Ethical responsibility and treatment errors.

Error disclosure is an important part of a healthcare provider's job. In a system such as healthcare, it is inevitable that mistakes will be made and that patients will suffer unnecessarily. Knowing this raises many questions. How does one determine when and how much to disclose? Is there such a thing as too much honesty? With all of the conflicting ideas about when, where, how and what to disclose, how can a provider decide for him or herself how to handle each situation? And should the provider be held responsible for the error or should the system or the patient accept some of the blame in many cases? This article will explore the factors influencing how errors are disclosed and will discuss the idea of responsibility in medical care and error disclosure.

Improved access to care or lowered standard of care?

Health disparities abound in every profession, dentistry included. The most recent attempt to solve dental disparities that has been brought to light is the idea of training dental therapists in order to expand the dental workforce. While dental therapists have been around since the 1970s, only recently has the issue of allowing them to practice in the continental US been so forcefully raised and questioned. With the new healthcare act that will provide access to millions more starting in 2014, these disparities are getting much harder to ignore. We as healthcare professionals have a duty to strive to improve access to quality care and we will not know what quality of care is being provided until these therapists prove (or disprove) themselves. However, we must remember that all three populations - patients, therapists and dentists - must be heard, respected and protected as we navigate this new road to collaboration.

Sensitivity of intravenous and oral alfentanil and pupillary miosis as minimal and noninvasive probes for hepatic and first-pass CYP3A induction.

Systemic and oral clearances of alfentanil (ALF) are in vivo probes for hepatic and first-pass cytochrome P450 (CYP) 3A. Both ALF single-point plasma concentrations and miosis are surrogates for area under the concentration-time curve (AUC) and clearance and are minimal and noninvasive CYP3A probes. This investigation determined ALF sensitivity for detecting graded CYP3A induction and compared it with that of midazolam (MDZ). Twelve volunteers (sequential crossover) received 0, 5, 10, 25, or 75 mg oral rifampin for 5 days. MDZ and ALF were given intravenously and orally on sequential days. Dark-adapted pupil diameter was measured with blood sampling. Graded rifampin decreased plasma MDZ AUCs to 83, 76, 62, and 59% (intravenous (i.v.)) and 78, 66, 39, and 24% (oral) of control. Hepatic and first-pass CYP3A induction were detected comparably by plasma MDZ and ALF AUCs. Single ALF concentrations detected all CYP3A induction, whereas MDZ was less sensitive. ALF miosis detected induction of first-pass but not hepatic CYP3A.

Concurrent assessment of hepatic and intestinal cytochrome P450 3A activities using deuterated alfentanil.

Alfentanil (ALF) is a validated probe for hepatic, first-pass, and intestinal cytochrome P450 (CYP) 3A activity, using plasma clearances, single-point concentrations, and noninvasive pupil diameter change (miosis). Assessing intravenous (i.v.) and oral drug disposition typically requires separate dosing. This investigation evaluated concurrent administration of oral deuterated and i.v. unlabeled ALF to assess both intestinal and hepatic CYP3A, and compare sequential and simultaneous dosing. ALF disposition was evaluated after strong hepatic and/or intestinal CYP3A induction and inhibition by rifampin, ketoconazole, and grapefruit juice. Using plasma ALF concentrations and area under the curve (AUC), clearance, or single-point concentrations, both simultaneous and sequential dosing provided equivalent results and detected hepatic and intestinal CYP3A induction and inhibition. Miosis better detected CYP3A modulation with sequential vs. simultaneous dosing. These results show that concurrent administration of oral deuterated and i.v. ALF, either sequentially or simultaneously, is an efficient and effective approach to assessing hepatic and intestinal CYP3A activity.

Blinded subjective rankings as a method of assessing treatment effect: a large sample example from the Systolic Hypertension in the Elderly Program (SHEP).

Because many randomized clinical trials study more than one important outcome variable, evaluation of efficacy is often difficult and not completely satisfactory. This paper considers the use of a procedure for endpoint determination described by Follmann et al., that allows raters to integrate subjectively all relevant information about an individual's clinical course into a single univariate assessment. To explore the method's feasibility, we tested the procedure with data from a completed clinical trial, the Systolic Hypertension in the Elderly Program (SHEP). We provided raters blinded to treatment assignment with cards that schematically represent the clinical trajectories of SHEP study participants. The raters independently ranked these trajectories. The method combined ranks across raters to determine a single rank for each study participant; we used a rank procedure to test treatment effect. The major findings were: (i) the raters showed a high level of concordance of rankings; (ii) tests of treatment effect were highly statistically significant; (iii) three statistical methods were effective for implementing the ranking in the large study size case. These methods were use of: (a) scoring rules; (b) incomplete block designs, and (c) categorical ranking.

Field trials of an asexual blood stage malaria vaccine: studies of the synthetic peptide polymer SPf66 in Thailand and the analytic plan for a phase IIb efficacy study.

Several years ago the Walter Reed Army Institute of Research (WRAIR) initiated an independent analysis of the candidate malaria blood stage vaccine SPf66. WRAIR contracted for the synthesis and formulation of SPf66 in United States Food and Drug Administration (FDA) inspected laboratories within the U.S., and in 1992, filed an Investigational New Drug (IND) application with the FDA. Preclinical studies indicated that the vaccine could be synthesized to meet its release specifications, and when adjuvanted with alum, was essentially equivalent to Colombian produced SPf66 in regards to immunogenicity in preclinical studies of rodents and primates, and in human volunteers in Phase I studies. The goal of these efforts was ultimately to conduct a Phase IIb field trial to determine the safety and efficacy of SPf66 produced under current Good Manufacturing Practices (cGMP). Such a trial is currently underway in a malaria endemic refugee camp along the Thai-Burmese border. Here we briefly describe the study and present the formal analytic plan that was submitted to regulatory authorities in the United States for analysis of the study results. We believe such independent confirmatory studies are an essential part of the vaccine development process and are required to provide important data regarding the safety and efficacy of candidate vaccines in diverse geographical regions, and as a means to assess their role in the context of broader malaria control programmes.

Rapid enzymatic method for the measurement of mannitol in urine.

A previously described method for mannitol in urine has been modified and improved. End product inhibition by fructose in the mannitol dehydrogenase method for mannitol has been minimized; the assay is linear over a sample mannitol concentration range of 0-12 mmol/L; no significant interference from other sugars or sugar alcohols could be demonstrated. The method is precise (within-batch CV less than 1%), rapid and shows excellent recovery of mannitol in spiked samples. Comparison with gas liquid chromatography shows excellent correlation (r = 0.994) between the two methods.

EMG needle electrodes: electrical impedance.

The electrical impedance of samples of stainless-steel monopolar needle electrodes and concentric electrodes from 3 manufacturers were measured in 154mM saline solution using sine-wave excitation at 4 frequencies from 10Hz to 10kHz. Current densities of less than 2.5x10(-5) amp/cm2 were used. Measurements on both needle and fine-wire electrodes were also made in live rats. Linear dimensions of the exposed tips were measured from which the areas of exposure were calculated. Surface areas of the monopolar needles varied between 0.06 and 0.15mm2. Presoaking of the electrodes for 20 minutes in saline solution containing a small concentration of a wetting agent produced a sixfold to twentyfold reduction in impedance. The average impedance magnitudes of the monopolar electrodes ranged from 1.4 megohms (Momega) at 10Hz to 6.6 kolohms (komega at 10kHz. The phase angle of the impedance due to the capacitive component of the needle-electrolyte impedance ranged between -45 and -71 degrees. The reduction in impedance resulting from presoaking and the concomitant reduction in electronic noise would be an advantage in observing lowamplitude potentials.