Review of Economic Submissions to NICE Medical Technologies Evaluation Programme

The economic evaluation of medical devices is increasingly used to inform decision making on adopting new or novel technologies; however, challenges are inevitable due to the unique characteristics of devices. Cost-consequence analyses are recommended and employed by the English National Institute for Health and Care Excellence (NICE) Medical Technologies Evaluation Programme (MTEP) to help address these challenges. The aim of this work was to review the critiques raised for previous MTEP submissions and explore if there were common problems across submissions. We reviewed a sample of 12 economic submissions to MTEP representing 50 % of 24 sets of guidance issued to July 2015. For each submission, we reviewed the External Assessment Centre's (EAC) report and the guidance document produced by NICE. We identified the main problems raised by the EAC's assessments and the committee's considerations for each submission, and explored strategies for improvement. We found that the identification and measurement of costs and consequences are the main shortcomings within economic submissions to MTEP. Together, these shortcomings accounted for 42 % of criticisms by the EACs among the reviewed submissions. In certain circumstances problems with these shortcomings may be unavoidable, for example, if there is a limited evidence base for the device being appraised. Nevertheless, strategies can often be adopted to improve submissions, including the use of more appropriate time horizons, whilst cost and resource use information should be taken, where possible, from nationally representative sources

The restorative role of annexin A1 at the blood–brain barrier

Annexin A1 is a potent anti-inflammatory molecule that has been extensively studied in the peripheral immune system, but has not as yet been exploited as a therapeutic target/agent. In the last decade, we have undertaken the study of this molecule in the central nervous system (CNS), focusing particularly on the primary interface between the peripheral body and CNS: the blood–brain barrier. In this review, we provide an overview of the role of this molecule in the brain, with a particular emphasis on its functions in the endothelium of the blood–brain barrier, and the protective actions the molecule may exert in neuroinflammatory, neurovascular and metabolic disease. We focus on the possible new therapeutic avenues opened up by an increased understanding of the role of annexin A1 in the CNS vasculature, and its potential for repairing blood–brain barrier damage in disease and aging

Neutrinos from Stored Muons nuSTORM: Expression of Interest

The nuSTORM facility has been designed to deliver beams of electron and muon neutrinos from the decay of a stored muon beam with a central momentum of 3.8 GeV/c and a momentum spread of 10%. The facility is unique in that it will: serve the future long- and short-baseline neutrino-oscillation programmes by providing definitive measurements of electron-neutrino- and muon-neutrino-nucleus cross sections with percent-level precision; allow searches for sterile neutrinos of exquisite sensitivity to be carried out; and constitute the essential first step in the incremental development of muon accelerators as a powerful new technique for particle physics. Of the world's proton-accelerator laboratories, only CERN and FNAL have the infrastructure required to mount nuSTORM. Since no siting decision has yet been taken, the purpose of this Expression of Interest (EoI) is to request the resources required to: investigate in detail how nuSTORM could be implemented at CERN; and develop options for decisive European contributions to the nuSTORM facility and experimental programme wherever the facility is sited. The EoI defines a two-year programme culminating in the delivery of a Technical Design Report

Obesity and osteoarthritis in knee, hip and/or hand: An epidemiological study in the general population with 10 years follow-up

<p>Abstract</p> <p>Background</p> <p>Obesity is one of the most important risk factors for osteoarthritis (OA) in knee(s). However, the relationship between obesity and OA in hand(s) and hip(s) remains controversial and needs further investigation. The purpose of this study was to investigate the impact of obesity on incident osteoarthritis (OA) in hip, knee, and hand in a general population followed in 10 years.</p> <p>Methods</p> <p>A total of 1854 people aged 24–76 years in 1994 participated in a Norwegian study on musculoskeletal pain in both 1994 and 2004. Participants with OA or rheumatoid arthritis in 1994 and those above 74 years in 1994 were excluded, leaving n = 1675 for the analyses. The main outcome measure was OA diagnosis at follow-up based on self-report. Obesity was defined by a body mass index (BMI) of 30 and above.</p> <p>Results</p> <p>At 10-years follow-up the incidence rates were 5.8% (CI 4.3–7.3) for hip OA, 7.3% (CI 5.7–9.0) for knee OA, and 5.6% (CI 4.2–7.1) for hand OA. When adjusting for age, gender, work status and leisure time activities, a high BMI (> 30) was significantly associated with knee OA (OR 2.81; 95%CI 1.32–5.96), and a dose-response relationship was found for this association. Obesity was also significantly associated with hand OA (OR 2.59; 1.08–6.19), but not with hip OA (OR 1.11; 0.41–2.97). There was no statistically significant interaction effect between BMI and gender, age or any of the other confounding variables.</p> <p>Conclusion</p> <p>A high BMI was significantly associated with knee OA and hand OA, but not with hip OA.</p

Nitric oxide differentially regulates renal ATP-binding cassette transporters during endotoxemia

Nitric oxide (NO) is an important regulator of renal transport processes. In the present study, we investigated the role of NO, produced by inducible NO synthase (iNOS), in the regulation of renal ATP-binding cassette (ABC) transporters in vivo during endotoxemia. Wistar–Hannover rats were injected with lipopolysaccharide (LPS+) alone or in combination with the iNOS inhibitor, aminoguanidine. Controls received detoxified LPS (LPS−). After LPS+, proximal tubular damage and a reduction in renal function were observed. Furthermore, iNOS mRNA and protein, and the amount of NO metabolites in plasma and urine, increased compared to the LPS− group. Coadministration with aminoguanidine resulted in an attenuation of iNOS induction and reduction of renal damage. Gene expression of 20 ABC transporters was determined. After LPS+, a clear up-regulation in Abca1, Abcb1/P-glycoprotein (P-gp), Abcb11/bile salt export pump (Bsep), and Abcc2/multidrug resistance protein (Mrp2) was found, whereas Abcc8 was down-regulated. Up-regulation of Abcc2/Mrp2 was accompanied by enhanced calcein excretion. Aminoguanidine attenuated the effects on transporter expression. Our data indicate that NO, produced locally by renal iNOS, regulates the expression of ABC transporters in vivo. Furthermore, we showed, for the first time, expression and subcellular localization of Abcb11/Bsep in rat kidney

Estudo exploratório de custos e conseqüências do pré-natal no Programa Saúde da Família

OBJECTIVE: To assess costs and consequences of prenatal care on perinatal morbidity and mortality. METHODS: Evaluation study using two types of analysis: implementation and efficiency analysis, carried out at 11 Family Health Units in the Recife, Northeastern Brazil, in 2006. The costs were calculated by means of the activity-based costing technique and the cost-effectiveness ratio was calculated for each consequence. Data sources were information systems of the Ministry of Health and worksheets of costs provided by the Health Department of Recife and Instituto de Medicina Integral Prof. Fernando Figueira. Healthcare units with implemented or partially implemented prenatal care were compared in terms of their cost-effectiveness and perinatal results. RESULTS: In 64% of the units, prenatal care was implemented with a mean total cost of R$39,226.88 and variation of R$ 3,841,87 to R$8,765.02 per healthcare unit. In the units with partially implemented prenatal care (36$ 30,092.61 (R$4,272.12 to R$ 11,774.68). The mean cost per pregnant woman was R$196.13 with implemented prenatal care and R$ 150.46 with partially implemented prenatal care. A higher proportion of low birth weight, congenital syphilis, perinatal and fetal deaths was found in the partially implemented group. CONCLUSIONS: Prenatal care is cost-effective for several studied consequences. The adverse effects measured by the health indicators were lower in the units with implemented prenatal care. The mean cost in the partially implemented group was higher, which suggests a possible waste of resources, as the teams' productivity is insufficient for the installed capacity.OBJETIVO: Avaliar custos e conseqüências da assistência pré-natal na morbimortalidade perinatal. MÉTODOS: Estudo avaliativo com dois tipos de análise - de implantação e de eficiência, realizado em 11 Unidades de Saúde da Família do Recife, PE, em 2006. Os custos foram apurados pela técnica activity-based costing e a razão de custo-efetividade foi calculada para cada conseqüência. As fontes de dados foram sistemas de informação do Ministério da Saúde e planilhas de custos da Secretaria de Saúde do Recife e do Instituto de Medicina Integral Prof. Fernando Figueira. As unidades de saúde com pré-natal implantado ou parcial foram comparadas quanto ao seu custo-efetividade e resultados perinatais. RESULTADOS: Em 64% das unidades, o pré-natal estava implantado com custo médio total de R$39.226,88 e variação de R$ 3.841,87 a R$8.765,02 por Unidade de Saúde. Nas unidades parcialmente implantadas (36$ 30.092,61 (R$4.272,12 a R$ 11.774,68). O custo médio por gestante foi de R$196,13 com pré-natal implantado e R$ 150,46 no parcial. Encontrou-se maior proporção de baixo peso ao nascer, sífilis congênita, óbitos perinatais e fetais no grupo parcialmente implantado. CONCLUSÕES: Pré-natal é custo-efetivo para várias conseqüências estudadas. Os efeitos adversos medidos pelos indicadores de saúde foram menores nas unidades com pré-natal implantado. O custo médio no grupo parcialmente implantado foi mais elevado, sugerindo possível desperdício de recursos, uma vez que a produtividade das equipes é insuficiente para a capacidade instalada.OBJETIVO: Evaluar costos y consecuencias de la asistencia prenatal en la morbimortalidad perinatal. MÉTODOS: Estudio evaluativo con dos tipos de análisis: de implantación y de eficiencia, realizado en 11 Unidades de Salud de la Familia de Recife, Sureste de Brasil, en 2006. Los costos fueron mejorados por la técnica activity-based costing y la razón de costo-efectividad fue calculada para cada consecuencia. Las fuentes de datos fueron sistemas de información del Ministerio de la Salud y planillas de costos de la Secretaria de la Salud de Recife y del Instituto de Medicina Integral Prof. Fernando Figueira. Las unidades de salud con prenatal implantado o parcial fueron comparadas con relación a su costo-efectividad y resultados perinatales. RESULTADOS: En 64% de las unidades, el prenatal estaba implantado con costo promedio total de R$39.226,88 y variación de R$ 3.841,87 a R$8.765,02 por unidad de salud. En las unidades parcialmente implantadas (36$ 30.092,61 (R$4.272,12 a R$ 11.774,68). El costo promedio por gestante fue de R$196,13 con prenatal implantado y R$ 150,46 en el parcial. Se encontró mayor proporción de bajo peso al nacer, sífilis congénita, óbitos perinatales y fetales en el grupo parcialmente implantado. CONCLUSIONES: El prenatal es costo-efectivo para varias consecuencias estudiadas. Los efectos adversos medidos por los indicadores de salud fueron menores en las unidades con prenatal implantado. El costo promedio en el grupo parcialmente implantado fue más elevado, sugiriendo posible desperdicio de recursos, dado que la productividad de los equipos es suficiente para la capacidad instalada

What is the empirical evidence that hospitals with higher-risk adjusted mortality rates provide poorer quality care? A systematic review of the literature

<p>Abstract</p> <p>Background</p> <p>Despite increasing interest and publication of risk-adjusted hospital mortality rates, the relationship with underlying quality of care remains unclear. We undertook a systematic review to ascertain the extent to which variations in risk-adjusted mortality rates were associated with differences in quality of care.</p> <p>Methods</p> <p>We identified studies in which risk-adjusted mortality and quality of care had been reported in more than one hospital. We adopted an iterative search strategy using three databases – Medline, HealthSTAR and CINAHL from 1966, 1975 and 1982 respectively. We identified potentially relevant studies on the basis of the title or abstract. We obtained these papers and included those which met our inclusion criteria.</p> <p>Results</p> <p>From an initial yield of 6,456 papers, 36 studies met the inclusion criteria. Several of these studies considered more than one process-versus-risk-adjusted mortality relationship. In total we found 51 such relationships in a widen range of clinical conditions using a variety of methods. A positive correlation between better quality of care and risk-adjusted mortality was found in under half the relationships (26/51 51%) but the remainder showed no correlation (16/51 31%) or a paradoxical correlation (9/51 18%).</p> <p>Conclusion</p> <p>The general notion that hospitals with higher risk-adjusted mortality have poorer quality of care is neither consistent nor reliable.</p

Drug-induced trafficking of p-glycoprotein in human brain capillary endothelial cells as demonstrated by exposure to mitomycin C.

P-glycoprotein (Pgp; ABCB1/MDR1) is a major efflux transporter at the blood-brain barrier (BBB), restricting the penetration of various compounds. In other tissues, trafficking of Pgp from subcellular stores to the cell surface has been demonstrated and may constitute a rapid way of the cell to respond to toxic compounds by functional membrane insertion of the transporter. It is not known whether drug-induced Pgp trafficking also occurs in brain capillary endothelial cells that form the BBB. In this study, trafficking of Pgp was investigated in human brain capillary endothelial cells (hCMEC/D3) that were stably transfected with a doxycycline-inducible MDR1-EGFP fusion plasmid. In the presence of doxycycline, these cells exhibited a 15-fold increase in Pgp-EGFP fusion protein expression, which was associated with an increased efflux of the Pgp substrate rhodamine 123 (Rho123). The chemotherapeutic agent mitomycin C (MMC) was used to study drug-induced trafficking of Pgp. Confocal fluorescence microscopy of single hCMEC/D3-MDR1-EGFP cells revealed that Pgp redistribution from intracellular pools to the cell surface occurred within 2 h of MMC exposure. Pgp-EGFP exhibited a punctuate pattern at the cell surface compatible with concentrated regions of the fusion protein in membrane microdomains, i.e., lipid rafts, which was confirmed by Western blot analysis of biotinylated cell surface proteins in Lubrol-resistant membranes. MMC exposure also increased the functionality of Pgp as assessed in three functional assays with Pgp substrates (Rho123, eFluxx-ID Gold, calcein-AM). However, this increase occurred with some delay after the increased Pgp expression and coincided with the release of Pgp from the Lubrol-resistant membrane complexes. Disrupting rafts by depleting the membrane of cholesterol increased the functionality of Pgp. Our data present the first direct evidence of drug-induced Pgp trafficking at the human BBB and indicate that Pgp has to be released from lipid rafts to gain its full functionality

Complementary and alternative medicine for patients with chronic fatigue syndrome: A systematic review

<p>Abstract</p> <p>Background</p> <p>Throughout the world, patients with chronic diseases/illnesses use complementary and alternative medicines (CAM). The use of CAM is also substantial among patients with diseases/illnesses of unknown aetiology. Chronic fatigue syndrome (CFS), also termed myalgic encephalomyelitis (ME), is no exception. Hence, a systematic review of randomised controlled trials of CAM treatments in patients with CFS/ME was undertaken to summarise the existing evidence from RCTs of CAM treatments in this patient population.</p> <p>Methods</p> <p>Seventeen data sources were searched up to 13th August 2011. All randomised controlled trials (RCTs) of any type of CAM therapy used for treating CFS were included, with the exception of acupuncture and complex herbal medicines; studies were included regardless of blinding. Controlled clinical trials, uncontrolled observational studies, and case studies were excluded.</p> <p>Results</p> <p>A total of 26 RCTs, which included 3,273 participants, met our inclusion criteria. The CAM therapy from the RCTs included the following: mind-body medicine, distant healing, massage, tuina and tai chi, homeopathy, ginseng, and dietary supplementation. Studies of qigong, massage and tuina were demonstrated to have positive effects, whereas distant healing failed to do so. Compared with placebo, homeopathy also had insufficient evidence of symptom improvement in CFS. Seventeen studies tested supplements for CFS. Most of the supplements failed to show beneficial effects for CFS, with the exception of NADH and magnesium.</p> <p>Conclusions</p> <p>The results of our systematic review provide limited evidence for the effectiveness of CAM therapy in relieving symptoms of CFS. However, we are not able to draw firm conclusions concerning CAM therapy for CFS due to the limited number of RCTs for each therapy, the small sample size of each study and the high risk of bias in these trials. Further rigorous RCTs that focus on promising CAM therapies are warranted.</p