Evaluating the effects of S-ketamine on postoperative delirium in elderly patients following total hip or knee arthroplasty under intraspinal anesthesia: a single-center randomized, double-blind, placebo-controlled, pragmatic study protocol.

Introduction: Postoperative delirium (POD) is an acute, transient brain disorder associated with decreased postoperative quality of life, dementia, neurocognitive changes, and mortality. A small number of trials have explored the role of S-ketamine in the treatment of POD due to its neuroprotective effects. Surprisingly, these trials have failed to yield supportive results. However, heterogeneity in delirium assessment methodologies, sample sizes, and outcome settings as well as deficiencies in S-ketamine use methods make the evidence provided by these studies less persuasive. Given the severe impact of POD on the health of elderly patients and the potential for S-ketamine to prevent it, we believe that designing a large sample size, and rigorous randomized controlled trial for further evaluation is necessary. Methods: This is a single-center, randomized, double-blind, placebo-controlled, pragmatic study. Subjects undergoing total hip or knee arthroplasty will be randomized in a 1:1 ratio to intervention (n = 186) and placebo (n = 186) groups. This trial aims to explore the potential role of S-ketamine in the prevention of POD. Its primary outcome is the incidence of POD within 3 postoperative days. Secondary outcomes include the number of POD episodes, the onset and duration of POD, the severity and subtype of POD, pain scores and opioid consumption, sleep quality, clinical outcomes, and safety outcomes. Discussion: To our knowledge, this is the first pragmatic study that proposes to use S-ketamine to prevent POD. We reviewed a large body of literature to identify potential preoperative confounding variables that may bias associations between the intervention and primary outcome. We will use advanced statistical methods to correct potential confounding variables, improving the test's power and external validity of test results. Of note, the patient population included in this trial will undergo intraspinal anesthesia. Although large, multicenter, randomized controlled studies have found no considerable difference in the effects of regional and general anesthesia on POD, patients receiving intraspinal anesthesia have less exposure to at-risk drugs, such as sevoflurane, propofol, and benzodiazepines, than patients receiving general anesthesia. At-risk drugs have been shown to negatively interfere with the neuroprotective effects of S-ketamine, which may be the reason for the failure of a large number of previous studies. There is currently a lack of randomized controlled studies evaluating S-ketamine for POD prevention, and our trial helps to fill a gap in this area.Trial registration: http://www.chictr.org.cn, identifier ChiCTR2300075796.

External control arms: COVID-19 reveals the merits of using real world evidence in real-time for clinical and public health investigations.

Randomized controlled trials are considered the 'gold standard' to reduce bias by randomizing patients to an experimental intervention, versus placebo or standard of care cohort. There are inherent challenges to enrolling a standard of care or cohorts: costs, site engagement logistics, socioeconomic variability, patient willingness, ethics of placebo interventions, cannibalizing the treatment arm population, and extending study duration. The COVID-19 pandemic has magnified aspects of constraints in trial recruitment and logistics, spurring innovative approaches to reducing trial sizes, accelerating trial accrual while preserving statistical rigor. Using data from medical records and databases allows for construction of external control arms that reduce the costs of an external control arm (ECA) randomized to standard of care. Simultaneously examining covariates of the clinical outcomes in ECAs that are being measured in the interventional arm can be particularly useful in phase 2 trials to better understand social and genetic determinants of clinical outcomes that might inform pivotal trial design. The FDA and EMA have promulgated a number of publicly available guidance documents and qualification reports that inform the use of this regulatory science tool to streamline clinical development, of phase 4 surveillance, and policy aspects of clinical outcomes research. Availability and quality of real-world data (RWD) are a prevalent impediment to the use of ECAs given such data is not collected with the rigor and deliberateness that characterizes prospective interventional control arm data. Conversely, in the case of contemporary control arms, a clinical trial outcome can be compared to a contemporary standard of care in cases where the standard of care is evolving at a fast pace, such as the use of checkpoint inhibitors in cancer care. Innovative statistical methods are an essential aspect of an ECA strategy and regulatory paths for these innovative approaches have been navigated, qualified, and in some cases published.

Implementation of tailored exercise programs for MG patients in a gym setting: a pragmatic feasibility case study.

Although supervised aerobic and resistance training in a hospital setting was proven safe and beneficial for well-controlled myasthenia gravis (MG) patients, implementation of similar programs in the community has not been studied. We conducted a pragmatic open-label study at a large gym in Uppsala, Sweden. Seven patients with generalized MG were recruited to participate in an individualized, tailored exercise program, based on individual baseline status and personal goals, with a personal trainer. All patients completed the entire training period. The individually tailored exercise program was implemented safely and effectively, with all patients improving in aerobic capacity, muscle strength, and balance. Our pragmatic open-label case study suggests that well-controlled patients with generalized MG can extend their physical exercise to personal training in the gym. This is an essential step towards reducing the barriers to implementing exercise procols and increasing the availability of these interventions to MG patients.

Comparing asthma control assessment using the Asthma Control Test and the Asthma APGAR in African American/Black and Hispanic/Latinx populations.

INTRODUCTION: The objective of this analysis was to compare the Asthma Control Test (ACT) and the Asthma APGAR asthma control assessment tools in African-Ancestry/Black (AA/B) and Hispanic/Latinx (H/L) adults with moderate to severe asthma. METHODS: This pre-planned sub-study of the PREPARE clinical trial compares the baseline ACT and Asthma APGAR scores for the PREPARE populations using correlation coefficients, generalized linear modeling and receiver operating curve (ROC) analyses. Correlations were also assessed for both control tests and the Asthma Symptom Utility Index (ASUI). RESULTS: Among the 1201 adults (603 AA/B and 598 H/L) with moderate to severe asthma, most had uncontrolled asthma by both the ACT and the Asthma APGAR. Correlation coefficients between the ACT, Asthma APGAR and ASUI were strong and did not differ significantly by race/ethnicity. The ACT consistently assessed more patients as uncontrolled compared with the Asthma APGAR. The differences in ACT and Asthma APGAR scores did not differ by age, gender, race/ethnicity, self-reported health literacy or medication adherence but did differ by education level. Both the ACT and Asthma APGAR had similar ROCs for predicting an asthma exacerbation in the next 3 months. CONCLUSIONS: Both the ACT and the Asthma APGAR can be used for asthma control assessment in AA/B and H/L populations with moderate to severe asthma, providing comparable rates of uncontrolled asthma and similar limited ability to predict exacerbations. Further work is required to better understand the basis and clinical implications of the higher rates of uncontrolled asthma identified using the ACT.

COVID-19 vaccine short-term adverse events in the real-life family practice in Krakow, Poland.

BACKGROUND: In manufacturers' trials, vaccination against COVID-19 proved to be safe and effective. The officially reported frequency of vaccine adverse events (VAEs) in Poland is lower than that declared by the manufacturers. The anti-vaccination activists questioned the trustworthiness of official data. OBJECTIVES: The aim was to explore the real-life prevalence of VAEs in general practice settings and the factors that may influence it. METHODS: In this pragmatic, mixed prospective and retrospective study, patients vaccinated against COVID-19 between May and October 2021 in three GP practices in Krakow, Poland, were enrolled. Their demographic (age, sex, level of education) and clinical data (weight and height, smoking status, history of allergies, COVID-19 and chronic diseases) were collected. Then, they were interviewed about VAEs they experienced. RESULTS: Out of 1530 patients invited to participate, 1051 (69%) agreed and were eligible for analyses. Only 8.8% did not report any VAE. Pain at the injection site was the most frequently reported reaction (800, 76.2%). The most prevalent systemic ones were excessive fatigue/lethargy (527, 50.6%), sleep/circadian rhythm disturbances (433, 41.6%) and headache (399, 38.3%). Fifty required medical assistance - 39 experienced presyncope (3.7%) and 11 loss of consciousness (1.1%). Only two others were hospitalised. Females, younger adults, those with higher education and with a history of COVID-19 reported systemic VAEs more frequently, while those who were older and obese were less likely to report local reactions. CONCLUSION: Although more than 90% of patients vaccinated against COVID-19 in general practice settings may experience VAEs, in short-term observation, the vast majority are localised and mild.

A real-world implementation of asthma clinic: Make it easy for asthma with Easy Asthma Clinic.

Background and objective: Asthma is a common disease. Although several practice guidelines for asthma exist, good control is still problematic, particularly in developing countries. The Easy Asthma Clinic (EAC) was established in 2004 with the aim of providing simplified asthma guidelines, a multidisciplinary approach, and an online database. This study aimed to evaluate the outcomes of EAC in a real-world setting. Method: Clinical data were collected from the EAC database between 2004 and 2017. Treatment data and asthma control data were evaluated during the study period. Results: In all, 358 182 patients with asthma were treated at EAC in 1171 hospitals throughout Thailand during the 14-year period. For 3 264 117 visits, inhaled corticosteroid (ICS) was given at the highest percentage (average of 50.00%) with an average percentage of controllers at 75.08% and a trend of increasing treatment (coefficient 0.007; p < 0.001). The percentage of controlled asthma also increased from 20.48% to 27.76% with a coefficient of 0.015 (p for trend <0.001). Conclusion: The EAC may facilitate controller use in patients with asthma thereby increasing asthma control according to a large sample size and long longitudinal study.

(Im)precise trial descriptions.

Terms such as prospective, interventional, and controlled are redundant in the context of randomised trials, and are therefore distracting. Pragmatic should probably be reserved for trials that intentionally control little except the exposure. The term pilot should be reserved for trials that were designated to a priori and registered as pilot trials, and have appropriate pilot outcomes. 'Pragmatic' and 'real-world' should not be inserted to excuse poor trial design; and similarly, 'pilot' should not be appended to excuse inadequate power.

A pragmatic outreach pilot to understand and overcome barriers to COVID-19 vaccination in abdominal organ transplant.

BACKGROUND: Solid organ transplant recipients (SOTRs) are at increased risk for adverse outcomes with coronavirus disease 19 (COVID-19). Early data show a lower severe acute respiratory syndrome virus 2 (SARS-CoV-2) spike antibody immune response among SOTRs leading to patient concerns about vaccine efficacy. Public health messaging has largely left out immunocompromized individuals leading to a higher risk of vaccine misinformation. The American Society of Transplantation recommends COVID-19 vaccination for all SOTRs; however, patient concerns and beliefs about vaccination are largely unknown. METHODS: We conducted a transplant-center-based, pragmatic pilot trial to encourage COVID-19 vaccination among 103 unvaccinated SOTRs. We assessed vaccine concerns, barriers to vaccination, answered questions about efficacy, side effects, and clinical recommendations. RESULTS: A total of 24% (n = 25) of SOTRs reported that they will schedule COVID-19 vaccination after the study call, 46% reported that they will consider vaccination in the future, and 30% said they will not consider vaccination. Older age and White race were associated with lower willingness to schedule the vaccine, whereas Black race and longer time from transplant were associated with higher willingness. Common vaccine concerns included lack of long-term data, inconsistent messaging from providers, scheduling inconvenience, and insufficient resources. Follow-up approximately 1 month after the initial outreach found 52% (n = 13) of liver transplant recipients, and 10% (n = 3) of kidney transplant recipients subsequently received COVID-19 vaccines for a vaccination rate of 29% among respondents. CONCLUSION: Transplant center-based vaccine outreach efforts can decrease misinformation and increase vaccination uptake; however, vaccine-related mistrust remains high.

Proximal caries infiltration - Pragmatic RCT with 4 years of follow-up.

OBJECTIVES: Efficacy of proximal caries infiltration to arrest lesion progression has been shown in university settings, but only once in a practice-based pragmatic design with a follow-up of 18 months. The aim of this randomized split-mouth placebo-controlled study was to follow-up this cohort for 3 years and those with high caries risk for 4 years. METHODS: Originally, in 87 children and young adults pairs of 238 proximal caries lesions, radiographically extending into inner half of enamel (E2) or outer third of dentin (D1), were randomly allocated to two groups: infiltration (Icon; DMG) or mock (control) treatment by five dentists in four private practices. All subjects received risk-related instructions for diet, flossing and fluoridation. The primary outcome was radiographic lesion progression (pairwise comparison) evaluated by two evaluators independently being blinded to treatment allocation. RESULTS: After 36 months [mean (SD): 1152 (166) days] 165 lesion pairs in 64 patients as well as after 48 months [mean (SD): 1496 (121) days] 71 lesion pairs in 20 high caries risk patients could be re-evaluated clinically as well as radiographically using individualized bitewing holders as at baseline. No adverse events could be observed. After 36 months, progression was recorded in 23/165 test (14%) and 64/165 control lesions (39%) [McNemar/Obuchowski test; p<0.001; relative risk reduction (CI95%): 64 (45-77%)]. After 48 months lesion progression was recorded in 13/71 test (18%) and 34/71 control lesions (48%) [p = 0.003; relative risk reduction (CI95%): 62 (34-78%)] of high caries risk patients. CONCLUSIONS: It can be concluded that also in a practice-setting proximal caries infiltration is more efficacious in reducing lesion progression compared with individualized non-invasive measures alone over a period of four years.

A population health approach to insomnia using internet-based cognitive behavioral therapy for insomnia.

STUDY OBJECTIVES: To determine if a population health approach to insomnia using internet-based cognitive behavioral therapy for insomnia (ICBT-I) affects dispensed medications and provider encounters compared with usual care. METHODS: A pragmatic hybrid study design was used to evaluate both the implementation strategy and the long-term effects of ICBT-I on health care utilization in an integrated health system. Adult members with insomnia (a diagnosis or insomnia medication dispensation) or at high risk of insomnia (a diagnosis of depression or anxiety) were randomized to receive information on either an ICBT-I program (intervention arm) or in-person classes on insomnia (usual-care arm). Outcomes included dispensed insomnia medications and provider encounters over 12 months. The effectiveness of our implementation of ICBT-I on the target population was determined by an intention-to-treat analysis and by regression models comparing those who engaged in ICBT-I with matched usual-care arm controls. RESULTS: A total of 136,630 participants were randomized. Six hundred thirty-eight (0.96%) accessed the ICBT-I program while 431 (0.66%) attended 1 or more usual-care insomnia classes. Dispensed insomnia medications and provider encounters were no different in the ICBT-I arm vs the usual-care arm (intention-to-treat) or among those who engaged in ICBT-I vs matched usual-care arm controls. CONCLUSIONS: Since ICBT-I program engagement was low, additional strategies to improve engagement should be explored. ICBT-I did not result in a reduction in several measures of health care utilization; nevertheless, it offers an alternative and accessible approach to managing population insomnia. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Trial of Internet-Based Cognitive Behavioral Therapy for Insomnia in Patients Prescribed Insomnia Medications; URL: https://clinicaltrials.gov/ct2/show/NCT03313466; Identifier: NCT03313466. CITATION: Derose SF, Rozema E, Chen A, Shen E, Hwang D, Manthena P. A population health approach to insomnia using internet-based cognitive behavioral therapy for insomnia. J Clin Sleep Med. 2021;17(8):1675-1684.

Effects of Mulligan Mobilization with Movement in Subacute Lateral Ankle Sprains: A Pragmatic Randomized Trial.

Objective: In a pragmatic and randomized clinical trial, patients with lateral ankle sprains were assessed, under blinded conditions, for their responsiveness and improvements during Mulligan mobilization-with-movement (MWM) therapy. Methods: Overall, 51 participants with subacute lateral ankle sprains (Grade I-II) were recruited. Following an MWM screening procedure, responders were randomized to either an intervention group (MWM) or a sham group. The MWM group received inferior tibiofibular, talocrural, or cubometatarsal MWM. The treatment or sham was administered upon three sessions, each 4 days apart. Changes from baseline were measured and compared between the sessions for dorsiflexion range of motion, pain, stiffness perception, and the Y-balance test. Results: In total, 43 participants were considered responders to MWM. Using a two-way repeated-measure ANOVA, a statistical and clinically meaningful improvement in dorsiflexion range of motion was revealed in the MWM group (p = 0.004, 1rst = +1.762 cm; 3rd = +2.714 cm), whereas no improvement following the first session occurred in the sham group (p = 0.454, 1rsttrial = +1.091 cm; 3rdtrial = +1.409 cm). Pain and stiffness significantly improved, yet below the clinically meaningful level. The MWM group demonstrated a significant improvement after three sessions for the Y-balance test (p = 0.001, +8.857 cm). Conclusion: More than 80% of participants with subacute lateral ankle sprains responded well to the MWM approach. Three sessions of pragmatically determined MWM provided a significant and clinically meaningful benefit in dorsiflexion range of motion and Y-balance test performance compared to a sham treatment.

A Multidisciplinary Integrative Medicine Team in the Treatment of Chronic Low-Back Pain: An Observational Comparative Effectiveness Study.

OBJECTIVES: Chronic low-back pain (CLBP) is burdensome and costly, and a common condition for which adults use integrative therapies. The effectiveness of multidisciplinary integrative approaches has not been well studied. The purpose of this observational study was to compare characteristics and outcomes of CLBP patients treated at the Osher Clinical Center (OCC) versus other clinics at Brigham and Women's Hospital. DESIGN: Observational comparative effectiveness study. SETTING: Tertiary care hospital. SUBJECTS: Patients ≥21 years with 3+ months of CLBP or 6+ months of intermittent low-back pain. INTERVENTION: All patients were observed for 12 months. OCC patients received care at the integrative clinic (7.3 visits on average over 13 weeks); non-OCC patients received usual care at other clinics of the same hospital. OUTCOME MEASURES: Primary outcomes: change from baseline to 6 months in functional status (Roland Disability Questionnaire [RDQ]) and bothersomeness of pain (BOP). SECONDARY OUTCOMES: change in RDQ and BOP at 3 and 12 months, percentages of patients with clinically meaningful (≥30%) improvements. RESULTS: One hundred fifty-six OCC and 153 non-OCC participants were enrolled; follow-up was 90.4 and 98.0%, respectively, at 12 months. There were substantial differences in baseline characteristics between groups. For RDQ, the adjusted mean group difference was nonsignificant at 6 months; for BOP, the differences were significant, but clinically small. At 12 months, the observed benefit on RDQ was significant and clinically meaningful; for BOP, there were significant, but clinically small differences. Percentages of patients with ≥30% improvements in RDQ were significantly greater in the OCC group only at 12 months, and both 6 and 12 months for BOP. CONCLUSIONS: Baseline characteristics can differ between those who select different sources of healthcare for CLBP. While benefits seen in the OCC versus non-OCC clinics were not large, further evaluation through randomized trials might be warranted to provide a more definitive evaluation.

Participatory Research to Advance Colon Cancer Prevention (PROMPT): Study protocol for a pragmatic trial.

BACKGROUND: Colon cancer is the second leading cause of cancer deaths in the United States. The Participatory Research to Advance Colon Cancer Prevention (PROMPT) study is a collaboration between two research institutions and a federally qualified health center (FQHC). The study seeks to raise colon cancer screening rates using a direct-mail fecal immunochemical testing (FIT) and reminder program in an FQHC serving a predominantly Latino population in California. METHODS: PROMPT is a pragmatic trial enrolling 16 clinics. The study will test automated and live prompts (i.e., alerts, reminders) to a direct-mail FIT program in two phases. In Phase I, we tailored and defined intervention components for the pilot using a community-based participatory research approach called boot camp translation. We then plan to conduct a three-arm patient-randomized comparative effectiveness trial in two pilot clinics to compare 1) automated prompts, 2) live prompts, and 3) a combination of automated plus live prompts to alert and remind patients to complete screening. In Phase II, the adapted best practice intervention will be spread to additional clinics within the FQHC (estimated population 27,000) and assessed for effectiveness. Patient and staff interviews will be conducted to explore receptivity to the program and identify barriers to implementation. DISCUSSION: This pragmatic trial applies innovative approaches to engage diverse stakeholders and will test the effectiveness and spread of a direct-mail plus reminder program. If successful, the program will provide a model for a cost-effective method to raise colon cancer screening rates among Latino patients receiving care in FQHCs. TRIAL REGISTRATION: National Clinical Trial (NCT) Identifier NCT03167125.

Evaluation and implementation of highly challenging balance training in clinical practice for people with Parkinson's disease: protocol for the HiBalance effectiveness-implementation trial.

BACKGROUND: If people with progressive neurological diseases are to avail of evidence-based rehabilitation, programs found effective in randomized controlled trials (RCT's) must firstly be adapted and tested in clinical effectiveness studies as a means of strengthening their evidence base. This paper describes the protocol for an effectiveness-implementation trial that will assess the clinical effectiveness of a highly challenging balance training program (the HiBalance program) for people with mild-moderate Parkinson's disease (PD) while simultaneously collecting data concerning the way in which the program is implemented. The HiBalance program is systemically designed to target balance impairments in PD and has been shown effective at improving balance control and gait in a previous RCT. Study aims are to i) determine the effectiveness of the adapted HiBalance program on performance and self-rated outcomes such as balance control, gait and physical activity level ii) conduct a process evaluation of program implementation at the various clinics iii) determine barriers and facilitators to program implementation in these settings. METHODS: This effectiveness-implementation type 1 hybrid study will use a non-randomized controlled design with consecutive inclusion of people with PD at multiple clinical sites. A mixed method approach will be used to collect clinical effectiveness data and process evaluation data which is both quantitative and qualitative in nature. The consolidated framework for implementation research (CFIR) will be used to guide the planning and collection of data concerning implementation barriers and facilitators. The HiBalance program will be provided by physical therapists as a part of standard rehabilitation care at the clinical sites, while the evaluation of the implementation process will be performed by the research group and funded by research grants. DISCUSSION: An effectiveness-implementation study design benefits patients by speeding up the process of translating findings from research settings to routine health care. Findings from this study will also be highly relevant for those working with neurological rehabilitation when faced with decisions concerning the translation of training programs from efficacy studies to everyday clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov march 2016, NCT02727478 .

Open discectomy vs microdiscectomy for lumbar disc herniation - a protocol for a pragmatic comparative effectiveness study.

Introduction:  Since the introduction of lumbar microdiscectomy in the 1970's, many studies have attempted to compare the effectiveness of this method with that of standard open discectomy with conflicting results. This observational study is designed to compare the relative effectiveness of microdiscectomy (MD) with open discectomy (OD) for treating lumbar disc herniation, -within a large cohort, recruited from daily clinical practice. Methods and analysis:   This study will include patients registered in the Norwegian Registry for Spine Surgery (NORspine). This clinical registry collects prospective data, including preoperative and postoperative outcome measures as well as individual and demographic parameters. The primary outcome is change in Oswestry disability index between baseline and 12 months after surgery. Secondary outcome measures are improvement of leg pain and changes in health related quality of life measured by the Euro-Qol-5D between baseline and 12 months after surgery, complications to surgery, duration of surgical procedures and length of hospital stay.

A Real Life Clinical Practice of Neurologists in the Ambulatory Setting in Thailand: A Pragmatic Study.

The burden of neurological disorders is high in developing countries. Real life data from neurologists as to how they practice in Thailand are limited in literature. Practices of neurologists in a university hospital clinical setting in Thailand were studied. A prospective study was performed at the ambulatory neurology clinic, Khon Kaen University Hospital, between 1 February and 31 October 2009. The following data were recorded: numbers of patients, characteristics of patients, consultation notes, and time spent for each patient. There were three neurologists, each of whom ran one afternoon clinic, once a week. There were 6137 visits during the 9 months, with an average of 681 visits per month. The total number of patients was 2834. The three most common diseases were cerebrovascular diseases (33%), epilepsy (16%), and movement disorders (non-Parkinson's disease, 12%). Neurologists spent an average of 6.34 minutes per patient. In conclusion, neurologists in medical schools have limited time to take care of each patient. Several strategies are needed in medical education and neurology training to improve the quality of care.

Strategies and Opportunities to STOP Colon Cancer in Priority Populations: design of a cluster-randomized pragmatic trial.

BACKGROUND: Colorectal cancer is the second-leading cause of cancer deaths in the United States. The Strategies and Opportunities to Stop Colorectal Cancer (STOP CRC) in Priority Populations study is a pragmatic trial and a collaboration between two research institutions and a network of more than 200 safety net clinics. The study will assess the effectiveness of a system-based intervention designed to improve the rates of colorectal-cancer screening using fecal immunochemical testing (FIT) in federally qualified health centers in Oregon and Northern California. MATERIAL AND METHODS: STOP CRC is a cluster-randomized comparative-effectiveness pragmatic trial enrolling 26 clinics. Clinics will be randomized to one of two arms. Clinics in the intervention arm (1) will use an automated, data-driven, electronic health record-embedded program to identify patients due for colorectal screening and mail FIT kits (with pictographic instructions) to them; (2) will conduct an improvement process (e.g. Plan-Do-Study-Act) to enhance the adoption, reach, and effectiveness of the program. Clinics in the control arm will provide opportunistic colorectal-cancer screening to patients at clinic visits. The primary outcomes are: proportion of age- and screening-eligible patients completing a FIT within 12months; and cost, cost-effectiveness, and return on investment of the intervention. CONCLUSIONS: This large-scale pragmatic trial will leverage electronic health record information and existing clinic staff to enroll a broad range of patients, including many with historically low colorectal-cancer screening rates. If successful, the program will provide a model for a cost-effective and scalable method to raise colorectal-cancer screening rates.

Maintaining patency in totally implantable venous access devices (TIVAD): a time-to-event analysis of different lock irrigation intervals.

PURPOSE: To evaluate the effectiveness of irrigating totally implantable venous access devices (TIVADs) every eight weeks instead of every four in maintaining the patency of the device. METHODS: An explorative, pragmatic, prospective study design was conducted in two day hospital centres located in the northeast of Italy, from January 2011 to September 2012. Twenty patients who had skipped an appointment and were thus washing their TIVAD every eight weeks (exposed) were included, as were 17 patients following the typical wash regimen of every four weeks (controls). TIVAD occlusion-defined as the inability of the device to aspirate blood and/or the inability to properly irrigate the device-was the principal study end-point. RESULTS: A total of six occlusions were documented in six patients. Four cases were observed among the exposed group (4/20; 20.0%), while two were observed among the control group (2/17; 11.7%). No statistically significant differences were observed in the occurrence of occlusion between the groups (RR: 1.29, 95%CI: 0.67-2.50, p = 0.49). No statistically significant differences emerged between groups in the time that elapsed from study inclusion to occlusion occurrence according to the time-to-event analysis performed using the Kaplan-Meier estimation model (Log Rank [Mantel-Cox] = χ(2) 0.284, df 1, p = 0.594). CONCLUSIONS: Within the limitations of the study which should be addressed with further research based on double-blinded randomised clinical trials, postponing the irrigation regimen of TIVADs to eight weeks seems to be sufficient to maintain device patency.