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This paper sets out a simple framework with which to examine the performance management process. It examines the organizational context within which performance management is undertaken, and notes that it becomes most important within hierarchical organizations that allow considerable autonomy amongst devolved units. The paper argues that performance management should embrace four broad functions: formulation of strategy; development of performance measurement instruments; interpreting such measures; and encouraging appropriate organizational responses to performance information. The paper notes that operational research has made significant contributions to all four functions, and suggests that the performance management movement offers enormous possibilities for OR. Keywords: performance management; performance measurement; strategy; organizational structure

BACKGROUND: As costs continue to outpace reimbursements, hospital administrators and clinicians face increasing pressure to justify new capital purchases. Massachusetts Health Care Reform has added further economic challenges for Disproportionate Share Hospitals (DSH), as resources formerly available to treat the uninsured have been redirected. In this challenging climate, many hospitals still lack a standardized process for technology planning and/or vendor negotiation. PURPOSE:: The purpose of this study was to determine whether a simple, coordinated clinical and financial analysis of a technology, Endoscopic Carpal Tunnel Release (ECTR), is sufficient to impact vendor pricing at Cambridge Health Alliance (CHA), a disproportionate share hospital (DSH) in Cambridge, Massachusetts. METHODOLOGY: This case study addressed the topic of technology adoption, a complex decision-making process every hospital administration faces. Taking note of other hospitals approaches to instill a strategic management culture, CHA combined a literature review on clinical outcomes and financial analysis on profitability. Clinical effectiveness was evaluated through a literature review. The financial analysis was based on a retrospective inquiry of fixed and variable costs, reimbursement rates, actual payer mix, and profitability of adopting ECTR over open carpal tunnel release at CHA. This clinical and financial analysis was then shared with the vendor. FINDINGS: A literature review revealed that although there are short-term benefits to ECTR, there is little to no difference in long-term outcomes to justify a calculated incremental loss of $91.49 in revenue per case. Sharing this analysis with the vendor resulted in a 30% price reduction. A revised cost analysis demonstrated a $53.51 incremental gain in revenue per case. CHA has since elected to offer ECTR to its patients. PRACTICE IMPLICATIONS: Smaller hospital systems often have modest leverage in vendor negotiations. Our results suggest that the development of adoption criteria and an evidence-based managerial approach can create dialogue with vendors and directly impact pricing. Coordinated clinical and financial analysis is a powerful tool, enabling administrators, clinicians, and medical device suppliers to work constructively to provide patients access to innovative technology, even in the face of a challenging payer mix. Ongoing assessment of clinical outcomes and financial data must be performed to reflect the most up-to-date scientific and economic climate. [ABSTRACT FROM AUTHOR]

We estimated the long-term carbon balance [net biome production (NBP)] of European (EU-25) croplands and its component fluxes, over the last two decades. Net primary production (NPP) estimates, from different data sources ranged between 490 and 846 gC m−2 yr−1, and mostly reflect uncertainties in allocation, and in cropland area when using yield statistics. Inventories of soil C change over arable lands may be the most reliable source of information on NBP, but inventories lack full and harmonized coverage of EU-25. From a compilation of inventories we infer a mean loss of soil C amounting to 17 g m−2 yr−1. In addition, three process-based models, driven by historical climate and evolving agricultural technology, estimate a small sink of 15 g C m−2 yr−1 or a small source of 7.6 g C m−2 yr−1. Neither the soil C inventory data, nor the process model results support the previous European-scale NBP estimate by Janssens and colleagues of a large soil C loss of 90 ± 50 gC m−2 yr−1. Discrepancy between measured and modeled NBP is caused by erosion which is not inventoried, and the burning of harvest residues which is not modeled. When correcting the inventory NBP for the erosion flux, and the modeled NBP for agricultural fire losses, the discrepancy is reduced, and cropland NBP ranges between −8.3 ± 13 and −13 ± 33 g C m−2 yr−1 from the mean of the models and inventories, respectively. The mean nitrous oxide (N2O) flux estimates ranges between 32 and 37 g C Eq m−2 yr−1, which nearly doubles the CO2 losses. European croplands act as small CH4 sink of 3.3 g C Eq m−2 yr−1. Considering ecosystem CO2, N2O and CH4 fluxes provides for the net greenhouse gas balance a net source of 42–47 g C Eq m−2 yr−1. Intensifying agriculture in Eastern Europe to the same level Western Europe amounts is expected to result in a near doubling of the N2O emissions in Eastern Europe. N2O emissions will then become the main source of concern for the impact of European agriculture on climate. [ABSTRACT FROM AUTHOR]

Silymarin, derived from the milk thistle plant Silybum marianum, is widely used for self-treatment of liver diseases, including hepatitis C virus (HCV), and its antiviral activity has been demonstrated in vitro and in HCV patients administered an intravenous formulation of the major silymarin flavonolignans, silybin A and silybin B. The safety and dose-exposure relationships of higher than customary oral doses of silymarin and its acute effects on serum HCV RNA were evaluated in noncirrhotic HCV patients. Four cohorts of 8 patients with well-compensated, chronic noncirrhotic HCV who failed interferon-based therapy were randomized 3:1 to silymarin or placebo. Oral doses of 140, 280, 560, or 700 mg silymarin were administered every 8 hours for 7 days. Steady-state exposures for silybin A and silybin B increased 11-fold and 38-fold, respectively, with a 5-fold increase in dose, suggesting nonlinear pharmacokinetics. No drug-related adverse events were reported, and no clinically meaningful reductions from baseline serum transaminases or HCV RNA titer were observed. Oral doses of silymarin up to 2.1 g per day were safe and well tolerated. The nonlinear pharmacokinetics of silybin A and silybin B suggests low bioavailability associated with customary doses of silymarin may be overcome with doses above 700 mg. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVES: Destruction of the supporting periodontal tissues is mediated by the action of several proteolytic enzymes. Urokinase is a serine protease that plays a key role in connective tissue destruction through conversion of plasminogen into plasmin. The present study was conducted to evaluate the effect of triclosan on the production and activity of urokinase in cultured gingival fibroblasts. MATERIAL AND METHODS: Urokinase production was studied in primary cultures of human gingival fibroblasts stimulated with tumor necrosis factor-alpha. Urokinase activity and production were evaluated using casein zymography and western blotting, respectively. Urokinase mRNA expression was evaluated using the reverse transcription-polymerase chain reaction. Triclosan was used to interfere with this stimulatory effect. The roles of different cell-signaling cascades involved in urokinase production were assessed through western blotting and immunofluorescence using several cell-signaling inhibitors. RESULTS: Tumor necrosis factor-alpha was found to be a strong stimulus for urokinase production and triclosan was able to inhibit this response at the protein and mRNA levels. Triclosan was also able to inhibit conversion of plasminogen into plasmin. Tumor necrosis factor-alpha-stimulated urokinase production was shown to be dependent on the nuclear factor-kappaB and c-Jun N-terminal kinase signaling pathways. Triclosan inhibited c-Jun N-terminal kinase phosphorylation and c-Jun production. CONCLUSIONS: Within the limits of this study, these results show that triclosan may inhibit urokinase production and plasminogen activation in gingival fibroblasts through modulation of the c-Jun N-terminal kinase signaling pathway. [ABSTRACT FROM AUTHOR]

Background and Objectives: Membrane type 1-matrix metalloproteinase (MT1- MMP) is a collagenolytic enzyme involved in connective tissue remodeling. In periodontal tissues, either cytokines or growth factors regulate the production of proteolytic enzymes. Mice deficient in epidermal growth factor receptor (EGFR) show a reduced expression of MT1-MMP, suggesting that this receptor may play an important role in MT1-MMP production. The present study evaluated the role of the inflammatory cytokine tumor necrosis factor-a (TNF-a) and EGFR in the production of MT1-MMP in gingival fibroblasts. Material and Methods: Primary cultures of human gingival fibroblasts were cultured over plastic or a type I collagen matrix and stimulated with TNF-a and EGF. A selective EGFR inhibitor (AG1478) was used to interfere with this signaling pathway. Production of MT1-MMP and activation of proMMP-2 were studied using Western blot and gelatin zymography, respectively. Activation of EGFR signaling was assessed through immunoprecipitation and Western blot. Expression of EGFR ligands was determined through reverse transcriptase-polymerase chain reaction. Results: Treatment of gingival fibroblasts cultured over a collagen matrix with TNF-a stimulated proMMP-2 activation and MT1-MMP production. However, after using AG1478, both responses were inhibited. Tumor necrosis factor-a induced EGFR transactivation and stimulated the expression of the mRNA for the EGFR ligands heparin binding-epidermal growth factor (HB-EGF) and transforming growth factor-a (TGF-a). [ABSTRACT FROM AUTHOR]

The United Kingdom of Great Britain and Northern Ireland has extensive experience in allocating health service funds to regions and localities using funding formulae. This paper focuses on England. Special attention is given to recent policy concerns to reduce avoidable health inequalities by broadening the remit of the resource allocation formulae. The paper also examines the issues that arise when seeking to allocate funds to very small organizational units, such as general practices. The English example is relevant to less-developed health systems, especially for those governments seeking to decentralize, to improve accountability and to promote equity. Copyright © 2008 World Health Organization [ABSTRACT FROM AUTHOR]

Background and Objectives: Myofibroblastic differentiation is an important event in gingival wound healing and chronic inflammation. Transforming frowth factor-[beta] 1 (TGF-[beta]1) is a potent growth factor that has been implicated in this process. Gingival myofibroblasts have an increased ability to remodel the extracellular matrix and this feature has been associated with changes in the distribution of F-actin and the expression of the myofibroblast marker [alpha]-smooth muscle actin. In the present study we have analyzed the role of TGF-[beta]1 and the signaling routes activated by this factor in the cytoskeletal changes that characterize the myofibroblastic differentiation process in human gingival fibroblasts. Materials and methods: The signalling pathways involved in myofibroblastic differentiation were studied in primary cultures of human gingival fibroblasts using several signal transduction inhibitors. RhoA activation was analyzed through a pull-down assay. Distribution of focal adhesions and actin cytoskeleton was assessed by means of immunofluorescence and western blot. A cell adhesion assay was performed in TGF-[beta]1-stimulated cells. Smooth muscle actin expression was studied through western blot and imunofluorescence. c-Jun N-terminal kinase phosphorylation was assessed through western blot. Results: Our observations show that TGF-[beta]1 activated the GTPase RhoA, a key regulator of the actin cytoskeleton. As a consequence of this event, this growth factor stimulated the generation of actin stress fibers and the reinforcement of vinculin-enriched focal adhesions. These responses were blocked after inhibiting ROCK, the main target of RhoA activation. TGF-[beta]1 also stimulated the adhesion of fibroblasts over fibronectin, an extracellular matrix molecule involved in myofibroblastic differentiation. Finally, induction of the myofibroblast marker [alpha]-smooth muscle actin by TGF-[beta]1 was abolished by the c-Jun N-terminal protein kinase inhibitor SP600125, suggesting a role for this signaling pathway during the induction of this phenotype. Conclusions: We propose that TGF-[beta]1 may promote the differentiation of myofibroblasts through the stimulation of cell spreading and adhesion, the reinforcement of focal adhesions, the maturation of the actin cytoskeleton, and the induction of [alpha]-smooth muscle actin. Activity of RhoA-ROCK and c-Jun N-terminal protein kinase signaling pathways are probably involved in these cellular events. [ABSTRACT FROM AUTHOR]

Chronic venous disease with skin changes of the leg is a common condition affecting up to 1 in 20 people in westernized countries. The causes of this problem are not fully understood, although research in recent years has revealed a number of important mechanisms that contribute to the disease process. Patients with chronic venous disease suffer persistently raised pressures in their deep and superficial veins in the lower limb. Leucocytes become 'trapped' in the circulation of the leg during periods of venous hyper-tension produced by sitting or standing. Studies of the plasma levels of neutrophil granule enzymes shows that these are increased during periods of venous hypertension, suggesting that this causes activation of the neutrophils. Investigation of the leucocyte surface ligands CD11b and CD62L shows that the more activated neutrophils and monocytes are sequestered during venous hypertension. Measurement of plasma levels of the soluble parts of the endothelial adhesion molecules VCAM, ICAM, and ELAM show that these are all elevated in patients with chronic venous disease compared to controls. Following 30 minutes of venous hypertension produced by standing, these levels are further increased. These data suggest that venous hypertension causes neutrophil and monocyte activation, which in turn causes injury to the endothelium. Chronic injury to the endothelium leads to a chronic inflammatory condition of the skin that we know clinically as lipodermatosclerosis. This is mediated by perivascular inflammatory cells, principally macrophages, in the skin microcirculation. These stimulate fibroblasts in the skin leading to tissue remodeling and laying down of fibrous tissue. Vascular endothelial growth factor stimulates proliferation of capillaries within the skin. Skin in this state has the potential to ulcerate in response to minor injury. [ABSTRACT FROM AUTHOR]

Transforming Growth Factor-beta1 (TGF-beta1) plays a key role in connective tissue remodeling and inflammation. Under pathological conditions, like periodontal disease, fibroblasts may display an altered response to this growth factor. To investigate this question, we have studied whether TGF-beta1 may differentially regulate the expression of urokinase at the protein level in primary cultures of fibroblasts derived from healthy gingiva, granulation tissue from gingival wounds, and chronic periodontal disease. We observed that TGF-beta1 may repress urokinase expression in healthy gingival fibroblasts and promote its production in granulation-tissue fibroblasts. A significant correlation was found between expression of the myofibroblast marker alpha-smooth-muscle actin and stimulation of urokinase production by TGF-beta1. Immunostaining of gingival wounds showed that myofibroblasts were involved in urokinase production. TGF-beta1-stimulated urokinase expression was blocked after inhibition of the c-jun-NH2 terminal kinase signaling pathway. We propose that stimulation of urokinase production by TGF-beta1 is involved in the responses of activated fibroblasts to tissue injury. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the effect of concurrent antibiotic administration on the disposition of mycophenolic acid (MPA) and mycophenolic acid glucuronide (MPAG) after oral administration of mycophenolate mofetil (MMF) in healthy subjects. Eleven healthy subjects were enrolled. The study was divided into 4 treatment periods. Subjects received MMF as a single oral 1-g dose alone and were then randomized to 3 antibiotic treatment periods. The 3 periods included norfloxacin, metronidazole, and a combination of norfloxacin and metronidazole. Antibiotic treatment was started 3 days prior to each MMF pharmacokinetic study day and was given for a total of 5 days. On day 4 of each antibiotic phase, subjects received a single 1-g oral dose of MMF. Plasma and urine samples were obtained over 48 hours after the MMF dose in all treatment periods and were quantitatively measured for MPA and MPAG. Pharmacokinetic parameters for MPA and MPAG were determined for all periods. Compared to MMF alone, the area under the plasma concentration versus time curve (AUC) of MPA was reduced by an average of 10%, 19%, and 33% when given with norfloxacin, metronidazole, and norfloxacin plus metronidazole, respectively. The AUC of MPAG was also reduced on average by 10%, 27%, and 41% in the corresponding periods. The combination of norfloxacin and metronidazole significantly reduced the AUC of MPA and MPAG in healthy subjects. This likely occurs as a result of reduced enterohepatic recirculation. [ABSTRACT FROM AUTHOR]

Clinical Inquiries provides answers to questions submitted by practicing family physicians to the Family Physicians Inquiries Network (FPIN). Members of the network select questions based on their relevance to family medicine. Answers are drawn from an approved set of evidence-based resources and undergo peer review. The strength of recommendations and the level of evidence for individual studies are rated using criteria developed by the Evidence-Based Medicine Working Group (http:// www.cebm.net/Ievels_of_ evidence.asp). The complete database of evidence-based questions and answers is copyrighted by FPIN. If interested in submitting questions or writing answers for this series, go to http://www.fpin. org or e-mail: questions@ fpin.org. A collection of FPIN's Clinical Inquiries published in AFP is available at http://www.aafp.org/ afp/fpin. [ABSTRACT FROM AUTHOR]

Manganese and calcium homeostasis and signalling, in eukaryotic organisms, are regulated through membrane located pumps, channels and exchangers, including the Mn 2+ /Ca 2+ uncharacterized protein family 0016 (UPF0016). Here we show that Plasmodiophora brassicae PbGDT1 is a member of the UPF0016 and an ortholog of Saccharomyces cerevisiae Gdt1p (GCR Dependent Translation Factor 1) protein involved in manganese homeostasis as well as the calcium mediated stress response in yeast. PbGDT1 complemented the ScGdt1p and ScPMR1 (Ca 2+ ATPase) double null mutant under elevated calcium stress but not under elevated manganese conditions. In both yeast and Nicotiana benthamiana, PbGDT1 localizes to the Golgi apparatus, with additional ER association in N. benthamiana. Expression of PbGDT1 in N. benthamiana, suppresses BAX-triggered cell death, further highlighting the importance of calcium homeostasis in maintaining cell physiology and integrity in a stress environment., 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 © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Objective: Forkhead box-O 1 (FOXO1) is a transcription factor actively involved in oral wound healing at the epithelial barrier. However, less is known regarding the role of FOXO1 during the tissue repair response in the connective tissue compartment. This study explored the involvement of FOXO1 in the modulation of fibroblast activity related to wound healing., Methods: Primary cultures of human gingival fibroblasts were obtained from four healthy young donors. Myofibroblastic differentiation, collagen gel contraction, cell migration, cell spreading, and integrin activation were evaluated in the presence or absence of a FOXO1 inhibitor (AS1842856). Variations in mRNA and proteins of interest were evaluated through qRT-PCR and western blot, respectively. Distribution of actin, α-smooth muscle actin, and β1 integrin was evaluated using immunofluorescence. FOXO1 and TGF-β1 expression in gingival wound healing was assessed by immunohistochemistry in gingival wounds performed in C57BL/6 mice. Images were analyzed using ImageJ/Fiji. ANOVA or Kruskal-Wallis test followed by Tukey's or Dunn's post-hoc test was performed. All data are expressed as mean ± SD. p < .05 was considered statistically significant., Results: FOXO1 inhibition caused a decrease in the expression of the myofibroblastic marker α-SMA along with a reduction in fibronectin, type I collagen, TGF-β1, and β1 integrin mRNA level. The FOXO1 inhibitor also caused decreases in cell migration, cell spreading, collagen gel contraction, and β1 integrin activation. FOXO1 and TGF-β1 were prominently expressed in gingival wounds in fibroblastic cells located at the wound bed., Conclusion: The present study indicates that FOXO1 plays an important role in the modulation of several wound-healing functions in gingival fibroblast. Moreover, our findings reveal an important regulatory role for FOXO1 on the differentiation of gingival myofibroblasts, the regulation of cell migration, and collagen contraction, all these functions being critical during tissue repair and fibrosis., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Leukocyte and Platelet-Rich Fibrin (L-PRF) is part of the second generation of platelet-concentrates. L-PRF derived from nonsmokers has been used in surgical procedures, with its beneficial effects in wound healing being proven to stimulate biological activities such as cell proliferation, angiogenesis, and differentiation. Cigarette smoking exerts detrimental effects on tissue healing and is associated with post-surgical complications; however, evidence about the biological effects of L-PRF derived from smokers is limited. This study evaluated the impact of L-PRF secretome (LPRFS) derived from smokers and nonsmokers on angiogenesis and osteoblast differentiation. LPRFS was obtained by submerging L-PRF membranes derived from smokers or nonsmokers in culture media and was used to treat endothelial cells (HUVEC) or SaOs-2 cells. Angiogenesis was evaluated by tubule formation assay, while osteoblast differentiation was observed by alkaline phosphatase and osterix protein levels, as well as in vitro mineralization. LPRFS treatments increased angiogenesis, alkaline phosphatase, and osterix levels. Treatment with 50% of LPRFS derived from smokers and nonsmokers in the presence of osteogenic factors stimulates in vitro mineralization significantly. Nevertheless, differences between LPRFS derived from smokers and nonsmokers were not found. Both LPRFS stimulated angiogenesis and osteoblast differentiation in vitro; however, clinical studies are required to determine the beneficial effect of LPRFS in smokers.

Perinatal mortality is a common problem in mouse breeding colonies. Few studies have examined the influence of environmental changes on mouse pup survival. In this study, monogamous breeding cages of C57BL/6J mice were set up and randomized into 3 cage change groups: 1) cage change at 8 d after parturition, 2) cage change at 3 d after parturition, or 3) cage change at 3 d after parturition with the addition of a polycarbonate hut in the cage. Pairs were bred to produce a minimum of 4 litters. Pup survival to weaning relative to experimental cage change date, and survival rates after cage change were evaluated. The results revealed no significant differences between experimental groups. The majority of pup loss occurred within the first 24 h after birth for those pups that were alive at birth. Overall, the postpartum day of cage change did not affect the perinatal survival of mouse pups.

Seasonal infection rates of individual viruses are influenced by synergistic or inhibitory interactions between coincident viruses. Endemic patterns of SARS-CoV-2 and influenza infection overlap seasonally in the Northern hemisphere and may be similarly influenced. We explored the immunopathologic basis of SARS-CoV-2 and influenza A (H1N1pdm09) interactions in Syrian hamsters. H1N1 given 48 h prior to SARS-CoV-2 profoundly mitigated weight loss and lung pathology compared to SARS-CoV-2 infection alone. This was accompanied by the normalization of granulocyte dynamics and accelerated antigen-presenting populations in bronchoalveolar lavage and blood. Using nasal transcriptomics, we identified a rapid upregulation of innate and antiviral pathways induced by H1N1 by the time of SARS-CoV-2 inoculation in 48 h dual-infected animals. The animals that were infected with both viruses also showed a notable and temporary downregulation of mitochondrial and viral replication pathways. Quantitative RT-PCR confirmed a decrease in the SARS-CoV-2 viral load and lower cytokine levels in the lungs of animals infected with both viruses throughout the course of the disease. Our data confirm that H1N1 infection induces rapid and transient gene expression that is associated with the mitigation of SARS-CoV-2 pulmonary disease. These protective responses are likely to begin in the upper respiratory tract shortly after infection. On a population level, interaction between these two viruses may influence their relative seasonal infection rates.

Aldehyde oxidase (AOX) is a cytosolic drug-metabolizing enzyme which has attracted increasing attention in drug development due to its high hepatic expression, broad substrate profile and species differences. In contrast, there is limited information on the presence and activity of AOX in extrahepatic tissues including ocular tissues. Because several ocular drugs are potential substrates for AOX, we performed a comprehensive analysis of the AOX1 expression and activity profile in seven ocular tissues from humans, rabbits, and pigs. AOX activities were determined using optimized assays for the established human AOX1 probe substrates 4-dimethylamino-cinnamaldehyde (DMAC) and phthalazine. Inhibition studies were undertaken in conjunctival and retinal homogenates using well-established human AOX1 inhibitors menadione and chlorpromazine. AOX1 protein contents were quantitated with targeted proteomics and confirmed by immunoblotting. Overall, DMAC oxidation rates varied over 10-fold between species (human ˃˃ rabbit ˃ pig) and showed 2- to 6-fold differences between tissues from the same species. Menadione seemed a more potent inhibitor of DMAC oxidation across species than chlorpromazine. Human AOX1 protein levels were highest in the conjunctiva, followed by most posterior tissues, whereas anterior tissues showed low levels. The rabbit AOX1 expression was high in the conjunctiva, retinal pigment epithelial (RPE), and choroid while lower in the anterior tissues. Quantification of pig AOX1 was not successful but immunoblotting confirmed the presence of AOX1 in all species. DMAC oxidation rates and AOX1 contents correlated quite well in humans and rabbits. This study provides, for the first time, insights into the ocular expression and activity of AOX1 among multiple species., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

A variety of methodologies have been developed to help health systems increase the 'value' created from their available resources. The urgency of creating value is heightened by population ageing, growth in people with complex morbidities, technology advancements, and increased citizen expectations. This study develops a policy framework that seeks to reconcile the various approaches towards value-based policies in health systems. The distinctive contribution is that we focus on the value created by the health system as a whole, including health promotion, thus moving from value-based health care towards a value-based health system perspective. We define health system value to be the contribution of the health system to societal wellbeing. We adopt a framework of five dimensions of value, embracing health improvement, health care responsiveness, financial protection, efficiency and equity, which we map onto a society's aggregate wellbeing. Actors within the health system make different contributions to value, and we argue that their perspectives can be aligned with a unifying concept of health system value. We provide examples of policy levers and highlight key actors and how they can promote certain aspects of health system value. We discuss advantages of value-based approach based on the notion of wellbeing and some practical obstacles to its implementation., Competing Interests: Declaration of Competing Interest We have no conflict of interest to declare., (Copyright © 2023. Published by Elsevier B.V.)