Peer support enhanced behavioural crisis response teams in the emergency department: protocol for a stepped-wedge cluster-randomised controlled trial

Introduction
Despite expert recommendations to prioritise non-invasive and patient-centred approaches for behavioural crisis management, physical restraints are commonly used in the emergency department (ED). Patients describe the restraint process as coercive and dehumanising. The use of peer support workers, who are individuals with lived experience of mental illness and behavioural conditions, has shown positive patient outcomes when assisting individuals experiencing behavioural crises. However, there is limited evidence of the implementation of such an approach in the ED setting. The goal of this study is to evaluate if the implementation of a Peer support enhanced Agitation Crisis response Team (PACT) for behavioural crisis management in the ED is more effective than usual care to reduce restraint use and improve outcomes among patients presenting to the ED with behavioural crises.

Methods and analysis
We will first conduct a stakeholder-informed needs assessment to codesign the protocol and then train staff and peers in PACT intervention readiness. Next, a stepped-wedge, cluster-randomised controlled trial will be conducted over 3 years at five ED sites across a healthcare system in the Northeast USA. The PACT intervention will integrate peer delivery of trauma-informed care within a structured, interprofessional, team-based response protocol for behavioural crisis management. The primary outcome is the rate of physical restraint and/or sedation use. The secondary outcome is the level of patient agitation during the ED visit. Analyses of primary and secondary outcomes will be conducted using generalised linear mixed models.

Ethics and dissemination
This protocol has been approved by the Yale University Human Investigation Committee (protocol number 2000037554). The study is deemed minimal risk and has been granted a waiver of consent for trial participants. However, verbal consent will be obtained for a subset of patients receiving follow-up data collection. Results will be disseminated through publications in open-access, peer-reviewed journals, via scientific presentations, or through direct mail notifications.

Trial registration number
Clinicaltrials.gov: NCT06556069.

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[Articles] Association between physical activity and risk of anxiety: a dose-response meta-analysis of 11 international cohorts

Our research confirmed a dose-response relationship between physical activity and anxiety risk, and increasing physical activity within the range recommended by the World Health Organization (WHO) (10–20 MET-h/week) can significantly reduce anxiety risk. Subgroup analysis showed that this protective effect was most significant during the 5-year follow-up period, with a maximum anxiety risk reduction of 49%. Exceeding the recommended dose, there may be additional smaller benefits between doses 20–30 MET-h/week, and exceeding 50 MET-h/week may become a risk factor.

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A Nationwide Factorial Randomized Trial of Electronic Nudges to Patients with Chronic Kidney Disease and Their General Practices for Increasing Guideline-Directed Medical Therapy: The NUDGE-CKD Trial

Circulation, Ahead of Print. Background: Many individuals with chronic kidney disease (CKD) face considerable but modifiable risk of cardiovascular and renal outcomes due to suboptimal implementation of guideline-directed medical therapy (GDMT). We investigated whether electronic letter-based nudges delivered to individuals with CKD and their general practices could increase GDMT uptake.Methods: This was a nationwide 2×2 factorial implementation trial, with randomization at the patient and general-practice level, and analyzed at the patient level. All Danish adults with a hospital-diagnosis of CKD and access to the official Danish electronic letter system were individually randomized in a 1:1 ratio to usual care (no letter) or to receive an electronic letter-based nudge on GDMT in CKD; general practices of individuals with CKD were independently randomized (1:1) to receive no letter or an electronic informational letter on GDMT. Intervention letters were delivered on August 19, 2024. Data were collected through the Danish administrative health registries. Primary endpoint was a filled prescription of a renin-angiotensin system inhibitor (RASi) or a sodium-glucose cotransporter-2 inhibitor (SGLT2i) within 6 months of intervention delivery.Results: A total of 22,617 patients with CKD were randomized to the patient-level intervention, with 11,223 allocated to receive the electronic nudge letter and 11,394 to usual care. Separately, 1,540 general practices caring for 28,069 patients with CKD were randomized to the provider-level intervention, with 774 practices (13,959 patients) allocated to the intervention and 766 practices (14,110 patients) to usual care. During follow-up, 7,303 (65.1%) allocated to the patient-directed nudge had filled a prescription of RASi or SGLT2i compared with 7,505 (65.9%) in usual care (difference, 0.79 percentage points; 95% confidence interval (CI), -2.03 to 0.45; P=0.21). Among patients of practices receiving the provider-directed letter, 8,921 (63.9%) filled a prescription for RASi or SGLT2i compared with 9,086 (64.4%) in the usual care group (difference, -0.49 percentage points; 95%CI, -1.64 to 0.66; P=0.41). No interaction was observed between the two interventions (pinteraction=0.85).Conclusions: In this nationwide pragmatic, 2×2 factorial implementation trial, electronic letter-based nudges on GDMT delivered to patients with CKD or their general practice did not increase the uptake of RASi or SGLT2i as compared with usual care.

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British Society of Gastroenterology practice guidance on the management of acute and chronic gastrointestinal symptoms and complications as a result of treatment for cancer

Background
Survival rates after a diagnosis of cancer are improving. Poorly managed gastrointestinal (GI) side effects can interfere with delivery of curative cancer treatment. Long-term physical side effects of cancer therapy impinge on quality of life in up to 25% of those treated for cancer, and GI side effects are the most common and troublesome.

Aim
To provide comprehensive, practical guidance on the management of acute and chronic luminal gastrointestinal symptoms arising during and after treatment for cancer

Methods
A multidisciplinary expert group including patients treated for cancer, divided into working parties to identify, and synthesise recommendations for the optimal assessment, diagnosis and appropriate interventions for luminal GI side effects of systemic and local cancer therapies. Recommendations were developed using the principles of the BMJ AGREE II reporting.

Results
103 recommendations were agreed. The importance of the patient perspective and what can be done to support patients are emphasised. Key physiological principles underlying the development of GI toxicity arising from cancer therapy are outlined. Individual symptoms or symptom clusters are poor at distinguishing the underlying cause(s), and investigations are required if empirical therapy does not lead rapidly to significant benefits. Patients frequently have multiple GI causes for symptoms; all need to be diagnosed and optimally treated to achieve resolution. Investigations and management approaches now known to be ineffective or of questionable benefit are highlighted.

Conclusions
The physical, emotional and financial costs to individuals, their families and society from cancer therapy can be considerable. Identifying and signposting affected patients who require specialist services is the role of all clinicians. Progress in the treatment of cancer increasingly means that patients require expert, multidisciplinary supportive care providing effective and safe treatment at every stage of the cancer journey. Development of such expertise should be prioritised as should the education of health professionals and the public in what, when and how acute and chronic gastrointestinal symptoms and complications should be managed.

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External validation of risk prediction models for post-stroke mortality in Berlin

Objectives
Prediction models for post-stroke mortality can support medical decision-making. Although numerous models have been developed, external validation studies determining the models’ transportability beyond the original settings are lacking. We aimed to assess the performance of two prediction models for post-stroke mortality in Berlin, Germany.

Design
We used data from the Berlin-SPecific Acute Treatment in Ischaemic or hAemorrhagic stroke with Long-term follow-up (B-SPATIAL) registry.

Setting
Multicentre stroke registry in Berlin, Germany.

Participants
Adult patients admitted within 6 hours after symptom onset and with a 10th revision of the International Classification of Diseases discharge diagnosis of ischaemic stroke, haemorrhagic stroke or transient ischaemic attack at one of 15 hospitals with stroke units between 1 January 2016 and 31 January 2021.

Primary outcome measures
We evaluated calibration (calibration-in-the-large, intercept, slope and plot) and discrimination performance (c-statistic) of Bray et al’s 30-day mortality and Smith et al’s in-hospital mortality prediction models. Information on mortality was supplemented by Berlin city registration office records.

Results
For the validation of Bray et al’s model, we included 7879 patients (mean age 75; 55.0% men). We observed 763 (9.7%) deaths within 30 days of stroke compared with 680 (8.6%) predicted. The model’s c-statistic was 0.865 (95% CI: 0.851 to 0.879). For Smith et al’s model, we performed the validation among 1931 patients (mean age 75; 56.2% men), observing 105 (5.4%) in-hospital deaths compared with the 92 (4.8%) predicted. The c-statistic was 0.891 (95% CI: 0.864 to 0.918). The calibration plots of both models revealed an underestimation of the mortality risk for high-risk patients.

Conclusions
Among Berlin stroke patients, both models showed good calibration performance for low and medium-risk patients and high discrimination while underestimating risk among high-risk patients. The acceptable performance of Bray et al’s model in Berlin illustrates how a small number of routinely collected variables can be sufficient for valid prediction of post-stroke mortality.

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Spatial and spatio-temporal analysis for malaria hotspot identification: a scoping review protocol

Introduction
Malaria hotspots have been the focus of public health managers during the last two decades because of the potential elimination gains that can be obtained by targeting them. Advances in spatial technologies in the 20th century such as geographic information systems, remotely sensed satellite data on climate and ecology, and statistical methods for spatial cluster detection have enhanced our ability to map fine-scale patterns of malaria transmission. This led to the diversification of analytical approaches and a lack of consensus on methods and standardised indicators for malaria hotspot detection, raising challenges for comparing and synthesising findings across different studies. This review aims to fill this gap by identifying and summarising all publicly available peer-reviewed articles on spatial and spatio-temporal analytical approaches used to detect malaria hotspots while highlighting research gaps.

Methods
This scoping review will follow the Joanna Briggs Institute Framework. A comprehensive search will be conducted in PubMed, Medline, Web of Science, Scopus and Embase using keywords related to malaria, hotspots and detection. Retrieved articles published between 1 January 2000 and 31 December 2024 in English or French will be uploaded to Covidence for screening. Empirical studies that apply spatial or spatio-temporal analytical methods to detect malaria hotspots will be included. Studies will be excluded if they rely solely on geographical visualisation without formal spatial analysis. Data extraction will be performed by two independent reviewers, with disagreements resolved by discussion. Data will be summarised using descriptive statistics and thematic analysis.

Ethics and dissemination
This scoping review will involve the secondary analysis of published literature on malaria hotspot analysis; therefore, ethics approval is not required. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews checklist will be used to ensure transparency and methodological rigour in reporting. The findings will be disseminated through publication in a peer-reviewed journal and presented at scientific conferences via abstracts, oral or poster presentations.

Trial egistration number
This review has been registered on the Open Science Framework under the DOI: https://doi.org/10.17605/OSF.IO/C8KUN.

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Studies on cognitive performance among older people living with HIV in eastern Europe and central Asia: a scoping review

Background
Despite the growth of the population of older people living with HIV (PLWH), data on cognitive disorders among older PLWH, particularly in low- and middle-income countries, are scarce. These data are especially underrepresented in the literature from eastern Europe and central Asia (EECA).

Objectives
This scoping review aimed to describe the peer-reviewed literature on cognitive health among PLWH in the EECA region.

Eligibility criteria
We selected articles from peer-reviewed journals that reported on cognitive assessments or the prevalence and characteristics of cognitive disorders among adult (≥18 years) PLWH in EECA countries (Armenia, Azerbaijan, Belarus, Estonia, Georgia, Kazakhstan, Kyrgyzstan, Latvia, Lithuania, Moldova, Russia, Tajikistan, Turkmenistan, Ukraine and Uzbekistan). Studies assessing cognition among PLWH related to traumatic brain injury, brain tumours, COVID-19, meningitis, neurosyphilis and/or other central nervous system infections were excluded.

Source of evidence
We searched for relevant data published up to March 2025 using four online databases (PubMed, CINAHL, Web of Science and PsycINFO).

Charting methods
Covidence, a web-based collaborative software platform, was used for data screening and extraction. Two independent reviewers screened abstracts and full texts, resolving disagreements through consensus. The data were extracted based on the predefined data extraction criteria.

Results
A total of 1388 peer-reviewed articles were identified; 295 articles were removed due to duplication; and 1053 and 25 articles were excluded based on the abstract/title and full-text screenings, respectively. Finally, 15 articles met the inclusion criteria. All 15 studies used different neuropsychological assessments to measure cognitive performance by domain and/or cognitive disorders among various subgroups of PLWH. One cross-sectional study focused on older populations (≥40 years old), using standardised cognitive performance assessment tests. However, it neither provided information about the prevalence estimate of cognitive disorders nor identified risk factors.

Conclusion
Existing literature on cognitive disorders among older PLWH in the EECA region is limited and insufficient to estimate prevalence, or identify risk factors, and ultimately develop appropriate policy addressing the needs of older PLWH in this region. This scoping review underscores the urgent need for large-scale, longitudinal studies employing standardised, culturally adapted neuropsychological batteries and adherence to rigorous reporting standards.

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[Articles] Risk of cardiovascular disease among cancer survivors: systematic review and meta-analysis

This meta-analysis provides an up-to-date comprehensive global overview that cancer survivors had increased risk of CVD and 17 CVD subtypes than non-cancer controls. CVD risk evaluation and management need to be prioritized in cancer survivors, particularly among male, younger, and specific cancer survivors (brain, hematological, respiratory, male genital, and breast). This study provides supporting evidence that may inform future updates to guidelines for CVD prevention in cancer survivors, highlighting its public health relevance.

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Glucagon-Like Peptide-1 Receptor Agonists and Risk of Nontraumatic Intracerebral Hemorrhage in Patients With Type 2 Diabetes

Stroke, Ahead of Print. BACKGROUND:GLP-1RAs (glucagon-like peptide-1 receptor agonists) have consistently demonstrated a protective effect against ischemic stroke. However, whether this benefit also extends to nontraumatic intracerebral hemorrhage (ICH) remains unknown. Given the blood pressure–lowering and anti-inflammatory properties of GLP-1RAs, we aimed to evaluate their potential impact on ICH risk in patients with type 2 diabetes.METHODS:We conducted a retrospective cohort study using global health care data from the TriNetX network. Patients with type 2 diabetes who used GLP-1RAs (n=326 777) were compared with those who did not (n=643 614). Propensity score matching (1:1) was performed to balance baseline characteristics, and follow-up was conducted for up to 4 years. The primary outcomes included all-cause mortality, ischemic stroke, and ICH (overall and by location). Hazard ratios and 95% CIs were calculated to assess the mean treatment effect in the treated group.RESULTS:After propensity score matching (resulting in 2 balanced groups of 255 460 individuals each), GLP-1RAs use was associated with a lower risk of ICH (hazard ratio, 0.743 [95% CI, 0.684–0.807]). The lower ICH risk associated with GLP-1RAs was observed across all ICH locations (allP≤0.01). In addition, exposure to GLP-1RAs was associated with a significantly lower rate of mortality (hazard ratio, 0.525 [95% CI, 0.512–0.538]) and ischemic stroke (hazard ratio, 0.871 [95% CI, 0.843–0.901]).CONCLUSIONS:This study highlights a novel potential association between GLP-1RAs and a lower risk of ICH in patients with type 2 diabetes. Prospective trials are needed to confirm the potential protective effect of GLP-1RAs on small vessel rupture.

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Cohort profile: characterisation, determinants, mechanisms and consequences of the long-term effects of COVID-19 – providing the evidence base for health care services (CONVALESCENCE) in the UK

Purpose
The pathogenesis of the long-lasting symptoms which can follow an infection with the SARS-CoV-2 virus (‘long covid’) is not fully understood. The ‘COroNaVirus post-Acute Long-term EffectS: Constructing an evidENCE base’ (CONVALESCENCE) study was established as part of the Longitudinal Health and Wellbeing COVID-19 UK National Core Study. We performed a deep phenotyping case-control study nested within two cohorts (the Avon Longitudinal Study of Parents and Children and TwinsUK) as part of CONVALESCENCE.

Participants
From September 2021 to May 2023, 349 participants attended the CONVALESCENCE deep phenotyping clinic at University College London. Four categories of participants were recruited: cases of long covid (long covid(+)/SARS-CoV-2(+)), alongside three control groups: those with neither long covid symptoms nor evidence of prior COVID-19 (long covid(-)/SARS-CoV-2(-); control group 1), those who self-reported COVID-19 and had evidence of SARS-CoV-2 infection, but did not report long covid (long covid(-)/SARS-CoV-2(+); control group 2) and those who self-reported persistent symptoms attributable to COVID-19 but no evidence of SARS-CoV-2 infection (long covid(+)/SARS-CoV-2(-); control group 3). Remote wearable measurements were performed up until February 2024.

Findings to date
This cohort profile describes the baseline characteristics of the CONVALESCENCE cohort. Of the 349 participants, 141 (53±15 years old; 21 (15%) men) were cases, 89 (55±16 years old; 11 (12%) men) were in control group 1, 75 (49±15 years old; 25 (33%) men) were in control group 2 and 44 (55±16 years old; 9 (21%) men) were in control group 3.

Future plans
The study aims to use a multiorgan score calculated as the cumulative total for each of nine domains (ie, lung, vascular, heart, kidney, brain, autonomic function, muscle strength, exercise capacity and physical performance). The availability of data preceding acute COVID-19 infection in cohorts may help identify the consequences of infection independent of pre-existing subclinical disease and also provide evidence of determinants that influence the development of long covid.

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Protocol for Shenzhen-working-age cohort study (SZ-working age): a prospective observational cohort study on eye health and myopia

Introduction
The widespread use of digital devices in modern workplaces has led to a rise in visual health problems, such as myopia and dry eye syndrome, among the working-age population. This study aims to investigate the incidence of eye disorders, associated risk factors and relevant biomarkers in Shenzhen, addressing a crucial gap in the research on visual health in rapidly urbanising Chinese cities.

Methods
This prospective observational cohort study, conducted from September 2024 to December 2029, will recruit 3000 full-time employees aged 18–65 in Shenzhen through multistage sampling across five job sectors. Data collection will include questionnaire surveys, standardised scale assessments, ophthalmic examinations, ophthalmic imaging and biomarker testing. Annual follow-ups will track the incidence of high myopia and dry eye, as well as associated factors and biomarker changes. Data accuracy will be ensured through double entry and continuous quality control.

Ethics and dissemination
The study has been approved by the Ethics Committee of Shenzhen Eye Hospital (2024KYPJ012; 04 February 2024). The results will be presented at professional conferences and submitted for publication in peer-reviewed journals.

Trial registration number
National Health Information Platform (MR-44-24-026548).

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Effectiveness of postpartum care to improve womens health and quality of life in Southeast Asia: a scoping review protocol

Introduction
The first 3 months post partum is a critical transition period for women and families, which is characterised by physical, psychological and social adaptation. The first year post partum is also a critical phase for women’s health, given their physical recovery and adjustment to motherhood. The WHO 2023 recommendations highlight the importance of a postnatal care focus, including maternal health assessment, mental health support, nutritional interventions, postpartum contraceptive use and home care visits. This scoping review aims to map the evidence of the effectiveness of postpartum care on women’s health and quality of life in the Southeast Asia region.

Methods and analysis
This scoping review will be guided by the methodological principles developed by Arksey and O’Malley. This review will also consider observational studies, including cohort studies, case-control studies and cross-sectional studies. For inclusion, studies should be selected for eligibility based on the following criteria: articles investigating the uptake of postpartum women (women who have had childbirth up to 42 days after delivery) in Southeast Asian countries. The search will comprise peer-reviewed articles from 2013 to 2023 from the following electronic databases: PubMed/MEDLINE, ProQuest, EBSCO, Scopus, Web of Science and Google Scholar. We use both keywords in the title and/or abstract and subject headings as appropriate. We will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Protocols to develop the protocol and use the PRISMA flow diagram to present the results for scoping reviews.

Ethics and dissemination
A scoping review is a novel approach for examining the breadth of literature regarding the connection between the effectiveness of postpartum care and women’s health and quality of life and, as a secondary analysis, does not require ethics approval. The results of this review will be submitted for publication in a peer-reviewed journal and presented at relevant conferences.

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Comparison of complications and recovery after laparoscopic and abdominal hysterectomy for benign disease: the LAparoscopic Versus Abdominal hysterectomy (LAVA) randomised controlled trial

Objective
To compare recovery after laparoscopic hysterectomy (LH) and abdominal hysterectomy (AH).

Design
A parallel, open, non-inferiority, multicentre, randomised controlled, expertise-based surgery trial.

Setting
10 NHS (National Health Service) hospitals within the UK.

Participants
Women undergoing hysterectomy for a benign gynaecological condition.

Interventions
Consenting women of 18–55 years were randomised to LH or AH using a secure internet facility by a surgeon with self-declared expertise. Major complications were recorded by clinicians, and recovery was assessed by regular text messaging and postal questionnaires.

Primary and secondary outcome measures
Major surgical complications (Clavien-Dindo≥level 3) up to six completed weeks postsurgery, time to resumption of normal activities measured by the Patient-Reported Outcomes Measurement Information System Physical Function tool and quality of recovery at 24 hours (Quality of Recovery 15 score; 0–150).

Results
75 women were randomised before early curtailment of the trial; 32/39 (82%) and 30/36 (83%) women underwent LH and AH, respectively. Major complications occurred in 2/32 (6%) LH versus 4/30 (13%) AH groups. No difference in time to resumption of usual activities was found (median [IQR, n] 7.5 weeks (3.6–8.2, 25) LH vs 7.5 weeks (5.5–10.6, 26) AH groups or quality of recovery (mean [SD, n] 81.1 (13.4, 27) vs 72.3 (17.6, 22), respectively; adjusted mean difference 7.2, 95% CI –3.2 to 17.6).

Conclusions
No differences were found in complications or recovery between LH and AH. However, early cessation of the trial due to recruitment challenges limits clinical inferences. It is important that larger comparative trials are conducted now that LH, including robotics, is becoming adopted as standard practice.

Trial registration number
ISRCTN14566195, IRAS ID 287988.

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Maintenance with niraparib in patients with stage III, stage IV, chemo-naïve recurrent or platinum-sensitive recurrent uterine serous carcinoma: study protocol for a phase II clinical trial

Introduction
Uterine serous carcinoma (USC) accounts for 40% of endometrial cancer-related deaths. The standard of care for stages III and IV USC yields a 20%–30% survival at 2 years and a 10%–20% survival at 3–5 years. Recent advances in the second-line treatment of advanced or recurrent USC are rapidly evolving. Targeted therapeutic approaches with the use of lenvatinib plus pembrolizumab, as well as the use of trastuzumab deruxtecan, offer new hope for successful second-line therapies for patients. However, further investigation into novel targeted therapeutic approaches is warranted, given the high burden of disease associated with this aggressive histological subtype. USC shares clinical and genomic similarities with epithelial ovarian cancer, suggesting a correlation with ‘BRCAness’. Niraparib, a potent PARP1 and PARP2 inhibitor, was shown to have a positive impact on platinum-sensitive recurrent ovarian cancer, regardless of the presence or absence of BRCA status. Our hypothesis is that patients with stage III, stage IV and platinum-sensitive recurrent USC receiving niraparib maintenance in addition to standard therapy for USC may have an improved progression-free survival.

Methods and analysis
Participating sites include the primary site, Northwell Health Zucker Cancer Centre, and secondary site, Rutgers Cancer Institute of NJ. Females over the age of 18 with stage III, stage IV or platinum-sensitive recurrent USC will be recruited and enrolled based on inclusion/exclusion criteria. 24 subjects will be enrolled during phase 1 and 21 subjects will be enrolled during phase 2, over a total of 3 years. Patients will receive an individualised dose of niraparib daily every 28 days per cycle for 1 year or until progression of disease. Follow-up of disease status will continue for 5 years poststudy treatment. This phase II clinical trial will employ a Simon two-stage minimax design to test the null hypothesis that the 1 year response rate is

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