Nuclear spin coherence in a quantum wire

We have observed millisecond-long coherent evolution of nuclear spins in a quantum wire at 1.2 K. Local, all-electrical manipulation of nuclear spins is achieved by dynamic nuclear polarization in the breakdown regime of the Integer Quantum Hall Effect combined with pulsed Nuclear Magnetic Resonance. The excitation thresholds for the breakdown are significantly smaller than what would be expected for our sample and the direction of the nuclear polarization can be controlled by the voltage bias. As a four-level spin system, the device is equivalent to two qubits.Comment: 5 pages, 5 figure

Combining Individual-Level Discrete Choice Experiment Estimates and Costs to Inform Health Care Management Decisions about Customized Care: The Case of Follow-Up Strategies after Breast Cancer Treatment

AbstractObjectiveCustomized care can be beneficial for patients when preferences for health care programs are heterogeneous. Yet, there is little guidance on how individual-specific preferences and cost data can be combined to inform health care decisions about customized care. Therefore, we propose a discrete choice experiment–based approach that illustrates how to analyze the cost-effectiveness of customized (and noncustomized) care programs to provide information for hospital managers.MethodsWe exploit the fact that choice models make it possible to determine whether preference heterogeneity exists and to obtain individual-specific parameter estimates. We present an approach of how to combine these individual-specific parameter estimates from a random parameter model (mixed logit model) with cost data to analyze the cost-effectiveness of customized care and demonstrate our method in the case of follow-up after breast cancer treatment.ResultsWe found that there is significant preference heterogeneity for all except two attributes of breast cancer treatment follow-up and that the fully customized care program leads to higher utility and lower costs than the current standardized program. Compared with the single alternative program, the fully customized care program has increased benefits and higher costs. Thus, it is necessary for health care decision makers to judge whether the use of resources for customized care is cost-effective.ConclusionsDecision makers should consider using the results obtained from our methodological approach when they consider implementing customized health care programs, because it may help to find ways to save costs and increase patient satisfaction

Clinical biological and genetic heterogeneity of the inborn errors of pulmonary surfactant metabolism

Pulmonary surfactant is a multimolecular complex located at the air-water interface within the alveolus to which a range of physical (surface-active properties) and immune functions has been assigned. This complex consists of a surface-active lipid layer (consisting mainly of phospholipids), and of an aqueous subphase. From discrete surfactant sub-fractions one can isolate strongly hydrophobic surf acta nt proteins B (SP-B) and C (SP-C) as well as collectins SP-A and SP-D, which were shown to have specific structural, metabolic, or immune properties. Inborn or acquired abnormalities of the surfactant, qualitative or quantitative in nature, account for a number of human diseases. Beside hyaline membrane disease of the preterm neonate, a cluster of hereditary or acquired lung diseases has been characterized by periodic acid-Schiff-positive material filling the alveoli. From this heterogeneous nosologic group, at least two discrete entities presently emerge. The first is the SP-B deficiency, in which an essentially proteinaceous material is stored within the alveoli, and which represents an autosomal recessive Mendelian entity linked to the SFTPB gene (MIM 1786640). The disease usually generally entails neonatal respiratory distress with rapid fatal outcome, although partial or transient deficiencies have also been observed. The second is alveolar proteinosis, characterized by the storage of a mixed protein and lipid material, which constitutes a relatively heterogeneous clinical and biological syndrome, especially with regard to age at onset (from the neonate through to adulthood) as well as the severity of associated signs. Murine models, with a targeted mutation of the gene encoding granulocyte macrophage colony-stimulating factor (GM-CSF) (Csfgm) or the beta subunit of its receptor (II3rb1) support the hypothesis of an abnormality of surfactant turnover in which the alveolar macrophage is a key player. Apart from SP-B deficiency, in which a near-consensus diagnostic chart can be designed, the ascertainment of other abnormalities of surfactant metabolism is not straightforward. The disentanglement of this disease cluster is however essential to propose specific therapeutic procedures: repeated broncho-alveolar ravages, GM-CSF replacement, bone marrow grafting or lung transplantation

Expression of parathyroid hormone-related protein during immortalization of human peripheral blood mononuclear cells by HTLV-1: Implications for transformation

<p>Abstract</p> <p>Background</p> <p>Adult T-cell leukemia/lymphoma (ATLL) is initiated by infection with human T-lymphotropic virus type-1 (HTLV-1); however, additional host factors are also required for T-cell transformation and development of ATLL. The HTLV-1 Tax protein plays an important role in the transformation of T-cells although the exact mechanisms remain unclear. Parathyroid hormone-related protein (PTHrP) plays an important role in the pathogenesis of humoral hypercalcemia of malignancy (HHM) that occurs in the majority of ATLL patients. However, PTHrP is also up-regulated in HTLV-1-carriers and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients without hypercalcemia, indicating that PTHrP is expressed before transformation of T-cells. The expression of PTHrP and the PTH/PTHrP receptor during immortalization or transformation of lymphocytes by HTLV-1 has not been investigated.</p> <p>Results</p> <p>We report that PTHrP was up-regulated during immortalization of lymphocytes from peripheral blood mononuclear cells by HTLV-1 infection in long-term co-culture assays. There was preferential utilization of the PTHrP-P2 promoter in the immortalized cells compared to the HTLV-1-transformed MT-2 cells. PTHrP expression did not correlate temporally with expression of HTLV-1 tax. HTLV-1 infection up-regulated the PTHrP receptor (PTH1R) in lymphocytes indicating a potential autocrine role for PTHrP. Furthermore, co-transfection of HTLV-1 expression plasmids and PTHrP P2/P3-promoter luciferase reporter plasmids demonstrated that HTLV-1 up-regulated PTHrP expression only mildly, indicating that other cellular factors and/or events are required for the very high PTHrP expression observed in ATLL cells. We also report that macrophage inflammatory protein-1α (MIP-1α), a cellular gene known to play an important role in the pathogenesis of HHM in ATLL patients, was highly expressed during early HTLV-1 infection indicating that, unlike PTHrP, its expression was enhanced due to activation of lymphocytes by HTLV-1 infection.</p> <p>Conclusion</p> <p>These data demonstrate that PTHrP and its receptor are up-regulated specifically during immortalization of T-lymphocytes by HTLV-1 infection and may facilitate the transformation process.</p

Effectiveness and cost-effectiveness of rubber band ligation versus sutured mucopexy versus haemorrhoidectomy in patients with recurrent haemorrhoidal disease (Napoleon trial):Study protocol for a multicentre randomized controlled trial

Background: Currently, there is no consensus regarding the best treatment option in recurrent haemorrhoidal disease (HD), due to a lack of solid evidence. The Napoleon trial aims to provide high-level evidence on the comparative effectiveness and cost-effectiveness of repeat rubber band ligation (RBL) versus sutured mucopexy versus haemorrhoidectomy in patients with recurrent HD. Methods: This is a multicentre randomized controlled trial. Patients with recurrent HD grade II and III, >= 18 years of age and who had at least two RBL treatments in the last three years are eligible for inclusion. Exclusion criteria include previous rectal or anal surgery, rectal radiation, pre-existing sphincter injury or otherwise pathologies of the colon and rectum, pregnancy, presence of hypercoagulability disorders, and medically unfit for surgery (ASA > III). Between June 2020 and May 2022, 558 patients will be randomized to receive either: (1) RBL, (2) sutured mucopexy, or (3) haemorrhoidectomy. The primary outcomes are recurrence after 52 weeks and patient-reported symptoms measured by the PROM-HISS. Secondary outcomes are impact on daily life, treatment satisfaction, early and late complication rates, health-related quality of life, costs and cost-effectiveness, and budget impact. Cost-effectiveness will be expressed in societal costs per Quality Adjusted Life Year (QALY) (based on EQ-5D-5L), and healthcare costs per recurrence avoided. Discussion: The best treatment option for recurrent HD remains unknown. The comparison of three generally accepted treatment strategies in a randomized controlled trial will provide high-level evidence on the most (cost) effective treatment

Is a preoperative multidisciplinary team meeting (cost)effective to improve outcome for high-risk adult patients undergoing noncardiac surgery:the PREPARATION study-a multicenter stepped-wedge cluster randomized trial

BACKGROUND: As a result of increased life expectancy and improved care for patients suffering from chronic disease, the number of patients with multimorbidity requiring surgical intervention is increasing. For complex surgical patients, it is essential to balance the potential benefits of surgical treatment against the risk of permanent loss of functional capacity and quality of life due to complications. European and US guidelines on perioperative care recommend preoperative multidisciplinary team (MDT) discussions for high-risk noncardiac surgical patients. However, the evidence underlying benefits from preoperative MDT meetings with all relevant perioperative specialties present is limited. The current study aims to investigate the effect of implementation of preoperative MDT discussions for high-risk patients undergoing noncardiac surgery on serious adverse events.METHODS/DESIGN: PREPARATION is a stepped-wedge cluster randomized trial in 14 Dutch hospitals without currently established preoperative MDT meeting. The intervention, preoperative MDT meetings, will be implemented sequentially with seven blocks of 2 hospitals switching from control (preoperative screening as usual) to the intervention every 3 months. Each hospital will be randomized to one of seven blocks. We aim to include 1200 patients. The primary outcome is the incidence of serious adverse events at 6 months. Secondary outcomes include (cost)effectiveness, functional outcome, and quality of life for up to 12 months.DISCUSSION: PREPARATION is the first study to assess the effectiveness of a preoperative MDT meeting for high-risk noncardiac surgical patients in the presence of an anesthesiologist. If the results suggest that preoperative MDT discussions for high-risk patients are (cost)-effective, the current study facilitates implementation of preoperative MDT meetings in clinical practice.TRIAL REGISTRATION: ClinicalTrials.gov NCT05703230. Registered on 11/09/2022.</p

Trial-based cost-effectiveness analysis of ultrathin Descemet stripping automated endothelial keratoplasty (UT-DSAEK) versus DSAEK

Purpose: To evaluate the cost-effectiveness of ultrathin Descemet stripping automated endothelial keratoplasty (UT-DSAEK) versus standard DSAEK. Methods: A cost-effectiveness analysis using data from a multicentre randomized clinical trial was performed. The time horizon was 12 months postoperatively. Sixty-four eyes of 64 patients with Fuchs’ endothelial dystrophy were included and randomized to UT-DSAEK (n = 33) or DSAEK (n = 31). Relevant resources from healthcare and societal perspectives were included in the cost analysis. Quality-adjusted life years (QALYs) were determined using the Health Utilities Index Mark 3 questionnaire. The main outcome was the incremental cost-effectiveness ratio (ICER; incremental societal costs per QALY). Results: Societal costs were €9431 (US$11 586) for UT-DSAEK and €9110 (US$11 192) for DSAEK. Quality-adjusted life years (QALYs) were 0.74 in both groups. The ICER indicated inferiority of UT-DSAEK. The cost-effectiveness probability ranged from 37% to 42%, assuming the maximum acceptable ICER ranged from €2500–€80 000 (US$3071–US$98 280) per QALY. Additional analyses were performed omitting one UT-DSAEK patient who required a regraft [ICER €9057 (US$11 127) per QALY, cost-effectiveness probability: 44–62$29 271) per QALY, cost-effectiveness probability: 36–59%]. Furthermore, the ICER was €2101 (US$2581) per patient with clinical improvement in best spectacle-corrected visual acuity (≥0.2 logMAR) and €3274 (US$4022) per patient with clinical improvement in National Eye Institute Visual Functioning Questionnaire-25 composite score (≥10 points). Conclusion: The base case analysis favoured DSAEK, since costs of UT-DSAEK were higher while QALYs were comparable. However, additional analyses revealed no preference for UT-DSAEK or DSAEK. Further cost-effectiveness studies are required to reduce uncertainty

Respiratory adverse effects of opioids for breathlessness: a systematic review and meta-analysis

Background: Previous studies have shown that opioids can reduce chronic breathlessness in advanced disease. However, physicians remain reluctant to prescribe opioids for these patients, commonly due to fear of respiratory adverse effects. Aim: To systematically review reported respiratory adverse effects of opioids in patients with advanced disease and chronic breathlessness. Methods: Pubmed, Embase, Cochrane central register of controlled trials, CINAHL, ClinicalTrials.gov and the reference lists of relevant systematic reviews were searched. Two independent researchers screened against predefined inclusion criteria and extracted data. Meta-analysis was conducted where possible. Results: We included 63 out of 1990 articles, describing 67 studies. Meta-analysis showed an increase in partial pressure of carbon dioxide (0.27 kPa; 95% CI 0.08 to 0.45) and no significant change in partial pressure of oxygen and oxygen saturation (both p>0.05). Non-serious respiratory depression (definition variable/not stated) was described in 4/1064 patients. One cancer patient pre-treated with morphine for pain needed temporary respiratory support following nebulized morphine for breathlessness (single case study). Conclusions: We found no evidence of significant or clinically relevant respiratory adverse effects of opioids for chronic breathlessness. Heterogeneity of design and study population, and low study quality are limitations. Larger studies designed to detect respiratory adverse effects are needed