Despite an elevated risk of psychopathology stemming from COVID-19-related stress, many essential workers stigmatise and avoid psychiatric care. This randomised controlled trial was designed to compare five versions of a social-contact-based brief video intervention for essential workers, differing by protagonist gender and race/ethnicity.We examined intervention efficacy on treatment-related stigma (‘stigma’) and openness to seeking treatment (‘openness’), especially among workers who had not received prior mental healthcare. We assessed effectiveness and whether viewer/protagonist demographic concordance heightened effectiveness.N = 2734) randomly viewed a control video or brief video of an actor portraying an essential worker describing hardships, COVID-related anxiety and depression, and psychotherapy benefits. Five video versions  followed an identical 3 min script. Half the intervention group participants rewatched their video 14 days later. Stigma and openness were assessed at baseline, post-intervention, and at 14- and 30-day follow-ups. Trial registration: NCT04964570.Essential workers  and increased openness . The initial increase in openness was largely maintained in the repeated-video group at day 14 , particularly among viewers without history of psychiatric treatment . Increases were not sustained at follow-up. Female participants viewing a female protagonist and Black participants viewing a Black protagonist demonstrated greater openness than other demographic pairings.All video intervention groups reported immediately decreased stigma (Brief video-based interventions improved immediate stigma and openness. Greater effects among female and Black individuals viewing demographically matched protagonists emphasise the value of tailored interventions, especially for socially oppressed groups. This easily disseminated intervention may proactively increase care-seeking, encouraging treatment among workers in need. Future studies should examine intervention mechanisms and whether linking referrals to psychiatric services generates treatment-seeking. Thus, they are exposed daily, sometimes unwillingly, to increased risk of infection.4 Moreover, Black and Latinx adults represent large proportions of essential workers in the USA; evidence suggests that members of underserved racial and ethnic groups have lower access to mental healthcare and often report more persistent and impairing depressive symptoms than non-Latinx individuals.6 These underserved groups are disproportionately affected by the pandemic, which raises their risk of mental health problems.9 Most research in this area has focused on healthcare workers; other essential workers have been relatively neglected.Essential workers are employed in critical occupations considered indispensable for daily life . According to recent research, essential workers have higher prevalence of anxiety and depressive disorders owing to the continuing stress of the COVID-19 pandemic.10 Another important obstacle is stigma towards mental healthcare.11 Treatment-related stigma involves perceiving mental-healthcare-seeking as weakness, anticipating negative attitudes from friends and families, and fearing discrimination from colleagues.13 Therefore, applying effective interventions to reduce treatment-related stigma and promote treatment-seeking may increase the likelihood that essential workers access care and may mitigate the risk of chronic, debilitating mental health problems.14There are many structural and other barriers to service use among essential workers and underserved racial and ethnic groups, including constraining work conditions and limited insurance.15 Social-contact-based interventions involve interaction with an empowered presenter with lived experience who describes coping successfully with distress and attaining their desired goals. Individuals interacting with these empowered presenters show decreased prejudice and discrimination related to mental health.16 Recent studies have reported that video-based social contact interventions have similar efficacy to in-person interventions in reducing stigma.18 Video-based interventions have the advantages of cost-effectiveness, scalability, replicability and ease of dissemination.19Previous research has shown that social-contact-based interventions are most effective in reducing stigma and increasing openness to seeking treatment.n = 350)20 and military veterans (n = 172).21 In some cases, we found greater efficacy when the viewer and the protagonist shared sociodemographic characteristics such as gender, race/ethnicity and occupation, possibly by enhancing viewers’ identification and emotional engagement with the video protagonist.22 These exploratory studies were the first to employ such an intervention and demonstrate its effect on openness to seeking treatment. Nonetheless, they had limitations, which the present study aims to address.Recently, our team demonstrated the efficacy of social-contact-based brief video interventions in increasing openness to seeking treatment for mental health conditions among US healthcare workers  of US non-healthcare essential workers. Essential workers were randomly assigned to one of the video interventions or to a video control group. Assessments of treatment-related stigma and openness to seeking treatment were conducted at baseline, immediately post-intervention, and at 14- and 30-day follow-ups. Among the intervention groups, half of the participants viewed the same video again on day 14. We hypothesised that: (a) the brief video-based intervention would have the immediate and, on re-viewing, repeated effect of reducing treatment-related stigma and increasing openness to seeking treatment compared with the control condition; (b) viewing the video twice would be associated with greater durability of effect compared with viewing it once and with the control condition; (c) participants without history of treatment would experience greater intervention effects; and (d) viewer–protagonist concordance with respect to gender and/or race/ethnicity would yield greater effects on stigma reduction and openness to seeking treatment.We conducted a randomised controlled trial to test the efficacy of five versions of a brief video-based intervention, differing by protagonist gender and/or race/ethnicity, in reducing treatment-related stigma and increasing openness to seeking treatment in a larger sample  and watched the video (170 s) before the ‘next’ button appeared. We also excluded respondents who failed our attention-testing questions .Participants were recruited through Prolific, a crowdsourcing tool frequently used in medical and psychology research with worldwide evidence of validity across tasks.Recruitment took place during August and September of 2021. We only included essential workers who were aged 18–80 years, English-speaking and US residents. We defined ‘essential work’ as: (a) non-healthcare-related indispensable occupations ; (b) occupations that required daily travel to work during the COVID-19 pandemic. Participants were compensated $9 for study participation. The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008. All procedures involving human subjects/patients were approved by the New York State Psychiatric Institute Institutional Review Board (#8128). Before study entry, participants reviewed an informed consent form. Those agreeing to participate completed the study procedures via Qualtrics.com, a secure, online data-collection platform.https://doi.org/10.1192/bjo.2022.575).Participants were randomised to either video intervention or video control groups. The video intervention group included five brief video versions, which varied by the race/ethnicity and gender of the protagonist – Black female, Latinx female, Latinx male, White female and White male. Participants were evenly divided between the Black, Latinx and White protagonists. The control group watched a same-length video featuring nature views and horses, accompanied by relaxing music. The pre-intervention survey included demographic and COVID-19-related information, and questionnaires assessing treatment-related stigma and openness to seeking treatment. The post-intervention survey, conducted immediately after the intervention, included the same assessments of treatment-related stigma and openness to seeking treatment as the baseline survey. Fourteen days later, half of the participants in the intervention groups rewatched the same video (‘repeated video’), whereas the remaining participants had no additional intervention (‘video’). Follow-ups included assessment of treatment-related stigma and openness to seeking treatment and were conducted at 14 and 30 days post-intervention  to 5 (strongly agree). Total scores ranged from 3 to 15, with lower scores indicating less stigma. In this study, Cronbach's alpha was 0.87.We measured treatment-related stigma with the Self-Stigma of Seeking Help (SSOSH-3) scale.25 The items were: ‘I would want to get psychological help if I were worried or upset for a long period of time’, ‘I might want to have psychological counseling in the future’ and ‘A person with an emotional problem is not likely to solve it alone; they are more likely to solve it with professional help’. Responses ranged from 1 (disagree) to 4 (agree), for a total score of 3 to 12, with higher scores indicating greater openness to seeking treatment. In this study, Cronbach's alpha was 0.83.Openness to seeking treatment was determined by the three ‘openness to help-seeking’ items from the Attitude Towards Seeking Professional Psychological Help (ATSPPH) scale – Short Form.t-tests were used to compare SSOSH (stigma) and ATSPPH (openness to treatment) scores between video intervention and control groups. Intervention effects were examined using generalised estimating equations (GEE),26 as recommended for randomised controlled trials.27 The GEE approach represents correlated repeated-measures analysis and calculates missing data via estimated marginal means based on the whole sample. It includes all randomised participants providing data for at least at one time point. To account for within-respondent dependencies in the models, we specified an unstructured correlation matrix. We applied a full factorial model across the four time points  for the SSOSH and ATSPPH. To test our first hypothesis, we examined the immediate and repeated effects (video versus control) with time-by-group interaction terms. Using the GEE model, we tested the 14-day video effects (single video versus repeated-video versus control), addressing our second hypothesis about durability of effects. For the third hypothesis, we first conducted a one-way ANOVA examining whether baseline SSOSH and ATSPPH mean scores of each participant subgroup  significantly differed. We then conducted the same GEE analysis separately for each subgroup. For the fourth hypothesis, we tested whether viewer–protagonist concordance in gender and/or race/ethnicity yielded a greater effect among respondents . We conducted two sets of analyses, first addressing concordance by gender and then concordance by race/ethnicity. The sample size was not large enough to address the intersectionality of gender and race/ethnicity simultaneously . To test the gender-concordance hypothesis, we expanded the GEE model to include fixed effects for the participant's and protagonist's genders and their interaction and the full factorial interaction of these with video condition and time; this allowed us to test for differential effects for each participant's gender as a function of protagonist gender immediately following the video or the repeated video, and any lasting effects. Contrasts measuring the concordance effect were formed specifically for gender and overall; that is, we obtained a concordance effect specifically for women separately from a concordance effect for men (gender-specific concordance) and we formed an overall gender-concordance effect  contrasting with overall gender discordance . Participants who indicated their gender to be other than male or female were excluded from this analysis owing to small numbers. Similar analyses were conducted to test the concordance hypothesis by race/ethnicity, including a fixed effect for participant and actor race/ethnicity. These analyses were limited to participants who self-identified as Black, Latinx, or White so that concordance was possible, as the actors were limited to these races/ethnicities. In the race/ethnicity-concordance analysis, we also included the gender of the participant as a control variable to account for any confounding imbalance due to there being only a female Black actor  condition. Finally, we ran all concordance analyses restricted to the subsample that had not previously received mental health treatment as we expected this group would have the largest effect sizes. Effect sizes are reported using Cohen's d, when appropriate, obtained by scaling mean differences between treatment groups by the standard deviation of the measure across all groups at baseline. All statistical tests were two-sided, using α < 0.05.Pearson's χ² and one-way analysis of variance (ANOVA) were used to compare sociodemographic and COVID-19-related characteristics across the five versions of the video intervention group and the control group, and independent We collected data on clinical symptoms including level of self-reported anxiety and depression. We found no association between symptom severity and intervention effect on stigma or treatment-seeking response.Mage = 27.1 ± 9.3 years, range 18–73) who completed the baseline and post-intervention assessments. Of those, 80% (n = 2175) completed the 14-day assessment and 72% (n = 1955) completed the 30-day assessment  individuals failed validity tests and were excluded from analyses. The final sample included 2374 essential workers . A significant group-by-time interaction emerged  for an immediate effect . We found no group-by-time interaction for the repeated-video effect, nor any lasting effects at 14-day or 30-day follow-up for the intervention groups.t-test: t = 0.70, P = 0.48). Analyses showed a group-by-time interaction  for an immediate effect  and a group-by-time interaction  for the repeated-video effect . We found no significant difference between the magnitude of immediate and repeated-video effects . There was no lasting effect at 14-day follow-up for the single-video or at 30-day follow-up for the repeated-video groups. Hence, repeating the video led to no significantly greater durability of effect.P < 0.001. Participants without prior therapy showed a group-by-time interaction  for an immediate effect  and a group-by-time interaction  for a repeated-video effect . Participants reporting therapy in the past but not currently showed a group-by-time interaction  for the immediate-video effect only . Participants who reported currently receiving therapy already had near-maximal scores and showed no immediate intervention effects. There was no lasting effect at 14-day follow-up for the single-video or at 30-day follow-up for the repeated-video for any subgroup.We repeated the above-described GEE analysis separately based on treatment status in line with participants’ answers to ‘Have you sought psychological counseling?’, with answers/groups being ‘no prior therapy’, ‘past therapy’, or ‘current therapy’ . BaselinP < 0.0001, Cohen's d = 0.15; discordant – baseline to post-intervention change: 0.21 [0.12], P = 0.07, Cohen's d = 0.08). Males watching male protagonists showed greater decreases in SSOSH scores than males watching female protagonists ; between-group change (concordant v. discordant): 0.22 [0.19], P = 0.009, Cohen's d = 0.08.In the full sample, protagonist gender or race/ethnicity did not influence changes in outcome of stigma and/or openness to seeking treatment. However, among respondents with no prior treatment, concordance between the viewer's and protagonist's gender and/or race/ethnicity yielded a greater effect in some groups (Supplementary Appendix 2 and 3). For example, regarding treatment-related stigma, overall gender concordance  yielded a greater immediate decrease in stigma scores. Females watching female protagonists showed greater decreases in SSOSH scores than females watching male protagonists . However, males watching male protagonists did not show any greater increase in ATSPPH scores than males watching female protagonists .Regarding openness to seeking treatment, females watching female protagonists showed greater increases in ATSPPH scores than females watching male protagonists . We found a similar pattern for the repeated-video effect . No concordance effect was observed for Latinx–Latinx or White–White pairings.Regarding ethnoracial concordance, no concordance effect was found for treatment-related stigma (SSOSH). For openness to seeking treatment, Black participants viewing Black protagonists showed greater immediate increases in ATSPPH scores than Black participants viewing non-Black protagonists  videos, essential workers described their emotional struggles during the COVID-19 pandemic and how mental health treatment helped them cope. As hypothesised, viewing any of the five versions of the video intervention led to immediate decreases in treatment-related stigma and increases in openness to seeking treatment compared with the control condition. The initial increase in openness to seeking treatment was largely maintained in the repeated-video group at day 14. These findings replicate our previous exploratory studies among healthcare workers22 and a greater increase in openness to seeking treatment among male veterans watching a male protagonist .21 Nonetheless, this is the first study to compare several versions of the same video differing in protagonist gender and/or race/ethnicity, thus enabling a test of the concordance hypothesis. Similarly, a study on patient–clinician communication showed higher patient ratings for satisfaction and participation in decision-making among race-concordant groups.28 However, few studies have examined cultural aspects of stigma-reduction interventions10 and, to our knowledge, no other studies on social-contact-based interventions have examined such an effect.Among participants without prior treatment, female or Black viewers watching female or Black protagonists demonstrated a greater immediate increase in openness to seeking treatment than those watching male or non-Black protagonists. These findings are consistent with our previous studies with a single protagonist, which showed secondary findings that may imply a concordance effect. For example, in a study about psychosis-related stigma, we demonstrated greater stigma reduction among females watching a female protagonist 29 whereas our sample included English-speaking Latinx individuals only. Perhaps we would find a greater concordance effect among Spanish-speaking Latinx people watching Spanish-speaking protagonists. Another explanation may be related to lack of power to detect such an effect. In addition to increased sample sizes, future studies should explore the mechanisms of action of the ethnoracial concordance and whether content adjusted to explicitly address these sociodemographic differences creates even greater effects, for example, a Black protagonist describing how their racial background imposes greater difficulties in accessing mental healthcare.Why were our concordance effect findings restricted only to female and Black participants, whereas responses of male or White participants did not vary by protagonist gender and/or race/ethnicity? One explanation lies in the core differences within each category: female and Black individuals are more likely to be socially oppressed than male and White individuals. This underscores the importance of matching viewer and protagonist sociodemographics, especially among members of marginalised groups who are more aware of discrimination and therefore may place greater value on solidarity and identification. However, we did not find similar effects among Latinx viewers. Past studies have shown that mental health stigma is higher among Spanish-speaking Latinx individuals, who also have lower perceptions of need of mental healthcare,n = 2734) allowed us to study this underserved group that has been disproportionally affected by the COVID-19 pandemic and faces an increased risk of mental health problems.30 This is the first study to show such an effect among non-healthcare essential workers. Second, we assessed intervention effects on stigma, a key deterrent to treatment-seeking,11 showing an immediate effect not only in increasing openness to seeking treatment but also in decreasing treatment-related stigma. We found a greater effect among respondents who had never sought or received treatment (53% of the sample), thus strengthening the intervention effect and emphasising its necessity within this in-need subgroup. Last, we tested five versions of the video intervention, altering the gender and race/ethnicity of the protagonist, thus increasing both external and internal validity.This study replicates and extends our previous pilot studies in several important ways. First, its larger sample size  have significantly increased efficacy compared with identical videos lacking this function. For healthcare access, adding a referral to crisis counsellors or an option to connect with a therapist might engage in-need essential workers with mental health services.Although results showed that the intervention had an immediate impact, no lasting effect emerged: effects did not persist at 14 day follow-up after a single video, or at 30 day follow-up following the repeated video. These findings corroborate those of other intervention studies33 Such issues are longstanding and are likely to remain well beyond this pandemic. Telehealth and digital solutions can be key strategies in linking mental health services to essential workers.35 For example, interventions informed by cognitive–behavioural therapy, delivered by mobile apps, may help address infrastructure barriers to accessing care.37 However, other studies show limited efficacy for such treatments.38Treatment-related stigma and treatment-seeking perceptions are not the only barriers to care for essential workers. Structural and other barriers to healthcare significantly impede access to timely care.v. 16% (US) Hispanic/Latino, 66% v. 64% non-Hispanic White, 10% v. 12% non-Hispanic Black and 7% v. 5% non-Hispanic Asian. Second, we did not assess a video featuring a Black male protagonist. Future studies should explore a wider range of gender and race/ethnicity, with sufficiently large samples to study their intersections. Third, we assessed openness to seeking treatment, a measure possibly influenced by social desirability.39 Unfortunately, no research to date, including our own, has measured effects on actual treatment-seeking behaviour. Last, our study may have lacked the power to detect concordance effects among Latinx and male groups. Future studies should explore whether greater tailoring creates a larger effect.This study had several limitations. First, the users of crowdsourcing platforms may differ sociodemographically from the essential worker population, limiting generalisability. Ethnoracially, however, our sample resembled the 2020 US census distribution fairly closely: 14% (study) In summary, this randomised controlled trial replicated and extended our previous findings, showing positive effects of five versions of a social-contact-based brief video intervention, differing with respect to protagonist gender and/or race/ethnicity, especially among essential workers who had received no prior treatment. The 3 min videos showed a modest effect size of reduced treatment-related stigma and increased immediate openness to seeking treatment, with greater effects among female and Black viewers who watched protagonists with matching sociodemographic characteristics. Policy makers and employee assistance programmes should consider using such easily disseminatable interventions to proactively encourage essential workers to seek help and to provide mental health services to those needing them. Future studies should examine the mechanisms of action of these brief video interventions and whether links to referrals could foster immediate behavioural change.


Significant resources are invested in the UK to collect data for National Clinical Audits (NCAs), but it is unclear whether and how they facilitate local quality improvement (QI). The perioperative setting is a unique context for QI due to its multidisciplinary nature and history of measurement. It is unclear which NCAs evaluate perioperative care, to what extent their data have been used for QI, and which factors influence this usage.NCAs were identified from the directories held by Healthcare Quality Improvement Partnership (HQIP), Scottish Healthcare Audits and the Welsh National Clinical Audit and Outcome Review Advisory Committee. QI reports were identified by the following: systematically searching MEDLINE, CINAHL Plus, Web of Science, Embase, Google Scholar and HMIC up to December 2019, hand-searching grey literature and consulting relevant stakeholders. We charted features describing both the NCAs and the QI reports and summarised quantitative data using descriptive statistics and qualitative themes using framework analysis.We identified 36 perioperative NCAs in the UK and 209 reports of local QI which used data from 19 (73%) of these NCAs. Six (17%) NCAs contributed 185 (89%) of these reports. Only one NCA had a registry of local QI projects. The QI reports were mostly brief, unstructured, often published by NCAs themselves and likely subject to significant reporting bias. Factors reported to influence local QI included the following: perceived data validity, measurement of clinical processes as well as outcomes, timely feedback, financial incentives, sharing of best practice, local improvement capabilities and time constraints of clinicians.public reporting of UK perioperative NCA data for local QI, despite evidence of improvement of most NCA metrics at the national level. It is therefore unclear how these improvements are being made, and it is likely that opportunities are being missed to share learning between local sites. We make recommendations for how NCAs could better support the conduct, evaluation and reporting of local QI and suggest topics which future research should investigate.There is limited CRD42018092993).The review was registered with the International Prospective Register of Systematic Reviews (PROSPERO: The online version contains supplementary material available at 10.1186/s13741-022-00273-0. Local quality improvement (QI) initiatives, including audit and feedback, have the potential to substantially improve healthcare services, but implementation can be variable and is not always sustainable .A scoping review methodology was deemed most appropriate to describe this heterogeneous literature and achieve our aims. Scoping reviews are used to explore the extent of existing research activity, map any gaps in the literature and inform policy, practice and research  delivering direct patient care’ Reported provider-level dataaIncluded in the NHS England Quality Account reporting requirements ORbIncluded in the list of Scottish Healthcare Audits run by Information Services Directorate Scotland ORcIncluded in the list of National Audits mandated by the Welsh National Clinical Audit and Outcome Review Advisory Committee (NCAORAC)Were either of the following:Two reviewers with expertise in the perioperative setting hand-searched the Healthcare Quality Improvement Partnership (HQIP) directory — the coordinator of NCAs in England and Wales, and the list of Scottish Healthcare Audits (SHA). The first search in November 2017 was updated in January 2020. Audits were selected for inclusion as follows:We excluded confidential enquiries or outcome programmes because these national projects investigate individual incidents or selected themes rather than auditing patient care.Evaluations of NCAs were conducted by HQIP in 2014, and Scottish Healthcare Audits in 2015, with NCAs completing questionnaires describing their design, conduct and impact : bibliographies of included articles; reports and websites of each perioperative NCA; supplements containing conference proceedings from the We consulted HQIP and twice contacted the NCA providers for examples of local QI. Preliminary results of this scoping review were presented to an independent panel of perioperative clinicians, academics, representatives of the RCOA and lay members in May 2018. Feedback from these consultations did not identify any gaps in our search strategy. Their comments have been included in our analysis.The search results were imported into Mendeley (© 2018 Elsevier B.V.). Duplicates were removed, titles were screened by one reviewer and then abstracts were screened independently by two reviewers. Discrepancies between these reviewers (involving five reports) were resolved after discussion. One reviewer reviewed all of the full-text reports, and a second reviewer independently reviewed a random sample of 10% of all manuscript types. No discrepancies were found between reviewers at this stage.A charting template  2.0 guidelines published in 2015  of the 36 NCAs , 12 (33%) NCAs focussed on specific procedure , 6 (17%) NCAs audited a whole specialty (e.g. Adult Cardiac Surgery) and 5 (14%) NCAs discussed aspects of perioperative care (e.g. PQIP). All NCAs analysed performance at the level of hospitals, but 16 (44%) also published outcomes of individual surgeons. Nineteen (53%) NCAs described taking a QI approach in their protocol or website. The most commonly stated purpose of NCAs was to reduce clinical variation at the national level.The median start time of the NCAs was 2011 (range 1994–2017). Surgical specialties and Royal Colleges constituted the largest group of perioperative NCA providers in England and Wales (48%). NCAs measured different aspects of care: 13 (33%) NCAs focussed on a Only 8/21 (38%) of the NCAs with self-assessments reported making real-time data available to providers. Education sessions were the most commonly employed intervention to support local improvement and have been used by 16 (44%) of NCAs. Clinical recommendations were universally made at a national level, but no evidence was found of an NCA providing individualised action plans for hospitals to make improvements. Financial incentives, in the format of best practice tariffs, have been used by five (14%) NCAs: the NHS patient-reported outcome measures (PROMs) audit, the National Hip Fracture Database (NHFD), the National Joint Registry (NJR), the Trauma Audit and Research Network audit (TARN) and recently the National Emergency Laparotomy Audit (NELA). One NCA (NHFD) had an accessible registry of local QI projects using their data. Four NCAs  reported awarding prizes to projects performing local QI with their data.At the national level, 97% of process/outcome measures for which longitudinal data were available demonstrated improvement in their most recent reports. A total of 16/21 (76%) NCAs self-assessed that their data had been used for local QI.Two-hundred nine reports of local QI using perioperative NCA data were identified Fig. .Fig. 1FlEvidence of local QI was found for 19 (73%) NCAs. Six (17%) NCAs collectively contributed 185 (89%) of all reports Table .Table 1TThe majority of reports (64%) were unstructured vignettes published within NCA annual reports or on their websites (online Supporting information SProcess indicators were the most common type of indicator to be used for QI projects (69% of reports), compared to 45% of reports using outcome indicators (online Supporting information Table SOne-hundred thirty-seven (66%) reports explicitly reported the impact of the QI project (online Supporting information Table SFactors which influenced the use of NCA data were cited in 60 29%) reports. Themes were classified as occurring predominantly at micro, meso or macro levels  reports. Five formats of collaborative groups were reported: dedicated prospective trials using NCA data (e.g. the Emergency Laparotomy Collaborative); regional QI collaboratives, often comprising trainee doctors (e.g. Liverpool Research Trainee Collaborative); groups leveraging clinical pathways ; Academic Health Science Networks; or between all hospitals participating in a particular NCA. Collaborative activities were popular with local participants, who welcomed social support and peer review of their data or QI ideas but were noted to be potentially difficult to scale if financial support was required.Twenty-five (12%) reports were suitable for quality assessment using the SQUIRE 2.0 guidelines  NCAs, whereas 185 (89%) reports were associated with just six (17%) NCAs. We suggest that this reflects a missed opportunity to support local QI, and that best practice could be spread from the two exemplar NCAs we identified (NHFD and NELA) which measured useful clinical processes, provided valid and timely feedback, facilitated productive collaborative QI efforts using their data involving multiple hospitals and actively sought out and reported case studies of local QI, either through abstract competitions or annual report vignettes.In keeping with the literature, we found that the nature of NCA feedback influenced how it was used  had a prospective registry of local QI reports, and no NCA reported a QI-output analysis. The abstracts, posters and annual report vignettes which dominated our findings often comprised unstructured narrative, making it hard for others to replicate successful projects. Only a minority of reports described factors influencing their data or projects. Where impacts of QI were explicitly reported, they were almost universally positive, lending weight to suspected publication bias and missing the vital opportunity for sharing learning from negative studies , and local QI can occur without NCA data; the number of QI projects which we found to be publicly reported may not correlate with the wider impact of these NCAs.There are several limitations to this review. By only examining the perioperative setting in the UK, we are unable to comment on measurement systems in other contexts, and it is possible that QI activity might be greater in other specialities or condition-specific audits. We found the majority of QI reports by hand-searching the literature and therefore some reports may have been missed. Further reports may have been published after the searches were made (ending December 2019). Some QI projects may have been reported locally, orally or via social media and would not have been found by our strategy. Furthermore, this review did not look for local improvement per se but for This review provides evidence of missed opportunities for local QI using NCA data in the UK perioperative setting. The two NCAs which were associated with the vast majority of QI reports provided valid and timely feedback, supported collaboration between hospitals and actively sought out local case studies. There was a high likelihood of reporting bias towards projects which achieved a positive impact.To improve this situation, we would recommend the following strategies. First, NCAs should ensure they measure process metrics amenable to QI. Second, they should deliver feedback in a timely and accessible manner, aimed at teams rather than individuals. Third, feedback should be linked to localised action plans and possibly financial incentives. Fourth, local QI projects and evaluations thereof should be prospectively recorded in accessible registries in order to better share learning from projects achieving both ‘positive’ and ‘negative’ impacts. The interaction between NCA practices with local contexts remains a question for future research, as does the most effective method(s) for promoting collaboration within and between hospitals.Additional file 1.


Nontuberculous mycobacteria (NTM), are natural inhabitants of natural waters, engineered water systems, and soils. As a consequence of their ubiquitous distribution, humans are surrounded by these opportunistic pathogens.Mycobacterium marinum infection associated with home tropical ornamental fish aquaria. A 43-years-old man reported progressively increasing nodules over his left forearm and hand for more than 7 months.In this report, we describe a case of scubcutaneous Based on NTM culture, pathological examination, identification by gene sequencing and matrix assisted laser desorption ionization time of flight mass spectrometry, the diagnosis of scubcutaneous NTM infection was confirmed.The patient was treated with itraconazole for suspected sporotrichosis over 1 month.The patient was treated with oral doxycycline hydrochloride capsules (200 mg/day) for 5 months, the nodules had resolved.Home aquarium environments may serve as a possible source of mycobacteria infection in urban family. Of these, Mycobacterium marinum is a slowly growing pigmented NTM responsible for “fish tank granuloma” due to its ability to cause localized skin and soft tissue infections in individuals who suffered puncture injuries or other types of trauma in freshwater or salt water.Nontuberculous mycobacteria (NTM) are normal inhabitants of a variety of environmental habitats that are shared with humans and animals, including natural waters, drinking water distribution systems, and soils.Mycobacterium marinum (M. marinum) (GenBank accession no. CP024190.1). Another subculture of the isolate was submitted to identification by matrix assisted laser desorption ionization time of flight mass spectrometry . The pretreatment method of mass spectrometry was based on literature and manufacturer’s suggestions. Extended direct transfer sample preparation procedure was performed in the biosafety cabinet. The picked colony was smeared as a thin film directly onto a sample position of a 96-plate polished steel target plate using a sample applicator, 1 μl 70% formic acid was then added to overlay the sample position. 1 μl of Bacterial Test Standard (BTS) was deposited onto a assigned BTS quality control position of the steel target plate. After sample position and BTS quality control position were air-dried at room temperature, the positions were overlayed with 1 μl α-cyano-4-hydroxycinnamic acid (HCCA) matrix solution. When the spots were air-dried again, the prepared steel target plate was loaded into the mass spectrometer. Acquisition of the spectra was done in the range of a mass/charge (m/z) ratio of 2000 to 20,000. The composite profile was analyzed using the Bruker MALDI Biotyper software (version 3.1) with the standard reference Mycobacteria Library (version 4.0) database. Scoring was done as per criteria established by Bruker Daltonics. The spectral patterns maximum protein peak intensity > 1000 were compared with the Bruker Mycobacteria Library database for identification, the result was M. marinum with score of 2.007  for 5 months, the nodules had resolved  antifungal agents due to misdiagnosis as sporotrichosis. Positive rates of NTM culture ranged from 2.9% to 96.8%.M. marinum has an optimal growth temperature of 25°C, colonies grown on Lowenstein-Jensen solid medium are wrinkled, and faint yellow after exposure to light. matrix assisted laser desorption ionization time of flight mass spectrometry technology can quickly and effectively identify NTM.The incidence of mycobacterial species in aquarium fish and water environments were as high as 42.9% and 75.4% respectively.Conceptualization: Xiujiao Xia.Data curation: Shi Chen.Formal analysis: Shi Chen.Funding acquisition: Zehu Liu.Methodology: Shi Chen.Project administration: Xiujiao Xia.Writing – original draft: Xiujiao Xia.Writing – review & editing: Shi Chen, Zehu Liu, Xiujiao Xia.


Phonon polariton (PhP) nanoresonators can dramatically enhance the coupling of molecular vibrations and infrared light, enabling ultrasensitive spectroscopies and strong coupling with minute amounts of matter. So far, this coupling and the resulting localized hybrid polariton modes have been studied only by far-field spectroscopy, preventing access to modal near-field patterns and dark modes, which could further our fundamental understanding of nanoscale vibrational strong coupling (VSC). Here we use infrared near-field spectroscopy to study the coupling between the localized modes of PhP nanoresonators made of h-BN and molecular vibrations. For a most direct probing of the resonator-molecule coupling, we avoid the direct near-field interaction between tip and molecules by probing the molecule-free part of partially molecule-covered nanoresonators, which we refer to as remote near-field probing. We obtain spatially and spectrally resolved maps of the hybrid polariton modes, as well as the corresponding coupling strengths, demonstrating VSC on a single PhP nanoresonator level. Our work paves the way for near-field spectroscopy of VSC phenomena not accessible by conventional techniques. Vibrational strong coupling (VSC) promises ultrasensitive IR spectroscopy and modification of material properties. Here, nanoscale mapping of VSC between organic molecules and individual IR nanoresonators is achieved by remote near-field spectroscopy. They offer intriguing possibilities for ultra-sensitive vibrational spectroscopy10 and for modifying chemical reactions4. Typically, VSC is achieved with molecules embedded into microcavities, implying large mode volumes and large amounts of molecules, which limits access to quantum phenomena that may be accesible only for nanoscale amounts of molecules or at the level of a few molecules. In this regard, plasmonic infrared resonators are a promising route to achieve VSC at the nanoscale8 owing to their dramatically reduced mode volumes as compared to microcavities. Alternatively, phonon polaritons (PhP) can be employed for VSC experiments, offering stronger polariton confinement and larger quality factors11. Unfortunately, the far-field extinction cross-section of individual PhP nanoresonators20 is extremely small , challenging infrared far-field spectroscopy. Further, subradiant dark modes—offering the advantage of longer lifetimes—are difficult to probe by far-field spectroscopy. These problems can be circumvented by nanoscale Fourier Transform Infrared (nano-FTIR) spectroscopy, which employs the strong field concentration at the apex of a metallic scanning probe tip (the near-field probe)22 to enable near-field spectroscopy and spatial mapping of both bright and dark modes of individual phononic nanoresonators18. However, the near-field mapping of VSC employing PhP nanoresonators has been elusive so far.Strong coupling between molecular vibrations and infrared photons  leads to hybrid light-matter states24, eventually reaching strong tip-resonator and tip-molecule coupling. Although this coupling may be exploited for on-demand control of VSC, it may challenge the probing of the hybrid polariton modes that are exclusively formed by the molecule-nanoresonator coupling.Nano-FTIR spectroscopy has been employed to study the coupling between molecular vibrations and plasmonic resonators, but the near-field probe itself can also couple with the plasmonic resonator and the moleculesIn ref. Here we demonstrate that hybrid polariton modes formed by vibrational strong coupling between a single PhP nanoresonator and molecular vibrations can be studied and imaged in real space by nano-FTIR spectroscopy. We minimize the influence of the tip by probing the molecule-free part of partially molecule-covered PhP nanoresonators with a non-resonant metallic tip, which we refer to as remote near-field probing. We also verify our experimental results via comparative numerical simulations, where the near-field probe is modeled either by a point-dipole source (representing a non-disturbing near-field probe) or by an oscillating metal tip .ωCBP = 1450 cm−1 (Supplementary Note 1), as can be recognized from the near-field spectrum of a thin CBP layer shown by the green curve in Fig. 25 of an atomic force microscope, is placed remotely with respect to the molecules at the opposite extremity of the h-BN rod. The tip  concentrates an illuminating broadband infrared laser beam at its apex to a nanoscale near-field spot, which excites phonon polaritons28 exhibiting Fabry-Perot (FP) resonances19 in the h-BN nanorod17. Figure s3(ω) and φ3(ω), respectively, where the index indicates that the detector signal was demodulated at 3Ω to suppress background signals .Our experiment is illustrated in Fig. L is shown in Fig. L is reduced from 1300 to 800 nm. However, the peak of the second order mode does not cross the CBP vibrational resonance at ωCBP = 1450 cm−1. Tracing the peak positions (marked by red lines) indeed reveals anti-crossing behavior, indicating that the nanoresonator near field couples with the molecular vibrations of the CBP layer. Most important, the nanoresonator-molecule coupling  can be well probed when the tip is placed on the left nanorod extremity, that is several 100 nm away from the molecules, where a direct near-field interaction between tip and molecules can be neglected . The experimental near-field spectra can be well reproduced by numerical simulations  at 1450 cm−1 clearly reveal the second-order (dark) FP mode. More important, the second-order FP modal near-field pattern of the half-covered nanoresonator exhibits a small spectral dip at the molecular vibrational resonance of CBP at 1450 cm−1  is nearly the same for both nanoresonators, whereas the peak of the second-order FP mode of the molecule-covered h-BN nanoresonator exhibits a spectral dip occurring at ωCBP, as typical for the coupling between molecular vibrations and nanoresonator modes23. The spatio-spectral observation presented in Fig. 29.Remote near-field spectroscopy can be applied for nanoscale spatial mapping of the resonator-molecule coupling via hyperspectral nanoimaging—even for dark modes that are not accessible by far-field spectroscopy. In the future, such a possibility could be applied, for example, to study advanced resonator structures where a variety of different resonator modes may coexist and couple with the molecular vibrations. In Fig. 30  component of the electric field below the dipole . Further simulation details are described in the Methods section. Importantly, the dipole moment of the source is kept constant and consequently is not modified by the fields of the nanoresonator. This simplified modeling of the tip allows for excluding a potential coupling of the tip with the nanoresonator and the molecules, and thus exclusively reveals the spectral near-field signature of the coupling between the nanoresonator and the molecular vibrations.To understand how the hybrid nanoresonator-molecule modes manifest in the near-field spectra, we first discuss in Fig. Ez(ω)| (open symbols), of a h-BN nanorod that is half covered with a layer of permittivity ε = 2.8 (corresponding to the permittivity of CBP without the molecular resonance at 1450 cm−1). Its length was chosen such that the second-order FP resonance is at ω = 1450 cm−1, which manifests as a single peak in the near-field amplitude spectrum. Repeating the simulation when the h-BN nanorod is half covered by a CBP layer . The two oscillators are coupled to each other through the coupling strength g. For a most reliable analysis, we performed complex-valued fitting of the simulated near-field spectra Ez(ω)| and φ(ω) are the amplitude and phase spectra , a negligible change of the sum of damping parameters, γPhP + γCBP, and only a slight reduction of the coupling strength by a factor of about 1.26. In a second simulation, we additionally implemented tip oscillation and signal demodulation. Fitting of the simulated spectra yields nearly the same coupling strengths and mode positions as before. However, for the sum of the damping parameters, γPhP + γCBP, we obtain values that are reduced by a factor of about 1.56 as compared to the results obtained from the simulations where the tip is modelled as a point-dipole source. Since the presence of the tip, its oscillation and signal demodulation can yield significantly different values for g and γPhP + γCBP, we re-evaluate the coupling regime obtained in the experiment according to a modified condition, 1.26 g/[1.56(γPhP + γCBP)] > 0.25, where g and γPhP + γCBP are the parameters (listed in Table L = 1.2 µm and L = 0.9 µm) satisfy the strong coupling criteria, whereas the other nanoresonators are at the onset of strong coupling. The transition from weak to strong coupling- according to this re-evaluation—is marked in Fig. g/[γPhP + γCBP] > 0.25), the transition occurs in Fig. g values. We note that the factors used to re-evaluate the coupling regime are specific for our study and may change for different tip oscillation amplitudes or signal demodulation orders.So far, we have not explicitly considered in the simulations that the tip is a long metallic cone, that the tip is oscillating, and that the detector signal is demodulated at higher harmonics of the tip oscillation frequency. To elucidate the influence and impact of these key features on the spectral mode positions and linewidths, we performed numerical simulations where the tip is modeled as a metal cone and the tip oscillation and signal demodulation are considered. The results are shown in the Supplementary Note In summary, we demonstrated that infrared near-field spectroscopy can be applied for nanoscale spatial mapping of strong coupling between molecular vibrations and resonating dark PhP modes. To that end, we introduced the concept of remote near-field probing with a non-resonant tip, where the tip and molecules are separated such that the direct near-field interaction between tip and molecules is avoided. Such minimal-invasive probing offers the advantage that the hybrid nanoresonator-molecule modes and coupling strengths can be determined within the model of two coupled harmonic oscillators without considering the tip as a third oscillator, which significantly simplifies the coupling analysis and increases its robustness. On the other hand, numerical simulations of remote near-field spectroscopy including the metal tip, its oscillation and signal demodulation reveal that damping parameters may be underestimated when tip oscillation and signal demodulation are not taken into account for fitting the near-field spectra with a coupled harmonic oscillator model.5 or MoO3 that cover various infrared frequency ranges) with molecular vibrations or excitons in various resonator geometries. The possibility to probe dark modes and spatially control the selective excitation and probing of coexisting modes could pave the way to explore strong coupling configurations that are not accessible by far-field spectroscopy.Since near-field spectroscopy is available in the wide spectral range between visible and terahertz frequencies, we envision remote near-field probing studies of strong coupling of different plasmonic and phononic resonators . Then the flakes were exfoliated from the tape onto a transparent polydimethyl-siloxane (PDMS) stamp. Flakes of appropriate thickness and size were then transferred onto a Si/SiO2 (250 nm) substrate using the deterministic dry transfer technique34. For patterning the h-BN nanoresonators we used high-resolution electron beam lithography using a double-layer poly(methyl methacrylate) (PMMA) resist (495 A4/950 A2). After development of the resist, a 3 nm-thick Cr layer was deposited onto the sample by e-beam evaporation, followed by thermal evaporation of 40 nm of Al. After lift-off in acetone, chemical etching of the h-BN flake was performed using a SF6/Ar 1:1 plasma mixture at 20 sccm flow, 100 mTorr pressure and 100 W power for 60 s (RIE OXFORD PLASMALAB 80 PLUS reactive ion etcher). For removing the Cr-Al mask from the h-BN structures, the sample was immersed in a chromium etchant  for 20 min. After rinsing in deionized water, the sample was dried using a N2 gun.We first mechanically exfoliated −9 mbar), at a rate of 0.1 nm s−1 using a Knudsen cell.4,4′-bis(N-carbazolyl)-1,1′-biphenyl with sublimed quality (99.9%) (Sigma Aldrich) was thermally evaporated in an ultra-high vacuum evaporator chamber  by focused Ga-ion beam (FIB) milling in a Helios 450S (FEI) dual beam system (milling conditions: 30 kV and 9.3 nA). Using an in situ platinum deposition, the diamond mask was attached to the tungsten tip of an Omniprobe micromanipulator and physically placed on top of the nanoresonators such that it covered half of each. The mask was fixed on the sample surface by in situ Pt-deposition. After CBP deposition by thermal evaporation (see above), the Omniprobe micromanipulator was approached to the mask. The mask was fixed to the Omniprobe by in situ Pt deposition. By FIB milling, the mask was detached from the sample and could be removed via the Omniprobe micromanipulator.−1). The detector signal was demodulated at a frequency 3 Ω for effective background suppression. Interferograms were measured by recording the demodulated detector signal as a function of the position of the reference mirror, d, at a fixed tip position. For apodization of the interferograms a Planck-taper window function with ε = 0.2 was applied. After zero-filling (4× padding) we Fourier transformed the interferograms to obtain complex-valued near-field point spectra, Es(ω). Each spectrum of Fig. y-axis. We normalized the obtained point spectra to a reference spectrum recorded on gold, Es,Au(ω). The spectral resolution was 6.25 cm−1.We used a commercial scattering-type scanning near-field optical microscope (s-SNOM) setup comprising a nano-FTIR module , in which the oscillating (at a frequency Ω ≅ 270 kHz) Pt/Ir-coated AFM tip  was illuminated by p-polarized mid-IR broadband radiation generated by a supercontinuum laser , d = 87 nm thickness  and variable length L . The resonators are on top of a 250 nm thick layer with the permittivity of SiO2, which is on top of a Si substrate. The CBP layer was modeled as a 50 nm thick layer covering half the length of the h-BN nanorod. The material permittivities are provided below. To ensure numerical convergence of the simulated near-field spectra, the complete structure  was located in a homogeneous rectangular box (filled with air) of 8 × w width, 25 × d depth and 4 × L length. We use perfectly matched layers (PML) for the boundaries of the simulation box and free triangular elements for the nanorod mesh and free tetrahedral elements for all other structures.We performed the numerical simulations Figs. , 4d, f uz-direction). This model assumes that the elongated tip in the experiment is oriented perpendicularly (z-direction) to the h-BN nanorod and is illuminated by p-polarized light. The experimental signal detected in the far field (Es) was approximated by the vertical component of the electric near field (Ez) at an evaluation point below the point-dipole source. In all the calculations, the point-dipole and the evaluation points were located at coordinates  and , respectively. We set the origin  at the middle of the top surface of the nanorod. The CBP layer covered the nanorod for y > 0. For comparison with the experimental near-field spectra, the simulated near-field spectra were normalized to Ez obtained when the dipole source is located above a gold (i.e. reference) substrate.To obtain the numerical results shown in Figs. 10B) enriched h-BN (in-plane 35j indicates the in-plane (⊥) or out-of-plane (||) component. In Eq.  represents the PhP mode with resonance frequency ωPhP and damping constant γPhP, and xCBP(t) represents the molecular vibration of CBP with resonance frequency ωCBP and damping constant γCBP. g is the coupling strength between the two resonators and FPhP(t), FCBP(t) represent the effective forces that drive each resonator. The effective forces are proportional to the near fields provided by the tip. In particular, we set FCBP(t) = 0 as in our experiment the near fields of the tip do not act directly on the CBP molecules.To fit the data shown in Figs. Through a time-to-frequency Fourier transform of Eqs.  and 5),,5), we fx0 + y0i), which accounts for the non-polaritonic near-field interaction between the tip and the nanoresonator:To fit the simulated spectra Figs.  and 4d, eiϕ) that accounts for the drift of the interferometer between the measurement of the nanoresonator spectra and the reference measurement on a flat gold surface:ωPhP, γPhP, g, x0, y0 and ϕ. The parameters ωCBP and γCBP are fitting parameters limited to the ranges  cm−1 and  cm−1, respectively. From the fit parameters we obtain the eigenfrequencies ω± of the coupled system using the following relationω = ωPhP-ωCBP and Δγ = γPhP-γCBP. Equation (To fit the experimental spectra Fig. , we multranges 140, 1452.5Supplementary Information


Obstetric infections are the third most common cause of maternal mortality, with the largest burden in low and middle-income countries (LMICs). We analyzed causes of infection-related maternal deaths and near-miss identified contributing factors and generated suggested actions for quality of care improvement.An international, virtual confidential enquiry was conducted for maternal deaths and near-miss cases that occurred in 15 health facilities in 11 LMICs reporting at least one death within the GLOSS study. Facility medical records and local review committee documents containing information on maternal characteristics, timing and chain of events, case management, outcomes, and facility characteristics were summarized into a case report for each woman and reviewed by an international external review committee. Modifiable factors were identified and suggested actions were organized using the three delays framework.Thirteen infection-related maternal deaths and 19 near-miss cases were reviewed in 20 virtual meetings by an international external review committee. Of 151 modifiable factors identified during the review, delays in receiving care contributed to 71/85 modifiable factors in maternal deaths and 55/66 modifiable factors in near-miss cases. Delays in reaching a GLOSS facility contributed to 5/85 and 1/66 modifiable factors for maternal deaths and near-miss cases, respectively. Two modifiable factors in maternal deaths were related to delays in the decision to seek care compared to three modifiable factors in near-miss cases. Suboptimal use of antibiotics, missing microbiological culture and other laboratory results, incorrect working diagnosis, and infrequent monitoring during admission were the main contributors to care delays among both maternal deaths and near-miss cases. Local facility audits were conducted for 2/13 maternal deaths and 0/19 near-miss cases. Based on the review findings, the external review committee recommended actions to improve the prevention and management of maternal infections.Prompt recognition and treatment of the infection remain critical addressable gaps in the provision of high-quality care to prevent and manage infection-related severe maternal outcomes in LMICs. Poor uptake of maternal death and near-miss reviews suggests missed learning opportunities by facility teams. Virtual platforms offer a feasible solution to improve routine adoption of confidential maternal death and near-miss reviews locally.The online version contains supplementary material available at 10.1186/s12884-022-04731-x. Obstetric infections are the third most common cause of maternal mortality, with the largest burden in low and middle-income countries (LMICs) 10·7%) compared with high-income countries (HICs) (4·7%) 0·7% comp. Among tInfection-related maternal mortality and severe morbidity can have many contributing factors, including delays in the decision to seek care, arrival at the appropriate health facility, and provision of adequate and timely management . MaternaMaternal deaths and near-miss reviews, when timely implemented with accurate and complete data , and in Considering the significance of infection-related maternal deaths and near-misses, and paucity of studies reporting on in-depth explorations of their causes and the surrounding circumstances in LMICs, this study sought to contribute to current knowledge on factors affecting the survival of pregnant or recently pregnant women after infection, using the GLOSS study .This manuscript describes the results of an international, virtual confidential enquiry into maternal deaths and near-miss cases identified within the frame of the GLOSS study. The international external review committee analyzed causes of infection-related maternal deaths and near miss, identified clinical and non-clinical modifiable factors from before admission until death or discharge and generated suggested actions for facility level care improvement to avoid preventable infection-related maternal deaths and near-miss.The Global Maternal Sepsis Study (GLOSS) was a facility-based, prospective, inception cohort study implemented in health care facilities located in pre-specified geographical areas in 52 countries . During This is an extension of the GLOSS protocol, that includes additional data collection, and where all maternal deaths and near-miss cases from health facilities reporting at least one infection-related death were eligible for inclusion. A total of 16 countries, out of 17 eligible, expressed interest to participate in this study. Therefore, 25 infection-related maternal deaths and 53 near-miss cases from 25 health facilities were considered for inclusion. Cause of deaths were classified using the WHO ICD-MM  system . Near-miEthical approvals were obtained from the WHO ethics review committee and as required by national or local entities.Health facility information was available from the GLOSS study , 20. As During the GLOSS study, information was collected from individual facility medical records on sociodemographic and obstetric characteristics of the woman; source of infections and management in the health facility; and maternal, perinatal, and neonatal outcomes. However, given that the design and initial objectives of the GLOSS study did not include a review component for maternal deaths and/or near-miss, comprehensive information for such reviews was not specifically collected. Additional data for this extended phase of the GLOSS study were requested using the form in Fig. S1, Additional file Index case anonymized available documents were collected from health facilities or local review committees, including anonymized copies of death certificates, autopsy reports, reports from local death reviews, or other documents relevant to each case.An external multi-country review committee was formed and tasked to perform independent assessments virtually of all included infection-related maternal deaths and near-miss cases. The external review committee consisted of 30 experts from 12 countries who indicated interest in taking part in the reviews, including GLOSS regional and country coordinators, and members of the country teams. All participants were health care providers, including gynecologists and obstetricians, internists and cardiologists, non-specialist medical doctors, nurses, and midwives. About half of the participants reported having extensive experience in review meetings, while half reported having little experience. Participants were divided into five multi-country review committees based on their preferred languages  and time zones. Five internationally recognized expert facilitators of maternal death and near-miss reviews and MPDSR were invited to serve as meeting moderators and were paired to the review committee groups. A team of WHO staff and consultants coordinated logistics for the review meetings.Case summaries were prepared for each maternal death and near-miss case by the WHO coordination team using the template in Fig. S2, Additional file To assess gaps in management from before admission until death or discharge and document the review findings, a note-taking form in Fig. S3, Additional file Over a three-month period, between August 31, 2020, and November 11, 2020, 20 virtual external review meetings were conducted. Each review meeting was scheduled for 75 minutes and facilitated by one of the international moderators. Maternal deaths and near-miss cases were grouped into three geographical groups based on the review languages and numbered sequentially. Using the numbers, the index cases were randomly allocated to committees outside the geographical area where the cases occurred. Two deaths and one near-miss cases were assigned for each meeting and the review committees were sent case summaries 10 to 14 days before the meeting. Individual members of the committees were tasked to prepare a presentation on one case to be presented at the virtual meetings and a facilitated discussion followed to build consensus. In cases where a team was unable to review all three cases assigned per session, the remaining case was reviewed in the subsequent meeting. Two assigned individuals from the coordination team took notes at the meetings to document the cause of death, missed opportunities and recommendations discussed.We described the numbers and proportions of maternal demographic, obstetric and clinical characteristics, as well as complications, and outcomes for maternal deaths and near-miss cases.The meeting notes for each case were reviewed by the coordination team and modifiable factors were identified and categorized following a structured process of thematic analysis , informeModifiable factors identified during the external review meetings were then organized into the following categories using the three delays framework  - (1) deRecommendations were classified into five thematic areas following the three delays framework and consolidated across all reviews to avoid repetition. Recommendations addressing delays 1 and 2 were combined into a single thematic area due to the paucity of data for these delays. Recommendations related to delay 3 (receiving adequate care when a facility is reached) and other clinical factors were sub-divided into three thematic areas namely clinical and laboratory examination, diagnosis, and treatment. A fifth thematic area addressed the gaps related to the managing team.Preliminary results and summary of the recommendations formulated during the review meetings were shared with the members of the five review committees in two joint virtual meetings providing an opportunity to discuss the relevance of findings and feasibility of recommendations across various local contexts.There were 25 infection-related maternal deaths and 53 near-miss cases from 25 health facilities in 16 countries eligible for inclusion. However, only 11 countries submitted the necessary additional data on 13 out of 15 maternal deaths and 19 out of 47 near-misses  (Table n = 6/13 deaths and n = 10/19 near-miss) and to multiparous women (n = 8/13 deaths and n = 12/19 near-miss). Close to a third of deaths (n = 4/13) and near-miss (n = 5/19) were from post-abortion complications. Among SMOs, at least one in every five had delivered by cesarean section with near-miss cases (n = 8/19) occurring almost twice as often in this group compared to maternal deaths (n = 3/13). Just over half of the women who died (n = 7/13) or had a near-miss (n = 10/19) were managed in intensive care (ICU) or in a high dependency unit (HDU). More than a third of women (n = 5/13) died within the first 48 hours of admission to the health facility. Two thirds of near-miss cases required more than a week of hospital admission (n = 13/19). Perinatal outcome was very poor – only 3/15 survived when there was a maternal death and 8/19 in the case of a near-miss. The results presented from the virtual review meetings are from 12 of the 13 maternal deaths as one death occurred within the first hour of presentation before the managing team commenced clinical management, and data was not sufficient to conduct a review of the case. Facility audits were conducted for only 2/13 maternal deaths and 0/19 near-miss cases  related to infection were between ages 20 and 35  was considered by the committee to have contributed to 71 of the 85 modifiable factors for maternal deaths Fig. , and 55 Inadequate or delayed treatment made up 32 of 71 modifiable factors related to a delay in receiving care (delay 3) for maternal deaths compared to 18 of 55 factors for near-miss cases . One of the study objectives was to compare findings and recommendations of local committee reviews and those from an external review committee. An extensive comparison was impossible given the low rates of internal audits conducted at the facilities.Lastly, external reviewers may not have been completely familiar with the context and the facility managing teams were not available for clarifications during the review which could have affected interpretation of events by the reviewers. In addition, the confidential nature of the reviews limited the ability of the reviewers to probe further into the local context, therefore the ensuing recommendations were not specific to each death or near-miss or to the facility or country involved.The lack of precision in management due to limited continuous clinical assessment, use of clinical skills and laboratory examinations contribute to missed opportunities in the provision of high-quality care to prevent and manage infection related SMO, and shortfalls in maternal death and near-miss review processes in facilities in LMICs. Poor uptake of maternal deaths and near-miss reviews suggests missed learning opportunities by facility teams. Routine confidential enquiries and review meetings should be incentivized at the facility level as part of quality improvement efforts. This study confirms the feasibility of multinational maternal death and near-miss reviews using a virtual platform. While locally conducted reviews would allow for more detailed and context specific recommendations, virtual review meetings allow for a confidential approach to reviewing deaths across a diverse number of settings. The authors recognize the need for additional evaluations to assess the quality of the review process, compare and validate findings, assess the feasibility of implementing and adapting actionable recommendations to different contexts.Additional file 1. Supplementary appendix to “International virtual confidential reviews of infection-related maternal deaths and near-miss in 11 low- and middle-income countries – Case report series and suggested actions. Study forms used for data collection and during the external review meetings. Results of a baseline assessment of maternal death review (MDR) committees and practices in participating GLOSS facilities. Additional information on the causes of deaths and distribution of modifiable factors described in this study.


Leveraging local ancestry and haplotype information in genome-wide association studies and downstream analyses can improve the utility of genomics for individuals from diverse and recently admixed ancestries. However, most existing simulation, visualization and variant analysis frameworks are based on variant-level analysis and do not automatically handle these features. We present haptools, an open-source toolkit for performing local ancestry aware and haplotype-based analysis of complex traits. Haptools supports fast simulation of admixed genomes, visualization of admixture tracks, simulation of haplotype- and local ancestry-specific phenotype effects and a variety of file operations and statistics computed in a haplotype-aware manner.https://github.com/cast-genomics/haptools.Haptools is freely available at https://haptools.readthedocs.io.Detailed documentation is available at Bioinformatics online. Existing frameworks for complex trait analysis are typically based on variant-level analysis. However, phenotypic effects may also be mediated by haplotypes  for flexible representation of haplotype-level and other information. These files consist of a collection of haplotypes. Each haplotype is defined by a set of one or more variants and their alleles, and optionally a local ancestry label, that tend to be inherited together on an individual chromosome . Unlike simgenotype utility simulates random mating between individuals of ancestral populations under a user-specified population history model, which defines admixture proportions and the number of generations of admixture. It outputs haplotype breakpoints and genotypes of simulated admixed individuals in VCF or PGEN format. simgenotype is adapted from admix-simu  supported by large existing datasets such as the 1000 Genomes Project (The mix-simu  with minmix-simu . We bencdmixSim2 . While Akaryogram takes breakpoints generated by simgenotype as input and generates a karyogram to visualize chromosome segments. It is adapted from an existing script (g script . Exampletransform produces a VCF file of pseudo-genotypes, in which each haplotype is encoded as a bi-allelic variant record, for a set of haplotypes in .hap format. This operation can facilitate downstream tasks which require variant-level information as input. For example, to perform association testing based on haplotypes, one could first use transform to generate a VCF encoding haplotypes as bi-allelic variants, and then use a standard framework such as PLINK (simphenotype utility simulates phenotypes for complex traits with variant-, haplotype- or local ancestry-specific effects. Causal haplotypes are loaded from a VCF file output by transform and their effect sizes are specified in a .hap file. By default, simphenotype simulates quantitative traits. Users may specify case–control traits by providing disease prevalence, which results in that percentage of individuals with the highest trait value being labeled as cases. We evaluated simphenotype by simulating quantitative traits under various scenarios, including individual causal variants (The variants , local avariants , and hapvariants .Accounting for ancestry and other more complex effects is becoming increasingly critical in association testing and downstream analysis pipelines. Haptools helps fulfill an unmet need to handle ancestry and haplotype level information in a standardized way that is compatible with existing file formats and workflows and is computationally efficient. It enables easily performing tasks such as genotype and phenotype simulation, local ancestry visualization and power analyses which previously have been done primarily using a variety of custom scripts. Overall, haptools will help enable more systematic incorporation of ancestry and haplotype-level features in future workflows.https://haptools.readthedocs.io/en/stable/project_info/example_files.html, and the haptools-paper repository, https://github.com/CAST-genomics/haptools-paper.The datasets used for validation and example generation are available from the haptools documentation page: btad104_Supplementary_DataClick here for additional data file.


Arteriovenous malformations (AVMs) of the posterior fossa represent just 5%–15% of all intracranial AVMs. Rupture often leads to devastating brainstem compression, with mortality reported as high as 67%. A life-saving decompressive craniectomy with or without hematoma evacuation may be necessary in the acute setting to alleviate mass effect before proceeding with definitive treatment of the vascular pathology. Here, the authors demonstrate the utility of using a generously sized temporizing decompressive suboccipital craniectomy to subsequently allow for a more judicious resection of a Spetzler-Martin grade III AVM fed by the right superior cerebellar artery using a sitting supracerebellar infratentorial approach.https://youtu.be/L195wmw3p_4The video can be found here:  She was taken emergently for a life-saving decompression, but the CTA had demonstrated a known AVM, just behind the brainstem at the mesencephalic-pontine junction. It was fed predominantly from the superior cerebellar artery on the right side, with the draining vein on the dorsum of the cerebellum going to the region of the torcula.1:07 We took her to the operating room, and 2.5 weeks later, do a sitting position, and use the previous decompression incision to open up and expose the region of the posterior fossa. We’ll extend the craniectomy above the region of the torcula to allow us an unimpeded view on the dorsum of the cerebellum.1:30 The dura is opened and elevated. A midline draining vein is identified and divided, but this is not the draining vein for the AVM. We’re going predominantly on the left side, as the draining vein from the AVM is on the right side of the dorsum of the cerebellum.1:51 We open up the roof of the cerebellum and identify the clot. After decompression of the hematoma, we identify the small AVM on its posterior aspect and dissect along the left side of the AVM, finding the interface between the cerebellum parenchyma and the AVM directly. The vessels are isolated, cauterized, and divided.2:22 We continue our dissection anteriorly and find the superior cerebellar artery on the patient’s left side, and carefully dissect and identify the feeding small arteries to the AVM from the native superior cerebellar artery. Now we’re coming along the anterior aspect of the AVM adjacent to the brainstem, taking care to divide all the feeding vessels but not embarrass the superior cerebellar arteries. The superior cerebellar arteries are left intact. This is the roof and the region of the venous confluence. We continue dissecting the AVM off of the back of the region of the brainstem, again carefully preserving the superior cerebellar artery branches.3:26 Now we’ll come along the right side of the AVM and dissect it from the cerebellar parenchyma on the right. We continue our dissection anteriorly. You can see the right superior cerebellar artery, and we’ll identify the draining vein as the final step in removal of the AVM. The AVM draining vein is cauterized and divided. The lesion is removed. We obtain hemostasis and inspect and ensure that there is no residual AVM along the posterior aspect of the brainstem.4:10 The hematoma cavity is covered with Surgicel, and the dura is closed with a dural substitute. The muscle is then closed in separate layers, and the skin is closed with a running nylon suture. Postoperatively, she improved significantly, and her postoperative CT shows complete resection of the hematoma, and the angiogram demonstrates no further AVM visualized. There is no early draining veins. She continued to make a good neurological recovery.Primary surgeon: Couldwell, Grandhi. Editing and drafting the video and abstract: Couldwell, Joyce. Critically revising the work: Couldwell, Joyce. Reviewed submitted version of the work: Couldwell, Joyce. Approved the final version of the work on behalf of all authors: Couldwell. Supervision: Couldwell.


Cerebellar arteriovenous malformations (AVMs) comprise 10%–15% of all intracranial AVMs and have a higher risk for morbidity and mortality than supratentorial AVMs. Patients with cerebellar AVMs present with hemorrhage more often than patients with cerebral AVMs, justifying an interventional treatment. Patient outcome can be predicted with specific grade systems, guiding vascular neurosurgeons in decision-making. The authors present the case of a 42-year-old man incidentally diagnosed with an unruptured cerebellar inferior vermian AVM, which was managed through a combined strategy of preoperative endovascular embolization of the main arterial feeders followed by microsurgical resection via midline suboccipital craniotomy, with a favorable outcome.https://youtu.be/3WESejZbk90The video can be found here:  The patient was 42 years old with headache for 3 months. He had a Glasgow Coma Scale score of 15 and no focal neurological deficits.0:36 Imaging. MRI showed an inferior vermian AVM.0:39 Left vertebral angiography shows the cerebellar AVM’s main arterial supply was the left PICA, and the basilar artery did not fill by the left vertebral artery due to steal phenomena. The size of the AVM was 2 cm.The blue arrows show that the left PICA had three flow aneurysms. In the figure on the right, we see the arterial supply of the AVM. It was done from the branches of the telovelotonsillar segment of the PICA.Regarding venous drainage, at the red arrow, we see a venous aneurysm in the vein of Galen; at the brown arrow, the basal veins of Rosenthal; at the green arrow, the straight sinus. The yellow arrow shows the main drainage vein of the AVM.1:32 This drawing  shows the AVM. The left PICA is shown transparent inside of the cerebellum and provides the final branches of the telovelotonsillar segment for supplying the AVM. There is a small cortical branch from the left vertebral artery that supplies the AVM. The AVM is shown transparently. Venous drainage is primarily performed to the inferior vermian vein. The vein is shown in purple here because it was an arterialized vein. The venous aneurysm is shown here near the vein of Galen.2:16 This was an infratentorial AVM with deep venous drainage, which are risk factors for rupture. Hemorrhage due to prenidal aneurysm also occurs more frequently in cerebellar AVMs than in cerebral AVMs.The Spetzler and Martin AVM classification indicated that this was a grade II AVM, which has a low surgical risk.The AVM classification by Nisson et al. indicates that this was a grade I AVM, which has a low risk assessment.Considering that flow-related aneurysms are distal and that, after treatment of the AVM, 80% of distal flow-related aneurysms disappear and that there was no hemorrhage in our case, we decided for conservative treatment of these aneurysms.This was an unruptured AVM with a high risk of bleeding and low surgical assessment risk. Therefore, we decided on interventional treatment with combined strategies with microsurgery after embolization.3:29 Embolization. We proceeded to embolize the large arterial feeders, identified by the pink arrow, with Onyx to decrease the blood flow and facilitate surgical resection. The yellow arrow indicates the cortical segment of the PICA that was not embolized.This video shows the result of the embolization of the terminal branches of the PICA. After the procedure, the basilar artery was filled.4:02 Positioning. The patient was in a three-quarter prone position with mild flexion and lateral rotation of the head. The jugular veins were made straight to prevent problems of venous return and cerebellar congestion. The advantage of this position is that the abdomen is entirely free, so there is no risk of increased intraabdominal pressure, which also avoids venous return problems. A left occipital EVD was placed.4:32 Exposure. An incision was made from the inion until the spinal process of C2.The muscular layer was opened in a Y shape. Here, we show the occipital bone exposed. The blue dot is the inion. The red dot is the squamous part of the occipital bone. The orange dot is the posterior atlantooccipital membrane. The green dot is the posterior arch of C1.A suboccipital craniotomy was performed, and the dura mater was opened. The blue arrow shows the foramen magnum.5:09 The arachnoid of the cisterna magna was opened, the main drainage vein of the AVM was viewed after the opening of the arachnoid membrane, and a corticectomy was performed. The lateral edge of the AVM was isolated to avoid creating a fox hole.The deep arterial feeders from the left PICA are shown here. These arteries are clipped to promote a decrease in the blood supply to the AVM. This helps to facilitate the dissection of the AVM and to avoid bleeding in the surgical field. The embolized vessels can be seen here.5:49 Then, these clipped arteries are cut, and the telovelotonsillar segment of the PICA can be seen preserved here.5:57 The drainage vein was identified, and after the complete removal of the arterial feeders, the vein started to shrink, and there was no more blood return to the vein. Then, the vein is clipped. After clipping, there was no blood flow to the AVM. When this was confirmed, the drainage vein was cut.We proceeded to hemostasis of the surgical field.6:27 This drawing shows the surgical field after the removal of the AVM. The arrow shows the dura mater. This is where the AVM was located. The clipped arterialized drainage vein is here. The PICA is depicted transparently in this drawing. These are the clipped final branches of the telovelotonsillar segment of the PICA, and this is the cortical segment of the PICA that was preserved.6:59 Closure. The dura mater was closed, and we used a flap of pericranium to perform the duraplasty. Then, we proceeded to the cranioplasty.The muscular layer was closed with an anchored suture using a multifilament absorbable suture. The subcutaneous tissue and the skin were closed.7:21 Postoperative Imaging. Here, postoperative arteriography of both the right and left vertebral arteries shows that the cerebellar AVM was completely removed. We observe that the cortical portion of the left PICA can still be seen.7:39 Postoperative Course. The patient had no neurological deficits. The EVD was removed 2 days postoperatively. The patient was discharged home at postoperative day 6.Regarding flow-related aneurysms, we initially follow up with CT angiography every 6 months.Primary surgeon: Dellaretti. Editing and drafting the video and abstract: all authors. Critically revising the work: all authors. Reviewed submitted version of the work: all authors. Approved the final version of the work on behalf of all authors: Dellaretti. Supervision: Dellaretti.Supplemental Fig. 1.https://thejns.org/doi/suppl/10.3171/2020.10.FOCVID2058.Supplemental material is available online.


The low-frequency component (LFC) of myopia gradually increased with time, reached a peak at 30 min, and then declined (p = 0.043). The high-frequency component (HFC) of myopia also reached a peak at 30 min (p = 0.036). Nevertheless, there was no significant difference in the LFC (p = 0.171) or HFC (p = 0.278) of the emmetropia group at each time point. There was no significant difference in the mean and standard deviation of the accommodative response and pupil diameter both in emmetropic and myopic juveniles. Compared with juvenile emmetropes, myopes exhibit an unstable tendency in their accommodation system for prolonged near work at a certain time point. Accommodative microfluctuations may be a sensitive, objective indicator of fatigue under sustained near work in juvenile myopes.Near work has been considered to be a potential risk factor for the onset of myopia, but with inadequate evidence. Chinese adolescents use digital devices for near work, such as study and entertainment purposes, especially during the COVID-19 pandemic. In this study, we investigated the influence of prolonged periods of near work on accommodative response, accommodative microfluctuations (AMFs), and pupil diameter between juvenile subjects of myopia and emmetropia. Sixty juveniles (30 myopes and 30 emmetropes) were recruited for the study. Participants were instructed to play a video game on a tablet PC at a distance of 33.3 cm for 40 min. Accommodative response and pupil diameter were measured with an open-field infrared refractometer in High-speed mode. Parameters of the subjects were measured once every 10 min, and analyzed by one-way repeated measure ANOVA for variation tendency. There were no significant differences between emmetropia and myopia groups with respect to age and sex ( Myopia has become a major public health challenge worldwide in recent decades, especially in East and Southeast Asia ,2. Some Near work has been considered to be a critical risk factor in the onset and development of myopia ; howeverSince hyperopic defocus induced by negative lenses or refractive surgery results in eye growth and myopia, as demonstrated in animal studies, it is suggested that accommodative lag during near work might generate the axial elongation of the eye in children ,8,9,10. Nevertheless, other factors have been taken into consideration. When viewing a stationary target, the accommodation of the eye is not stable but constantly varies at a rapid speed within a range of approximately 0.50 D, a phenomenon termed: accommodative microfluctuations. Fluctuations at lower temporal frequencies (<0.6 Hz) are likely to be important for the control process of accommodation, which may make use of the associated changes in the spatial frequency spectrum and the contrast of the retinal image. The AMFs show a high degree of correlation of the two eyes, and the AMFs were similar under binocular and monocular observing conditions when the target conditions were the same ,13,14. TDigital screen time has been considered to be a modifiable environmental risk factor that may increase the risk of myopia. A massive number of children begin to use mobile devices even before the age of one, and most of them own a digital device by the age of four . HoweverPrevious studies focused on the role of microfluctuations in the accommodation system. However, only a few investigations have been carried out on accommodative behaviors during sustained periods of reading books or watching digital screens in natural visual environments. For a better understanding of the relationship between near work, accommodation, and the development of myopia, the current study aimed to investigate the differences in accommodative behaviors between myopic and emmetropic children during a prolonged period of digital near work, and to determine the optimal duration of digital near work in Chinese children.This clinical study was conducted at Zhongshan Ophthalmic Center (ZOC) in Guangzhou, China, after obtaining approval from the ZOC ethical committee prior to the initiation of the study. All experiments adhered to the Declaration of Helsinki. Written informed consent was obtained from the children and their parents or guardians. Sixty subjects aged between 7 to 12 years with a refractive error ranging from emmetropia to moderate myopia participated in the study, and all of them had a visual acuity of 0.1 logMAR or better with normal binocular vision. Children with astigmatism or anisometropia more than 1.0 D, those with amblyopia or manifesting strabismus, or those with a history of significant ocular disease and surgery were excluded from the study. Children who had undergone keratoplasty or were medicated with atropine in the past two years for controlling the progression of myopia were eliminated from the study. Emmetropia was defined as a mean spherical equivalent refractive (SER: sphere + (0.5 × cyl) between −0.50 and +0.50 D, and subjects with SER < −0.50 D were considered myopic.During the test, myopic subjects were fully corrected with suitable contact lenses. All of them had a visual acuity of 0.1 logMAR or better with the contact lenses. Participants were instructed to close their eyes and rest for at least 20 min to ensure relaxed accommodation and the stability of tear film after wearing their best-suited corrected visual distance contact lenses. Previous research has shown that there is no significant effect of contact lenses on the measurement of accommodation microfluctuations .2 (average) and the illumination of the background was 300 lux. Subjects were instructed to play the game in a usual manner. The visual display terminal was adjusted to be fixed on the machine in front of the participant at 33.3 cm for a conserved angular subtense within 5° horizontal and 5° vertical. Subjects were asked to concentrate on the game and maintain their head in the chin-rest throughout the 40 min of play.Subjects were asked to play a link game with a wireless mouse connected to a tablet computer (HUAWEI-M5) (1920 × 1200 pixels) at a distance of 33.3 cm corresponding to accommodative demands of 3.0 D. During the visual task, the luminance of the visual display terminal (brightness) was 210 cd/mPrevious studies have confirmed that 3–5 min adaption is enough for accommodation ,30,31. MOnly the left eye was measured while the task was performed in a natural, binocular state of vision. The accommodative response and pupil diameter were dynamically measured every 0.2 s (5 Hz) with an open-field instrument called Grand Seiko Auto Ref/Keratometer WAM-5500  in high-speed mode. The instruments have a sensitivity of 0.01 D and 0.1 mm for the accommodative response and pupil size, respectively ,36. PrevThe participants were encouraged to score in the game to remain focused. Pupil diameter and the accommodation response of the subjects were measured once at the beginning of the game, and taken as the baseline. Subsequently, the parameters of the subjects were measured once every 10 min. The participants were instructed to stop the game and stare at the midmost pattern in the screen with both eyes (the link game consisted of patterns of the same size during the process) to maintain the stability of the fixation. The subjects were asked to keep the pattern clear during the measurement and allow blinking. After a minute of continuous inspection, the participants continued to play the game. The measurements were repeated five times, and the data at the baseline, 10, 20, 30, and 40 min were obtained.Microfluctuations vary with a series of factors, such as target luminance, spatial frequency, and stimulus demand; therefore, these factors should be taken into consideration while measuring the accommodative microfluctuations . The aboData with no more than two blinks every 10 s were selected for analysis . Blinks In the present study, the mean value and standard deviation of the accommodation response and pupil diameter, and microfluctuations of accommodation (including LFC and HFC) were compared by one-way repeated measure ANOVA within refractive groups. Only the data of the left eye were included in this study.p < 0.00). The age of the two groups had no statistical difference. The baseline values of LFC were not significantly different between emmetropia and myopia groups. There was no significant difference in the mean and standard deviation of the accommodation response and pupil diameter between the two groups . The baseline value of LFC was lowest during the near work test. The LFC of the myopia group gradually increased with time and reached the peak at 30 min before a gradual decline. There was no significant difference in the LFC of the emmetropia group at each time point (p = 0.171)  , Table 2p = 0.036). In general, the HFC of the myopia group gradually increased with time and reached a peak at 30 min. There was no significant difference in the HFC of the emmetropia group at each time point (p = 0.278)  , Table 2p = 0.096) (p = 0.357). Similarly, for the emmetropia group, the mean and standard deviation value of the accommodative response were not significantly different between the various time points (p = 0.079) (p = 0.354).For the myopia group, the mean and standard deviation of the accommodative response were not significantly different between the baseline and periods of sustained near work of 10, 20, 30, and 40 min, as revealed by one-way repeated measures ANOVA (p = 0.398) (p = 0.357). Likewise, for the emmetropia group, the mean and standard deviation values of pupil diameter were not statistically significant between the various time points (p = 0.069) (p = 0.354).For the myopia group, the mean and standard deviation of pupil diameter were not statistically significant between the baseline and periods of sustained near work of 10, 20, 30, and 40 min, as revealed by one-way repeated measures ANOVA (Two main findings were identified in the current study. First, the myopia group displayed markedly different accommodative microfluctuations, especially in LFC, which increased during digital near work over time, but reached a peak at approximately 30 min and then decreased. However, the emmetropic juveniles showed no significant changes in accommodative microfluctuations throughout the near task. Second, the study found that both myopes and emmetropes exhibited a stable manifestation in the mean and standard deviation of the accommodation response and the pupil diameter in the period of near work.On the basis of our findings, we propose three possible explanations: First, compared with the emmetropic eyes, myopic eyes exhibited an unstable tendency accompanied by the extension of the near work time. Myopia is inclined to fatigue, compared with emmetropia, in prolonged digital near work; however, it is difficult to isolate the causes or effects of this change in myopia. Second, the accommodative microfluctuations of myopic juveniles reached a peak and then declined during sustained near work, suggesting that there may be a time point of highest fatigue during prolonged near work for the accommodation system. Third, consistent with previous studies, the mean and standard deviation of the accommodation response and the pupil diameter of myopia remained constant over a period of prolonged near work ,41. MicrPrevious research focused on the discrepancy of accommodation in myopic and emmetropic eyes at a certain time point, but rarely concentrated on accommodative behaviors of sustained near work. Woodman et al.  found thIt should be noted that although near work and digital devices have long been considered to be risk factors of myopia, there is little direct evidence. Our study aimed to emphasize the latent role of sustained digital near work in the pathogenesis of myopia by providing objective evidence of accommodation microfluctuations which vary at different time points in prolonged digital near work. Our study indicated that there may be an optimal time point for adolescents to perform sustained digital near work, which could be monitored by the sensitive, objective measure of accommodative microfluctuations.There are some limitations in the present study. First, the apparatus used to assess accommodation was an open-field instrument with a frequency of 5 Hz, which may be insufficient for measuring microfluctuations in accommodation. A more positive result may be obtained by an instrument with a frequency of more than 25 Hz because of the dense data and a smaller standard deviation . AlthougIn brief, there are still many clinically valuable investigations that warrant our attention. First, it is indispensable to conduct prospective longitudinal studies with a large sample size of children in the process of emmetropization to analyze whether the changes in the accommodative microfluctuations in myopia are simple or causal. Second, the time points of highest fatigue should be further investigated in juveniles with different rates of myopia progression in order to provide clinical evidence for the optimal duration for adolescents of sustained near work.The present study revealed that, compared with stable emmetropes, myopes exhibit an unstable tendency in their accommodation system for prolonged near work at a certain time point. The accommodative microfluctuations could be a sensitive, objective indicator of fatigue in sustained near work.