Plasma amprenavir pharmacokinetics and tolerability following administration of 1,400 milligrams of fosamprenavir once daily in combination with either 100 or 200 milligrams of ritonavir in healthy volunteers

Once-daily (QD) fosamprenavir (FPV) at 1,400 mg boosted with low-dose ritonavir (RTV) at 200 mg is effective when it is used in combination regimens for the initial treatment of human immunodeficiency virus infection. Whether a lower RTV boosting dose (i.e., 100 mg QD) could ensure sufficient amprenavir (APV) concentrations with improved safety/tolerability is unknown. This randomized, two 14-day-period, crossover pharmacokinetic study compared the steady-state plasma APV concentrations, safety, and tolerability of FPV at 1,400 mg QD boosted with either 100 mg or 200 mg of RTV QD in 36 healthy volunteers. Geometric least-square (GLS) mean ratios and the associated 90% confidence intervals (CIs) were estimated for plasma APV maximum plasma concentrations (Cmax), the area under the plasma concentration-time curve over the dosing period (AUC0-tau), and trough concentrations (Ctau) during each dosing period. Equivalence between regimens (90% CIs of GLS mean ratios, 0.80 to 1.25) was observed for the plasma APV AUC0-tau (GLS mean ratio, 0.90 [90% CI, 0.84 to 0.96]) and Cmax (0.97 [90% CI, 0.91 to 1.04]). The APV Ctau was 38% lower with RTV at 100 mg QD than with RTV at 200 mg QD (GLS mean ratio, 0.62 [90% CI, 0.55 to 0.69]) but remained sixfold higher than the protein-corrected 50% inhibitory concentration for wild-type virus, with the lowest APV Ctau observed during the 100-mg QD period being nearly threefold higher. The GLS mean APV Ctau was 2.5 times higher than the historical Ctau for unboosted FPV at 1,400 mg twice daily. Fewer clinical adverse drug events and smaller increases in triglyceride levels were observed with the RTV 100-mg QD regimen. Clinical trials evaluating the efficacy and safety of FPV at 1,400 mg QD boosted by RTV at 100 mg QD are now under way with antiretroviral therapy-na?ve patients.     

Correlation of capillary and venous blood glucometry with laboratory determination

Background

During resuscitation in the Singapore Armed Forces, blood glucose samples are often obtained for analysis using the capillary glucometer. A drop of venous blood from the intravenous cannula is sometimes used to ascertain the patient's blood glucose level. Venous samples may be sent to a commercial laboratory, but this does not allow immediate results.

Objective

To establish the correlation between the glucose levels of the capillary fingerprick sample analyzed by the glucometer (Cap), the venous sample analyzed by the glucometer (Ven), and the venous sample tested by the commercial laboratory (Lab).

Methods

This multicenter, prospective study enrolled subjects from Selarang, Clementi, and Maju Camp Medical Centers in the Singapore Armed Forces from November 2002 to January 2003. All subjects provided at least two samples; because provision of the capillary blood glucose sample was voluntary, only some gave consent for capillary fingerprick and provided three samples. There were no exclusion criteria. Bland-Altman plots were then constructed to compare the capillary and venous-on-capillary values with the laboratory results.

Results

A total of 270 subjects were recruited. One hundred seventy subjects (63.0%) gave consent for capillary glucose measurement and, thus, had three readings for comparison. There was a mean difference of 0.97 mmol/L (17.46 mg/dL) between the Ven and Lab results. There was an insignificant mean difference of 0.01 mmol/L (0.18 mg/dL) between the Cap and Lab results.

Conclusion

Capillary whole-blood glucose values best approximated venous plasma glucose values from the laboratory. Measuring the venous whole-blood glucose using the glucometer resulted in an overestimation of the venous plasma glucose compared with the laboratory result by about 0.97 mmol/L (17.46 mg/dL). This may result in the withholding of intravenous glucose for patients who are actually hypoglycemic.     

The plantaris tendon graft: An ultrasound study

To assess the value of ultrasound in imaging the plantaris tendon, ultrasounds were done on 26 legs in 25 patients who had a variety of surgical procedures on the posterior leg. Eighteen ultrasounds were done and interpreted before operation and eight after operation by a radiologist. The sonographic results were compared with the status of the plantaris as determined at surgery. The plantaris was present in 21 of 23 patients for a prevalence of 91%. Eighteen plantaris tendons were well visualized on ultrasound for a sensitivity of 86%. Of the three false-negative results, two occurred with thinned plantaris tendons that were less than 2 mm thick and hence considered inadequate for grafting. Therefore, the sensitivity for detecting a tendon suitable for grafting was 95%. All patients with positive studies had a plantaris tendon present for a specificity of 100%. A learning curve for the radiologist was demonstrated. Ultrasound appears to be effective in the preoperative imaging of the plantaris tendon.     

Comparison of stationary vs ambulatory 24-hour pH monitoring recording systems

Twenty-four-hour pH monitoring of the esophagus is frequently performed to assess gastroesophageal reflux. We performed a prospective study to determine if results obtained from stationary and ambulatory pH recording systems are comparable. Two groups of patients were studied. Group I consisted of 12 patients monitored simultaneously by both a stationary and an ambulatory pH recording system, each system having a separate pH and reference electrode. In group II, in order to eliminate electrode variability, 10 patients were monitored simultaneously with both systems and a common single pH and reference electrode. In group I, significant correlations were found in six reflux parameters measured and in the 24-hr composite score (r0.8722). However, in three of the 12 patients, marked discrepancies were noted in the composite score calculated by the stationary and ambulatory recording systems. Small variations in the pH level recorded by different pH electrodes may have accounted for the discrepancies. In group II, where electrode variability was eliminated, a better correlation was noted between all parameters measured (r 0.991), and no discrepancies were noted between calculated composite scores. We concluded that the stationary and ambulatory recording systems tested are comparable in measuring 24-hr esophageal pH.This protocol (WR-1477) was approved by the WRAMC Human Use Committee/Institutional Review Board and supported by Department of Clinical Investigation Funding.The opinions and assertions contained herein are the private ones of the authors and are not to be construed as official policy or reflecting the views of the Department of the Army or the Department of Defense.     

Management of a subcutaneous colostomy perforation

Colostomy perforation is an infrequent but often diasastrous and lethal complication. In the majority of patients, the traumatic performation occurs during irrigation through the colostomy stoma. This case report reviews the clinical course of a patient with a subcutaneous colostomy perforation and the subsequent development of an extensive abscess. Aspects of the management included mobilization of the colostomy and thorough surgical debridement and drainage. In addition, the report introduces the use of the new semisynthetic biologic dressing, BioBrane^®. This synthetic, semipermeable skin substitute served as a temporary dessing, provided good stability, and supported the application of a stoma appliance.     

Prognostic assessments of medical therapy and vestibular testing in post-traumatic migraine-associated dizziness patients

Objective

The aim of this study was to characterize our clinical population of patients suffering with post-traumatic migraine-associated dizziness (PTMAD) and determine any associations with medical interventions and vestibular testing metrics to help predict response to treatments.

Study Design

Retrospective chart review.

Setting

Tertiary referral center.

Subjects and Methods

The electronic medical records of 83 patients presenting to a tertiary referral center who were given a diagnosis of PTMAD and who had been treated were retrospectively reviewed. General characteristics, clinical treatment, pre- and post-vestibular therapy testing metrics, and success and failure outcomes were assessed. Patients were assigned into responder and nonresponder groups related to their headaches and evaluated at two specific time points. Medication failures and vestibular test metrics were compared to identify and predict clinical outcomes.

Results

Seventy-two of 82 patients (88%) were analyzed at two time points. Use of verapamil, topiramate, gabapentin, amitryptiline, and valproic acid showed no comparative treatment benefit in responders compared to nonresponders (P = 0.294). Findings associated with successful treatments include response to initial medication (P = 0.001), final dynamic gait index (DGI) scores (P = 0.029), final vertical dynamic visual acuity test (DVAT) scores (up, 0.007; down, 0.006), and both final and change in computerized dynamic posturography–sensory organization test (CDP-SOT) scores (P = 0.001, P = 0.032). The antipsychotic quetiapine was specifically associated with outcome failures (P = 0.003).

Conclusion

Specific prophylactic antimigraine medications were not associated with improved outcomes in PTMAD patients. Initial clinical responses and vestibular test metrics may guide physicians to predict successful outcomes.     

Hypotonic duodenoscopy

Inducing duodenal hypotonia by the intravenous injection of propantheline bromide is a simple, safe procedure that will permit this organ to be visualized adequately by endoscopy. Twenty-five consecutive patients with suspected duodenal pathology received an intravenous injection of propantheline at the time the pylorus was being viewed through the endoscope. Immediately after the injection, the pylorus dilated and the endoscope was passed easily into the duodenal bulb, where good visualization was achieved. A small bulb syringe attached to the air channel of the endoscope and gentle insufflation of air permitted good visualization of the second portion of duodenum. While the propantheline method is not necessary in all patients undergoing duodenoscopy, those in whom it is difficult to pass the endoscope through the pylorus or in whom antroduodenal motility precludes adequate examination, injection of the antispasmodic provides one easy, safe method for examining the duodenum by duodenoscopy.     

Compact Quadruple Therapy with the Lamivudine/Zidovudine Combination Tablet Plus Abacavir and Efavirenz,Followed by the Lamivudine/Zidovudine/Abacavir Triple Nucleoside Tablet Plus Efavirenz in Treatment-Naïve HIV-Infected Adults

Abstract

Purpose: To assess efficacy, safety, and adherence with compact quadruple therapy comprising one lamivudine 150-mg/zidovudine 300-mg tablet (COM) twice daily + one abacavir (ABC) 300-mg tablet twice daily + three efavirenz (EFV) 200-mg capsules at bedtime for 24 weeks, followed by one lamivudine 150-mg/zidovudine 300-mg/ABC 300-mg triple nucleoside tablet (TZV) twice daily + three EFV 200-mg capsules at bedtime for 24 weeks. Method: A pilot 48-week, prospective, open-label trial in which 38 antiretroviral-naïve HIV-infected adults (baseline median HIV-1 RNA 5.1 log₁₀ copies/mL, CD4+ cell count 285/μL) received the above treatment and were monitored regularly with respect to plasma HIV-1 RNA levels, CD4+ cell counts, T-cell receptor excision circles (TRECs), adherence, and adverse events. Results: At Week 48, intent-to-treat, switch-included analysis showed plasma HIV-1 RNA levels <400 copies/mL in 100% (29/29) of patients and <50 copies/mL in 93% (27/29); 59% of patients who achieved <50 copies/mL had <3 copies/mL (16/27). Similar virologic suppression was observed in patients with baseline HIV-1 RNA above or below 100,000 copies/mL. HIV-1 RNA and CD4+ cell counts changed from baseline by a median of –3.4 log₁₀ copies/mL and +172 cells/μL, respectively. One virologic failure occurred at Week 16. Median TRECs/100,000 peripheral blood lymphocytes increased 6-fold between baseline and Week 48. Median adherence rates were consistently 100% by self-report and 94% by pill count. Grade 2-4 treatment-related adverse events included dreams (16%), nausea (13%), decreased white cells (8%), dizziness (8%), sleep disorders (8%), and malaise and fatigue (8%). A suspected ABC hypersensitivity reaction occurred in 8% (3/38) of patients. Conclusion: COM/ABC/EFV or TZV/EFV produced potent, durable virologic suppression and immunologic benefits, was associated with high adherence rates, and was generally well tolerated.