Characterizing modifications to a comparative effectiveness research study: the OPTIMIZE trial-using the Framework for Reporting Adaptations and Modifications to Evidence-based Interventions (FRAME).

BACKGROUND: The OPTIMIZE trial is a multi-site, comparative effectiveness research (CER) study that uses a Sequential Multiple Assessment Randomized Trial (SMART) designed to examine the effectiveness of complex health interventions (cognitive behavioral therapy, physical therapy, and mindfulness) for adults with chronic low back pain. Modifications are anticipated when implementing complex interventions in CER. Disruptions due to COVID have created unanticipated challenges also requiring modifications. Recent methodologic standards for CER studies emphasize that fully characterizing modifications made is necessary to interpret and implement trial results. The purpose of this paper is to outline the modifications made to the OPTIMIZE trial using the Framework for Reporting Adaptations and Modifications to Evidence-Based Interventions (FRAME) to characterize modifications to the OPTIMIZE trial in response to the COVID pandemic and other challenges encountered. METHODS: The FRAME outlines a strategy to identify and report modifications to evidence-based interventions or implementation strategies, whether planned or unplanned. We use the FRAME to characterize the process used to modify the aspects of the OPTIMIZE trial. Modifications were made to improve lower-than-anticipated rates of treatment initiation and COVID-related restrictions. Contextual modifications were made to permit telehealth delivery of treatments originally designed for in-person delivery. Training modifications were made with study personnel to provide more detailed information to potential participants, use motivational interviewing communication techniques to clarify potential participants' motivation and possible barriers to initiating treatment, and provide greater assistance with scheduling of assigned treatments. RESULTS: Modifications were developed with input from the trial's patient and stakeholder advisory panels. The goals of the modifications were to improve trial feasibility without compromising the interventions' core functions. Modifications were approved by the study funder and the trial steering committee. CONCLUSIONS: Full and transparent reporting of modifications to clinical trials, whether planned or unplanned, is critical for interpreting the trial's eventual results and considering future implementation efforts. TRIAL REGISTRATION: ClinicalTrials.gov NCT03859713. Registered on March 1, 2019.

Hierarchical Spatio-Temporal Graph Neural Networks for Pandemic Forecasting

The spread of COVID-19 throughout the world has led to cataclysmic consequences on the global community, which poses an urgent need to accurately understand and predict the trajectories of the pandemic. Existing research has relied on graph-structured human mobility data for the task of pandemic forecasting. To perform pandemic forecasting of COVID-19 in the United States, we curate Large-MG, a large-scale mobility dataset that contains 66 dynamic mobility graphs, with each graph having over 3k nodes and an average of 540k edges. One drawback with existing Graph Neural Networks (GNNs) for pandemic forecasting is that they generally perform information propagation in a flat way and thus ignore the inherent community structure in a mobility graph. To bridge this gap, we propose a Hierarchical Spatio-Temporal Graph Neural Network (HiSTGNN) to perform pandemic forecasting, which learns both spatial and temporal information from a sequence of dynamic mobility graphs. HiSTGNN consists of two network architectures. One is a hierarchical graph neural network (HiGNN) that constructs a two-level neural architecture: county-level and region-level, and performs information propagation in a hierarchical way. The other network architecture is a Transformer-based model that captures the temporal dynamics among the sequence of learned node representations from HiGNN. Additionally, we introduce a joint learning objective to further optimize HiSTGNN. Extensive experiments have demonstrated HiSTGNN's superior predictive power of COVID-19 new case/death counts compared with state-of-the-art baselines. © 2022 Owner/Author.

Telemedicine and Socioeconomics in Orthopaedic Trauma Patients: A Quasi-Experimental Study During the COVID-19 Pandemic.

INTRODUCTION: Socioeconomic factors may introduce barriers to telemedicine care access. This study examines changes in clinic absenteeism for orthopaedic trauma patients after the introduction of a telemedicine postoperative follow-up option during the COVID-19 pandemic with attention to patient socioeconomic status (SES). METHODS: Patients (n = 1,060) undergoing surgical treatment of pelvic and extremity trauma were retrospectively assigned to preintervention and postintervention cohorts using a quasi-experimental design. The intervention is the April 2020 introduction of a telemedicine follow-up option for postoperative trauma care. The primary outcome was the missed visit rate (MVR) for postoperative appointments. We used Poisson regression models to estimate the relative change in MVR adjusting for patient age and sex. SES-based subgroup analysis was based on the Area Deprivation Index (ADI) according to home address. RESULTS: The pre-telemedicine group included 635 patients; the post-telemedicine group included 425 patients. The median MVR in the pre-telemedicine group was 28% (95% confidence interval [CI], 10% to 45%) and 24% (95% CI, 6% to 43%) in the post-telemedicine group. Low SES was associated with a 40% relative increase in MVR (95% CI, 17% to 67%, P < 0.001) compared with patients with high SES. Relative MVR changes between pre-telemedicine and post-telemedicine groups did not reach statistical significance in any socioeconomic strata (low ADI, -6%; 95% CI, -25% to 17%; P = 0.56; medium ADI, -18%; 95% CI, -35% to 2%; P = 0.07; high ADI, -12%; 95% CI, -28% to 7%; P = 0.20). CONCLUSIONS: Low SES was associated with a higher MVR both before and after the introduction of a telemedicine option. However, no evidence in this cohort demonstrated a change in absenteeism based on SES after the introduction of the telemedicine option. Clinicians should be reassured that there is no evidence that telemedicine introduces additional socioeconomic bias in postoperative orthopaedic trauma care. LEVEL OF EVIDENCE: III.

The impact of COVID-19 restrictions on participant enrollment in the PREPARE trial.

Background: At the initiation of the COVID-19 pandemic, restrictions forced researchers to decide whether to continue their ongoing clinical trials. The PREPARE (Pragmatic Randomized Trial Evaluating Pre-Operative Alcohol Skin Solutions in Fractured Extremities) trial is a pragmatic cluster-randomized crossover trial in patients with open and closed fractures. PREPARE was enrolling over 200 participants per month at the initiation of the pandemic. We aim to describe how the COVID-19 research restrictions affected participant enrollment. Methods: The PREPARE protocol permitted telephone consent, however, sites were obtaining consent in-person. To continue enrollment after the initiation of the restrictions participating sites obtained ethics approval for telephone consent scripts and the waiver of a signature on the consent form. We recorded the number of sites that switched to telephone consent, paused enrollment, and the length of the pause. We used t-tests to compare the differences in monthly enrollment between July 2019 and November 2020. Results: All 19 sites quickly implement telephone consent. Fourteen out of nineteen (73.6%) sites paused enrollment due to COVID-19 restrictions. The median length of enrollment pause was 46.5 days (range, 7-121 days; interquartile range, 61 days). The months immediately following the implementation of restrictions had significantly lower enrollment. Conclusion: A pragmatic design allowed sites to quickly adapt their procedures for obtaining informed consent via telephone and allowed for minimal interruptions to enrollment during the pandemic.

Characterizing Modifications to a Comparative Effectiveness Research Study – the OPTIMIZE Trial - Using the framework for reporting adaptations and modifications to evidence-based interventions (FRAME) (preprint)

Background The OPTIMIZE trial is a multi-site, comparative effectiveness research (CER) study that uses a sequential multiple assessment randomized trial (SMART) designed to examine the effectiveness of complex health interventions (cognitive behavioral therapy, physical therapy and mindfulness) for adults with chronic low back pain. Modifications are anticipated when implementing complex interventions in CER. Disruptions due to COVID have created unanticipated challenges also requiring modifications. Recent methodologic standards for CER studies emphasize that fully characterizing modifications made is necessary to interpret and implement trial results. The purpose of this paper is to outline the modifications made to the OPTIMIZE trial using the framework for reporting adaptations and modifications to evidence-based interventions (FRAME) to characterize modifications to the OPTIMIZE trial in response to the COVID pandemic and other challenges encountered.  Methods The FRAME outlines a strategy to identify and report modifications to evidence-based interventions or implementation strategies, whether planned or unplanned. We use the FRAME to characterize the process used to modify aspects of the OPTIMIZE trial. Modifications were made to improve lower than anticipated rates of treatment initiation and COVID-related restrictions. Contextual modifications were made to permit telehealth delivery of treatments originally designed for in-person delivery. Training modifications were made with study personnel to provide more detailed information to potential participants, use motivational interviewing communication techniques to clarify potential participants motivation and possible barriers to initiating treatment, and to provide greater assistance with scheduling of assigned treatments.  Results Modifications were developed with input from the trial’s patient and stakeholder advisory panels. Goals of the modifications were to improve trial feasibility without compromising interventions’ core functions. Modifications were approved by the study funder and the trial steering committee.  Conclusions Full and transparent reporting of modifications to clinical trials, whether planned or unplanned, is critical for interpreting the trial’s eventual results and considering future implementation efforts. Trial Registration: Clinicaltrials.gov NCT03859713, registered March 1, 2019

A Crossover Randomized Controlled Trial of Priming Interventions to Increase Hand Hygiene at Ward Entrances

Background Research conducted in the United States suggests that two primes (citrus smells and pictures of a person's eyes) can increase hand gel dispenser use on the day they are introduced in hospital. The current study, conducted at a hospital in the United Kingdom, evaluated the effectiveness of these primes, both in isolation and in combination, at the entry way to four separate wards, over a longer duration than the previous work. Methods A crossover randomized controlled trial was conducted. Four wards were allocated for 6 weeks of observation to each of four conditions, including “control,” “olfactory,” “visual,” or “both” (i.e., “olfactory” and “visual” combined). It was hypothesized that hand hygiene compliance would be greater in all priming conditions relative to the control condition. The primary outcome was whether people used the gel dispenser when they entered the wards. After the trial, a follow up survey of staff at the same hospital assessed the barriers to, and facilitators of, hand hygiene compliance. The trial data were analyzed using regression techniques and the survey data were analyzed using descriptive statistics. Results The total number of individuals observed in the trial was 9,811 (female = 61%), with similar numbers across conditions, including “control” N = 2,582, “olfactory” N = 2,700, “visual” N = 2,488, and “both” N = 2,141. None of the priming conditions consistently increased hand hygiene. The lowest percentage compliance was observed in the “both” condition (7.8%), and the highest was observed in the “visual” condition (12.7%). The survey was completed by 97 staff (female = 81%). “Environmental resources” and “social influences” were the greatest barriers to staff cleaning their hands. Conclusions Taken together, the current findings suggest that the olfactory and visual priming interventions investigated do not influence hand hygiene consistently. To increase the likelihood of such interventions succeeding, future research should focus on prospectively determined mechanisms of action.

Association of COVID-19 With Achieving Time-to-Surgery Benchmarks in Patients With Musculoskeletal Trauma.

Importance: In response to the COVID-19 pandemic, many hospital systems were forced to reduce operating room capacity and reallocate resources. The outcomes of these policies on the care of injured patients and the maintenance of emergency services have not been adequately reported. Objective: To evaluate whether the COVID-19 pandemic was associated with delays in urgent fracture surgery beyond national time-to-surgery benchmarks. Design Setting and Participants: This retrospective cohort study used data collected in the Program of Randomized Trials to Evaluate Preoperative Antiseptic Skin Solutions in Orthopaedic Trauma among at 20 sites throughout the US and Canada and included patients who sustained open fractures or closed femur or hip fractures. Exposure: COVID-19-era operating room restrictions were compared with pre-COVID-19 data. Main Outcomes and Measures: Surgery within 24 hours after injury. Results: A total of 3589 patients (mean [SD] age, 55 [25.4] years; 1913 [53.3%] male) were included in this study, 2175 pre-COVID-19 and 1414 during COVID-19. A total of 54 patients (3.1%) in the open fracture cohort and 407 patients (21.8%) in the closed hip/femur fracture cohort did not meet 24-hour time-to-surgery benchmarks. We were unable to detect any association between time to operating room and COVID-19 era in either open fracture (odds ratio [OR], 1.40; 95% CI, 0.77-2.55; P = .28) or closed femur/hip fracture (OR, 1.01; 95% CI, 0.74-1.37; P = .97) cohorts. In the closed femur/hip fracture cohort, there was no association between time to operating room and regional COVID-19 prevalence (OR, 1.07; 95% CI, 0.70-1.64; P = .76). Conclusions and Relevance: In this cohort study, there was no association between meeting time-to-surgery benchmarks in either open fracture or closed femur/hip fracture during the COVID-19 pandemic compared with before the pandemic. This is counter to concerns that the unprecedented challenges associated with managing the COVID-19 pandemic would be associated with clinically significant delays in acute management of urgent surgical cases and suggests that many hospital systems within the US were able to effectively implement policies consistent with time-to-surgery standards for orthopedic trauma in the context of COVID-19-related resource constraints.

The potential roles of nuclear medicine in the evaluationof long haulers from the COVID-19 pandemic

Introduction: Although most studies on the symptomatology associated with the coronavirus disease 2019(COVID-19) have been focused on the clinical presentations of hospitalized patients in acute settings, an increasingnumber of reports show a rise in “COVID-19 long haulers”-patients who continue to experience or developpersistent symptoms weeks or months after recovering from initial illness. Over 66-87% of COVID-19 patientsreported at least one persistent symptom related to the disease, the most common of which includes: fatigue,cough, dyspnea, anosmia, headaches, arthralgia, and chest pain. These lingering symptoms affect those whoexperienced mild as well as moderate or severe COVID-19 both as inpatients and outpatients. The field of NuclearMedicine offers non-invasive tests that has the potential to help monitor and evaluate COVID-19 long haulers. Methods: We discuss the role of Nuclear Medicine in evaluating COVID-19 long-haulers by presenting the relevanttechniques available in the field. We describe potential applications of these tests to provide both anatomic andfunctional evaluation with the potential to identify medical issues in the long-haulers. Results: COVID-19 has been shown to be a disease that affects multiple organ systems in a variety of ways.Infection and inflammation due to COVID-19 can damage several organs, most notably the lungs, heart, andkidneys. In examining injuries in the lungs, the use of 18F-FDG PET not only highlights the ground-glass opacitiesand lung consolidations consistent with CT findings of COVID-19 patients, but also shows increased 18F-FDGuptake in specific infected areas such as the lymph nodes, allowing us to detect and accurately map the location ofinfection and inflammation. On the other hand, myocardial injury due to COVID-19 can be observed by myocardialperfusion scintigraphy. This is especially useful when assessing microcirculation and coronary flow reserve for riskstratification and therapeutic planning. Finally, due to the high incidence of acute kidney injuries and subsequentrenal complications among COVID-19 patients, the use of renal scintigraphy with Tc-99m MAG-3 and DMSA mayhelp identify renal injuries and scarring. Conclusion: Diagnostic procedures in Nuclear Medicine such as PET/CTand body scintigraphy has the potential to allow us to detect, monitor and evaluate COVID-19 disease complicationsand related organ damage in long-haulers. When utilized in conjunction to other imaging techniques, NuclearMedicine can help provide additional anatomic and functional information to evaluate issues in COVID-19 longhaulers.

“Out of sight”: Nuclear medicine, eye strain andteleradiology during the COVID-19 pandemic

Objectives: Digital eye strain (DES) or computer vision syndrome is a term used to describe a constellation ofvisual problems arising from prolonged digital screen exposure. Radiologists have long been vulnerable to thisoccupational hazard given the extended hours spent behind digital screens reviewing images. Given that excellentvisual acuity is perhaps the most important requirement a nuclear physician must possess in order to effectivelyanalyze images, it is important to shed light on this growing health concern, particularly during the COVID-19pandemic. Methods: During the COVID-19 pandemic imaging became even more crucial in diagnosing and managing clinicalconditions. Due to the high risk of exposure, shortages in personal-protective equipment and increasing healthcareburnout, the amount of time providers spent obtaining histories and examining patients decreased significantly.Consequently, imaging became central in helping clinicians in reaching diagnoses and tailoring patient treatmentplans accordingly. In 2020, imaging in the emergency department setting increased to 42% from 39% in 2019, whereas inpatient imaging increased from 24% to 33% in 2020. The unpredictability of the COVID disease courseresulted in more emergent imaging being ordered by clinicians, which put additional strain on radiologists toincrease turnaround time to help provide answers. Results: There has also been a shift towards Teleradiology during the COVID-19 pandemic with more nuclearmedicine physicians and radiologists working remotely or from home. Although telemedicine has helped decreaserisk of COVID 19 exposure, it has resulted in fewer in person interactions with consultants, as well as with radiologyresidents at academic institutions. Conclusions: Utilizing videoconferencing services has become the new norm and has resulted in increased digitalscreen time. During these unprecedented times, nuclear medicine physicians and radiologists should be morecognizant of DES and focus on measures to help mitigate its potential long-term effects such as by taking frequentbreaks, using appropriate lighting, adjusting image settings and utilizing artificial tears.

“no hard feelings”: Empathy training for nuclearmedicine technologists: A review and methods ofimprovement during the COVID-19 pandemic

Objectives: Empathy is the capacity of an individual to understand and share the feelings, emotions, or experiencesof another person and to observe that person's perspective. In a professional setting, particularly in health caredepartments during the COVID-19 pandemic, empathy becomes a necessary tool in the care of patients. During theCOVID-19 pandemic, a new wave of stress, anxiety and fear has been experienced by all patients, which posesnew challenges for health care professionals who work closely with patients on a daily basis. Here, we discuss theimportance of empathy training of nuclear medicine technologists, and how we can better improve the experienceand care of our patients through methods which implement empathy in the nuclear medicine department. Methods: There are three components of empathy: cognitive, affective and behavioral. Cognitive refers to the abilityto view the perspective of others;in other words, putting oneself in another's shoes. The affective component refers to experiencing the feelings of others. The behavioral component involves communication to reflect understandingof another's feelings;therefore, it must be perceived that one person understands another in a meaningful way. Inempathy training, not all components are necessary to master in order to express empathy. Empathy can still beexperienced by patients even if only one of the components are met. Empathy training is effective and can beenhanced through didactic training and experiential techniques, whereby the student gains insight and educationabout empathy through lectures on empathy theories, followed by experience, whether simulated or in the form of agame. Skill training is another effective method, whereby students are given a list of skills to learn, the skills aremodeled for the students, and finally the students practice performing such skills. Results: Nuclear medicine technologists should actively practice empathy in the workplace, which involves theaction of active listening, framing, reflecting back to the patient, identifying emotions, and looking for feedback.Patients who interact with empathetic medical professionals feel understood, respected, and validated. Thispromotes patient satisfaction, enhances the quantity and quality of clinical data, improves adherence, and fostersbetter relationships. Conclusions: Empathy training is an essential and necessary component to the training ofhealth care professionals, especially in light of the COVID-19 pandemic. Patients are scared and anxious, and usingempathy training to our advantage may help alleviate these fears in our patients during such a difficult time. Byimplementing empathy training techniques, technologists will be better able to make patients comfortable and lessenfears during imaging.

“Better late than never”: Methods of dealing with no-shows in nuclear medicine during the COVID-19pandemic

Objectives: In scheduling, “no-shows” are patients who make appointments, but neither keep nor cancel them. No-shows in the nuclear medicine department lead to waste of valuable resources, revenue and staffing;all which costtime and money, regardless if patients show up or not. During the COVID-19 pandemic, hospitals havedemonstrated a profound lack of appointment adherence, leading to even more waste of resources. Here, wediscuss methods of dealing with no-show patients to reduce anxieties around the virus and to promote adherence toappointments. Methods: Fear is a natural biological defense mechanism used to deal with threats acutely. When chronic, this canbecome disproportionate and unbeneficial to the health of the organism. During the COVID-19 pandemic, fear hasbeen shown to perpetuate anxiety and stress in healthy patients, while intensifying symptoms in less healthy patients. This fear has also decreased appointment adherence, which negatively impacts the nuclear medicinedepartment. Thus, it becomes important to understand our patients and their fears, beliefs, or reasons for notkeeping their appointments, if we seek to reduce the no-show rate. One particular method we may use is thehuman-centered design method, which consists of patient interviews and qualitative research to better understandhuman behavior in order to develop innovative ways to combat problems we may face. By collecting information onwhy patients do not attend their appointments, we may be able to understand, and thus formulate creative ways toimprove compliance tailored to our communities. Another useful method can be retrospective and qualitative datacollection of patients who “no-show” in the electronic health record. By compiling the patients who no-show andidentifying psychosocial factors, we may be better able to identify obstacles to care and develop ways to combatthem in ways that are tailored to the patient. Overall, a humanistic approach to our patients might prove beneficial inthe long run if our aim is to reduce no-shows going forward. Results: Common fears of patients during the COVID-19 pandemic have been due to misinformation and lack ofeducation about the virus, skewed information from the media, the fear of death from the virus, and hospitals beingthought of as infectious reservoirs for the virus. Through patient interviews, data collection, and examining theelectronic health record of our patients, we can design flyers, informational pamphlets, advertisements or posterswhich seek to target these populations and distribute information to them in order to reduce their anxieties. Inaddition, by identifying obstacles to care, we can develop methods that remove or lessen these burdens so that ourpatients have improved access to the care they need. Conclusions: Through use of humanistic methods and data collection to understand our patients fears, we arebetter able to appreciate their motives, particularly their reasons for appointment non-adherence. This way, we canhelp our patients quell those fears, and promote the importance of keeping appointments so that we maximize boththeir care and the use of resources in the nuclear medicine department.