Oncologi, ‘è un cambio di paradigma significativo’
Search Results for: Sorveglianza nella post polipectomia nel cancro al colon-retto
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Tumori, creato un test che prevede se cancro resisterà a chemio
Consentirà di personalizzare cure sin dal momento della diagnosi
Impact of 2014 Japanese practice guidelines on treatment patterns in patients with myasthenia gravis: an insurance claims database study
Objectives
To evaluate changes in oral corticosteroid (OCS) use after the publication of the 2014 Japanese clinical practice guidelines for myasthenia gravis (MG).
Design
Retrospective cohort study performed in three Japanese health insurance databases: the JMDC database between 2005 and 2021; the DeSC database covering the National Health Insurance (NHI) and the DeSC database covering the Late-Stage Elderly Healthcare Service (LSEHS) between 2014 and 2021. Achievement of OCS ≤5 mg/day was defined as ≥90 days of consecutive OCS ≤5 mg/day during follow-up, without any gap longer than 60 days between two consecutive claims. The time to achieve OCS ≤5 mg/day was estimated using Kaplan-Meier survival analysis.
Setting
Real-world treatment setting in Japan.
Participants
Patients aged ≥16 years with a record of MG (International Classification of Diseases 10th edition code: G70.0) with a serological test, who had baseline period ≥180 days before inclusion with no MG claim and who started immunotherapy (including OCS) within 90 days of MG diagnosis.
Outcome measures
Prescription of OCS and other therapies for MG.
Results
Overall, 811 patients were included. The mean age was 49 years in the JMDC, 61 years in the NHI and 80 years in the LSEHS. In the JMDC, the median time to achieve OCS ≤5 mg/day was significantly shorter (p=0.042; log-rank test) in patients included in 2015 or later (11.0 months) than in patients included before 2015 (17.9 months). The median time to achieve OCS ≤5 mg/day was shorter in the LSEHS (6.5 months) than in the JMDC (11.0 months) and the NHI (11.7 months).
Conclusions
Faster tapering of the OCS dose was observed in patients starting treatment after the publication of the 2014 guidelines, although use of higher-dose OCS remained widespread after this date. This highlights the need to improve awareness of guidelines by healthcare providers in order to decrease the burden of higher-dose OCS.
Trial registration number
Clinical Trials Registry (UMIN-CTR): UMIN000051155; Post-results.
La partita più bella del mondo con i ragazzi guariti dal cancro
In campo squadre dei Centri oncoematologia pediatrica d’Italia
Economic evaluation of a lifestyle intervention for individuals with overweight or obesity suffering from chronic low back pain (the BO2WL trial): a protocol for a health economic analysis
Introduction
Low back pain (LBP) is highly prevalent across the Western world, including Switzerland (CH) and Belgium (BE), with women experiencing higher disability rates than men. Chronic LBP (CLBP), persisting beyond 3 months, leads to diminished health-related quality of life and increased healthcare and societal costs. Evidence indicates a direct relationship between body mass index (BMI) and CLBP severity, with high BMI significantly driving LBP-related healthcare expenses. Current evidence supports combining pain neuroscience education (PNE) with cognition-targeted exercise therapy (CTET) to effectively manage CLBP.
An economic evaluation alongside a randomised controlled trial, entitled ‘Lifestyle Intervention in Overweight/Obese CLBP Patients: an International Multi-centre RCT’ (BO2WL), will be conducted in CH and BE. It aims to evaluate the addition of a lifestyle intervention to PNE and CTET compared with PNE and CTET alone for treating individuals with CLBP and overweight or obesity. This protocol outlines the details of the economic evaluation of this trial.
Methods and analysis
The trial consists of a 14-week intervention followed by a 52-week post-intervention follow-up. Primary outcomes include direct and indirect costs, as well as quality-adjusted life years and pain intensity. Cost data will be converted into 2026 Belgium (BE) and 2026 Swiss Francs (CHF) for CH, with a discount rate of 3.5%. Incremental cost-utility and cost-effectiveness ratios will be calculated from a societal perspective for each country.
Ethics and dissemination
Ethics approval was obtained by the local ethics committees (Bern, CH: project ID 2022–02210; Brussels and Geel, BE: BUN 1432022000296). Results of the main trial and economic evaluation will be submitted for publication in a peer-reviewed journal.
Trial registration number
NCT05811624.
Supplementary effects of low-frequency transcutaneous electrical nerve stimulation on individuals with obesity combined with metabolic syndromes: study protocol for a randomised controlled trial
Introduction
Obesity combined with metabolic syndrome is a major global public health problem. This trial aims to investigate the therapeutic effects of low-frequency transcutaneous electrical nerve stimulation (Lo-TENS) in individuals with obesity and coexisting metabolic syndrome. The study will also delve into the underlying mechanisms through which Lo-TENS may mitigate the symptoms of metabolic syndrome, providing insights into its potential as a novel treatment approach.
Methods and analysis
This randomised controlled trial will enrol 63 individuals with obesity and metabolic syndrome, and randomly assign them to one of the three groups: (1) peripheral stimulation group, (2) central stimulation group and (3) sham stimulation group. Each participant will receive a 30 min daily session of their assigned stimulation, conducted 5 days a week for a duration of 12 weeks. The primary outcomes of interest are body mass index and fasting blood glucose, with secondary outcomes encompassing blood pressure, triglyceride levels and various metabolic biomarkers. Comprehensive assessments will be performed at baseline, immediately post intervention, and followed by a 12-week follow-up evaluation to monitor long-term effects and sustainability of potential benefits.
Ethics and dissemination
The trial has been granted ethical approval by the ethics committee of the Second People’s Hospital of Kunming (approval number: 202305001). The study’s findings will be disseminated through peer-reviewed journal publications and international conference presentations.
Trial registration number
Chinese Clinical Trial Registry Platform: www.chictr.org.cn (No. ChiCTR2400089104).
Leishmaniases in Ethiopia: a scoping review
Objectives
With recent efforts to eliminate visceral leishmaniasis in East Africa, we aimed to map the breadth of research on leishmaniases in Ethiopia, one of the high-endemic countries in the region, to help understand the current literature landscape and highlight priority areas for future research.
Design
The scoping review was conducted in accordance with the JBI Scoping Review Methodology Group’s guidance and reported following Preferred Reporting Items for Systematic Reviews and Meta-Analyses—Extension for Scoping Reviews guidelines.
Data sources
We searched the following databases and sources: PubMed, Embase, Web of Science, Cochrane Library, Global Medicus Index, PROSPERO, ClinicalTrials.gov and the Pan African Clinical Trials Registry and known local journals.
Eligibility criteria
We included studies addressing the issue of leishmaniasis in Ethiopia that were published in English language.
Data extraction and synthesis
Two reviewers independently extracted data from each study, with conflicts resolved by a third reviewer. The identified studies were analysed using an extensive codebook, which was previously developed by this team and adapted to the Ethiopian context to classify the research into different categories.
Results
A total of 8698 articles were identified. A stepwise review was conducted, and 639 papers were selected for inclusion. The research spans different themes and designs and has steadily increased over the past 14 years. Research on prevention and control, health systems/policies and post-kala-azar dermal leishmaniasis, as well as randomised controlled trials, was lacking. Studies on coinfections with other diseases accounted for 14% of research.
Conclusions
The findings underscore the growing amount of research on leishmaniasis in Ethiopia, addressing several themes and emphasising the need for more research in prevention, control, health systems/policy and high-quality studies for evidence-based treatment.
Promoting smoking cessation and preventing relapse to tobacco use following a smoke-free mental health inpatient stay (SCEPTRE feasibility study): a multicentre randomised controlled feasibility study protocol
Introduction
Thousands of patients with mental illness are admitted to acute adult mental health wards every year in England, where local guidance recommends that all mental health settings be entirely smokefree. Mental health Trusts presently invest substantial effort and resources to implement smoke-free policies and to deliver tobacco dependence treatment to patients. Providing adequate support can help those who smoke remain abstinent or quit smoking during their smoke-free inpatient stay and beyond. At present, little is known about how best to support patients to prevent their return to pre-admission smoking behaviours after discharge from a smoke-free mental health inpatient stay. We have developed an intervention which includes targeted resources to support smoking-related behaviour change in patients following discharge from a smoke-free mental health setting. The aim of this trial is to determine the feasibility of a large-scale clinical trial to test the effectiveness and cost-effectiveness of the SCEPTRE intervention, compared with usual care.
Methods and analysis
This feasibility study will be an individually randomised, controlled trial in eight National Health Service mental health Trusts recruiting adults (≥18 years) admitted to an acute adult mental health inpatient setting who smoke tobacco on admission, or at any point during their inpatient stay. Consenting participants will be randomised to receive a 12-week intervention consisting of components aimed at promoting or maintaining positive smoking-related behaviour change following discharge from a smoke-free mental health inpatient setting or usual care. Data will be collected at baseline, 3 months and a second timepoint between 4 and 6 months post-randomisation. With 64 participants (32 in each group), the trial will allow a participation rate of 15% and completion rate of 80% to be estimated within a 95% CI of ±3% and ±10%, respectively. The analysis will be descriptive and follow a prespecified plan.
Ethics and dissemination
Ethics approval was obtained from the North West—Greater Manchester West Research Ethics Committee. We will share results widely through local, national and international academic, clinical and patient and public involvement networks. The results will be disseminated through conference presentations, peer-reviewed journals and will be published on the trial website: https://sceptreresearch.com/.
Trial registration number
ISRCTN77855199.
Cuff leak test and airway obstruction in mechanically ventilated ICU patients (COSMIC): a pilot feasibility randomized controlled trial protocol
Introduction
The cuff leak test (CLT) is hypothesised to help optimise extubation by assessing for laryngeal oedema which, if unrecognised and untreated, could lead to post-extubation stridor, post-extubation airway obstruction, and reintubation. However, the diagnostic accuracy of the CLT to detect post-extubation stridor (and hence potentially airway obstruction) remains uncertain. Given the equipoise that exists surrounding the CLT, we are conducting a pilot randomised clinical trial (RCT) examining the CLT as part of the pathway to extubation. Herein, we report the protocol for the Cuff Leak Test and Airway Obstruction in Mechanically Ventilated ICU Patients (COSMIC): a Pilot Feasibility Randomized Clinical trial (RCT).
Methods and analysis
This is a multicentre, international, parallel-group, pragmatic, pilot RCT. We will enrol 100 mechanically ventilated patients in the intensive care unit (ICU) who are deemed ready for extubation and have at least one risk factor for laryngeal oedema. In the intervention arm, respiratory therapists will perform a qualitative CLT before extubation. If a patient passes the CLT (suggesting no laryngeal oedema), extubation will be performed in keeping with standard care. If the patient fails the CLT (suggesting laryngeal oedema), extubation will be delayed allowing for administration of dexamethasone, consideration of diuresis, and the CLT will be repeated in 12–24 hours. In the control arm, patients will be extubated without completing a CLT, without steroid administration, and without delay. Randomization will be by a 1:1 allocation, stratified by centre. The primary feasibility outcomes will include recruitment and protocol adherence. Secondary outcomes will include post-extubation stridor, reintubation within 72 hours, emergency surgical airway within 72 hours, and ICU and hospital mortality within 30 days.
Ethics and dissemination
This trial has been approved by Clinical Trials Ontario, Hamilton Integrated Research Ethics Board, State of Kuwait Ministry of Health, University of Texas Health Committee for the Protection of Human Subjects and Brant Community Health Systems Research Ethics Committee. The trial has received a No Objection Letter from Health Canada. Trial results will be disseminated via publication in peer-reviewed journals.
Trial registration number
NCT05456542.
CT Perfusion for Predicting Ischemic Stroke in Patients With Symptomatic Carotid or Middle Cerebral Artery Occlusion: A Post Hoc Analysis of the CMOSS Study
Stroke, Ahead of Print. BACKGROUND:It is unknown whether computed tomographic perfusion (CTP) parameters predict ischemic stroke in patients with symptomatic chronic carotid or middle cerebral artery occlusion.METHODS:A post hoc analysis of medically treated patients enrolled in the CMOSS trial (Carotid or Middle Cerebral Artery Occlusion Surgery Study; REGISTRATION: URL:https://www.clinicaltrials.gov; Unique identifier: NCT01758614), a randomized controlled trial conducted at 13 centers in China between June 2013 and March 2018. It aimed to compare extracranial-intracranial bypass surgery to medical therapy in patients with symptomatic carotid or middle cerebral artery occlusion and hemodynamic insufficiency. CTP-derived mean transit time and relative cerebral blood flow were collected. The primary outcome was defined as ischemic stroke in the territory of the qualifying artery within 2 years after randomization. The predictive value of CTP for the primary outcome was analyzed by a Cox regression model. Receiver operating characteristic curves were used to calculate optimal cutoff values of CTP parameters.RESULTS:All 165 per-protocol patients (median age=53.7 years, 81.2% males) treated with medical treatment alone were analyzed. Sixteen (9.7%) patients suffered the primary outcome during the 2-year follow-up. Cutoff values of mean transit time >6.5 seconds (symptomatic side) and relative cerebral blood flow ≤0.5 were associated with recurrent stroke. In multivariate Cox regression, mean transit time (adjusted hazard ratio, 3.50 [95% CI, 1.19–10.30];P=0.02) and relative cerebral blood flow (adjusted hazard ratio, 7.36 [95% CI, 2.27–23.85];P=0.001) were independently associated with the primary outcome.CONCLUSIONS:CTP-based hemodynamic parameters are predictive of recurrent ischemic stroke in symptomatic patients with chronic carotid or middle cerebral artery occlusion. CTP could be used in patient selection for stratified secondary prevention of stroke in future studies.REGISTRATION:URL:https://www.clinicaltrials.gov; Unique identifier: NCT01758614.
Modulating verticality representation and uprightness by virtual reality: rationale and protocol for a within-person randomised intervention associating a basic study in healthy individuals and a pilot clinical trial in individuals exhibiting post-stroke lateropulsion (VIRGIL)
Introduction
Balance and gait disorders represent the most frequent and disabling sequelae after stroke. Impaired body orientation with respect to gravity (lateropulsion) is one of the primary underlying mechanisms, increasingly investigated. After hemisphere stroke, lateropulsion is caused by an impaired internal representation of verticality, for which developing rehabilitation techniques has become a priority. Among various approaches, virtual reality appears to be a promising tool for modulating spatial reference frame. The objective of this study is to investigate the effects of immersion in virtual tilted reality (VTR) on the postural vertical (PV) as a primary outcome, as well as main secondary outcomes on the visual vertical (VV) and the active standing posture (body orientation with respect to gravity and weight-bearing (WB) distribution on lower limbs), both in healthy individuals and individuals exhibiting lateropulsion at the subacute phase after a hemispheric stroke. The cumulative effect of the VTR on the post-stroke lateropulsion will also be analysed.
Methods and analysis
This pilot study is a single-centre, within-person randomised trial conducted in the department of Physical and Rehabilitation Medicine of the University Hospital of Grenoble-Alpes (France). We will include 40 individuals from 18 to 85 years old, 20 healthy individuals and 20 individuals with lateropulsion tested 0.5 on the Scale for Contraversive Pushing), the study lasts 4 weeks: W1 for inclusion, randomisation, planning and conventional rehabilitation; W2 and W4 to collect clinical data and conventional rehabilitation; and W3 for the VTR intervention over four consecutive mornings at the same time: 2 to test the VTR effects on verticality perception (PV and VV) and 2 to test the VTR effects on active standing (body orientation and WB distribution on lower limbs). Immediate effects and post-effects of the VTR immersion are analysed by comparing results of the following time points: for verticality perception baseline, during and after VTR and for active standing at only baseline and during VTR immersion. Linear mixed-effect models will be run with different factors/covariates according to objectives. We will analyse the proportion and features of responders (PV modulation ≥2°). The cumulative effect of the 4 days of VTR sessions will be analysed by comparing scores of the SCAle for LAteropulsion assessed at the end of every week.
Ethics and dissemination
The study was approved by an institutional review board at the national level (Comité de Protection des Personnes Ile de France X; 2020-A02941-38, amendment 2024). All participants will provide written informed consent before enrolment. Findings will be submitted to peer-reviewed journals related to rehabilitation, stroke or neuroscience.
Trial registration number
ClinicalTrials.gov, NCT04911738.
Timely post-discharge medication reviews to Improve Continuity–the Transitions Of Care stewardship (TIC TOC) study in rural and regional Australia: a parallel-group randomised controlled trial study protocol
Introduction
Transition of care from hospital is a period when the risks of medication errors and adverse events are high, with 50% of adults discharged having at least one medication-related problem. Pharmacist-led medication reviews can reduce medication errors and unplanned readmission when completed promptly post-discharge; however, they are underutilised. A Transition of Care Stewardship pharmacist has been proposed to facilitate and coordinate a patient’s discharge process and facilitate a timely post-discharge medication review. Access to pharmacist medication review in rural and regional areas can be limited. This protocol describes a randomised controlled trial (RCT) to determine whether a virtual Transition of Care Stewardship pharmacist reduces medication-related harm in rural and regional Australia.
Method and analysis
Multicentre RCT involving patients at high risk of medication-related harm discharged from regional and rural hospitals to a domiciliary residence. Eligible patients must be aged≥18 years, admitted under a medical specialty, be discharged to a domiciliary setting, have a regular general practitioner (GP) or be willing to visit a GP or an Aboriginal Medical Service after discharge for medical follow-up, have a Medicare card and be at high risk of readmission. High risk of readmission is defined as either a previous admission to the hospital or Emergency Department (ED) presentation in the past 6 months AND≥three regular medications OR on at least ONE high-risk medication. A total of 922 participants will be recruited into the study. Enrolled participants will be randomised to the intervention or control (usual care). The intervention will include a virtual Transition Of Care Stewardship pharmacist to ensure that patients receive discharge medication reconciliation, medication counselling, medication list and communicate directly with primary care providers to facilitate a timely post-discharge medication review. Usual care will include informing the patient’s clinical inpatient treating team that the patient is at high risk of medication misadventure and may benefit from a post-discharge Home Medicines Review (a GP-referred pharmacist medication review funded by the Australian Government).
Data analysis will be performed on a modified intent-to-treat basis. The primary outcome assessed is a composite of a first unplanned medication-related hospitalisation or ED presentation within 30 days of hospital discharge. Comparisons between the intervention and usual care groups for the primary outcome will be made using a mixed-effects logistic regression model, adjusting for site-level clustering as a random effect.
Ethics and dissemination
This study is approved to be conducted at the Western New South Wales Local Health District via the Research Ethics and Governance Information System (approval number: 2023/ETH00978). To ensure the needs of Aboriginal and Torres Strait Islander patients are appropriately addressed, ethics for this study were submitted and approved by the Aboriginal Health and Medical Research Council (approval number: 2148/23). Manuscripts resulting from this trial will be submitted to peer-reviewed journals. Results may also be disseminated at scientific conferences and meetings with key stakeholders.
Trial registration number
ACTRN12623000727640.
The MOTILITY Mother-Child Cohort: a Danish prospective longitudinal cohort study of the infant gut microbiome, nutrition and bowel habits – a study protocol
Introduction
Concurrent with infants’ progression in dietary complexity and gut microbiome diversity, infants gradually change their defecation patterns during the first year of life. However, the links between bowel habits, the gut microbiota and early life nutrition remain unclear. The primary outcome is to characterise the gut microbiome development from birth to 1 year of age. Second, to investigate how bowel habits and nutrition in early life relate to the gut microbiome and metabolome during this period of life, and to explore how the development of the gut microbiome associates with host development.
Methods and analysis
The MOTILITY Mother-Child Cohort (MOTILITY) is a Danish prospective longitudinal cohort study enrolling up to 125 mother–infant dyads. Assessments occur at 36 weeks gestation (visit 1), birth (screening of infant) and 3, 6, 9 and 12 months (±2 weeks) post partum (visits 2–5). At visit 1, maternal anthropometrics, self-collected faecal and urine samples, and questionnaires on bowel habits and lifestyle are obtained. Between visits, infant faecal (biweekly), urine (monthly) and maternal breast milk (monthly until 6 months of age) samples are collected at home, and bowel habits and dietary intake are assessed biweekly by self-reported questionnaires. At visits 2–5, infant blood and saliva samples are collected, and anthropometric measurements are obtained. In addition, dietary intake is recorded thrice throughout the study period for mother and infant, respectively, and infant whole-gut transit time is estimated by sweet corn tests at 9 and 12 months of age. Birth, growth, motor development, sleep patterns, tooth development, overall health and well-being are assessed using questionnaires. Univariate and multivariate statistics will be applied to identify associations between the gut microbiome, early life nutrition and host physiology including bowel habits during the first year of life.
Ethics and dissemination
The MOTILITY study has been approved by the Research Ethics Committee for the Capital Region of Denmark (reference number: H-21063016). Selected results will be made available to the participants in the form of a summary document. Results will be published in peer-review journals and by means of national and international conferences.
Trial registration number
NCT05491161.
Linee guida sul parto cesareo
Queste linee guida aggiornate riguardano il parto cesareo, gli aspetti […]
Epidemiological association of the COVID-19 pandemic on Mycoplasma pneumoniae infections in children in Tianjin, China: a single-centre retrospective study (2017-2024)
Objective
To investigate the epidemiological characteristics and temporal-spatial distribution of Mycoplasma pneumoniae (MP) infections among paediatric inpatients with respiratory tract infections in Tianjin, China, across three distinct phases: pre-pandemic (2017–2019), pandemic (2020–2022) and post-pandemic (2023–2024). The primary hypothesis is that the COVID-19 pandemic altered the epidemiology of MP infections in children.
Design
Retrospective, single-centre study.
Setting
Secondary care paediatric hospital in a metropolitan area.
Participants
A total of 60 213 paediatric patients hospitalised with respiratory infections between January 2017 and December 2024 were included. The study population consisted of children aged 0–18 years, with a male-to-female ratio of 1.22:1.00. Selection criteria included children admitted with a diagnosis of respiratory infection, while those with incomplete clinical data or non-respiratory infections were excluded.
Primary and secondary outcome measures
The primary outcome was the overall positive detection rate of MP-RNA. Secondary outcomes included annual and seasonal variations in MP-RNA detection rates, differences by sex and age group, and the impact of the COVID-19 pandemic on MP epidemiology. All statistical methods, including those used to control for confounding, involved the use of ² tests for comparing positive rates between groups.
Results
The overall positive detection rate of MP-RNA among children hospitalised for respiratory infections during the study period was 36.58% (22 023/60 213). The annual MP-RNA-positive detection rates from 2017 to 2024 were as follows: 50.74% (411/810) in 2017, 36.28% (1150/3170) in 2018, 27.41% (1459/5323) in 2019, 10.18% (222/2181) in 2020, 11.42% (928/8129) in 2021, 13.27% (579/4364) in 2022, 28.97% (3064/10575) in 2023 and 55.38% (14 210/25 661) in 2024. The highest annual positivity rate was observed in 2024 (55.38%, 14 210/25 661), while the lowest rate occurred in 2020 (10.18%, 222/2181). Statistical analysis revealed significant differences in MP-RNA detection rates across different years (²=8331.511, p
Determinants of post COVID-19 clinic attendance among SARS-CoV-2-infected individuals in Stockholm, Sweden: a population-based cohort study
Objectives
Investigate determinants of post-COVID-19 condition (PCC) clinic attendance among participants not hospitalised versus hospitalised during the SARS-CoV-2 infection.
Design
Retrospective cohort study.
Setting
Six population-based registers with high coverage to cover all adults residing in Stockholm County, Sweden.
Participants
Adults residing in Stockholm County on 31 January 2020, with a SARS-CoV-2 infection through 30 November 2022, who did not die or move out of Stockholm County within 90 days.
Primary outcome measures
PCC clinic attendance from 90 days after the SARS-CoV-2 test until date of death, date of moving out, or 30 November 30,2023.
Results
Of non-hospitalised and hospitalised participants, 737 of 464 674 (0.2%) and 433 of 23 374 (1.9%), respectively, attended a PCC clinic. A total of 75 878 (16.3%) of non-hospitalised participants and 6190 (26.5%) of hospitalised participants presented with new-onset symptoms that could indicate PCC in primary care. The strongest determinants of attendance among non-hospitalised participants were mental health disorder (adjusted risk ratio (aRR) 2.57, 95% CI 2.21 to 2.98), asthma (2.39, 1.97–2.92) and >4 PCC symptoms in 2019 (2.27, 1.60–3.24), and among hospitalised participants were >31 sick days in 2019 (1.94, 1.47–2.56), 1–30 sick days in 2019 (1.56, 1.06–2.29) and obesity (1.51, 1.19–1.93). The most common clinical presentation was fatigue (n=526, 71.4%) among non-hospitalised and dyspnoea (n=148, 34.2%) among hospitalised participants.
Conclusions
PCC clinic attendance characteristics differed between non-hospitalised and hospitalised participants. Distinguishing PCC from conditions with overlapping symptoms and determining the appropriate level of care may be challenging, with risk of resource displacement effects and inappropriate care.