Randomised trials in maternal and perinatal health in low and middle-income countries from 2010 to 2019: a systematic scoping review

Objectives
To identify and map all trials in maternal health conducted in low and middle-income countries (LMIC) over the 10-year period from 2010 to 2019, to identify geographical and thematic trends, as well as comparing to global causes of maternal death and preidentified priority areas.

Design
Systematic scoping review.

Primary and secondary outcome measures
Extracted data included location, study characteristics and whether trials corresponded to causes of mortality and identified research priority topics.

Results
We searched the Cochrane Central Register of Controlled Trials database, a combined registry of trials from multiple sources. Our search identified 7269 articles, 874 of which were included for analysis. Between 2010 and 2019, maternal health trials conducted in LMICs more than doubled (50–114). Trials were conducted in 61 countries—231 trials (26.4%) were conducted in Iran. Only 225 trials (25.7%) were aligned with a cause of maternal mortality. Within these trials, pre-existing medical conditions, embolism, obstructed labour and sepsis were all under-represented when compared with number of maternal deaths globally. Large numbers of studies were conducted on priority topics such as labour and delivery, obstetric haemorrhage and antenatal care. Hypertensive disorders of pregnancy, diabetes and health systems and policy—despite being high-priority topics—had relatively few trials.

Conclusion
Despite trials conducted in LMICs increasing from 2010 to 2019, there were significant gaps in geographical distribution, alignment with causes of maternal mortality and known research priority topics. The research gaps identified provide guidance and insight for future research conduct in low-resource settings.

Trial registration number
10.17605/OSF.IO/QUJP5.

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Luglio 2022

Cognitive prehabilitation for geriatric patients undergoing elective surgery: a PRISMA-P-compliant protocol for a systematic review

Introduction
The ageing of the population, as well as advances and improvements in surgery, and anaesthesia have greatly increased the demand for surgical services in geriatric patients. Neurocognitive disorders are the most common complications experienced in the postoperative period by older individuals. Improving perioperative brain health in older adults has become key actions for the multidisciplinary perioperative care teams. This comprehensive systematic review will assess the effectiveness and safety of cognitive prehabilitation programmes prior to surgery on cognitive functional capacity and postoperative cognitive outcomes in geriatric patients undergoing elective surgery.

Methods and analysis
This protocol was prepared using the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. The following key electronic bibliographic databases will be searched from inception to July 2022: MEDLINE, EMBASE, CINAHL, CENTRAL, PEDro, PsycINFO, CBM, CNKI, WANFANG database and VIP. We will include randomised controlled trials published in English or Chinese that examine the effects of cognitive prehabilitation programmes on geriatric patients undergoing elective surgery. To construct the search strategy, the Patient, Intervention, Comparison, Outcome, Study scheme will be used. Two reviewers will independently complete the study screening, selection, data extraction and quality rating. The Physiotherapy Evidence Database scale will be used to assess the methodological quality of the included studies. A narrative or quantitative synthesis will be conducted based on the final data. The planned start and end dates for the study were 1 September 2021 and 1 August 2023.

Ethics and dissemination
Ethical approval will not be required for this protocol. The results of the final review will be disseminated via peer-reviewed journals and conference presentations.

PROSPERO registration number
CRD42021277191.

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Luglio 2022

Measuring anti-transgender stigma in low-income and middle-income countries: a scoping review protocol

Introduction
Globally, transgender and other gender diverse (trans) people face pervasive stigma, which contributes to health inequities across multiple health outcomes. Stigma is a fundamental cause of health inequities because it simultaneously limits access to resources, contributes to systemic vulnerability and generates chronic stress. Anti-trans stigma occurs across multiple socioecological levels, resulting in multiple possible definitions and measurements of trans stigma. Understanding how trans stigma has been measured in low-income and middle-income countries (LMICs) is critical to health promotion efforts for trans communities. Accordingly, this scoping review will identify and examine how anti-trans stigma has been measured in existing LMIC-specific research to inform best practices for measurement of anti-trans stigma that includes consideration of local context.

Methods and analysis
This is the protocol for a scoping review of anti-trans stigma in LMICs. We will search (from January 2001 to December 2021) PubMed, WHO Global Medicus and EBSCO. Study selection will conform to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews Checklist. Original studies in English, Spanish, Arabic or Russian will be included. Reviewers will independently screen all citations, full-text articles and abstract data. Data analysis will involve quantitative and qualitative methods. A narrative summary of findings will be conducted.

Ethics and dissemination
As a scoping review (no direct interaction with participants), this study is exempt from human subjects oversight. Understanding context-specific ways to measure anti-trans stigma is urgently needed to support trans health globally. The planned scoping review will help to address this gap. Results of the review will be disseminated in a peer-reviewed journal and likely in other media such as conferences, seminars and symposia.

Protocol registration number
osf.io/qcs2v

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Luglio 2022

Pivotal role of environmental toxicants on developing infectious diseases in LMICs: a protocol for a systematic review and meta-analysis

Introduction
Environmental toxicants such as chemical pollution have an enormous impact on the health of people and the planet. Emerging findings suggest that non-communicable diseases are linked to early and chronic environmental exposures. However, the rapid globalisation in developing countries, environmental change and the emergence, spread, persistence and severity of infectious diseases are not yet well understood. The aim of this study is to understand which environmental toxicants are commonly associated with infectious diseases in low-income and middle-income countries (LMICs).

Methods and analysis
A total of four electronic databases, MEDLINE through PubMed, Scopus, Web of Science and CENTRAL (the Cochrane Library) be searched to identify relevant studies and will be screened by two independent reviewers. The Cochrane risk of bias (ROB) tool for randomised control trials (RCTs) and ROB assessment tool for non-randomised studies for non-RCTs will be used to assess the ROB. A meta-analysis will be used to determine the pooled effect if we find out the included articles have similar environmental exposure, participant groups, study design and outcome measures. A narrative synthesis of the findings will be provided, along with summaries of the intervention effect. Heterogeneity between the studies will be assessed, and sensitivity analysis will be conducted based on study quality.

Ethics and dissemination
Findings will be summarised in a single manuscript. This review attempts to explore the pivotal role of environmental toxicants in predisposing, developing, persistent and severity of infectious diseases in LMICs. Findings from this study will highlight the effects of individual environmental toxicants’ role on infectious disease outcomes for the early prevention and limit toxic exposure to guide individual, community, and occupational health policy for future strategies.

PROSPERO registration number
CRD42021274359.

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Luglio 2022

Codesign approaches involving older adults in the development of electronic healthcare tools: a systematic review

Objective
The primary aim was to review and synthesise the current evidence of how older adults are involved in codesign approaches to develop electronic healthcare tools (EHTs). The secondary aim was to identify how the codesign approaches used mutual learning techniques to benefit older adult participants.

Design
Systematic review following the Preferred Reporting Items for Systematic Reviews 2020 checklist.

Data sources
PubMed, Embase and Scopus databases were searched for studies from January 2010 to March 2021.

Eligibility criteria
Inclusion criteria were studies employing codesign approaches to develop an EHTs, and the study population was aged 60 years and older.

Data extraction and synthesis
Data were extracted for analysis and risk of bias. We evaluated the quality of studies using the Agency for Healthcare Research and Quality Evidence-based Practice Center approach.

Results
Twenty-five studies met the inclusion criteria for this review. All studies used at least two involvement processes, with interviews and prototypes used most frequently. Through cross-classification, we found an increased utilisation of functional prototypes in studies reaching the ‘empower’ level of participation and found that studies which benefitted from mutual learning had a higher utilisation of specific involvement processes such as focus groups and functional prototyping.

Conclusions
We found gaps to support which involvement processes, participation levels and learning models should be employed when codesigning with older adults. This is important because higher levels of participation may increase the user’s knowledge of technology, enhance learning and empower participants. To ensure studies optimise participation and learning of older adults when developing EHTs, there is a need to place more emphasis on the approaches promoting mutual learning.

PROSPERO registration number
CRD42021240013.

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Luglio 2022

Effects of inulin-type fructans supplementation on cardiovascular disease risk factors: a protocol for a systematic review and meta-analysis of randomised controlled trials

Introduction
This review aims to assess the effects of dietary supplementation with inulin-type fructans (ITF) compared with no supplementation on cardiovascular disease risk factors in adults and assess the quality of trial reporting using the Consolidated Standards of Reporting Trials (CONSORT) and CONSORT for abstract (CONSORT-A) checklists.

Methods and analysis
We will search randomised controlled trials (RCTs) in MEDLINE, EMBASE, CINAHL, Emcare, AMED and the Cochrane Database of Systematic Reviews from inception to 31 March 2022, without any language restrictions. The RCTs need to administer ITF in adults for at least 2 weeks and assess effects on at least one cardiovascular risk factor. We will exclude RCTs that (1) assessed the postprandial effects of ITF; (2) included pregnant or lactating participants; (3) enrolled participants undergoing treatment that might affect the response to ITF. We will assess the study risk of bias (RoB) using V.2 of the Cochrane RoB tool for RCTs (RoB 2) and the certainty of the evidence using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. We will pool data using a random-effects model. We will use the 2 test to compare compliance of CONSORT and CONSORT-A checklists and Poisson regression to identify factors associated with better reporting.

Ethics and dissemination
Ethics approval is not required for secondary analysis of already published data. We will publish the reviews in a peer-review journal.

PROSPERO registration number
CRD42019136745.

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Luglio 2022

Resurgence of blackwater fever among children in sub-Saharan Africa: a scoping review protocol

Introduction
Blackwater fever (BWF), a complication of malaria, has in the past been considered as a rare complication of malaria in children living in high transmission settings. More recently, however, a growing number of paediatric clusters of BWF cases have been reported predominantly in sub-Saharan Africa (SSA). The aim of this study is to map evidence on BWF among children in SSA from 1 January 1960 to 31 December 2021.

Methods and analysis
This review will be guided by Arksey and O’ Malley’s methodological framework for scoping reviews with methodological refinements by Levac et al and will comply with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews’ guidelines. Five electronic databases (MEDLINE via PubMed, Embase, the Cochrane Library, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and PsycINFO) will be systematically searched using predefined keywords. In addition, reference lists of included articles will be searched. Our multidisciplinary team has formulated search strategies and two reviewers will independently complete study eligibility screening, final selection and data extraction. A third reviewer will adjudicate the final decision on disputed articles. Bibliographic data and abstract content will be collected and analysed using a data-charting tool developed iteratively by the research team.

Ethics and dissemination
This scoping review being a secondary analysis does not require ethics approval. We anticipate results of this review will broaden understanding of paediatric BWF in SSA and identify its research gaps in SSA. We will be disseminating results through journals and conferences targeting primary care providers.

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Luglio 2022

Systematic review and meta-analysis to examine intrapartum interventions, and maternal and neonatal outcomes following immersion in water during labour and waterbirth

Objectives
Water immersion during labour using a birth pool to achieve relaxation and pain relief during the first and possibly part of the second stage of labour is an increasingly popular care option in several countries. It is used particularly by healthy women who experience a straightforward pregnancy, labour spontaneously at term gestation and plan to give birth in a midwifery led care setting. More women are also choosing to give birth in water. There is debate about the safety of intrapartum water immersion, particularly waterbirth. We synthesised the evidence that compared the effect of water immersion during labour or waterbirth on intrapartum interventions and outcomes to standard care with no water immersion. A secondary objective was to synthesise data relating to clinical care practices and birth settings that women experience who immerse in water and women who do not.

Design
Systematic review and meta-analysis.

Data sources
A search was conducted using CINAHL, Medline, Embase, BioMed Central and PsycINFO during March 2020 and was replicated in May 2021.

Eligibility criteria for selecting studies
Primary quantitative studies published in 2000 or later, examining maternal or neonatal interventions and outcomes using the birthing pool for labour and/or birth.

Data extraction and synthesis
Full-text screening was undertaken independently against inclusion/exclusion criteria in two pairs. Risk of bias assessment included review of seven domains based on the Robbins-I Risk of Bias Tool. All outcomes were summarised using an OR and 95% CI. All calculations were conducted in Comprehensive Meta-Analysis V.3, using the inverse variance method. Results of individual studies were converted to log OR and SE for synthesis. Fixed effects models were used when I2 was less than 50%, otherwise random effects models were used. The fail-safe N estimates were calculated to determine the number of studies necessary to change the estimates. Begg’s test and Egger’s regression risk assessed risk of bias across studies. Trim-and-fill analysis was used to estimate the magnitude of effect of the bias. Meta-regression was completed when at least 10 studies provided data for an outcome.

Results
We included 36 studies in the review, (N=157 546 participants). Thirty-one studies were conducted in an obstetric unit setting (n=70 393), four studies were conducted in midwife led settings (n=61 385) and one study was a mixed setting (OU and homebirth) (n=25 768). Midwife led settings included planned home and freestanding midwifery unit (k=1), alongside midwifery units (k=1), planned homebirth (k=1), a freestanding midwifery unit and an alongside midwifery unit (k=1) and an alongside midwifery unit (k=1). For water immersion, 25 studies involved women who planned to have/had a waterbirth (n=151 742), seven involved water immersion for labour only (1901), three studies reported on water immersion during labour and waterbirth (n=3688) and one study was unclear about the timing of water immersion (n=215).
Water immersion significantly reduced use of epidural (k=7, n=10 993; OR 0.17 95% CI 0.05 to 0.56), injected opioids (k=8, n=27 391; OR 0.22 95% CI 0.13 to 0.38), episiotomy (k=15, n=36 558; OR 0.16; 95% CI 0.10 to 0.27), maternal pain (k=8, n=1200; OR 0.24 95% CI 0.12 to 0.51) and postpartum haemorrhage (k=15, n=63 891; OR 0.69 95% CI 0.51 to 0.95). There was an increase in maternal satisfaction (k=6, n=4144; OR 1.95 95% CI 1.28 to 2.96) and odds of an intact perineum (k=17, n=59 070; OR 1.48; 95% CI 1.21 to 1.79) with water immersion. Waterbirth was associated with increased odds of cord avulsion (OR 1.94 95% CI 1.30 to 2.88), although the absolute risk remained low (4.3 per 1000 vs 1.3 per 1000). There were no differences in any other identified neonatal outcomes.

Conclusions
This review endorses previous reviews showing clear benefits resulting from intrapartum water immersion for healthy women and their newborns. While most included studies were conducted in obstetric units, to enable the identification of best practice regarding water immersion, future birthing pool research should integrate factors that are known to influence intrapartum interventions and outcomes. These include maternal parity, the care model, care practices and birth setting.

PROSPERO registration number
CRD42019147001.

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Luglio 2022

Correction: Reports of myocarditis and pericarditis following mRNA COVID-19 vaccination: a systematic review of spontaneously reported data from the UK, Europe and the USA and of the scientific literature

Lane S, Yeomans A, Shakir S. Reports of myocarditis and pericarditis following mRNA COVID-19 vaccination: a systematic review of spontaneously reported data from the UK, Europe and the USA and of the scientific literature. BMJ Open 2022;12:e059223. doi: 10.1136/bmjopen-2021-059223
This article was previously published with an error.
The authors have been made aware of an error in table 7 against row 20 (Lai, reference 61), for the percentage of carditis cases who had received a second vaccine dose. This inaccuracy has been corrected in the table, and now reads ‘75.0% followed 2nd dose.’

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Luglio 2022

Epidemiology and risk factors of self-reported systemic allergic reactions to a Hymenoptera venom in beekeepers worldwide: a protocol for a systematic review of observational studies

Introduction
Systemic allergic reaction (SAR) to a Hymenoptera venom is a potentially life-threatening disorder. The rate of SAR between beekeepers in comparison with a healthy individual is different. The risk for an SAR is particularly high in beekeepers due to their persistent or seasonal exposure to the stinging Hymenoptera. We aim to provide a critical appraisal and a synthesis of evidence-based data from epidemiological observational studies, focusing on SARs to a Hymenoptera venom and the associated risk factors for SARs in beekeepers worldwide.

Methods and analysis
Searching will include seven electronic databases for published studies without language restrictions, from inception up to 3 August 2021, and it will be rerun for all electronic databases prior publication. Only epidemiological observational studies in beekeepers will be included. The risk of bias in the included studies will be appraised by using the Joanna Briggs Institute Critical Appraisal Checklist for Analytical Cross-Sectional Studies and the Newcastle-Ottawa Scale, adapted for cross-sectional studies. For the certainty of evidence, the Grading of Recommendations Assessment, Development and Evaluation approach will be used. Qualitative synthesis will be presented in a tabulated format with the selected characteristics across primary studies and the main outcome of interest. A meta-analysis is planned to be performed if there will be a sufficient number of homogeneous studies with complete data. The Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 statement will guide the reporting of this systematic literature review.

Ethics and dissemination
No ethics approval is needed to conduct the systematic literature review since it will be solely based on the published literature. Findings will be disseminated through the relevant conferences, peer-review and open-access journals.
PROSPERO registration number
CRD42021260922.

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Luglio 2022

Why do acute healthcare staff engage in unprofessional behaviours towards each other and how can these behaviours be reduced? A realist review protocol

Introduction
Unprofessional behaviours encompass many behaviours including bullying, harassment and microaggressions. These behaviours between healthcare staff are problematic; they affect people’s ability to work, to feel psychologically safe at work and speak up and to deliver safe care to patients. Almost a fifth of UK National Health Service staff experience unprofessional behaviours in the workplace, with higher incidence in acute care settings and for staff from minority backgrounds. Existing analyses have investigated the effectiveness of strategies to reduce these behaviours. We seek to go beyond these, to understand the range and causes of such behaviours, their negative effects and how mitigation strategies may work, in which contexts and for whom.

Methods and analysis
This study uses a realist review methodology with stakeholder input comprising a number of iterative steps: (1) formulating initial programme theories drawing on informal literature searches and literature already known to the study team, (2) performing systematic and purposive searches for grey and peer-reviewed literature on Embase, CINAHL and MEDLINE databases as well as Google and Google Scholar, (3) selecting appropriate documents while considering rigour and relevance, (4) extracting data, (5) and synthesising and (6) refining the programme theories by testing the theories against the newly identified literature.

Ethics and dissemination
Ethical review is not required as this study is a secondary research. An impact strategy has been developed which includes working closely with key stakeholders throughout the project. Step 7 of our project will develop pragmatic resources for managers and professionals, tailoring contextually-sensitive strategies to reduce unprofessional behaviours, identifying what works for which groups. We will be guided by the ‘Evidence Integration Triangle’ to implement the best strategies to reduce unprofessional behaviours in given contexts. Dissemination will occur through presentation at conferences, innovative methods (cartoons, videos, animations and/or interactive performances) and peer-reviewed journals.

PROSPERO registration number
CRD42021255490.

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Luglio 2022

Review of drug recalls and quality of pharmaceutical products in Nepal

Objectives
To evaluate the pattern of substandard and falsified pharmaceutical products recall in Nepal.

Setting
We analysed drug recall notices issued by the Department of Drug Administration (DDA), Nepal, and systematically reviewed peer-reviewed research articles during January 2010 to December 2020.

Participants
This study did not include human participants. However, data were collected from 72 drug recall notices issued by DDA and four research papers.

Results
A total of 346 pharmaceutical products were recalled during the reported period. The number of recalled pharmaceutical products has increased significantly over the past decade in Nepal. The most frequently recalled drugs were antimicrobials followed by gastrointestinal medicines, vitamins and supplements and pain and palliative medicines among others. Number of imported recalled drugs were slightly higher (42.2%) than domestic recalled drugs (40.7%). Sixty-two percentage of recalled drugs were substandard, 11% were falsified and remaining 27% were not registered at the DDA. Similarly, higher number of modern drugs (62%) were recalled than traditional ones (35%). Hand sanitisers used to minimise COVID-19 transmission contributed significantly to the list of recalled pharmaceutical products in 2020. Most of these sanitisers contained significant amounts of methanol (as high as 75% v/v) instead of appropriate amount of ethyl or isopropyl alcohol. The peer-reviewed research papers reported issues with labelling, unregistered drugs and drugs failed in several laboratory testing.

Conclusion
Our analysis showed that number of recalls of substandard and falsified drugs are increasing in Nepal. Since the recall data in this paper did not include number of samples tested and location of samples collected, more studies to understand the prevalence of substandard and falsified drugs in Nepal is recommended.

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Luglio 2022

Impact of COVID-19 on paediatric admissions to a Chinese hospital: a single-centre retrospective chart review

Objective
To explore the impact of the COVID-19 on the distribution, type and patterns of diseases in hospitalised children under local antiepidemic measures.

Design
Retrospective chart review.

Setting
Electronic medical records of patients hospitalised in the paediatric department of a tertiary hospital in South China from 21 January 2019 to 20 January 2021.

Participants
Records of 2139 patients.

Outcome measures
Data were analysed before and during the COVID-19 pandemic. Disease characteristics were analysed based on the 10th revision of the International Statistical Classification of Diseases and Related Health Problems. Features of the length of hospital stay were investigated. Categorical variables involving more than three groups were analysed using an overall 2 test, followed by pairwise comparisons.

Results
During the COVID-19 outbreak period, paediatric hospitalisation was reduced by 29.6%, from 1255 to 884. The proportions of infection-related diseases (36.3% (455 cases) vs 20.8% (184 cases)), respiratory system-related diseases (22.5% (283 cases) vs 9.4% (83 cases)); and endocrine, nutritional and metabolic diseases (17.1% (214 cases) vs 9.2% (81 cases)) decreased significantly, whereas that of musculoskeletal and connective tissue diseases increased from 11.0% (138 cases) to 20.1% (178 cases), thereby becoming the most common reason for hospitalisation. The proportions of diseases of the nervous system (12.4% (156 cases) to 18.8% (166 cases)) and mental and behavioural disorders (0.2% (3 cases) to 2.1% (19 cases)) increased significantly. The average length of hospital stay increased after the outbreak (7.57±6.53 vs 8.36±6.87).

Conclusion
The number of hospitalisation cases decreased during the COVID-19 period. The prominent decreases in hospitalisation associated with infections and respiratory system diseases were likely attributed to the improved epidemic prevention work, enhancement of people’s health awareness and fear of possible exposure to COVID-19. Describing the impact of COVID-19 on disease patterns may provide a reference for resource planning during the pandemic.

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Luglio 2022

Diagnostic accuracy of ultrasound, CT and their combination in detecting cervical lymph node metastasis in patients with papillary thyroid cancer: a systematic review and meta-analysis

Objectives
To determine the diagnostic accuracy of ultrasound (US), CT and their combination in detecting cervical lymph node metastasis (CLNM) in patients with papillary thyroid cancer (PTC).

Methods
Medline (via PubMed), Web of Science, Embase were searched to identify studies published till 5 December 2021 that used US and CT to detect CLNM in patients with PTC. The primary outcomes were sensitivity, specificity and diagnostic ORs in neck-level-based (lymph nodes are analysed by neck level) or patient-based (lymph nodes are analysed by patient) analysis. Secondary outcomes were sensitivity, specificity and DORs in the central and lateral compartments.

Results
Fourteen studies (6167 patients with 11 601 neck lymph nodes) met the inclusion criteria. Based on the neck-level-based analysis, the pooled sensitivity, specificity and DORs were 0.35 (95% CI 0.34 to 0.37), 0.95 (95% CI 0.94 to 0.95) and 13.94 (95% CI 9.34 to 20.82) for US, were 0.46 (95% CI 0.44 to 0.47), 0.88 (95% CI 0.87 to 0.89) and 7.24 (95% CI 5.46 to 9.62) for CT, were 0.51 (95% CI 0.49 to 0.52), 0.85 (95% CI 0.84 to 0.86), 6.01 (95% CI 3.84 to 9.40) for the combination of US and CT. In the patient-based analysis, the pooled estimates of sensitivity, specificity and DOR were 0.41 (95% CI 0.36 to 0.46), 0.92 (95% CI 0.89 to 0.94) and 7.56 (95% CI 4.08 to 14.01) for US, were 0.49 (0.44 to 0.54), 0.91 (0.89 to 0.94), 9.40 (5.79 to 15.27) for CT, and were 0.64 (95% CI 0.57 to 0.71), 0.83 (95% CI 0.77 to 0.88), 8.59 (95% CI 5.37 to 13.76) for the combination of US and CT.

Discussion
These findings suggest US, with a DOR almost twice that of CT in the neck-level-based analysis, was superior to CT in detecting CLNM in patients with PTC, especially in the lateral compartment. The combination of US and CT increased the sensitivity from 41%–49% for the individual modalities to 64% for combined modalities in the patient-based analysis.

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Luglio 2022