Efficacy of Prehabilitation Including Exercise on Postoperative Outcomes Following Abdominal Cancer Surgery: A Systematic Review and Meta-Analysis

OBJECTIVE: This systematic review set out to identify, evaluate and synthesise the evidence examining the effect of prehabilitation including exercise on postoperative outcomes following abdominal cancer surgery. METHODS: Five electronic databases (MEDLINE 1946-2020, EMBASE 1947-2020, CINAHL 1937-2020, PEDro 1999-2020, and Cochrane Central Registry of Controlled Trials 1991-2020) were systematically searched (until August 2020) for randomised controlled trials (RCTs) that investigated the effects of prehabilitation interventions in patients undergoing abdominal cancer surgery. This review included any form of prehabilitation either unimodal or multimodal that included whole body and/or respiratory exercises as a stand-alone intervention or in addition to other prehabilitation interventions (such as nutrition and psychology) compared to standard care. RESULTS: Twenty-two studies were included in the systematic review and 21 studies in the meta-analysis. There was moderate quality of evidence that multimodal prehabilitation improves pre-operative functional capacity as measured by 6 min walk distance (Mean difference [MD] 33.09 metres, 95% CI 17.69–48.50; p = <0.01) but improvement in cardiorespiratory fitness such as preoperative oxygen consumption at peak exercise (VO2 peak; MD 1.74 mL/kg/min, 95% CI −0.03–3.50; p = 0.05) and anaerobic threshold (AT; MD 1.21 mL/kg/min, 95% CI −0.34–2.76; p = 0.13) were not significant. A reduction in hospital length of stay (MD 3.68 days, 95% CI 0.92–6.44; p = 0.009) was observed but no effect was observed for postoperative complications (Odds Ratio [OR] 0.81, 95% CI 0.55–1.18; p = 0.27), pulmonary complications (OR 0.53, 95% CI 0.28–1.01; p = 0.05), hospital re-admission (OR 1.07, 95% CI 0.61–1.90; p = 0.81) or postoperative mortality (OR 0.95, 95% CI 0.43–2.09, p = 0.90). CONCLUSION: Multimodal prehabilitation improves preoperative functional capacity with reduction in hospital length of stay. This supports the need for ongoing research on innovative cost-effective prehabilitation approaches, research within large multicentre studies to verify this effect and to explore implementation strategies within clinical practise

Facilitators and Barriers to Person-centred Care in Child and Young People Mental Health Services: A Systematic Review

Implementation of person-centred care has been widely advocated across various health settings and patient populations, including recent policy for child and family services. Nonetheless, evidence suggests that service users are rarely involved in decision-making, whilst their preferences and goals may be often unheard. The aim of the present research was to systematically review factors influencing person-centred care in mental health services for children, young people and families examining perspectives from professionals, service users and carers. This was conducted according to best practice guidelines, and seven academic databases were searched. Overall, 23 qualitative studies were included. Findings from the narrative synthesis of the facilitators and barriers are discussed in light of a recently published systematic review examining person-centred care in mental health services for adults. Facilitators and barriers were broadly similar across both settings. Training professionals in person-centred care, supporting them to use it flexibly to meet the unique needs of service users whilst also being responsive to times when it may be less appropriate and improving both the quantity and quality of information for service users and carers are key recommendations to facilitate person-centred care in mental health services with children, young people and families

What approaches for promoting shared decision-making are used in child mental health? A scoping review

OBJECTIVE: Whilst the benefits of shared decision-making (SDM) have been promoted across different health settings, its implementation is complex, particularly for children and young people with mental health difficulties. The aim of this scoping review was to identify and describe SDM approaches (tools, techniques, and technologies) used in child and youth mental health. METHOD: Electronic databases and grey literature were searched. Papers were included if they satisfied these criteria: English language; described an SDM approach (tool, technique, or technology); included sufficient detail on the SDM approach for quality assessment; did not use only a questionnaire to provide feedback on SDM or related concepts (e.g., therapeutic alliance) without another SDM approach; child or adolescent population (up to 18 years); carers of children or adolescents; and mental health setting. Screening and data extraction were performed by two co-authors, and each included record was quality assessed against a set of essential ingredients of SDM identified by previous studies. RESULTS: Of the 8,153 initial results, 22 were eligible for final inclusion. These could be grouped into six approaches: therapeutic techniques, psychoeducational information, decision aids, action planning or goal setting, discussion prompts, and mobilizing patients to engage. The quality of approaches identified ranged from one to seven of the nine essential elements of SDM. CONCLUSION: Evidence suggests that a range of approaches are being developed to support SDM in child and youth mental health. Rigorous research evaluating the effectiveness of these approaches is urgently needed, particularly from the perspective of children and young people. Key practitioner message This scoping review is the first to categorise and outline different shared decision-making (SDM) approaches (tools, techniques, and technologies) as suggested by The Health Foundation and has identified six distinct approaches used in child and youth mental health Each of the six extant SDM approaches has been qualitatively assessed using a most comprehensive list of essential elements of SDM available so far in the area Whilst evidence suggests that a range of approaches is being developed to support SDM in child and youth mental health, rigorous research evaluating the effectiveness of these approaches is largely lacking The current review may serve as a useful guideline for those institutions and health service organisations that are keen to implement an SDM approach for children and young people in their care Further research is urgently needed to establish the effect of SDM on clinical outcomes, as well as whether such approaches are cost effective

Lipid-peptide nanocomplexes for mRNA delivery in vitro and in vivo

Despite recent advances in the field of mRNA therapy, the lack of safe and efficacious delivery vehicles with pharmaceutically developable properties remains a major limitation. Here, we describe the systematic optimisation of lipid-peptide nanocomplexes for the delivery of mRNA in two murine cancer cell types, B16-F10 melanoma and CT26 colon carcinoma as well as NCI-H358 human lung bronchoalveolar cells. Different combinations of lipids and peptides were screened from an original lipid-peptide nanocomplex formulation for improved luciferase mRNA transfection in vitro by a multi-factorial screening approach. This led to the identification of key structural elements within the nanocomplex associated with substantial improvements in mRNA transfection efficiency included alkyl tail length of the cationic lipid, the fusogenic phospholipid, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), and cholesterol. The peptide component (K16GACYGLPHKFCG) was further improved by the inclusion of a linker, RVRR, that is cleavable by the endosomal enzymes cathepsin B and furin, and a hydrophobic motif (X-S-X) between the mRNA packaging (K16) and receptor targeting domains (CYGLPHKFCG). Nanocomplex transfections of a murine B16-F10 melanoma tumour supported the inclusion of cholesterol for optimal transfection in vivo as well as in vitro. In vitro transfections were also performed with mRNA encoding interleukin-15 as a potential immunotherapy agent and again, the optimised formulation with the key structural elements demonstrated significantly higher expression than the original formulation. Physicochemical characterisation of the nanocomplexes over time indicated that the optimal formulation retained biophysical properties such as size, charge and mRNA complexation efficiency for 14 days upon storage at 4 °C without the need for additional stabilising agents. In summary, we have developed an efficacious lipid-peptide nanocomplex with promising pharmaceutical development properties for the delivery of therapeutic mRNA

Young People Who Meaningfully Improve Are More Likely to Mutually Agree to End Treatment

Objective: Symptom improvement is often examined as an indicator of a good outcome of accessing mental health services. However, there is little evidence of whether symptom improvement is associated with other indicators of a good outcome, such as a mutual agreement to end treatment. The aim of this study was to examine whether young people accessing mental health services who meaningfully improved were more likely to mutually agree to end treatment. / Methods: Multilevel multinomial regression analysis controlling for age, gender, ethnicity, and referral source was conducted on N = 8,995 episodes of care [Female = 5,469, 61%; meanAge = 13.66 (SD = 2.87) years] using anonymised administrative data from young people's mental health services. / Results: Compared to young people with no change in mental health difficulties, those showing positive meaningful changes in mental health difficulties were less likely to have case closure due to non-mutual agreement (Odds Ratio or OR = 0.58, 95% Confidence Interval or CI = 0.50–0.61). Similarly, they were less likely to transfer (OR = 0.61, 95% CI = 0.49–0.74) or end treatment for other reasons (OR = 0.59, 95% CI = 0.50–0.70) than by case closure due to mutual agreement. / Conclusion: The findings suggest that young people accessing mental health services whose symptoms meaningfully improve are more likely to mutually agree to end treatment, adding to the evidence that symptom improvement may be appropriate to examine as an indicator of a good outcome of accessing mental health services

The Depression: Online Therapy Study (D:OTS)—A Pilot Study of an Internet-Based Psychodynamic Treatment for Adolescents with Low Mood in the UK, in the Context of the COVID-19 Pandemic

Introduction: Face-to-face therapy is unavailable to many young people with mental health difficulties in the UK. Internet-based treatments are a low-cost, flexible, and accessible option that may be acceptable to young people. This pilot study examined the feasibility, acceptability and effectiveness of an English-language adaptation of internet-based psychodynamic treatment (iPDT) for depressed adolescents, undertaken during the COVID-19 pandemic in the UK. Methods: A single-group, uncontrolled design was used. A total of 23 adolescents, 16–18 years old and experiencing depression, were recruited to this study. Assessments were made at baseline and end of treatment, with additional weekly assessments of depression and anxiety symptoms. Results: Findings showed that it was feasible to recruit to this study during the pandemic, and to deliver the iPDT model with a good level of treatment acceptability. A statistically significant reduction in depressive symptoms and emotion dysregulation was found, with large effect size, by the end of treatment. Whilst anxiety symptoms decreased, this did not reach statistical significance. Conclusions: The findings suggest that this English-language adaptation of iPDT, with some further revisions, is feasible to deliver and acceptable for adolescents with depression. Preliminary data indicate that iPDT appears to be effective in reducing depressive symptoms in adolescents

Implications for post critical illness trial design: sub-phenotyping trajectories of functional recovery among sepsis survivors.

This is a post-peer-review, pre-copyedit version of an article published in Critical Care. The final authenticated version is available online at: https://doi.org/10.1186/s13054-020-03275-wBACKGROUND: Patients who survive critical illness suffer from a significant physical disability. The impact of rehabilitation strategies on health-related quality of life is inconsistent, with population heterogeneity cited as one potential confounder. This secondary analysis aimed to (1) examine trajectories of functional recovery in critically ill patients to delineate sub-phenotypes and (2) to assess differences between these cohorts in both clinical characteristics and clinimetric properties of physical function assessment tools. METHODS: Two hundred ninety-one adult sepsis survivors were followed-up for 24 months by telephone interviews. Physical function was assessed using the Physical Component Score (PCS) of the Short Form-36 Questionnaire (SF-36) and Activities of Daily Living and the Extra Short Musculoskeletal Function Assessment (XSFMA-F/B). Longitudinal trajectories were clustered by factor analysis. Logistical regression analyses were applied to patient characteristics potentially determining cluster allocation. Responsiveness, floor and ceiling effects and concurrent validity were assessed within clusters. RESULTS: One hundred fifty-nine patients completed 24 months of follow-up, presenting overall low PCS scores. Two distinct sub-cohorts were identified, exhibiting complete recovery or persistent impairment. A third sub-cohort could not be classified into either trajectory. Age, education level and number of co-morbidities were independent determinants of poor recovery (AUROC 0.743 ((95%CI 0.659-0.826), p < 0.001). Those with complete recovery trajectories demonstrated high levels of ceiling effects in physical function (PF) (15%), role physical (RP) (45%) and body pain (BP) (57%) domains of the SF-36. Those with persistent impairment demonstrated high levels of floor effects in the same domains: PF (21%), RP (71%) and BP (12%). The PF domain demonstrated high responsiveness between ICU discharge and at 6 months and was predictive of a persistent impairment trajectory (AUROC 0.859 (95%CI 0.804-0.914), p < 0.001). CONCLUSIONS: Within sepsis survivors, two distinct recovery trajectories of physical recovery were demonstrated. Older patients with more co-morbidities and lower educational achievements were more likely to have a persistent physical impairment trajectory. In regard to trajectory prediction, the PF score of the SF-36 was more responsive than the PCS and could be considered for primary outcomes. Future trials should consider adaptive trial designs that can deal with non-responders or sub-cohort specific outcome measures more effectively

Implications of ICU triage decisions on patient mortality: a cost-effectiveness analysis

INTRODUCTION: Intensive care is generally regarded as expensive, and as a result beds are limited. This has raised serious questions about rationing when there are insufficient beds for all those referred. However, the evidence for the cost effectiveness of intensive care is weak and the work that does exist usually assumes that those who are not admitted do not survive, which is not always the case. Randomised studies of the effectiveness of intensive care are difficult to justify on ethical grounds; therefore, this observational study examined the cost effectiveness of ICU admission by comparing patients who were accepted into ICU after ICU triage to those who were not accepted, while attempting to adjust such comparison for confounding factors. METHODS: This multi-centre observational cohort study involved 11 hospitals in 7 EU countries and was designed to assess the cost effectiveness of admission to intensive care after ICU triage. A total of 7,659 consecutive patients referred to the intensive care unit (ICU) were divided into those accepted for admission and those not accepted. The two groups were compared in terms of cost and mortality using multilevel regression models to account for differences across centres, and after adjusting for age, Karnofsky score and indication for ICU admission. The analyses were also stratified by categories of Simplified Acute Physiology Score (SAPS) II predicted mortality (40%). Cost effectiveness was evaluated as cost per life saved and cost per life-year saved. RESULTS: Admission to ICU produced a relative reduction in mortality risk, expressed as odds ratio, of 0.70 (0.52 to 0.94) at 28 days. When stratified by predicted mortality, the odds ratio was 1.49 (0.79 to 2.81), 0.7 (0.51 to 0.97) and 0.55 (0.37 to 0.83) for 40% predicted mortality, respectively. Average cost per life saved for all patients was $103,771 (€82,358) and cost per life-year saved was$7,065 (€5,607). These figures decreased substantially for patients with predicted mortality higher than 40%, $60,046 (€47,656) and$4,088 (€3,244), respectively. Results were very similar when considering three-month mortality. Sensitivity analyses performed to assess the robustness of the results provided findings similar to the main analyses. CONCLUSIONS: Not only does ICU appear to produce an improvement in survival, but the cost per life saved falls for patients with greater severity of illness. This suggests that intensive care is similarly cost effective to other therapies that are generally regarded as essential

Predicting mental health improvement and deterioration in a large community sample of 11- to 13-year-olds

Multivariate analysis of psychological dat