Evaluation of Incremental Siliconization Levels on Soluble Aggregates, Submicron and Subvisible Particles in a Prefilled Syringe Product.

The evaluation of stability with respect to particles in prefilled syringes is complicated by the presence of silicone oil. The mobility, colloidal characteristics, and kinetic instability of silicone oil in contact with a protein formulation may be influenced in unpredictable ways by pharmaceutical variables, storage, and handling conditions. To provide insight into the impact of these variables on silicone oil originating specifically from the siliconized prefillable syringe (PFS), a series of studies were conducted at incremental syringe barrel siliconization levels.

Orthogonal Methods for Characterizing the Unfolding of Therapeutic Monoclonal Antibodies: Differential Scanning Calorimetry, Isothermal Chemical Denaturation, and Intrinsic Fluorescence with Concomitant Static Light Scattering.

Evaluating prospective protein pharmaceutical stability from accelerated screening is a critical challenge in biotherapeutic discovery and development. Measurements of protein unfolding transitions are widely employed for comparing candidate molecules and formulations; however, the interrelationships between intrinsic protein conformational stability and pharmaceutical robustness are complex and thermal unfolding measurements can be misleading. Beyond the discovery phase of drug development, astute formulation design is one of the most crucial factors enabling the protein to resist damage to its higher order structure-initially from bioprocessing stresses, then from stresses encountered during its journey from the product manufacturing site to the bloodstream of the patient.

Examination of thermal unfolding and aggregation profiles of a series of developable therapeutic monoclonal antibodies.

Screening for pharmaceutically viable stability from measurements of thermally induced protein unfolding and short-term accelerated stress underpins much molecule design, selection, and formulation in the pharmaceutical biotechnology industry. However, the interrelationships among intrinsic protein conformational stability, thermal denaturation, and pharmaceutical stability are complex. There are few publications in which predictions from thermal unfolding-based screening methods are examined together with pharmaceutically relevant long-term storage stability performance.

Amyloid histology stain for rapid bacterial endospore imaging.

Bacterial endospores are some of the most resilient forms of life known to us, with their persistent survival capability resulting from a complex and effective structural organization. The outer membrane of endospores is surrounded by the densely packed endospore coat and exosporium, containing amyloid or amyloid-like proteins. In fact, it is the impenetrable composition of the endospore coat and the exosporium that makes staining methodologies for endospore detection complex and challenging.

Healthcare utilization in community-acquired pneumonia episodes of care: a comparison across the continuum of managed care.

Objective: Compare healthcare utilization and total payments for community-acquired pneumonia (CAP) episodes-of-care among 5 health plan designs spanning the continuum of managed care.

Research Design: Medical and prescription claims analysis of CAP episodes among enrollees of employer-sponsored health plans. Episode characteristics, healthcare utilization, and payments were compared across fee-for-service, Preferred Provider Organizations (PPO), point of service, partial capitation, and Health Maintenance Organizations as defined by the employers.

The influence of age and body mass index on the metabolic syndrome and its components.

Objective: The aim of this study was to evaluate the influence of ageing and body mass index (BMI) on the revised National Cholesterol Education Program (NCEP)-defined metabolic syndrome, its components, diabetes and coronary heart disease prevalence using the Third National Health and Nutrition Examination Survey.

Methods: Data from adults aged 20 and older who received morning physical examinations after a fast of at least 9 h (n = 7959), representing 196.8 million Americans were used in this analysis.

Nonlithographic fabrication of microfluidic devices.

A facile nonlithographic method for expedient fabrication of microfluidic devices of poly(dimethylsiloxane) is described. Positive-relief masters for the molds are directly printed on smooth substrates. For the formation of connecting channels and chambers inside the polymer components of the microfluidic devices, cavity-forming elements are adhered to the surfaces of the masters.

Reassessment of cardiovascular risk in diabetes.

Purpose Of Review: To review recent trials and reassess cardiovascular risk in people with diabetes.

Recent Findings: Recent clinical trials have tended to focus on lower-risk participants with diabetes who have had event rates considerably lower than participants in the early lipid trials. Statin studies have generally shown benefit in those without cardiovascular disease and at lower levels of low-density lipoprotein cholesterol.

Impact of 3-tier pharmacy benefit design and increased consumer cost-sharing on drug utilization.

Objective: To estimate responsiveness of prescription demand within 9 therapeutic classes to increased cost-sharing compared with constant cost-sharing.

Study Design: Retrospective prescription claims analysis.

Methods: Between 1999 and 2001, 3 benefit plans changed from a 2-tier to a 3-tier design (cases); 1 plan kept a 2-tier design (controls).

Estimating cholesterol treatment rates among individuals with multiple risk factors and without coronary heart disease.

This retrospective study examined lipid-lowering therapy treatment rates from 2000 to 2001 using the Ingenix LabRx Database. Patients with multiple risk factors without coronary heart disease were identified based on the presence of >/=2 of the following: men >/=45 years, women >/=55 years, hypertension, high-density lipoprotein cholesterol <40 mg/dl, total cholesterol >/=200 mg/dl, or obesity. Lipid treatment rates were estimated among those needing therapy (defined as low-density lipoprotein cholesterol >/=130 mg/dl or currently receiving lipid-lowering therapy).

Pharmacy benefits and the use of drugs by the chronically ill.

Context: Many health plans have instituted more cost sharing to discourage use of more expensive pharmaceuticals and to reduce drug spending.

Objective: To determine how changes in cost sharing affect use of the most commonly used drug classes among the privately insured and the chronically ill.

Design, Setting, And Participants: Retrospective US study conducted from 1997 to 2000, examining linked pharmacy claims data with health plan benefit designs from 30 employers and 52 health plans.

NCEP-defined metabolic syndrome, diabetes, and prevalence of coronary heart disease among NHANES III participants age 50 years and older.

Although the individual components of the metabolic syndrome are clearly associated with increased risk for coronary heart disease (CHD), we wanted to quantify the increased prevalence of CHD among people with metabolic syndrome. The Third National Health and Nutrition Examination Survey (NHANES III) was used to categorize adults over 50 years of age by presence of metabolic syndrome (National Cholesterol Education Program [NCEP] definition) with or without diabetes. Demographic and risk factor information was determined for each group, as well as the proportion of each group meeting specific criteria for metabolic syndrome.

Distributions of intramolecular distances in the reduced and denatured states of bovine pancreatic ribonuclease A. Folding initiation structures in the C-terminal portions of the reduced protein.

The purpose of this investigation is to characterize the reduced state of RNase A (r-RNase A) in terms of (i) intramolecular distances, (ii) the sequence of formation of stable loops in the initial stages of folding, and (iii) the unfolding transitions induced by GdnHCl. This is accomplished by identifying specific subdomain structures and local and long-range interactions that direct the folding process of this protein and lead to the native fold and formation of the disulfide bonds. Eleven pairs of dispersed sites in the RNase A molecule were labeled with fluorescent donor and acceptor probes, and the distributions of intramolecular distances (IDDs) were determined by means of time-resolved dynamic nonradiative excitation energy transfer (TR-FRET) measurements.

Diabetes mellitus, impaired fasting glucose, atherosclerotic risk factors, and prevalence of coronary heart disease.

Patients with diabetes mellitus (DM), both diagnosed (history of) and undiagnosed (by fasting glucose [FG] only), as well as impaired FG have an increased risk of coronary heart disease (CHD), compared with those with normal FG. Elevations in FG levels, even in normoglycemic subjects (<110 mg/dl), may be significantly related to CHD morbidity and mortality. Improving lipid profiles and blood pressure can decrease both CHD morbidity and mortality in these patients.

Patients with prior fractures have an increased risk of future fractures: a summary of the literature and statistical synthesis.

Numerous studies have reported increased risks of hip, spine, and other fractures among people who had previous clinically diagnosed fractures, or who have radiographic evidence of vertebral fractures. However, there is some variability in the magnitudes of associations among studies. We summarized the literature and performed a statistical synthesis of the risk of future fracture, given a history of prior fracture.

Enhanced access to primary care for patients with congestive heart failure. Veterans Affairs Cooperative Study Group on Primary Care and Hospital Readmission.

Objective: To determine whether enhanced access to primary care affects the diagnostic evaluation, pharmacologic management, or health outcomes of patients hospitalized with congestive heart failure (CHF).

Design: Multisite randomized, controlled trial.

Setting: Nine Veterans Affairs medical centers.

Race, treatment, and survival among colorectal carcinoma patients in an equal-access medical system.

Background: The aim of this study was to assess the influence of race on the treatment and survival of patients with colorectal carcinoma.

Methods: This retrospective cohort study included all white or black male veterans given a new diagnosis of colorectal carcinoma in 1989 at Veterans Affairs Medical Centers nationwide. After adjusting for patient demographics, comorbidity, distant metastases, and tumor location, the authors determined the likelihood of surgical resection, chemotherapy, radiation therapy, and death in each case.

The cost-effectiveness of a clinical pharmacist intervention among elderly outpatients.

We estimated the cost and cost-effectiveness of a clinical pharmacist intervention known to improve the appropriateness of drug prescribing. Elderly veteran outpatients prescribed at least five drugs were randomized to an intervention (105 patients) or control (103) group and followed for 1 year. The intervention pharmacist provided advice to patients and their physicians during all general medicine visits.

Adverse events after discontinuing medications in elderly outpatients.

Background: Discontinuation of drug therapy is an important intervention in elderly outpatients receiving multiple medications, but it may be associated with adverse drug withdrawal events (ADWEs).

Objective: To determine the frequency, types, timing, severity, and factors associated with ADWEs after discontinuing medications in elderly outpatients.

Patients: One hundred twenty-four ambulatory elderly participants in 1-year health service intervention trial at the Durham Veterans Affairs General Medicine Clinic in Durham, NC, who stopped taking medications.

Adverse drug events in high risk older outpatients.

Objective: To describe the prevalence, types, and consequences of adverse drug events (ADEs) in older outpatients with polypharmacy.

Design: A cohort study.

Setting: General Medicine Clinic at the Durham Veterans Affairs Medical Center.

Influence of projected complication rates on estimated appropriate use rates for carotid endarterectomy. Appropriateness Project Investigators. Academic Medical Center Consortium.

Objective: To examine specifically the influence of estimated perioperative mortality and stroke rate on the assessment of appropriateness of carotid endarterectomy.

Data Sources/study Setting: An expert panel convened to rate the appropriateness of a variety of potential indications for carotid endarterectomy based on various rates of perioperative complications. We then applied these ratings to the charts of 1,160 randomly selected patients who had carotid endarterectomy in one of the 12 participating academic medical centers.

Reliability of a modified medication appropriateness index in ambulatory older persons.

Objective: To evaluate the reliability of a medication appropriateness index (MAI) modified for elderly outpatients in a non-Veterans Affairs setting.

Design: Reliability study.

Setting: General community.

Reliability of drug utilization evaluation as an assessment of medication appropriateness.

Objective: To test the reliability of drug utilization evaluation (DUE) applied to medications commonly used by the ambulatory elderly.

Methods: A DUE model was developed for four domains: (1) justification for use, (2) critical process indicators, (3) complications, and (4) clinical outcomes. DUE criteria specific to use in the elderly were developed for angiotensin-converting enzyme (ACE) inhibitors and histamine2 (H2)-antagonists, and consensus was reached by an external expert panel.