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Acne rosacea, a common medical problem that often goes unrecognized, is easily diagnosed and treated in primary care. Timely interventions can alter the outcome of this disease and significantly improve the patient's quality of life. [ABSTRACT FROM AUTHOR]

Irritable bowel syndrome is the most common functional disorder of the gastrointestinal tract and is frequently treated by family physicians. Despite patients' worries about the symptoms of irritable bowel syndrome, it is a benign condition. The diagnosis should be made using standard criteria after red flags that may signify organic disease have been ruled out. An effective physician-patient relationship is vital to successful management. Episodes of diarrhea are best managed with loperamide, while constipation often will respond to fiber supplements. Antispasmodics or anticholinergic agents may help relieve the abdominal pain of irritable bowel syndrome. Refractory cases are often treated with tricyclic antidepressants. Newer agents such as tegaserod and ondansetron target neurotransmitter receptors in the gastrointestinal tract Some forms of psychologic treatment may be helpful, and gastroenterology consultation is occasionally needed to reassure the patient. Comorbid conditions such as depression or anxiety should be investigated and treated. [ABSTRACT FROM AUTHOR]

Discusses the role of bioavailability and bioequivalence of drug products in drug development, regulatory review and approval and in clinical use of drug products. Factors that affect their bioavailability and bioequivalence; Recommendations.

Rosacea often goes unrecognized, but it is easily diagnosed and treated in primary care. Timely interventions can alter the outcome of this disease and significantly improve a patient's quality of life. [ABSTRACT FROM AUTHOR]

Introduction: Longitudinal data on how acute respiratory illness (ARI) affects behavior, namely school or work participation, and nonpharmaceutical intervention (NPI) usage before and during the COVID-19 pandemic is limited. The authors assessed how ARIs and specific symptoms affected school, work, and health-related behaviors over time., Methods: From November 2019 to June 2021, participating households with children in King County, Washington, were remotely monitored for ARI symptoms weekly. Following ARIs, participants reported illness-related effects on school, work, and NPI use. Using logistic regression with generalized estimating equations, the authors examined associations between symptoms and behaviors., Results: Of 1,861 participants, 581 (31%) from 293 households reported 884 ARIs and completed one-week follow-up surveys. Compared with the prepandemic period, during the period of the pandemic pre-COVID-19 vaccine, ARI-related school (56% vs 10%, p <0.001) absenteeism decreased and masking increased (3% vs 28%, p <0.001). After vaccine authorization in December 2020, more ARIs resulted in masking (3% vs 48%, p <0.001), avoiding contact with non-household members (26% vs 58%, p <0.001), and staying home (37% vs 69%, p <0.001) compared with the prepandemic period. Constitutional symptoms such as fever were associated with work disruptions (OR=1.91; 95% CI=1.06, 3.43), staying home (OR=1.55; 95% CI=1.06, 2.27), and decreased contact with non-household members (OR=1.58; 95% CI=1.05, 2.36)., Conclusions: This remote household study permitted uninterrupted tracking of behavioral changes in families with children before and during the COVID-19 pandemic, identifying increased use of some NPIs when ill but no additional illness-associated work or school disruptions., (© 2024 The Authors.)

Controlled-release, and especially long-acting, drug delivery systems hold promise for improving treatments for numerous medical conditions. Previously, we reported an additive manufacturing or "three-dimensional (3D) printing" approach for fabricating liquid-core-shell-cap microcarriers comprising standard photoresists. Here we explore the potential to extend this strategy to achieve microcarriers comprising biodegradable materials as a new pathway to controlled-release drug delivery options. Specifically, we investigate the use of "Two-Photon Direct Laser Writing (DLW)" as a means to 3D print microcarriers composed of: ( i ) a bottle-shaped "shell" with an orifice, ( ii ) an aqueous liquid "core", and ( iii ) a biodegradable "cap". The cap, which is DLW-printed directly onto the shell's orifice, is designed to degrade over time in the body- e.g ., with degradation time proportional to cap thickness-to ultimately facilitate release of the liquid core at desired time points. Fabrication results based on the use of a biodegradable poly(ethylene glycol) diacrylate (PEGDA) photomaterial for the cap revealed that shell designs incorporating microfluidic obstruction structures appeared to limit undesired entry of the liquid-phase PEGDA into the shell ( i.e ., directly preceding cap printing), thereby resulting in improved retention of the liquid core after completion of the cap printing process. These results mark an important first step toward evaluating the utility of the presented DLW 3D printing strategy for possible drug delivery applications., Competing Interests: CONFLICT OF INTEREST Sharon Flank is Founding CEO of InfraTrac, Inc., which has a potential interest in commercializing the microcarriers presented in this work.

These proceedings contain presentation summaries and discussion highlights from the University of Maryland Center of Excellence in Regulatory Science and Innovation (M-CERSI) Workshop on Co-processed API, held on July 13 and 14, 2022. This workshop examined recent advances in the use of co-processed active pharmaceutical ingredients as a technology to improve drug substance physicochemical properties and drug product manufacturing process robustness, and explored proposals for enabling commercialization of these transformative technologies. Regulatory considerations were discussed with a focus on the classification, CMC strategies, and CMC documentation supporting the use of this class of materials from clinical studies through commercialization. The workshop format was split between presentations from industry, academia and the FDA, followed by breakout sessions structured to facilitate discussion. Given co-processed API is a relatively new concept, the authors felt it prudent to compile these proceedings to gain further visibility to topics discussed and perspectives raised during the workshop, particularly during breakout discussions. Disclaimer: This paper reflects discussions that occurred among stakeholder groups, including FDA, on various topics. The topics covered in the paper, including recommendations, therefore, are intended to capture key discussion points. The paper should not be interpreted to reflect alignment on the different topics by the participants, and the recommendations provided should not be used in lieu of FDA published guidance or direct conversations with the Agency about a specific development program. This paper should not be construed to represent FDA's views or policies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 American Pharmacists Association. All rights reserved.)

Background: Respiratory viruses might influence Streptococcus pneumoniae nasal carriage and subsequent disease risk. We estimated the association between common respiratory viruses and semiquantitative S. pneumoniae nasal carriage density in a household setting before and during the COVID-19 pandemic., Methods: From November 2019-June 2021, we enrolled participants in a remote household surveillance study of respiratory pathogens. Participants submitted weekly reports of acute respiratory illness (ARI) symptoms. Mid-turbinate or anterior nasal swabs were self-collected at enrollment, when ARI occurred, and, in the second year of the study only, from household contacts after SARS-CoV-2 was detected in a household member. Specimens were tested using multiplex reverse-transcription PCR for respiratory pathogens, including S. pneumoniae , rhinovirus, adenovirus, common human coronavirus, influenza A/B virus, respiratory syncytial virus (RSV) A/B, human metapneumovirus, enterovirus, and human parainfluenza virus. We estimated differences in semiquantitative S. pneumoniae nasal carriage density, estimated by the inverse of S. pneumoniae relative cycle threshold (Crt) values, with and without viral detection for any virus and for specific respiratory viruses using linear generalized estimating equations of S. pneumoniae Crt values on virus detection adjusted for age and swab type and accounting for clustering of swabs within households., Results: We collected 346 swabs from 239 individuals in 151 households that tested positive for S. pneumoniae ( n  = 157 with and 189 without ≥1 viruses co-detected). Difficulty breathing, cough, and runny nose were more commonly reported among individuals with specimens with viral co-detection compared to without (15%, 80% and 93% vs. 8%, 57%, and 51%, respectively) and ear pain and headache were less commonly reported (3% and 26% vs. 16% and 41%, respectively). For specific viruses among all ages, semiquantitative S. pneumoniae nasal carriage density was greater with viral co-detection for enterovirus, RSV A/B, adenovirus, rhinovirus, and common human coronavirus ( P  < 0.01 for each). When stratified by age, semiquantitative S. pneumoniae nasal carriage density was significantly greater with viral co-detection among children aged <5 ( P  = 0.002) and 5-17 years ( P  = 0.005), but not among adults aged 18-64 years ( P  = 0.29)., Conclusion: Detection of common respiratory viruses was associated with greater concurrent S. pneumoniae semiquantitative nasal carriage density in a household setting among children, but not adults., Competing Interests: HC reports consulting with Ellume, Merck, Abbvie, Pfizer, The Bill and Melinda Gates Foundation. She has received research funding from Sanofi Pasteur, and support and reagents from Ellume and Cepheid outside of the submitted work. JE reports consulting with Ark Biopharmaceuticals, Sanofi Pasteur, Moderna, Meissa Vaccines, Astra Zeneca, and Pfizer, Inc. outside of the submitted work, and has received research funding from AstraZeneca, GlaxoSmithKline, and Pfizer. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Bennett, Emanuels, Heimonen, O'Hanlon, Hughes, Han, Chow, Ogokeh, Rolfes, Lockwood, Pfau, Uyeki, Shendure, Hoag, Fay, Lee, Sibley, Rogers, Starita, Englund and Chu.)

Purpose: Despite evidence suggesting that high-quality primary care can prevent unnecessary hospitalizations, many primary care practices face challenges in achieving this goal, and there is little guidance identifying effective strategies for reducing hospitalization rates. We aimed to understand how practices in the Comprehensive Primary Care Plus (CPC+) program substantially reduced their acute hospitalization rate (AHR) over 2 years., Methods: We used Bayesian analyses to identify the CPC+ practice sites having the highest probability of achieving a substantial reduction in the adjusted Medicare AHR between 2016 and 2018 (referred to here as AHR high performers). We then conducted telephone interviews with 64 respondents at 14 AHR high-performer sites and undertook within- and cross-case comparative analysis., Results: The 14 AHR high performers experienced a 6% average decrease (range, 4% to 11%) in their Medicare AHR over the 2-year period. They credited various care delivery activities aligned with 3 strategies for reducing AHR: (1) improving and promoting prompt access to primary care, (2) identifying patients at high risk for hospitalization and addressing their needs with enhanced care management, and (3) expanding the breadth and depth of services offered at the practice site. They also identified facilitators of these strategies: enhanced payments through CPC+, prior primary care practice transformation experience, use of data to identify high-value activities for patient subgroups, teamwork, and organizational support for innovation., Conclusions: The AHR high performers observed that strengthening the local primary care infrastructure through practice-driven, targeted changes in access, care management, and comprehensiveness of care can meaningfully reduce acute hospitalizations. Other primary care practices taking on the challenging work of reducing hospitalizations can learn from CPC+ practices and may consider similar strategies, selecting activities that fit their context, personnel, patient population, and available resources., (© 2023 Annals of Family Medicine, Inc.)

COVID-19 can lead to severe outcomes in children (1). Vaccination decreases risk for COVID-19 illness, severe disease, and death (2). On December 13, 2020, CDC recommended COVID-19 vaccination for persons aged ≥16 years, with expansion on May 12, 2021, to children and adolescents (children) aged 12-15 years, and on November 2, 2021, to children aged 5-11 years (3). As of March 8, 2023, COVID-19 vaccination coverage among school-aged children remained low nationwide, with 61.7% of children aged 12-17 years and approximately one third (32.7%) of those aged 5-11 years having completed the primary series (3). Intention to receive COVID-19 vaccine and vaccination coverage vary by demographic characteristics, including race and ethnicity and socioeconomic status (4-6). Seattle Public Schools (SPS) implemented a program to increase COVID-19 vaccination coverage during the 2021-22 school year, focusing on children aged 5-11 years during November 2021-June 2022, with an added focus on populations with low vaccine coverage during January 2022-June 2022. † The program included strategic messaging, school-located vaccination clinics, and school-led community engagement. Vaccination data from the Washington State Immunization Information System (WAIIS) were analyzed to examine disparities in COVID-19 vaccination by demographic and school characteristics and trends over time. In December 2021, 56.5% of all SPS students, 33.7% of children aged 5-11 years, and 81.3% of children aged 12-18 years had completed a COVID-19 primary vaccination series. By June 2022, overall series completion had increased to 80.3% and was 74.0% and 86.6% among children aged 5-11 years and 12-18 years, respectively. School-led vaccination programs can leverage community partnerships and relationships with families to improve COVID-19 vaccine access and coverage., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Janet A. Englund reports institutional support from Pfizer, GlaxoSmithKline, AstraZeneca, and Merck; consulting fees from Pfizer, Moderna, Abbvie, Merck, and AstraZeneca; and travel support to attend the 2022 European Society for Paediatric Infectious Diseases meeting from AstraZeneca. No other potential conflicts of interest were disclosed.

The taro plant, Colocasia esculenta , contains bioactive proteins with potential as cancer therapeutics. Several groups have reported anti-cancer activity in vitro and in vivo of taro-derived extracts (TEs). We reported that TE inhibits metastasis in a syngeneic murine model of Triple-Negative Breast Cancer (TNBC)., Purpose: We sought to confirm our earlier studies in additional models and to identify novel mechanisms by which efficacy is achieved., Methods: We employed a panel of murine and human breast and ovarian cancer cell lines to determine the effect of TE on tumor cell viability, migration, and the ability to support cancer stem cells. Two syngeneic models of TNBC were employed to confirm our earlier report that TE potently inhibits metastasis. Cancer stem cell assays were employed to determine the ability of TE to inhibit tumorsphere-forming ability and to inhibit aldehyde dehydrogenase activity. To determine if host immunity contributes to the mechanism of metastasis inhibition, efficacy was assessed in immune-compromised mice., Results: We demonstrate that viability of some, but not all cell lines is inhibited by TE. Likewise, tumor cell migration is inhibited by TE. Using 2 immune competent, syngeneic models of TNBC, we confirm our earlier findings that tumor metastasis is potently inhibited by TE. We also demonstrate, for the first time, that TE directly inhibits breast cancer stem cells. Administration of TE to mice elicits expansion of several spleen cell populations but it was not known if host immune cells contribute to the mechanism by which TE inhibits tumor cell dissemination. In novel findings, we now show that the ability of TE to inhibit metastasis relies on immune T-cell-dependent, but not B cell or Natural Killer (NK)-cell-dependent mechanisms. Thus, both tumor cell-autonomous and host immune factors contribute to the mechanisms underlying TE efficacy. Our long-term goal is to evaluate TE efficacy in clinical trials. Most of our past studies as well as many of the results reported in this report were carried out using an isolation protocol described earlier (TE). In preparation for a near future clinical trial, we have now developed a strategy to isolate an enriched taro fraction, TE-method 2, (TE-M2) as well as a more purified subfraction (TE-M2F1) which can be scaled up under Good Manufacturing Practice (GMP) conditions for evaluation in human subjects. We demonstrate that TE-M2 and TE-M2F1 retain the anti-metastatic properties of TE., Conclusions: These studies provide further support for the continued examination of biologically active components of Colocasia esculenta as potential new therapeutic entities and identify a method to isolate sufficient quantities under GMP conditions to conduct early phase clinical studies., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Background: Patients with heart failure with preserved ejection fraction (HFpEF) experience poor exercise tolerance and quality of life. Little is known about the feasibility or effects of HFpEF exercise training (ET) in a community hospital setting., Objective: The aim of this study was to examine the feasibility and pilot data of a community-based HFpEF ET intervention., Methods: This was a single-group (n = 16), pretest-posttest, 9-week ET intervention. The Minnesota Living With Heart Failure Questionnaire, Patient Health Questionnaire-9, cardiopulmonary exercise test (peak VO2), and 6-minute walk test were used for evaluation., Results: Participants (n = 16) attended 88% of prescribed ET sessions and 94% completed all pretest-posttest assessments. Significant improvements in Minnesota Living With Heart Failure Questionnaire (P = .01), Patient Health Questionnaire-9 (P ≤ .01), exercise test time (P = .01) and 6-minute walk test (P = .001), but not in peak VO2 (P = .16), were found., Conclusions: The ET intervention was feasible and safe, and findings support improved quality of life, depressive symptoms, and exercise tolerance. Larger controlled trials are warranted., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Current return to learn (RTL) after concussion guidelines lack specificity for individualized student care, limiting potential for adoption and implementation. We used a community-engaged research framework to develop and evaluate the implementation of a student-centered care plan that assists school personnel in facilitating RTL., Methods: We used best-practice RTL guidelines and input from administrators and medical experts to iteratively develop a flexible student-centered care plan. Thirteen schools participated. Coding completion of care plans indicated feasibility and fidelity; interviews with RTL coordinators indicated acceptability., Results: The care plan includes educational materials, symptom checklists, and guidelines for classroom adjustments linked to student symptoms. Care plans were initiated for 24 (70.6%) of 34 students with concussions, indicating feasibility. Fidelity was high, with the following subsections completed: Action Checklist (90%), Symptom Evaluation (91%), Temporary Adjustment Recommendations (95%). Qualitative analysis of interviews suggested care plans were acceptable and facilitate consistent communication, prioritization of individual needs of students, and increased ability to delegate tasks to other school staff., Conclusions: Implementation of a student-centered, individually tailored care plan for RTL is feasible and acceptable in public high schools. Future research should examine how to expediently initiate student-centered concussion care plans after diagnosis to optimize recovery., (© 2020, American School Health Association.)

From 2012 to 2015, Sanford Health, a large health care system, integrated behavioral health services and chronic condition care management in some of its primary care practices in the Dakotas and rural Minnesota. Using difference-in-differences analyses for fee-for-service Medicare beneficiaries attributed to 22 participating practices and 91 matched comparison practices, we found that the program increased the receipt of four recommended diabetes care processes by 8.6% (p=.048) and, by slowing the increase in emergency department (ED) visits, reduced them by 4.9% (p=.07) relative to the comparison group. However, the findings are mixed: the program did not affect hospital admissions, readmissions, or Medicare spending. In addition, the program increased admissions for ambulatory care-sensitive conditions by 13.6% (p=.07) relative to the comparison group. Sanford's program provides a concrete example of how to incorporate behavioral health services in primary care in underserved areas with some positive results on quality-of-care processes and ED utilization.

Background: The Center for Medicare & Medicaid Innovation (CMMI) tests new models of paying for or delivering health care services and expands models that improve health outcomes while lowering medical spending. CMMI gave TransforMED, a national learning and dissemination contractor, a 3-year Health Care Innovation Award (HCIA) to integrate health information technology systems into physician practices. This paper estimates impacts of TransforMED's HCIA-funded program on patient outcomes and Medicare parts A and B spending., Research Design: We compared outcomes for Medicare fee-for-service (FFS) beneficiaries served by 87 treatment practices to outcomes for Medicare FFS beneficiaries served by 286 matched comparison practices, adjusting for differences in outcomes between the 2 groups during a 1-year baseline period. We estimated impacts in 3 evaluation outcome domains: quality-of-care processes, service use, and spending., Results: We estimated the program led to a 7.1% reduction in inpatient admissions and a 5.7% decrease in the outpatient emergency department visits. However, there was no evidence of statistically significant effects in outcomes in either the quality-of-care processes or spending domains., Conclusions: These results indicate that TransforMED's program reduced service use for Medicare FFS beneficiaries, but also show that the program did not have statistically significant favorable impacts in the quality-of-care processes or spending domains. These results suggest that providing practices with population health management and cost-reporting software-along with technical assistance for how to use them-can complement practices' own patient-centered medical home transformation efforts and add meaningfully to their impacts on service use.

Importance: CareFirst, the largest commercial insurer in the mid-Atlantic Region of the United States, runs a medical home program focusing on financial incentives for primary care practices and care coordination for high-risk patients. From 2013 to 2015, CareFirst extended the program to Medicare fee-for-service (FFS) beneficiaries in participating practices. If the model extension improved quality while reducing spending, the Centers for Medicare and Medicaid Services could expand the program to Medicare beneficiaries broadly., Objective: To test whether extending CareFirst's program to Medicare FFS patients improves care processes and reduces hospitalizations, emergency department visits, and spending., Design, Setting, and Participants: This difference-in-differences analysis compared outcomes for roughly 35 000 Medicare FFS patients attributed to 52 intervention practices (grouped by CareFirst into 14 "medical panels") to outcomes for 69 000 Medicare patients attributed to 42 matched comparison panels during a 1-year baseline period and 2.5-year intervention at Maryland primary care practices., Main Outcomes and Measures: Hospitalizations (all-cause and ambulatory-care sensitive), emergency department visits, Medicare Part A and B spending, and 3 quality-of-care process measures: ambulatory care within 14 days of a hospital stay, cholesterol testing for those with ischemic vascular disease, and a composite measure for those with diabetes., Interventions: CareFirst hired nurses who worked with patients' usual primary care practitioners to coordinate care for 3656 high-risk Medicare patients. CareFirst paid panels rewards for meeting cost and quality targets for their Medicare patients and advised panels on how to meet these targets based on analyses of claims data., Results: On average, each of the 14 intervention panels had 9.3 primary care practitioners and was attributed 2202 Medicare FFS patients in the baseline period. The panels' attributed Medicare patients were, on average, 73.8 years old, 59.2% female, and 85.1% white. The extension of CareFirst's program to Medicare patients was not statistically associated with improvements in any outcomes, either for the full Medicare population or for a high-risk subgroup in which impacts were expected to be largest. For the full population, the difference-in-differences estimates were 1.4 hospitalizations per 1000 patients per quarter (P = .54; 90% CI, -2.1 to 5.0), -2.5 outpatient ED visits per 1000 patients per quarter (P = .26; 90% CI, -6.2 to 1.1), and -$1 per patient per month in Medicare Part A and B spending (P = .98; 90% CI, -$40 to $39). For hospitalizations and Medicare spending, the 90% CIs did not span CareFirst's expected impacts. Hospitalizations for the intervention group declined by 10% from baseline year to the final 18 months of the intervention, but this was matched by similar declines in the comparison group., Conclusion and Relevance: The extension of CareFirst's program to Medicare did not measurably improve quality-of-care processes or reduce service use or spending for Medicare patients. Further program refinement and testing would be needed to support scaling the program more broadly to Medicare patients.

This study explored the utility of mechanistic absorption models to describe the in vivo performance of a low solubility/low permeability compound in normal healthy subjects. Sixteen healthy human volunteers received three oral formulations and an intravenous infusion in a randomized crossover design. Plasma ciprofloxacin concentrations were estimated by HPLC. In vitro ciprofloxacin release from the oral tablets was tested under a variety of conditions. A mechanistic model was used to explore in vivo dissolution and intestinal absorption. Although dissolution rate influenced the location of drug release, absorption challenges appeared to be associated with permeability limitations in the lower small intestine and colon. The apparent relationship between drug solubilization within the upper small intestinal and formulation overall bioavailability suggested the presence of an intestinal absorption window in many individuals. Failure to absorb drug within this window appeared to be linked with the likelihood of in vivo drug precipitation. Challenges encountered during this modeling exercise included large intersubject variability in product in vivo dissolution and the apparent limitations in ciprofloxacin absorption. Although transporter activity was not included as a model parameter, this evaluation demonstrated how identifying the location of drug absorption across several formulations provided an opportunity to identify factors to consider when formulating similar low solubility/low permeability compounds. The use of mechanistic models was invaluable for our understanding of in vivo product performance and for the assessment of individual profiles rather than means. The latter was essential for understanding the potential challenges that may be encountered when introducing a formulation into a patient population.

Bioequivalence (BE) studies are often required to ensure therapeutic equivalence for major product and manufacturing changes. Waiver of a BE study (biowaiver) is highly desired for such changes. Current regulatory guidelines allow for biowaiver of proportionally similar lower strengths of an extended release (ER) product provided it exhibits similar dissolution to the higher strength in multimedia. The objective of this study is to demonstrate that (1) proportionally similar strengths of ER tablets exhibiting similar in vitro dissolution profiles do not always assure BE and (2) different strengths that do not meet the criteria for dissolution profile similarity may still be bioequivalent. Four marketed ER tablets were used as model drug products. Higher and lower (half) strength tablets were prepared or obtained from commercial source. In vitro drug release was compared using multi-pH media (pH 1.2, 4.5, 6.8) per regulatory guidance. In vivo performance was assessed based on the available in vivo BE data or established in vitro-in vivo relationships. This study demonstrated that the relationship between in vitro dissolution and in vivo performance is complex and dependent on the characteristics of specific drug molecules, product design, and in vitro test conditions. As a result, proportionally similar strengths of ER dosage forms that meet biowaiver requirements per current regulatory guidelines cannot ensure bioequivalence in all cases. Thus, without an established relationship between in vitro and in vivo performance, granting biowaiver based on passing in vitro tests may result in the approval of certain bioinequivalent products, presenting risks to patients. To justify any biowaiver using in vitro test, it is essential to understand the effects of drug properties, formulation design, product characteristics, test method, and its in vivo relevance. Therefore, biowaiver requirements of different strengths of ER dosage forms specified in the current regulatory guidance should be reevaluated to assure consistent safety and efficacy among different strengths.

Objectives: We investigated how access to and continuity of care might be affected by transitions between health insurance coverage sources, including the Marketplace (also called the Exchange), Medicaid, and the Children's Health Insurance Program (CHIP)., Methods: From January to February 2014 and from August to September 2014, we searched provider directories for networks of primary care physicians and selected pediatric specialists participating in Marketplace, Medicaid, and CHIP in 6 market areas of the United States and calculated the degree to which networks overlapped., Results: Networks of physicians in Medicaid and CHIP were nearly identical, meaning transitions between those programs may not result in much physician disruption. This was not the case for Marketplace and Medicaid and CHIP networks., Conclusions: Transitions from the Marketplace to Medicaid or CHIP may result in different degrees of physician disruption for consumers depending on where they live and what type of Marketplace product they purchase.

Instability in film coating formulations can arise from interactions between aluminum lake pigments and aqueous polymeric dispersions. The purpose of this study was to characterize the interactions between three polymethacrylate-based aqueous polymeric dispersions (Eudragit RS 30 D, Eudragit L 30 D-55, and Eudragit NE 30 D) and aluminum lakes. Particle size measurements, pH stability profiles, zeta potential measurements, and microscopy were used to study mixed dispersions of the polymeric latices and the lakes. Interactions leading to dispersion instability were related to the surface charge of the components in the formulation. Interactions between the ionic polymers and the lakes arose from instability of the lakes outside a certain pH range resulting in the release of electrolytes, which led to aggregation of the polymeric particles. Interactions between the nonionic polymer and the lakes were related to the polymer modifying the surface charge of the lakes, resulting in aggregation of the pigment particles., (Copyright 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association)

An annular shear cell was constructed for powder flow testing, the influence of design and process parameters was characterized, and the results were compared with other flow methods. The shear cell was designed with interchangeable parts to mimic other shear cells. The texture of the powder-metal interface and the gap distance between the lid and side wall of the trough were varied, and the effects of shear rate, powder bed thickness, and consolidation times were tested. Shear parameters, such as cohesion, angles of friction, and flow factors, were measured for microcrystalline cellulose, anhydrous lactose, spray-dried lactose, mannitol, dibasic calcium phosphate dihydrate, anhydrous theophylline, and theophylline monohydrate powder. The results were then compared with the Carr index, mass flow rate, and flowability index. Design parameters such as surface texture and the gap distance significantly affected the shear call results, whereas for the process parameters studied, the shear rate, consolidation time, and powder bed height had a minimal effect on the shear cell results. Of the shear parameters obtained, the angles of friction best represented the known flow properties of powders and were in general agreement with those from other flow tests., (Copyright 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association.)

Tennessee created TennCare in 1994 to address the needs of "poor and uninsured citizens ... excluded from the health care system." Under TennCare, Tennessee implemented managed care in its Medicaid program and used savings anticipated from the switch to expand insurance coverage to uninsured and uninsurable adults and children. Our analysis of the expansion suggests that it improved access to care, reduced unmet need, and encouraged use of preventive services, particularly for children. These changes coincided with higher levels of satisfaction with care among TennCare beneficiaries.

The purpose of this study is to test the hypothesis that in tablet formulations, moisture-sensitive drugs formulated with lactose monohydrate have the same stability as formulations containing anhydrous lactose, and to characterize the kinetics of niacinamide degradation in the solid state. Aspirin and niacinamide decomposition were used as indicators of stability. Aspirin and niacinamide tablets containing either lactose monohydrate or anhydrous lactose were separately investigated at different temperatures and relative humidities; the stability tests were done at 25 degrees C--60% RH, 40 degrees C--80% RH, 60 degrees C--60% RH, 60 degrees C--80% RH, and 80 degrees C--80% RH. Official U.S. Pharmacopeia methods were used for the aspirin and niacinamide assays. Statistical analysis showed that tablets containing lactose monohydrate have the same stability as tablets containing anhydrous lactose, which means that even though water is present in the crystal structure, the bound water does not influence the reaction rate. In addition, niacinamide degradation in the solid-state can be described by a third order rate equation.

This article reviews the experiences of federally qualified health centers (FQHCs) in Hawaii, Rhode Island, and Tennessee before and after Medicaid managed care demonstrations began. Adapting to managed care proved challenging, but all FQHCs survived. Overall, FQHCs performed better financially than anticipated, partly because demonstrations expanded coverage to previously uninsured individuals, and because FQHCs in two States formed plans that paid FQHCs more than other plans. Service encounters declined; it is unclear if this is negative, since it may indicate more efficient care delivery. In some cases, supportive State policies aided FQHCs' survival. Continued adaptation is critical for FQHCs' longer term prospects.