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141.
OBJECTIVES: To compare third-party payor reimbursement for patients evaluated in a university-based pediatric weight management clinic in central Kentucky. STUDY DESIGN: Demographic and reimbursement data were reviewed for 120 patients evaluated January to December 2004. Statistical analysis included Kruskal-Wallis test and Friedman's test. RESULTS: Overall, median reimbursement was 60%. For new appointments, contracted (56%) and capitated (60%) reimbursements were higher than Medicaid (55%). For established appointments, Medicaid reimbursement (100%) was higher than contracted (37%) and capitated (58%). CONCLUSION: Our data suggest that reimbursement is influenced by regional factors and is improving in central Kentucky.  相似文献   
142.
BACKGROUND: In the Canadian Model of Occupational Performance, meaningful occupation involves interaction between spirituality and environment. However little research exists on the process of giving meaning to occupation. PURPOSE: This study explored both meaningful occupation and the definition of spirituality from the perspective of community-dwelling older adults with autonomy loss. METHOD: Using a qualitative approach, grounded theory method of Glaser and Strauss (1967), eight cognitively intact persons were interviewed individually. RESULTS: The process of giving meaning to occupation involves an intrinsic link between identity and meaningful occupation, with identity being central to the person. Following autonomy loss, a process of adjusting identity, involving social, psychological and spiritual aspects, occurs over time. Spirituality is defined in terms of its close links to religion and belief in a benevolent greater power. IMPLICATIONS OF RESEARCH: This study contributes to the discussion of the concepts of spirituality, identity and meaning in occupational therapy.  相似文献   
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Pharmacists will play a key role in evaluating biosimilars for formulary inclusion in the United States. As defined by US law, a biosimilar is a biologic that is highly similar to its reference product, notwithstanding minor differences in clinically inactive components, and should not have clinically meaningful differences from its reference product in safety, purity, and potency. We review biosimilars and the current European Union and US regulatory pathways for biosimilars. Furthermore, we propose a checklist of considerations to ensure that US pharmacists thoroughly evaluate future biosimilars for formulary inclusion. Included in the checklist are considerations related to the availability of preapproval and postapproval safety and efficacy data; differences in product characteristics and immunogenicity between the biosimilar and reference product; manufacturer-related parameters that can affect a reliable supply of quality products; health-system and patient perspectives on product packaging, labeling, storage, and administration; costs and insurance coverage; patient education; interchangeability and differences in the range of indications; and evaluation of institutions’ information technology systems.Key Words: biologics, biosimilars, formulary, pharmacovigilance, reference productThe first biosimilar was licensed for use in humans in the European Union (EU) in 2006; since that time, a total of 11 distinct biosimilar products have been approved for marketing in the EU under 19 different trade names (2 have since been withdrawn) (1 As more patents for biologic drugs approach expiration, the number of biosimilars entering the market is expected to grow.2,3 Yet, as the market awaits the first US biosimilar approval, questions remain about how this new class of drugs will be evaluated for incorporation into US formularies. In the US, the Biologics Price Competition and Innovation Act of 2009 (BPCI Act)—a part of the Affordable Care Act of 2009—provided for an abbreviated regulatory approval pathway for biosimilars.4,5 As defined by the BPCI Act, a biosimilar is a biologic product that is highly similar to its reference product, notwithstanding minor differences in clinically inactive components; a biosimilar is to have no clinically meaningful differences from its reference product in terms of safety, purity, and potency. 4

Table 1.

Biosimilars authorized in the European Uniona
BiosimilarActive substanceManufacturerbMarketing authorization holder/applicant
Granulocyte colony-stimulating factors

BiograstimfilgrastimSicor Biotech UABCT Arzneimittel GmbH
Filgrastim HexalfilgrastimSandoz GmbHHexal AG
Filgrastim ratiopharmcfilgrastimSicor Biotech UABRatiopharm GmbH
GrastofilfilgrastimIntas Biopharmaceuticals Ltd.; Apotex Nederland BVApotex Europe BV
NivestimfilgrastimHospira ZagrebHospira UK Ltd.
RatiograstimfilgrastimSicor Biotech UABRatiopharm GmbH
TevagrastimfilgrastimSicor Biotech UABTeva Generics GmbH
ZarziofilgrastimSandoz GmbHSandoz GmbH

Erythropoietins

Abseamedepoetin alfaRentschler Biotechnologie GmbH;
Lek Pharmaceuticals
Medice Arzneimittel
Pütter GmbH & Co. KG
Binocritepoetin alfaRentschler Biotechnologie GmbH;
Lek Pharmaceuticals
Sandoz GmbH
Epoetin Alfa Hexalepoetin alfaRentschler Biotechnologie GmbH;
Lek Pharmaceuticals
Hexal AG
Retacritepoetin zetaNorbitec GmbHHospira UK Ltd.
Silapoepoetin zetaNorbitec GmbHStada Arzneimittel AG

Growth hormones

OmnitropesomatropinSandoz GmbHSandoz GmbH
ValtropincsomatropinLG Life Sciences Ltd.BioPartners GmbH

Follicle-stimulating hormone

Bemfolafollitropin alfaPolymun Scientific
Immunbiologische Forshung GmbH;
Finox Biotech AG
Finox Biotech AG
Ovaleapfollitropin alfaMerckle Biotec GmbH;
Teva Pharmaceuticals;
Europe BV
Teva Pharma BV

Anti-human tumor necrosis factor alpha 2 monoclonal antibody

InflectrainfliximabCelltrion Inc.Hospira UK Ltd
RemsimainfliximabCelltrion Inc.Celltrion Healthcare Hungary Kft
Open in a separate windowaAs of September 3, 2014.bThe same biosimilar from one manufacturer (eg, Sicor Biotech UAB) may be marketed under different brand names.cMarketing authorization in the EU withdrawn at the request of the marketing authorization holder.Small-molecule generic drugs can be produced using well-defined chemical processes, but biologic drugs are typically large molecules with a complex structure that are manufactured in bioreactors using living cells.6 Because the details of manufacturing processes for biologic drugs are often proprietary to the innovator manufacturer, the processes for biosimilar production, such as cell culture, fermentation, and purification, must be independently developed by the biosimilar manufacturer.6 Consequently, there is potential for subtle differences between biosimilars and their reference products.68 Thus, biosimilars will require more extensive evaluation than small molecule generic drugs9; the type and amount of clinical data required will be determined on a case-bycase basis.10The US Food and Drug Administration (FDA) approval pathway for biosimilars recommends a side-by-side comparison with an approved reference product that should include comparative analytic studies to characterize the product and to identify impurities, animal studies to assess toxicity, clinical studies to assess pharmacokinetics and/or pharmacodynamics and immunogenicity, and additional studies as needed to demonstrate safety and efficacy in the intended conditions of use.10,11 Because this abbreviated approval pathway is based on demonstrated similarity to a well characterized, approved reference product, it is expected that some biosimilars will be approved with fewer patients studied and less clinical efficacy and safety data than were required for the reference product, but with more required analytical information (eg, structure and function).12,13 However, based on the US definition of a biosimilar, clinical data are not anticipated to significantly differentiate a biosimilar from its reference product. According to the FDA’s interpretation of the BPCI Act, a biosimilar can be approved with fewer indications of use, fewer routes of administration, fewer product presentations, and different formulations and container closures than the reference product.14 Although no clinically relevant differences in safety or efficacy between a biosimilar and its reference products are permitted, there could be some differences in immunogenicity profiles that are not considered clinically relevant; in some cases, these differences may only become apparent through postapproval safety monitoring.10 Therefore, it is important for pharmacists to consider additional product- and manufacturer-related parameters when evaluating biosimilars for potential formulary inclusion.9Given the unique nature of biosimilars and their abbreviated regulatory pathway, formulary review and therapeutic interchange options will need to be considered for this class of medicines. This review provides an overview of biosimilars, offers insights into EU and US regulatory pathways for biosimilars, and recommends a checklist of considerations for pharmacists when evaluating biosimilars for inclusion in a US health-system formulary.  相似文献   
145.
In the Covid-19 pandemic, being older means being in a special focus: Probabilities for severe infections and mortality rise with increasing age and protective measures for this population group have been increased. This was accompanied by public discourse that portrayed older adults stereotypically as vulnerable and frail but also highlighted the hardships younger people have to endure to protect them. Given the possibly detrimental effects of ageism on individuals and societies, we were interested in older adults’ perception of ageism in the Corona-crisis and its relation to their health and well-being. Furthermore, we were interested in subjective aging variables as moderators in the ageism–health relationship. In June 2020, N = 611 independently living people aged 60 + from the Grand Duchy of Luxembourg were recruited via a survey research institute and interviewed online or by phone. They reported on perceived ageism in different contexts, their life satisfaction, subjective health, subjective age and self-perceptions of aging. Depending on context, ageism was perceived by around 20% of participants, and overall negatively related to subjective health and life satisfaction after the onset of the pandemic. Moderated hierarchical regressions showed that a younger subjective age buffered the negative effect of ageism on subjective health, while perceiving aging as social loss increased its effect on life satisfaction. We discuss the importance of addressing and reducing ageism (not only) in times of crisis and the consequences for individuals and societies.  相似文献   
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147.
The rapidly growing mycobacteria (RGM) differ from slow-growing mycobacteria such as Mycobacterium tuberculosis by virtue of their more rapid growth in culture media and their in vitro resistance to standard antituberculosis drugs. The RGM can produce numerous infections including chronic lung disease. The most common causes of pulmonary disease are Mycobacterium abscessus and Mycobacterium fortuitum. This article reviews the management of patients with lung disease caused by RGM.  相似文献   
148.
Glutathione: interorgan translocation, turnover, and metabolism.   总被引:19,自引:20,他引:19       下载免费PDF全文
Glutathione is translocated out of cells; cells that have membrane-bound gamma-glutamyl transpeptidase can utilize translocated glutathione, whereas glutathione exported from cells that do not have appreciable transpeptidase enters the blood plasma. Glutathione is removed from the plasma by the kidney and other organs that have transpeptidase. Studies in which mice and rats were treated with buthionine sulfoximine, a selective and potent inhibitor of gamma-glutamylcysteine synthetase and therefore of glutathione synthesis, show that glutathione turns over at a significant rate in many tissues, especially kidney, liver, and pancreas; the rate of turnover in mouse skeletal muscle is about 60% of that in the kidney. Experiments on rats surgically deprived of one or both kidneys and treated with the gamma-glutamyl transpeptidase inhibitor D-gamma-glutamyl-(o-carboxy)phenylhydrazide establish that extrarenal gamma-glutamyl transpeptidase activity accounts for the utilization of about one-third of the total blood plasma glutathione. Normal animals treated with the transpeptidase inhibitor excrete large amounts of glutathione in their urine. They also excrete gamma-glutamylcysteine, suggesting that cleavage of glutathione at the cysteinylglycine bond may be of metabolic significance. The present and earlier findings lead to a tentative scheme (presented here) for the metabolism and translocation of glutathione, gamma-glutamyl amino acids, and related compounds.  相似文献   
149.
Substrate analogs have been obtained that selectively inhibit the reactions of the gamma-glutamyl cycle or that are susceptible to only limited metabolism by the cycle. Thus, glutathione synthesis may be inhibited and analogs of glutathione may be synthesized that do not participate in transpeptidation. Specific inhibitors of gamma-glutamylcyclotransferase and 5-oxoprolinase have been obtained. The findings offer new approaches to the in vivo study of the cycle and also to the design of more specifically directed analogs of inhibitors such as methionine sulfoximine and 6-diazo-5-oxonorleucine.  相似文献   
150.
Delayed donor red cell engraftment and pure red cell aplasia (PRCA) are well-recognized complications of major ABO-incompatible hematopoietic stem cell transplantation (SCT) performed by means of myeloablative conditioning. To evaluate these events following reduced-intensity nonmyeloablative SCT (NST), consecutive series of patients with major ABO incompatibility undergoing either NST (fludarabine/cyclophosphamide conditioning) or myeloablative SCT (cyclophosphamide/high-dose total body irradiation) were compared. Donor red blood cell (RBC) chimerism (initial detection of donor RBCs in peripheral blood) was markedly delayed following NST versus myeloablative SCT (median, 114 versus 40 days; P <.0001) and strongly correlated with decreasing host antidonor isohemagglutinin levels. Antidonor isohemagglutinins declined to clinically insignificant levels more slowly following NST than myeloablative SCT (median, 83 versus 44 days; P =.03). Donor RBC chimerism was delayed more than 100 days in 9 of 14 (64%) and PRCA occurred in 4 of 14 (29%) patients following NST, while neither event occurred in 12 patients following myeloablative SCT. Conversion to full donor myeloid chimerism following NST occurred significantly sooner in cases with, compared with cases without, PRCA (30 versus 98 days; P =.008). Cyclosporine withdrawal appeared to induce graft-mediated immune effects against recipient isohemagglutinin-producing cells, resulting in decreased antidonor isohemagglutinin levels and resolution of PRCA following NST. These data indicate that significantly delayed donor erythropoiesis is (1) common following major ABO-incompatible NST and (2) associated with prolonged persistence of host antidonor isohemagglutinins. The clinical manifestations of these events are affected by the degree and duration of residual host hematopoiesis.  相似文献   
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