Risultati per: Cardio-oncology: rivista open access

Introduction
Laparoscopic colectomy has been widely used clinically due to its minimally invasive advantages, and many studies have also demonstrated its safety and efficacy. However, the efficacy of laparoscopic left hemicolectomy remains unclear due to the differences in pathogenesis and surgical details between left and right colon cancers. Therefore, we plan to conduct a systematic review and meta-analysis to investigate whether laparoscopic techniques can be safely used in left hemicolectomy.

Method and analysis
This meta-analysis protocol will be completed and reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines. A systematic search was performed for all articles related to laparoscopic left hemicolectomy in PubMed, Web of Science, Medline, EMBASE and the Cochrane Library from inception to 5 November 2021. Article screening and data extraction were performed independently by two authors and cross-checked after completion. The literature to be included will use corresponding tools for bias risk assessment. Subgroup analyses and sensitivity analyses will be used to explore potential heterogeneity.

Ethics and dissemination
Because this systematic review is based on studies with published results and does not involve intervention in patients, no ethical review is required. The results of this study will be published in a peer-reviewed journal.

PROSPERO registration number
CRD42022291526.

Introduction
At least one in four people treated by the primary care improving access to psychological therapies (IAPT) programme in England experiences distressing psychotic experiences (PE) in addition to common mental disorder (CMD). These individuals are less likely to achieve recovery. IAPT services do not routinely screen for nor offer specific treatments for CMD including PE. The Tailoring evidence-based psychological therapY for People with common mental disorder including Psychotic EXperiences study will evaluate the clinical and cost-effectiveness of an enhanced training for cognitive behavioural therapists that aims to address this clinical gap.

Methods and analysis
This is a multisite, stepped-wedge cluster randomised controlled trial. The setting will be IAPT services within three mental health trusts. The participants will be (1) 56–80 qualified IAPT cognitive behavioural therapists and (2) 600 service users who are triaged as appropriate for cognitive behavioural therapy in an IAPT service and have PE according to the Community Assessment of Psychic Experiences—Positive 15-items Scale. IAPT therapists will be grouped into eight study clusters subsequently randomised to the control-intervention sequence. We will obtain pseudonymous clinical outcome data from IAPT clinical records for eligible service users. We will invite service users to complete health economic measures at baseline, 3, 6, 9 and 12-month follow-up. The primary outcome will be the proportion of patients with common mental disorder psychotic experiences who have recovered by the end of treatment as measured by the official IAPT measure for recovery.

Ethics and dissemination
The study received the following approvals: South Central—Berkshire Research Ethics Committee on 28 April 2020 (REC reference 20/SC/0135) and Health Research Authority (HRA) on 23 June 2020. An amendment was approved by the Ethics Committee on 01 October 2020 and HRA on 27 October 2020. Results will be made available to patients and the public, the funders, stakeholders in the IAPT services and other researchers.

Trial registration number
ISRCTN93895792.

Introduction
Postoperative delirium is common in older cardiac surgery patients and associated with negative short-term and long-term outcomes. The alpha-2-adrenergic receptor agonist dexmedetomidine shows promise as prophylaxis and treatment for delirium in intensive care units (ICU) and postoperative settings. Clonidine has similar pharmacological properties and can be administered both parenterally and orally. We aim to study whether repurposing of clonidine can represent a novel treatment option for delirium, and the possible effects of dexmedetomidine and clonidine on long-term cognitive trajectories, motor activity patterns and biomarkers of neuronal injury, and whether these effects are associated with frailty status.

Methods and analysis
This five-centre, double-blind randomised controlled trial will include 900 cardiac surgery patients aged 70+ years. Participants will be randomised 1:1:1 to dexmedetomidine or clonidine or placebo. The study drug will be given as a continuous intravenous infusion from the start of cardiopulmonary bypass, at a rate of 0.4 µg/kg/hour. The infusion rate will be decreased to 0.2 µg/kg/hour postoperatively and be continued until discharge from the ICU or 24 hours postoperatively, whichever happens first.
Primary end point is the 7-day cumulative incidence of postoperative delirium (Diagnostic and Statistical Manual of Mental Disorders, fifth edition). Secondary end points include the composite end point of coma, delirium or death, in addition to delirium severity and motor activity patterns, levels of circulating biomarkers of neuronal injury, cognitive function and frailty status 1 and 6 months after surgery.

Ethics and dissemination
This trial is approved by the Regional Committee for Ethics in Medical Research in Norway (South-East Norway) and by the Norwegian Medicines Agency. Dissemination plans include publication in peer-reviewed medical journals and presentation at scientific meetings.

Trial registration number
NCT05029050.

Objectives
Through analysis of claims and payment data, we quantified several implications of shifting ancillary healthcare services from regulated, more expensive to unregulated, less expensive sites. We also quantified the implications of this shift on access to services, with a focus on differences in access between rural and urban patients for a Medicaid (disadvantaged) population in Maryland, USA.

Design
Using a dataset of all Medicaid claims records for 1 year, we identified and extracted all bundles of regulated and unregulated ancillary services. Geospatial computing was used to approximate transportation costs required to access services. Including transportation enabled us to estimate net savings of any added transportation costs. We used location-allocation optimisation models to find the optimal sites to minimise net costs.

Setting
Coverage area included Medicaid patients throughout the state of Maryland.

Participants
All rural and urban members of this Medicaid cohort.

Primary and secondary outcome measures
Change in payer costs and member travel times on shifting ancillary bundles from regulated to unregulated sites.

Results
Procedure cost and travel time differentials between regulated and unregulated sites strongly correlated with the percentage of procedures referred to regulated sites. Shifting regulated bundles to unregulated sites, while imposing the constraint of no increase in travel time, reduced expenditures by 15.9%. This figure exceeded 30% if no limit was placed on travel-time increases.

Conclusion
With reasonable constraints on allowable travel time increases, shifting ancillary service bundles from regulated to unregulated sites can benefit both patients and payers in terms of cost and access.

Introduction
The prognosis of patients with advanced pancreatic ductal adenocarcinoma (PDAC) is dismal and conventional chemotherapy treatment delivers limited survival improvement. Immunotherapy may complement our current treatment strategies. We previously demonstrated that the combination of an allogeneic tumour-lysate dendritic cell (DC) vaccine with an anti-CD40 agonistic antibody resulted in robust antitumour responses with survival benefit in a murine PDAC model. In the Rotterdam PancrEAtic Cancer Vaccination-2 trial, we aim to translate our findings into patients. This study will determine the safety of DC/anti-CD40 agonistic antibody combination treatment, and treatment-induced tumour-specific immunological responses.

Methods and analysis
In this open-label, single-centre (Erasmus Univsersity Medical Center, Rotterdam, Netherlands), single-arm, phase I dose finding study, adult patients with metastatic pancreatic cancer with progressive disease after FOLFIRINOX chemotherapy will receive monocyte-derived DCs loaded with an allogeneic tumour lysate in conjunction with a CD40 agonistic antibody. This combination-immunotherapy regimen will be administered three times every 2 weeks, and booster treatments will be given after 3 and 6 months following the third injection. A minimum of 12 and a maximum of 18 patients will be included. The primary endpoint is safety and tolerability of the combination immunotherapy. To determine the maximum tolerated dose, DCs will be given at a fixed dosage and anti-CD40 agonist in a traditional 3+3 dose-escalation design. Secondary endpoints include radiographic response according to the RECIST (V.1.1) and iRECIST criteria, and the detection of antitumour specific immune responses.

Ethics and dissemination
The Central Committee on Research Involving Human Subjects (CCMO; NL76592.000.21) and the Medical Ethics Committee (METC; MEC-2021-0566) of the Erasmus M.C. University Medical Center Rotterdam approved the conduct of the trial. Written informed consent will be required for all participants. The results of the trial will be submitted for publication in a peer-reviewed scientific journal.

Trial registration number
NL9723.

Objectives
To compare the efficacy and safety of two Schlemm’s canal-based microinvasive glaucoma surgery (MIGS) devices, the Hydrus Microstent and the iStent Trabecular Bypass combined with phacoemulsification for treatment of open-angle glaucoma.

Design
Systematic review and network meta-analysis.

Methods
Literature searches were conducted on PubMed, Web of Science, Cochrane Library and ClinicalTrials.gov to identify randomised controlled trials (RCTs) assessing the Hydrus or the iStent implantation combined with phacoemulsification for treatment of open-angle glaucoma until September 2020. Risk of bias was assessed using a six-item modified Jadad scale. Effects were estimated using the intraocular pressure (IOP) reduction (IOPR), the percentage of IOPR and the proportion of medication-free patients at follow-up end. Safety was estimated using the proportions of adverse events. The network meta-analysis was conducted within a Bayesian framework using the Markov Chain Monte Carlo method in ADDIS software.

Results
Six prospective RCTs comprising 1397 patients were identified. Regarding the absolute value and the percentage of IOPR, the Hydrus and 2-iStent implantation combined with phacoemulsification were significantly more effective than phacoemulsification alone. Rank probability analysis revealed the Hydrus might be the best choice to lower IOP. There was no significant difference in the proportion of medication-free patients among groups. The Hydrus and 2-iStent implantation had a higher probability to achieve the medication-free status versus the 1-iStent implantation and phacoemulsification alone. Overall safety profiles were good for each device with the focal peripheral anterior synechiae more frequently reported in Hydrus eyes.

Conclusions
The Hydrus implantation may have a slight advantage over the 1-iStent or 2-iStent implantation in combination with phacoemulsification to treat open-angle glaucoma. Our findings might be of some uncertainty due to the limited included data. Further studies are needed to investigate whether our findings are robust, including high-quality RCTs to directly compare these MIGS devices.

Objective
Teenage pregnancies and childbirths are associated with negative health outcomes. Access to health information enables adolescents to make appropriate decisions. However, the relationship between access to health information through mass media and teenage pregnancy has not received much attention in existing literature. We therefore examined the association between access to mass media and teenage pregnancy in Zambia.

Design
Cross-sectional.

Setting
Zambia.

Participants
Weighted sample of 3000 adolescents aged 15–19 years.

Outcome measure
Teenage pregnancy that included adolescents who were currently pregnant or had had an abortion or had given birth in the last 5 years preceding the survey.

Results
Out of 3000 adolescents, 897 (29.9%, 95% CI: 28.1% to 31.3%) were pregnant or had ever been pregnant. Majority of the adolescents resided in rural areas (55.9%) and had secondary education (53.6%). Adolescents who had exposure to internet, newspapers or magazines, radio and television were 10.5%, 22.6%, 43.1% and 43.1%, respectively. Adolescents who had daily access to newspapers or magazines (adjusted OR (AOR): 0.33, 95% CI: 0.13 to 0.82) or using internet (AOR: 0.54, 95% CI: 0.30 to 0.95) were less likely to be pregnant or to have had a pregnancy compared with those with no access to newspapers and internet, respectively.

Conclusion
Our study suggests that internet use and reading of newspapers or magazines may trigger behavioural change as an effective approach to reducing teenage pregnancy. Behavioural change communicators can implement mass media campaigns using newspapers, magazines and the internet to publicise adolescent health messages that can encourage adolescents to adopt healthy behaviours and prevent teenage pregnancies.

Introduction
Sepsis is a common, potentially life-threatening complication of infection. The optimal treatment for sepsis includes prompt antibiotics and intravenous fluids, facilitated by its early and accurate recognition. Currently, clinicians identify and assess severity of suspected sepsis using validated clinical scoring systems. In England, the National Early Warning Score 2 (NEWS2) has been mandated across all National Health Service (NHS) trusts and ambulance organisations. Like many clinical scoring systems, NEWS2 should not be used without clinical judgement to determine either the level of acuity or a diagnosis. Despite this, there is a tendency to overemphasise the score in isolation in patients with suspected infection, leading to the overprescription of antibiotics and potentially treatment-related complications and rising antimicrobial resistance. The biomarker procalcitonin (PCT) has been shown to be useful in specific circumstances to support appropriate antibiotics prescribing by identifying bacterial infection. PCT is not routinely used in the care of undifferentiated patients presenting to emergency departments (EDs), and the evidence base of its optimal usage is poor. The PROcalcitonin and NEWS2 evaluation for Timely identification of sepsis and Optimal (PRONTO) study is a randomised controlled trial (RCT) in adults with suspected sepsis presenting to the ED to compare standard clinical management based on NEWS2 scoring plus PCT-guided risk assessment with standard clinical management based on NEWS2 scoring alone and compare if this approach reduces prescriptions of antibiotics without increasing mortality.

Methods and analysis
PRONTO is a parallel two-arm open-label individually RCT set in up to 20 NHS EDs in the UK with a target sample size of 7676 participants. Participants will be randomised in a ratio of 1:1 to standard clinical management based on NEWS2 scoring or standard clinical management based on NEWS2 scoring plus PCT-guided risk assessment. We will compare whether the addition of PCT measurement to NEWS2 scoring can lead to a reduction in intravenous antibiotic initiation in ED patients managed as suspected sepsis, with at least no increase in 28-day mortality compared with NEWS2 scoring alone (in conjunction with local standard care pathways). PRONTO has two coprimary endpoints: initiation of intravenous antibiotics at 3 hours (superiority comparison) and 28-day mortality (non-inferiority comparison). The study has an internal pilot phase and group-sequential stopping rules for effectiveness and futility/safety, as well as a qualitative substudy and a health economic evaluation.

Ethics and dissemination
The trial protocol was approved by the Health Research Authority (HRA) and NHS Research Ethics Committee (Wales REC 2, reference 20/WA/0058). In England and Wales, the law allows the use of deferred consent in approved research situations (including ED studies) where the time dependent nature of intervention would not allow true informed consent to be obtained. PRONTO has approval for a deferred consent process to be used. Findings will be disseminated through peer-reviewed journals and presented at scientific conferences.

Trial registration number
ISRCTN54006056.

Introduction
Persons with haemophilia A (PwHA) commonly experience regular bleeding into joints, which may result in joint damage and complications such as degenerative arthritis. Emicizumab has previously demonstrated efficacy in reducing the occurrence of joint bleeds and target joints, along with having a favourable safety profile; however, data on the long-term effects on joint health are lacking. The AOZORA study will evaluate the long-term safety and joint health of paediatric PwHA without factor (F)VIII inhibitors taking emicizumab; here, we report the details of the study protocol and baseline data.

Methods and analysis
AOZORA is a multicentre, open-label, phase IV clinical study in Japan that aims to enrol approximately 30 PwHA aged

Introduction
Neoantigens derived from tumour somatic mutations are recognised as ideal vaccine targets. Tumour neoantigens have been studied in a wide range of tumours. Most of research on neoantigens has focused just on a unique tumour and a single mutated gene. Currently, a few studies have reported using a mixture of neoantigen peptides derived from multiple genetic mutation sites in the treatment of genomic unstable advanced solid malignancies. The trial aims to evaluate the safety and efficacy of individualised tumour neoantigen peptide mixtures in the treatment of genomic unstable advanced solid malignant tumours.

Methods and analysis
This is a prospective, non-randomised, open, single-centre, single-arm, phase I trial. Patients with genomic unstable advanced solid malignancies are eligible for study participations. 20 patients will be included in the trial. Through the whole exome and transcriptome sequencing analysis of the fresh blood and tumour tissues of the enrolled patients, the 20 25-33aa antigen peptides with the highest mutation scores of the patients will be screened out, and the corresponding new antigen peptides will be synthesised and prepared. Patients will be treated with their own individualised neoantigen polypeptide combined with a polypeptide adjuvant (human granulocyte-macrophage colony-stimulating factor). The primary endpoint is safety indicators, including general and specific adverse events which will be monitored continuously. Secondary endpoints are progression-free survival, objective response rate, objective duration of remission, 1-year survival rate and overall survival.

Ethics and dissemination
This study has received approval from the Ethics Committee of Chongqing University Cancer Hospital on 21 November 2019 (207/2019). The findings of this trial will be disseminated through national and international presentations and peer-reviewed publications.

Trial registration number
ChiCTR1900025364.

Objectives
We assessed the relative difficulty in meeting food needs during the COVID-19 pandemic compared with before; determined the relationship between pandemic-associated difficulties in food access and household, maternal and child food security; and identified resiliency-promoting strategies.

Design
A cross-sectional survey of households undertaken in November 2020.

Setting
Rural districts of Luang Prabang Province, Lao People’s Democratic Republic.

Participants
Households (N=1122) with children under 5 years.

Primary and secondary outcomes measured
Survey respondents reported the relative ease of access of food and healthcare as well as changes in income and expenditures compared with before March 2020. We determined indicators of food security and source of foods consumed for households, women and children, as well as prevalence of malnutrition in children under 5.

Results
Nearly four-fifths (78.5%) found it harder to meet household food needs during the pandemic. The most common reasons were increased food prices (51.2%), loss of income (45.3%) and decreased food availability (36.6%). Adjusting for demographics, households with increased difficulty meeting food needs had lower food consumption scores and child dietary diversity. Over 85% of households lost income during the pandemic. Decreased expenditures was associated with reliance on more extreme coping strategies to meet food needs. The households who experienced no change in meeting food needs produced a greater percentage of their food from homegrown methods (4.22% more, 95% CI 1.28 to 7.15), than households who found it more difficult.

Conclusions
Pandemic-associated shocks may have large effects on food insecurity. Action is needed to mitigate consequences of the pandemic on nutrition. Local food production and safety net programmes that offset income losses may help.

Introduction
Enhanced recovery after surgery (ERAS) guidelines strongly recommends that patients be in early postoperative ambulation within 24 hours. This study aims to assess the effectiveness and safety of the self-fatigue assessment method to guide patients’ early postoperative ambulation.

Methods and analysis
This is a single-centre, randomised, open, parallel-controlled trial. Five hundred and fifty-two patients who meet the inclusion criteria for gynaecological oncology surgery are randomly assigned in a 1:1 ratio to either a self-fatigue assessment group (study group) or a fixed activity distance assessment group (control group). The fixed activity distance group adopts a fixed early postoperative ambulation distance to guide the patient’s activity, while the self-fatigue assessment group uses the Borg Exercise Scale to assess the patient’s fatigue and stops activity when the fatigue level reaches 5–6. The primary outcome measure is the time to first postoperative flatus. Secondary outcome measures are the time to first bowel movement, the incidence of moderate to severe bloating, the incidence of bowel obstruction or venous thromboembolism, the incidence of adverse events (nausea, vomiting, dizziness), patient satisfaction, sleep quality scores, patient compliance with activities, hospital costs and days in hospital.

Ethics and dissemination
This study was approved by the Independent Ethics Committee of Xiangyang Central Hospital affiliated with Hubei University of Arts and Sciences and registered with the China Clinical Trials Registry in May 2021. The results of the trial will be disseminated through open access peer-reviewed journals and abstracts will be submitted to relevant national and international conferences.

Trial registration number
CTR2100046035.

Introduction
The widespread prevalence of type 2 diabetes (T2D) not only influences patients’ daily lives but also has an economic impact on society. Increasing physical activity and a healthy diet can delay the progression of T2D. Although there are evidence-based recommendations on diet and physical activity, patients with T2D have difficulties implementing them. An appropriate lifestyle intervention can address this problem.

Methods and analysis
This study is based on the need to develop an intervention that helps patients to establish behavioural changes in order to achieve glycaemic control. The intervention will be evaluated in a monocentric, open-label, pragmatic, two-arm randomised controlled trial with a sample ratio of 1:1 and a parallel design. This superiority study will be conducted in Switzerland. All enrolled patients (n=90) will receive the standard medical treatment for T2D. The intervention group will receive personal health coaching by telephone and access to a smartphone and web application for 1 year. The control group will receive access to the application for 1 year and a one-time written diet and exercise recommendation. The primary outcomes are objectively measured physical activity and glycated haemoglobin. Secondary outcomes are self-reported physical activity, nutrition, cognitive mediators of changes in sport-related behaviour, blood values, medication and nutritional supplements, anthropometric data, quality of life, neuropathy and cost-effectiveness. All outcomes will be measured at baseline, at 27 weeks after inclusion and at 54 weeks after inclusion. The recruitment of participants and the measurements will be completed after 2 years. Linear mixed-effects models will be applied for each outcome variable to analyse the intervention effects.

Ethics and dissemination
This study was approved by the Ethics Committee North-western and Central Switzerland in February 2021 (ref: 2020-02755). All participants will be required to provide written informed consent. The results will be published in international peer-reviewed journals.

Trial registration number
ISRCTN79457541.

Stroke, Ahead of Print.

BackgroundOut-of-Hospital Cardiac Arrest (OHCA) is a major health problem with low survival. Cardio-Pulmonary-Resuscitation (CPR) quality is associated with survival, and includes chest compression depth (CCD), rate (CCR), and fraction (CCF) within international guideline recommendations1. In 2020 overall survival in Denmark reached 16% placing Denmark as one of the leading countries for OHCA survival. The aim of this study was to examine the effect on CPR quality with the introduction of real-time CPR feedback in a high OHCA survival area, as well as the effect of adding post-event clinical debriefings.MethodThis cohort study collected non-traumatic OHCA data from ambulances within the Capital Region of Denmark using ZOLL X-series defibrillator. Three variables; CCD, CCR and CCF were collected on three consecutive phases: Phase one (no feedback) from October 2018 to May 2019; Phase two (real-time feedback) from May 2019 to February 2020 and phase three (real-time + post-event debriefings) from February 2020 to December 2020. Data were compared against guidelines at each phase.ResultsWe included 1545 patients. Preliminary results revealed guideline compliant CCD in 21.8% of the compressions (no feedback) compared to 30.9% (real-time feedback) and 33.0% (real-time + post-event feedback). For CCR the results were 60.2%/ 74.6%/ 75.1% respectively. Combination of guideline compliant CCD and CCR simultaneously was 13.6%/ 23.3%/ 25.8% respectively. CCF was 76.8%/ 80.9%/ 81.3% respectively.ConclusionReal-time feedback and post-event clinical debriefings have the potential to improve EMS CPR quality in a high survival OHCA area.ReferencePerkins GD. et al. (2021) ‘European Resuscitation Council Guidelines 2021: Executive summary’, Resuscitation, 161, pp. 1–60. doi:10.1016/j.resuscitation.2021.02.003.Conflict of interestNone.FundingTrygFoundation.

BackgroundMathematical optimisation can be used to maximise public access defibrillator (PAD) accessibility for out-of-hospital cardiac arrests (OHCA). It is unclear whether enforcing ‘fairness’ (defined as parity of PAD accessibilty) across city wards would impact resulting PAD accessibility compared to an unconstrained approach.MethodWe included all suspected OHCAs responded to by the Scottish Ambulance Service (SAS) in the cities of Glasgow, Edinburgh, Aberdeen, and Dundee between Jan. 2011 – Sept. 2017, and PADs registered with SAS as of Feb. 2020. We computed the accessibility (defined as within 100 m of OHCA) for existing PADs and developed a mathematical model to select locations for additional PADs under two scenarios: (1) select optimal locations across whole cities, and (2) select optimal locations distributed equally between city wards. Up to 20 additional PAD locations per ward were considered. For both scenarios, we compared PAD accessibility on out-of-sample OHCAs using McNemar’s test and fairness across wards using the Nash social welfare function.ResultsWe identified 14,674 OHCA responses and 424 existing PADs. Existing PADs were within range of 1.1% of OHCAs (0.4–2.0% per city). Optimising new PAD locations per city, regardless of wards, increased PAD accessibility to 15.4% of OHCAs (14.9–17.9% per city). Constraining an equal number of PADs in each ward resulted in accessibility loss of 0.2–1.4 percentage points depending on the quantity of PADs placed (P