Toward Patient-Centered Innovation: A Conceptual Framework for Patient-Reported Outcome Measures for Transformative Kidney Replacement Devices

Individuals with dialysis-dependent kidney failure experience considerable disease- and treatment-related decline in functional status and overall well-being. Despite these experiences, there have been few substantive technological advances in KRT in decades. As such, new federal initiatives seek to accelerate innovation. Historically, integration of patient perspectives into KRT product development has been limited. However, the US Food and Drug Administration recognizes the importance of incorporating patient perspectives into the total product life cycle (i.e., from product conception to postmarket surveillance) and encourages the consideration of patient-reported outcomes in regulatory-focused clinical trials when appropriate. Recognizing the significance of identifying patient-reported outcome measures (PROMs) that capture contemporary patient priorities, the Kidney Health Initiative, a public-private partnership between the American Society of Nephrology and US Food and Drug Administration, convened a workgroup to (1) develop a conceptual framework for a health-related quality of life PROM; (2) identify and map existing PROMs to the conceptual framework, prioritizing them on the basis of their supporting evidence for use in the regulatory environment; and (3) describe next steps for identifying PROMs for use in regulatory clinical trials of transformative KRT devices. This paper summarizes the proposed health-related quality-of-life PROM conceptual framework, maps and prioritizes PROMs, and identifies gaps and future needs to advance the development of rigorous, meaningful PROMS for use in clinical trials of transformative KRT devices

Low-Level Laser Application in the Early Myocardial Infarction Stage Has No Beneficial Role in Heart Failure

Low-level laser therapy (LLLT) has been targeted as a promising approach that can mitigate post infarction cardiac remodeling. There is some interesting evidence showing that the beneficial role of the LLLT could persist long-term even after the end of the application, but it remains to be systematically evaluated. Therefore, the present study aimed to test the hypothesis that LLLT beneficial effects in the early post-infarction cardiac remodeling could remain in overt heart failure even with the disruption of irradiations. Female Wistar rats were subjected to the coronary occlusion to induce myocardial infarction or Sham operation. A single LLLT application was carried out after 60 s and 3 days post-coronary occlusion, respectively. Echocardiography was performed 3 days and at the end of the experiment (5 weeks) to evaluate cardiac function. After the last echocardiographic examination. LV hemodynamic evaluation was performed at baseline and on sudden afterload increases. Compared with the Sham group, infarcted rats showed increased systolic and diastolic internal diameter as well as a depressed shortening fraction of LV. The only benefit of the LLLT was a higher shortening fraction after 3 days of infarction. However, treated-LLLT rats show a lower shortening fraction in the 5th week of study when compared with Sham and non-irradiated rats. A worsening of cardiac function was confirmed in the hemodynamic analysis as evidenced by the higher LV end-diastolic pressure and lower +dP/dt and dP/dt with five weeks of study. Cardiac functional reserve was also impaired by infarction as evidenced by an attenuated response of stroke work index and cardiac output to a sudden afterload stress, without LLLT repercussions. No significant differences were found in the myocardial expression of Akti NEGF pathway. Collectively, these findings illustrate that LLLT improves LV systolic function in the early post-infarction cardiac remodeling. However, this beneficial effect may be dependent on the maintenance of phototherapy. Long-term studies with LLLT application are needed to establish whether these effects ultimately translate into improved cardiac remodeling.Conselho Nacional de Desenvolvimento Cientifico e TecnologicoFAPESPNove de Julho Univ, Lab Biophoton, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Lab Cardiac Physiol, Sao Paulo, SP, BrazilNove de Julho Univ, Program Med, Sao Paulo, BrazilUniv Sao Judas Tadeu, Brazil Phys Educ & Aging Sci Program, Translat Physiol Lab, Sao Paulo, BrazilUniv Fed Sao Paulo, Lab Cardiac Physiol, Sao Paulo, SP, BrazilCNPq: 4400851/2014-8FAPESP: 09-54225/8FAPESP: 15/11028-9Web of Scienc

Construction, assembly and tests of the ATLAS electromagnetic barrel calorimeter

The construction and assembly of the two half barrels of the ATLAS central electromagnetic calorimeter and their insertion into the barrel cryostat are described. The results of the qualification tests of the calorimeter before installation in the LHC ATLAS pit are given

Telepsychiatry During the COVID-19 Pandemic: Development of a Protocol for Telemental Health Care

Background: The rapid spread of the Coronavirus disease 2019 (COVID-19) has forced most countries to take drastic public health measures, including the closure of most mental health outpatient services and some inpatient units. This has suddenly created the need to adapt and expand telepsychiatry care across the world. However, not all health care services might be ready to cope with this public health demand. The present study was set to create a practical and clinically useful protocol for telemental health care to be applied in the context of the current COVID-19 pandemic. Methods: A panel of psychiatrists from 15 different countries covering all World Health Organization (WHO) regions was convened. The panel used a combination of reactive Delphi technique and consensus development conference strategies to develop a protocol for the provision of telemental health care during the COVID-19 pandemic. Results: The proposed protocol describes a semi-structured initial assessment and a series of potential interventions matching mild, moderate, or high-intensity needs of target populations. Conclusions: Telemedicine has become a pivotal tool in the task of ensuring the continuous provision of mental health care for the population, and the outlined protocol can assist with this task. The strength of this protocol lies in its practicality, clinical usefulness, and wide transferability, resulting from the diversity of the consensus group that developed it. Developed by psychiatrists from around the globe, the proposed protocol may prove helpful for many clinical and cultural contexts, assisting mental health care providers worldwide. © Copyright © 2020 Ramalho, Adiukwu, Gashi Bytyçi, El Hayek, Gonzalez-Diaz, Larnaout, Grandinetti, Nofal, Pereira-Sanchez, Pinto da Costa, Ransing, Teixeira, Shalbafan, Soler-Vidal, Syarif and Orsolini

COVID-19 mental health care toolkit: An international collaborative effort by Early Career Psychiatrists section

The collaborative effort of an international research team from the Early Career Psychiatrists section of the World Psychiatry Association has brought about an easy-to-use, quick and stepwise mental health care toolkit for the identification and appropriate referral of those in need of mental health care during the pandemic. This simple guide can be applied in the general outpatient setting and is catered for all healthcare professionals, regardless of their expertise within the mental health field with minimal training. It is our hope that by incorporating this toolkit into our daily clinical care during the pandemic for high-risk patients and patients with non-specific complaints, we will be able to bridge the mental health gap present in our society. © 2020 Author(s) (or their employer(s)) 2020

Infectious disease outbreak related stigma and discrimination during the COVID-19 pandemic: Drivers, facilitators, manifestations, and outcomes across the world

Being part of a social minority (e.g. migrants, people of color or Asian descent in Western countries) is not itself a risk factor for contracting Coronavirus disease-2019 (COVID-19). However, certain groups of people across the world are being targeted by COVID-19 related stigma (COS) and discrimination, which constitutes a growing concern (Bagcchi, 2020). There is an urgent need to better understand it, as it may pose a barrier for accessing testing and health care and for maintaining treatment adherence (Stangl et al., 2019). It is very likely that COS is the consequence of multiple socio-ecological drivers (e.g., fear, misinformation) and facilitators (e.g., racism, poverty) (Logie, 2020). In this letter, we attempt to explore COS related factors based on the real-life experiences of a group of psychiatrists from thirteen countries using the health stigma and discrimination framework (HSDF) (Stangl et al., 2019). We categorized these experiences as per the process domains (such as drivers, facilitators); and these process domains along with examples/responses are depicted in Fig. (1)

Comparison of gene transfection and cytotoxicity mechanisms of linear poly(amidoamine) and branched poly(ethyleneimine) polyplexes

Purpose: This study aimed to further explore the mechanisms behind the ability of certain linear polyamidoamines (PAAs) to transfect cells with minimal cytotoxicity. Methods: The transfection efficiency of DNA complexed with a PAA of a molecular weight over 10 kDa or 25 kDa branched polyethyleneimine (BPEI) was compared in A549 cells using a luciferase reporter gene assay. The impact of endo/lysosomal escape on transgene expression was investigated by transfecting cells in presence of bafilomycin A1 or chloroquine. Cytotoxicity caused by the vectors was evaluated by measuring cell metabolic activity, lactate dehydrogenase release, formation of reactive oxygen species and changes in mitochondrial membrane potential. Results: The luciferase activity was 3-fold lower after transfection with PAA polyplexes than with BPEI complexes at the optimal polymer to nucleotide ratio (RU:Nt). However, in contrast to BPEI vectors, PAA polyplexes caused negligible cytotoxic effects. The transfection efficiency of PAA polyplexes was significantly reduced in presence of bafilomycin A1 while chloroquine enhanced or decreased transgene expression depending on the RU:Nt. Conclusions: PAA polyplexes displayed a pH-dependent endo/lysosomal escape which was not associated with cytotoxic events, unlike observed with BPEI polyplexes. This is likely due to their greater interactions with biological membranes at acidic than neutral pH

Global economic burden of unmet surgical need for appendicitis

Background: There is a substantial gap in provision of adequate surgical care in many low-and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods: Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results: Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion: For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112