician to use these agents appropriately.