Since December 2010, Florida’s Bureau of Tobacco Free Florida has aired a statewide tobacco education campaign to encourage smoking cessation. The Tobacco Free Florida campaign consists of evidence-based advertisements primarily characterized by strong emotional content and graphic imagery designed to increase awareness of the health risks of tobacco use. We evaluated the effect of the media campaign on population-level quit attempts by using a statewide representative sample of Florida adults aged 18 or older.We examined data from 5,418 Florida adult cigarette smokers and recent quitters aged 18 or older from the Florida Adult Tobacco Survey, an annual, cross-sectional survey conducted from 2011 through 2018. The primary outcome was incidence of quit attempts in the previous 12 months. We used multivariable logistic regression models to estimate the odds of making a quit attempt as a function of advertising levels across state media markets. Rates of quit attempts in Florida were also estimated.P = .02) among smokers and recent quitters. The Tobacco Free Florida campaign was associated with an estimated 332,604 additional smokers making quit attempts per year during the study period.Approximately 66% of smokers in the study made at least 1 quit attempt. Exposure to the campaign was associated with increased odds of a quit attempt in the previous 12 months (odds ratio = 1.25; The Tobacco Free Florida campaign affected cessation-related behaviors in Florida over an 8-year period. Evidence-based state tobacco education campaigns can accelerate progress toward the goal of reducing adult smoking. Statewide media campaigns are an evidence-based component of comprehensive tobacco control programs. However, because of budget limitations, few state tobacco control programs can devote resources to both create and consistently air media campaigns.From 2011 through 2018, the Bureau of Tobacco Free Florida aired hard-hitting advertisements from successful national and state campaigns as part of their Tobacco Free Florida campaign. The study found that exposure to the Tobacco Free Florida campaign influenced the rate of quit attempts among adult smokers in Florida.Statewide media campaigns can use existing effective advertising materials to affect population-level quit attempts.Research shows that mass media campaigns can effectively encourage smoking cessation and contribute to reductions in smoking prevalence among adults aged 18 or older . An inteAs a result of a ballot initiative, the Florida Constitution was amended in 2007 to allocate funds to a comprehensive statewide tobacco education program. The Florida Department of Health Bureau of Tobacco Free Florida is one of the largest statewide tobacco control programs in the United States. The program’s goal is to protect people from the health hazards of using tobacco by discouraging its use. From 2011 through 2018, the bureau invested approximately $160 million in paid advertising to educate residents about the health risks of tobacco use and the dangers of secondhand smoke exposure. The Tobacco Free Florida media campaign (TFF) primarily used advertisements with highly emotional or graphic content; such content is more likely to be attended to and perceived as effective than less hard-hitting content . EmpiricThe extent to which Florida’s statewide campaign affects behavior change at the population level is a crucial question for both state and federal agencies given their limited resources and the high cost of airing televised mass media campaigns. Our study examined the association between exposure to the state’s anti-tobacco television advertisements and quit attempts among smokers and recent quitters over an 8-year period.The Florida Adult Tobacco Survey  is an anResponse rates were available from 2013 through 2018 and were as follows: 10.7% for 2013, 9.1% for 2014, 8.8% for 2015, 7.8% for 2016, 8.7% for 2017, and 6.5% for 2018 , which are the standard unit of measurement for media delivery . TRPs arQuit attempts, which mark progress in achieving successful tobacco cessation, are the standard outcome measure of effectiveness for anti-tobacco mass media campaigns. The outcome variable was whether a respondent made a quit attempt during the past year: “During the past 12 months, have you stopped smoking for one day or longer because you were trying to quit smoking?” Interviewers asked this question only if a person reported 1) smoking at least 100 cigarettes in their life and 2) smoking cigarettes “some days” or “every day” at the time of the survey. We included recent quitters, defined as former cigarette smokers who successfully stopped smoking in the past year, in the group of respondents who made a quit attempt in the past year.Demographic and smoking-related variables included indicators for 4 age categories (age 18–24 was used as the reference); an indicator for male ; indicators for non-Hispanic black, Hispanic, and other non-Hispanic race/ethnicity (non-Hispanic white was the reference category); employment (employed for wages/self-employed versus neither); indicators for 4 educational attainment categories (less than completion of high school was the reference category); the presence of a youth under the age of 18 in the household; and the heaviness of smoking index (HSI). HSI incorporates responses to 2 questions: “On average, on days when you smoked during the past 30 days, about how many cigarettes did you smoke a day?” and “On the days that you smoke, how soon after you wake up do you have your first cigarette?” Each item response had a value between 0 and 3, producing an HSI ranging from 0 to 6. A higher HSI reflects greater nicotine dependence .We also used 2 media-related variables to control for time spent watching television and exposure to the CDC’s national Tips advertisements, which intermittently ran concurrent to TFF campaign advertisements. The wording of the item assessing time spent watching television changed twice over the years analyzed. From 2011 through 2015 it read “Please think back to the last 7 days. On average, how many hours per day did you watch television?” In 2016, the item changed to: “Think about how much you watched television yesterday. About how much time did you spend watching television shows or movies on any platform including a television set, a computer, a laptop, a tablet, a smartphone, or an iPod or MP3 player?” In 2017, the item changed to: “About how much time did you spend watching television shows or movies yesterday? Include time spent watching on a television, computer, laptop, tablet, or smartphone.” We created a dichotomous measure based on the median split of responses. We measured potential exposure to Tips advertisements for each respondent by summing Tips TRPs in the DMA of residence for 1 year before the respondent’s survey date.We used a multivariable logistic regression model to examine the likelihood of making a quit attempt in the past year as a function of past-year TFF campaign TRPs. We divided past-year TRPs by 2,000 to yield estimated odds ratios for the changes in the likelihood of a smoker making a quit attempt in the past year, given a unit increase of 2,000 total TRPs in a media market. Scaling TRPs in this way is a common practice to aid in the interpretation of results when advertisement exposure is the independent variable of interest ,15. As iAs in other assessments of the effect of smoking cessation media campaigns on quit attempts, we included numerous additional variables in the multivariable logistic regression model ,10,17. TWe calculated the percentage of smokers who made quit attempts attributable to the TFF campaign by taking the difference between the actual quit attempt percentage from the analysis sample and the predicted quit attempt percentage in a hypothetical scenario where exposure to the campaign was 0 for each year of the analysis sample. We then applied these differences in quit attempt rates to corresponding annual state populations of smokers in Florida . We perfThe sample of 5,418 current smokers and recent quitters in Florida from 2011 through 2018 was evenly split between women and men, with similar unweighted and weighted distributions by race/ethnicity . Almost P = .02). Hispanic smokers were more likely to make a quit attempt than non-Hispanic white adults. Smokers with children in the household aged younger than 18 years were more likely to try to quit than smokers with no children in the household aged younger than 18 years. Smokers with higher HSI scores were less likely to try to quit than those with lower scores.Results from the multivariable logistic regression model  indicateBy using estimates from the multivariable logistic regression model, we predicted the probability of making a past-year quit attempt at various levels of total annual TFF TRPs. In the hypothetical absence of the campaign, where TRPs were 0, we predicted the overall quit attempt probability for adult Florida smokers to be 55.3%  . PredictTo illustrate the influence of the campaign on quit attempts, we estimated the annual number of Florida smokers who made quit attempts attributable to the TFF campaign during the study period. The overall difference between the actual quit attempt percentage for the sample and the predicted quit attempt percentage in a hypothetical scenario where no exposure to the campaign occurred  was 10.5 percentage points  for the study period, and differences varied from 6.6 to 14.7 percentage points annually across survey years. Applied to the state population of adult smokers in Florida, we estimated that from 2011 through 2018, the TFF campaign was associated with a population weighted average of 332,604 additional smokers making quit attempts per year , with annual estimates ranging from 183,369 additional smokers making quit attempts in 2016 to 443,044 additional smokers making quit attempts in 2011 .Ours is the first study to assess the multiyear impact of Florida’s tobacco education campaign on statewide quit attempts in the context of other nationwide mass media campaigns airing over the past 8 years. We examined the association between temporal and geographic variation in campaign exposure and quit attempts over an 8-year period. Our study used an exogenous measure of media dose, market-level TRPs, which is the most rigorous approach to measurement in natural experiments like media campaigns when control groups are unfeasible . Our stuThis study has several limitations. First, the data are cross-sectional and thus show an association between TRPs and quit attempts that is not as strong as in longitudinal designs . Second,Despite their positive benefits to public health, state tobacco control programs were outspent almost 10 to 1 by the tobacco industry in Florida during the study period . State m


To the Editor—When public pressure mounted for the use of hydroxychloroquine (HCQ) for prophylaxis or treatment of coronavirus disease 2019 (COVID-19), our nation’s leading scientists exercised prudence and recommended awaiting the results of randomized controlled trials (RCTs) before considering its use. Such restraint proved to be invaluable because evidence from these RCTs ultimately showed that there is no benefit but rather harm with HCQ use in the treatment of COVID- 19.2 A similar focus on high-quality evidence has not been taken for masks and effect on mitigating the spread of disease. Internationally, public health mandates for masks in the community, has varied from no masks to mandatory masks when outside in crowds to wearing masks when symptomatic.5 Acknowledging the lack of evidence from RCTs of masks having any additive effects on mitigating the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2),5 public mask use was recommended by the Center for Disease Control (CDC) for protective effect  and not just source control .6 The DANMASK-19 trial was consistent with the 12 previous RCTs7 which showed, with moderate certainty evidence, that there were negligible additive effects from masks in the prevention of respiratory infections. The DANMASK-19 trial showed the mask’s protective effect to be inconclusive and difference between the 2 groups to not be statistically significant in the community setting. Despite the evidence from previous RCTs on influenza and other respiratory viral infections, there was suspicion from observational studies8 that severe acute respiratory syndrome SARS-CoV-2 behaved differently and that droplet transmission could be mitigated by mask use in the presymptomatic phase.5 Therefore, the implementation of universal mask use was justified while awaiting the results DANMASK 19. In light of the inconclusive evidence from DANMASK 19 and the previous RCTs, the case for a protective effect from COVID 19 lacks evidence and requires modification from public health officials.The DANMASK-19 was a well-powered randomized controlled trial  with 46% proper and 47% predominantly proper adherence to mask use in a setting of uncommon mask use, moderate spread of infection, and reasonable adherence to social distancing and handwashing.9 Hence, mask use among symptomatic individuals and their contacts is evidence based. On the contrary, long-term effects of mask use among healthy individuals is unknown,3 and short-term effects include breathing difficulties, self infection through touching eyes due to irritation from exhaled air from masks, and a false sense of security from mask while neglecting social distancing.10 The argument for masks having a variolation effect in COVID-19 is compelling,11 but it lacks the support of evidence from cohort studies. Hence, with the current data available, the best case for masks appears to be in symptomatic patients and recommended (not mandatory) use in crowded settings. Wisdom to use measured language in what we “mandate” and “recommend” would be advised. We must decide with prudence, as we did with HCQ, what we choose to be “absolutely essential” measures, and we must decide these based upon robust evidence. In the haste of establishing “life saving” measures, we may be instead be losing the public’s trust by not having the supportive evidence and unintentionally placing the lives of the community and healthcare workers at risk.Although this study did not assess source control, the effect of masks is compelling, when restricted to contacts of index cases receiving the intervention within 36 hours of symptom onset.


As a form of experiential education, service learning (SL) shows great potential for promoting students' knowledge transfer as it offers students opportunities to apply what they have learned in classrooms to serve communities in real-life contexts. To explore how students' knowledge transfer evolves during SL, we collected longitudinal survey data from 96 Chinese college students in a 9-week SL program. Results indicate that (a) students' perceived knowledge transfer in SL did not follow a linear trajectory. Although students' perceived knowledge transfer at the end of SL was significantly higher than those at the beginning, a slight drop was observed in the middle of SL; (b) the developmental pattern of perceived knowledge transfer varied across students; and (c) students' perceived knowledge transfer development during SL was associated with mastery goal orientation and perceptions of psychologically controlling behaviors from their SL supervisors. By providing evidence of the dynamic process and mechanisms of students' knowledge transfer development, the present study adds to our understanding of how, when, and why the benefits of SL are realized. Knowledge transfer, the ability to apply knowledge and skills learned in school into a new situation, is an important indicator of educational success . First, how do students' perceived knowledge transfer change during a 9-week SL program (RQ1)? Second, are there different developmental patterns of perceived knowledge transfer across students (RQ2)? Third, we asked what factors affected students' perceived knowledge transfer development (RQ3)? The first and second research questions are exploratory in nature. Since students' engagement varies across developmental stages of SL  consented to participate in the research. All participants were sophomore students from the Department of Psychology. The research procedures and student surveys were approved by the institution's ethical committee.Participants in the study were undergraduates at a leading research university in China. This university is well-known for teacher education, education science, and basic learning in arts and sciences. We recruited participants from a psychology course entitled Students learned various learning principles  in their regular classroom learning. During weekends, they worked in a group of four to interact with children with special needs. Although the overall goal of the SL activity was “applying the knowledge and skills learned from the course of Psychology of Learning to serve children with special needs,” the specific SL goals and activities were determined by the undergraduates themselves and might vary across groups. For instance, one group may focus on teaching the child to express his/her needs using appropriate words, while the other group may aim to teach the child to pass and catch a ball. Each service group had a supervisor who provided support during and after SL activities. Students wrote reflective journal entries immediately after each service activity. Students also completed a series of questionnaires prior to and after SL regarding themselves and their SL experiences.r = 0.51, p <0.001).To investigate the development of knowledge transfer during SL, students' perceived knowledge transfer was assessed at eight time points. We asked students to report their levels of knowledge transfer in their weekly reflective journal entries. A single-item measure was used (“Please rate to what extent you applied the knowledge you've learned into this week's SL activity”), with the scale ranging from 0 “none” to 4 “a lot.” To ensure the validity of the self-report item, the first author went over students' reflective journal entries and found that students who had high scores  on this item used more psychology terms and concepts in their reflective journal entries. Furthermore, the sum of the eight perceived knowledge transfer scores was positively associated with the overall perceived knowledge transfer score in their post-SL reflective journal entries , we assessed their perceived knowledge transfer across eight time points from Week 6 to 14 in an 18-week semester. Data from previous studies suggest that there are four developmental stages of student engagement during a 9-week SL program  = 8.82, p <0.05, η2 = 0.05]. Pairwise comparisons suggested that students' perceived knowledge transfer significantly increased from Stage 1 to Stage 2 (p <0.001). No significant difference was found between Stages 2 and 3, although we observed a slight drop in the level of perceived knowledge transfer during Stage 3. students' perceived knowledge transfer rose to a high point and peaked during the last stage of the 9-week SL program. students' perceived knowledge transfer during Stage 4 was significantly higher than those in Stage 1 (p <0.001), suggesting that participating in the 9-week SL program might foster students' perceived knowledge transfer.As shown in F = 8.32, p <0.001, η2 = 0.19. This result suggests that the developmental pattern of perceived knowledge transfer varied across groups of students. Students' perceived knowledge transfer scores across four stages were used in model-based cluster analysis for the categorization of groupings. Based on the best BIC values, the cluster analysis approach produced five clusters with 27 students in Group 1, 12 students in Group 2, 46 students in Group 3, four students in Group 4, and seven students in Group 5. We found a significant interaction effect between time and group on students' perceived knowledge transfer, Group 1 accounted for 29% of the whole sample. Students in this group reported moderate levels of perceived knowledge transfer in Stage 1. There was a slight rise in perceived knowledge transfer from Stage 1 to 2; however, it gradually decreased since Stage 2. Group 2 accounted for 14% of the sample. These students demonstrated a high level of perceived knowledge transfer at the beginning of the SL program; however, their perceived knowledge transfer steadily declined for the rest of the program. Group 3 accounted for the largest proportion (46%) of the sample. Perceived knowledge transfer score increased from Stage 1 to 2. Although there was a slight drop in Stage 3, it rebounded and peaked in the last stage of SL. Groups 4 and 5 accounted for 7 and 4% of the sample, respectively. These two groups had similar patterns during Stages 1 and 2. Students had relatively low perceived knowledge transfer scores at first. Then, the scores increased in Stage 2. Dramatic differences between Groups 4 and 5 were observed after Stage 2. For Group 4, there was a steady decline in students' perceived knowledge transfer; in contrast, Group 5's perceived knowledge transfer increased sharply from Stage 2 to 3, and it maintained the same level until the end.To further understand the differences among students in terms of their perceived knowledge transfer development, we tested the predicting effects of perception of psychological control and mastery goal orientation on group membership (profile). Groups 4 and 5 were excluded from the following analyses as the sample sizes of these two were limited. The results of multinomial logistic regression are shown in Groups 1 and 3 accounted for 75% of the whole sample. As shown in Although the positive impact of SL on college students' knowledge transfer has been well-established  was significantly higher than those at the beginning , a drop was observed in the middle of SL during Stage 3 (4th to 7th time). The drop in perceived knowledge transfer might be related to the development of the SL activities. After implementing and revising interaction plans several times, students started to establish routines for their SL activities during Stage 3. Rather than setting new goals or designing new interactive activities, students were more likely to make minor modifications to their interaction plans. Although they still used the knowledge they learned from classes to serve children with special needs, students tended to underrate their levels of knowledge transfer as the learning principles that were included in their interaction plans or activities were mostly adopted from previous ones rather than newly added. The changes in SL activities may also explain the rebound in perceived knowledge transfer during Stage 4 (8th time). In the last SL activities, students not only implemented their accustomed interaction activities but also designed new activities to celebrate the end of SL with the recipients. Unlike behavior modifications, a farewell celebration focuses on emotional communication and creating a relaxing atmosphere, which offers students opportunities to apply new knowledge and techniques related to learning sciences.Another important finding was that the developmental pattern of perceived knowledge transfer in SL varied across students. Although five groups were identified with model-based clustering, 75% of the students belong to Groups 1 and 3. The developmental pattern of perceived knowledge transfer for Group 3 is similar to the one for the whole sample. Despite a slight drop during Stage 3, students' perceived knowledge transfer increased throughout the SL program. Students in Group 1 had a similar developmental pattern as Group 3 between Stages 1 and 3; however, their perceived knowledge transfer did not pick up during the last stage of the program. Compared to Group 1, students in Group 3 demonstrated a more adaptive developmental pattern of perceived knowledge transfer. The variability in college students' perceived knowledge transfer development suggests that teachers should be mindful of students' cognitive and emotional states when implementing SL activities and provide them with distinct interventions.Drawing from two contemporary motivation theories, we examined the associations of two social-cognitive variables—mastery goal orientation and psychological control—with patterns of perceived knowledge transfer development. The present investigation contributes to our understanding of the social and cognitive factors influencing students' learning development when in SL contexts. The findings showed that students who perceived less psychological control from their supervisors and possessed higher levels of mastery goal orientation had higher possibilities of membership in Group 3. That is, they were more likely to demonstrate adaptive development patterns in perceived knowledge transfer during a 9-week SL program. Mastery goal orientation and psychological control play essential roles in affecting college students' perceived knowledge transfer development and raise the question as to what strategies instructors may use to promote mastery goal orientation and stop being psychologically controlling in the context of SL. Evidence from self-determination theory research suggests a number of approaches, such as providing students with choices, acknowledging students' perspectives, providing meaningful rationales, avoiding controlling language , and staying away from salient reward contingencies (Ryan and Deci, Psychology of Learning. As such, the sample does not represent all fields and potentially over-samples students along gender lines. It would be beneficial to replicate these results in a variety of different types of courses and fields. Second, students' perceived knowledge transfer was assessed with a single-item measure. Although single-item measures generally perform well when gauging a holistic perception (Youngblut and Casper, The current study has several limitations we should note. First, the findings are exploratory in that they represent student experiences within a single SL program that was embedded in the course of The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Beijing Normal University. The patients/participants provided their written informed consent to participate in this study.CW and MY designed the study. CW, FG, YL, and MY collected the data. CW and WY formulated the hypotheses. CW performed the statistical analyses and drafted the manuscript. CW, WY, FG, YL, and MY revised and edited the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Hip fracture is common, affecting 20% of women and 10% of men during their lifetime. The trajectory of patients’ recovery as they transition from the acute hospital setting to their usual residence is poorly understood. Recently, the use of activity trackers to monitor physical activity during recovery has been investigated as a way to explore this trajectory.This prospective observational cohort study followed patients from hospital to home as they recovered from a hip fracture. Participants were recruited from a single centre and provided with a 3-axis logging accelerometer worn as a pendant, for 16 weeks from recruitment. Participants received monthly follow-up visits which included questions about wearing the monitor. Monthly activity monitor data were also downloaded. Participant activity was estimated from the monitor data using the calibrated “Euclidean Norm Minus One” (ENMO) metric. Polynomial mixed-effects modelling was used to evaluate the difference between the weekly activity trends of 2 groups of participants: those with and without independent mobility at 16 weeks .Twenty-nine participants from 125 eligible patients were recruited. Of these, 19 (66%) reported being aware of wearing the monitor at least some of the time. Fourteen (48%) participants withdrew before study completion. Data for thirteen (45%) participants were of sufficient quantity to be included in the activity modelling procedure. Of these, 8 reported independent mobility at 16 weeks post-surgery, and 5 did not. By week 7, the weekly predicted mean ENMO  Study (ISRCTN 63982700). Hip fracture is a common injury, affecting 20% of women and 10% of men during their lifetime. In 2018, the James Lind Alliance identified the top two research priorities in fragility fracture of the lower limb as firstly understanding the best in-hospital and secondly best out-of-hospital physiotherapy regimes for recovery .In 2018, the UK National Hip Fracture Database Report revealed that just 38.4% patients receive follow-up of their mobility at 120 days post injury . Most peThere is a need for more detailed and objective information concerning recovery of patient mobility following a hip fracture, particularly at the critical point of transition from hospital to home, where continuity of rehabilitative care is frequently not achieved. Small and lightweight activity monitors provide an opportunity to measure the recovery of mobility with greater objectivity and frequency in this population.Investigate the acceptability of wearing the activity monitor for the duration of the 4-month follow-up period through participant self-report about wearing the monitorAssessment of participant recruitmentAssessment of participant retention rateInvestigating whether an algorithm can be developed and applied to analyse low-intensity raw activity data obtained from the monitors.Investigating whether this can appropriately differentiate between those participants who report independent mobility versus requiring assistance with mobility at 16 weeks.Assess feasibility of using 3-axis logging accelerometers to collect activity data in this population by:The overall aim of this study was to assess feasibility and acceptability of collecting individual-level activity data via a wearable activity monitor worn on a pendant, to better understand the recovery of mobility in patients during the first 4 months following hip fracture. Study objectives were as follows:A 5-item mobility scale  from May 2018 to August 2019. At the point of recruitment, participants were provided with a 3-axis logging accelerometer, the AX-3 , worn within a pouch attached to a pendant as shown in Fig. At all visits , the participant was supplied with a replacement, fully-charged, monitor.(i)Cognitive impairment(ii)Discharged from hospital to a nursing home as permanent place of residence(iii)Discharged to an area outside the hospital’s neighbouring counties of Berkshire, Buckinghamshire and Oxfordshire.Patients eligible for recruitment to MoHIP were those who met eligibility criteria for, and were recruited to, the World Hip Trauma Evaluation (WHiTE) cohort study . WHiTE iPatients with cognitive impairment were not eligible for inclusion owing to the potential safety implications that might arise from prolonged wear of a pendant system to house the activity monitor. Participants who were discharged to a temporary rehabilitation facility were eligible for inclusion and received the same research follow-up visits as those who were discharged to their own homes.Eligible patients were approached at the first appropriate time during the post-operative period when they had regained capacity . They were provided with study information including detailed information about the monitor, its capability, and how it would be worn. Participants were provided with the opportunity to ask questions and discuss the study with the researcher, their family, and carers for as long as required. All patients were required to give written consent to both the WHiTE study and MoHIP sub-study to participate.Baseline data were collected for recruited participants including demographic data , baseline comorbidities, pre-fracture mobility, type of fracture, type of anaesthesia, type of surgery and health status using the EuroQol 5-Dimension 5-Level measure (EQ-5D-5 L) .g. This configuration enabled the capture of the movements of interest in this study, most in the range up to 12 Hz [Monitors were configured to record activity for 28 days at a sampling frequency of 25 Hz and range of ± 8 i.Participant wear timeii.Percentage participants who reported feeling positive about wearing the monitor half or more of the time.The primary outcome measure was acceptability of using a CE-marked activity-monitoring device worn as a pendant, to assess participants’ physical activity during their recovery from a hip fracture. Acceptability was measured according to:We assessed feasibility of using the activity monitor devices to estimate activity in this patient population through:i.Participant recruitment ratesii.Completion of study protocoliii.Identifying patterns of activity extracted from monitor data, looking for correlations with standard core outcome measures and investigating whether the activity data can identify patients who are inactive. Participants were required to have activity data for ≥ 50% (≥ 8 weeks) of the study period to be included in this analysis.A threshold of 80% is frequently considered an appropriate cut-off for assessing measures of acceptability and feasibility in pilot studies and was therefore adopted for this study . For exaIn order to limit sampling bias, all participants recruited to the WHiTE cohort study were screened for eligibility for MoHIP. Participants of all levels of baseline mobility and functional ability were screened for inclusion. Recruited participants were not provided with feedback regarding their activity levels, minimising risk of observation bias.All participants recruited to the study received usual medical and rehabilitative care.This study was designed to investigate acceptability and feasibility of the use of a wearable activity monitor in an older and complex patient population. We have estimated that with a sample size of 29 participants, we would be able to detect a 20% withdrawal rate with a 95% confidence interval of ± 12%.Study data were managed using REDCap electronic data capture tools hosted at the University of Oxford, providing a secure electronic data capture system , 15.Hz (highpass) and 12 Hz (lowpass) [mg, in each of the three axes, or with an absolute value of less than 50 mg in at least 2 of the axes. Additionally, given that most participants did not wear the activity monitors during the night, only the accelerometer data recorded between 06:30 and 21:30 were considered.Figure lowpass) . A non-wx, y, and z represent each of the axes of the accelerometer sensor; the standard gravity created at the Earth’s surface (1 g) is subtracted; and negative ENMO values are set to zero. The latter may be a result from calibration errors, noise or negligible body movement [W thereafter.The “Euclidean Norm Minus One” metric, activity , 16–18, W (dependent variable) and the number of post-operative recovery weeks and the mobility outcome, i.e. those with and without independent mobility . The latter was modelled as a fixed-effect (binary variable denoted “mobility” coded 1 for participants reporting independent mobility and 0 otherwise). Random-effects were considered at the participant level for the number of post-operative weeks variable (coded as “week”). A normal prior was considered for both the random-effects terms and for the model error term, and the model fit achieved by maximum likelihood estimation. The model polynomial order was varied from 1 to 5, and the cubic model was found to have both the lowest Akaike and Bayesian Information Criteria. The latter is named “baseline model”  was used to assess if the baseline model with an additional clinically relevant parameter  achieved a significantly better model fit. We identified three additional parameters for investigation. Firstly, receipt of physiotherapy in the first month post hospital discharge  which was selected due to the nationally low reported rates of continuity of physiotherapy upon discharge  and prevn = 171, 44.7%). Of the eligible 125 participants, 81 (65%) were approached and 29 (36%) of these were recruited to MoHIP, meaning that the study did not meet the recruitment feasibility threshold of enrolling ≥ 80% of those eligible and approached. The flow diagram of screening and enrolment is shown in Fig. Between May 2018 and August 2019, 125 of 382 participants recruited to the WHiTE Cohort Study were eligible for recruitment to MoHIP. The most common reason for exclusion was cognitive impairment  wore the activity monitor for 13 weeks or more, but two of these participants had data missing for ≥ 50% (8 weeks) of the study period and were therefore ineligible for inclusion in the activity data modelling procedure. The study therefore did not achieve the feasibility thresholds of ≥ 80% participants wearing the monitor for ≥ 80% of the follow-up period. Of the 29 participants, 19 (68%) reported being aware of the monitor at least some of the time. Fourteen (48%) participants withdrew before study completion. Reasons for withdrawal broadly related to two themes: firstly, participants reported the pendant system “got in the way” or was too visible; secondly, some participants reported that ongoing study participation involving daily monitor use and monthly visits was too high a demand in the context of an already high medical burden.Of the 15 participants who completed the study protocol, 2 (13%) reported being unaware of the monitor during periods of wear, and 9 reported being aware of the monitor at least some of the time; 8 of these participants reported a negative awareness such as the monitor getting in the way, being too visible or irritating them. However, 7 (50%) of the 14 participants who completed the study protocol reported feeling positive or very positive about wearing the monitor at half or more of their follow-up visits, and 3 participants reported feeling positive or very positive about wearing the monitor throughout the study period.Overall, participant wear of the Axivity monitor in the pendant system as defined for this study did not meet pre-defined thresholds for feasibility and acceptability.The participants started wearing monitors after a median of 2 IQR 1.8, 5) days post-surgery and were discharged from the hospital after a median of 6  days post-surgery. Only four participants had complete 16-week ENMO data, whilst 2 participants had half or more data missing and were excluded from the mixed-effects modelling. Thirteen patients  were included in the modelling procedure; 9 reported independent mobility at 16 weeks post-surgery, and the remaining 4 reported reliance on mobility aids or personal assistance. Demogpaphics for all participants and those who were included in the modelling analysis are presented in Table .8, 5 dayW recovery trend is shown in Fig. W from week 4 onwards (a participant reaching a maximum ENMOW of 13 g versus 6 g in each group). The average ENMOW ± SE is presented in Fig. W, from 3.7 g  to 8 g , can be seen for the independently mobile group, versus an average ENMOW increase from 3.3 g  to 5.0 g , for the aid-dependent mobility group, from 1 to 16 post-operative weeks.Each participant’s ENMOFigure Finally, using the LRT statistic, it was verified that none of the other clinical factors  provided a better model fit when added to the baseline model.We recruited 29 participants to this study, which assessed feasibility of using a pendant-worn activity monitor to better understand the recovery of mobility in patients during the first 4 months of recovery post-hip fracture injury. We observed low consent rates and a high withdrawal rate. However, this study is novel in its collection of meaningful activity data through an axial-worn activity monitor in this patient cohort, with previous studies being limited to monitors worn on the wrist or thigh , 7. By wWhilst we established feasibility of the monitor’s ability to capture meaningful activity data when worn in this way, feasibility of using such a monitor for future research or clinical practice is limited by the limited feasibility of recruitment and retention of participants, as well as acceptability of the monitor observed in this study. The high withdrawal rate (48%), coupled with some reports of a negative awareness of the monitor from those who completed the study protocol, demonstrates that the method of wearing the monitor employed in this study is not optimally suited to this demographic of the population. This adds an important contribution to the currently limited literature regarding optimal sensor placement and method of wear .This observational study excluded the large proportion of the hip fracture population who have concomitant cognitive impairment. The decision to exclude this group of patients was made owing to the potential safety implications that might arise from prolonged wear of a pendant system to house the activity monitor. The exclusion of this patient group limits the generalisability of our findings. However, whilst it is known that dementia is known to be a risk factor for poorer outcomes after hip fracture , there iW dataset may be too small to derive conclusions from the LRT. The availability of data may have been further impaired by the design of the monitor.Further limitations include the number of participants that we were able to recruit (29 participants) and the number of those with sufficient accelerometer data available to generate an activity trend model (13 participants). Participant self-report of mobility was used to define which participants were independently mobile and which were reliant on aids or assistance. Self-report is vulnerable to bias, and the study may have been improved by the inclusion of a mobility assessment, performed by a healthcare professional. However, an observational study of over 88,000 non-institutionalised older adults observed a concordance rate of 80% between self-report and professional assessment of mobility [In summary, although we were able to demonstrate a significant difference in the average activity between the group that gained full mobility at 16 weeks and the group that did not, this model is not generalisable to the full cohort of patients undergoing hip-fracture surgery, and could potentially be an overfitting to these data. Future work should evaluate its predictive performance on a held-out dataset.This is the first study to our knowledge to investigate acceptability and feasibility of a pendant-worn activity monitor in this patient cohort. We have demonstrated that the ENMO metric may serve as a proxy for the level of physical activity of hip fracture patients during their post-operative recovery period. However, feasibility of recruitment, retention of participants and acceptability of the method of wearing the monitor in this study were notably limited. We have therefore not been able to demonstrate that this specific approach to monitoring activity of hip fracture patients would be feasible for larger-scale research studies. Further research into the use of activity monitors in this patient population should use minimally intrusive devices which are acceptable and safe for a more inclusive population, such as those with cognitive impairment.Additional file 1. Appendices.


They completed a 16-week combined exercise program 3 times/week. We measured physical activity level, physical functioning, depression level, and health-related quality of life at baseline and after 16 weeks. A significant time effect was found in both groups for the physical activity level (p = 0.012). There was also a significant group–time interaction effect for the one-leg standing test (OLST) (p = 0.049) and a significant time effect for the Short Physical Performance Battery (p = 0.013), timed up-and-go test (p = 0.005), sit-to-stand-10 (p = 0.027), right and left hand handgrip , one-heel left leg raise (p = 0.019), and 6-minute walking (p = 0.006), depression (p = 0.017). HRQoL remained unchanged. There was no difference between the two interventions on the tested outcomes (besides OLST). Both interventions were associated with positive changes of the physical activity levels and physical function.Intradialytic exercise (ID) programs are effective and safe for hemodialysis (HD) patients to avoid functional deterioration. However, exercise is not routinely undertaken in most HD units, and we do not know if home-based (HB) programs are as effective as ID programs. The purpose of this study was to compare the effects of 16 weeks of ID exercise versus a HB exercise program for HD patients. A total of 46 patients were randomly assigned to the ID group ( In addition, this population often presents symptoms of depression and anxiety5. Exercise programs for people with CKD have been implemented since the beginning of 1980s6. For optimal benefits, these programs should include a combination of aerobic exercise and strength resistance7. The few studies carried out in HD units in Spain have tested different exercise types including strength-resistance8, resistance9, low intensity endurance training11, neuromuscular electrostimulation13, and virtual reality14.Chronic kidney disease (CKD) patients undergoing hemodialysis (HD) present a progressive functional deterioration, poor health-related quality of life (HRQoL), and low levels of physical activity compared to their healthy age-matched counterparts15 because adherence to this modality is higher than with other formats16. Nevertheless, to the best of our knowledge, HD units in Spain do not currently include exercise as part of routine HD treatments, perhaps because of the financial cost associated with ID exercise programs. Thus, home-based (HB) programs may be an option that could compensate for these cost-related constraints17. To our knowledge, only a few studies have applied HB exercise programs. We found a total of twelve HB studies in HD patients28: 9 of them were randomized controlled trials28, and only 318 implemented a combined HB exercise program comprising both aerobic and strength exercises. Several studies measured physical functioning through physical performance tests but none analyzed the effect of the interventions on physical activity levels.Different exercise modalities have been studied in the literature, but intradialytic (ID) exercise is considered the best approach31. Sedentary behavior is associated with physical deterioration and usually results in limitations in the performance of the activities of daily living which could lead to disability34. This can increase both the number of comorbid conditions presented by patients with HD as well as their mortality risk 35. Thus, it is important to implement interventions to increase the physical activity level of patients with HD.It is well known that the physical activity levels of patients in maintenance HD are lower than their healthy age-matched counterpartsTherefore, the primary aim of this study was to compare the effects of ID versus HB exercise programs on the physical activity level of patients on maintenance HD. The secondary aims were (i) to compare the effects of ID versus HB exercise on physical function, (ii) HRQoL, (iii) the symptoms of depression, and (iv) on adherence. We hypothesized that the ID program would result in more benefits than the HB exercise program.Forty-six patients undergoing HD were recruited and randomly allocated into the ID or HB exercise groups. There were 13 dropouts in the ID group and 10 in the HB group  and 53% for the HB group (number of sessions completed P25 = 11 P75 = 37 and number of missed session HB P25 = 3-P75 = 37).F = 7.642, p = 0.012). Another secondary measure of physical activity showed similar results , 1 who was moderately active (AAS = 53–74 points), and 3 active patients (AAS > 74 points), whereas at the end of the HB, 5 individuals were moderately active. Regarding the ID group, at baseline 5 individuals had impaired activity, 3 were moderately active, and 3 were active; by the end of the program 4 individuals were moderately active and 5 were active. Both interventions lifted participants from the impaired activity category.p = 0.049, p = 0.013). The time–group interaction was not significant for the STS-10, SPPB, TUG, HG, or 6MWT. However, we observed a significant time effect, indicating that performance improved in both intervention groups.Table The values obtained for the CES-D and HRQoL in each group at baseline and after 16 weeks are shown in Table The purpose of this study was to compare the effect on HD patients of performing an ID versus HB 16-week exercise program. To our knowledge, this is the first HB exercise program devised and tested in Spain. We wanted to discover if, in a Spanish population on HD, performing a HB program improved patient physical activity, physical functioning, and HRQoL and CES-D scores.The study design tried to implement two different interventions balanced in exercise intensity and volume. Both programs aimed at improving lower limb muscle strength of the most commonly used muscle groups in activities of daily living, although the restricted position for the ID group limited how to perform strengthening exercises, and at HB group was not restricted at all regarding positions to do strength exercises. We tried also to mimic the aerobic component, though ID group cycled while the HB group walked. Sessions per week, exercise volume  and exercise time was quite similar in both groups.3. Thus, we believe the increase we found is important and hope it will inspire nephrologists and renal nurses to implement interventions designed to encourage exercise among patients in HD units. A previous study did not find any significant differences between 12 weeks of resistance training versus a group receiving an anabolic steroid (nandrolone) in terms of physical activity outcomes in terms of the AAS36. It is possible that combined exercise for a longer time (16 weeks) had a higher impact on daily physical activity.Increased physical activity levels may result in a better physical condition37. This result, since is the only functional measure that showed a group per time interaction effect, could also be found by chance.In terms of physical function, a significant group–time interaction was found only for the OLST, while the OLST time also increased in the ID group. To our knowledge, ours is the first study to use the OLST to measure physical functioning in a population on HD. The fact that balance improved only in the ID group is surprising because the ID program did not include any exercise that specifically targeted this ability. However, this outcome may be explained by the improved lower limb muscle activity generally associated with exercise and the higher exercise adherence rate in the ID program38. The results for the ID group concur with those from previous studies reporting improvements in this test ranging from 2.5 to 5.75 seconds41. However, the magnitude of improvement in the HB group was less than in a previous study18. Compared with these previous studies, our patients required more time at baseline to perform the tests. Moreover, poor adherence in the HB group may have negatively affected our results.The impact of exercise programs on the other physical function metrics was not significantly different between groups. Thus, like the physical activity level outcome, the functional level of the participants improved in both programs. The STS-10 results improved from baseline to 16 weeks although we did not achieve the minimal detectable change (MDC) of 8.4 seconds38. We detected a similar change in the ID group as in previous studies44. Nevertheless, the improvement in the HB group we achieved was lower than in previous studies20, perhaps because these participants had used a pedometer for walking training, thus providing them with direct feedback which could have been a motivational factor. The 6MWT increased in one study28 that implemented walking training in a home-based program. This study ensured the education of the dialysis personnel in the exercise program, who also assisted in the training phase of the trial. Thus, the nursing team could encourage patients to complete the program and this fact could have resulted in increased adherence to exercise.The 6MWT results significantly improved between the baseline and 16 weeks, even though the MDC of 66.3 meters was not achieved18, after 16 weeks of ID or HB training neither the group–time interaction or time significantly affected self-reported HRQoL (KDQoL-36). There was a non-significant physical component improvement over time. Other studies that evaluated the HRQoL via the SF-36 also revealed inconsistent results, perhaps because of the different exercise program durations, the variety and intensity of exercise types used, and the different characteristics of the participants in each study.In agreement with a previous studyp = 0.017). Previous studies measuring depression with others questionnaires  also found a significant improvement in this variable after exercise.Although we did not find significant mental composite results in this study using the KDQoL, the CES-D–time factor did significantly change 23. This fact underscores the essential importance of HD unit nurses and nephrologists as a means to identify and overcome barriers to exercise. In our study, the fact that the physical therapist was external to the unit was a previously described barrier46. Even though adherence was low, we observed an improvement in the physical condition of all the patients when they participated in a HB exercise program.In our study, the HB participants reported that they completed only 53% of the proposed sessions and it was very difficult to convince them to exercise on their own. We found that patients did not undertake the exercise as suggested and did not implement the program in their life routine. We implemented several strategies to try to improve adherence, but none were very successful. Our HB exercise adherence rate was similar to that reported in a previous study in which the HB group completed 58% of the sessions (using a pedometer)Although the findings of this study are positive for both the ID and HB groups, some limitations should be acknowledged. We had a high number of dropouts in both groups and some participants did not want to exercise in the group to which they were randomly allocated: the majority preferred the ID exercise training format. Most of the participants from the HB group did not have support at home and were not supervised or supported by a relative. The only motivational support that they had was when the physical therapist approached them. Moreover, the difficulty level of the strength exercises in the ID group may have been insufficient, even though we measured the 10 repetition maximum every two weeks to ensure their resistance training progression.This was a randomized controlled clinical trial. Eligible participants were randomly assigned either to the ID or HB exercise group. The exercise program lasted 16 weeks and the patient metrics were recorded at baseline and after the intervention.The study participants were recruited from two HD units in Valencia (Spain) and were assessed for eligibility by the consulting nephrologist at each unit. For inclusion the patients had to have a stable medical condition and have been receiving HD therapy for at least 3 months. The exclusion criteria were as follows: (a) myocardial infarction in the 6 weeks prior; (b) cardiovascular disease that could worsen with exercise; (c) above the knee amputation without a prothesis; (d) cerebral vascular disease; (e) musculoskeletal and respiratory disorders that might worsen with exercise; and (f) inability to complete functional testing.Hospital Universitario Doctor Peset in Valencia . Participants provided their written informed consent to participation. This study respected the fundamental principle set out in the Declaration of Helsinki. It met the requirements set out in legislation in accordance with the Data Protection Act. This study was registered at Clinical Trials .This research was approved by the Ethics Committee at the www.randomization.com webpage. The allocation was concealed and the researchers performing the assessments were blinded to the random assignment throughout the whole study period.Participants were randomized by an external investigator in blocks, 4 codes per block, based on age and sex simultaneously, either into the ID or HB group using the Both the ID and the HB exercise interventions lasted 16 weeks and are detailed in Fig. 47.Patient clinical and anthropometric data were collected. Physical function was assessed with a battery of functional tests at baseline and after 16 weeks. Physical therapists who were blinded to the individuals’ allocation assessed the participants immediately before their HD session. To standardize the procedure, we followed a previous study that developed a detailed script for all the functional testsHuman Activity Profile (HAP) questionnaire which has been validated in populations with CKD3. The HAP comprises a list of 94 activities each assigned a number relating to the vigorousness of the task and the participants must report whether they still do this activity, no longer perform the activity, or never did the activity. The HAP assesses the maximal activity score  and the adjusted activity score . Depending on the AAS, individuals can be classified as having impaired activity (AAS < 53), being moderately active (AAS = 53–74), or as active (AAS > 74)48. This questionnaire, especially the AAS, has a high test-retest reliability in this population 49.As primary outcome we evaluated patient physical activity levels using the Short Physical Performance Battery (SPPB), one-leg standing test (OLST), and timed up-and-go (TUG) test. The SPPB is a battery of functional tests that assesses balance in three different positions  for 10 seconds each; gait speed in 4 meters at normal pace; and ability to stand up from a chair 5 repetitions. The score ranges from 0 to 12. The OLST measured the time that each participant could keep a one-leg balance position with eyes open and allowing free movement of the arms. The participants were given 3 trials to try to achieve 45 seconds. The TUG measures the best time of two consecutive trials in standing up from a chair, walking 3 meters, turn back and sit down again. During the second weekly HD session, the sit-to-stand 10/60 (STS-10/60) one-leg heel raise (OLHR), and handgrip strength (HG). The STS-10 measures the time required to complete 10 consecutive full stands from a sitting position, and the STS-60 measured the number of repetitions of sitting down on and getting up from a chair achieved in 60 seconds. The OLHR measures the functional strength of the triceps surae muscle in each leg. The handgrip strength was used to measure the amount of strength developed by each hand, three consecutive repetitions were recorded and the highest peak force was recorded. Finally, in the third weekly HD session the 6-minute walking test (6MWT) was performed and assess the longest distance that a patient can walk during 6 minutes, using any ambulation aid if required. Further detail of the measuring protocol, so as the reliability of all these tests has been reported in previous studies (ICC = 0.83–0.97)50.Prior to the first weekly HD session, participants performed the Physical Activity Scale for Elderly (PASE) questionnaire which has been validated a population with CKD3. The PASE assesses the time spent in the week prior doing specific activities commonly performed by elderly individuals. The total score is recorded as the sum of the amount of time that the person spent on each activity (hours per week) multiplied by the weight assigned to each activity51.To evaluate the physical activity level, the participants also completed the Center for Epidemiologic Studies Depression (CES-D) scale, which comprises 20 questions about depressed mood. Individuals respond to the CES-D by rating the frequency with which they experienced each mood in the week prior on scale ranging from 0 to 3. The total score ranges from 0 to 60 points with higher scores indicating the presence of more symptoms of depression. Participants undergoing HD with a score of 18 or more points were considered at risk for depression52.To assess the symptoms of depression, the participants completed the Kidney Disease Quality of Life-Short Form (KDQoL-36) survey which comprises 36 items that describe the individual’s perception of their health in the 4 weeks prior. It is divided into five categories: (i) symptoms/problems; (ii) kidney disease burden; (iii) kidney disease effects; (iv) physical components; and (v) mental components. The maximum score per category is 100 points and higher scores indicate better perceived health status53. This Spanish version of the questionnaire has been validated and is reliable, with ICCs ranging from 0.62 to 0.77 for each dimension4.To assess HRQoL in patients with CKD, we used the 54, and considering an alpha error of 0.05 and a statistical power of 80%, a total sample size of 26 participants were required to detect an effect size of 0.288 . We should add 20–30%% for dropouts that happen in most of the studies in this cohort, and then we should have included 31 participants at least. Since the effect size used (from previous data) is low, we consider this study to be a pilot trial.The sample size was calculated by detecting changes in physical activity using the average AAS HAP score. Taking previous data from an exercise-based intervention in HD patients into accountWe performed a post-hoc power calculation. Considering an effect size of 0.17, alfa 0.05, total sample size 23, 2 groups and 2 measurements, the power achieved was 0.34 .SD]). The Mann–Whitney U test was used to check differences between groups since the data did not follow a parametric distribution at baseline. Differences on categorical variables were checked with the Chi-Squared test. To analyze the effect of the exercise programs we used the ANOVA mixed model with time as the within-group factor and the exercise group as the between-group factor. A per-protocol analysis was performed instead of an intention to treat analysis. The SPSS package, version 20.0 for Windows  was used for all the statistical analyses, results were recognized as statistically significant at a threshold cut-off of p ≤ 0.05 for all the statistical analyses.The normal distribution as well as the skewness and kurtosis of the data was checked using the Kolmogorov–Smirnov test. Results are presented as the median or mean . Both interventions were associated with positive changes of the outcomes


Cervical spondylotic myelopathy (CSM) is the most severe type of cervical spondylosis and the most common cause of spinal cord dysfunction among adults over 55 years old. MRI plays an important role in the diagnosis and evaluation of CSM, which can directly demonstrate the correlation between disc, spinal cord, posterior structures and abnormal signal in spinal cord. Static MRI can only show the static and neutral position of spinal cord, which is not enough to understand the pathogenesis of CSM. Dynamic MRI demonstrating the extension and flexion position of spinal cord can be a better tool for the treatment of CSM, especially the surgical decision making.A total of 180 CSM patients who have indications for surgery will be recruited in outpatient of Peking University Third Hospital and assigned to three groups  based on their static MRI after consent. Group A (incomplete dura compression) means the signal of cerebral spinal fluid (CSF) is still visible. Group B (complete dura compression) means no CSF signal and no shape change of spinal cord. Group C  means shape change of spinal cord. Two surgical plans will be made for each participant by one professional surgeon according to the static MRI and dynamic MRI respectively and we will randomly choose one to perform via a random number system. Follow-up will be maintained at 3, 6, and 12 months after surgery through outpatient or telephone interview, including mJOA score, 10-s G&R (grip and release) and 10-s step test, SF-36 score, radiographic examination and complications. Finally, data collection and statistical analysis will be finished by researchers who are blinded to recruitment and treatment.This study will help us to explore the indication of dynamic MRI and the value of dynamic MRI in the treatment of CSM, especially the surgical decision making. Dynamic MRI can be a useful tool in the treatment of CSM patients.ChiCTR1900023014. Registered on May 7th, 2019. Cervical spondylotic myelopathy (CSM) is the most severe type of cervical spondylosis and the most common cause of spinal cord dysfunction among adults over 55 years old –4. The cDecompressive and reconstructive surgical techniques for the treatment of CSM may be divided into anterior, posterior, and combined surgical approaches. A systematic review comparing these approaches found similar outcomes that suggest the location of the pathoanatomy may guide the surgical decision making. The choice of which approach and surgical segment to use depends on the desired region of decompression and stabilization , 17. HowThis study is a prospective, two arm, superiority and open-label randomized controlled trial, including the feasibility research and validation research Fig. Static MRI will be performed for all patients with CSM who are going to receive surgery. There are three levels of spinal cord compression, incomplete dura compression , complete dura compression  and spinal cord compression . All participants will be assigned to three groups  based on their static MRI and receive dMRI after consent. The compression degree and T2 high-intensity signal (T2-HIS) on those two MRI will be collected for statistical analysis.The professional surgeon will make two surgical plans for each participant according to the static MRI and dMRI, respectively. Then we will randomly choose one via a random number system to perform. Follow-up will be maintained at 3, 6 and 12 months after surgery including modified Japanese Orthopaedic Association score (mJOA), SF-36 score, 10-s G&R and 10-s step test, frontal and lateral radiography of cervical spine and complications.Finally, we will statistically analyze the difference between static MRI and dynamic MRI to explore the indication of dMRI for CSM patients in the feasibility research. The validation research aims to identify the clinical effectiveness of dMRI in the treatment of CSM patients, especially the surgical decision making.This single-center study will be conducted in Peking University Third Hospital. Patients with CSM who need surgical treatment will be recruited from outpatient of Peking University Third Hospital. After confirming the eligibility of the patients, the researcher will discuss the study goals, procedures, activities and possible alternatives for approximately 20 min, and answer all questions. After enrolment, participants will be coded as a unique number and general information will be collected.The inclusion and exclusion criteria are as follows.➢ Diagnosis of cervical spondylotic myelopathy (CSM)➢ No surgical contraindications➢ Willing to receive surgery➢ Willing to take part in our studyThe inclusion criteria:➢ Other diseases in cervical vertebra ➢ Age < 18The exclusion criteria:Patients will be recruited from outpatient and eligible participants will be enrolled in the study after informed consent. The treating surgeon will also confirm the eligibility before making two surgical plans based on the static MRI and dMRI, respectively. A researcher will randomly choose one from the two surgical plans via a random number system. Randomization of experiment group (dMRI) and control group (static MRI) will be on a 1:1 basis.As the surgical plans should be informed to patients clearly, the patients cannot be blind to their surgery. However, all patients won’t know which MRI the surgical plan is from. In addition, the treating surgeon will also not be blind to the treatment but will not take part in the preoperative and postoperative research assessment. The clinical outcome data will be collected by independent research assistants who are blind to the surgical decision making.The surgical indication of Patients with CSM is mainly based on the symptoms, physical and radiographic examination. All participants will receive routine examination at admission, including blood routine and evaluation of general condition. Imaging examination as X-ray, CT and MRI will be accomplished before making surgical plan. All patients will receive imaging examination immediately after surgery and follow-up will be continued at 3, 6 and 12 months after surgery. This trial will involve two types of MRI: static MRI and dynamic MRI. These two types of MRI will be performed in the supine position.Static MRI will just take the neutral position of cervical spine. Static MRI is the routine examination for CSM patients and could demonstrate the disc, vertebrae, cerebral spinal fluid (CSF), spinal cord and the abnormal signal in spinal cord. In this study, the degree of spinal cord compression on static MRI will be assessed according to the three-level classification described above. Also, T2-HIS will be a parameter and collected as exist or non-exist.Dynamic MRI will show the flexional and extensional position of cervical spine other than neutral position. The angle of extension and flexion is as can be tolerated and it will take longer time than static MRI. The extension and flexion are accomplished by a self-designed posture cushion Fig. . All parAccording to the article review by Zhu et al.  from ourThe level to decompression would be largely determined by patient history, physical examination findings, X-rays, CT, and conventional MRI, and dMRI would always be interpreted with the grain of salt that the compression levels might be increased by dMRI, particularly with neck extension. Additionally, the general condition and expectation of patients will also be taken into consideration before making surgical decision.All participants will be assessed by research assistants who are blinded to the allocation and analysis at different time points shown in Table We have discussed the difference of cervical canal stenosis between static MRI and dMRI in the previous study . DynamicThe modified Japanese Orthopaedic Association score (mJOA) is a commonly used research tool in the evaluation of cervical myelopathy. It is comprised of 4 domains that evaluate motor function of the upper and lower extremity, sensory function of the upper extremity and bladder function. Previous studies have demonstrated that the mJOA has the validity of evaluation for CSM patients after surgery , 23.The treating clinical team will evaluate the mJOA score for all CSM patients before surgery. The treating clinicians will not be part of the research team. At 3, 6 and 12 months after surgery, mJOA will be assessed via either outpatient or telephone interview during follow-up. The improvement rate of mJOA score at 3, 6, and 12 months compared to baseline will be calculated finally.For CSM patients, T2-HIS  and decreased signal intensity on T1-weighted MRI are well-known changes in spinal cord lesions. A study showed that the preoperative and postoperative evaluation of CSM patients were better in the patients without T2-HIS compared with patients with T2-HIS. However, T2-HIS grading was not associated with the severity of myelopathy and outcomes, which was reported in the static MRI research . In thisThe SF-36 is a multipurpose, short-form health survey with only 36 questions. It yields an eight-scale profile of scores as well as physical and mental health summary measures . AccordiThe mJOA score alone may be insufficient to effectively assess the neurological condition in CSM. The 10-s grip and release (G&R) test and 10-s step test were reported to be useful tools to evaluate the severity of cervical myelopathy quantitatively. These tests were useful for quantitatively evaluating the surgical outcomes in CSM , 28.. FoThe cobb angle between C2 and C7 will be measured before surgery and at 3, 6 and 12 months after surgery during follow-up in the neutral and maximal flexion-extension lateral radiographic view. The fusion and cage subsidence will be recorded as descriptive outcome in the Case Report Form. Cage subsidence in anterior approach is defined as decrease in the total intervertebral height (TIH) between two fused vertebral bodies comparing to the first postoperative radiographs. Usually, decrease in TIH ≥ 3 mm is defined as significant subsidence .All complications and interventions related to the evaluation and treatment for participants will be recorded.Adverse events (AEs) are defined as any untoward medical occurrence in a clinical trial subject and which do not necessarily have a causal relationship with the treatment. In this study, the extra interventions for participants who are willing to receive surgery are dynamic MRI and function assessment, which are non-invasive and safe. The events related to surgery and other diseases which have no correlation with CSM will be counted as the complications and system disease. All participants Experiencing Significant Adverse Events (SAEs) will be followed up as per protocol until the end of the trial.All participants will receive a study number and all data about patients will be recorded via this number. All information about participants including baseline information, radiographic outcomes, surgery and follow-up will be secured in Peking University Third Hospital. Data will be collected at baseline admission and 3, 6 and 12 months after surgery. One professional surgeon will make the surgical plan and finish the surgery in Peking University Third Hospital. The researchers will collect the baseline information and maintain the follow-up after surgery. Data entry, transfer and subsequent maintenance will be performed by a data manager. Access to study data is restricted to the study research team.Participants in this study are going to receive surgical treatment. All extra interventions except surgery in this study are non-invasive but there is the possibility of neurological deterioration with the several minutes for neck extension position, which will be explained to patients when obtaining the consent. The angle of extension and flexion during dMRI is just as the patients can tolerate and there will be a researcher to assist during the examination. Moreover, all expected or unexpected adverse events from this study will be recorded and monitored. Patients suffered from this study will also receive free treatment.The sample size is calculated with reference to previous study and based on the sample size calculation formula. The average mJOA score improvement rate of surgical treatment according to static MRI in our hospital was 60.8%. we assume that the mJOA score improvement rate12 months after surgery in group dynamic MRI is 85%. We will recruit a sample of 180 participants including three groups stratified according to the spinal cord compression of static MRI. One hundred and eighty is based on a two-sided t-test, a type I error at 0.025 and type II error at 0.1 after taking into consideration a 1:1 allocation rate and a dropout rate of 20%.P < 0.05 will be reported as statistically significant. All analysis will be carried out using SPSS 20.0 software by a researcher blinded to the recruitment and collection.Pre-treatment baseline characteristics will be compared between randomized groups to monitor the chance imbalances. Statistical analyses will be performed following the intention-to-treatment (ITT) analysis. The experimental arm (dMRI) will be compared against the control (static MRI) for all primary analysis. We will use chi-squared test for binary outcomes and T-test for continuous outcomes. Spearman’s correlation coefficient will be used to analyze the correlation between the mJOA improvement rate and covariates. A value of We have presented the rationale and design of a prospective randomized controlled trial on the therapeutic value of dMRI in CSM patients, especially the surgical decision making. The RCT introduced here includes feasibility and validation research. The feasibility research will compare dynamic MRI with static MRI and explore the indication of dMRI for CSM patients. The validation research will identify the clinical effectiveness of dMRI in the treatment of CSM, especially the surgical decision making.The long-term follow-up of radiographic outcomes, nerve function recovery and quality of life will provide more evidence about the clinical use of dMRI in the treatment of CSM.As is noted in some studies, there are many patterns or more cord compression on dMRI of CSM patients which are usually invisible on static MRI and it is significant for the diagnosis and prognostic evaluation for CSM patients , 15, 31.Up to now, limited studies focused on the surgical decision made by dMRI. Two studies of dMRI just mentioned it may be helpful for CSM patients to determine the surgical management by dMRI , 15. TwoDynamic MRI may play a significant role in the treatment of CSM while there is no enough clinical evidence. The RCT introduced here will have a long period of follow-up after surgery (12 months), comprehensive CSM outcomes, calculated sample size and two stages of research to provide more evidence for clinical effectiveness of dMRI in the treatment of CSM. This new design will help us to modify the surgical decision making of CSM and draw individualized therapeutic schedule for CSM patients according to dMRI.


Purpose: For prostate cancer treatment, comparable or superior biochemical control was reported when using External-Beam-Radiotherapy (EBRT) with High-Dose-Rate-Brachytherapy (HDRB)-boost, compared to dose-escalation with EBRT alone. The conformal doses produced by HDRB could allow further beneficial prostate dose-escalation, but increase in dose is limited by normal tissue toxicity. Previous works showed correlation between urethral dose and incidence of urinary toxicity, but there is a lack of established guidelines on the dose constraints to this organ. This work aimed at fitting a Normal-Tissue-Complication-Probability model to urethral stricture data collected at one institution and validating it with an external cohort, looking at neo-adjuvant androgen deprivation as dose-modifying factor.Materials and Methods: Clinical and dosimetric data of 258 patients, with a toxicity rate of 12.8%, treated at a single institution with a variety of prescription doses, were collected to fit the Lyman–Kutcher–Burman (LKB) model using the maximum likelihood method. Due to the different fractionations, doses were converted into 2 Gy-equivalent doses (α/β = 5 Gy), and urethral stricture was used as an end-point. For validation, an external cohort of 187 patients treated as part of the TROG (Trans Tasman Radiation Oncology Group) 03.04 RADAR trial with a toxicity rate of 8.7%, was used. The goodness of fit was assessed using calibration plots. The effect of neo-adjuvant androgen deprivation (AD) was analyzed separating patients who had received it prior to treatment from those who did not receive it.Results: The obtained LKB parameters were TD50 = 116.7 Gy and m = 0.23; n was fixed to 0.3, based on numerical optimization of the likelihood. The calibration plot showed a good agreement between the observed toxicity and the probability predicted by the model, confirmed by bootstrapping. For the external validation, the calibration plot showed that the observed toxicity obtained with the RADAR patients was well-represented by the fitted LKB model parameters. When patients were stratified by the use of AD TD50 decreased when AD was not present.Conclusions: Lyman–Kutcher–Burman model parameters were fitted to the risk of urethral stricture and externally validated with an independent cohort, to provide guidance on urethral tolerance doses for patients treated with a HDRB boost. For patients that did not receive AD, model fitting provided a lower TD50 suggesting a protective effect on urethra toxicity. In the treatment of unfavorable prostate cancer, several studies have shown that the use of High-Dose-Rate Brachytherapy (HDRB) as a boost in combination with External Beam Radiotherapy (EBRT) provides biochemical control and prostate-cancer specific survival comparable or superior to dose-escalation with EBRT alone –6. TheseDue to the variety of fractionation regimens used for HDRB boost treatments in different centers, ranging from multiple fractions to monotherapy , it is sUsing the long term data and experience accumulated in our department in treating prostate cancer patients with HDRB boost the purpose of this work has been to establish NTCP model parameters specific for the urethra by fitting a normal tissue toxicity curve on urethral stricture data recorded in our institution. This curve has then been validated with an independent external cohort, in order to provide general applicability and a tool to guide treatment design and fractionation selection criteria.Clinical and three dimensional (3D) treatment planning data of 258 patients treated at Alfred Health Radiation Oncology (AHRO) from 2001 to 2013 were retrospectively collected for this analysis. These 258 patients were selected as a subset of a larger group of more than 500 patients treated at our institution, receiving a curative regimen that included a boost of HDRB, in combination with EBRT, since they had complete retrievable 3D planning and associated toxicity information with at least 4 years of follow-up. Most patients were classified in the intermediate and high risk group, and details of the CT-planning based treatment technique are presented in previous publications , 23. In D90% > 100% (at least 100% of prescribed dose covering 90% of PTV), V100% > 95% , V150% = 15–32% , V200% = 5–9% . For the OARs: urethra D10% <110% , and rectal wall D2cc <66% .For all patients, clinical, demographic, and toxicity data were extracted from our institutional prospective brachytherapy database BrachyNET. All patients had a review after 6, 12, 24 months and every year until 10 years after the HDRB implant, and no patient was lost to follow-up. At each review, patients completed the Expanded Prostate Cancer Index Composite (EPIC-26) form . In the 2) considering an α/β ratio of 5 Gy, as previously used by Gloi and Buchanan  or in Oncentra treatment planning system (Elekta). In order to limit differences due to different Dose Volume Histogram (DVH) estimates, all plans were de-identified and re-imported in Oncentra, and DVHs were recalculated and exported. Since the patients were treated with four different fractionation regimens, and due to the inhomogeneous dose in the urethra, each fraction's physical doses were converted into equivalent doses in 2 Gy per fraction (EQDBuchanan  (of noten) value descriptive of the relationship between urethral “architecture” and the considered toxicity endpoint in the available dataset. Then this value was fixed, and TD50 (Gy) (EUD that causes 50% probability of toxicity) and m (slope of the response curve at TD50) were fitted. As the most recent patients were rescanned and replanned on the 2nd day of treatment, EUD from day 1 and 2 were considered in the model.The Lyman–Kutcher–Burman model (LKB) was used in this analysis , 26, andInternal validation was performed by bootstrapping the original dataset 1,000 times as previously described , and recGoodness of fit was determined by using a model calibration plot to establish the relationship between the observed and predicted probability. Due to the binary nature of the stricture data (yes/no) the observed probabilities were obtained by dividing the 258 patients studied into four dose-bin groups and determining the corresponding rate of toxicity of each group. These observed rates were then plotted against those predicted by the model and a trend line derived. This line was then compared against the identity line which represents a perfect prediction . CalibraThe discriminative ability of the model, that is, the ability to distinguish patients with different outcomes, was also evaluated with the area under the receiver operating characteristic curve (AUC).2 (α/β = 5 Gy)], the stricture rate at 8.6% was comparable to AHRO patients, and all patients had ~5 months of AD prior to radiotherapy, as part of a randomized total of 6 or 18 months of AD. The urethral toxicity end-point was considered to be equivalent to the one chosen for the AHRO patients, as the time of the first urethrotomy. The RADAR cohort was also treated with EBRT doses of 46 in 2 Gy fractions. For this group urethral structures were initially contoured by the RO as the visible lumen of the urinary catheter (3 and AHRO 1.4 cm3).Data from a second cohort of 187 patients from a different institution treated as part of the TROG (Trans Tasman Radiation Oncology Group) 03.04 RADAR trial  were colBoth structures' DVHs  and associated clinical data were used to externally validate the LKB parameters obtained with the AHRO cohort. Model calibration, as described above, was used to establish agreement between the AHRO model estimated probabilities and RADAR observed stricture rates.n and m value of the LKB model parameters were fixed and the fit was re-done separating the patients with (241/258) and without AD (17/258) to obtain two different TD50s as proposed by Peeters et al. , m = 0.23  was modeled by means of a sigmoid function of EUD . The numR2 = 0.71 for apparent calibration and calibration in the large = 0.01 and slope = 0.91 after correction for optimism.The LKB NTCP curve was obtained and compared with the AHRO observed data . The calR2 = 0.94). As shown in R2 = 0.93; The external validation performed using the urethra data exported from the RADAR cohort gave the best agreement with the AHRO prediction model when the urethra contours were expanded to be similar to AHRO's contours  for patients who did not receive AD, suggesting a protective effect of AD .Interest in understanding the nature of long term side effects in OARs produced by prostate radiotherapy has grown due to the increase in utilization of hypofractionated regimens in EBRT –36. Of pThis work has focused on fitting the LKB model parameters of urethral stricture data collected on a large cohort of patients treated with HDRB boost at one single institution for a time-period of 12 years. This NTCP model was created by considering urethrotomy recorded in the first 4 years after the treatment as an end-point. All toxicity data were prospectively recorded in a database and the follow-up was meticulously done by reviewing the patients at well set time intervals. Additionally, any correspondence with the treating doctors after brachytherapy was analyzed in order to look for additional urethrotomy recorded.The predictive model fitted in this work showed a clear dose-effect relationship between the incidence of urethral stricture and the dose delivered to the urethra , and it n was larger than expected (0.3), suggesting that the architecture of the urethra could be more parallel than generally believed, due to its shape and similarity to structures such as the spinal cord or the esophagus. However, this result could be related to the small volumes involved (ranging from 0.02 to 3.6 cm3 for the AHRO cohort), and the limitation in fitting the parameter with the data available. Additional studies have been undertaken in order to analyze surface or voxelized dose maps  suggesting a protective effect on urethral toxicity, as previously highlighted for EBRT studies.The datasets generated for this study will not be made publicly available due to the ethics considerations.The studies involving human participants were reviewed and approved by Alfred Hospital Ethics Committee (Project 323/14). Use of RADAR data was approved by the TROG Publications Committee. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.VP has designed the study, collected the data, performed the MATLAB calculations described in the methods, and has written the draft of the manuscript. TR has provided extensive technical advice on the implementation of the work, model building, and validation and has revised several versions of both calculations and manuscript. EO has provided the MATLAB code used in the study and has provided advice on the technical component. ME, JD, DJ, and AS have provided the RADAR data used for the external validation and JM has provided advice and patients data used for model building. All co-authors contributed to proof-reading of the manuscript.DJ was employed by GenesisCare and 5D Clinics. ME has an honorary position at 5D Clinics. DJ and ME each have a financial shareholding in 5D Clinics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.