Modeling Second Order Impacts of Healthcare Innovation

Any single health service organization today is likely engaged in dozens of concurrent, often times unrelated change initiatives. Each of these change initiatives is likely supported by evidence that demonstrates the innovation’s intended, first order impact. However, very little attention has been paid to the unintended, second order impacts of innovation. In this dissertation we introduce a model to provide a framework for inquiring about this very type of non-immediate impact. Next, using three innovations currently being implemented in the healthcare industry—training primary care residents to perform in-office colonoscopies, Studer Group’s ‘Evidence Based Leadership,’ and implementation of electronic health records in a hospital-integrated pediatric network—we model the innovations’ second order impacts within the context of our second order impact conceptual model. Cost effectiveness analysis, multiple analysis of variance (MANOVA), and two-level fixed effects modeling are used to across the three interventions. Results from the primary care residency intervention support further investment in colorectal cancer screening training for primary care residents. Results from the Studer Group’s ‘Evidence Based Leadership’ intervention demonstrate mixed results across change interventions and across categories of tenure, suggesting receptivity towards change and organization tenure is highly dependent upon the nuances of a specific change intervention. Finally, results from the implementation of the electronic health record demonstrate improved charge capture. We conclude that this further probing of popular innovations in the industry is warranted for multiple reasons. For one, it is entirely possible that social scientists and economists are prematurely ‘moving on’ to other innovations as soon they have published results from an initial round of inquiry. However, as we will demonstrate in our model, it is conceivable that after the “lights have dimmed” on an innovation’s initial glow, the artifacts of the innovation could very well continue to disrupt structures and processes long after its implementation. If these latent disruptions adversely affect the organization, one could argue that any initial positive impacts were likely overstated. Conversely, if these latent disruptions go on to produce additional benefit to the organization one could argue that any initial positive results were actually understated

Drivers with and without Obesity Respond Differently to a Multi-Component Health Intervention in Heavy Goods Vehicle Drivers

Funding This project was funded by the National Institute for Health Research (NIHR) Public Health Research programme (reference: NIHR PHR 15/190/42). The study was also supported by the NIHR Leicester Biomedical Research Centre which is a partnership between University Hospitals of Leicester NHS Trust, Loughborough University and the University of Leicester. Laura Gray is supported by the National Institute for Health Research (NIHR) Applied Research Collaboration East Midlands (ARC EM). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. Funding to cover the intervention costs (Fitbits and cab workout equipment) was provided by the Higher Education Innovation Fund, via the Loughborough University Enterprise Projects Group. The Colt Foundation provided funding for a PhD Studentship, awarded to Amber Guest (reference: JD/618), which covered Amber’s time and contributions to this project. The funders played no role in study design, data collection, data analysis, data interpretation or in the preparation of this manuscript.Peer reviewedPublisher PD

A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Physical, cognitive, and mental health impacts of COVID-19 after hospitalisation (PHOSP-COVID): a UK multicentre, prospective cohort study

Background The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes. Methods The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a multicentre, long-term follow-up study of adults (aged ≥18 years) discharged from hospital in the UK with a clinical diagnosis of COVID-19, involving an assessment between 2 and 7 months after discharge, including detailed recording of symptoms, and physiological and biochemical testing. Multivariable logistic regression was done for the primary outcome of patient-perceived recovery, with age, sex, ethnicity, body-mass index, comorbidities, and severity of acute illness as covariates. A post-hoc cluster analysis of outcomes for breathlessness, fatigue, mental health, cognitive impairment, and physical performance was done using the clustering large applications k-medoids approach. The study is registered on the ISRCTN Registry (ISRCTN10980107). Findings We report findings for 1077 patients discharged from hospital between March 5 and Nov 30, 2020, who underwent assessment at a median of 5·9 months (IQR 4·9–6·5) after discharge. Participants had a mean age of 58 years (SD 13); 384 (36%) were female, 710 (69%) were of white ethnicity, 288 (27%) had received mechanical ventilation, and 540 (50%) had at least two comorbidities. At follow-up, only 239 (29%) of 830 participants felt fully recovered, 158 (20%) of 806 had a new disability (assessed by the Washington Group Short Set on Functioning), and 124 (19%) of 641 experienced a health-related change in occupation. Factors associated with not recovering were female sex, middle age (40–59 years), two or more comorbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial but only weakly associated with the severity of acute illness. Four clusters were identified with different severities of mental and physical health impairment (n=767): very severe (131 patients, 17%), severe (159, 21%), moderate along with cognitive impairment (127, 17%), and mild (350, 46%). Of the outcomes used in the cluster analysis, all were closely related except for cognitive impairment. Three (3%) of 113 patients in the very severe cluster, nine (7%) of 129 in the severe cluster, 36 (36%) of 99 in the moderate cluster, and 114 (43%) of 267 in the mild cluster reported feeling fully recovered. Persistently elevated serum C-reactive protein was positively associated with cluster severity. Interpretation We identified factors related to not recovering after hospital admission with COVID-19 at 6 months after discharge (eg, female sex, middle age, two or more comorbidities, and more acute severe illness), and four different recovery phenotypes. The severity of physical and mental health impairments were closely related, whereas cognitive health impairments were independent. In clinical care, a proactive approach is needed across the acute severity spectrum, with interdisciplinary working, wide access to COVID-19 holistic clinical services, and the potential to stratify care. Funding UK Research and Innovation and National Institute for Health Research

Modeling Second Order Impacts of Healthcare Innovation

Any single health service organization today is likely engaged in dozens of concurrent, often times unrelated change initiatives. Each of these change initiatives is likely supported by evidence that demonstrates the innovation’s intended, first order impact. However, very little attention has been paid to the unintended, second order impacts of innovation. In this dissertation we introduce a model to provide a framework for inquiring about this very type of non-immediate impact. Next, using three innovations currently being implemented in the healthcare industry—training primary care residents to perform in-office colonoscopies, Studer Group’s ‘Evidence Based Leadership,’ and implementation of electronic health records in a hospital-integrated pediatric network—we model the innovations’ second order impacts within the context of our second order impact conceptual model. Cost effectiveness analysis, multiple analysis of variance (MANOVA), and two-level fixed effects modeling are used to across the three interventions. Results from the primary care residency intervention support further investment in colorectal cancer screening training for primary care residents. Results from the Studer Group’s ‘Evidence Based Leadership’ intervention demonstrate mixed results across change interventions and across categories of tenure, suggesting receptivity towards change and organization tenure is highly dependent upon the nuances of a specific change intervention. Finally, results from the implementation of the electronic health record demonstrate improved charge capture. We conclude that this further probing of popular innovations in the industry is warranted for multiple reasons. For one, it is entirely possible that social scientists and economists are prematurely ‘moving on’ to other innovations as soon they have published results from an initial round of inquiry. However, as we will demonstrate in our model, it is conceivable that after the “lights have dimmed” on an innovation’s initial glow, the artifacts of the innovation could very well continue to disrupt structures and processes long after its implementation. If these latent disruptions adversely affect the organization, one could argue that any initial positive impacts were likely overstated. Conversely, if these latent disruptions go on to produce additional benefit to the organization one could argue that any initial positive results were actually understated

Long-Term Effects of the University of Wisconsin--Eau Claire Civil Rights Pilgrimage

Color poster with text and bar graphs.The Civil Rights Pilgrimage (CRP) is an immersion experience that has been offered 20 times with 1206 total participants available for study. Participants go on a ten-day pilgrimage, visiting key historical locations of the civil rights movement, touring museums, and speaking with influential foot soldiers. Anecdotally, many participants report a life-changing experience, bringing what they learned back to the University of Wisconsin-Eau Claire and into their own lives. In order to understand the CRP’s impact, we will investigate how or if the CRP has changed participants’ lives one to ten years after the experience by acquiring descriptive research. This research supports the claim that cultural immersion experiences have a positive and lasting impact (https://www.aacu.org).Blugold Commitment Differential Tuition Grant; University of Wisconsin--Eau Claire Office of Research and Sponsored Programs

The views of GPs about using sit–stand desks: an observational study

Background Occupational sitting is associated with negative health outcomes. Sit–stand workstations have been shown to reduce sitting time in office workers, although there is no evidence on whether this change to practice would be acceptable to GPs. Aim To investigate GPs views about the use of sit–stand desks within general practice and the potential impact they may have on the nature and quality of consultations with adult patients. Design & setting Observational study involving GPs located across the UK. Method An online survey was emailed to members of the Royal College of General Practitioners (RCGP) and shared on social media. Only GPs working in the UK were eligible. The survey included questions on socio-demographics, GPs views about the use of sit–stand desks within their work, their levels of physical activity, total time spent sitting at work each day, and time spent at work. Results 14 142 surveys were sent by the RCGP to their members with 810 GPs responding, with a further 33 responding via social media. 60.6% of GPs would like a sit–stand desks in their consultation room, while 19.2% already had one. Most GPs thought sit–stand desks could be used for telephone consultations (91.9%) and administration tasks (92.3%). There was less agreement about whether they could be used during face-to-face consultations (35.0% agreed), with the potential impact on the doctor–patient relationship raised as the primary concern. Conclusion The implementation of sit–stand desks had support from GPs, but their possible impact on the doctor–patient relationship should be considered in future research.</p

Data supporting "Modes of action of the archaeal Mre11-Rad50 DNA-repair complex revealed by Fast-scan atomic force microscopy"

See the README.txt file for a description of the dataset. The supplementary data files contain the raw data and preliminary unprocessed atomic force microscope (AFM) images and the DNA data for Supplementary Figure 5. Using these it is possible to replicate the AFM images and related statistics presented in the paper. Individual images that form the basis of the movies/videos contained in the ’Supplementary Index’ to the paper are also included. The AFM images are in common formats (JPEG, PNG etc). The AFM data files are in the format generated by proprietary Bruker Nanoscope software. They can be opened and interpreted using versions of that software (available by contacting https://www.bruker.com/contact/select-division.html). Other commercial AFM analysis software can be used to open the files and analyse the data contained therein. These include the commonly used SPIP (Scanning Probe Image Processor -used in this study), produced by Image Metrology and recently replaced by MountainsSPIP https://www.imagemet.com/products/mountainsspip-8/, which is marketed by Digital Surf (https://www.digitalsurf.com/). Open source software for AFM analysis is also available, indluding Gwyddion (http://gwyddion.net/) and WSxM (http://www.wsxm.es/)