Evidence-based prescribing: combining network meta-analysis with multicriteria decision analysis to choose among multiple drugs

What is the drug of choice for condition x? is among the most commonly asked questions in primary care.1 Reflecting the complexity of prescribing decisions, answering this question requires a difficult trade-off between the benefits and harms of multiple drugs for a given condition. The principles of evidence-based medicine suggest that prescribing decisions should be guided by an objective benchmark, namely scientific evidence.2 Such evidence is particularly important when choosing a first-line treatment among multiple alternatives. Unfortunately, existing clinical evidence on benefits and harms is rarely adequate to inform prescribing decisions. A randomized controlled trial comparing all relevant drugs would provide such information. However, clinical trials are often designed for regulatory purposes and, therefore, include selective patient populations and do not include all available comparator drugs.3,4 To obtain insight into the comparative benefits and harms of multiple drugs, prescribers turn to summaries of evidence to discern the most promising drugs from their less effective comparators. Recent methods used to synthesize existing evidence provide much-needed information on the comparative benefits and harms of multiple drugs. Network meta-analysis is one such method that allows for the combination of direct and indirect evidences from randomized trials, facilitating the comparison of all relevant drugs even when they are not directly compared with each other in clinical trials.5 The recent surge in the number of network meta-analyses in the general medical literature is a testament to the increasing need for comparative evidence in prescribing decisions

Metallic atomically-thin layered silicon epitaxially grown on silicene/ZrB2

Using low energy electron diffraction (LEED) and scanning tunnelling microscopy (STM), we observe a new two-dimensional (2D) silicon crystal that is formed by depositing additional Si atoms onto spontaneously-formed epitaxial silicene on a ZrB2 thin film. From scanning tunnelling spectroscopy (STS) studies, we find that this atomically-thin layered silicon has distinctly different electronic properties. Angle resolved photoelectron spectroscopy (ARPES) reveals that, in sharp contrast to epitaxial silicene, the layered silicon exhibits significantly enhanced density of states at the Fermi level resulting from newly formed metallic bands. The 2D growth of this material could allow for direct contacting to the silicene surface and demonstrates the dramatic changes in electronic structure that can occur by the addition of even a single monolayer amount of material in 2D systems

Impact of generic alendronate cost on the cost-effectiveness of osteoporosis screening and treatment

Introduction: Since alendronate became available in generic form in the Unites States in 2008, its price has been decreasing. The objective of this study was to investigate the impact of alendronate cost on the cost-effectiveness of osteoporosis screening and treatment in postmenopausal women. Methods: Microsimulation cost-effectiveness model of osteoporosis screening and treatment for U.S. women age 65 and older. We assumed screening initiation at age 65 with central dual-energy x-ray absorptiometry (DXA), and alendronate treatment for individuals with osteoporosis; with a comparator of "no screening" and treatment only after fracture occurrence. We evaluated annual alendronate costs of $20 through$800; outcome measures included fractures; nursing home admission; medication adverse events; death; costs; quality-adjusted life-years (QALYs); and incremental cost-effectiveness ratios (ICERs) in 2010 U.S. dollars per QALY gained. A lifetime time horizon was used, and direct costs were included. Base-case and sensitivity analyses were performed. Results: Base-case analysis results showed that at annual alendronate costs of $200 or less, osteoporosis screening followed by treatment was cost-saving, resulting in lower total costs than no screening as well as more QALYs (10.6 additional quality-adjusted life-days). When assuming alendronate costs of$400 through $800, screening and treatment resulted in greater lifetime costs than no screening but was highly cost-effective, with ICERs ranging from$714 per QALY gained through $13,902 per QALY gained. Probabilistic sensitivity analyses revealed that the cost-effectiveness of osteoporosis screening followed by alendronate treatment was robust to joint input parameter estimate variation at a willingness-to-pay threshold of$50,000/QALY at all alendronate costs evaluated. Conclusions: Osteoporosis screening followed by alendronate treatment is effective and highly cost-effective for postmenopausal women across a range of alendronate costs, and may be cost-saving at annual alendronate costs of $200 or less. © 2012 Nayak et al

Should Research Ethics Encourage the Production of Cost-Effective Interventions?

This project considers whether and how research ethics can contribute to the provision of cost-effective medical interventions. Clinical research ethics represents an underexplored context for the promotion of cost-effectiveness. In particular, although scholars have recently argued that research on less-expensive, less-effective interventions can be ethical, there has been little or no discussion of whether ethical considerations justify curtailing research on more expensive, more effective interventions. Yet considering cost-effectiveness at the research stage can help ensure that scarce resources such as tissue samples or limited subject popula- tions are employed where they do the most good; can support parallel efforts by providers and insurers to promote cost-effectiveness; and can ensure that research has social value and benefits subjects. I discuss and rebut potential objections to the consideration of cost-effectiveness in research, including the difficulty of predicting effectiveness and cost at the research stage, concerns about limitations in cost-effectiveness analysis, and worries about overly limiting researchers’ freedom. I then consider the advantages and disadvantages of having certain participants in the research enterprise, including IRBs, advisory committees, sponsors, investigators, and subjects, consider cost-effectiveness. The project concludes by qualifiedly endorsing the consideration of cost-effectiveness at the research stage. While incorporating cost-effectiveness considerations into the ethical evaluation of human subjects research will not on its own ensure that the health care system realizes cost-effectiveness goals, doing so nonetheless represents an important part of a broader effort to control rising medical costs

The influence of the team in conducting a systematic review

There is an increasing body of research documenting flaws in many published systematic reviews' methodological and reporting conduct. When good systematic review practice is questioned, attention is rarely turned to the composition of the team that conducted the systematic review. This commentary highlights a number of relevant articles indicating how the composition of the review team could jeopardise the integrity of the systematic review study and its conclusions. Key biases require closer attention such as sponsorship bias and researcher allegiance, but there may also be less obvious affiliations in teams conducting secondary evidence-syntheses. The importance of transparency and disclosure are now firmly on the agenda for clinical trials and primary research, but the meta-biases that systematic reviews may be at risk from now require further scrutiny

Expanding the clinical spectrum of hereditary fibrosing poikiloderma with tendon contractures, myopathy and pulmonary fibrosis due to <i>FAM111B </i>mutations

BACKGROUND: Hereditary Fibrosing Poikiloderma (HFP) with tendon contractures, myopathy and pulmonary fibrosis (POIKTMP [MIM 615704]) is a very recently described entity of syndromic inherited poikiloderma. Previously by using whole exome sequencing in five families, we identified the causative gene, FAM111B (NM_198947.3), the function of which is still unknown. Our objective in this study was to better define the specific features of POIKTMP through a larger series of patients. METHODS: Clinical and molecular data of two families and eight independent sporadic cases, including six new cases, were collected. RESULTS: Key features consist of: (i) early-onset poikiloderma, hypotrichosis and hypohidrosis; (ii) multiple contractures, in particular triceps surae muscle contractures; (iii) diffuse progressive muscular weakness; (iv) pulmonary fibrosis in adulthood and (v) other features including exocrine pancreatic insufficiency, liver impairment and growth retardation. Muscle magnetic resonance imaging was informative and showed muscle atrophy and fatty infiltration. Histological examination of skeletal muscle revealed extensive fibroadipose tissue infiltration. Microscopy of the skin showed a scleroderma-like aspect with fibrosis and alterations of the elastic network. FAM111B gene analysis identified five different missense variants (two recurrent mutations were found respectively in three and four independent families). All the mutations were predicted to localize in the trypsin-like cysteine/serine peptidase domain of the protein. We suggest gain-of-function or dominant-negative mutations resulting in FAM111B enzymatic activity changes. CONCLUSIONS: HFP with tendon contractures, myopathy and pulmonary fibrosis, is a multisystemic disorder due to autosomal dominant FAM111B mutations. Future functional studies will help in understanding the specific pathological process of this fibrosing disorder

A review of current and future food applications of natural hydrocolloids

The main aim of this review paper was to focus on current and potential future sources and food applications of natural hydrocolloids in the food industry. The emerging research trends, problems, new methods and alternative approaches in production, environmental concerns, market trends and newly discovered health benefits have been discussed for natural hydrocolloids of commercial relevance. The rheological and surface active properties, interactions, functional properties, films and coatings, encapsulation applications and nanotechnology uses of natural hydrocolloids have been discussed in the light of recent developments. This review also reflected the most up-to-date concepts of applying natural hydrocolloids to meet consumer's and food sector's sophisticated demands related to food products

Magnetic properties of ultrathin Co(0001) films on vicinal Si(111) substrate

In the present work we report on magnetization reversal process, anisotropy and domain structures in ultrathin Au/Co(0001)/Au films deposited on vicinal Si(111) substrates. The measurements were performed using a magneto-optical Kerr effect based magnetometer, a polarizing optical microscope and a ferromagnetic resonance spectrometer. Co thickness induced spin-reorientation from out-of-plane into in-plane magnetization was studied. Changes of in-plane magnetic anisotropy symmetry were deduced from shapes of magneto-optical hysteresis loops and from analysis of angular dependences of the resonance field. The experimental data have been discussed taking into account both uniaxial out-of-plane anisotropy and step-induced uniaxial in-plane anisotropy. A preferential orientation of domain walls in 3ML thick Co films was observed. The finding is explained by the step-induced magnetic anisotropy