SHAPS-C: the Snaith-Hamilton pleasure scale modified for clinician administration

Anhedonia, a diminished or lack of ability to experience and anticipate pleasure represents a core psychiatric symptom in depression. Current clinician assessment of anhedonia is generally limited to one or two all-purpose questions and most well-known psychometric scales of anhedonia are relatively long, self-administered, typically not state sensitive, and are unsuitable for use in clinical settings. A user-friendly tool for a more in-depth clinician assessment of hedonic capacity is needed. The present study assessed the validity and reliability of a clinician administered version of the Snaith-Hamilton Pleasure Scale, the SHAPS-C, in 34 depressed subjects. We compared total and specific item scores on the SHAPS-C, SHAPS (self-report version), Montgomery-Åsberg Depression Rating Scale (MADRS), and the Inventory of Depressive Symptomatology-Self Rating version (IDS-SR). We also examined construct, content, concurrent, convergent, and discriminant validity, internal consistency, and split-half reliability of the SHAPS-C. The SHAPS-C was found to be valid and reliable. The SHAPS and the SHAPS-C were positively correlated with one another, with levels of depression severity, as measured by the MADRS, and the IDS-SR total scores, and with specific items of the MADRS and IDS-SR sensitive to measuring hedonic capacity. Our investigation indicates that the SHAPS-C is a user friendly, reliable, and valid tool for clinician assessment of hedonic capacity in depressed bipolar and unipolar patients

SMA-MAP: A Plasma Protein Panel for Spinal Muscular Atrophy

Objectives: Spinal Muscular Atrophy (SMA) presents challenges in (i) monitoring disease activity and predicting progression, (ii) designing trials that allow rapid assessment of candidate therapies, and (iii) understanding molecular causes and consequences of the disease. Validated biomarkers of SMA motor and non-motor function would offer utility in addressing these challenges. Our objectives were (i) to discover additional markers from the Biomarkers for SMA (BforSMA) study using an immunoassay platform, and (ii) to validate the putative biomarkers in an independent cohort of SMA patients collected from a multi-site natural history study (NHS). Methods: BforSMA study plasma samples (N = 129) were analyzed by immunoassay to identify new analytes correlating to SMA motor function. These immunoassays included the strongest candidate biomarkers identified previously by chromatography. We selected 35 biomarkers to validate in an independent cohort SMA type 1, 2, and 3 samples (N = 158) from an SMA NHS. The putative biomarkers were tested for association to multiple motor scales and to pulmonary function, neurophysiology, strength, and quality of life measures. We implemented a Tobit model to predict SMA motor function scores. Results: 12 of the 35 putative SMA biomarkers were significantly associated (p\u3c0.05) with motor function, with a 13th analyte being nearly significant. Several other analytes associated with non-motor SMA outcome measures. From these 35 biomarkers, 27 analytes were selected for inclusion in a commercial panel (SMA-MAP) for association with motor and other functional measures. Conclusions: Discovery and validation using independent cohorts yielded a set of SMA biomarkers significantly associated with motor function and other measures of SMA disease activity. A commercial SMA-MAP biomarker panel was generated for further testing in other SMA collections and interventional trials. Future work includes evaluating the panel in other neuromuscular diseases, for pharmacodynamic responsiveness to experimental SMA therapies, and for predicting functional changes over time in SMA patients. © 2013 Kobayashi et al

Protection levels of N95-level respirator substitutes proposed during the COVID-19 pandemic: Safety concerns and quantitative evaluation procedures

OBJECTIVE: The COVID-19 pandemic has precipitated widespread shortages of filtering facepiece respirators (FFRs) and the creation and sharing of proposed substitutes (novel designs, repurposed materials) with limited testing against regulatory standards. We aimed to categorically test the efficacy and fit of potential N95 respirator substitutes using protocols that can be replicated in university laboratories. SETTING: Academic medical centre with occupational health-supervised fit testing along with laboratory studies. PARTICIPANTS: Seven adult volunteers who passed quantitative fit testing for small-sized (n=2) and regular-sized (n=5) commercial N95 respirators. METHODS: Five open-source potential N95 respirator substitutes were evaluated and compared with commercial National Institute for Occupational Safety and Health (NIOSH)-approved N95 respirators as controls. Fit testing using the 7-minute standardised Occupational Safety and Health Administration fit test was performed. In addition, protocols that can be performed in university laboratories for materials testing (filtration efficiency, air resistance and fluid resistance) were developed to evaluate alternate filtration materials. RESULTS: Among five open-source, improvised substitutes evaluated in this study, only one (which included a commercial elastomeric mask and commercial HEPA filter) passed a standard quantitative fit test. The four alternative materials evaluated for filtration efficiency (67%-89%) failed to meet the 95% threshold at a face velocity (7.6 cm/s) equivalent to that of a NIOSH particle filtration test for the control N95 FFR. In addition, for all but one material, the small surface area of two 3D-printed substitutes resulted in air resistance that was above the maximum in the NIOSH standard. CONCLUSIONS: Testing protocols such as those described here are essential to evaluate proposed improvised respiratory protection substitutes, and our testing platform could be replicated by teams with similar cross-disciplinary research capacity. Healthcare professionals should be cautious of claims associated with improvised respirators when suggested as FFR substitutes

Cancer Care Delivery Research: Building the Evidence Base to Support Practice Change in Community Oncology

Understanding how health care system structures, processes, and available resources facilitate and/or hinder the delivery of quality cancer care is imperative, especially given the rapidly changing health care landscape. The emerging field of cancer care delivery research (CCDR) focuses on how organizational structures and processes, care delivery models, financing and reimbursement, health technologies, and health care provider and patient knowledge, attitudes, and behaviors influence cancer care quality, cost, and access and ultimately the health outcomes and well-being of patients and survivors. In this article, we describe attributes of CCDR, present examples of studies that illustrate those attributes, and discuss the potential impact of CCDR in addressing disparities in care. We conclude by emphasizing the need for collaborative research that links academic and community-based settings and serves simultaneously to accelerate the translation of CCDR results into practice. The National Cancer Institute recently launched its Community Oncology Research Program, which includes a focus on this area of research

Increasing illness severity in very low birth weight infants over a 9-year period

BACKGROUND: Recent reports have documented a leveling-off of survival rates in preterm infants through the 1990's. The objective of this study was to determine temporal changes in illness severity in very low birth weight (VLBW) infants in relationship to the outcomes of death and/or severe IVH. METHODS: Cohort study of 1414 VLBW infants cared for in a single level III neonatal intensive care unit in Delaware from 1993–2002. Infants were divided into consecutive 3-year cohorts. Illness severity was measured by two objective methods: the Score for Neonatal Acute Physiology (SNAP), based on data from the 1(st )day of life, and total thyroxine (T(4)), measured on the 5(th )day of life. Death before hospital discharge and severe intraventricular hemorrhage (IVH) were investigated in the study sample in relation to illness severity. The fetal death rate was also investigated. Statistical analyses included both univariate and multivariate analysis. RESULTS: Illness severity, as measured by SNAP and T(4, )increased steadily over the 9-year study period with an associated increase in severe IVH and the combined outcome of death and/or severe IVH. During the final 3 years of the study, the observed increase in illness severity accounted for 86% (95% CI 57–116%) of the variability in the increase in death and/or severe IVH. The fetal death rate dropped from 7.8/1000 (1993–1996) to 5.3/1000 (1999–2002, p = .01) over the course of the study. CONCLUSION: These data demonstrate a progressive increase in illness in VLBW infants over time, associated with an increase in death and/or severe IVH. We speculate that the observed decrease in fetal death, and the increase in neonatal illness, mortality and/or severe IVH over time represent a shift of severely compromised patients that now survive the fetal time period and are presented for care in the neonatal unit

Reproducibility of CRISPR-Cas9 methods for generation of conditional mouse alleles: A multi-center evaluation

Background CRISPR-Cas9 gene-editing technology has facilitated the generation of knockout mice, providing an alternative to cumbersome and time-consuming traditional embryonic stem cell-based methods. An earlier study reported up to 16% efficiency in generating conditional knockout (cKO or floxed) alleles by microinjection of 2 single guide RNAs (sgRNA) and 2 single-stranded oligonucleotides as donors (referred herein as “two-donor floxing” method). Results We re-evaluate the two-donor method from a consortium of 20 laboratories across the world. The dataset constitutes 56 genetic loci, 17,887 zygotes, and 1718 live-born mice, of which only 15 (0.87%) mice contain cKO alleles. We subject the dataset to statistical analyses and a machine learning algorithm, which reveals that none of the factors analyzed was predictive for the success of this method. We test some of the newer methods that use one-donor DNA on 18 loci for which the two-donor approach failed to produce cKO alleles. We find that the one-donor methods are 10- to 20-fold more efficient than the two-donor approach. Conclusion We propose that the two-donor method lacks efficiency because it relies on two simultaneous recombination events in cis, an outcome that is dwarfed by pervasive accompanying undesired editing events. The methods that use one-donor DNA are fairly efficient as they rely on only one recombination event, and the probability of correct insertion of the donor cassette without unanticipated mutational events is much higher. Therefore, one-donor methods offer higher efficiencies for the routine generation of cKO animal models.This work was supported by the National Collaborative Research Infrastructure (NCRIS) via the Australian Phenomics Network (APN) (to Gaetan Burgio and Paul Thomas), by an Institutional Development Award (PI: Shelley Smith) P20GM103471 (to CBG, RMQ, DWH, JDE, and RR), by NIGMS 1P30GM110768-01 and P30CA036727 (as part of support to University of Nebraska Mouse Genome Engineering and DNA Sequencing Cores), the British Heart Foundation FS12-57, FS12/57/29717, and CH/13/2/30154 and the program grant RG/15/12/31616 (to Kathryn Hentges and Bernard Keavney), the Wellcome Trust grants 107849/Z/ 15/Z, 097820/Z11/B, and 105610/Z/14/Z, the Medical Research Council MR/ N029992/1 (to DB and CBL), the National BioResource Project of Ministry of Education, Culture, Sports, Science and Technology/Japan Agency for Medical Research and Development (MEXT/AMED), Japan, the Canadian Institutes of Health Research MOP#142452 (MCB and LJM). LJM is a member of the Research Centre of the McGill University Health Centre which is supported in part by FQRS. Dr. William Thompson was supported by the Indiana Clinical and Translational Sciences Institute, funded in part by grant #UL1 TR001108 from the National Institute of Health (NIH), National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award. KC Kent Lloyd is supported by the NIH (UM1OD023221), and work contributed by staff from the UC Davis Mouse Biology Program (MBP) is supported by a grant from the American College of Laboratory Animal Medicine. The work contributed from Xiande Liu, Chad Smith, Eric Jonasch, Xuesong Zhang, and Jan ParkerThornburg is supported by the NIH under the award number P30CA16672 (XL, CS, EJ, XZ, JPT) and R50CA211121 (JPT). Joseph Miano is supported by the NIH under the award number HL138987. R Sedlacek was supported by LM2015040 (Czech Centre for Phenogenomics), CZ.1.05/1.1.00/02.0109 (BIOCEV), and CZ.1.05/2.1.00/19.0395 by the Ministry of Education, Youth and Sports (MEYS) and by Academy of Sciences of the Czech Republic (RVO 68378050). David Ray was supported by a Wellcome Trust Investigator (107849/Z/15/Z) and the Medical Research Council (MR/P011853/1 and MR/P023576/) grants. Andrew Loudon was supported by a Wellcome Trust Investigator (107849/Z/15/Z), Biotechnology and Biological Sciences Research Council (BB/N015584/1), Medical Research Council (MR/P023576/1). The work contributed from Gloria Lopez-Castejon is supported by the Wellcome Trust (104192/Z/14/Z) and the Royal Society. Pilar Alcaide was supported by the NIH (HL 123658). The work contributed from Surinder K. Batra is supported by the NIH under the award number P01 CA217798

An economic evaluation of Alexander Technique lessons or acupuncture sessions for patients with chronic neck pain : A randomized trial (ATLAS)

OBJECTIVES: To assess the cost-effectiveness of acupuncture and usual care, and Alexander Technique lessons and usual care, compared with usual GP care alone for chronic neck pain patients. METHODS: An economic evaluation was undertaken alongside the ATLAS trial, taking both NHS and wider societal viewpoints. Participants were offered up to twelve acupuncture sessions or twenty Alexander lessons (equivalent overall contact time). Costs were in pounds sterling. Effectiveness was measured using the generic EQ-5D to calculate quality adjusted life years (QALYs), as well as using a specific neck pain measure-the Northwick Park Neck Pain Questionnaire (NPQ). RESULTS: In the base case analysis, incremental QALY gains were 0.032 and 0.025 in the acupuncture and Alexander groups, respectively, in comparison to usual GP care, indicating moderate health benefits for both interventions. Incremental costs were £451 for acupuncture and £667 for Alexander, mainly driven by intervention costs. Acupuncture was likely to be cost-effective (ICER = £18,767/QALY bootstrapped 95% CI £4,426 to £74,562) and was robust to most sensitivity analyses. Alexander lessons were not cost-effective at the lower NICE threshold of £20,000/QALY (£25,101/QALY bootstrapped 95% CI -£150,208 to £248,697) but may be at £30,000/QALY, however, there was considerable statistical uncertainty in all tested scenarios. CONCLUSIONS: In comparison with usual care, acupuncture is likely to be cost-effective for chronic neck pain, whereas, largely due to higher intervention costs, Alexander lessons are unlikely to be cost-effective. However, there were high levels of missing data and further research is needed to assess the long-term cost-effectiveness of these interventions