Six-Month Real-World Study to Assess the Effectiveness of Ixekizumab After Switching from IL-23 Inhibitors and Other Biologic Therapies: The CorEvitas Psoriasis Registry.

BACKGROUND: Prior work showed that patients from the CorEvitas Psoriasis Registry who had previously failed a prior biologic and then initiated ixekizumab demonstrated improvements in disease severity and patient-reported outcomes after 6 months. However, newer therapies such as interleukin-23 inhibitors (IL-23i) were not considered. Here, with more recent data including IL-23i, 6-month effectiveness of ixekizumab following a switch from any biologic was assessed as well as whether 6-month effectiveness of ixekizumab was impacted by prior biologic class. METHODS: We included CorEvitas Psoriasis Registry patients who initiated ixekizumab after discontinuing another biologic therapy and had a corresponding 6-month follow-up visit following ixekizumab initiation (N = 743, 2016-2023). Immediate prior biologic class was categorized as tumor necrosis factor inhibitor (TNFi) or interleukin-12/23 inhibitors (IL-12/23i, n = 405), non-ixekizumab interleukin-17i (IL-17i, n = 237), or IL-23i (n = 101). Adjusted mean changes in body surface area (BSA), Dermatology Life Quality Index (DLQI), itch, and skin pain were calculated for prior biologic class groups using analysis of covariance (ANCOVA). Proportions achieving ≥ 75%, ≥ 90%, and ≥ 100% improvement in Psoriasis Area and Severity Index (PASI75, PASI90, and PASI100, respectively), Investigator's Global Assessment (IGA) 0/1, and DLQI 0/1 were calculated for all patients and compared among prior biologic classes via relative risks (RRs) and 95% confidence intervals (CIs) using multivariable modified Poisson regression. RESULTS: Mean improvements in BSA, DLQI, itch, and skin pain, were 7.6, 3.6, 23.3, and 16.7, respectively, for ixekizumab patients who switched from TNFi or IL-12/23i (all p < 0.05); 6.8, 3.3, 19.6, and 14.1, respectively, for those who switched from non-ixekizumab IL-17i (all p < 0.05); and 7.8, 3.4, 22.2, and 12.8, respectively, for those who switched from IL-23i (all p < 0.05). Overall, 54%, 41%, and 31% of ixekizumab initiators achieved PASI75, PASI90, and PASI100, respectively, 50% maintained or achieved IGA 0/1, and 48% maintained or achieved DLQI 0/1. The prior TNFi or IL-12/23i group was 31% more likely to achieve PASI100 (RR = 1.31, 95% CI 1.01, 1.69) and 32% more likely to maintain or achieve IGA 0/1 (RR = 1.32, 95% CI 1.11, 1.57), but not significantly more likely to achieve PASI90. The prior IL-23i group was 45% more likely to achieve PASI90 (RR = 1.45, 95% CI 1.10, 1.91), 55% more likely to achieve PASI100 (RR = 1.55, 95% CI 1.12, 2.13), and 39% more likely to maintain or achieve IGA 0/1 (RR = 1.39, 95% CI 1.12, 1.73) compared to the prior non-ixekizumab IL-17i group. Achievement of PASI75 and DLQI 0/1 was consistent across the prior TNFi or IL-12/23i, IL-23i, and non-ixekizumab IL-17i groups. CONCLUSIONS: These updated findings with IL-23i data reaffirm that patients with psoriasis who switch to ixekizumab after discontinuing another biologic demonstrate improvement in disease severity and patient-reported outcomes at 6 months in real-world settings. Compared to patients who switched from another IL-17i, patients who switched class from a TNFi or IL-12/23i were more likely to achieve PASI100 and IGA 0/1, and patients who switched class from an IL-23i were more likely to achieve PASI90 in addition to PASI100 and IGA 0/1.

n-Bu4NI/K2S2O8 Mediated Csp2-Csp2 Bond Cleavage - Transformylation from p-Anisaldehyde to Primary Amides.

n-Bu4NI/K2S2O8 mediated transformylation from p-anisaldehyde to primary amides is reported. The mechanistic studies suggest the reaction occurs via a single electron transfer pathway. Based on the DFT electronic structure calculations of various reaction pathways, the most plausible mechanism involves the formation of a phenyl radical cation and an arenium ion as the key intermediates. It represents the first example where p-anisaldehyde is employed as a formyl source via a non-metal mediated Csp2-Csp2 bond cleavage.

Low-latency gravitational wave alert products and their performance at the time of the fourth LIGO-Virgo-KAGRA observing run.

Multimessenger searches for binary neutron star (BNS) and neutron star-black hole (NSBH) mergers are currently one of the most exciting areas of astronomy. The search for joint electromagnetic and neutrino counterparts to gravitational wave (GW)s has resumed with ALIGO's, AdVirgo's and KAGRA's fourth observing run (O4). To support this effort, public semiautomated data products are sent in near real-time and include localization and source properties to guide complementary observations. In preparation for O4, we have conducted a study using a simulated population of compact binaries and a mock data challenge (MDC) in the form of a real-time replay to optimize and profile the software infrastructure and scientific deliverables. End-toend performance was tested, including data ingestion, running online search pipelines, performing annotations, and issuing alerts to the astrophysics community. We present an overview of the low-latency infrastructure and the performance of the data products that are now being released during O4 based on the MDC. We report the expected median latency for the preliminary alert of full bandwidth searches (29.5 s) and show consistency and accuracy of released data products using the MDC. We report the expected median latency for triggers from early warning searches (-3.1 s), which are new in O4 and target neutron star mergers during inspiral phase. This paper provides a performance overview for LIGO-Virgo-KAGRA (LVK) low-latency alert infrastructure and data products using theMDCand serves as a useful reference for the interpretation of O4 detections.

Geospatial analysis and participant characteristics associated with colorectal cancer screening participation in Alberta, Canada: a population-based cross-sectional study.

BACKGROUND: Colorectal cancer (CRC) is a leading cause of death in Canada and early detection can prevent deaths through screening. However, CRC screening in Alberta, Canada remains suboptimal and varies by sociodemographic and health system characteristics, as well as geographic location. This study aimed to further the understanding of these participant and health system characteristics associated with CRC screening in Alberta and identify clusters of regions with higher rates of overdue or unscreened individuals. METHODS: We included Albertans aged 52 to 74 as of December 31, 2019 (index date) and we used data from administrative health data sources and linked to the Alberta Colorectal Cancer Screening Program database to determine colorectal cancer screening rates. We used multivariable multinomial logistic regression analysis to investigate the relationship between sociodemographic, health system characteristics and participation in CRC screening. We used optimized Getis-Ord Gi* hot-spot analysis to identify hot and cold-spots in overdue for and no record of CRC screening. RESULTS: We included 919,939 Albertans, of which 65% were currently up to date on their CRC screening, 21% were overdue, and 14% had no record of CRC screening. Compared to Albertans who were currently up to date, those who were in older age groups, those without a usual provider of care, those who were health system non-users, and those living in more deprived areas were more likely to have no record of screening. Areas with high number of Albertans with no record of screening were concentrated in the North and Central zones. CONCLUSIONS: Our study showed important variation in colorectal cancer screening participation across sociodemographic, health system and geographical characteristics and identified areas with higher proportions of individuals who have no record of screening or are under-screened in Alberta, Canada.

From SARS to COVID-19: the role of experience and experts in Hong Kong's initial policy response to an emerging pandemic.

As one of the most densely populated places in the world, Hong Kong fared relatively well in the first year of the COVID-19 pandemic, with a very low number of cases and fatalities per capita. This was mostly due to the Hong Kong government, healthcare workers, and the general public's institutional and individual memory after they successfully overcame the deadly severe acute respiratory syndrome (SARS) epidemic in 2003. However, while Hong Kong was well accustomed to measures such as wearing masks and social distancing, the cooperation of the Hong Kong public to government restrictions was highly affected by its local political context, especially after widespread anti-government protests began mid-2019. This brought the public's trust in government to an all-time low, creating a political 'new normal', which underpinned how COVID-19 policies would be proposed, accepted, and implemented, if at all. To understand how science advice was offered and how public health decisions were made, this research investigates the evolution of Hong Kong's science advisory mechanisms for public health from before SARS, after SARS, and during COVID-19 in 2020, including the roles of key organisations and departments, the establishment of new centres and committees, and the creation of workgroups and expert advisory panels. This paper compares and analyses the reasons behind these differences in science advisory mechanisms between SARS and COVID-19. The findings from this research reinforce the unquestionable need for robust science advisory structures and knowledgeable scientific experts to solve health-related crises, though more research is required to understand the ways in which science advice influences both policy decisions and public acceptance of these policies.

Accuracy and safety of in-house surgeon-designed three-dimensional-printed patient-specific implants for wafer-less Le Fort I osteotomy.

OBJECTIVES: The design and fabrication of three-dimensional (3D)-printed patient-specific implants (PSIs) for orthognathic surgery are customarily outsourced to commercial companies. We propose a protocol of designing PSIs and surgical guides by orthognathic surgeons-in-charge instead for wafer-less Le Fort I osteotomy. The aim of this prospective study was to evaluate the accuracy and post-operative complications of PSIs that are designed in-house for Le Fort I osteotomy. MATERIALS AND METHODS: The post-operative cone beam computer tomography (CBCT) model of the maxilla was superimposed to the virtual surgical planning to compare the discrepancies of pre-determined landmarks, lines, and principal axes between the two models. Twenty-five patients (12 males, 13 females) were included. RESULTS: The median linear deviations of the post-operative maxilla of the x, y, and z axes were 0.74 mm, 0.75 mm, and 0.72 mm, respectively. The deviations in the principal axes for pitch, yaw, and roll were 1.40°, 0.90°, and 0.60°, respectively. There were no post-operative complications related to the PSIs in the follow-up period. CONCLUSIONS: The 3D-printed PSIs designed in-house for wafer-less Le Fort I osteotomy are accurate and safe. CLINICAL RELEVANCE: Its clinical outcomes and accuracy are comparable to commercial PSIs for orthognathic surgery. TRIAL REGISTRATION: Clinical trial registration number: HKUCTR-2113. Date of registration: 29 July 2016.

Investigating the early impacts of the COVID-19 pandemic on modifiable risk factors for cancer and chronic disease: a repeated cross-sectional study in Alberta, Canada.

OBJECTIVES: This study contributes to empirical evidence by examining the impact of the first and second waves of the COVID-19 pandemic on modifiable risk factors (MRF) and whether these patterns differ according to level of material deprivation among people living in Alberta. METHODS: Using data from a repeated cross-sectional provincial health survey (Alberta Community Health Survey (ACHS): 2018-2021), we conducted logistic regression analyses examining the impacts of the COVID-19 pandemic on meeting national guidelines on four MRFs (tobacco use, physical activity, fruit and vegetable consumption, alcohol use) (n=11,249). We compared population-level changes in MRFs from one year before the COVID-19 pandemic (March 2019-February 2020) to one year during the pandemic (March 2020-February 2021) in Alberta. We also assessed whether these trends differed by a measure of material deprivation. RESULTS: Compared to the pre-COVID-19 period, the fully adjusted odds of meeting recommended guidelines for fruit and vegetable consumption (OR=0.42) decreased during the pandemic. Individuals experiencing high material deprivation had lower odds of meeting recommended guidelines for physical activity (OR=0.65) and higher odds of not being current tobacco users (OR=1.36) during the pandemic versus during the pre-pandemic period. CONCLUSION: At a population level, analyses from the ACHS showed minimal impacts of the first year of the COVID-19 pandemic on MRFs, besides fruit and vegetable consumption. Yet, stratifying results showed statistically significant differences in pandemic impacts on MRFs by level of material deprivation. Therefore, understanding the influence of material deprivation on MRFs during the pandemic is key to tailoring future public health interventions promoting health and preventing cancer and chronic disease.

RéSUMé: OBJECTIFS: Notre étude contribue aux preuves empiriques en examinant l'impact de la première et de la deuxième vague de la pandémie de COVID-19 sur les facteurs de risque modifiables (FRM) et en déterminant si ces tendances diffèrent selon le niveau de défavorisation matérielle chez les personnes vivant en Alberta. MéTHODE: À l'aide des données d'une enquête de santé transversale provinciale répétée (Alberta Community Health Survey [ACHS] : 2018-2021), nous avons mené des analyses de régression logistique pour étudier les impacts de la pandémie de COVID-19 sur le respect des directives nationales pour quatre FRM (tabagisme, activité physique, consommation de fruits et légumes, consommation d'alcool) (n = 11 249). Nous avons comparé les changements populationnels dans les FRM une année avant la pandémie de COVID-19 (mars 2019 à février 2020) et une année durant la pandémie (mars 2020 à février 2021) en Alberta. Nous avons aussi cherché à déterminer si ces tendances différaient selon un indicateur de défavorisation matérielle. RéSULTATS: Comparativement à la période ayant précédé la COVID-19, le rapport de cotes entièrement ajusté pour le respect des directives de consommation de fruits et légumes recommandées (RC = 0,42) a diminué durant la pandémie. Les personnes aux prises avec une importante défavorisation matérielle ont présenté une probabilité plus faible de respecter les directives recommandées pour l'activité physique (RC = 0,65) et une probabilité accrue de ne pas être des consommateurs actuels de produits du tabac (OR = 1,36) durant la pandémie qu'avant la pandémie. CONCLUSION: Pour l'ensemble de la population, nos analyses de l'ACHS montrent que la première année de la pandémie de COVID-19 a eu très peu d'impact sur les FRM, sauf pour la consommation de fruits et légumes. Pourtant, la stratification des résultats montre des écarts significatifs dans les impacts de la pandémie sur les FRM selon le niveau de défavorisation matérielle. Il est donc essentiel de comprendre l'influence de la défavorisation matérielle sur les FRM durant la pandémie pour adapter les futures interventions de promotion de la santé et de prévention du cancer et des maladies chroniques.

Promoting deceased organ and tissue donation registration in family physician waiting rooms (RegisterNow-1): a pragmatic stepped-wedge, cluster randomized controlled registry trial.

BACKGROUND: The shortage of available organs for life-saving transplants persists worldwide. While a majority support donating their organs or tissue when they die, many have not registered their wish to do so. When registered, next of kin are much more likely to follow-through with the decision to donate. In many countries, most people visit their family physician office each year and this setting is a promising, yet underused, site where more people could register for deceased organ donation. Our primary aim was to evaluate the effectiveness of an intervention to promote organ donation registration in family physician's offices. METHODS: We developed an intervention to address barriers and enablers to organ donation registration that involved physician office reception staff inviting patients to register on a tablet in the waiting room while they waited for their appointment. We conducted a cross-sectional stepped-wedge cluster randomized controlled registry trial to evaluate the intervention. We recruited six family physician offices in Canada. All offices began with usual care and then every two weeks, one office (randomly assigned) started the intervention until all offices delivered the intervention. The primary outcome was registration for deceased organ donation in the provincial organ registration registry, assessed within the 7 days of the physician visit. At the end of the trial, we also conducted interviews with clinic staff to assess any barriers and enablers to delivering the intervention. RESULTS: The trial involved 24,616 patient visits by 13,562 unique patients: 12,484 visits in the intervention period and 12,132 in the control period. There was no statistically significant difference in the percentage of patients registered for deceased organ donation in the intervention versus control period (48.0% vs 46.2%; absolute difference after accounting for the secular trend: 0.12%; 95% CI: - 2.30, 2.54; p=0.92). Interviews with clinic staff indicated location of the tablet within a waiting room, patient rapport, existing registration, confidence and motivation to deliver the intervention and competing priorities as barriers and enablers to delivery. CONCLUSIONS: Our intervention did not increase donor registration. Nonetheless, family physician offices may still remain a promising setting to develop and evaluate better interventions to increase organ donation registration. TRIAL REGISTRATION: NCT03213171.

The safety and efficacy of autologous adipose-derived stromal vascular fraction for nonscarring alopecia: A systematic review.

IMPORTANCE: Nonscarring alopecia, including androgenetic alopecia and alopecia areata, are common and can negatively impact quality of life. Recent clinical studies have investigated autologous, adipose-derived stromal vascular fraction (SVF) as a potentially beneficial treatment option. OBJECTIVE: To assess the available evidence on the utility and safety of SVF for nonscarring alopecia. EVIDENCE REVIEW: A systematic review of the literature was performed using MEDLINE (PubMed), Embase, and CENTRAL from inception to November 2020. Included articles were prospective, observational or interventional studies of SVF for nonscarring alopecia in humans. FINDINGS: Six studies of 188 patients were identified, including three randomized controlled trials. There were no reported severe adverse events. All studies found improved hair density with SVF compared to control or pre-treatment baseline. One study reported that improvement in hair density varied based on time for follow-up, severity of hair loss, and concentration of adipose-derived stem cells (ADSCs) within the SVF. Two studies reported an increase in hair diameter from baseline, and two studies reported an improvement in hair pull test outcomes. CONCLUSIONS AND RELEVANCE: SVF may be safe and effective for nonscarring alopecia in the appropriate patients. Hair loss severity, method of SVF preparation and frequency of treatment, and adjunctive therapies may be important considerations for treatment success. Additional studies evaluating appropriate patient selection and treatment methods are needed.

Identifying behaviour change techniques within randomized trials of interventions promoting deceased organ donation registration.

OBJECTIVE: Increasing deceased organ donation registration may increase the number of available organs for transplant to help save lives. This study aimed to identify which behaviour change techniques (BCTs; or 'active ingredients') are reported within randomized trials of interventions promoting deceased organ donation registration and of those, which are associated with a larger intervention effect. METHODS: We conducted a secondary analysis of 45 trials included in a Cochrane systematic review of deceased organ donation registration interventions. Two researchers used the BCT Taxonomy v1 to independently code intervention content in all trial groups. Outcome data were pooled and we used meta-regression to explore associations between individual and combinations of recurring BCTs and effect on registration intention and/or registration behaviour. RESULTS: A total of 27 different BCTs (mean = 3.7, range = 1-9) were identified in intervention groups across the 45 trials. The five most common BCTs were: 'Information about health consequences' (71%); 'Instruction on how to perform the behaviour' (47%); 'Salience of consequences' (40%); 'Adding objects to the environment' (28%); and 'Credible source' (27%). Comparator groups in 20/45 trials also included identifiable BCTs (n = 12, mean = 3.1, range = 1-7). Meta-regression revealed that a combination of the three most common BCTs was associated with a larger intervention effect size for registration behaviour (k = 8, ß = .19, p = .02). CONCLUSIONS: Trials of deceased organ donation registration interventions focus predominantly on providing information, instruction, and a means to register. While potentially effective, a much wider set of possible BCTs could be leveraged to address known barriers to registration.

Risk Factors and Outcomes of Early Hospital Readmission in Canadian Kidney Transplant Recipients: A Population-Based Multi-Center Cohort Study.

BACKGROUND: Early hospital readmissions (EHRs) occur commonly in kidney transplant recipients. Conflicting evidence exists regarding risk factors and outcomes of EHRs. OBJECTIVE: To determine risk factors and outcomes associated with EHRs (ie, hospitalization within 30 days of discharge from transplant hospitalization) in kidney transplant recipients. DESIGN: Population-based cohort study using linked, administrative health care databases. SETTING: Ontario, Canada. PATIENTS: We included 5437 kidney transplant recipients from 2002 to 2015. MEASUREMENTS: Risk factors and outcomes associated with EHRs. We assessed donor, recipient, and transplant risk factors. We also assessed the following outcomes: total graft failure, death-censored graft failure, death with a functioning graft, mortality, and late hospital readmission. METHODS: We used multivariable logistic regression to examine the association of each risk factor and the odds of EHR. To examine the relationship between EHR status (yes vs no [reference]) and the outcomes associated with EHR (eg, total graft failure), we used a multivariable Cox proportional hazards model. RESULTS: In all, 1128 kidney transplant recipients (20.7%) experienced an EHR. We found the following risk factors were associated with an increased risk of EHR: older recipient age, lower income quintile, several comorbidities, longer hospitalization for initial kidney transplant, and older donor age. After adjusting for clinical characteristics, compared to recipients without an EHR, recipients with an EHR had an increased risk of total graft failure (adjusted hazard ratio [aHR]: 1.46, 95% CI: 1.29, 1.65), death-censored graft failure (aHR: 1.62, 95% CI: 1.36, 1.94), death with graft function (aHR: 1.34, 95% CI: 1.13, 1.59), mortality (aHR: 1.41, 95% CI: 1.22, 1.63), and late hospital readmission in the first 0.5 years of follow-up (eg, 0 to <0.25 years: aHR: 2.11, 95% CI: 1.85, 2.40). LIMITATIONS: We were not able to identify which readmissions could have been preventable and there is a potential for residual confounding. CONCLUSIONS: Results can be used to identify kidney transplant recipients at risk of EHR and emphasize the need for interventions to reduce the risk of EHRs. TRIAL REGISTRATION: This is not applicable as this is a population-based cohort study and not a clinical trial.

CONTEXTE: Les réadmissions précoces à l'hôpital (RPH) sont fréquentes chez les receveurs d'une greffe rénale. Les données sur les facteurs de risque d'une RPH et sur les résultats qui y sont associés restent toutefois contradictoires. OBJECTIF: Définir les facteurs de risque et les effets associés à une RPH (soit une hospitalization dans les 30 jours suivant la sortie de l'hôpital après la transplantation) chez les receveurs de greffe rénale. TYPE D'ÉTUDE: Étude de cohorte représentative d'une population, réalisée à partir des bases de données administratives en santé. CADRE: Ontario, Canada. SUJETS: Ont été inclus 5 437 adultes receveurs d'une greffe rénale entre 2002 et 2015. MESURES: Les facteurs de risque et les résultats associés à une RPH. Nous avons évalué les facteurs de risque du donneur, du receveur et de la transplantation. Nous avons également évalué les résultats suivants : l'échec du greffon, l'échec du greffon censuré par le décès, le décès avec un greffon fonctionnel, la mortalité et les réadmissions tardives. MÉTHODOLOGIE: Nous avons utilisé la régression logistique multivariée pour examiner l'association de chaque facteur de risque et les probabilités de RPH. Un modèle multivarié des risques proportionnels de Cox a par ailleurs servi à examiner la relation entre le statut des RPH (oui vs non [référence]) et les résultats associés à celles-ci (p. ex., l'échec de la greffe). RÉSULTATS: Dans la cohorte étudiée, 1 128 receveurs d'une greffe rénale (20,7 %) ont été réadmis précocement à l'hôpital. Les facteurs de risque suivants ont été associés à un risque accru de RPH : âge plus avancé du receveur, provenance d'un quartier au quintile de revenu inférieur, présence de plusieurs comorbidités, hospitalization initiale plus longue pour la transplantation rénale et âge plus avancé du donneur. Après ajustement pour les caractéristiques cliniques, par rapport aux receveurs de greffe qui n'avaient pas été réadmis précocement, les patients avec une RPH présentaient un risque accru d'échec du greffon (risque relatif corrigé [RRc] : 1,46; IC 95 % : 1,29-1,65), d'échec du greffon censuré par le décès (RRc: 1,62; IC 95 % : 1,36-1,94), de décès avec un greffon fonctionnel (RRc: 1,34; IC 95 % : 1,13-1,59), de mortalité (RRc: 1,41; IC 95 % : 1,22-1,63) et de réadmission tardive au cours des premiers six mois de suivi (p. ex., entre 0 et moins de 0,25 an de suivi, le RRc était de 2,11; [IC 95 % : 1,85-2,40]). LIMITES: Nous n'avons pas été en mesure d'identifier les réadmissions qui auraient pu être prévenues et il existe un risque de facteurs de confusion résiduels. CONCLUSION: Ces résultats peuvent être employés pour identifier les receveurs d'une greffe rénale susceptibles d'être réadmis rapidement à l'hôpital. Ces résultats soulignent en outre la nécessité d'interventions pour réduire le risque de RPH. ENREGISTREMENT DE L'ESSAI: Sans objet puisqu'il s'agit d'une étude de cohorte basée sur la population et non d'un essai clinique.

Use of technology for the objective evaluation of scratching behavior: A systematic review.

INTRODUCTION: Pruritus is a common symptom across various dermatologic conditions, with a negative impact on quality of life. Devices to quantify itch objectively primarily use scratch as a proxy. This review compares and evaluates the performance of technologies aimed at objectively measuring scratch behavior. METHODS: Articles identified from literature searches performed in October 2020 were reviewed and those that did not report a primary statistical performance measure (eg, sensitivity, specificity) were excluded. The articles were independently reviewed by 2 authors. RESULTS: The literature search resulted in 6231 articles, of which 24 met eligibility criteria. Studies were categorized by technology, with actigraphy being the most studied (n = 21). Wrist actigraphy's performance is poorer in pruritic patients and inherently limited in finger-dominant scratch detection. It has moderate correlations with objective measures (Eczema and Area Severity Index/Investigator's Global Assessment: rs(ρ) = 0.70-0.76), but correlations with subjective measures are poor (r2 = 0.06, rs(ρ) = 0.18-0.40 for itch measured using a visual analog scale). This may be due to varied subjective perception of itch or actigraphy's underestimation of scratch. CONCLUSION: Actigraphy's large variability in performance and limited understanding of its specificity for scratch merits larger studies looking at validation of data analysis algorithms and device performance, particularly within target patient populations.

Effects of hospital funding reform on wait times for hip fracture surgery: a population-based interrupted time-series analysis.

BACKGROUND: Health care funding reforms are being used worldwide to improve system performance but may invoke unintended consequences. We assessed the effects of introducing a targeted hospital funding model, based on fixed price and volume, for hip fractures. We hypothesized the policy change was associated with reduction in wait times for hip fracture surgery, increase in wait times for non-hip fracture surgery, and increase in the incidence of after-hours hip fracture surgery. METHODS: This was a population-based, interrupted time series analysis of 49,097 surgeries for hip fractures, 10,474 for ankle fractures, 1,594 for tibial plateau fractures, and 40,898 for appendectomy at all hospitals in Ontario, Canada between April 2012 and March 2017. We used segmented regression analysis of interrupted monthly time series data to evaluate the impact of funding reform enacted April 1, 2014 on wait time for hip fracture repair (from hospital presentation to surgery) and after-hours provision of surgery (occurring between 1700 and 0700 h). To assess potential adverse consequences of the reform, we also evaluated two control procedures, ankle and tibial plateau fracture surgery. Appendectomy served as a non-orthopedic tracer for assessment of secular trends. RESULTS: The difference (95 % confidence interval) between the actual mean wait time and the predicted rate had the policy change not occurred was - 0.46 h (-3.94 h, 3.03 h) for hip fractures, 1.46 h (-3.58 h, 6.50 h) for ankle fractures, -3.22 h (-39.39 h, 32.95 h) for tibial plateau fractures, and 0.33 h (-0.57 h, 1.24 h) for appendectomy (Figure 1; Table 3). The difference (95 % confidence interval) between the actual and predicted percentage of surgeries performed after-hours - 0.90 % (-3.91 %, 2.11 %) for hip fractures, -3.54 % (-11.25 %, 4.16 %) for ankle fractures, 7.09 % (-7.97 %, 22.14 %) for tibial plateau fractures, and 1.07 % (-2.45 %, 4.59 %) for appendectomy. CONCLUSIONS: We found no significant effects of a targeted hospital funding model based on fixed price and volume on wait times or the provision of after-hours surgery. Other approaches for improving hip fracture wait times may be worth pursuing instead of funding reform.

A skin-conformable wireless sensor to objectively quantify symptoms of pruritus.

Itch is a common clinical symptom and major driver of disease-related morbidity across a wide range of medical conditions. A substantial unmet need is for objective, accurate measurements of itch. In this article, we present a noninvasive technology to objectively quantify scratching behavior via a soft, flexible, and wireless sensor that captures the acousto-mechanic signatures of scratching from the dorsum of the hand. A machine learning algorithm validated on data collected from healthy subjects (n = 10) indicates excellent performance relative to smartwatch-based approaches. Clinical validation in a cohort of predominately pediatric patients (n = 11) with moderate to severe atopic dermatitis included 46 sleep-nights totaling 378.4 hours. The data indicate an accuracy of 99.0% (84.3% sensitivity, 99.3% specificity) against visual observation. This work suggests broad capabilities relevant to applications ranging from assessing the efficacy of drugs for conditions that cause itch to monitoring disease severity and treatment response.

Interventions for increasing solid organ donor registration.

BACKGROUND: A solution for increasing the number of available organs for transplantation is to encourage more individuals to register a commitment for deceased organ donation. However, the percentage of the population registered for organ donation remains low in many countries. OBJECTIVES: To evaluate the benefits and harms of various interventions used to increase deceased organ donor registration. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 11 August 2020 through contact with an Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: We included all randomised controlled trials (RCTs), cluster RCTs and quasi-RCTs of interventions to promote deceased organ donor registration. We included studies if they measured self-reported or verified donor registration, intention to donate, intention to register a decision or number of individuals signing donor cards as outcomes. DATA COLLECTION AND ANALYSIS: Two authors independently assessed retrieved studies and extracted data from included studies. We assessed studies for risk of bias. We obtained summary estimates of effect using a random-effects model and expressed results as risk ratios (RR) (95% confidence intervals; CI) for dichotomous outcomes and mean difference (MD; 95% CI) or standardised mean difference (SMD; 95% CI) for continuous outcomes. In multi-arm trials, data were pooled to create single pair-wise comparisons. Analyses were stratified by specific intervention setting where available. MAIN RESULTS: Our search strategy identified 46 studies (47 primary articles, including one abstract) comprising 24 parallel RCTs, 19 cluster RCTs and 3 quasi-RCTs. Sample sizes ranged from 138 to 1,085,292 (median = 514). A total of 16 studies measured registration behaviour, 27 measured intention to register/donate and three studies measured both registration behaviour and intention to register. Interventions were delivered in a variety of different settings: schools (14 studies), driver's motor vehicle (DMV) centres (5), mail-outs (4), primary care centres (3), workplaces (1), community settings (7) and general public (12). Interventions were highly varied in terms of their content and included strategies such as educational sessions and videos, leveraging peer leaders, staff training, message framing, and priming. Most studies were rated as having high or unclear risk of bias for random sequence generation and allocation concealment and low risk for the remainder of the domains. Data from 34/46 studies (74%) were available for meta-analysis. Low certainty evidence showed organ donation registration interventions had a small overall effect on improving registration behaviour (16 studies, 1,294,065 participants: RR 1.30, 95% CI 1.19 to 1.43, I2 = 84%), intention to register/donate (dichotomous) (10 studies, 10,838 participants: RR 1.21, 95% CI 1.03 to 1.42, I2 = 91%) and intention to register/donate (continuous) (9 studies, 3572 participants: SMD 0.23, 95% CI 0.11 to 0.36, I2 = 67%). Classroom-based interventions delivered in a lecture format by individuals from the transplant community may be effective at increasing intention to register/donate (3 studies, 675 participants: RR 1.33, 95% CI 1.15 to 1.55, I² = 0%). Community interventions targeting specific ethnic groups were generally effective at increasing registration rates (k = 5, n = 4186; RR 2.14, 95% CI 1.35 to 3.40, I² = 85%), although heterogeneity was high. In particular, interventions delivered in the community by trained peer-leaders appear to be effective (3 studies, 3819 participant: RR 2.09, 95% CI 1.08 to 4.06, I² = 87%), although again, the data lacked robustness. There was some evidence that framing messages (e.g. anticipated regret) and priming individuals (e.g. reciprocity) in a certain way may increase intention to register/donate, however, few studies measured this effect on actual registration. Overall, the studies varied significantly in terms of design, setting, content and delivery. Selection bias was evident and a quarter of the studies could not be included in the meta-analysis due to incomplete outcome data reporting. No adverse events were reported. AUTHORS' CONCLUSIONS: In our review, we identified a variety of approaches used to increase organ donor registration including school-based educational sessions and videos, leveraging peer leaders in the community, DMV staff training, targeted messaging and priming. The variability in outcome measures used and incompleteness in reporting meant that most data could not be combined for analysis. When data were combined, overall effect sizes were small in favour of intervention groups over controls, however, there was significant variability in the data. There was some evidence that leveraging peer-leaders in the community to deliver organ donation education may improve registration rates and classroom-based education from credible individuals (i.e. members of the transplant community) may improve intention to register/donate, however, there is no clear evidence favouring any particular approach. There was mixed evidence for simple, low-intensity interventions utilising message framing and priming. However, it is likely that interest in these strategies will persist due to their reach and scalability. Further research is therefore required to adequately address the question of the most effective interventions for increasing deceased organ donor registration.

Quantifying the Effects of Antimicrobials on In vitro Biofilm Architecture using COMSTAT Software.

Biofilms are aggregates of microorganisms that rely on a self-produced matrix of extracellular polymeric substance for protection and structural integrity. The nosocomial pathogen, Pseudomonas aeruginosa, is known to adopt a biofilm mode of growth, causing chronic pulmonary infection in patients with cystic fibrosis (CF). The computer program, COMSTAT, is a useful tool for quantifying antimicrobial-induced changes in P. aeruginosa biofilm architecture by extracting data from three-dimensional confocal images. However, standardized operation of the software is less commonly addressed, which is important for optimal reporting of biofilm behavior and cross-center comparison. Thus, the aim of this protocol is to provide a simple and reproducible framework for quantifying in vitro biofilm structures under varying antimicrobial conditions via COMSTAT. The technique is modeled using a CF P. aeruginosa isolate, grown in the form of biofilm replicates, and exposed to tobramycin and the anti-Psl monoclonal antibody, Psl0096. The step-by-step approach aims to reduce user ambiguity and minimize the chance of overlooking crucial image-processing steps. Specifically, the protocol emphasizes the elimination of subjective variations associated with the manual operation of COMSTAT, including image segmentation and the selection of appropriate quantitative analysis functions. Although this method requires users to spend additional time processing confocal images prior to running COMSTAT, it helps minimize misrepresented biofilm heterogenicity in automated outputs.

Effects of quality-based procedure hospital funding reform in Ontario, Canada: An interrupted time series study.

BACKGROUND: The Government of Ontario, Canada, announced hospital funding reforms in 2011, including Quality-based Procedures (QBPs) involving pre-set funds for managing patients with specific diagnoses/procedures. A key goal was to improve quality of care across the jurisdiction. METHODS: Interrupted time series evaluated the policy change, focusing on four QBPs (congestive heart failure, hip fracture surgery, pneumonia, prostate cancer surgery), on patients hospitalized 2010-2017. Outcomes included return to hospital or death within 30 days, acute length of stay (LOS), volume of admissions, and patient characteristics. RESULTS: At 2 years post-QBPs, the percentage of hip fracture patients who returned to hospital or died was 3.13% higher in absolute terms (95% CI: 0.37% to 5.89%) than if QBPs had not been introduced. There were no other statistically significant changes for return to hospital or death. For LOS, the only statistically significant change was an increase for prostate cancer surgery of 0.33 days (95% CI: 0.07 to 0.59). Volume increased for congestive heart failure admissions by 80 patients (95% CI: 2 to 159) and decreased for hip fracture surgery by 138 patients (95% CI: -183 to -93) but did not change for pneumonia or prostate cancer surgery. The percentage of patients who lived in the lowest neighborhood income quintile increased slightly for those diagnosed with congestive heart failure (1.89%; 95% CI: 0.51% to 3.27%) and decreased for those who underwent prostate cancer surgery (-2.08%; 95% CI: -3.74% to -0.43%). INTERPRETATION: This policy initiative involving a change to hospital funding for certain conditions was not associated with substantial, jurisdictional-level changes in access or quality.

Exploring the experiences and perspectives of substitute decision-makers involved in decisions about deceased organ donation: a qualitative study protocol.

INTRODUCTION: In Canada, deceased organ donation provides over 80% of transplanted organs. At the time of death, families, friends or others assume responsibility as substitute decision-makers (SDMs) to consent to organ donation. Despite their central role in this process, little is known about what barriers, enablers and beliefs influence decision-making among SDMs. This study aims to explore the experiences and perspectives of SDMs involved in making decisions around the withdrawal of life-sustaining therapies, end-of-life care and deceased organ donation. METHODS AND ANALYSIS: SDMs of 60 patients admitted to intensive care units will be enrolled for this study. Ten hospitals across five provinces in Canada in a prospective multicentre qualitative cohort study. We will conduct semistructured telephone interviews in English or French with SDMs between 6 and 8 weeks after the patient's death. Our sampling frame will stratify SDMs into three groups: SDMs who were not approached for organ donation; SDMs who were approached and consented to donate and SDMs who were approached but did not consent to donate. We will use two complementary theoretical frameworks-the Common-Sense Self-Regulation Model and the Theoretical Domains Framework- to inform our interview guide. Interview data will be analysed using deductive directed content analysis and inductive thematic analysis. ETHICS AND DISSEMINATION: This study has been approved by the Centre Hospitalier de l'Université de Montréal Research Ethics Board. The findings from this study will help identify key factors affecting substitute decision-making in deceased organ donation, reasons for non-consent and barriers to achieve congruency between SDM and patient wishes. Ultimately, these data will contribute to the development and evaluation of tools and training for healthcare providers to support SDMs in making decisions about organ donation. TRIAL REGISTRATION NUMBER: NCT03850847.