Alternative Mode Of Administration Research Articles

Exploring the Comparability of Face-to-Face Versus Video Conference-Based Composite Time Trade-Off Interviews: Insights from EQ-5D-Y-3L Valuation Studies in Belgium and Spain.

BackgroundFace-to-face interviews are recommended for the collection of composite time trade-off (cTTO) data. The coronavirus disease 2019 (COVID-19) social distancing measures made researchers consider videoconferencing interviews as an alternative mode of administration, but little evidence about the implementation of videoconferencing in valuation studies is available. This study provides insights into the effect of videoconferencing on the quality of data, evaluating interviewers’ and respondents’ engagement level in videoconferences compared with face-to-face interviews.MethodsWe used cTTO data collected in Belgium and Spain following the EQ-5D-Y-3L valuation protocol. Due to the COVID-19 pandemic, both projects interrupted the face-to-face data collection before reaching the target sample. The remaining interviews were conducted by videoconference. We compared both modes of administration in terms of interviewers’ engagement (task duration and number of moves in each example) and respondents’ engagement (task duration and proportions of specific response values, in half-year units). To minimise interviewers’ learning effects, we split our sample into three groups: (1) first 20 interviews conducted face-to-face; (2) subsequent interviews conducted face-to-face; and (3) videoconferencing interviews.ResultsThe comparison between videoconferencing and subsequent face-to-face interviews showed the interviewer’s engagement was not affected by the mode of administration as almost no significant results were found either in the task duration or the numbers of moves shown in the examples. Similarly, none of the respondents’ task duration or proportion of specific responses or half-year units were affected by the mode of administration in either of the two countries.ConclusionsNo evidence suggested that the quality of cTTO data is reduced when using videoconferencing compared with face-to-face interviews.

Patient Preferences for Treating "OFF" Episodes in Parkinson's Disease: A Discrete Choice Experiment.

IntroductionSeveral on-demand treatments are available for management of “OFF” episodes in patients with Parkinson’s disease (PD). We evaluated patients’ preferences for features of theoretical on-demand treatment options.MethodsIn a discrete choice experiment, US adults with self-reported PD of ≥5 years, or <5 years with “OFF” episodes, taking oral carbidopa/levodopa, selected between pairs of theoretical on-demand treatments that varied by mode of administration (with and without mode-specific adverse events [AEs]), time to FULL “ON,” duration of “ON,” and out-of-pocket cost for a 30-day supply. Data were analyzed with a random parameters logit model; results were used to calculate relative importance of treatment attributes, preference shares, and willingness to pay.ResultsAmong 300 respondents, 98% had “OFF” episodes. Across the range of attribute levels included in the survey, avoiding $90 cost was most important to respondents, followed by a preferable mode of administration with associated AEs and decreasing time to FULL “ON.” Duration of “ON” was relatively less important. On average, respondents preferred a theoretical dissolvable sublingual film versus other theoretical treatments with alternative modes of administration. Respondents were willing to pay $28–$52 US dollars to switch from least- to more-preferred mode of administration with associated AEs, $58 to reach FULL “ON” in 15 versus 60 min, and $9 to increase duration of FULL “ON” from 1 to 2 h.ConclusionRespondents with PD valued lower out-of-pocket cost and a sublingual mode of administration with its associated AEs when choosing an on-demand treatment for “OFF” episodes.

Local anaesthesia in dentistry – achieving effective painless injections

A feared aspect of dental care for patients is their expectation of pain and injections. Local anaesthesia in dentistry is an important means of reducing procedural pain and increasing patient comfort during treatment. However, it can be a source of pain in itself. Fear of needles and painful injections is a significant contributing factor to dental anxiety and is a commonly reported concern among patients. This review aims to discuss modes by which the painless and effective injection can be achieved, exploring the causative factors of discomfort and how they can be modulated. Although a wide array of techniques and technologies exist within the field of local anaesthesia (which are outlined in this paper), there is no definitive method for delivering the perfect injection for each and every patient. By being more mindful of current research and understanding with regards to local anaesthesia, however, clinicians may become more confident in their ability to provide a more atraumatic experience. CPD/Clinical Relevance: The aim of this review is to make clinicians aware of evidence-based suggestions for reducing the discomfort associated with delivering conventional local anaesthesia in routine dental practice, as well as to inform clinicians about alternative modes of administration of local anaesthesia which may serve as adjuncts in the management of anxious patients.

Occular Drug Delivery System – A Review

The unique Anatomy of the eye makes it a highly protected organ and unique structure restricts entry of the drug into the target site of action. Designing an effective therapy for ocular diseases has been considered as a difficult task. Major barriers in eye medication are the ability to maintain a therapeutic level of the drug at the site of action. Therapeutic drug levels are not maintained for a longer duration in target tissues. Limitations of the traditional route of administration have challenged scientists to find an alternative mode of administration like periocular routes. The ophthalmic formulations are available as buffered, isotonic, sterile solution. A number of types of dosage forms are applied as the drug delivery system for the ocular delivery. The topical ocular drop is the most suitable and patient compliant route of drug administration, especially for the management of anterior segment diseases. Ideal ophthalmic drug formulation must be able to prolong the drug release and to remain in the area of the front of the eye for prolong period. It is necessary to optimize ophthalmic drug delivery; one way to do so is by adding polymers, development of in situ gel or using erodible or nonerodible insert orcolloidal suspension to extend the precorneal drug retention.

From the voices of people with haemophilia A and their caregivers: Challenges with current treatment, their impact on quality of life and desired improvements in future therapies.

IntroductionHaemophilia A is a chronic disease requiring frequent intravenous infusions of recombinant factor VIII. Previous studies have shown that challenges associated with current treatments may have significant impacts on quality of life (QoL) that are as important as the health outcomes conferred by the therapy. Emerging therapeutic innovations offer the potential to mitigate treatment‐related challenges, and it is therefore important to develop a better understanding of patient and caregiver experiences with existing haemophilia A treatments in order to characterize the full value of new treatments.AimTo gather firsthand perspectives from people with haemophilia A (PWHA) and caregivers on the challenges with current treatment, their impact on QoL and desired improvements in future therapies.MethodsQualitative insights were gathered from 20 non‐inhibitor PWHA or caregivers of PWHA across Canada through one‐on‐one interviews; insights were further explored through focus group sessions to uncover overarching themes and prioritize issues with current treatments.ResultsPWHA and caregivers identified several challenges, including administration of intravenous infusions, coordination of treatment schedules and ensuring adequate medication and supplies. Participants described how these challenges impact psychosocial well‐being, physical health, personal/social life and work. Alternate modes of administration and longer‐lasting treatment effects were identified as desired improvements over current treatments.ConclusionThis study emphasizes the impact that existing haemophilia A treatments have on psychological well‐being, employment opportunities and adherence to treatment regimens. These considerations may help to inform decision‐making for policymakers and health systems around the true value of new therapies entering the haemophilia market.

Gelatin Porous Scaffolds as Delivery Systems of Calcium Alendronate

The systemic administration of bisphosphonates (BPs) for the treatment of metabolic diseases characterized by abnormal bone loss suffers from several adverse side effects, which can be reduced by implementation of alternative modes of administration. In this work, glutaraldehyde cross-linked gelatin scaffolds are proposed as delivery systems of calcium alendronate monohydrate (CaAL•H2 O). The 3D highly porous scaffolds display a relevant interconnected porosity (>94%), independently from CaAL•H2 O content (0, 3, and 6 wt%). At variance, pore size varies with composition. The relative increase of the number of smaller pores on increasing BP content is in agreement with the parallel significant increase of the compressive modulus and collapse strength. The scaffolds exhibit a sustained CaAL•H2 O release profile, and a significant amount of the drug is retained in the scaffolds even after 14 d. In vitro tests are carried out using cocultures of osteoblast (OB) and osteoclast (OC). The evaluation of differentiation markers is performed both on the supernatants of cell culture and by means of quantitative polymerase chain reaction. The results indicate that BP containing scaffolds support osteoblast proliferation and differentiation, whereas they inhibit osteoclast viability and activity, displaying a promising beneficial role on bone repair processes.

Nanosized Drug Delivery Systems for Direct Nose to Brain Targeting: A Review.

Drug targeting to brain has always been problematic due to Blood-Brain Barrier (BBB), which, does not allow most of the drugs to pass through it as they are hydrophilic and macromolecular drugs. So, in order to bypass the BBB, alternative modes of administration were searched and nasal to brain delivery route was tried by many workers. Such studies yielded patented nano-formulations with the ability to cross blood brain barrier. Nanoparticles being smaller in size and large surface area help in increasing the rate of drug permeation to the brain. In this review work, emphasis has been laid on discussion on various works done in the field of nasal delivery of drugs to brain over the last decade. The works that are discussed in this paper show better drug targeting of brain when given through nasal route as nanoparticles. Experiments performed in animal models have clearly exhibited that nano-sized formulations are able to facilitate the delivery of drugs to brain through nose in comparison to tantamount drug solutions. However, it is not yet confirmed whether the drug is freed from the formulation in the nasal cavity and then absorbed or the nanoparticles themselves are absorbed and then the drug is released in the CNS. Furthermore, the toxicity studies were not carried out extensively in suitably designed model, which should be considered before going for further studies and application.

Population Pharmacokinetics and Pharmacodynamics of Piperacillin/Tazobactam in Patients with Nosocomial Infections

The study was to establish a population pharmacokinetic (PPK) model of piperacillin (PIP) and tazobactam (TAZ) that explain pharmacokinetic variability and to propose optimized dosage regimens in patients with nosocomial infections. In total, 310 PIP and 280 TAZ concentration-time points were collected at steady state over multiple dosing intervals from 50 patients who received PIP/TAZ infused within 30min or over 3h. Drug analysis was performed by high-performance liquid chromatography (HPLC). Nonlinear mixed effects modeling was employed to develop PPK model and 1000 Monte Carlo simulation was used to predict the probability of target attainment (PTA) with a target time of non-protein-bound concentration above MIC>50% of the dosing interval. A model with one-compartment model had the best predictive performance for the PPK model. The population estimates of PIP were 13.8L/h (31.1%) for clearance (CL) and 21.7 L (38%) for volume of distribution (V). The population estimates of TAZ were 9.3L/h (29.1%) for CL and 16L (35.3%) for V. Influence of creatinine clearance (CLcr) and body weight were identified as important covariates for PIP/TAZ CL and V, respectively. A 30-min infusion of 4g every 6h achieved robust (≥90%) PTAs for MIC≤16mg/L. As an alternative mode of administration, a 3-h infusion of 4g every 6h achieved robust PTAs for Pseudomonas aeruginosa and Klebsiella pneumoniae. Prolonged infusions achieved better PTAs compared with shorter infusions at similar daily doses. This benefit was most pronounced for MICs between 16 and 40mg/L.

Correlates and Consequences of Opioid Misuse among High-Risk Young Adults.

Background. Prescription opioids are the most frequently misused class of prescription drug among young adults aged 18–25, yet trajectories of opioid misuse and escalation are understudied. We sought to model opioid misuse patterns and relationships between opioid misuse, sociodemographic factors, and other substance uses. Methods. Participants were 575 young adults age 16–25 who had misused opioids in the last 90 days. Latent class analysis was performed with models based on years of misuse, recency of misuse, and alternate modes of administration within the past 12 months, 3 months, and 30 days. Results. Four latent classes emerged that were differentially associated with heroin, cocaine, and methamphetamine use, tranquilizer misuse, daily opioid misuse, and opioid withdrawal. Alternate modes of administering opioids were associated with increased risk for these outcomes. Sociodemographic factors, homelessness, prescription history, and history of parental drug use were significantly associated with riskier opioid misuse trajectories. Conclusion. Young adults who reported more debilitating experiences as children and adolescents misused opioids longer and engaged in higher risk alternate modes of administering opioids. Data on decisions both to use and to alter a drug's form can be combined to describe patterns of misuse over time and predict important risk behaviors.

Effects of Yogurt and Applesauce on the Oral Bioavailability of Nilotinib in Healthy Volunteers

Nilotinib, a potent orally bioavailable BCR-ABL tyrosine kinase inhibitor, is currently available as a hard gelatin capsule that must be swallowed whole. For patients who may have difficulty swallowing the intact capsule, an alternative mode of administration is desirable. The authors compared the bioavailability of nilotinib from the following administrations in 48 healthy subjects: (1) 400 mg nilotinib given as two 200-mg nilotinib intact capsules; (2) contents of two 200-mg nilotinib capsules, each capsule dispersed in 1 teaspoon of nonfat plain yogurt; and (3) contents of two 200-mg nilotinib capsules, each capsule dispersed in 1 teaspoon of applesauce. Nilotinib absorption was modestly increased following the administration of nilotinib dispersed in yogurt. The geometric mean ratios (90% confidence intervals) for nilotinib C(max), AUC(0-tlast), and AUC(0-inf) were 1.31 (1.22-1.41), 1.11 (1.05-1.16), and 1.08 (1.02-1.15), respectively. Administration of nilotinib dispersed in applesauce showed equivalent bioavailability compared with administration of nilotinib as intact capsules. The geometric mean ratios (90% confidence intervals) for nilotinib C(max), AUC(0-tlast), and AUC(0-inf) were 0.95 (0.88-1.02), 0.99 (0.94-1.04), and 0.97 (0.90-1.03), respectively. Each treatment was well tolerated in the study subjects. The data support a feasible alternative method of nilotinib administration; each capsule's contents may be dispersed in 1 teaspoon of applesauce and taken immediately.

Two formulations of venlafaxine are bioequivalent when administered as open capsule mixed with applesauce to healthy subjects

Venlafaxine is a unique antidepressant approved for treatment of various depressive disorders. A single dose, cross-over bioequivalence study was performed with two different formulations of venlafaxine 150 mg extended-release capsules in which the contents of capsule were mixed with applesauce and administered to healthy subjects under fed condition. A total of 24 healthy adult male subjects participated in this randomized, single-dose, non-blinded, two-way crossover study conducted at a single centre and 23 subjects completed the study as per the study protocol. After an overnight fast of 10 h, a high-fat and high-calorie breakfast was served 30 min before dosing. The subjects then received a single dose of either formulation administered with apple sauce followed by 240 ml of water as per randomized schedule in each period separated by a washout period of 7 days. A series of blood samples were collected upto 72 h for estimation of venlafaxine and its active metabolite, O-desmethylvenlafaxine. The quantification of venlafaxine and O-desmethylvenlafaxine was done by LC-MS/MS method and pharmacokinetic and statistical analysis by WinNonlin® 5.2 and SAS® 9.1.3. The results of the study demonstrated bioequivalence of two formulations as the 90% confidence interval for the intra-individual mean ratio of log-transformed Cmax, AUC0-t and AUC0-inf of the test to the reference formulation were found within the defined bioequivalence range of 80.00%-125.00%. Both the formulations were well tolerated. This alternative mode of administration may provide benefits to patients who have difficulty in swallowing the capsule as a whole.

Nonlinear pharmacokinetics of piperacillin in healthy volunteers--implications for optimal dosage regimens.

(i) To describe the first-order and mixed-order elimination pathways of piperacillin, (ii) to determine the between occasion variability (BOV) of pharmacokinetic parameters and (iii) to propose optimized dosage regimens. We performed a five-period replicate dose study in four healthy volunteers. Each subject received 4g piperacillin as a single 5min intravenous infusion in each study period. Drug analysis was performed by HPLC. We used NONMEM and S-ADAPT for population pharmacokinetic analysis and Monte Carlo simulation to predict the probability of target attainment (PTA) with a target time of non-protein bound concentration above MIC >50% of the dosing interval. A model with first-order nonrenal elimination and parallel first-order and mixed-order renal elimination had the best predictive performance. For a 70kg subject we estimated 4.40lh(-1) for nonrenal clearance, 5.70lh(-1) for first-order renal clearance, 170mgh(-1) for V(max) , and 49.7mgl(-1) for K(m) for the mixed-order renal elimination. The BOV was 39% for V(max) , 117% for K(m) , and 8.5% for total clearance. A 30min infusion of 4g every 6h achieved robust (≥90%) PTAs for MICs ≤12mgl(-1) . As an alternative mode of administration, a 5h infusion of 6g every 8h achieved robust PTAs for MICs ≤48mgl(-1) . Part of the renal elimination of piperacillin is saturable at clinically used doses. The BOV of total clearance and volume of distribution were low. Prolonged infusions achieved better PTAs compared with shorter infusions at similar daily doses. This benefit was most pronounced for MICs between 12 and 48mgl(-1) .

Using factor analysis to confirm the validity of children's self-reported health-related quality of life across different modes of administration

The measurement of pediatric health-related quality of life (HRQOL) in pediatric medicine and health services research has grown significantly over the past decade. While HRQOL instruments are often administered in clinic settings, alternative modes of administration are also utilized such as mail and telephone surveys. In order for comparisons across in-person, mail, and telephone administration to be valid, items on a HRQOL measure must have equivalent meaning across mode of administration. That is, they must demonstrate factorial invariance (stable factor structure) across mode of administration. The objective of the present study was to implement the multigroup confirmatory factor analysis (CFA) method for invariance testing across mode of administration for children's self-reported HRQOL. Multigroup CFA was performed specifying a five-factor model across three modes of administration groups (in-person, mail, and telephone survey). The 23-item PedsQL(TM) 4.0 Generic Core Scales was utilized as the measure of children's self-reported HRQOL in a sample of 3741 children ages 5-18. Strong factorial invariance across the mode of administration groups was demonstrated based on stability of the Comparative Fit Index (CFI) between the models, and several additional indices of practical fit including the Root Mean Squared Error of Approximation (RMSEA), the Non-Normed Fit Index (NNFI), and the Parsimony Normed Fit Index (PNFI). The mode of administration subpopulations in our study differed with regard to health status. The multigroup CFA statistical methods utilized in the present study have important implications for clinical trials in which mixed modes of administration are used. The present findings support an equivalent five-factor structure of the PedsQL( TM) 4.0 Generic Core Scales across the three modes of administration studied. Based on these data, it can be concluded that children across the three modes of administration groups interpreted items on the PedsQL( TM) 4.0 Generic Core Scales in a similar manner.

TAK-390MR, a Novel Dual Delayed Release Formulation of a PPI, Is Bioequivalent When Administered as Granules Sprinkled Over Applesauce or as an Intact Capsule

Purpose: Alternative oral delivery options are useful for patients who prefer or require administration flexibility. TAK-390MR is a Dual Delayed Release™ (DDR) formulation of TAK-390, an enantiomer of lansoprazole, designed to prolong the plasma concentration-time profile of TAK-390 following oral once-daily administration. We compared the bioavailability of TAK-390MR given as granules from an intact capsule sprinkled over applesauce vs an intact capsule. Methods: In this phase 1, open-label, 2-way crossover study, 60 healthy subjects (18–55 years of age) were randomized to 2 sequence groups that determined the order in which they received a single oral dose of TAK-390MR 90 mg administered as granules from a capsule sprinkled over 1 tablespoon of applesauce or as an intact capsule with 240 mL of water after approximately a 10-hour fast. The dosing in each of the 2 study periods was separated by a ≥5 day washout interval. Blood samples were collected predose and up to 24 hours postdose in each period. Plasma concentrations were analyzed by a validated LC-MS/MS assay. Pharmacokinetic parameters were estimated using standard noncompartmental methods. Bioequivalence was assessed by point estimates and 90% CIs for the ratios of the central values for the Cmax, AUCt, and AUC∞ of TAK-390 using ANOVA. Results: A total of 50 subjects were included in the bioequivalence analysis. The mean concentration-vs-time profiles for the 2 regimens were nearly superimposable, with the characteristic 2 plasma peaks resulting from the DDR technology. The point estimates and corresponding 90% CIs for the ratios of the central values of the Cmax, AUCt, and AUC∞ of TAK-390 following administration of TAK-390MR as granules sprinkled over applesauce vs as an intact capsule were within the bioequivalency range of 0.80–1.25. TAK-390MR was well tolerated in healthy subjects in this study by either mode of administration. Conclusion: Bioequivalence was demonstrated when TAK-390MR was administered either as granules sprinkled over applesauce or as an intact capsule. This alternative mode of administration may benefit patients who prefer or require an alternate route of administration.Table: Bioavailability of TAK-390 After Administration of TAK-390MR 90 mg as Granules Sprinkled Over Applesauce Relative to an Intact Capsule

Development of EMPRO: A Tool for the Standardized Assessment of Patient-Reported Outcome Measures

Objective This study was aimed to develop a tool for the standardized assessment of patient-reported outcomes (PROs) to assist the choice of instruments. Methods An expert panel adapted the eight attributes proposed by the Medical Outcomes Trust as evaluation review criteria, created items to evaluate them, and included a response scale for each item. A pilot test was designed to test the new tool's feasibility and to obtain preliminary information concerning its psychometric properties. The Spanish versions of five measures were selected for assessment: the SF-36 Health Survey, the Nottingham Health Profile, the COOP-WONCA charts, the EuroQol-5D, and the Quality of Life Questionnaire EORTC-QLQ-C30. We assessed the new tool's reliability (Cronbach's alpha and intraclass correlation coefficient [ICC]) and construct validity. Results The new EMPRO (Evaluating the Measurement of Patient-Reported Outcomes) tool has 39 items covering eight key attributes: conceptual and measurement model, reliability, validity, responsiveness, interpretability, burden, alternative modes of administration, and cross-cultural and linguistic adaptations. Internal consistency was high (α = 0.95) as was interrater concordance (ICC: 0.87–0.94). Positive associations consistent with a priori hypotheses were observed between EMPRO attribute scores and the number of articles identified for the measures, the years elapsed since the publication of the first article, and the number of citations. Conclusion A new tool for the standardized assessment of PRO measures is available. It has shown good preliminary reliability and validity and should be a useful aid to investigators who need to choose between alternative measures. Further assessment of the tool is necessary.

Therapeutic drug monitoring of vancomycin in severe sepsis and septic shock

The sudden changes (increase in capillary permeability, edema formation, vasodilation and hypotension) observed in septic patients and the measurements taken in order to revert this situation make vancomycin concentrations difficult to interpret. Therapeutic drug monitoring (TDM) of vancomycin is routinely performed at steady state, target concentrations are peaks between 20 and 40 mg/l and troughs of 5-10 mg/l. Lately, continuous infusion of vancomycin (CIV) has been used as an alternative mode of administration mainly in critically ill patients with sepsis or septic shock. Despite this novel mode of administration, the need of drug monitoring in this population is under discussion. The aim of our study was to test the usefulness of a multi-compartment model in order to understand the rapid changes that occur in critically ill patients. A prospective, cohort study was carried out in the intensive care unit of the University Hospital. 25 intensive care unit adults patients with severe sepsis or septic shock receiving vancomycin in CIV modality for documented gram-positive infections were included in the study. Once the infusion was started, blood samples were drawn periodically and analyzed by fluorescence polarisation immunoassay (FPIA, TDx, Abbott Laboratories, Chicago, IL, USA). A multi-compartment model was used to predict vancomycin level evolution throughout the treatment of patients with sepsis. High doses of vancomycin were administered in order to rescue patients from septic shock. Plasma drug concentration dropped while clinical condition of patients worsened. Conversely, drug levels increased spontaneously once the infection was reverted. The theoretical model provided greater insight into pharmacokinetic features related with the use of vancomycin in septic patients. There was consistency between the model based prediction and the experimental data so dose adjustment was performed in order to reach target concentrations above 20 mg/l and an initial dose of 3 grams of vancomycin per day was recommended to reach these levels.

Misoprostol and pregnancy: ever-increasing indications of effective usage.

The subject of misoprostol in the field of reproductive health care has courted much controversy. The aim of this review is to survey the literature published in this field over the past year, and to evaluate developments in this area. This article will cover termination of pregnancy, induction of labor and the issue of postpartum hemorrhage. The use of misoprostol as a single agent remains of clinical value when mifepristone is unavailable. The sublingual and rectal routes are alternative modes of administration. For induction of labor, the optimum dose and route of misoprostol is still undetermined. Lower doses of between 20 microg to 40 microg may increase the safety profile for labor induction. Misoprostol may be a useful adjunct to the therapeutic options available for the prevention and treatment of postpartum hemorrhage. There are many potential uses for misoprostol in pregnancy. However clinicians must judge the evidence and the emotive debate surrounding this field and decide how it will influence their clinical practice depending on the priorities of their own clinical circumstances.

Esomeprazole 40mg Capsules are Bioequivalent when Administered Intact or as the Contents Mixed with Applesauce*

This study was conducted to determine whether administration of the contents of an open capsule of esomeprazole (enteric-coated pellets) 40mg with applesauce is bioequivalent to administration of an intact capsule in healthy volunteers. 45 adult male and female volunteers participated in this randomised, single-dose, nonblinded, two-way crossover study conducted at a single centre. 41 volunteers completed the trial. Time to maximum plasma concentration (Cmax) for esomeprazole (tmax) was approximately 2.4 hours and elimination half-life (t1/2) was approximately 0.9 hours by either mode of administration. The ratios of the geometric means for Cmax and area under the plasma concentration-time curve (AUC) for capsule contents with applesauce relative to intact capsule were 0.93 (90% confidence interval [CI]: 0.86 to 1.01) and 0.99 (90% CI: 0.94 to 1.04), respectively. The finding that the 90% CIs were within 0.80 to 1.25 for both parameters indicates bioequivalence. Esomeprazole was well tolerated by the study group irrespective of mode of administration. Esomeprazole is bioequivalent when administered either as an intact capsule or as the contents of a capsule mixed with applesauce in healthy volunteers. This latter alternative mode of administration may provide benefits to patients who have difficulty swallowing.

Patient-centered quality measures for Asian Americans: research in progress.

We aim to develop and validate a questionnaire that examines quality of care from the patient's perspective for limited-English-proficient Asian Americans (AA) of Chinese and Vietnamese descent. We will conduct focus groups of patients to identify issues important to them, with an emphasis on communication and access to care. We will then draft a questionnaire and test its validity using standard survey research methods and direct observation of patient-provider encounters. Subsequent field testing will involve face-to-face patient interviews 1 month after an outpatient visit. We will evaluate alternate modes of administration to test feasibility and to maximize response. The result of our study will be a validated, culturally sensitive, patient-centered instrument that measures health care quality for limited-English-proficient AA patients. Our research will provide a template for developing future quality measures for other vulnerable populations.

Physiology and molecular biology brought to single-cell level

This chapter reviews an antisense knockout approach that permits the direct correlation of a gene-expression pattern, in a living cell and in its native cellular environment, with the functional properties expressed by the targeted protein. The chapter discusses the strategy employed to assign biological functions to several native proteins found in excitable cells using a combination of antisense oligodeoxynucleotide approaches with electrophysiological techniques. Oligodeoxynucleotides corresponding to the antisense orientation of messenger RNAs coding for different proteins can be synthesized easily. These antisense probes specifically block the translation of the corresponding messages into proteins. For this approach to be effective, the oligonucleotide must be capable of crossing the cell membrane, of resisting nuclease degradation, and of hybridizing selectively to its target nucleotide sequence. Unmodified oligonucleotides are negatively charged and will not enter cells readily, but modification of the internucleoside phosphate linkages to uncharged methyl phosphonates enables the oligonucleotides to gain access to the cell interior when added to the incubation medium. An alternative mode of administration is by direct application of the oligonucleotides to the nucleus or the cytoplasm of individual cells either by microinjection using a sharp electrode or by diffusion from the patch electrode into the cytoplasm. In the latter approach, a sequential patch-clamp procedure allowed recording from the same cell, at several days' interval. Compared with the addition of antisense oligonucleotides to the cell medium, these two techniques are more direct and reliable. This chapter reviews briefly these two direct means of introducing the antisense probes into living cells.