Palliative medicine trainees be should learn about frailty: meta-synthesis and Delphi study to establish curriculum content.

OBJECTIVES: Frailty is common and highly associated with morbidity and mortality, a fact that has been highlighted by COVID-19. Understanding how to provide palliative care for frail individuals is an international priority, despite receiving limited mention in Palliative Medicine curricula or examinations worldwide. This study aimed to synthesise evidence and establish expert consensus on what should be included in a Palliative-Medicine Specialist Training Curriculum for frailty. METHODS: Literature Meta-synthesis conducted by palliative medicine, frailty and education experts produced a draft curriculum with Bologna based Learning-Outcomes. A Delphi study asked experts to rate the importance of Learning-Outcomes for specialist-training completion and propose additional Learning-Outcomes. This process was repeated until 70% consensus was achieved for over 90% of Learning-Outcomes. Experts divided Learning-Outcomes into specific (for inclusion in a frailty subsection) or generic (applicable to other palliative conditions). The Delphi panel was Subject Matter Experts: Palliative-Medicine Consultants (n=14) and Trainees (n=10), representing hospital, community, hospice and care home services and including committee members of key national training organisations. A final reviewing panel of Geriatric Medicine Specialists including experts in research methodology, national training requirements and frailty were selected. RESULTS: The meta-synthesis produced 114 Learning-Outcomes. The Delphi Study and Review by Geriatric Medicine experts resulted in 46 essential and 33 desirable Learning-Outcomes. CONCLUSIONS: This frailty curriculum is applicable internationally and highlights the complex and unique palliative needs of frail patients. Future research is required to inform implementation, educational delivery and service provision.

Patient activation is associated with healthy behaviors and ease in managing diabetes in an indigent population.

PURPOSE: The purpose of this study is to assess the validity of the patient activation construct as measured by the Patient Activation Measure (PAM) survey by correlating PAM scores with diabetes self-management behaviors, attitudes, and knowledge in a predominantly minority and uninsured population. METHODS: A convenience sample of patients presenting to an urban public hospital diabetes clinic was surveyed and contacted by phone 6 months later. The survey included questions about activation, health behaviors, and health care utilization. RESULTS: A total of 287 patients agreed to participate. Most were African American, female, and uninsured. Most respondents (62.2%) scored in the highest category of activation according to the PAM. Activated patients were more likely to perform feet checks, receive eye examinations, and exercise regularly. Activation was consistently associated with less reported difficulty in managing diabetes care but not with A1C knowledge. PAM scores at the initial interview were highly correlated with scores at 6-month follow-up. Activation level did not predict differences in health care utilization during the 6 months following the survey. CONCLUSIONS: Higher scores on the PAM were associated with higher rates of self-care behaviors and ease in managing diabetes; however, the indigent urban population reported higher activation scores than found in previous studies. The relationship between activation and outcomes needs to be explored further prior to expanding use of this measure in this patient population.

PDA Biosimilars Workshop Report (September 27-28, 2018)-Getting It Right the First Time for Biosimilar Marketing Applications.

This workshop report summarizes the presentations, the breakout session outcomes, and the speaker panel discussions from the PDA Biosimilars Workshop held September 27-28, 2018, in Washington, DC. This format was deliberately selected for the workshop with the expectation of delivering a post-workshop paper on current best practices and existing challenges for sponsors. The event, co-chaired by Dr. Stephan Krause (AstraZeneca Biologics) and Dr. Emanuela Lacana (CDER/FDA), was attended by 140 agency and industry representatives. The workshop was separated into three major sessions P1: Regulatory Perspective, P2: Challenges in Biosimilar Development, and P3: Demonstrating Analytical Similarity. Each of the three sessions started with agency and industry presentations. Participants then split into two concurrent roundtable discussion groups to hear the answers to questions that had been provided to all participants one week prior to the event. The sessions were recorded. This paper provides consolidated answers to specific case studies for current challenges to sponsors and agencies. In addition, the panel discussion notes following each breakout roundtable session, as well as brief talk summaries of all speakers, are provided. The first session explored the challenges encountered with submission of biosimilar marketing applications from the perspectives of regulatory agencies. Expectations for a successful submission of the chemistry, manufacturing, and controls (CMC) information were described. The second session addressed high-level technical challenges and how to avoid pitfalls frequently encountered during biosimilar candidate development, including data quality expectations, creation of the final control strategy, and strategic choices necessary for candidate selection and development. Both regulatory perspectives and industry experience were shared. The last session explored the use of statistical tools to provide meaningful contributions to the demonstration of analytical similarity. The presentations highlighted common issues and practical challenges that arise during the application of statistical tools.LAY ABSTRACT: Significant challenges are still-remaining for sponsors and agencies to successfully develop and license Biosimilars. A Biosimilars Workshop was therefore held on 27-28 September 2018 in Washington, DC, to find practical solutions to the remaining challenges. The workshop planning committee with members from industry and agencies prepared specific case studies focused on some of most difficult situations. The workshop was separated into three major sessions (P1 - Regulatory Perspective; P2 - Challenges in Biosimilar Development; P3 - Demonstrating Analytical Similarity) and each session attempted to provide practical solutions to the relevant case studies. This first session explored the challenges encountered with submission of biosimilar marketing applications from the regulatory agencies' perspectives. Expectations for a successful submission of the CMC information were described. The second session addressed high-level technical challenges frequently encountered during biosimilar candidate development, including data quality expectations, the creation of the final control strategy, and strategic choices necessary for candidate selection and development. The last session explored the use of statistical tools to provide meaningful contributions to the demonstration of analytical similarity and practical challenges that arise during the application of statistical tools.

Suture-reinforced electrospun polydioxanone-elastin small-diameter tubes for use in vascular tissue engineering: a feasibility study.

This study characterizes the cross-linking of electrospun elastin and the mechanical properties of suture-reinforced 1.5mm internal diameter electrospun tubes composed of blended polydioxanone (PDO) and soluble elastin. Several tube configurations were tested to assess the effects of reinforcement on tube mechanical properties. Between the electrospun layers of each double-layered prosthetic, zero, one or two 6-0 sutures were wound, maintaining 1mm spacing with a pitch of 9 degrees . Single-layered tubes without suture were also examined. Samples were cross-linked and tested for compliance and burst strength. Compliance decreased significantly (p <0.05) and burst strength significantly increased (p <0.01) with reinforcement. Uncross-linked tubes were also tested to determine the effects of cross-linking. Results demonstrated that cross-linking significantly decreases burst strength (p <0.01), while decreases in compliance for cross-linked tubes were not significant. Cross-linked suture-reinforced PDO-elastin tubes had burst pressures more than 10 times greater than normal systolic pressures and exhibited a range of compliance values, including those matching native artery. These tubes display many characteristics of the "ideal" small-diameter graft, having mechanical properties that can be tailored to match those desired in vascular replacement applications.

Sequential whole report accesses different states in visual working memory.

Working memory (WM) enables a rapid access to a limited number of items that are no longer physically present. WM studies usually involve the encoding and retention of multiple items, while probing a single item only. Hence, little is known about how well multiple items can be reported from WM. Here we asked participants to successively report each of up to 8 encoded Gabor patches from WM. Recall order was externally cued, and stimulus orientations had to be reproduced on a continuous dimension. Participants were able to sequentially report items from WM with an above-chance precision even at high set sizes. It is important that we observed that precision varied systematically with report order: It dropped steeply from the first to the second report but decreased only slightly thereafter. The observed trajectory of precision decrease across reports was better captured as a discontinuous rather than an exponential function, suggesting that items were reported from different states in visual WM. The following 3 experiments replicated these findings. In particular, they showed that the observed drop could not be explained by a retro-cueing benefit of the first report, a longer delay duration for later reports or a visual interference effect of the first report. Instead, executive interference of the first report reduced precision of subsequent reports. Together, the results show that a sequential whole-report procedure allows the assessment of qualitatively different states in visual WM. (PsycINFO Database Record

Performance of the 4Kscore Test in Plasma and Serum and Stability of the Component Analytes in Clinical Samples.

BACKGROUND: The 4Kscore Test determines a personalized risk score for aggressive prostate cancer by combining the blood sample measurements of total prostate-specific antigen (tPSA), free PSA (fPSA), intact PSA (iPSA), and human kallikrein-related peptidase 2 (hK2) with patient clinical information to generate the patient risk's score; thus, accuracy and precision of the 4Kscore depend on the reliability of these measurements. Although tPSA and fPSA are measured on a Food and Drug Administration (FDA)-approved platform, the performance of the iPSA and hK2 assays in the clinical setting has not previously been reported. METHODS: Analytical performance was determined for the iPSA and hK2 assays in both serum and EDTA plasma, according to Clinical and Laboratory Standards Institute guidelines. Equivalence of the 4Kscore in both sample matrices was demonstrated in a 353-patient clinical cohort, and the stability of endogenous iPSA and hK2 for at least 3 days was demonstrated in a smaller subset. RESULTS: Intralaboratory and interlaboratory precision of the iPSA and hK2 assays in both matrices was comparable with that of FDA-approved tPSA and fPSA assays (<18% for iPSA; <8% for hK2). The picogram per milliliter sensitivity and wide dynamic range of the iPSA and hK2 assays allowed for accurate measurements in the target population. The 4Kscore generated in either matrix up to 3 days after collection is equivalent to that measured within 24 h of collection (Passing-Bablok slope 95% CI: plasma, 0.999-1.034; serum, 0.997-1.040). CONCLUSIONS: The robust performance of component assays and reliable stability of the endogenous analytes in clinical samples proven here ensures an accurate 4Kscore Test result.

Nanofiber technology: designing the next generation of tissue engineering scaffolds.

Tissue engineering is an interdisciplinary field that has attempted to utilize a variety of processing methods with synthetic and natural polymers to fabricate scaffolds for the regeneration of tissues and organs. The study of structure-function relationships in both normal and pathological tissues has been coupled with the development of biologically active substitutes or engineered materials. The fibrillar collagens, types I, II, and III, are the most abundant natural polymers in the body and are found throughout the interstitial spaces where they function to impart overall structural integrity and strength to tissues. The collagen structures, referred to as extracellular matrix (ECM), provide the cells with the appropriate biological environment for embryologic development, organogenesis, cell growth, and wound repair. In the native tissues, the structural ECM proteins range in diameter from 50 to 500 nm. In order to create scaffolds or ECM analogues, which are truly biomimicking at this scale, one must employ nanotechnology. Recent advances in nanotechnology have led to a variety of approaches for the development of engineered ECM analogues. To date, three processing techniques (self-assembly, phase separation, and electrospinning) have evolved to allow the fabrication of nanofibrous scaffolds. With these advances, the long-awaited and much anticipated construction of a truly "biomimicking" or "ideal" tissue engineered environment, or scaffold, for a variety of tissues is now highly feasible. This review will discuss the three primary technologies (with a focus on electrospinning) available to create tissue engineering scaffolds that are capable of mimicking native tissue, as well as explore the wide array of materials investigated for use in scaffolds.

Cross-linking electrospun type II collagen tissue engineering scaffolds with carbodiimide in ethanol.

In trying to assess the structural integrity of electrospun type II collagen scaffolds, a modified but new technique for cross-linking collagen has been developed. Carbodiimides have been previously used to cross-link collagen in gels and in lyophilized native tissue specimens but had not been used for electrospun mats until recently. This cross-linking agent, and in particular 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC), is of extreme interest, especially for tissue-engineered scaffolds composed specifically of native polymers (e.g., collagen), because it is a zero-length cross-linking agent that has not been shown to cause any cytotoxic reactions. The unique aspect of the cross-linking protocol in this study involves the use of ethanol as the solvent for the cross-linking agent, because the pure collagen electrospun mats immediately disintegrate when placed in an aqueous solution. This study examines 2 concentrations of EDC with and without the addition of N-hydroxysuccinimide to the reaction (which has been shown to result in higher cross-linking yields in aqueous solutions) to test the hypothesis that the use of EDC in a nonaqueous solution will cross-link electrospun type II collagen fibrous matrices in a comparable manner to typical glutaraldehyde fixation protocols. The use of EDC is compared with the cross-linking effects of glutaraldehyde via mechanical testing (uniaxial tensile testing) and biochemical testing (analysis of the percentage of free amino groups). The stress-strain curves of the cross-linked samples demonstrated uniaxial tensile behavior more characteristic of native tissue than do the dry, untreated samples. The heated, 50% glutaraldehyde cross-linking protocol resulted in a mean peak stress of 0.76 MPa, a mean strain at break of 127.30%, and a mean tangential modulus of 0.89 MPa; mean values for the samples treated with the EDC protocols ranged from 0.35 to 0.60 MPa for peak stress, from 111.83 to 159.23% for strain at break, and from 0.57 to 0.92 MPa for tangential modulus. Low and high concentrations (20 mM and 200 mM, respectively) of EDC alone were comparable in extent of cross-linking (29% and 29%, respectively) to the heated 50% glutaraldehyde cross-linking protocol (30% cross-linked).

Electrospun fibrinogen: feasibility as a tissue engineering scaffold in a rat cell culture model.

Fibrinogen has a well-established tissue engineering track record because of its ability to induce improved cellular interaction and scaffold remodeling compared to synthetic scaffolds. While the feasibility of electrospinning fibrinogen scaffolds of submicron diameter fibers and their mechanical properties have been demonstrated, in vitro cellular interaction has not yet been evaluated. The goal of this study was to demonstrate, based on cellular interaction and scaffold remodeling, that electrospun fibrinogen can be used successfully as a tissue engineering scaffold. Electrospun fibrinogen scaffolds were disinfected, seeded with neonatal rat cardiac fibroblasts, and cultured for 2, 7, and 14 days. Cultures were treated to regulate scaffold degradation by either supplementing serum-containing media with aprotinin or crosslinking the scaffolds with glutaraldehyde vapor. Biocompatibility was assessed through a WST-1 cell proliferation assay. Postculture scaffolds were evaluated by scanning electron microscopy and histology. Cell culture demonstrated that fibroblasts readily migrate into and remodel electrospun fibrinogen scaffolds with deposition of native collagen. Supplementation of culture media with different concentrations of aprotinin-modulated scaffold degradation in a predictable fashion, but glutaraldehyde vapor fixation was less reliable. Based on the observed cellular interactions, there is tremendous potential for electrospun fibrinogen as a tissue engineering scaffold.

An intervention to overcome clinical inertia and improve diabetes mellitus control in a primary care setting: Improving Primary Care of African Americans with Diabetes (IPCAAD) 8.

BACKGROUND: Although clinical trials have shown that proper management of diabetes can improve outcomes, and treatment guidelines are widespread, glycated hemoglobin (HbA1c) levels in the United States are rising. Since process measures are improving, poor glycemic control may reflect the failure of health care providers to intensify diabetes therapy when indicated--clinical inertia. We asked whether interventions aimed at health care provider behavior could overcome this barrier and improve glycemic control. METHODS: In a 3-year trial, 345 internal medicine residents were randomized to be controls or to receive computerized reminders providing patient-specific recommendations at each visit and/or feedback on performance every 2 weeks. When glucose levels exceeded 150 mg/dL (8.33 mmol/L) during visits of 4038 patients, health care provider behavior was characterized as did nothing, did anything (any intensification of therapy), or did enough (if intensification met recommendations). RESULTS: At baseline, residents did anything for 35% of visits and did enough for 21% of visits when changes in therapy were indicated, and there were no differences among intervention groups. During the trial, intensification increased most during the first year and then declined. However, intensification increased more in the feedback alone and feedback plus reminders groups than for reminders alone and control groups (P<.001). After 3 years, health care provider behavior in the reminders alone and control groups returned to baseline, whereas improvement with feedback alone and feedback plus reminders groups was sustained: 52% did anything, and 30% did enough (P<.001 for both vs the reminders alone and control groups). Multivariable analysis showed that feedback on performance contributed independently to intensification and that intensification contributed independently to fall in HbA1c (P<.001 for both). CONCLUSIONS: Feedback on performance given to medical resident primary care providers improved provider behavior and lowered HbA1c levels. Similar approaches may aid health care provider behavior and improve diabetes outcomes in other primary care settings.

Mechanical properties of electrospun fibrinogen structures.

Fibrin and fibrinogen have a well-established track record in tissue engineering due to their innate ability to induce improved cellular interaction and subsequent scaffold remodeling compared to synthetic scaffolds. Use of fibrinogen as a primary scaffold component, however, has been limited by traditional processing techniques that render scaffolds with insufficient mechanical properties. The goal of this study was to demonstrate, based on mechanical properties, that electrospun fibrinogen overcomes these limitations and can be successful as a tissue engineering scaffold or wound dressing. Electrospun fibrinogen scaffolds were characterized for fiber diameter and pore area and subsequently tested for uniaxial mechanical properties while dry and hydrated. In addition, uniaxial mechanical testing was conducted on scaffolds treated to regulate scaffold degradation in serum-containing media by supplementing the media with aprotinin or cross-linking the scaffolds with glutaraldehyde vapor. A linear relationship between electrospinning solution concentration and measured fiber diameter was seen; fiber diameters ranged from 120 to 610 nm over electrospinning concentrations of 80 to 140 mg/ml fibrinogen, respectively. Pore areas ranged from 1.3 microm(2) to 13 microm(2) over the same fibrinogen concentrations. Aprotinin in the culture media inhibited scaffold degradation in a predictable fashion, but glutaraldehyde vapor fixation produced less reliable results as evidenced by mechanical property testing. In conclusion, the mechanical characteristics of electrospun fibrinogen strongly support its potential use as a tissue engineering scaffold or wound dressing.

Use of a glucose algorithm to direct diabetes therapy improves A1C outcomes and defines an approach to assess provider behavior.

PURPOSE: The purpose of this study was to determine whether an algorithm that recommended individualized changes in therapy would help providers to change therapy appropriately and improve glycemic control in their patients. METHODS: The algorithm recommended specific doses of oral agents and insulin based on a patient's medications and glucose or A1C levels at the time of the visit. The prospective observational study analyzed the effect of the algorithm on treatment decisions and A1C levels in patients with type 2 diabetes. RESULTS: The study included 1250 patients seen in pairs of initial and follow-up visits during a 7-month baseline and/or a subsequent 7-month algorithm period. The patients had a mean age of 62 years, body mass index of 33 kg/m(2), duration of diabetes of 10 years, were 94% African American and 71% female, and had average initial A1C level of 7.7%. When the algorithm was available, providers were 45% more likely to intensify therapy when indicated (P = .005) and increased therapy by a 20% greater amount (P < .001). A1C level at follow-up was 90% more likelyto be <7% in the algorithm group, even after adjusting for differences in age, sex, body mass index, race, duration of diabetes and therapy, glucose, and A1C level at the initial visit (P < .001). CONCLUSIONS: Use of an algorithm that recommends patient-specific changes in diabetes medications improves both provider behavior and patient A1C levels and should allow quantitative evaluation of provider actions for that provider's patients.

An endocrinologist-supported intervention aimed at providers improves diabetes management in a primary care site: improving primary care of African Americans with diabetes (IPCAAD) 7.

OBJECTIVE: Management of diabetes is frequently suboptimal in primary care settings, where providers often fail to intensify therapy when glucose levels are high, a problem known as clinical inertia. We asked whether interventions targeting clinical inertia can improve outcomes. RESEARCH DESIGN AND METHODS: A controlled trial over a 3-year period was conducted in a municipal hospital primary care clinic in a large academic medical center. We studied all patients (4,138) with type 2 diabetes who were seen in continuity clinics by 345 internal medicine residents and were randomized to be control subjects or to receive one of three interventions. Instead of consultative advice, the interventions were hard copy computerized reminders that provided patient-specific recommendations for management at the time of each patient's visit, individual face-to-face feedback on performance for 5 min every 2 weeks, or both. RESULTS: Over an average patient follow-up of 15 months within the intervention site, improvements in and final HbA1c (A1C) with feedback + reminders (deltaA1C 0.6%, final A1C 7.46%) were significantly better than control (deltaA1C 0.2%, final A1C 7.84%, P < 0.02); changes were smaller with feedback only and reminders only (P = NS vs. control). Trends were similar but not significant with systolic blood pressure (sBP) and LDL cholesterol. Multivariable analysis showed that the feedback intervention independently facilitated attainment of American Diabetes Association goals for both A1C and sBP. Over a 2-year period, overall glycemic control improved in the intervention site but did not change in other primary care sites (final A1C 7.5 vs. 8.2%, P < 0.001). CONCLUSIONS: Feedback on performance aimed at overcoming clinical inertia and given to internal medicine resident primary care providers improves glycemic control. Partnering generalists with diabetes specialists may be important to enhance diabetes management in other primary care settings.

Electrospinning polydioxanone for biomedical applications.

Polydioxanone (PDS) is a colorless, crystalline, bioabsorbable polymer that was first developed specifically for wound closure sutures. The compatibility, degradation rate, and mechanical properties (including shape memory) of PDS are of interest when considering the design of tissue engineering scaffolds. This research presents the electrospinning of PDS to fabricate unique nanofibrous structures for a variety of biomedical applications. Electrospinning is a polymer processing technique that utilizes an electric field to form fibers from a polymer solution or melt and allows the fabrication of nanofibrous non-woven structures. Results demonstrate the ability to control the fiber diameter of PDS as a function of solution concentrations and the fiber orientation with our prototype electrospinning apparatus. The results also show dependence between the fiber orientation and the elastic modulus, peak stress, and strain to failure of PDS in a uniaxial model.

Patient adherence improves glycemic control.

PURPOSE: The purpose of this study was to assess the influence of appointment keeping and medication adherence on HbA1c. METHODS: A retrospective evaluation was performed in 1560 patients with type 2 diabetes who presented for a new visit to the Grady Diabetes Clinic between 1991 and 2001 and returned for a follow-up visit and HbA1c after 1 year of care. Appointment keeping was assessed by the number of scheduled intervening visits that were kept, and medication adherence was assessed by the percentage of visits in which self-reported diabetes medication use was as recommended at the preceding visit. RESULTS: The patients had an average age of 55 years, body mass index (BMI) of 32 kg/m2, diabetes duration of 4.6 years, and baseline HbA1c of 9.1%. Ninety percent were African American, and 63% were female. Those who kept more intervening appointments had lower HbA1c levels after 12 months of care (7.6% with 6-7 intervening visits vs 9.7% with 0 intervening visits). Better medication adherence was also associated with lower HbA1c levels after 12 months of care (7.8% with 76%-100% adherence). After adjusting for age, gender, race, BMI, diabetes duration, and diabetes therapy in multivariate linear regression analysis, the benefits of appointment keeping and medication adherence remained significant and contributed independently; the HbA1c was 0.12% lower for every additional intervening appointment that was kept (P = .0001) and 0.34% lower for each quartile of better medication adherence (P = .0009). CONCLUSION: Keeping more appointments and taking diabetes medications as directed were associated with substantial improvements in HbA1c. Efforts to enhance glycemic outcomes should include emphasis on these simple but critically important aspects of patient adherence.

Clinical inertia contributes to poor diabetes control in a primary care setting.

PURPOSE: The purpose of this study was to determine whether "clinical inertia"-inadequate intensification of therapy by the provider-could contribute to high A1C levels in patients with type 2 diabetes managed in a primary care site. METHODS: In a prospective observational study, management was compared in the Medical Clinic, a primary care site supervised by general internal medicine faculty, and the Diabetes Clinic, a specialty site supervised by endocrinologists. These municipal hospital clinics serve a common population that is largely African American, poor, and uninsured. RESULTS: Four hundred thirty-eight African American patients in the Medical Clinic and 2157 in the Diabetes Clinic were similar in average age, diabetes duration, body mass index, and gender, but A1C averaged 8.6% in the Medical Clinic versus 7.7% in the Diabetes Clinic (P < .0001). Use of pharmacotherapy was less intensive in the Medical Clinic (less use of insulin), and when patients had elevated glucose levels during clinic visits, therapy was less than half as likely to be advanced in the Medical Clinic compared to the Diabetes Clinic (P < .0001). Intensification rates were lower in the Medical Clinic regardless of type of therapy (P < .0001), and intensification of therapy was independently associated with improvement in A1C (P < .001). CONCLUSIONS: Medical Clinic patients had worse glycemic control, were less likely to be treated with insulin, and were less likely to have their therapy intensified if glucose levels were elevated. To improve diabetes management and glycemic control nationwide, physicians in training and generalists must learn to overcome clinical inertia, to intensify therapy when appropriate, and to use insulin when clinically indicated.

Diabetes management by residents in training in a municipal hospital primary care site (IPCAAD 2).

PURPOSE: Since diabetes is largely a primary care problem but we know little about management by residents in training--the primary care practitioners of the future--we examined surrogate outcomes reflective of their performance. METHODS: A seven-week observational study was conducted in a typical training site- a municipal hospital internal medicine resident "continuity" (primary care) clinic in a large, academic, university-affiliated training program. We evaluated control of glucose, blood pressure, and lipids; screening for proteinuria; and use of aspirin relative to national standards. RESULTS: Five hundred fifty-six (556) patients were 72% female and 97% African-American, with mean age 63 years, duration of diabetes 12 years, and BMI 34 kg/m2. Patients were managed largely with diet alone (22%) or oral agents alone (40%); 7% used oral agents and insulin in combination, and 30% insulin alone. Hemoglobin A1c (mean 8.2%) was above goal (<7.0%) in 61% of patients. Low density lipoprotein cholesterol (mean 128 mg/dL) was above goal (<100) in 76% of patients, but high density lipoprotein (mean 53 mg/dL) was at goal in 46%, and triglycerides (mean 138 mg/dL) were at goal in 85%. Diastolic pressure (mean 75 mm Hg) was at goal (<85) in 77% of patients, but systolic pressure (mean 143) was at goal (<130) in only 25% of patients. An average of only 53% of the patients had urine protein screening per 12 months, and use of aspirin was documented for only 39% of patients. CONCLUSIONS: Patients with type 2 diabetes in a typical internal medicine resident primary care clinic frequently do not achieve national standard of care goals. Since skills and attitudes developed in residency are likely to carry over into later practice, local diabetes educators may need to work with medical faculty to develop new interventions to improve postgraduate medical education in diabetes management.

Utility of casual postprandial glucose levels in type 2 diabetes management.

OBJECTIVE: Because readily available glycemic indicators are needed to guide clinical decision-making for intensification of diabetes therapy, our goals were to define the relationship between casual postprandial plasma glucose (cPPG) levels and HbA(1c) in patients with type 2 diabetes and to determine the predictive characteristics of a convenient glucose cutoff. RESEARCH DESIGN AND METHODS: We examined the relationship between cPPG levels (1-4 h post meal) and HbA(1c) levels in 1,827 unique patients who had both determinations during a single office visit. RESULTS: The population studied was predominantly African American and middle-aged, with average cPPG of 201 mg/dl and HbA(1c) of 8.4%. The prevalence of HbA(1c) > or = 7.0% was 67% and HbA(1c) >6.5% was 77%. Overall, cPPG and HbA(1c) were linearly correlated (r = 0.63, P < 0.001). The correlation between cPPG and HbA(1c) was strongest in patients treated with diet alone (n = 348, r = 0.75, P < 0.001) and weaker but still highly significant for patients treated with oral agents (n = 610, r = 0.64, P < 0.001) or insulin (n = 869, r = 0.56, P < 0.001). A cutoff cPPG >150 mg/dl predicted an HbA(1c) level > or = 7.0% in the whole group, with a sensitivity of 78%, a specificity of 62%, and an 80% positive predictive value. The same cPPG cutoff of 150 mg/dl predicted an HbA(1c) level >6.5%, with a sensitivity of 74%, a specificity of 66%, and an 88% positive predictive value. CONCLUSIONS: When rapid-turnaround HbA(1c) determinations are not available, a single cPPG level >150 mg/dl may be used during a clinic visit to identify most inadequately controlled patients and allow timely intensification of therapy.

Rapid A1c availability improves clinical decision-making in an urban primary care clinic.

OBJECTIVE: Failure to meet goals for glycemic control in primary care settings may be due in part to lack of information critical to guide intensification of therapy. Our objective is to determine whether rapid-turnaround A1c availability would improve intensification of diabetes therapy and reduce A1c levels in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: In this prospective controlled trial, A1c was determined on capillary glucose samples and made available to providers, either during ("rapid") or after ("routine") the patient visit. Frequency of intensification of pharmacological diabetes therapy in inadequately controlled patients and A1c levels were assessed at baseline and after follow-up. RESULTS: We recruited 597 subjects. Patients were 79% female and 96% African American, with average age of 61 years, duration of diabetes 10 years, BMI 33 kg/m(2), and A1c 8.5%. The rapid and routine groups had similar clinical demographics. Rapid A1c availability resulted in more frequent intensification of therapy when A1c was >/=7.0% at the baseline visit (51 vs. 32% of patients, P = 0.01), particularly when A1c was >8.0% and/or random glucose was in the 8.4-14.4 mmol/l range (151-250 mg/dl). In 275 patients with two follow-up visits, A1c fell significantly in the rapid group (from 8.4 to 8.1%, P = 0.04) but not in the routine group (from 8.1 to 8.0%, P = 0.31). CONCLUSIONS: Availability of rapid A1c measurements increased the frequency of intensification of therapy and lowered A1c levels in patients with type 2 diabetes in an urban neighborhood health center.

Development of LC-IMS-CID-TOFMS techniques: analysis of a 256 component tetrapeptide combinatorial library.

Recent improvements in ion mobility/time-of-flight mass spectrometry techniques have made it possible to incorporate nano-flow liquid chromatography and collision induced dissociation techniques. This combination of approaches provides a new strategy for detailed characterization of complex systems--such as, combinatorial libraries. Our work uses this technology to provide a detailed analysis of a tetrapeptide library having the general form Xxx1-Xxx2-Xxx3-Xxx4 where Xxx1 = Glu, Phe, Val, Asn; Xxx2 = Glu, Phe, Val, Tyr; Xxx3 = Glu, Phe, Val, Thr; and Xxx4 = Glu, Phe, Val, Leu--a system that is expected to contain 256 different peptide sequences. The results corroborate the presence of many expected peptide sequences and indicate that some synthetic steps appear to have failed. Particularly interesting is the observation of a t-butyl protecting group on the tyrosine (Tyr) residue. It appears that most Tyr containing peptides that have this t-butyl group attached favor formation of [2M + 2H]2+ dimers, which can be readily distinguished from [M + H]+ monomers based on differences in their gas-phase mobilities. In this case, we demonstrate the use of the mobility differences between [2M + 2H]2+ and [M + H]+ ions as a signature for a failure of a synthetic step.