Biomedical subjects
J Cash
Publications and source records attributed to J Cash.
Pharmacokinetics and pharmacodynamics of ranitidine in critically ill children.
OBJECTIVE: To determine the pharmacokinetics and pharmacodynamics of ranitidine in critically ill children and to design a dosage regimen that achieves a gastric pH > or =4. DESIGN: Prospective, open-label, pharmacokinetic-pharmacodynamic study. SETTING: Pediatric intensive care unit in a tertiary care children's hospital. PATIENTS: Mechanically ventilated, critically ill children > or =10 kg who required intravenous ranitidine for stress ulcer prophylaxis. INTERVENTIONS: Ranitidine pharmacokinetics were determined after a single intravenous dose. Gastric pH was monitored hourly via nasogastric pH probe. After the last blood sample, patients received an intravenous bolus of ranitidine (0.5 mg/kg) followed by a continuous infusion (0.1 mg x kg(-1) x hr(-1)). The infusion was increased incrementally (0.05 mg x kg(-1) x hr(-1)) until reaching gastric pH > or =4 for > or =75% of a 24-hr period, after which steady-state plasma concentrations were measured. Plasma concentrations were analyzed by high-pressure liquid chromatography. MEASUREMENTS AND MAIN RESULTS: Twenty-three children (ranging in age from 1.4 to 17.1 yrs) were studied. Pharmacokinetic variables included a clearance of 511.7 +/- 219.7 mL x kg(-1) x hr(-1), volume of distribution of 1.53 +/- 0.99 L/kg, and half-life of 3.01 +/- 1.35 hrs. After the single intravenous dose (1.52 +/- 0.47 mg/kg), gastric pH increased from 1.6 +/- 1.0 to 5.1 +/- 1.1 (p <.001), which was associated with a plasma concentration of 373 +/- 257 ng/mL. Based on the pharmacokinetic variables, the dose of intravenous ranitidine required to target 373 ng/mL as the average steady-state concentration is 1.5 mg/kg administered every 8 hrs. During the continuous infusion, the mean steady-state ranitidine concentration associated with gastric pH > or =4 was 287 +/- 133 ng/mL. This concentration may be achieved with an intravenous loading dose of 0.45 mg/kg followed by a continuous infusion of 0.15 mg x kg(-1) x hr(-1). CONCLUSIONS: The pharmacokinetics of ranitidine in critically ill children are variable. The description of ranitidine's pharmacokinetics and pharmacodynamics in this study may used to design an initial ranitidine dosage regimen that targets a gastric pH > or =4. Thereafter, gastric pH should be monitored and the dose of ranitidine adjusted accordingly.
Enteral methadone to expedite fentanyl discontinuation and prevent opioid abstinence syndrome in the PICU.
STUDY OBJECTIVE: To determine if enterally administered methadone can facilitate fentanyl discontinuation and prevent withdrawal in children at high risk for opioid abstinence syndrome. DESIGN: Retrospective analysis. SETTING: Pediatric intensive care unit (PICU) in a tertiary care children's hospital. PATIENTS: Twenty-two children (aged 6.1 +/- 5.4 yrs) who received continuous fentanyl infusion for 9 days or longer. INTERVENTION: Guidelines for initiating enteral methadone, rapidly tapering and discontinuing fentanyl infusions, and tapering methadone were implemented in the PICU. Development of opioid abstinence syndrome was evaluated during fentanyl and methadone dosage reductions and for 72 hours thereafter. MEASUREMENTS AND MAIN RESULTS: Children received fentanyl by continuous infusion for 17.8 +/- 8.4 days. Peak fentanyl infusion rate was 5.9 +/- 3.8 microg/kg/hour, and the median cumulative dose was 1302 microg/kg (range 354-7535 microg/kg). Methadone 0.50 +/- 0.22 mg/kg/day was begun 1.6 +/- 1.9 days before tapering fentanyl. The fentanyl infusion rate on starting the taper was 5.0 +/- 3.6 microg/kg/hour. Fentanyl was tapered and discontinued in a median of 2.6 days (range 0-11.9 days). Twenty-one patients had no opioid abstinence syndrome during or after fentanyl taper. One patient experienced significant opioid withdrawal after fentanyl discontinuation, which resolved after reinstitution of fentanyl and increasing the dosage of methadone to 0.3 mg/kg every 6 hours. Overall, methadone was tapered and discontinued in 18.2 +/- 11.9 days without precipitating opioid abstinence syndrome. CONCLUSION: Enteral administration of methadone may expedite fentanyl discontinuation and reduce the risk of withdrawal in critically ill children at high risk for opioid abstinence syndrome.
Prognostic role of serum prostatic acid phosphatase for 103Pd-based radiation for prostatic carcinoma.
PURPOSE: To establish the prognostic role of serum enzymatic prostatic acid phosphatase (PAP) in patients treated with palladium (103Pd) and supplemental external beam irradiation (EBRT) for clinically localized, high-risk prostate carcinoma. METHODS AND MATERIALS: One hundred twenty-four consecutive patients with Stage T2a-T3 prostatic carcinoma were treated from 1992 through 1995. Each patient had at least one of the following risk factors for extracapsular disease extension: Stage T2b or greater (100 patients), Gleason score 7-10 (40 patients), pretreatment prostate specific antigen (PSA) >15 ng/ml (32 patients), or elevated serum PAP (25 patients). Patients received 41 Gy conformal EBRT to a limited pelvic field, followed 4 weeks later by a 103Pd boost (prescription dose 80 Gy). Biochemical failure was defined as a PSA greater than 1 ng/ml (normal <4 ng/ml). RESULTS: The overall, actuarial freedom from biochemical failure at 4 years after treatment was 79%. In Cox-proportional hazard multivariate analysis, the strongest predictor of failure was elevated pretreatment acid phosphatase (p = 0.02), followed by Gleason score (p = 0.1), and PSA (p = 0.14). CONCLUSION: PAP was the strongest predictor of long-term biochemical failure. It may be a more accurate indicator of micrometastatic disease than PSA, and as such, we suggest that it be reconsidered for general use in radiation-treated patients.
Blood transfusion: Bayer's initiative.
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A cost analysis of enterally administered lorazepam in the pediatric intensive care unit.
OBJECTIVE: To determine the cost savings of replacing intravenous midazolam with enterally administered lorazepam in mechanically ventilated children who require long-term continuous sedation. DESIGN: Retrospective review of patients treated according to a preestablished pediatric intensive care unit (ICU) sedation protocol. SETTING: Twenty-six-bed pediatric ICU in a tertiary care children's hospital. PATIENTS: The records of 30 mechanically ventilated children were analyzed. The median age was 1.5 yrs and the median weight was 8.0 kg. Patients required continuous sedation for a total of 16 days (median). INTERVENTIONS: According to our pediatric ICU sedation protocol, midazolam infusion was continued until the hourly midazolam requirement was stable for at least 24 hrs. Thereafter, patients with a nasojejunal tube who were likely to require a minimum of three additional days of continuous sedation were transitioned from intravenous midazolam to enterally administered lorazepam. The goal in transitioning therapy was to titrate the lorazepam dose and reduce midazolam administration while maintaining an unchanged level of sedation. MEASUREMENTS AND MAIN RESULTS: The rate of midazolam administration was significantly (p<.05) reduced beginning on day 1 of lorazepam treatment. Midazolam was successfully discontinued in 24 (80%) patients in 3 days (median), and adequate and appropriate sedation was maintained with lorazepam monotherapy. Six patients in whom midazolam could not be discontinued experienced a 52% reduction in the rate of midazolam administration as a result of adding lorazepam. Total projected midazolam utilization was defined as the sum of midazolam administration before initiating lorazepam and the projected midazolam requirement after initiating lorazepam. Projected midazolam cost was calculated as the product of total projected midazolam utilization and midazolam acquisition cost. Actual expenditures for both midazolam and lorazepam were subtracted from the projected midazolam cost to calculate the estimated cost savings. Overall, midazolam utilization (in milligrams) was reduced by 46.7+/-27.6% (median 52). Total projected midazolam cost for the 30 patients was $90,771. The actual cost of midazolam and lorazepam combined was $47,867, resulting in a cost savings of $42,904. CONCLUSIONS: Transitioning from intravenous midazolam to enterally administered lorazepam in critically ill children who require long-term sedation results in significant cost savings. The oral formulation of lorazepam was convenient to use, inexpensive, and effective in maintaining a continuous and appropriate level of sedation once midazolam was discontinued.
Human papillomavirus typing and the reduction of cervical cancer risk.
Minor cervical cytologic abnormalities are common, but knowing which low-grade lesions will progress to cervical cancer--and therefore deserve biopsy and excision--is difficult. Since some human papillomavirus (HPV) types are strongly associated with cervical cancer, HPV typing may be a means of determining which patients with minor abnormalities require biopsy and treatment and which need only follow-up smears. This paper reviews the association between cervical cancer and HPV infection, the pathogenesis of HPV infection, the utility of HPV typing in training patients with a diagnosis of atypical squamous cells of undetermined significance, and the prospects for the development of an HPV vaccine.
The hospitalist: will inpatient specialists improve care?
The number of hospitalists--i.e., practitioners who specialize in the care of hospital inpatients--is growing rapidly in the United States. In part a response to managed care's push for better health outcomes with a minimum waste of time, effort, and money, this new specialty has its own national organization, affiliated with the American College of Physicians. Challenges to hospitalists include minimizing the use of consultations and unnecessary laboratory tests for inpatient care, and ensuring continuity of care once patients leave the hospital.
Proposed medical academy. Profession should resist further fragmentation.
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103Pd brachytherapy and external beam irradiation for clinically localized, high-risk prostatic carcinoma.
PURPOSE: To summarize biochemical failure rates and morbidity of external beam irradiation (EBRT) combined with palladium (103Pd) boost for clinically localized high-risk prostate carcinoma. METHODS AND MATERIALS: Seventy-three consecutive patients with stage T2a-T3 prostatic carcinoma were treated from 1991 through 1994. Each patient had at least one of the following risk factors for extracapsular disease extension: Stage T2b or greater (71 patients), Gleason score 7-10 (40 patients), prostate specific antigen (PSA) > 15 (32 patients), or elevated prostatic acid phosphatase (PAP) (17 patients). Patients received 41 Gy EBRT to a limited pelvic field, followed 4 weeks later by a 103Pd boost (prescription dose: 80 Gy). Biochemical failure was defined as a PSA greater than 1.0 ng/ml (normal < 4.0 ng/ml). Patients whose PSA was still decreasing at the last follow-up were censored at that time. Patients whose PSA plateaued at a value greater than 1.0 were scored as failures at the time the PSA first plateaued. RESULTS: The overall, actuarial freedom from biochemical failure at 3 years after treatment was 79%. In Cox proportional hazard multivariate analysis, the strongest predictor of failure was elevated acid phosphatase (p = 0.04), followed by PSA (p = 0.17), Stage (p = 0.23), and Gleason score (p = 0.6). Treatment-related morbidity was usually limited to temporary, RTOG Grade 1-2 urinary symptoms. One patient, who had both a transurethral incision of the prostate (TUIP) and a transurethral resection of the prostate (TURP), developed low-volume urinary incontinence. The actuarial potency rate at 3 years after implantation was 77% for 46 patients who were sexually potent prior to implant. CONCLUSION: Biochemical freedom from failure rates following combined EBRT and 103Pd brachytherapy for clinically localized, high-risk prostate cancer compare favorably with that reported after conventional dose EBRT alone. Morbidity has been acceptable.
State of dermatology training: the residents' perspective.
Changes in health care delivery necessitate modification in dermatology training. While the residents at The University of Alabama at Birmingham were planning their 1995-1996 curriculum, several questions regarding the most appropriate allocation of time and resources arose. Interest in other residency curricula prompted the development of a national survey of dermatology residents. Our purpose was to provide comprehensive data regarding the didactic, clinical, surgical, and other aspects of today's U.S. dermatology residency training from the perspective of the residents. It is hoped these data will assist dermatology residency programs with evaluation of their current curricula. A comprehensive 31-question multiplechoice survey was mailed to 631 residents in 70 U.S. dermatology residency programs. Results were tabulated and median values and percentages of responses were obtained. A Wilcoxon rank-sum test, a chi-square analysis, and logistic regression analysis were performed on survey items on the basis of residents' satisfaction with the training program. Two hundred forty-eight responses (39%) were returned with all years of training well represented. Median values and percentages obtained outlined the didactic, clinical, surgical, and other aspects of dermatology residency training. Seventeen percent of residents believed they were not being adequately trained. Satisfaction with training was noted with more didactic faculty involvement, consultations and research, and surgical procedures performed per month. Residents with enriched didactic, clinical, and surgical training experiences are more satisfied with their training programs.
Faulty blood bags. Reputation of English blood transfusion service has been unjustly damaged.
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Fresh frozen plasma: is it farewell?
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Aerosolized pentamidine for the prevention of Pneumocystis carinii pneumonia in children with cancer intolerant or allergic to trimethoprim/sulfamethoxazole.
PURPOSE: Trimethoprim/sulfamethoxazole (TMP/SMX) is the drug of choice for Pneumocystis carinii pneumonia (PCP) prophylaxis in immunocompromised patients. In children with malignancy, TMP/SMX is well tolerated, but adverse reactions that necessitate discontinuation can occur. We evaluated the safety and efficacy of aerosolized pentamidine (AP) as an alternative prophylaxis modality in children with malignancy who are intolerant of or allergic to TMP/SMX. PATIENTS AND METHODS: AP (200 mg/m2 every 4 weeks) was administered to 60 children with malignancy receiving chemotherapy who had experienced severe adverse reactions to TMP/SMX. Seven hundred twenty doses of AP have been administered during a 3 1/2-year period (21,600 patient-days), with 30 patients treated for > or = 12 months (range, 12 to 25). RESULTS: Adverse reactions occurred during 79 (10%) of the 720 treatments and included bronchospasm in 23, cough in 40, vomiting in 10, and nausea in six. Only two patients had severe bronchospasm. AP was discontinued due to toxicity in three patients (5%). None of the patients (upper 95% confidence limit, 0.049) have developed PCP. CONCLUSION: AP appears to be well tolerated and effective in the prevention of PCP in children with malignancy.
Fresh frozen plasma. Viral inactivation may be false reassurance.
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Imprisonment of J-P Allain.
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National Blood Authority.
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The yield of routine chest radiography in children with cancer hospitalized for fever and neutropenia.
A routine admission chest radiograph (CXR) in pediatric patients with cancer who are admitted to the hospital for fever and neutropenia has been advised because the signs and symptoms of pneumonia may be absent. The authors studied 131 consecutive patient admissions for fever and neutropenia to evaluate the diagnostic yield of routine CXR. All patients had a complete history, physical examination, complete blood count, blood culture, urinalysis, urine culture, and CXR. Patients routinely started ceftazidime monotherapy. Results of the CXR were correlated with the presence or absence of signs and symptoms of respiratory disease. Of 128 CXR results, 26 (20%) were abnormal (13 with known malignant disease, 2 with atelectasis, 3 with peribronchial cuffing, and 8 with pneumonia [6%]). Three patients with pneumonia were asymptomatic. Therefore, only 3 of 128 patients (2.3%) had pneumonia on CXR not suspected by physical examination. None would have had initial therapy modified based on the CXR finding alone. The authors concluded that the incidence of pneumonia in a child with fever and neutropenia is low and that routine CXR at diagnostic evaluation is unnecessary in the asymptomatic ambulatory patient.