Patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) are often managed conservatively. Clinical practice guidelines recommend treating these patients with the same pharmacological drugs as those who receive invasive treatment. We analyze the use of new antiplatelet drugs (NADs) and other recommended treatments in people discharged following an NSTE-ACS according to the treatment strategy used, comparing the medium-term prognosis between groups.Prospective observational multicenter registry study in 1717 patients discharged from hospital following an ACS; 1143 patients had experienced an NSTE-ACS. We analyzed groups receiving the following treatment: No cardiac catheterization (NO CATH): n = 134; 11.7%; Cardiac catheterization without revascularization (CATH-NO REVASC): n = 256; 22.4%; percutaneous coronary intervention (PCI): n = 629; 55.0%; and coronary artery bypass graft (CABG): n = 124; 10.8%. We assessed major adverse cardiovascular events (MACE), all-cause mortality, and hemorrhagic complications at one year.NO CATH was the oldest, had the most comorbidities, and was at the highest risk for ischemic and hemorrhagic events. Few patients who were not revascularized with PCI received NADs . Non-revascularized patients also received fewer beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARB), and statins (p<0.001). At one year, MACE incidence in NO CATH group was three times that of the other groups , and all-cause mortality was also much higher . There were no significant differences in hemorrhagic events. Belonging to NO CATH group was an independent predictor for MACE at one year in the multivariate analysis .Despite current invasive management of NSTE-ACS, patients not receiving catheterization are at very high risk for under treatment with recommended drugs, including NADs. Their medium-term prognosis is poor, with high mortality. Patients treated with PCI receive better pharmacological management, with high use of NADs. Clinical practice guidelines for non-ST-elevation acute coronary syndrome (NSTE-ACS) recommend a standard invasive strategy, consisting of coronary catheterization followed by coronary revascularization ,2. HowevSeveral studies report that the population who does not undergo coronary catheterization is a high-risk group, with higher comorbidities and incidence of cardiovascular events in the medium and long term ,4. DespiThe CURE study found that at one-year follow-up, the NSTE-ACS patients receiving dual antiplatelet therapy  presented lower combined rates of cardiovascular death, myocardial infarction, and stroke compared to those taking aspirin alone . This reMoreover, new antiplatelet drugs (NADs) such as ticagrelor have shown better outcomes than older agents like clopidogrel for improving the prognosis of patients managed medically following acute coronary syndrome (ACS) ,8. In liThe objective of this study is to assess the use of NADs and other recommended treatments in patients discharged following an NSTE-ACS according to the initial treatment strategy used. We also evaluate the medium-term prognosis and its association with different inpatient treatment strategies.The rationale and design of this study have been described previously . In brieOur study protocol complies with the Helsinki Declaration and was approved by the Ethical Research and Reference Committee after being accepted by the Department of Medicine for Human Use from the National Agency for Medicines and Medical Devices, with reference JRN-NAG-2014-01.An independent clinical research organization (CRO) performed an external audit of the registry, evaluating the appropriateness of patient inclusion and the accuracy of the data in all participating hospitals, as well as the possible existence of eligible patients who may have been excluded during the recruitment period.Of the 1717 patients included in the study, we analyzed 1143 who were discharged following a diagnosis of NSTE-ACS . We assessed the use of different therapies recommended by clinical practice guidelines according to the treatment that patients received during hospitalization. The four treatment categories were coded as follows: 1-NO CATH: medical treatment without catheterization; 2-CATH-NO REVASC: catheterization without revascularization; 3-PCI: percutaneous coronary intervention; 4-CABG: coronary artery bypass graft.We analyzed the use of antiplatelet drugs during hospital stay and upon discharge, comparing prescriptions for the traditional agent, clopidogrel, versus prescriptions for NADs. We also evaluated the use of other drugs indicated for managing NSTE-ACS, such as beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), and statins.We recorded patients’ baseline clinical characteristics and carried out clinical follow-up  at three months and one year. During this period we recorded any major adverse cardiovascular event (MACE), defined as cardiovascular death, non-fatal myocardial infarction, or non-fatal ischemic stroke. We also collected data on all-cause mortality and hemorrhagic complications according to the Bleeding Academic Research Consortium (BARC) definitions  and the 2statistic. Continuous variables were expressed as mean (standard deviation [SD]) if normally distributed and as median (interquartile range) if the distribution was non-parametric. We used analysis of variance (ANOVA) to compare groups by continuous variables and the Kruskal-Wallis test if the distribution was not normal.We expressed categorical variables as frequencies (percentages), comparing them by the χWe performed Cox regression models  to determine which variables showed an independent association at one year follow-up with MACE, all-cause mortality, or major hemorrhage (BARC ≥3).We considered p values <0.05 as statistical significant for all tests performed. We used SPSS statistical software  for all analyses. The authors of this registry study are solely responsible for the study design, analysis, and development of this paper.We included 1143 patients with NSTE-ACS. Mean age was 68±12.7 years, and 69.1% were men. At discharge, 298 (26.1%) patients had unstable angina and 845 (73.9%) had NSTEMI. Most patients  underwent catheterization during hospitalization.The distribution of patients by treatment groups was as follows: 1-NO CATH, 134 (11.7%) patients; 2-CATH-NO REVASC: 256 (22.4%) patients; 3-PCI: 629 (55.0%) patients; 4-CABG: 124 (10.8%) patients . The maiMean age in the NO-CATH group was significantly higher (p<0.001) than in the rest of groups . Moreove12 inhibitors in the first 24 hours of admission, and they also showed less use of beta-blockers, ACE inhibitors/ARBs, and statins  compared to the other groups (p<0.001)  . Those tOne-year follow-up was achieved in 98.25% of the sample. In our registry, the NO-CATH group presented the worst prognosis, with three times higher incidence of MACE compared to the other groups . All-cauWith regard to the incidence of hemorrhagic events within a year of discharge, we did not observe significant differences between groups in total hemorrhages or in the most serious hemorrhages (major hemorrhage according to TIMI criteria and BARC ≥ 3).Cox regression analysis  identifiIn addition, hemoglobin was the only variable showing to be an independent risk factor for major hemorrhage (BARC ≥3) at one year . This outcome was not associated with the use of NADs.In this contemporary registry, our data suggest that: (i) patients with NSTE-ACS who do not undergo catheterization are a high-risk population undertreated with NADs and other recommended drugs; (ii) this group also has a poor prognosis in the medium term, with an elevated incidence of MACE and high mortality, although a similar prevalence of hemorrhagic events to other NSTE-ACS patients; (iii) optimal medical treatment and prescription of NADs takes place primarily in patients treated with PCI.In our registry, patients managed with medical treatment alone constitute a third of all those diagnosed with NSTE-ACS. In agreement with most similar studies ,6 the prAs other authors have previously noted ,4,6, the12 inhibitors at discharge—just 60%—while virtually all patients who undergo revascularization with PCI receive them. In line with this data, a previous large controlled study demonstrated that less than half of the conservatively managed patients received clopidogrel at discharge [Although double antiplatelet therapy is supported by a class I recommendation ,2,9, witischarge .vs. 14.3%; HR 0.85, 95% CI 0.73–1.00; p = 0.04), with similar results for all-cause mortality  and without a significant increase in major bleeding.In this study, in patients who did not undergo catheterization, the most commonly used antiplatelet agent was clopidogrel. Thus, it seems that NADs is basically reserved for patients treated with PCI, even though numerous studies have shown comparable benefits across treatment groups , 13, 16.Clinicians’ reluctance to use more potent antiplatelet drugs in this group may be partly due to the higher prevalence of comorbidities, advanced age, history of stroke and hemorrhagic risk in this population, which makes difficult to discern when the risks outweigh the potential benefits of these drugs. Conservatively managed patients are also prescribed the highest relative proportion of anticoagulants at discharge (17.9%), which is a contraindication for NADs.With regard to medium-term prognosis, and in agreement with most registries published to date , patientAdditionally, and despite the higher baseline bleeding risk in this elderly subgroup, the group of patients managed conservatively did not show significant differences with other groups in terms of total or major hemorrhages. Although the low use of DAPT could be the reason for these results, it is also true that this population showed the highest use of oral anticoagulants at discharge. Thus, ischemic events determine the poor prognosis, as is shown graphically in the survival curves.While patients who do not undergo catheterization are at the highest risk for harmful outcomes and have the worst prognosis, they are also the most undertreated group, especially with regard to DAPT. Thus, this subgroup is the main target for improved clinical management, even if their overall clinical profile makes unlikely that the rates of optimal treatment in this group remain optimal. There is a need for more real-world data emphasizing the potential benefits of DAPT and especially NADs for the prognosis of these patients .12 inhibitors (34.7%). CABG provides more complete revascularization than PCI , although in our cohort both groups presented similar ischemic and hemorrhagic prognoses in the medium term. Of note, incidence of stroke in the CABG group was more than double than one of the PCI group , which is consistent with the results of the SYNTAX trial, showing a significant trend toward higher incidence of stroke in surgical patients  [With regard to the type of revascularization, both techniques resulted in a similar prognosis. The presence of multivessel or left main disease is the main determinant of surgical revascularization. Antiplatelets are also underused in patients treated with CABG, who receive less aspirin than those treated with PCI and lower prescription rates of P2Y = 0.09) .Among the predictive factors for adverse events, we note that the treatment strategy influenced the prognosis in the medium term since the NO-CATH group was predictive of MACE, as were other clinically important factors such as Killip class and the presence of peripheral artery disease. Moreover, the NO-CATH group also showed a borderline statistically significant association with all-cause mortality.Our study has several potential limitations inherent to the non-randomized observational design. Although registry studies often provide a more comprehensive picture of usual clinical practice, the included population tends to be heterogeneous, with diverse clinical characteristics what make difficult to draw generalized conclusions around certain therapeutic attitudes. Moreover, the inclusion criterion of “patients discharged with a diagnosis of NSTE-ACS” precluded consideration of people who died during their hospital stay. The fact that the patients included in our registry were admitted to hospitals equipped with a hemodynamic unit may have also introduced some selection bias, as these patients would have had easy and fast access to invasive care.Furthermore, it is worth mentioning that the indication for different antiplatelets is not protocolized, rather, treatment was indicated by the attending physician. However, this can be considered a strength of the registry rather than a limitation, as it reflects usual practice for treating ACS, where many different professionals and services are involved in managing patients’ treatment.Despite these limitations, we believe that our conclusions are of great interest because they derive from a voluntary registry where investigators’ role was limited to collecting data upon patient discharge. Thus, the performance of the study did not affect the clinical decisions made by attending physicians in any way. This voluntary character of the registry therefore ensures that the data are of excellent quality, a fact that has been corroborated by an independent external auditor.In this contemporary registry including patients with ACS, those NSTE-ACS patients who did not undergo catheterization during hospitalization represented a high-risk subgroup. They were undertreated with recommended therapies and showed lower prescription rates for NADs. The prognosis in the medium term was poor, with high mortality.


Many countries are grappling with growing numbers of parents who delay or refuse recommended vaccinations for their children. This has created a need for strategies to address vaccine hesitancy (VH) and better support parental decision-making regarding vaccination.To assess vaccination intention (VI) and VH among parents who received an individual motivational-interview (MI) based intervention on infant immunisation during post-partum stay at a maternity ward between March 2014 and February 2015.This non-controlled pre-/post-intervention study was conducted using the results from parents enrolled in the intervention arm of the PromoVaQ randomised control trial (RCT), which was conducted in four maternity wards across the Province of Quebec. Participants  completed pre- and post-intervention questionnaires on VI and VH using Opel’s score. Pre-/post-intervention measures were compared using McNemar’s test for categorical variables and Wilcoxon signed-rank test for continuous variables.Pre-intervention: overall VI was 78% and significantly differed across maternity wards . Post-intervention: VI rose significantly across maternity wards  and the overall increase in VI was 12% . VH corroborated these observations, pre- vs post-intervention, for each maternity ward . Overall, VH was curbed post-intervention by 40% .Compared with pre-intervention status, participants who received the MI-based intervention on immunisation displayed lower hesitancy and greater intention to vaccinate their infant at 2 months of age. Supplement S1. Only 50% of children aged 24 months received all recommended vaccinations (excluding rotavirus and hepatitis B) within 1 month after the recommended age for each dose [According to data from the World Health Organization (WHO), 19.5 million children worldwide failed to receive routine life-saving vaccinations in 2016 while ca 90,000 children died from measles, a vaccine-preventable disease . In the A reason for falling vaccine coverage is parental vaccine hesitancy (VH); a concept first recognised by the WHO Strategic Advisory Group of Experts (SAGE) on Immunisation in 2012, with a clear definition published in 2015  and therFace-to-face interventions have been proposed as a strategy to address VH and to increase vaccination awareness among parents. A scoping review and meta-analysis, published in 2015, concluded that while there is no strong evidence to support the use of any specific intervention to address VH , interveTraditional educational methods  have proven inefficient in addressing VH . It is kThe ‘PromoVaQ’ study aimed to scale-up our regional pilot, monocentric, quasi-experimental study (‘PromoVac’ March 2010–February 2011) to a Province-wide multicentric study, conducted in four university hospital maternity wards between March 2014 and February 2015, in order to measure how our MI-based post-partum intervention impacted post-intervention VI and VH in participant parents of newborns.To assess the post-intervention impact on VI and VH, we designed a nested non-controlled pre-/post-intervention study using data from consenting parents enrolled in the intervention arm of a pragmatic, unblinded, parallel-randomised controlled trial (RCT) (NCT02666872); this study design is recognised as being suitable to determine the impact of an experimental intervention in a single arm study .This study was a pragmatic, unblinded, parallel-randomised controlled trial (RCT) powered to compare the impact of our MI-based intervention to the standard of care provided to parents of 2-day-old newborns on the overall vaccine coverage for children aged 24 months .The RCT was conducted in four university hospital maternity wards of the Province of Quebec, collectively accounting for over 20% of all births province wide. The hospitals were located in Sherbrooke (CIUSSS de l’Estrie - CHUS), Montreal  and Québec city (CHU de Quebec). These hospitals were selected in order to increase external generalisability of results, characterise feasibility issues and determine efficacy of the intervention, irrespective of regional disparities in maternity ward organisation and/or socioeconomic and cultural diversities. However, it was beyond the scope of this study to further dissect sites differences.Enrolment took place between March 2014 and February 2015. Mothers were eligible to participate in the study if their newborn was delivered in one of the four participating university hospital maternity wards and they had not yet been discharged. Mothers were excluded if: (i) they were aged 18 years or younger, (ii) did not speak either French or English, (iii) participated in the pilot study conducted at the CIUSSS de l’Estrie - CHUS between 2010 and 2011, (iv) if their newborn presented an unstable condition requiring intensive care management, or (iv) if interviewing was incompatible with the mother’s health. If the father was also at the maternity ward, he was invited to receive the intervention and answer the questionnaires jointly with the mother.Parents who consented to participate in the study were randomised through a web-based system (Dacima). Randomisation was conducted using a block size strategy (eight participants/block) and was stratified by maternity ward using a 1:1 allocation ratio to ensure proportionate allocation among sites and groups.Parents enrolled on the standard of care arm of the RCT did not complete post-intervention questionnaires, as it has been shown that providing parents with a copy of the public health vaccine brochure (standard of care), does not alter parental VI or VH .This study was reviewed and approved by the institutional research ethics review board at each site ; CHU Ste-Justine: 2014-601, 3793; CHU de Québec: 2014-1742, B13-07-1742)). Written informed consent was obtained from all participants before study inclusion and participation as required by law.The study intervention has been described previously ,17. BrieThe primary outcome was VI measured using a validated questionnaire ,17,21 baAs this study is nested within a larger RCT’s objective, no sample-size calculation was defined a priori to answer this study’s primary outcome. Based on our previous study evaluating a 77.5% baseline VI in parents  and a saAnalyses were performed under the intention-to-treat principle, i.e. with all participants enrolled in the intervention arm of the pilot PromoVac RCT, with the aim to provide descriptive data for the four study sites. Results were not adjusted for study site baseline criteria. Categorical variables are presented as frequencies (percentages) with a chi-squared Pearson test used for comparisons. Comparative analyses of pre- and post-intervention questionnaires were performed using McNemar’s test for categorical variables and the Wilcoxon signed-rank test for continuous variables. Sensitivity analyses were performed to demonstrate the impact of selected socioeconomic factors on the pre-/post-impact, on the post-/pre-difference of the intervention on VI as well as on VH scores. All statistics were two-tailed. P values of 0.05 or less were considered significant. SAS Institute software version 9.4  was used for statistical analyses.The PromoVaQ RCT was initially proposed to 4,185 parents between March 2014 and February 2015. Of these, we randomised 2,695 consenting participants from the hospital maternity wards at the four following university hospital centres: the CIUSSS de l’Estrie - CHUS (n = 819), the McGill University Health Centre (n = 627), the CHU Ste-Justine (n = 624) and the CHU de Quebec (n = 625). Participants were equally randomised to the intervention  or to the control arm .In the nested study, we only included the 1,347 participants who had been randomised to the intervention arm; of these, 1,289 received the study intervention. The most frequent reasons not receiving the intervention at this stage (n = 58) were refusal to participate, earlier than expected hospital discharge, or a health condition in the mother or her newborn. Of 1,289 participants who received the intervention, 1,246 completed the pre- and post-intervention questionnaires. Of the latter, 1,223 completed the question on VI pre- and post-intervention  and their results are thus the focus of this report; 43 participants completed the pre-intervention questionnaire, received the intervention, but did not complete the post-intervention questionnaire. Compared with the 1,246 participants included in the analyses, these 43 participants were not significantly more vaccine hesitant at the pre-intervention stage . However, they were significantly less likely to vaccinate their infant . Participant VH significantly decreased post-intervention. Overall, the combined data from the four study sites showed that the relative proportion of participants with lowest VH (score 0–29) rose from 55.9% to 78.8% (41% increase), while those with intermediate and highest levels of VH (score 30–49 and > 50) decreased from 44.1% to 21.1% . Prior tWith regard to the intention to vaccinate their infant at 2 months of age, results from sensitivity analyses demonstrated that the mother’s age at delivery, i.e. being under or 30 years old, less educated, i.e. only completed high school, or being a primipara, all significantly increased the difference in pre-/post-impact of the intervention between categories. We also found that the VH scores were significantly lower in mothers who were French speakers, of Canadian origin, aged 30 years or younger, had completed at least high school, were in the middle-class income category  and primipara.This study assessed the impact of an MI-based intervention conducted with parents post-partum regarding VH and VI for their newborn. We found that the pre-/post-impact of the intervention was effective, irrespective of the potential confounding sociodemographic and cultural factors. These results highlight the generalisability of this novel approach to help parental decision-making regarding immunisation and reduce VH.A systematic review of literature on currently available interventions aimed at reducing parental vaccine refusal and hesitancy, concluded that reports on such interventions were scarce and given the lack of data to adequately inform policy and decision makers well-designed trials were needed ; the resOur results indicate that an MI-based intervention is effective in parents presenting high levels of VH – the population that has been identified as crucial for effective intervention; Leask et al. emphasised that these parents’ needs must be met in order for them to be able to modify their perception of childhood vaccination . We founOur results demonstrated the MI-based intervention consolidated decision making of participants who were immunisation favourable at baseline. Post-intervention, an additional 41% fell into the 0–30 Opel score category (lowest VH) and an additional 12% into the ‘certainly’ category of VI. Interestingly, as reported in a meta-analysis, VI may be predictive of behaviour ,32. One This study builds on a variety of strengths increasing external validity including, (i) a unique parent-centred MI-based intervention, (ii) a parent-tailored approach, (iii) the use of validated reliable questionnaires and tools to secure internal validity and outcome assessment ), and  was associated with an incomplete immunisation status in Quebec and Canada ,34-36. HTo our knowledge, this is the first study of its kind comparing the efficacy of an MI-based intervention on VI and VH in a large number of participants pre- and post-intervention. Although non-controlled (as per the study’s design), our results show the efficacy of our MI-based post-partum intervention in providing parents of newborns with individually-tailored immunisation decision-making and educational support. This intervention reduced parental VH while enhancing VI for their infant at 2 months of age. Going forward, we aim to assess the impact of such an intervention on child vaccine coverage at later ages and to correlate these with VI and VH scores.


In this work we explore the deposition of gold onto a silicoaluminophosphate, using a variety of known nanoparticle deposition techniques. By comparing the gold particles deposited on a traditional microporous aluminophosphate, with an analogous hierarchical species, containing both micropores and mesopores, we explore the influence of this dual porosity on nanoparticle deposition. We show that the presence of mesopores has limited influence on the nanoparticle properties, but allows the system to maintain porosity after nanoparticle deposition. This will aid diffusion of reagents through the system, allowing continued access to the active sites in hierarchical systems, which offers significant potential in catalytic oxidation/reduction reactions. The controlled synthetic design of metallic nanoparticles has generated significant interest in recent decades due to their implementation in a range of fields, including medicine , optics MP-SAPO-5 was synthesised according to our previous work , giving All three deposition methods  were carried out on both HP-SAPO-5 and MP-SAPO-5 with an intended theoretical loading of 1 wt % Au. Metal analysis on the deposited MP-SAPO-5  [To probe the influence of the support on the deposited metal, a range of characterisation techniques were used to explore the nature of the Au species. UV–vis measurements show signals attributed to localised surface plasmon resonance for both Au/MP-SAPO-5  . In all  S11, 0) , despite0 features  data  was in gfeatures . Howeverom XANES . As XPS the bulk . In bothWe have thus shown that pore blockage can be minimised by immobilising metal nanoparticles onto hierarchical systems, allowing tailored zeotype catalysts to act as hosts through the inclusion of mesopores, with their inherent porosity aiding nanoparticle reduction. Such materials have potential in catalytic oxidations/reductions, with Au/HP-SAPO-5 IW yielding a turn over number (TON) of 35 (Table S5, File 1Additional experimental data.


Therapeutic virtual reality (VR) has emerged as an effective, drug-free tool for pain management, but there is a lack of randomized, controlled data evaluating its effectiveness in hospitalized patients. We sought to measure the impact of on-demand VR versus “health and wellness” television programming for pain in hospitalized patients.We performed a prospective, randomized, comparative effectiveness trial in hospitalized patients with an average pain score of ≥3 out of 10 points. Patients in the experimental group received a library of 21 VR experiences administered using the Samsung Gear Oculus headset; control patients viewed specialized television programming to promote health and wellness. Clinical staff followed usual care; study interventions were not protocolized. The primary outcome was patient-reported pain using a numeric rating scale, as recorded by nursing staff during usual care. Pre- and post-intervention pain scores were compared immediately after initial treatment and after 48- and 72-hours.There were 120 subjects . The mean within-subject difference in immediate pre- and post-intervention pain scores was larger in the VR group  than in the control group ; this difference was significant in favor of VR (P < .04). When limited to the subgroup of patients with severe baseline pain (≥7 points), the effect of VR was more pronounced vs. control . In regression analyses adjusting for pre-intervention pain, time, age, gender, and type of pain, VR yielded a .59 (P = .03) and .56 (P = .04) point incremental reduction in pain versus control during the 48- and 72-hour post-intervention periods, respectively.VR significantly reduces pain versus an active control condition in hospitalized patients. VR is most effective for severe pain. Future trials should evaluate standardized order sets that interpose VR as an early non-drug option for analgesia. Effective and safe pain management is an important challenge in the acute-care setting. Nearly half of hospitalized patients experience pain, of which one quarter is considered “unbearable.” Pain treFig 1). A proposed mechanistic theory of VR suggests that by stimulating the visual cortex while engaging other senses, VR acts as a distraction to limit the user’s processing of nociceptive stimuli.[Therapeutic virtual reality (VR) has emerged as an effective, non-pharmacological treatment modality for pain., 5 Users stimuli. The ubiq stimuli., 7–11 Fo stimuli. Similarl stimuli. and dent stimuli.Our group has previously investigated the role of VR in hospitalized patients. After demonstrating initial feasibility of using VR in the inpatient setting, we conduIn this study, we performed a comparative effectiveness study evaluating a scalable VR intervention vs. “health and wellness” television programming in a diverse group of hospitalized patients with pain.We conducted a prospective, randomized comparative effectiveness study between November 2016 and July 2017 to compare pain scores of hospitalized patients exposed to either an on-demand, immersive video experience consisting of VR and 360-videos, or an active control consisting of an in-room television tuned to the “Health and Wellness Channel”. We recruited adults aged 18 years or over admitted to the hospitalist, orthopedic, gastrointestinal, or psychiatric consultative services at Cedars-Sinai Medical Center, a large, urban, tertiary care hospital. the CONSORT diagram for patient flow through the study.Patients with an average pain score of ≥3 out of 10 points during the 24 hours preceding patient screening were eligible for inclusion. We chose this pain score cutoff because past studies have found it corresponds to the boundary between mild and moderate pain-related interference with mood and activity. We excluUpon providing written informed consent, eligible patients were randomized one-to-one between groups using the Microsoft Excel random number generator. Patients in both groups were informed that researchers were testing the effect of “two types of audiovisual experiences” on the perception of pain. Because it was important for research staff to exhibit equipoise when describing the competing interventions, we prepared a script that used neutral language regarding both interventions. In both arms, we minimized investigator interactions with the study participants, relying on non-study nursing staff to collect pain scores and allowing patients to use their assigned audiovisual experience on their own terms without a formal protocol or order set. In this manner, we designed the study to be a pragmatic assessment of VR compared to an inherent, active control condition already found in the treatment environment, described below.Fig 1). We selected the Samsung Gear because it is commercially available, widely used, relatively inexpensive, has minimal visual latency, and offers an acceptable patient experience based on our previous research.[S1 Fig), and a partial list is included in Fig 3.We administered VR using the Samsung  Gear Oculus headset fitted with a Samsung Galaxy S7 phone , discussions about health and wellness topics, and poetry readings. We selected the programming as a control condition because there is evidence that offering in-room relaxation programming can reduce pain and psychosocial distress in hospitalized patients.–23 FolloThe primary outcome was pain intensity collected via repeated measures in the course of usual care by hospital staff. At three-to-four hour intervals during waking hours, subjects were asked by their assigned nurse to rate their pain using a standard 11-point numeric rating scale (NRS), where 0 is “no pain” and 10 is “worst imaginable pain.” The 11-level pain NRS is supported by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) as a valAt the conclusion of their participation in the study, subjects were asked “Would you recommend the audiovisual experience you received here in the hospital to your family and friends?” Responses were collected on a 5-point Likert-type scale ranging from “Definitely Not” to “Definitely Yes”.We measured relevant aspects of global patient satisfaction using four selected items from HCAHPS collected from participants 5-weeks post discharge. Two of these items are conceptually related to pain: item 13 of HCAHPS, which reads “During this hospital stay, how often was your pain well controlled?’; and item 14, which reads, “During this hospital stay, how often did the hospital staff do everything they could to help you with your pain?”. Two other HCAHPS questions measured general satisfaction: item 21, which reads, “Using any number from 0 to 10, where 0 is the worst hospital possible and 10 is the best hospital possible, what number would you use to rate this hospital during your stay?”; and item 22, which reads, “Would you recommend this hospital to your friends and family?”Opioid usage was defined as mean total milligrams of morphine equivalent (MME), calculated by first multiplying the quantity of each prescribed medication by the strength of that medication (milligrams of given opioid per unit dispensed), and then multiplying this quantity-strength product by conversion factors derived from published sources to estimate the milligrams of morphine equivalent to the opioids dispensed in the prescription. The mean pre-intervention MME for subjects in each arm was calculated by adding the morphine equivalents for each prescription dispensed during the 48 hours before intervention, while the post-intervention MME for subjects in each arm was calculated by adding the morphine equivalents for each prescription dispensed during the 48 hours after intervention.We calculated descriptive statistics for demographic and clinical characteristics of the sample including age, sex, race, ethnicity, primary reason for hospitalization, and baseline pain scores. We performed bivariate analyses to evaluate for significant differences between groups, using two-sample t-tests for continuous variables and chi-square tests for categorical variables.identity covariance structure. The control variables  were time-invariant and therefore included in the fixed-effects portion of the model only. To test the appropriateness of using mixed models for these data, we performed likelihood ratio tests comparing ordinary least square and mixed models.For the primary outcome, we first compared within-subject differences in immediate pre- and post-intervention pain scores between groups to evaluate the initial impact of the first treatment session, similar to our previous non-randomized trial, using twWe compared satisfaction with audiovisual experiences between groups using t-tests. We compared HCAHPS item scores between groups using chi-square tests for four-level responses and t-tests for responses collected on the 11-point scale. We compared mean pre- and post-intervention MME between groups using t-tests.Using power calculations based on a predicted mean VAS pain score of 5.4 (SD 2.7), assuming a change in pain score of 1.5, and targeting a power of 80% , we calculated a total study sample required of 104 using the Stata .power twomeans command. We expanThe Cedars-Sinai Institutional Review Board approved this study (IRB Pro00045641) and it was registered with ClincialTrials.gov (NCT02887989).Table 1 provides baseline demographic and clinical characteristics for the two groups. There were no significant differences between groups for age, sex, race, ethnicity, or pre-intervention pain scores. The reasons for admission were similar between groups. The mean cumulative pre-intervention pain scores were not significantly different between the groups, nor was the mean of the last pain measurement taken pre-intervention. Mean pain-scores for each group at 12-hour intervals during the 72-hours before and after the intervention are displayed in Fig 4. We report usage data for the intervention period in the supplement .One hundred twenty eligible patients completed the protocol, with 61 patients in the VR arm and 59 patients in the control arm. Table 2), exposure to VR conferred a 1.17-point incremental reduction in pain vs. controls (P = 0.048). Age was also a significant predictor in this multivariable model, with each additional 10-years of age predicting a 0.6-point reduction in pain (P = .001).The distribution of the within-subject differences in immediate pre- and post-intervention pain scores was tested for normality using the Shapiro-Wilk test (P = 0.19). A T-test showed the mean difference significant in favor of VR (P < .04). When limited to the subgroup of patients with the most severe baseline pain , the effect of VR was more pronounced vs. control . After adjusting for age, gender, and type of pain using linear regression analysis (Table 3) found VR was associated with significant drops in pain for each period when adjusting for time, study group, age, gender, and type of pain. Models describing the 48- and 72-hour post-intervention periods found .59 (P = .03) and .56 (P = .04) incremental reductions in pain versus controls, respectively.When extending the analysis to include pain scores collected in the 48- and 72-hour periods before and after the intervention, the multilevel mixed model regression analyses .Global measures of patient satisfaction, as recorded with selected HCAHPS items administered after discharge, exhibited a ceiling effect in both groups. Patients across the trial were broadly satisfied with their hospital stay upon 5-week reflection, rendering it difficult to identify incremental differences between the experimental groups. Specifically, there were no differences in perceived pain control (P = .48), efforts of the staff to manage pain (P = .42), overall perception of the hospital (P = .69), and willingness to recommend the hospital to a friend (P = .31); scores across all these HCAHPS items were high in both groups.There was no difference in the quantity of opioids consumed between groups in either pre-intervention or post-intervention periods. The mean MME in the VR vs. control groups pre-intervention was 80.83 (SD 51.82) and 75.07 (SD 52.78), respectively (P = .57), and the mean MME in the VR vs. control groups post-intervention was 81.04 (SD 45.09) and 77.08 (SD 43.94), respectively (P = .66).There were no significant treatment-related adverse events reported in either group. Three patients in the VR group (4.9%) reported transient dizziness at some point during their VR therapy, and all these individuals reported symptomatic resolution upon removing the headset without lasting effects.Although previous research has demonstrated therapeutic benefits of VR for pain, there has been no prospective, randomized, adequately powered, pragmatic trial of VR versus an active control in hospitalized patients. In this study, we found that on-demand use of VR in a diverse group of hospitalized patients was well tolerated and resulted in statistically significant improvements in pain versus a control group exposed to an in-room “health and wellness” television channel. These results build upon earlier studies and further indicate that VR is an effective adjunctive therapy to complement traditional pain management protocols in hospitalized patients.Notably, the VR group achieved improved pain scores despite the pragmatic and comparative effectiveness design of the study. Specifically, the trial minimized investigator interactions, did not enforce a VR usage protocol beyond initial patient instructions, relied solely on non-study nursing staff to collect the primary outcome measure, and utilized a control intervention with potential for therapeutic benefits. Moreover, the trial enrolled hospitalized patients with all forms of somatic and visceral pain, including oncologic, neurological, orthopedic, and gastrointestinal pain, among other types. Many of the patients suffered from complex, multi-factorial causes of biopsychosocial distress and received multi-modal treatments, making it difficult for any single intervention to offer consistent pain benefits across this diverse, hospitalized patient population. Nonetheless, the VR intervention achieved statistically significant benefits both initially and after 48-hours and 72-hours of use. Patients also reported higher satisfaction with the VR experience than watching television, indicating an improvement over the current standard of care for in-room audiovisual engagement.Although the effect of VR was statistically significant, the absolute reduction in pain scores was relatively small. After multivariable adjustment, VR accounted for an incremental 1.17-point drop in pain compared to the control group after the initial treatment; the incremental benefit dropped to 0.59 points when evaluating cumulative pain scores over the subsequent 48-hours. These differences fall below the 2-point threshold for a minimal clinical important difference (MCID) on the NRS, as reported by Farrar and colleagues. However,We did not observe a difference in opioid prescribing between the study groups. This is not altogether surprising, as treating physicians were free to manage pain according to usual practice and the protocol did not specify whether or how VR should impact clinical decision-making. Pain medications are typically ordered upon admission, and nurses work with their patients to dispense analgesics according to on-demand need within the constraints of physician orders. Our pragmatic study did not instruct nurses on whether to substitute VR for opioids or any other analgesic. Nonetheless, it is notable that patients in the VR group had lower pain scores despite receiving an equivalent MME as the control group. Future research should evaluate structured and standardized order sets that explicitly interpose VR as an early option prior to initiating or escalating opioids; this may promote earlier and more frequent use of VR and has potential to reduce subsequent use of opioids and other analgesics.It is notable that despite evaluating 591 patients for participation, only 120 enrolled and completed the protocol. Although this study is, to our knowledge, the largest randomized trial of inpatient VR for pain management, it is important to emphasize the drop-off between patient identification and study completion. This result is consistent with our previous research using VR in hospitalized patients, 14 and It remains unknown exactly how VR works to reduce pain perception and experience or whether different forms of VR have varying efficacy. Most proposed mechanisms attribute the benefit to simple distraction. When theNonetheless, important unanswered clinical questions include: (1) does enhanced VR that applies principles of Acceptance and Commitment Therapy (ACT) such as mindful meditation and/or physiologic biofeedback outperform conventional VR that employs simple distraction? (2) Are there patient characteristics that predict enhanced response to VR beyond baseline pain severity? (3) Are there usage patterns or engagement characteristics that predict enhanced response to VR? (4) Can VR reduce pain while also reducing opioid requirements? Although the current study further supports the effectiveness of VR for managing inpatient pain, it also raises additional questions that deserve inquiry as the field of therapeutic VR broadens and evolves.S1 FigRepublished under a CC BY license, with permission from AppliedVR, original copyright 2016.(PDF)Click here for additional data file.S2 Fig(PDF)Click here for additional data file.S1 Doc(DOC)Click here for additional data file.S2 Doc(PDF)Click here for additional data file.


Antimicrobial-resistant Gram-negative bacteria are a major cause of morbidity and mortality in hospitalized neonates in South and South-East Asia. This study aimed to determine the dynamics of colonization with antimicrobial-resistant Gram-negative bacteria amongst patients in a neonatal intensive care unit (NICU) in Thailand. From 97 enrolled patients, 52% were colonized by an extended-spectrum β-lactamase (ESBL) organism at some point during their stay and 64% were colonized by a carbapenem-resistant organism. Rapid acquisition of ESBL-positive and carbapenem-resistant organisms was found. Once colonized with an antibiotic-resistant organism, patients remained colonized for the remainder of their NICU stay. Acinetobacter baumannii and Pseudomonas aeruginosa have been identified by the World Health Organization (WHO) as critical priorities for new treatment options Antibiotic-resistant Gram-negative bacteria including Enterobacteriaceae, Staphylococcus aureus (a Gram-positive pathogen) in the NICU setting in Thailand Patients in neonatal intensive care units (NICUs) are particularly vulnerable to life-threatening infections with these organisms. Previous work has highlighted the importance of asymptomatic carriage for understanding the transmission dynamics of methicillin-resistant This study was conducted at a large referral centre in Bangkok, Thailand. The centre has 426 beds for outpatient, inpatient, intensive care and surgical departments, with approximately 15,400 inpatients and 401,000 outpatients annually. The NICU has eight beds. There is no maternity unit at the centre so all patients are born off-site.This longitudinal study included all patients admitted to the NICU between February and September 2015. Written informed consent was given for all subjects enrolled in the study by their parents or legal guardians. Ethical approval was obtained from Oxford Tropical Research Ethics Committee (Reference 7–15) and from the local hospital ethics committee.th edition, January 2016) using disk diffusion on Mueller-Hinton agar . A full description of microbiological testing is given in Supplementary Material I (see online).After enrolment in the study, patients underwent twice-weekly colonization screening, comprising rectal swabs  and throat swabs (only if intubated/ventilated). A stool sample was collected weekly from each patient where possible. Samples underwent full microbiological testing using standard microbiological techniques and API 20E/20NE . Comprehensive antimicrobial resistance profiles were determined following current US Clinical and Laboratory Standards Institute guidelines . Supplementary Material II (see online) gives a full description of statistical analysis.In total, 97 patients were enrolled in the study . Ninety-two patients were born at another hospital, one patient was born in a healthcare centre, one patient was born at home, and the birth place was not known for the remaining three patients. Sixty-six patients (68%) were premature. Sixty-nine patients were 0 days old on admission, 16 patients were aged 1–3 days, five patients were aged 3–7 days, and nine patients were aged between 8 and 28 days. The median duration of admission in the NICU was 7 days (range 1–98 days). Two patients were re-admitted to the NICU during the study, and there were 12 deaths (12%) during NICU admission. The mean discharge weight was 1.93 kg (weight at enrolment was unknown).Klebsiella pneumoniae, 223 Pseudomonas aeruginosa, 190 Acinetobacter baumannii, 115 Enterobacter spp., 38 Escherichia coli and two Acinetobacter lwoffii . Based on initial swabs on admission to the NICU, 26 of 97 patients were colonized by an ESBL-positive organism and 37 of 97 patients were colonized by an IPM-R organism. An additional 24 patients who were ESBL-negative on their initial sample became colonized with an ESBL-positive organism within 3–75 days of admission (median 8 days), and 25 patients had an IPM-R organism isolated after their initial sample within 3–20 days of admission (median 7 days). The number of patients with antimicrobial-resistant organisms at and during admission is summarized in Medians of two (range one to 18) rectal swabs, two (range one to 18) tracheal swabs and one (range one to five) stool sample were collected per patient. From a total of 660 samples , 890 organisms with some form of antimicrobial resistance were isolated; 165 samples had no organism isolated. There were 322 All isolates from day 13 or later of a patient's stay in the NICU from which an organism was grown were positive for an IPM-R organism. After 22 days in the NICU, all isolates from which an organism was grown were positive for an ESBL-positive organism . In bothK. pneumoniae isolates, 183 of 190 Acinetobacter spp. isolates, 108 of 115 Enterobacter spp. isolates, 79 of 222 P. aeruginosa isolates and 28 of 38 E. coli isolates). Antibiotic resistance patterns for organisms are summarized in Gentamicin resistance was also common, with 52 patients having a gentamicin-resistant organism  1.22–8.57) and 3.75 (95% CI 1.52–9.22), from the multi-variable regression respectively . In the The prevalence rates of carriage were high on initial screening for ESBL-positive and IPM-R organisms , with a similar number of patients found to be negative on their initial sample subsequently becoming positive during their NICU stay . Nearly half of all patients were colonized with at least one 3GC-R organism on admission to the NICU, while a further 21% who were 3GC-R negative on admission became positive during their NICU stay. There were rapid increases in the proportion of isolates testing positive for ESBL-positive and IPM-R organisms over the course of patients' stays on the NICU; and, amongst specimens which grew an organism, 100% of isolates taken from patients who had stayed in the NICU for more than 3 weeks were positive for both. Two different processes could be driving these increases: transmission on the NICU to patients who were ESBL-/IPM-R negative on admission, or selection for initially undetectable resistant subpopulations. Future genomic and epidemiological studies are needed to quantify the relative importance of these processes. The high persistence of carriage of ESBL-positive and IPM-R organisms over timescales relevant to ward-level dynamics was highlighted by the fact that once a patient tested positive for an ESBL-positive or IPM-R organism, all subsequent isolates were positive during the NICU stay.E. coli as the predominant ESBL-positive organism; in contrast, in the present study population, K. pneumoniae accounted for the majority of ESBLs, with 50% of patients colonized at some time during their NICU stay K. pneumoniae is one of the most important neonatal pathogens in developing countries, with reported case fatality rates of 18–68% from bloodstream infections. Gut colonization by K. pneumoniae is increasingly recognized as a key risk factor for subsequent bloodstream infection.Two previous ESBL carriage studies from adults in Thailand identified The high levels of neonatal carriage found from initial samples on admission to the NICU may reflect high community prevalence. One study of rural Thai communities reported a prevalence of 69.3% for ESBL-positive carriage in stools Acinetobacter spp. at some point during their NICU stay, with 30% becoming colonized after admission following initial negative samples. Over half were IPM-R. In contrast, in Cambodia, neonatal colonization with Acinetobacter spp. was rare, with 1.7% of patients becoming colonized after admission, and 6% of all Acinetobacter spp. positive samples were IPM-R Acinetobacter spp. isolated in this study were from tracheal samples, over half of the patients with Acinetobacter spp. had positive results from their rectal swabs, with 70% IPM-R. High rates of healthcare-associated infection and colonization with Acinetobacter spp. have been reported previously in Thailand, especially in adult intensive care units, and some studies have found Acinetobacter spp. to be the most common hospital-acquired antibiotic-resistant organism More than half of the patients were found to be carrying Acinetobacter spp., resistance was also common in P. aeruginosa and K. pneumoniae. In 2017, the World Health Organization classified carbapenem-resistant A. baumannii, P. aeruginosa and Enterobacteriaceae as pathogens of critical importance requiring research and development of new antimicrobials A. baumannii has previously been identified as a major problem in Thailand Nearly two-thirds of patients were colonized with carbapenem-resistant organisms in this study. Although the highest amount of carbapenem resistance was seen in A key limitation of this study was the lack of maternal carriage data, which prevents identification of the role of vertical transmission. Another limitation is that it was only possible to take initial samples from patients within 48 h of NICU admission in less than one-third of the patients. As a result, some of the patients with initial positive samples may have become positive between the time of admission and the initial sample being taken. Unfortunately, information on infection control practices and ward hygiene was not available. This information would be helpful for guiding future infection prevention. Also, lack of high-resolution genotyping data prevents reliable reconstruction of transmission pathways. This will be addressed in future work.In conclusion, this study found high colonization and acquisition rates of antibiotic-resistant Gram-negative organisms from an NICU in Thailand. After day 13 of stay on the NICU, all patients that grew an organism were positive for an IPM-R organism, and after 22 days of NICU stay, all isolates were positive for an ESBL-positive organism. Once patients were found to be colonized by an ESBL-positive or IPM-R organism, they remained colonized for the rest of their NICU stay. Results from this study highlight the need to quantify the relative importance of selection and transmission, and develop effective interventions to reduce the resistance burden.None declared.UK Medical Research Council and Department for International Development (Grant No. MR/K006924/1 to BSC) and the Wellcome Trust as part of the Wellcome Trust-Mahidol University-Oxford Tropical Medicine Research Programme (Grant No. 106698/Z/14/Z).This study was supported by the


The precise content and frequency of follow-up of patients with colorectal cancer (CRC) is variable and guideline adherence is low. The aim of this study was to assess the view of colorectal surgeons on their local follow-up schedule and to clarify their opinions about risk-stratification and organ preserving therapies. Equally important, adherence to the Dutch national guidelines was determined.Colorectal surgeons were invited to complete a web-based survey about the importance and interval of clinical follow-up, CEA monitoring and the use of imaging modalities. Furthermore, the opinions regarding physical examination, risk-stratification, organ preserving strategies, and follow-up setting were assessed. Data were analyzed using quantitative and qualitative analysis methods.A total of 106 colorectal surgeons from 52 general and 5 university hospitals filled in the survey, yielding a hospital response rate of 74% and a surgeon response rate of 42%. The follow-up of patients with CRC was mainly done by surgeons (71%). The majority of the respondents (68%) did not routinely perform physical examination during follow-up of rectal patients. Abdominal ultrasound was the predominant modality used for detection of liver metastases (77%). Chest X-ray was the main modality for detecting lung metastases (69%). During the first year of follow-up, adherence to the minimal guideline recommendations was high (99–100%). The results demonstrate that, within the framework of the guidelines, some respondents applied a more intensive follow-up and others a less intensive schedule. The majority of the respondents (77%) applied one single follow-up imaging schedule for all patients that underwent treatment with curative intent.Dutch colorectal surgeons’ adherence to minimal guideline recommendations was high, but within the guideline framework, opinions differed about the required intensity and content of clinical visits, the interval of CEA monitoring, and the importance and frequency of imaging techniques. This national survey demonstrates current follow-up practice throughout the Netherlands and highlights the follow-up differences of curatively treated patients with CRC. Colorectal cancer (CRC) is the third most common cancer in both men and women . Over thThe goal, frequency and content of outpatient visits are a subject of debate in many cancer types and scheduled out-patient visits are generally of limited value –7. StillA recent review of European guidelines conducted by Bastiaenen et al. demonstrated that although multimodal follow-up after curative treatment of CRC is recommended in all countries, the precise content and intervals of these modalities are variable . The DutThe aim of this study was to assess the view of Dutch Colorectal Surgeons on their local follow-up schedule, clarify their opinions about risk-stratification and organ preserving therapies. Equally important, adherence to the Dutch national guidelines was determined.N = 250). Two reminders were sent; one after 2 weeks, and a final reminder in which closing of the survey was announced and invitees were requested to either fill in the survey or finish their survey. The survey was locked after completion in order to prevent answer changes.All members of the Dutch Taskforce Coloproctology (WCP: Werkgroep Coloproctologie) were invited to complete a web-based survey in October and November 2018. Invitations were sent by email with the purpose of the survey, a request to participate anonymously, and the hyperlink to the actual questionnaire. Only colorectal surgeons treating patients with CRC were included. . The survey was conducted in Dutch and consisted of 36 multiple-choice questions, 2 open questions and another 9 open and 16 multiple-choice additional questions depending upon previous answers  classification. Adherence to the national guidelines was defined as the percentage that adhered to the minimal recommendations.  Least intensive clinical follow-up was defined as two clinic visits, two yearly CEA sampling and two-yearly use of abdominal US. Most intensive follow-up was defined as performing four clinical visits, four CEA measurements, and two-yearly US.In this qualitative study, descriptive statistics were used. Data were depicted as frequencies and percentages. Data from open questions, comments and views were analyzed in a qualitative fashion.Analyses were done using SPSS .A total of 106 colorectal surgeons from 52 general and 5 university hospitals in the Netherlands filled in the survey, yielding a hospital response rate of 74% and a surgeons response rate of 42%.The follow-up of patients with CRC was mainly done by surgeons (71%). Other involved clinicians were nurse practitioners (10%), gastroenterologists (3%), surgical residents (2%), or a combination of the above (14%). Colonoscopy surveillance was mainly performed by gastroenterologists (87%). More than half (55%) of the respondents did not follow patients with pT1N0 colorectal disease at the outpatient clinic. These patients were only followed according to the colonoscopy surveillance guideline but did not undergo regular visits, CEA, or imaging tests.The majority (55%) reported that geriatric patients were followed regardless of their age, while others ended surveillance of patients older than 80 (8%), 85 (19%) or 90 years (11%).Physical examination was not routinely performed by 68 and 67% of the respondents in patients with colon or rectal cancer, respectively. Components of physical examination are shown in Table Questionnaires are taken routinely in 24% of the cases during clinical visits, mainly European Organization for Research and Treatment of Cancer (EORTC)-Quality of Life forms (4%), distress thermometer and problem list (15%), Brief Pain Inventory or other related pain questionnaires (1%), patient satisfaction surveys (2%), adverse event/complication questionnaires such as the Low Anterior Resection Syndrome Score (13%), or other Patient Related Outcome Measure questionnaires (4%).CEA was routinely used as a tumor marker (99%) during follow-up. One respondent applied an intensive CEA measurement protocol, with blood sampling every 6 weeks during the first 2 years and every 3 months hereafter , followed by CT-scan (11%) or a combination of both (10%) with the remaining 2% being “otherwise, not specified”. US is generally performed every 6 months in the first 2 years and yearly hereafter :In rectal cancer follow-up, preferably after 1–2 years of follow-up (24%)In high-risk patients or young patients (19%)Intermittent CT-abdomen/US liver (14%)Follow-up of specific findings/lesions (9%)When CT performed for other reasons such as follow-up of atypical lung lesions (9%)Elevated CEA (5%)Adiposity/ hepatic steatosis (5%)Determined by multidisciplinary team (5%)CT at diagnosis for comparison purposes (5%)When indicated, “not otherwise specified” (5%)Surgeon reported free text answers reasoning the use of CT-abdomen, were as follows (The majority of the respondents (77%) applied one single follow imaging schedule for all patients that underwent treatment with curative intent. However, they did not use a uniform schedule; 26% had a different scheme for high-risk patients citing various definitions Table .Table 3In high-risk patients, there is a higher tendency to perform physical examination including DRE or colonoscopy, to use CT-thorax/abdomen instead of US and chest X-ray, and to perform pelvic MRI or PET-CT scanning. Also, several colorectal surgeons reported intensifying the diagnostic modality interval  to every 3–4 months in the first 2 years of follow-up or at least perform a yearly CT-thorax/abdomen in high-risk patients.The majority of the respondents (82%) made routine use of imaging to detect lung metastases in rectal cancer patients. Chest X-ray was the main diagnostic modality according to 69% of the respondents, while the remaining 31% used CT-thorax.Most respondents (59%) provided rectum preserving treatment in their own institution. Almost all of the rectal cancer patients (96%) that had been treated with neo-adjuvant radiotherapy (5x5Gy) or neo-adjuvant (long course) radiation and chemotherapy underwent a routine preoperative restaging pelvic MRI on a routine basis, while only 29% of the respondents use endoscopy to assess tumor response. Almost all surgeons (92%) provide follow-up according to the Wait and See protocols as alternative treatment for surgery in selective patients.N = 89).The current national CRC guidelines are clear and usefulThe current national CRC guidelines are too complicated and could be more conciseFollow-up of patients with CRC can be done by nurse practitioners and/or case managersSurgeons should be the primary responsible clinicians for CRC follow-upGeneral practitioners are well able to take over the CRC follow-upPhysical examination should be performed routinely during follow-up of patients with CRCThere is enough evidence that only CEA monitoring is cost-effective and useful in colorectal follow-upPatients with CRC should have a CT- thorax/abdomen at 12- and 24-months post-treatment to detect metastasis earlyColorectal follow-up can be finished after 2 years because there is low risk of disease recurrencePatients with CRC are well able to coordinate their own follow-up and appointmentsSurgeons opinions about current practice and developments. Surgeons expressed their opinion regarding the ten statements below Fig. , N = 89.. .Based on the national average cost of an outpatient clinic visit (€195), CEA blood sampling (€8), abdominal US (€93), and chest X-ray €44), the total cost difference between least and most intensive follow-up of patients with colon or rectal cancer in the first year of follow-up was €406  of the respondents wrote that tailored follow-up schedules accounting for disease stage, patient age and clinical condition are required. According to them, the national guidelines are designed as a single size to fit all patients. Three respondents noted that follow-up is not always useful since there is no survival benefit of intensive follow-up schedules. Two respondents felt that the current guidelines are outdated and too much determined by radiation oncologists. Respondents called for the development of personalized follow-up strategies. Around 39% of them requested more research into setting of follow-up , the value of separate elements of the follow-up schedule, and the required duration of surveillance.The findings of this survey among colorectal surgeons in the Netherlands demonstrate differences and variety in current follow-up of patients with CRC that have undergone curative surgery. Adherence to minimal guideline recommendations was high. With a hospital response rate of 74%, including university centers, the survey was representative for daily practice throughout our country.The current study demonstrates that in the Netherlands, follow-up is primarily performed by surgeons. Although there is some evidence that follow-up improves survival , there iFrom a patient perspective, there is also willingness regarding non-physician follow-up such as GP-led or nurse-led follow-up –19. DiffDespite the little existing agreement between different European guidelines, most recommend clinical visits, CEA monitoring and liver imaging as part of follow-up . This suThe Dutch guidelines recommend using the high-risk criteria of the ASCO guidelines for identifying high-risk stage II disease patients. Our results revealed heterogeneity in defining high-risk patients. Some participants in our survey based high-risk status on tumor size, biology, and histopathological characteristics, while others based it on intra-operative findings and adjuvant treatment. This variation underlines the need of guidelines and clear definitions regarding low and high-risk status.Respondents mentioned that tailoring means stratifying by disease stage, age, clinical condition, and patient preferences and capacities. In geriatric patients with high co-morbidity burden, surgeons considered ending follow-up since the high mortality and morbidity related to secondary or salvage surgery for recurrent disease outweighs the advantages of routine follow-up. Recently, several cost effectiveness studies about follow-up schedules have been performed. In a randomized clinical trial of Mant et al. high intensity follow-up after curative colorectal surgery was costly and did not have any impact on survival or QALYs . For thaWe calculated an estimated difference of €406 per patient, per year between minimal and maximal follow-up. These costs represent only the costs for the laboratory and imaging costs, without considering the potential cost minimization of implementing nurse-led instead of surgeon-led follow-up. Since many studies have shown that there is no survival benefit of costly, intensive follow-up , 9, 11 fThe Dutch guidelines allow, to a certain extent, for different interpretations and therefore variation in practice. Also, surgeons can deviate from the guidelines as long as they demonstrate due care and consideration. Knowing that our survey respondents adhered strongly to the guidelines, it is interesting to note that there is variation in content and frequency of follow-up modalities. Several factors might have contributed to this variety. First, the presence of broad and less detailed follow-up guidelines. Second, the existence of intra- and inter-surgeon variation in the interpretation of, and adherence to guidelines. Third, variation in patient selection.A strong aspect of this survey is the fact that it demonstrates current follow-up practice throughout the Netherlands and highlights the differences regarding duration, content and intensity of follow-up. Nevertheless, there are some limitations. First, surveys harbor potential reporting bias since self-formulated questions and statements can be interpreted differently by respondents or yield socially desirable answers. We cautiously formulated the questions and tried to formulate non-ambiguous and non-directive questions. Second, the surgeon response rate was relatively low, but hospital response rate was high. The survey yielded response from hospital representatives from various regions of the country. Moreover, comparable surgeon response rates were reported in other studies , 23–26.Adherence to national follow-up guidelines was high although guidelines are interpreted differently by colorectal surgeons working in the Netherlands. Dutch colorectal surgeons practiced and thought different about the intensity and content of clinical visits, the interval of CEA monitoring, the importance and intensity of imaging techniques such as ultrasound and computed-tomography. Also, heterogeneity exists in defining high-risk status of patients with CRC.In summary, this national survey demonstrates current follow-up practice throughout the Netherlands and highlights the follow-up differences of curatively treated patients with CRC.Additional file 1. Short outline of the Dutch guidelines.Additional file 2. English translated copy of the actual Online survey (held in Dutch).


Background and purpose — The theoretical mechanical advantages of metal-on-metal hip resurfacing (MoM-HR) compared with conventional total hip arthroplasty (THA) have been questioned. Studies including measures of patient-reported function, physical activity, or health-related quality of life have been sparse. We compared patient-reported outcomes in MoM-HR patients with a matched group of patients with conventional THA at 7 years post-surgery.Patients and methods — Patients and patient data were retrieved from the Swedish Hip Arthroplasty Register. The case group, consisting of 363 patients with MoM-HR, was matched 1:1 with a control group, consisting of patients with a conventional THA. Patients were sent a postal patient-reported outcome measures (PROM) questionnaire including the Hip Disability and Osteoarthritis Outcome Score (HOOS), EQ-5D, and VAS pain. We used multivariable linear regression analyses to investigate the influence of prosthesis type.Results — 569 patients (78%) returned the questionnaire with complete responses . MoM-HR was associated with better scores in HOOS function of daily living (4 percentage units) and HOOS function in sport and recreation (8 percentage units) subscales. Type of prosthesis did not influence HOOS quality of life, HOOS pain, HOOS symptoms, EQ-5D index, hip pain, or satisfaction as measured with visual analog scales.Interpretation — At mean 7 years post-surgery, patients with hip resurfacing had somewhat better self-reported hip function than patients with conventional THA. The largest difference between groups was seen in the presumed most demanding subscale, i.e., function in sport and recreation. Hip arthroplasty in young and active patients is an orthopedic challenge. In 2011, the Finnish Arthroplasty Register  gained popularity in the mid-1990s due to advances in metallurgy and tribology, allowing manufacturing of thin acetabular cups accepting large-diameter components  at a single institution (Karolinska Huddinge) between the years 2002 and 2013, was matched 1:1 with a control group, consisting of patients with a conventional THA selected from the Register. In the case of bilateral MoM-HR (n = 105) or bilateral THA (n = 102) during the study period, we included data regarding the first operation. Patients deceased by December 2015 (n = 6) were excluded. The groups were matched by baseline characteristics: age, sex, surgical approach, year of surgery, and preoperative EQ-5D score when available.726 patients  were selected for the study . In DeceIn addition to the postal questionnaire we used information from the Swedish Hip Arthroplasty Register covering surgical data, demography, data on subsequent reoperations and, when available, pre- and postoperative PROMs data including hip pain and the EQ-5D . Using the Directed Acyclic Graph from Figure 1 and d-separation to infer associational statements  adjusting for age, sex, preoperative EQ-5D index, and time from surgery. R . This research did not receive any specific grants from commercial funding agencies or bodies. The study was supported by public funding from the Swedish Hip Arthroplasty Register and research funds from Stockholm County Council. No competing interest declared.Supplementary data).569 patients (78%) returned the questionnaire with complete responses. Mean follow-up time (F-U) was 7 years (IQR 2.2–13 years). The proportion of patients who had undergone any reoperation was similar between groups . The preThe case group had better unadjusted outcomes in all subscales of HOOS whereas EQ-5D index, VAS pain, and VAS satisfaction were equal between the groups .Both the crude and adjusted estimates  showed tPatients who underwent hip resurfacing reported better postoperative functional outcomes  at mean 7 years post-surgery compared with a group of matched patients with conventional hip arthroplasty. We found no statistically significant differences in EQ-5D index, hip pain, or satisfaction. The largest difference between the groups was seen in the presumed most demanding subscale, i.e., function in sport and recreation.Our observation is in accordance with the study of Haddad et al. , showingWhen functional outcome scores were compared prospectively in 89 consecutively operated hips it was found that the resurfacing patients had greater improvement in Harris Hip scores, in UCLA activity score, and had a higher postoperative UCLA activity score than those operated with conventional THA  between MoM-HR and conventional THA, it was concluded that the choice of implant should not be based solely on any expectation that either yields superior clinical outcomes compared with the other at short-term follow-up . However, missing preoperative EQ-5D data were successfully imputed and the EQ-5D scores were subsequently used for case-mix adjustment based on preoperative health status. Another limitation pertains to the lack of prospective HOOS data. Although groups were matched based on demography and baseline EQ-5D index, level of functioning in ADL and sports and recreation may have differed preoperatively. The occurrence of reoperations could be a potential source of bias albeit repeat surgeries were evenly distributed between the groups.Whilst conventional THA is performed in most orthopedic units in Sweden, hip resurfacing was only performed in a few specialist centers during the study period. Therefore, all patients operated with HR either actively searched for institutions performing resurfacing prosthesis or were referred from other orthopedic units. Patients operated with conventional THAs likely did not actively request a certain implant, suggesting a biased selection that cannot be adjusted for. Moreover, almost all HR surgeries were performed by 2 experienced surgeons following well-established principles of surgical innovation in contrast to the control group, which was selected from the registry not considering surgeon experience. It must be constantly emphasized that introduction of new devices should follow a systematic approach even if the theoretical basis or preclinical results are excellent. Recently, Reito et al.  describeThe strengths of our study include the careful 1:1 matching of the groups for the various demographic factors, surgical approach, time of surgery, and preoperative EQ-5D scores, which reduced many confounding factors. Our study also comprised a fairly large number of patients in the groups and with a satisfactory response rate. To our knowledge no study comparing functional outcome scores between MoM-HR and conventional THA has been undertaken with such a large number of patients followed for a comparable period of time.Although the type of hip prosthesis did not influence the level of satisfaction, postoperative pain relief, or quality of life, MoM-HR patients had better postoperative HOOS scores in the function of daily living and function in sports and recreation domains. Translating the adjusted regression estimates of these 2 HOOS subscales into effect sizes, the influence of MoM-HR was moderate . Furthermore, there was no statistically significant difference in reoperation rates using a Birmingham Hip Replacement (BHR) compared with a conventional implant in these 2 age- and sex-matched patient groups. As MoM-HR was developed to address the special demands of a younger and more active population, our results support the rationale for using the technique in this group of patients.Choice of hip arthroplasty for young and active patients with high expectations is still challenging, mostly due to higher risks of wear, dislocation, and need of revision surgery. In summary, by comparing MoM-HR with conventional THA in a matched study design (mean 7 years F-U) of a selected group of patients we have shown MoM-HR to yield better functional outcome scores in 2/5 HOOS subscales; all other outcome measures were similar. When a BHR implant is considered, patients should be informed of the risk of developing of adverse reactions and uncertain long-term results. We highly recommend subsequent close follow-up for this matter.supplementary data in the online version of this article, http://dx.doi.org/10.1080/ 17453674.2019.1604343Figure 1 and OR, HH, and LFT conceived and designed the study. OR and HH obtained ethical approval. OR and SN collected data. SN performed statistical analysis. AO drafted the manuscript. All authors interpreted the results and reviewed, edited, and approved the final version of the manuscript.Acta thanks Nina Mathijssen and Marc Nijhof for help with peer review of this study.