Adenovirus type 37 (Ad37) is a leading cause of epidemic keratoconjunctivitis (EKC), a severe and highly contagious ocular disease. Whereas most other adenoviruses infect cells by engaging CD46 or the coxsackie and adenovirus receptor (CAR), Ad37 binds previously unknown sialic acid-containing cell surface molecules. By glycan array screening, we show here that the receptor-recognizing knob domain of the Ad37 fiber protein specifically binds a branched hexasaccharide that is present in the GD1a ganglioside and that features two terminal sialic acids. Soluble GD1a glycan and GD1a-binding antibodies efficiently prevented Ad37 virions from binding and infecting corneal cells. Unexpectedly, the receptor is constituted by one or more glycoproteins containing the GD1a glycan motif rather than the ganglioside itself, as shown by binding, infection and flow cytometry experiments. Molecular modeling, nuclear magnetic resonance and X-ray crystallography reveal that the two terminal sialic acids dock into two of three previously established sialic acid-binding sites in the trimeric Ad37 knob. Surface plasmon resonance analysis shows that the knob-GD1a glycan interaction has high affinity. Our findings therefore form a basis for the design and development of sialic acid-containing antiviral drugs for topical treatment of EKC.
Background
Value-based reimbursement programs have become increasingly common. However, little is known about the effect of such programs on patient reported outcomes. Thus, the aim of this study was to analyze the effect of introducing a value-based reimbursement program on patient reported outcome measures and to explore whether a selection bias towards less complicated patients occurred.
Methods
This is a retrospective observational study with a before and after design based on the introduction of a value-based reimbursement program in Region Stockholm, Sweden. We analyzed patient level data from inpatient and outpatient care of patients undergoing lumbar spine surgery during 2006–2015. Patient reported outcome measures used was Global Assessment, EQ-5D-3L and Oswestry Disability Index. The case-mix of surgically treated patients was analyzed using medical and socioeconomic factors.
Results
The value-based reimbursement program did not have any effect on targeted or non-targeted patient reported outcome measures. Moreover, the share of surgically treated patients with risk factors such as having comorbidities and being born outside of Europe increased after the introduction. Hence, the value-based reimbursement program did not encourage discrimination against sicker patients. However, the income was higher among patients surgically treated after the introduction of the value-based reimbursement. This indicates that a value-based reimbursement program may contribute to increased inequalities in access to healthcare.
Conclusions
The value-based reimbursement program did not have any effect on patient reported outcome measures. Our study contributes to the understanding of the effects of a value-based reimbursement program on patient reported outcome measures and to what extent cherry-picking arises.
Reimbursement programmes are used to manage care through financial incentives. However, their effects are mixed and the programmes can motivate behaviour that goes against professional values. Value-based reimbursement programmes may better align professional values with financial incentives. The aim of this study is to analyse if and how healthcare providers adapt their practices to a value-based reimbursement programme that combines bundled payment with performance-based payment.Forty-one semi-structured interviews were conducted with representatives from healthcare providers within spine surgery in Sweden. Data were analysed using thematic analysis with an abductive approach and a conceptual framework based on neo-institutional theory. Healthcare providers were positive to the idea of a value-based reimbursement programme. However, during its introduction it became evident that some aspects were easier to adapt to than others. The bundled payment provided a more comprehensive picture of the patients' needs but to an increased administrative burden. Due to the financial impact of the bundled payment, healthcare providers tried to decrease the amount of post-discharge care. The performance-based payment was appreciated. However, the lack of financial impact and transparency in how the payment was
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