IntroductionIleus is a common and distressing condition characterised by gut dysfunction after surgery. While a number of interventions have aimed to curtail its impact on patients and healthcare ...systems, ileus is still an unmet challenge. Electrical stimulation of the vagus nerve is a promising new treatment due to its role in modulating the neuro-immune axis through a novel anti-inflammatory reflex. The protocol for a feasibility study of non-invasive vagus nerve stimulation (nVNS), and a programme of mechanistic and qualitative studies, is described.Methods and analysisThis is a participant-blinded, parallel-group, randomised, sham-controlled feasibility trial (IDEAL Stage 2b) of self-administered nVNS. One hundred forty patients planned for elective, minimally invasive, colorectal surgery will be randomised to four schedules of nVNS before and after surgery. Feasibility outcomes include assessments of recruitment and attrition, adequacy of blinding and compliance to the intervention. Clinical outcomes include bowel function and length of hospital stay. A series of mechanistic substudies exploring the impact of nVNS on inflammation and bowel motility will inform the design of the final stimulation schedule. Semistructured interviews with participants will explore experiences and perceptions of the intervention, while interviews with patients who decline participation will explore barriers to recruitment.Ethics and disseminationThe protocol has been approved by the Tyne and Wear South National Health Service (NHS) Research Ethics Committee (19/NE/0217) on 2 July 2019. Feasibility, mechanistic and qualitative findings will be disseminated to national and international partners through peer-reviewed publications, academic conferences, social media channels and stakeholder engagement activities. The findings will build a case for or against progression to a definitive randomised assessment as well as informing key elements of study design.Trial registration numberISRCTN62033341.
Aim
Vagus nerve stimulation has emerged as a plausible intervention to reduce ileus after surgery. An early development study was undertaken with the aim of exploring the feasibility of ...self‐administered, noninvasive vagus nerve stimulation (nVNS) after major colorectal surgery.
Method
A parallel‐group, randomized controlled trial was undertaken between 1 January 2018 and 31 August 2019. Forty patients undergoing colorectal surgery for malignancy were allocated equally to Sham and Active stimulation groups. Electrical vagus nerve stimulation was self‐administered bilaterally over the cervical surface landmarks for 5 days before and after surgery. Outcomes of interest were postoperative complications and adverse events measured using the Clavien–Dindo scale, treatment compliance, device usability according to the Systems Usability Scale (SUS) and clinical measures of bowel recovery.
Results
Forty patients were randomized and one withdrew, leaving 39 for analysis. Postoperative complications occurred in 9/19 (47.4%) participants receiving Sham and 11/20 (55.0%) receiving Active stimulation and were mostly minor. Compliance with treatment before surgery was 4.7 ± 0.9 days out of 5 days in the Sham group and 4.7 ± 1.1 in the Active group. Compliance with treatment after surgery was 4.1 ± 1.1 and 4.4 ± 1.5, respectively. Participants considered the intervention to be ‘acceptable’ according to the SUS. The most prominent differences in bowel recovery were days to first flatus (2.35 ± 1.32 vs 1.65 ± 0.88) and tolerance of solid diet (2.18 ± 2.21 vs 1.75 ± 0.91) for Sham and Active groups, respectively.
Conclusion
This study supports the safety, treatment compliance and usability of self‐administered nVNS in patients undergoing major colorectal surgery.
Aim
Adhesive small bowel obstruction (ASBO) is a common surgical emergency condition. Research in the field is plentiful; however, inconsistency in outcome reporting makes comparisons challenging. ...The aim of this study was to define a core outcome set (COS) for studies of ASBO.
Methods
The long list of outcomes was identified through systematic review, and focus groups across different geographical regions. A modified Delphi consensus exercise of three rounds was undertaken with stakeholder groups (patients and clinicians). Items were rated on a 9‐point Likert scale. Items exceeding 70% rating at 7–9 were passed to the consensus meeting. New item proposals were invited in round 1. Individualised feedback on prior voting compared to other participants was provided. An international consensus meeting was convened to ratify the final COS.
Results
In round 1, 56 items were rated by 118 respondents. A total of 18 items reached consensus, and respondents proposed an additional 10 items. Round 2 was completed by 90 respondents, and nine items achieved consensus. In round 3, 80 surveys were completed; one item achieved consensus, and five borderline items were identified. The final COS included 26 outcomes, mapped to the following domains: Interventions, need for stoma, septic complications, return of gut function, patient reported outcomes, and recurrence of obstruction, as well as mortality, failure to rescue, and time to resolution.
Conclusion
This COS should be used in future studies in the treatment of adhesive SBO. Further studies to define a core measurement set are needed to identify the optimum tools to measure each outcome.
Implementation trials aim to test the effects of implementation strategies on the adoption, integration or uptake of an evidence-based intervention within organisations or settings. Feasibility and ...pilot studies can assist with building and testing effective implementation strategies by helping to address uncertainties around design and methods, assessing potential implementation strategy effects and identifying potential causal mechanisms. This paper aims to provide broad guidance for the conduct of feasibility and pilot studies for implementation trials.
We convened a group with a mutual interest in the use of feasibility and pilot trials in implementation science including implementation and behavioural science experts and public health researchers. We conducted a literature review to identify existing recommendations for feasibility and pilot studies, as well as publications describing formative processes for implementation trials. In the absence of previous explicit guidance for the conduct of feasibility or pilot implementation trials specifically, we used the effectiveness-implementation hybrid trial design typology proposed by Curran and colleagues as a framework for conceptualising the application of feasibility and pilot testing of implementation interventions. We discuss and offer guidance regarding the aims, methods, design, measures, progression criteria and reporting for implementation feasibility and pilot studies.
This paper provides a resource for those undertaking preliminary work to enrich and inform larger scale implementation trials.
Abstract Objective Implementation science is an emerging area in physical activity (PA) research. We sought to establish the current state of the evidence related to implementation of school-based PA ...models to explore 1) the relationship between implementation and health outcomes, and 2) factors that influence implementation. Methods We searched 7 electronic databases (1995–2014) and included controlled studies of school-based PA programmes for healthy youth (6–18 y) measuring at least one physical health-related outcome. For objective 1, studies linked implementation level to student-level health outcome(s). For objective 2, studies reported factors associated with implementation. Results There was substantial variability in how health outcomes and implementation were assessed. Few studies linked implementation and health outcomes (n = 15 interventions). Most (11/15) reported a positive relationship between implementation and at least one health outcome. Implementation factors were reported in 29 interventions. Of 22 unique categories, time was the most prevalent influencing factor followed by resource availability/quality and supportive school climate. Conclusions Implementation evaluation supports scale-up of effective school-based PA interventions and thus population-level change. Our review serves as a call to action to 1) address the link between implementation and outcome within the school-based PA literature and 2) improve and standardize definitions and measurement of implementation.
From 4 to 7 April 2016, 24 researchers from 8 countries and from a variety of academic disciplines gathered in Snekkersten, Denmark, to reach evidence-based consensus about physical activity in ...children and youth, that is, individuals between 6 and 18 years. Physical activity is an overarching term that consists of many structured and unstructured forms within school and out-of-school-time contexts, including organised sport, physical education, outdoor recreation, motor skill development programmes, recess, and active transportation such as biking and walking. This consensus statement presents the accord on the effects of physical activity on children's and youth's fitness, health, cognitive functioning, engagement, motivation, psychological well-being and social inclusion, as well as presenting educational and physical activity implementation strategies. The consensus was obtained through an iterative process that began with presentation of the state-of-the art in each domain followed by plenary and group discussions. Ultimately, Consensus Conference participants reached agreement on the 21-item consensus statement.
Flow-mediated dilation (FMD) provides a valid bioassay of vascular function in humans. Although water immersion induces hemodynamic effects that modify brachial artery shear stress, it is unclear ...whether water-based exercise modifies FMD. We hypothesized that exercise in 32°C water would decrease brachial artery shear and FMD relative to land-based exercise, whereas exercise in 38°C would increase brachial shear and FMD. Ten healthy participants (8 males; 23.9 ± 3.3 yr) completed 30 min of resistance-matched cycle exercise in three separate conditions: on land and in 32°C and 38°C water. Brachial artery shear rate area under the curve (SRAUC) was measured throughout each condition, with FMD measured pre- and postexercise. Brachial SRAUC increased during exercise in all conditions and was highest across the 38°C condition compared with Land and 32°C conditions (38°C: 27,507 ± 8,350 vs. Land: 9,908 ± 4,738 vs. 32°C: 13,840 ± 5,861 1/s,
< 0.001). Retrograde diastolic shear was greater during 32°C than both Land and 38°C conditions (32°C:-3,869 ± 2,198 vs. Land:-1,602 ± 1,334 vs. 32°C:-1,036 ± 1,754,
< 0.01). FMD increased as a result of 38°C (6.2 ± 1.9 vs. 8.5 ± 2.7%,
= 0.03), with no change in the Land exercise (6.3 ± 2.4 vs. 7.7 ± 2.4%,
= 0.10) or 32°C condition (6.4 ± 3.2 vs. 6.7 ± 3.2%,
= 0.99). Our findings indicate that cycle exercise in hot water attenuates retrograde shear, increases antegrade shear, and FMD. Exercise in 32°C water induces central hemodynamic changes relative to land-based exercise, but these do not translate to increases in FMD in either condition, likely due to the impact of increased retrograde shear. Our findings indicate that modification of shear has direct acute impacts on endothelial function in humans.
Purpose
Recent studies suggest that episodic increases in cerebral blood flow (CBF) may contribute to the improvement in brain health associated with exercise training. Optimising CBF during exercise ...may enhance this benefit. Water immersion in ~ 30–32 °C augments CBF at rest and during exercise; however, the impact of water temperature on the CBF response has not been investigated. We hypothesised that cycle ergometry in water would increase CBF compared to land-based exercise, and that warm water would attenuate the CBF benefits.
Methods
Eleven young heathy participants (nine males; 23.8 ± 3.1 yrs) completed 30 min of resistance-matched cycle exercise in three separate conditions; non-immersion (Land), 32 °C and 38 °C water immersion up to the level of the waist. Middle cerebral artery velocity (MCAv), blood pressure, and respiratory measures were assessed throughout the exercise bouts.
Results
Core temperature was significantly higher in the 38 °C immersion than 32 °C (+ 0.84 ± 0.24 vs + 0.04 ± 0.16,
P
< 0.001), whilst mean arterial pressure was lower during 38 °C exercise compared to Land (84 ± 8 vs 100 ± 14 mmHg,
P
< 0.001) and 32 °C (92 ± 9,
P
= 0.03). MCAv was higher in 32 °C immersion compared to the Land and 38 °C conditions throughout the exercise bout (68 ± 10 vs 64 ± 11 vs 62 ± 12 cm/s,
P
= 0.03 and
P
= 0.02, respectively).
Conclusion
Our findings suggest that cycle exercise in warm water attenuates the beneficial impact of water immersion on CBF velocity due to redistribution of blood flow to subserve thermoregulatory demand. Our findings suggest that, whilst water-based exercise can have beneficial effects on cerebrovascular function, water temperature is a key determinant of this benefit.
Objective To evaluate the impact of translating into a large US health plan, the Transitional Care Model (TCM), an evidence‐based approach to address the needs of chronically ill older adults ...throughout acute episodes of illness.
Methods A prospective, quasi‐experimental study of 172 at‐risk Aetna Medicare Advantage members in the mid‐Atlantic region who received the TCM. A baseline and post‐intervention (average of 2 months) comparison of enrolees' health status and quality of life was conducted. Member and physician satisfaction were assessed within 1 month post intervention. Health resource utilization and cost outcomes were compared to a matched control group of Aetna members at multiple intervals through 1 year.
Results Improvements in all health status and quality of life measures were observed post‐ intervention compared to pre‐intervention. Among 155 stringently matched pairs, a significant decrease in number of re‐hospitalizations (45 vs. 60, P < 0.041) and total hospital days (252 vs. 351, P < 0.032) were observed at 3 months. Reductions in other utilization outcomes or time points were not statistically significant. The TCM was associated with a short‐term decrease of $439 per member per month in total health care costs at 3 months and cumulative per member savings of $2170 at 1 year (P < 0.037).
Conclusions Findings demonstrate that a rigorously tested model of transitional care for chronically ill older adults can be successfully translated into a real‐world organization and achieve higher value.
There is an emerging paradigm that the human microbiome is central to many aspects of health and may have a role in preventing enteric infection. Entamoeba histolytica is a major cause of amebic ...diarrhea in developing countries. It colonizes the colon lumen in close proximity to the gut microbiota. Interestingly, not all individuals are equally susceptible to E. histolytica infection. Therefore, as the microbiota is highly variable within individuals, we sought to determine if a component of the microbiota could regulate susceptibility to infection. In studies utilizing a murine model, we demonstrated that colonization of the gut with the commensal Clostridia-related bacteria known as segmented filamentous bacteria (SFB) is protective during E. histolytica infection. SFB colonization in this model was associated with elevated cecal levels of interleukin 17A (IL-17A), dendritic cells, and neutrophils. Bone marrow-derived dendritic cells (BMDCs) from SFB-colonized mice had higher levels of IL-23 production in response to stimulation with trophozoites. Adoptive transfer of BMDCs from an SFB(+) to an SFB(-) mouse was sufficient to provide protection against E. histolytica. IL-17A induction during BMDC transfer was necessary for this protection. This work demonstrates that intestinal colonization with a specific commensal bacterium can provide protection during amebiasis in a murine model. Most importantly, this work demonstrates that the microbiome can mediate protection against an enteric infection via extraintestinal effects on bone marrow-derived dendritic cells.
Entamoeba histolytica is the causative agent of amebiasis, an infectious disease that contributes significantly to morbidity and mortality due to diarrhea in the developing world. We showed in a murine model that colonization with the commensal members of the Clostridia known as SFB provides protection against E. histolytica and that dendritic cells from SFB-colonized mice alone can recapitulate protection. Understanding interactions between enteropathogens, commensal intestinal bacteria, and the mucosal immune response, including dendritic cells, will help in the development of effective treatments for this disease and other infectious and inflammatory diseases. The demonstration of immune-mediated protection due to communication from the microbiome to the bone marrow represents an emerging field of study that will yield unique approaches to the development of these treatments.
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