HTA – algorithm or process? Comment on ‘Expanded HTA: enhancing fairness and legitimacy’

Daniels, Porteny and Urrutia et al make a good case for the idea that that public decisions ought to be made not only “in the light of ” evidence but also “on the basis of ” budget impact, financial protection and equity. Health technology assessment (HTA) should, they say, be accordingly expanded to consider matters additional to safety and cost-effectiveness. They also complain that most HTA reports fail to develop ethical arguments and generally do not even mention ethical issues. This comment argues that some of these defects are more apparent than real and are not inherent in HTA – as distinct from being common characteristics found in poorly conducted HTAs. More generally, HTA does not need “extension” since (1) ethical issues are already embedded in HTA processes, not least in their scoping phases, and (2) HTA processes are already sufficiently flexible to accommodate evidence about a wide range of factors, and will not need fundamental change in order to accommodate the new forms of decision-relevant evidence about distributional impact and financial protection that are now starting to emerge. HTA and related techniques are there to support decision-makers who have authority to make decisions. Analysts like us are there to support and advise them (and not to assume the responsibilities for which they, and not we, are accountable). The required quality in HTA then becomes its effectiveness as a means of addressing the issues of concern to decisionmakers. What is also required is adherence by competent analysts to a standard template of good analytical practice. The competencies include not merely those of the usual disciplines (particularly biostatistics, cognitive psychology, health economics, epidemiology, and ethics) but also the imaginative and interpersonal skills for exploring the “real” question behind the decision-maker’s brief (actual or postulated) and eliciting the social values that necessarily pervade the entire analysis. The product of such exploration defines the authoritative scope of an HTA

Electrical conductivity and electromagnetic interference shielding of multiwalled carbon nanotube composites containing Fe catalyst

Thin and flexible composite films of raw or purified multiwalled carbon nanotube (MWCNT) with various mass fractions and poly(methylmethacrylate) (PMMA) were synthesized for electromagnetic interference (EMI) shielding material. From scanning electron microscopy and high-resolution transmission electron microscopy photographs, we observed the formation of a conducting network through MWCNTs in an insulating PMMA matrix and the existence of an Fe catalyst in MWCNTs. The dc conductivity (sigma(dc)) of the systems increased with increasing MWCNT mass fraction, showing typical percolation behavior. The measured EMI shielding efficiency (SE) of MWCNT-PMMA composites by using the extended ASTM D4935-99 method (50 MHz-13.5 GHz) increased with increasing MWCNT mass fraction as sigma(dc). The highest EMI SE for raw MWCNT-PMMA composites was similar to27 dB, indicating commercial use for far-field EMI shielding. The contribution of absorption to total EMI SE of the systems is larger than that of reflection. Based on magnetic permeability, we suggest raw MWCNTs and their composites can be used for near-field EMI shielding.open28629

Volume-based referral for cardiovascular procedures in the United States: a cross-sectional regression analysis

BACKGROUND: We sought to estimate the numbers of patients affected and deaths avoided by adopting the Leapfrog Group's recommended hospital procedure volume minimums for coronary artery bypass graft (CABG) surgery and percutaneous coronary intervention (PCI). In addition to hospital risk-adjusted mortality standards, the Leapfrog Group recommends annual hospital procedure minimums of 450 for CABG and 400 for PCI to reduce procedure-associated mortality. METHODS: We conducted a retrospective analysis of a national hospital discharge database to evaluate in-hospital mortality among patients who underwent PCI (n = 2,500,796) or CABG (n = 1,496,937) between 1998 and 2001. We calculated the number of patients treated at low volume hospitals and simulated the number of deaths potentially averted by moving all patients to high volume hospitals under best-case conditions (i.e., assuming the full volume-associated reduction in mortality and the capacity to move all patients to high volume hospitals with no related harms). RESULTS: Multivariate adjusted odds of in-hospital mortality were higher for patients treated in low volume hospitals compared with high volume hospitals for CABG (OR 1.16, 95% CI 1.10–1.24) and PCI (OR 1.12, 95% CI 1.05–1.20). A policy of hospital volume minimums would have required moving 143,687 patients for CABG and 87,661 patients for PCI from low volume to high volume hospitals annually and prevented an estimated 619 CABG deaths and 109 PCI deaths. Thus, preventing a single death would have required moving 232 CABG patients or 805 PCI patients from low volume to high volume hospitals. CONCLUSION: Recommended hospital CABG and PCI volume minimums would prevent 728 deaths annually in the United States, fewer than previously estimated. It is unclear whether a policy requiring the movement of large numbers of patients to avoid relatively few deaths is feasible or effective

A trapped single ion inside a Bose-Einstein condensate

Improved control of the motional and internal quantum states of ultracold neutral atoms and ions has opened intriguing possibilities for quantum simulation and quantum computation. Many-body effects have been explored with hundreds of thousands of quantum-degenerate neutral atoms and coherent light-matter interfaces have been built. Systems of single or a few trapped ions have been used to demonstrate universal quantum computing algorithms and to detect variations of fundamental constants in precision atomic clocks. Until now, atomic quantum gases and single trapped ions have been treated separately in experiments. Here we investigate whether they can be advantageously combined into one hybrid system, by exploring the immersion of a single trapped ion into a Bose-Einstein condensate of neutral atoms. We demonstrate independent control over the two components within the hybrid system, study the fundamental interaction processes and observe sympathetic cooling of the single ion by the condensate. Our experiment calls for further research into the possibility of using this technique for the continuous cooling of quantum computers. We also anticipate that it will lead to explorations of entanglement in hybrid quantum systems and to fundamental studies of the decoherence of a single, locally controlled impurity particle coupled to a quantum environment

Pathogen burden, inflammation, proliferation and apoptosis in human in-stent restenosis - Tissue characteristics compared to primary atherosclerosis

Pathogenic events leading to in-stent restenosis (ISR) are still incompletely understood. Among others, inflammation, immune reactions, deregulated cell death and growth have been suggested. Therefore, atherectomy probes from 21 patients with symptomatic ISR were analyzed by immunohistochemistry for pathogen burden and compared to primary target lesions from 20 stable angina patients. While cytomegalovirus, herpes simplex virus, Epstein-Barr virus and Helicobacter pylori were not found in ISR, acute and/or persistent chlamydial infection were present in 6/21 of these lesions (29%). Expression of human heat shock protein 60 was found in 8/21 of probes (38%). Indicated by distinct signals of CD68, CD40 and CRP, inflammation was present in 5/21 (24%), 3/21 (14%) and 2/21 (10%) of ISR cases. Cell density of ISR was significantly higher than that of primary lesions ( 977 +/- 315 vs. 431 +/- 148 cells/mm(2); p < 0.001). There was no replicating cell as shown by Ki67 or PCNA. TUNEL+ cells indicating apoptosis were seen in 6/21 of ISR specimens (29%). Quantitative analysis revealed lower expression levels for each intimal determinant in ISR compared to primary atheroma (all p < 0.05). In summary, human ISR at the time of clinical presentation is characterized by low frequency of pathogen burden and inflammation, but pronounced hypercellularity, low apoptosis and absence of proliferation. Copyright (C) 2004 S. Karger AG, Basel

Improvements in 25 Years of Implantable Cardioverter Defibrillator Therapy

In 1980, Dr. Michel Mirowski and his team inserted the first implantable cardioverter defibrillator (ICD) in a patient. Initially, ICD therapy was not widely accepted, and many physicians actually considered this therapy unethical. Large secondary and primary prevention trials, demonstrating a beneficial effect of ICD therapy in selected patients not only on arrhythmic death but also on all-cause mortality, stimulated a rapid growth in the number of implants and increased patient’s and physician’s acceptance. Improvements in size and weight, arrhythmia discrimination capabilities, battery technology, shock waveform and output, monitoring capabilities and defibrillator electrode technology eventually resulted in the current large number of yearly implants. Today, almost 40 years after the conception of the ICD and 25 years after the first human implant, ICD therapy is the treatment of choice for patients at risk for life-threatening arrhythmias either as secondary or primary prevention. Furthermore, with the more recent addition of resynchronisation therapy to standard ICD therapy, it became possible to treat selected patients with advanced symptoms of heart failure and to lower the risk of sudden death

Outcome measurement in functional neurological disorder: a systematic review and recommendations.

OBJECTIVES: We aimed to identify existing outcome measures for functional neurological disorder (FND), to inform the development of recommendations and to guide future research on FND outcomes. METHODS: A systematic review was conducted to identify existing FND-specific outcome measures and the most common measurement domains and measures in previous treatment studies. Searches of Embase, MEDLINE and PsycINFO were conducted between January 1965 and June 2019. The findings were discussed during two international meetings of the FND-Core Outcome Measures group. RESULTS: Five FND-specific measures were identified-three clinician-rated and two patient-rated-but their measurement properties have not been rigorously evaluated. No single measure was identified for use across the range of FND symptoms in adults. Across randomised controlled trials (k=40) and observational treatment studies (k=40), outcome measures most often assessed core FND symptom change. Other domains measured commonly were additional physical and psychological symptoms, life impact (ie, quality of life, disability and general functioning) and health economics/cost-utility (eg, healthcare resource use and quality-adjusted life years). CONCLUSIONS: There are few well-validated FND-specific outcome measures. Thus, at present, we recommend that existing outcome measures, known to be reliable, valid and responsive in FND or closely related populations, are used to capture key outcome domains. Increased consistency in outcome measurement will facilitate comparison of treatment effects across FND symptom types and treatment modalities. Future work needs to more rigorously validate outcome measures used in this population

Strategically Equivalent Contests

Using a two-player Tullock-type contest, we show that intuitively and structurally different contests can be strategically equivalent. Strategically equivalent contests generate the same best response functions and, as a result, the same equilibrium efforts. However, strategically equivalent contests may yield different equilibrium payoffs. We propose a simple two-step procedure to identify strategically equivalent contests. Using this procedure, we identify contests that are strategically equivalent to the original Tullock contest, and provide new examples of strategically equivalent contests. Finally, we discuss possible contest design applications and avenues for future theoretical and empirical research

Spina bifida-predisposing heterozygous mutations in Planar Cell Polarity genes and Zic2 reduce bone mass in young mice

Fractures are a common comorbidity in children with the neural tube defect (NTD) spina bifida. Mutations in the Wnt/planar cell polarity (PCP) pathway contribute to NTDs in humans and mice, but whether this pathway independently determines bone mass is poorly understood. Here, we first confirmed that core Wnt/PCP components are expressed in osteoblasts and osteoclasts in vitro. In vivo, we performed detailed µCT comparisons of bone structure in tibiae from young male mice heterozygous for NTD-associated mutations versus WT littermates. PCP signalling disruption caused by Vangl2 (Vangl2Lp/+) or Celsr1 (Celsr1Crsh/+) mutations significantly reduced trabecular bone mass and distal tibial cortical thickness. NTD-associated mutations in non-PCP transcription factors were also investigated. Pax3 mutation (Pax3Sp2H/+) had minimal effects on bone mass. Zic2 mutation (Zic2Ku/+) significantly altered the position of the tibia/fibula junction and diminished cortical bone in the proximal tibia. Beyond these genes, we bioinformatically documented the known extent of shared genetic networks between NTDs and bone properties. 46 genes involved in neural tube closure are annotated with bone-related ontologies. These findings document shared genetic networks between spina bifida risk and bone structure, including PCP components and Zic2. Genetic variants which predispose to spina bifida may therefore independently diminish bone mass