To describe self-care practices among Saudi heart failure (HF) patients and identify sociodemographic characteristics contributing to self-care practices.A cross-sectional study utilizing the Arabic-language version of the revised Self-Care of Heart Failure Index (SCHFI), version 7-2. A convenience sample of 245 people treated for HF at a tertiary heart center in the Kingdom of Saudi Arabia were recruited from June to August 2020.p=0.023) and confidence (p=0.002) were significantly higher than male participants. In addition, education level and employment status had a significant effect on HF monitoring with a p-value of 0.006 for the 4 employment categories . The effect size was small to medium for education level and employment status in the abovementioned results. Confidence significantly contributed to explaining all self-care sub-scale scores. Independent variables significantly predicted monitoring subscale scores .Statistical descriptions of SCHFI showed that confidence level was 84%, maintenance level was 67.5%, and monitoring level was 67.2%. Females’ HF management (Self-care practices in this study showed higher scores than those reported in international studies. Further studies are warranted to explore everyday self-care needs and challenges among HF patients. Cardiovascular diseases (CVD) account for approximately 18 million deaths per year worldwide, with an increase of 14% since 2006, an estimated prevalence of 6.2 million heart failure (HF) cases in the United States. Moreover, estimated HF mortality with a 12-month incidence in developing regions was highest in Africa (34%), followed by India (23%), and 9% in the Middle East. According to AlHabeeb et al, there are 1.35 million people with HF in Egypt, Saudi Arabia, and the United Arab Emirates. The estimated HF population in Saudi Arabia is 320,933 people with a yearly healthcare expenditure of more than one Billion American dollars ($1.045B), expended mainly on hospitalization. Patient hospitalization costs ranged between $3,671-16,447 on yearly basis. The burden of HF is not limited to the healthcare system and patients financial lose, HF consequences are impacting the entire society in terms of economic burden, minimized citizens’ quality of life, decreased productions, overwhelming family members and carers’ obligations, and patients’ inability to care for themselves. Numerous strategies have been implemented internationally to minimize the impact of HF. The British Heart Foundation adapted the community HF specialist nurse, which resulted in a 35% reduction in the re-admission rate and an estimated cost savings of 169,000 pound (£) per 1000 patients.Heart failure is a progressive condition that may result in disability. Aging, expansion of non-communicable diseases, and sedentary lifestyles are factors contributing to HF being a leading epidemic with severe negative health, economic, and social impacts. Proper self-care practices had a positive influence on enhancing health-related quality of life (HRQoL) and clinical outcomes. Despite these outcomes, patients may still do not follow the recommended self-care practices and do not get proper attention from healthcare teams in the continuum.In specific, international initiatives have mainly targeted the improvement of self-care practices/behavior among people diagnosed with HF, with the assistance of a multidisciplinary healthcare team.Self-care practices are influenced by external as well as individual’s sociodemographic factors. Socio-demographics such as age, gender, education level, income level, and employment status were explored in several studies. However, the outcomes of these studies were inconsistent with each other in terms, which factor was positively correlated to higher self-care practices. Reviewing the guidelines revealed minimal identification of self-care interventions, which appeared only as a brief recommendation in the section on “Multidisciplinary team management.” Moreover, exploring factors contributing to HF self-care was cited in few Saudi studies compared to international HF literature. Elkhateeb et al explored the effect of education level on hospital readmission and mortality rates in King Abdullah Medical City, Riyadh, Saudi Arabia, for 167 patients monitored in a 12-month follow-up. The study did not identify significant differences between highly educated participants and those with lower levels. Regarding medication adherence, Raffaah et al found that optimum adherence was evident in 7.3% of the study sample. In addition, researchers identified sociodemographic factors  as predictors of low medication adherence. A structured program to improve HF patients’ outcomes was tested in a randomized control trial and found that those who received the intervention were 95% less likely to be readmitted during the 4-month study period.From a national standpoint, Saudi Arabia had no standardized HF management protocols until 2019. The recent Saudi Heart Association (SHA) guidelines for HF management were developed to bridge this gap in Saudi healthcare organizations. The position statement of the American Association of Heart Failure Nurses (AAHFN) recommended that nurses should work to understand the factors contributing to enhanced HF self-care practices.The scarcity of HF nursing studies in Saudi Arabia may contribute to the limited number of studies devoted to HF self-care, as nurses are more concerned with patient-centered care and advocacy.In general, international self-care recommendations could not be transformed into Saudi context due to difference in individual and cultural characteristics. Therefore, the aims of this study were to describe self-care practices among Saudi HF patients and determine the sociodemographic factors that contribute to self-care practices. The outcome of this study will inform healthcare team as well as contribute to HF self-care body of knowledge in Saudi Arabia.A cross-sectional descriptive correlational design was applied. The study was carried out in Al-Madinah Cardiac Center, Al-Madinah Al-Munawarah, Saudi Arabia, one of 25 heart care centers and departments across the Kingdom. The study site was selected as a representative of other centers in Saudi Arabia due to its characteristics in terms of patients’ number, case variety, and advanced cardiac services. It is a 100-bed facility with an estimated 30,000 registered patients and 80,000 annual outpatient department (OPD) visits. The study was carried out in the OPD. The study included patients who: I) were diagnosed with HF; II) had a reduced ejection fraction (EF) of ≤45%; III) were at least 18 years old; IV) were able to agree to voluntary participation without mental or medical limitations and contraindications; and V) were registered in the cardiac center outpatient clinics. Inclusion criteria were checked through electronic medical records. People who were unable to communicate properly in Arabic or English were excluded. The sample size (n=160) was calculated via G*Power . However, 270 questionnaires were distributed to compensate for potential invalid or incomplete responses.A convenience sampling technique was used to recruit patients with HF who were attending their follow-up consultation appointments at Al-Madinah Cardiac Center, Al-Madinah Al-Munawarah, Saudi Arabia. The sampling approach was adapted from an earlier study in Jordan.The study protocol was approved by Al-Madinah Cardiac Center Institutional Review Board (no.: 2020R29). The study conforms with the principles outlined in the Declaration of Helsinki. The Strengthening the Reporting of Observational studies in Epidemiology (STROBE) checklist was utilized to enhance study methodology. The instrument identifies the outcome variable (self-care) by exploring 3 concepts: I) self-care (10 items); II) self-care maintenance (9 items plus 2 on patients’ ability to detect symptoms); and III) symptom perception and self-care management (8 items). Because the SCHFI is a multidimensional instrument, the reliability coefficient (RC) is a better fit than the popular Cronbach’s alpha reliability measure. Reliability coefficients of the original instrument were ≥70. For the translated Arabic version, they were ≥87.The study utilized the Arabic version of the revised Self-Care of Heart Failure Index (SCHFI V.7-2), which is available in the public domain.Responses are ranked on a Likert scale. The scoring system provided by the instrument’s owner standardizes responses to 100 (a higher score indicates more effective self-care practices). The instrument has shown acceptable psychometric properties and has been translated into various languages, including Arabic.Data were collected during the period from June 2020 to August 2020. The cardiac clinic nurse or the outpatient clinic nursing supervisor invited qualified potential participants upon their attendance for their clinic visit. The nursing supervisor referred those who were willing to participate to the data collection team (2 nursing interns who were trained to carry out data collection interview). Data collection was carried out in the clinic waiting area. Potential participants were introduced to the study verbally and given the study information sheet that included the consent form agreeing to participate. Some who did not wish to sign were included, considering their responses to the study questionnaire as consent to participate. Participants were offered the option to record their responses through the data collection team, who documented them in the study questionnaire using paper and pencil. Completed questionnaires were returned weekly to the researcher. Duration of data collection for each participant was between 8-12 minutes.Descriptive and correlational statistical analyses were carried out using the Statistical Package for the Social Sciences, version 20.0 . Patient’s characteristics and socio-demographic variables were tested to explore self-care practices. Mean and standard deviation (SD) of continuous variables and frequencies for categorical variables were used to describe the participants’ characteristics and the instrument’s subscales. Independent sample t-tests and ANOVA were used to explore significant differences in self-care practices among various participants’ characteristics. A multiple linear regression analysis was carried out to identify factors associated with self-care practices including confidence .A sample of 245 HF participants responded to the survey, with an overall response rate of 90.7%. Those who did not respond were mainly concerned on the time that the questionnaire may take. Sociodemographic characteristics  reveal tValues are presented as numbers and precentages or mean ± standard deviation (SD).p=0.023). Similarly, the mean on the confidence scale for females was significantly higher than that of males . Level of education had a significant effect on HF management with a p-value of 0.006 for the 3 categories . In addition, employment status had a significant effect on HF monitoring with a p-value of 0.008 for the 4 employment categories . The effect size was small to medium for education level and employment status in the aforementioned results.p=0.072). However, ID variables significantly predicted monitoring subscale scores , details are provided in =0.153; F=43.7; p=0.000); monitoring subscale scores ; and management subscale scores .Multiple linear regression analysis revealed some significant factors contributing to self-care practices. The total score was not significantly explained by ID variables despite it was close to the significance level alpha  in this study were within the range of earlier Saudi studies. The lower threshold of accepted self-care practices was ≥70. In specific, continuous healthcare delivery capabilities may keep HF patients under close monitoring. This explanation was supported by the significant explanation of the hospital admissions to 85% of the monitoring scale.In general, the study result accomplished the main 2 aims that are describing self-care practices among Saudi HF patients and determining the sociodemographic factors that contribute to self-care practices. From the first study aim stand, the self-care maintenance sub-scale scored 67.5% and monitoring sub-scale scored 67.2%, which are higher than those reported in earlier international studies. For instance, the maintenance subscale was 48% in China, 62% in the United States of America, and 53% in Jordan.However, this may not reflect a high patient engagement approach as much as the healthcare system’s monitoring capabilities. Specifically, checking the 2 extra items in the monitoring sub-scale; “How quickly did you recognize that you had symptoms” and “How quickly did you know that the symptom was due to heart failure” revealed low scores. Therefore, participants were unable to identify or recognize symptoms because they were dependent on the healthcare system regarding disease-related matters. Following the treatment plan was the highest item on the sub-scale (4.53±0.738), contrasting with earlier poor medication adherence reported by an earlier national study. Therefore, future studies should use recommended international approaches to measure HF patients’ medication adherence, such as continuous data monitoring.Self-care management (75%) was also higher than that of earlier international studies, where the reported scores ranged between 45-68%. In this study, education level had a significant effect on HF management. Participants with a general education (public education) scored higher than other groups. Such significance was not evident in the earlier national study. International literature suggests that health literacy contributes to medication adherence. In general, interventions to enhance patients’ HF literacy are crucial for building their self-care capabilities.From the second study aim stand to determine the factors contributing to self-care practices; interestingly management score was higher in female participants, indicating a higher application of the treatment plan. Gender was not a factor in earlier international studies. In this study, confidence significantly predicted 15.3% of the maintenance, 26% of the monitoring, and 21.9% of the management subscale scores. However, international studies showed higher prediction score. For example, in Lebanon, confidence predicted 26% of the maintenance, 34% of the monitoring, and 24% of management.Explaining independent variables’ contribution to self-care through multiple linear regression analysis revealed some significant factors but not to the total self-care practices score. The total score was not significantly explained by IV’s despite it being close to the significance level alpha value of 0.050. However, IV’s significantly predicted 8.2% of the monitoring subscale scores. Similar to previous international studies, confidence significantly predicted the Self-Care of Heart Failure Index subscales. thus, this study may also contribute to a better understanding of such factors among Saudi HF patients.Assessing HF self-care practices in the Saudi population using the Arabic version of the revised Self-Care of Heart Failure Index (V.7-2) and other widely used international instruments is crucial for comparisons between national and international outcomes. Moreover, understanding factors and approaches to engage HF patients’ participation in their healthcare practices identified as self-care or self-management is a cornerstone for successful healthcare interventions;The generalizability is limited due to cross-sectional design, convenience sampling, and single data collection location. On the other side, these factors facilitate smooth HF participants’ flow to the study location during the study period. In addition, comparisons with national and international studies revealed acceptable compatibility, in terms of gender and age representation. This does not preclude the need for further studies with more representative sample utilizing a longitudinal study design. From a positive perspective, the study is a positive step towards addressing HF patients’ self-care practices and factors that may enhance their care management and quality of life.In conclusion, this study shed light on HF patient self-care practices in one cardiac healthcare organization in Saudi Arabia. Participants showed sub-optimal HF self-care practices as well as the confidence to practice self-care activities. Female gender, education status, and hospital admissions were correlated with higher self-care. Confidence was a major predictor for all self-care sub-scales. Therefore, focusing on building confidence among HF patients could be an area of a priority in healthcare interventions.


Premature ventricular complexes (PVCs) are a potentially reversible cause of heart failure. However, the characteristics of patients most likely to develop impaired left ventricular function are unclear. Hence, the objective of this study is to systematically assess risk factors for the development of PVC-induced cardiomyopathy.We performed a structured database search of the scientific literature for studies investigating risk factors for the development of PVC-induced cardiomyopathy (PVC-CM). We investigated the reporting of PVC-CM risk factors (RF) and assessed the comparative association of the different RF using random-effect meta-analysis.A total of 26 studies (9 prospective and 17 retrospective studies) involving 16,764,641 patients were analyzed . Eleven RF were suitable for quantitative analysis (≥ 3 occurrences in multivariable model assessing a binary change in left ventricular (LV) function). Among these, age , the presence of symptoms , non-sustained ventricular tachycardias (VT) , LV origin , epicardial origin , the presence of interpolation , PVC duration , and PVC burden  were all significantly associated with PVC-CM.In this meta-analysis, the most consistent risk factors for PVC-CM were age, non-sustained VT, LV, epicardial origin, interpolation, and PVC burden, whereas the presence of symptoms significantly reduced the risk. These findings help tailor stringent follow-up of patients presenting with frequent PVCs and normal LV function.The online version contains supplementary material available at 10.1007/s10840-022-01421-8. Premature ventricular complex-induced cardiomyopathy (PVC-CM) is defined as the development of left ventricular dysfunction (left ventricular ejection fraction (LVEF) of < 50%) caused solely by frequent PVCs . SuperimClinical studies have found that a high PVC burden is associated with an increased risk of systolic heart failure (HF) (hazard ratio [HR]: 1.48 to 1.8) , 4. Two Prior studies investigating risk factors for PVC-CM were retrospective and were not designed with the main objective of assessing these RFs , 11, 12.We therefore conducted a systematic review and meta-analysis of studies addressing clinical, ECG, Holter, or echocardiographic risk factors able to differentiate patients having a PVC-induced CM from other forms of CM.This systematic review and meta-analysis received approval from the ethics committee and was registered on PROSPERO (CRD42021243622). The reporting of our results was done according to the PRISMA statement about systematic reviews and meta-analyses   RCTs, prospective, or retrospective observational studies and registers; (2) with at least 50 patients total (with and without PVC-CM); (3) assessing adult patients with at least part of the cohort diagnosed with PVC-CM and at least part of the cohort presenting with PVCs; (4) investigating risk factors for the development of PVC-CM (which were not defined beforehand); (5) reporting summary statistics such as regression coefficients, odds ratios (OR) or HR; (6) assessing the incidence, prevalence, or recovery of heart failure thought to be related to PVCs or the change in ejection fraction (EF) due to the presence, increase, or reduction of PVCs; (7) providing either time-to-event data or cross-sectional data; and (8) providing at least one adjusted (multivariable) risk-factor model.The primary endpoint of this meta-analysis was the quantitative meta-analysis of risk factors for the development of PVC-CM. We pre-defined that risk factors should be reported in at least 3 different studies with a compatible definition in order to allow for a meaningful quantitative summary.Secondary endpoints were either the qualitative analysis of risk factors reported in ≥ 3 different studies or important study characteristics, such as (1) the prevalence of comprehensive work-up to ensure patients diagnosed with PVC-CM did not present with another cause for heart failure; (2) the differences in the reported definitions of PVC-CM; and (3) the assessment of study quality using the validated QUIPS  tool .The primary outcome of this meta-analysis was the presence of PVC-CM, which we pre-defined either as the development, presence, or recovery from heart failure with reduced ejection fraction (HFrEF) in patients with CMP in whom no other cause of heart failure was evident. Further details are available in the supplemental.A meta-analysis was conducted on risk factors presenting ≥ 3 times throughout the studies. When continuous risk factors were presented using cutoffs, the exposure per group (above and below the respective cutoff) was derived as recommended in previous dose-exposure meta-analyses and corresponding guidelines –19.Further details regarding the analysis of risk factors are given in the supplemental.Study quality was assessed according to the QUIPS tool  and summThe analysis was performed according to the recommendations of the Cochrane Collaboration  and the We recorded quantitative measures of baseline characteristics as mean with standard deviation (SD) or median with interquartile range (IQR). To allow for quantitative summaries, we transformed the median with IQR into mean with SDs using a mathematical transformation as proposed in previous research .For the main analysis, in order to increase the number of studies available for the quantitative summary of each risk factor, we summarized odds ratios and hazard ratios as a common measure of risk ratio, as it has been conducted in previous meta-analyses , 22.I2 statistic [To allow for the expected heterogeneity in effect measures across studies, summary relative risk estimates and their 95% CIs were estimated from a random effect model  that usetatistic .Details of the dose–response analysis are available in the supplemental.I2 statistic of > 50%.Significant heterogeneity was defined as an Evidence for publication bias was assessed for PVC burden graphically using contour-enhanced funnel plots  and the The risk of bias within each study was assessed using the QUIPS tool.P values < 0.05 were considered as significant.All statistical analyses were performed using the Statistical Software “R” . A total of 1567 studies were identified and 1540 were excluded. There were 65 full-text publications reviewed, of which 39 were excluded: 31 studies were based on the same cohorts (mostly representing abstracts of otherwise available complete studies) and 8 studies did not provide risk factors of interest or appropriate statistics. This resulted in 26 studies included in the present systematic review and meta-analysis , 28–46  studies provided a definition of PVC-CM: the CMP was mostly defined as an LVEF < 50% and 9/26 (34.6%) studies took a time component into account . The requirement for LVEF improvement in the PVC-CM definition varied from 10 to 15% in these studies.Often, several groups were analyzed in each study, which did not always report data for the overall cohort. The analyzed groups are presented in Table Most of the studies assessed the presence of PVC-CM (17/26), the recovery of LVEF after PVC-CM 4/27 (defined as a binary variable), or the worsening of LVEF suspected to be due to PVC-CM 2/27 . We conducted a pooled analysis for these three outcomes, as these are solely different ways to define a PVC-CM. Studies reporting continuous LVEF change over time 3/26) were rare , followed by sex (13/26), PVC origin (11/26), PVC and morphology (10/26), and PVC and QRS duration (each in 8/26 studies). Only few other risk factors  were investigated in ≥ 3 studies and suitable for quantitative summary. Further investigated risk factors were baseline LVEF, coupling interval, polymorphic PVCs, and outflow tract origins. These risk factors did not appear often enough (< 3 appearances) or were differently defined, hence not suitable for quantitative summary.When summarized quantitatively, age , the presence of symptoms , non-sustained VTs , LV origin , epicardial origin , the presence of interpolation , PVC burden , and PVC duration  were all significantly associated with PVC-CM , non-suQ test for residual heterogeneity was highly significant, with an I2 statistic of 89.7%.In the dose–response analysis encompassing 7 studies reporting PVC burden at different cutoffs, there was a highly significant association between increase in PVC burden and an exponential increase in risk for PVC-CM  with each increase in publication year, meaning that studies published in 2020 displayed a non-significant 2.8% lower risk association of PVC-CM with PVC burden as compared with the studies published in 2010.The PVC-CM risk associated with PVC burden decreased of 0.28%  with each increase in quality point of the summed QUIPS tool, meaning that studies with a low risk of bias (in mean 45 points in the summed QUIPS tool) presented a 2.7% higher risk association of PVC-CM with PVC burden as compared with the studies with high risk of bias (in mean 15 points in the summed QUIPS tool).Inversely, the PVC-CM risk associated with PVC burden increased of 0.09% .On funnel plot analysis of PVC burden, study distribution was mildly asymmetric Fig.  but the As presented in Fig. four major findings. First, despite screening abstracts published over 30 years of scientific research, only few studies presented a multivariable assessment of risk factors potentially associated with PVC-CM and the quality of the research currently does not allow for definitive conclusion. Second, although many candidate risk factors were proposed by the analyzed studies, only 13 risk factors  were reported often enough with appropriate statistics to allow for a quantitative summary. Many other predictors remain possible candidates for the risk stratification of PVC-CM development. Third, age, non-sustained VTs, LV and epicardial origin, interpolation, PVC duration, and PVC burden were all associated with an increased risk for PVC-CM, whereas the presence of symptoms significantly reduced the risk. Fourth, there was a clear association between increasing PVC burden and increasing PVC-CM risk. In the dose–response analysis encompassing 7 studies reporting PVC burden at different cutoffs, there was a highly significant association between increase in PVC burden and an increasing risk for PVC-CM. Specifically, per % increase in PVC burden, there was an exponential increase in the absolute risk of PVC-CM. This association was not significantly impacted by the study publication year, suggesting that despite improvements in heart failure treatments and prevention over years, the burden remains an important predictor of PVC-CM development.This systematic review and meta-analysis investigated 26 studies to investigate risk factors associated with the development of PVC-CM. We report To the best of our knowledge, this is the first systematic review and meta-analysis comprehensively assessing the risk factors for the development of PVC-induced cardiomyopathy. The optimal approach to frequent PVCs (> 10% burden) without LV dysfunction, symptoms, or idiopathic ventricular fibrillation is unclear, but patients should probably be monitored every 6–12 months with echocardiography and PVC burden assessment . TherefoSeveral studies have confirmed a correlation between a higher PVC burden and development of cardiomyopathy, although no precise burden of PVCs consistently predicts the development of a cardiomyopathy. In this meta-analysis, we found a highly significant association between an increase in PVC burden and increasing risk for PVC-CM.This systematic review and meta-analysis has several limitations. First, the quantitative summary of risk factors we are presenting summarizes different measures of risks (odds and hazard ratios) together. While this has been conducted in previous research and is acknowledged by recent guidelines as a possible necessary simplification , this miThird, as several studies did not thoroughly assess other underlying heart failure etiologies in their patients collectively, our estimates may have been occasionally confounded by other causes of heart failure. Fourth, as most of the studies providing a PVC burden cutoff only provided two categories, we had to assume a linear trend between PVC exposure and the associated increase in risk . With more detailed data, quadratic estimations could lead to more accurate dose–response relationship modelling.In this meta-analysis, the most consistent risk factors for PVC-CM were age, non-sustained VTs, LV and epicardial origin, interpolation, PVC duration, and PVC burden, while the presence of symptoms significantly reduced the risk. These findings help tailor stringent follow-up to patients presenting with frequent PVCs and normal LV function.Supplementary file1 (DOCX 861 KB)Below is the link to the electronic supplementary material.


We found evidence for reducing psychological distress and/or subclinical symptoms in 9 out of 15 RCTs, 2 out of 3 controlled pre–post studies, and 9 out of 9 uncontrolled pre–post studies. One RCT provided evidence of increasing well-being. Innovative brief interventions have been developed to reduce distress and/or subclinical symptoms that have an emerging evidence base.A substantial number of survivors of disasters, pandemics, and other severe stressors develop persistent distress that impairs mental health and well-being. However, only a few brief psychological interventions target distress or subclinical symptoms. This systematic review aimed to identify and describe brief psychological interventions to reduce distress or subclinical symptoms in survivors of disasters, pandemics, and other severe stressors. Based on a systematic literature search , we reviewed published studies and study protocols on self-help, psychosocial support, or brief psychotherapeutic interventions to reduce distress and/or subclinical symptoms following natural hazards and man-made disasters, pandemics, or other traumatic events. We included 27 published studies or study protocols ( Natural hazards and man-made disasters , pandemBrief evidence-based interventions might be useful to promote recovery and prevent mental disorders. For example, psychological first aid (PFA) is widely known as an evidence-based approach to help individuals and communities cope in the immediate aftermath of a traumatic event . FurtherHowever, developing and evaluating brief interventions to target subclinical distress after disaster and trauma is a relatively new research field. A couple of narrative or systematic reviews summarized brief interventions on the specific subtypes of disasters, e.g., mental health impacts in response to climate change  or the IThe aims of this systematic review were to (1) systematically identify brief interventions to reduce psychological distress and/or subclinical symptoms in survivors of disasters, pandemics, and other traumatic events and (2) describe their effectiveness.Our report of this systematic review followed the ‘Preferred Reporting Items for Systematic Reviews and Meta-Analyses’ reporting guidelines, PRISMA; . The revWe included published peer-reviewed studies or study protocols in the German or English language (1) that evaluated or planned to evaluate brief psychosocial support, self-help, or brief (≤12 sessions) psychotherapeutic interventions for survivors of disasters, pandemics, and other traumatic events (2) that described or examined interventions to reduce psychological distress, subclinical symptoms of any type of mental disorder, or symptoms of adjustment disorder. To provide an overview not only of completed studies but also of planned or ongoing studies of brief interventions, we included study protocols in this review.We excluded studies or study protocols that (1) aimed to treat a mental disorder except for adjustment disorder, and studies (2) published before 2010.We performed a systematic literature search in five databases  from 1 January 2010 to 1 October 2021. Additionally, we identified studies by hand searching reference lists and contacting researchers.The search strategy was based on the PICOS  approach : SectionTwo reviewers (IL and AP) independently screened the titles and abstracts following the inclusion and exclusion criteria. The characteristics of the published studies or study protocols were extracted in an excel table . When disagreements occurred between the two reviewers, a third reviewer (AL) was consulted to decide together to include or exclude the study or protocol.Data from the included studies were extracted independently by two reviewers (IL and AP) in an excel sheet. When disagreements in the extracted data occurred between the two reviewers, a third reviewer (AL) was consulted. The following data were extracted: study, intervention name and description, study design, timepoint of intervention after stressor exposure , number of sessions, type of stressor, target population, delivery format, assessed outcomes, and results see .n = 319 records; 5 additional records were found through searching reference lists and contacting researchers  were RCTs; nine studies (33.3%) used an uncontrolled pre–post study design, and three studies (11.1%) were designed as a controlled pre–post study. Out of the 27 articles/study protocols, 11 articles/study protocols (40.7%) described studies on the survivors of natural hazards, 3 (11.1%) described studies on the survivors of man-made disasters, 8 (29.6%) described studies on the survivors of pandemics, and 5 (18.5%) described studies on survivors of other types of trauma. Twelve (44.4%) articles/protocols described studies examining the efficacy of psychosocial support interventions; nine (33.3%) articles/protocols described studies on the efficacy of brief psychotherapeutic treatments; and six (22.2%) articles/protocols reported on studies of self-help interventions.The study characteristics are listed in The characteristics of the brief interventions described in the included articles/protocols are summarized in Five self-help programs targeted adults, and one intervention focused on adolescents and their parents. The interventions were mostly conducted online; only one intervention was designed in a hybrid format. Four of the six self-help interventions were developed in a pandemic context, and the remaining two interventions were designed to be applied after disasters. Three of the six interventions comprised additional psychotherapeutic or psychological support.N = 252 adult COVID-19-infected patients [Computerized CBT (cCBT)  is a onepatients . A signiN = 71 female Chinese nurses working in an emergency isolation department during the COVID-19 pandemic [The Individualized Short-term Training Program  is a selpandemic . A signiN = 80 Canadian adults with anxiety symptoms during the COVID-19 pandemic [Online Psychotherapy Tool (OPTT)  is a 9-wpandemic . The effN = 120 French healthcare workers during the COVID-19 pandemic. In an RCT, the intervention group is compared to an active control group receiving bibliotherapy. No results have been published to date.“My Health too”  is a sevN = 979 US adolescents affected by tornadoes in Missouri and Alabama in 2011 [The web-based Bounce Back Now (BBN)  is a fou in 2011  revealedN = 1249 adult survivors [The Disaster Recovery Web (DRW) Project  is a selurvivors  found noFive psychosocial support programs targeted adults, and one intervention was developed for children and their parents. Two of the six psychosocial support programs were pandemic-focused, one intervention was disaster-focused, and three interventions targeted other types of trauma. Four interventions were designed as face-to-face interventions, although two of them could be applied either in a face-to-face or online format. The remaining two interventions were designed as online or phone-based interventions.N = 160 bereaved Chinese adults who have lost their first-degree relative during the COVID-19 pandemic [Grief Counseling for Adults  is a psypandemic . The resN = 1440 economically disadvantaged and vulnerable Indian adults during the COVID-19 pandemic [Resiliency Engagement and Care in Health (REaCH)  is a 4-wpandemic . The intN = 480 adults exposed to earthquakes and floods in Haiti [The Mental Health Integrated Disaster Preparedness (MHIDP) intervention  is aimedin Haiti . The proN = 121 participants [N = 611 adults from disaster-prone regions in Nepal received 5 weekly sessions of approximately 2.5 h. The PM+ group showed lower psychological distress and depression symptoms, and had fewer “heart-mind” problems compared to the control group at 3-months post-treatment. However, the PM+ group did not show an improvement in functional impairment and PTSD symptoms. An adapted version of PM+ for participants living in conflict-affected Peshawar in Pakistan was tested in a pilot RCT [N = 60 participants, compared to enhanced TAU . Functioning and PTSD symptoms improved more in the PM+ group post-intervention, but no significant changes in psychological distress could be observed between the groups. The effects of PM+ were compared to facility-based enhanced TAU provided by community nurses in an RCT in N = 421 Kenyan women exposed to physical or sexual abuse [N = 240 adults in a group context of 3–4 participants in Sydney, Australia. The intervention will be delivered over 6 weekly 60 min sessions and will specifically target COVID-19-related distress. The control group will receive enhanced TAU (emailed handouts with PM+ strategies and no expert assistance). In addition to psychological distress, rumination, sleep problems, anhedonia, social support, and COVID-19-related stress will be examined.Problem Management Plus (PM+)  is a briicipants  in earthicipants  investigilot RCT  in N = 6al abuse . The PM+al abuse  is plannN = 15 Australian bushfire survivors [N = 99 Pacific Islanders that were exposed to Tropical Cyclone Pam in 2015. SOLAR was administered in a group format of up to 10 participants compared to a TAU control group, which included informal familial, community, and church-based support. Reductions in psychological distress, PTSD symptoms, and functional impairment were found in the intervention group relative to the control group from pre- to post-intervention. The SOLAR group program was evaluated in a randomized controlled feasibility study in N = 30 German survivors of different types of trauma [The Skills fOr Life Adjustment and Resilience program (SOLAR)  is a briurvivors  demonstrurvivors  proved tf trauma . ParticiN = 20 US-American children impacted by the Great Flood of Iowa in 2008 to reduce PTSD symptoms [Listen Protect Connect (LPC)  is a schsymptoms . The schWe identified ten brief psychotherapeutic interventions, of which four were developed for children or adolescents. Two brief psychotherapeutic interventions were disaster-focused; the remaining eight interventions addressed survivors of other types of trauma, although some of these interventions could also be applied in the aftermath of natural hazards and man-made disasters. There were no interventions specifically designed for use during a pandemic. All interventions were designed as face-to-face interventions.N = 22 adolescents affected by the Great East Japan Earthquake in 2011 were divided into 2 groups, each with 11 adolescents. The results showed significant improvements in PTSD symptoms post-intervention which were maintained at a 4-month follow-up. There was no significant reduction in depressive symptoms.The Brief School-Based Cognitive Behavioral Intervention  is a oneN = 6 American children exposed to Hurricane Katrina in 2005 [Strength after Trauma (StArT)  is a bri in 2005 . The resN = 342 adults from New York State, US, exposed to Hurricane Sandy in 2012 [Cognitive Behavioral Therapy for Post-disaster Distress (CBT-PD)  is an 8- in 2012 , were asN = 52 children and adolescents aged from 4 to 18, 6 months after the explosion of a fireworks company in Enschede, Netherlands. Participants with disaster-related clinical symptoms were included in the study. They received up to 4 individual sessions delivered by a clinical psychologist over 4–8 weeks along with up to 4 sessions of parental guidance. Both treatment approaches produced significant reductions in PTSD symptoms, anxiety symptoms, depressive symptoms, and behavioral problems post-intervention. The study did not find significant differences in the outcomes between the groups.Exposure-based Cognitive Behavioral Therapy for children  aims to N = 55 Australian male adolescent refugees from Afghanistan and Pakistan with flight experience [The Preventive Resilience Training for Unaccompanied Refugee Minors  is a CBTperience . The intN = 50 US-American adult women with a history of interpersonal childhood trauma. The results showed a significant reduction in perceived distress, depressive symptoms, anxiety, emotion dysregulation, and PTSD symptoms at post-intervention and 1-month follow-up compared to baseline. Mindfulness also significantly increased.Mindfulness-Based Stress Reduction (MBSR)  is a traN = 429 emergency service professionals from the UK [The Trauma Therapy Program  is an inm the UK . The intN = 55 US veterans from Iraq or Afghanistan war [Emotional Freedom Techniques (EFT)  is a bristan war . The EFTN = 76 Chinese adolescents to reduce anxiety symptoms during the COVID-19 pandemic [Solution Focused Brief Therapy (SFBT)  is a bripandemic . The intThis systematic review aimed to identify and synthesize brief interventions to reduce distress and/or subclinical symptoms in individuals exposed to disasters, pandemics, or other traumatic events. We considered 27 published articles or study protocols (including 15 RCTs) that reported on 22 different brief interventions to reduce distress and/or subclinical symptoms. Out of the 27 included articles or protocols, 10 were published articles describing intervention studies, and 5 were study protocols.Six published articles or study protocols described studies on the efficacy of brief self-help interventions. Two articles reported on an RCT or an uncontrolled pre–post study evaluating self-help programs for COVID-19 survivors . Both studies reported significant reductions in anxiety at one-month follow-up after the application of cCBT  and postTwo published studies evaluated self-help programs (BBN and the DRW Project) for survivors of natural hazards . One article reported on a controlled pre–post study that found a significant decline in PTSD symptoms in adolescents and their parents at follow-up measurements after the application of BBN ; anotherWe found no published articles or study protocols on studies evaluating a self-help program for survivors of other types of traumatic events.Twelve published articles or study protocols described the evaluation of psychosocial support programs. We did not identify any evidence for the efficacy of psychosocial support programs for COVID-19 survivors. Two study protocols have been published ,32 that We identified evidence for one psychosocial support program (MHIDP intervention) targeting survivors of natural hazards  to improve depressive, anxiety, and PTSD symptoms at follow-up assessments .Nine identified published articles or study protocols described psychosocial support programs originally developed for survivors of other severe stressors, e.g., exposure to community adversity, crises, or interpersonal abuse. However, most of these interventions could be applied to other types of stressors, such as natural hazards. An uncontrolled pre–post study  showed tWe found five published articles or study protocols that described PM+  for commOverall, in the field of psychosocial support programs, most evidence for their efficacy is currently available for PM+, for which some RCTs have been conducted. SOLAR is another promising psychosocial support program with an emerging evidence base.Nine studies examined or planned to examine the efficacy of brief  psychotherapeutic interventions. No studies described interventions designed for an application during a pandemic. Two articles ,47 descrSeven published articles or study protocols described brief psychotherapeutic interventions originally developed for survivors of other severe stressors, such as terrorism or traumatic events. Most of these interventions can also be applied to other types of stressors, such as disasters or pandemics. Overall, the results of five studies showed that the interventions EFT, exposure-based CBT, EMDR, MBSR, CBT-PD, and the Trauma Therapy Program were successful in reducing psychological distress and/or subclinical symptoms ,56,57,60Overall, these findings suggest that there is the first evidence, especially on the efficacy of exposure-based CBT, EMDR, and EFT based on one RCT each. Additionally, there is a preliminary indication based on one uncontrolled pre–post study each that CBT-PD, MBSR, and Trauma Therapy Program may be effective in reducing psychological distress and/or subclinical symptoms.The interpretation of results synthesized in this systematic review should be interpreted considering the quality of the included studies. Thus, this systematic review is not without limitations. Several studies consisted of small sample sizes; more than half of the included studies considered fewer than 100 participants. Although a larger sample size would be desirable to achieve greater statistical power and generalizability in the results, there are challenges such as resource limitations and participant dropout making this difficult. In addition to 15 RCTs, 9 uncontrolled pre–post studies and 3 controlled pre–post studies were included in this review. Pre–post studies suffer from impaired internal validity and the associated limited interpretability of results. Furthermore, the long-term effectiveness of some interventions cannot be assessed because ten completed studies on these interventions did not report follow-up measurements ,47,53,57This systematic review extends previous research since, to our knowledge, no systematic review of studies describing or evaluating brief interventions aiming at reducing psychological distress and/or subclinical symptoms has been conducted before. We considered different types of stressors  as well as different types of interventions  to provide a broad overview of brief interventions for reducing distress and/or subclinical symptoms. Therefore, some of the interventions and target groups might not be directly comparable.This systematic review identified novel brief self-help programs, psychosocial support programs, or brief psychotherapeutic interventions that addressed distress and/or subclinical symptoms in survivors of disasters, pandemics, and other severe stressors. A few interventions showed the first evidence of being effective in reducing psychological distress and/or subclinical PTSD symptoms. Effective interventions mostly covered psychosocial support programs and brief psychotherapeutic interventions that focused on disasters or other severe stressors. Interventions that focused on the COVID-19 pandemic mainly involved self-help programs that showed limited evidence of effectiveness. Future research should further investigate the effectiveness of psychosocial support interventions and brief psychotherapeutic interventions for COVID-19 survivors.


Salmonella Typhimurium, Escherichia coli O157, Hepatitis E Virus, African swine fever virus and so on. Rapid and early detection of infectious and foodborne pathogens display a dramatic impact in controlling and preventing an outbreak. To face current challenges regarding infectious and foodborne pathogens, a point-of-care testing (POCT) concept has been introduced to detection technologies and devices. POCT technologies displayed the advance of user-friendly, rapid detection, so they can be directly used on-site or at home. This Research Topic is focused on novel ideas in POCT technologies and devices for infectious and foodborne pathogens, aimed at improving on-site application of rapid diagnostic techniques by detecting analytes including antigens, nucleic acids and specific antibodies for microorganisms.Infectious and foodborne pathogens usually pose emergency threat to the human and animal health. In recent years, they are gaining more attention due to emerging and re-emerging outbreaks, such as Influenza virus, Severe acute respiratory syndrome virus (SARS), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Ebola virus, Norovirus, Cui et al. established a real-time reverse transcription recombinase-aided amplification  assay targeting conserved positions in the matrix protein gene (M gene) of IAVs. The assay can be completed within 20 min at 42°C. The sensitivity of the real-time RT-RAA assay was 142 copies per reaction at 95% probability, which was comparable to the sensitivity of the RT-qPCR assay. The specificity assay showed that the real-time RT-RAA assay was specific to IAVs, and there was no cross-reactivity with other important viruses. In addition, 100% concordance between the real-time RT-RAA and RT-qPCR assays was achieved after testing 65 clinical specimens. The results suggested that the real-time RT-RAA assay was a specific, sensitive and reliable diagnostic tool for the rapid detection of IAVs. It will be critical for fast and sensitive detection of IAVs and controlling the spread of this disease.Influenza A viruses (IAVs) are important pathogens of respiratory infections, causing not only seasonal influenza but also influenza pandemics and posing a global threat to public health. IAVs infection spreads rapidly, widely, and across species, causing huge losses, especially zoonotic IAVs infections that are more harmful. In this Research Topic, Wang et al. developed a reverse transcription recombinase polymerase amplification assay targeting the ORF2 gene to rapid detect HEV by integrating the fluorescence detection platform (qRT-RPA) and the visible lateral flow biosensor by naked eyes (LFB RT-RPA). The qRT-RPA assay effectively detected HEV RNA with a limit of detection (LOD) of 154 copies/μL at 41°C for 20 min. Besides, the LFB RT-RPA detected the HEV RNA with a LOD of 24 copies/μL. The developed RT-RPA assays also showed good specificity for HEV with no cross-reactions with any of the other important swine pathogens examined in this work. The performance of the developed RT-RPA assays was validated on 14 HEV RNA positive and 66 HEV RNA negative raw pork liver samples identified by a previously described qRT-PCR. Consequently, 11 and 12 samples were HEV RNA positive as detected by the qRT-RPA and LFB RT-RPA, respectively. Compared to qRT-PCR, the qRT-RPA and LFB RT- RPA assays revealed a coincidence rate of 96.3% and 97.5%, as well as a Kappa value of 0.858 and 0.908, respectively. These results ascertain that the developed RT-RPA assays are effective diagnostic tools for the point-of-care detection of HEV in resource-limited settings.Hepatitis E virus (HEV) is a zoonotic pathogen that causes global hepatitis E. Outbreaks of Hepatitis E are directly linked to the consumption of pork liver products. Herein, Chlamydia trachomatis and Neisseria gonorrhoeae remain a major public health concern worldwide, particularly in less developed nations. It is crucial to use a POCT diagnostic method that is quick, specific, sensitive, and user-friendly to treat and control these infections effectively. Here, Chen et al. devised a novel molecular diagnostic assay, combining multiplex loop-mediated isothermal amplification (mLAMP) with a visual gold nanoparticles-based lateral flow biosensor (AuNPs-LFB), used for highly specific, sensitive, rapid, visual, and easy identification of Chlamydia trachomatis and Neisseria gonorrhoeae. Two unique independent primer pairs were successful designed against the ompA and orf1 genes of C. trachomatis and N. gonorrhoeae, respectively. The optimal mLAMP-AuNPs-LFB reaction conditions were determined to be 67°C for 35 min. The detection procedure, involving crude genomic DNA extraction (~5 min), LAMP amplification (35 min), and visual results interpretation (<2 min), can be completed within 45 min. This assay has a detection limit of 50 copies per test, displaying no cross-reactivity with any other bacteria. Hence, this assay can potentially be used for POCT to detect C. trachomatis and N. gonorrhoeae in clinical settings, particularly in underdeveloped regions.Sexually transmitted chlamydia and gonorrhea infections caused by the bacteria Streptococcus suis infection, serotype 2 and 14 is the most prevalent zoonotic strains. The establishment of a sensitive and extremely accurate method for POCT of Streptococcus suis serotype 2 and 14 strains on-site is highly desired. A loop primer probe-introduced loop-mediated isothermal amplification assay was developed by Meng et al. to differentiate Streptococcus suis serotype 2 and 14 based on SNP. The specific fluorescent probes were designed for the SNP site specific for serotype 2 and 14 Streptococcus suis cpsK genes, and the loop primer probe-introduced loop-mediated isothermal amplification assay was activated by the specific cleavage properties of RNase H2 enzyme. By using swarm primers to accelerated speed and efficiency of LAMP assays, the amplification reaction can be performed efficiently at isothermal 59°C within 40 minutes. The resuts can be real time detected or judged by using a smartphone and a 3D printed visualization cassette. The sensitivity of the Streptococcus suis LAMP assay can reach 18.4 CFU. The detection rate of the assay system was evaluated using clinical 19 samples with suspected Streptococcus suis infection, and the detection rate was consistent with the sequencing method, which is highly practical. This assay is specific and sensitive, not dependent on instruments and professional operators. Therefore, it is potential for field testing and differentiation of Streptococcus suis serotypes 2 and 14.As to Song et al. reported a sensitive and simple Fluorescent Probe Hydrolysis-Insulated isothermal PCR (iiPCR) that can detect and differentiate two genotypes of ASFV within 40 minutes. The positive or negative results of tested samples displayed on the screen of device automatically after PCR amplification was complete. The detection limit of the iiPCR was tested to be 20 copies for both genotype I and genotype II ASFVs. There was no cross-reactivity with other swine viruses by using the established iiPCR. Fifty-eight ASFV positive samples confirmed by National ASF Reference Laboratory were subjected to the established duplex iiPCR for genotype differentiation. The results showed that all these ASFV-positive samples belong to genotype II. Meanwhile, they found serum samples could be directly used as the templates for iiPCR without comprising sensitivity and specificity. Therefore, the duplex iiPCR was proved to be a useful tool for ASFV onsite detection and genotype differentiation.Genotype II African swine fever virus (ASFV) has been plaguing Asian pig industry since 2018. Recently, genotype I ASFV was reported for the first time in China. Since there is no commercial vaccine available against ASFV, early onsite detection and quick culling procedures are commonly used by many countries all over the world. It is desirable that the above two genotypes of ASFV could be quickly differentiated during onsite detection at the same time. In general, RPA, LAMP and isothermal PCR methods were mainly employed for POCT of infectious and foodborne pathogens in This Research Topic. Compared with RPA, LAMP and isothermal PCR methods only utilize single enzyme to realize the amplification reaction, showing huge advantage in use-cost. However, most reports in this Research Topic have not yet to be fully applied in POCT. Complex nucleic acid extraction process is the critical defectives of these methods. Indeed, POCT requires that all of the analytical processes, from sample collection to result communication, should be performable in one or a few simple steps to reduce time and costs. In addition to new amplification methods and devices, rapid nucleic acid extraction methods suitable for POCT should also be paid more attention in the future.HG drafted the manuscript. JZ and ML participated the revision of this manuscript. All the authors read and approved the final manuscript.


Neovison vison), used in fur production. Since 2020, passive surveillance of SARS-CoV-2 in mink farms was implemented in Lithuania. Here, we describe data from a survey of all 57 active Lithuanian mink farms carried out during November–December 2021 to complement passive surveillance in the country. In all 57 mink farms, nasopharyngeal swab samples were collected from dead or live mink and tested by real-time RT-PCR. Dead mink samples were tested in pools of 5, while live mink samples were tested individually. In 19 mink farms, blood serum was collected and tested for antibodies to determine previous exposure to the virus. Environmental samples from 55 farms were also collected and tested in pooled samples by real-time RT-PCR. The present survey has detected 22.81% viral RNA-positive mink farms and a high number of mink farms that were exposed  to the virus. The increasing exposure of mink farms to the virus due to growing human COVID-19 cases and limitations of passive surveillance could explain the observed epidemiological situation of SARS-CoV-2 in Lithuanian mink farms, compared to the few positive farms previously detected by passive surveillance. The unexpected widespread exposure of mink farms to SARS-CoV-2 suggests that passive surveillance is ineffective for early detection of SARS-CoV-2 in mink. Further studies are needed to reveal the present status in previously infected mink farms.The newly emerged SARS-CoV-2, causing COVID-19 in humans, is also infecting American mink ( After the first report in Dutch mink farms in April 2020 (The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 19 (COVID-19), was first detected in humans in December 2019 and soon became a global pandemic . Among tril 2020 , the virril 2020 . Furtherril 2020 , 7, and ril 2020 , 9. The ril 2020 . The risril 2020 . FurtherAccording to European Food Safety Authority (EFSA) and European Centre for Disease Prevention and Control (ECDC), all mink farms are at risk of infection and should be under surveillance . An actiSince 2020, the State Food and Veterinary Service of the Republic of Lithuania (SFVS) implemented mandatory passive surveillance of the virus in the country’s mink farms. Mink farm owners were obligated to report higher than usual mink mortality/morbidity rates, reduced feed consumption, and confirmed COVID-19 infection in farm personnel to territorial SFVS. Furthermore, mink farms had to provide factual numbers of mink mortality and morbidity to territorial SFVS on a weekly basis. In November 2020, the SFVS carried out a sampling of dead minks in all active mink farms in the country with negative results, although relatively few nasopharyngeal swab samples were tested per farm by real-time RT-PCR (89 samples from 69 mink farms). In November and December 2020, the first two SARS-CoV-2 infected mink farms have been detected by passive surveillance in Lithuania . While n2.In November–December 2021, according to an order of SFVS, all active mink farms  in Lithuania had to be sampled and tested for SARS-CoV-2. Sampling on farms was done by official veterinarians. During the survey, no movement of minks was allowed in the country.At least 30 nasopharyngeal swab samples from either dead, sick or live mink were taken at every mink farm, with the aim of detecting a 10% within-farm infection prevalence at 95% confidence. In very few cases, less than 30 samples were taken due to intensive pelting and high workload, as well as in some farms—more than 30 samples were taken, where more than one epidemiological unit was present. The priority was to take samples from dead and diseased minks. The rest of the samples were taken from minks killed for pelting or live animals. In the latter situation, samples were collected to ensure that each sector of a farm was sampled.Nineteen mink farms out of 57 were convenience sampled for mink blood serum to determine previous exposure to the virus. Thirty mink blood samples were collected from each farm. Both adult (more than 1-year-old) and juvenile (less than 1-year-old) minks were sampled from various places of a farm. Additionally, environmental swab samples were collected from 55 mink farms using the same swabs that were used for nasopharyngeal sample collection. Each farm was divided by area size into five roughly equal parts, and one sample was taken from every area. Environmental swab samples were collected from surfaces of mink cages, walls, ceilings, and floors of open houses, as well as from household items that had contact with the minks or farm staff. Risk-based sampling was performed as samples were first collected from open houses with increased mink mortality or morbidity if present.Information about the exact location of every taken mink or environmental sample was collected, as well as the total number of minks present on farms. Information about the age of sampled minks was collected from most of the farms. All samples from one farm were collected and delivered to the laboratory on the same day. All laboratory testing was done at the National Food and Veterinary Risk Assessment Institute in Lithuania.2.1.™ Viral/Pathogen II (MVP II) Nucleic Acid Isolation Kit  and KingFisher Flex system (Thermo Fisher Scientific) were used for viral RNA extraction, and TaqPath™ COVID-19 RT-PCR Kit  was used for real-time RT-PCR reaction, according to the manufacturer’s protocol.Swab samples from dead mink and the environment were tested by real-time reverse transcription-polymerase chain reaction  in pools of 5 individual samples from the same mink farm. Live mink swab samples were tested individually. All samples were kept so they could be tested individually. MagMAX2.2.Mink blood serum samples were tested individually. Blood samples were centrifuged, and the serum was collected. ID Screen SARS-CoV-2 Double Antigen Multi-Species kit (ID.VET) was used to detect anti-SARS-CoV-2 antibodies in mink serum. The solutions were prepared, and testing was done according to the manufacturer’s protocol.2.3.z-test for sample proportion comparisonMicrosoft Excel Spreadsheet Software  and Epitools software were used for statistical analysis. A 2-sample 2.4.No experimental procedures were performed on animals. All animal samples were taken by official veterinarians for a compulsory animal health surveillance program. Therefore, no ethical approval was required.3.During the survey period, a total of 57 mink farms in Lithuania were tested for SARS-CoV-2, and 25 were found positive  either by RT-PCR for the presence of the virus or ELISA for the presence of antibodies. None of the sampled farms reported increased mortality or morbidity during the study. The positive farms were situated across the country with no signs of obvious clustering. At the time of sampling, the number of mink present on all sampled farms varied widely and ranged from 120 to 159,916, with an average of 14,597 animals present on farms .Information about infected staff in mink farms showed that in 11 farms, at least one staff was confirmed to have been infected with SARS-CoV-2 from 4 days up to 1 year before a farm was sampled. Four of these farms were viral RNA-positive, and 10 of them were positive for anti-SARS-CoV-2 antibodies. No infected staff was reported in SARS-CoV-2-negative farms .3.1.In total, 13 (22.81%) out of 57 tested farms were found SARS-CoV-2 RT-PCR positive .p = 0.6081).A total of 943 dead mink nasopharyngeal swab samples were taken from 34 mink farms. Data about the age of tested dead mink were collected from 26 farms. Seventeen pooled samples were taken and tested from adult dead mink, and one pooled sample  tested positive for viral RNA. Meanwhile, 140 pooled samples from juvenile mink were tested, and 19 of them  tested positive by real-time RT-PCR . There wp = 0.3689).In total, 1,015 live mink swab samples were collected from 35 farms. Data about the age of tested live mink were collected from 22 of these farms. Samples from 76 adult live mink were collected, and 4 of them  tested positive for viral RNA. Meanwhile, 565 juvenile live mink samples were collected, and 15 of them  tested positive by real-time RT-PCR . The dif3.2.A total of 55 pooled environmental swab samples were collected from 55 different mink farms, five samples each. From one farm out of 55 , only one of the five individual environmental swab samples tested positive for SARS-CoV-2 RNA. The positive sample was taken from the surface of a mink cage. Dead and live mink nasopharyngeal swab samples collected from this farm also tested positive for viral RNA , but no 3.3.Nineteen mink farms were sampled and tested for anti-SARS-CoV-2 antibodies. The limited blood serum sampling was due to intensive swab sampling and reduced resources of veterinary and farm personnel because of the COVID-19 pandemic. In total, 570 mink serum samples from 19 farms were tested by ELISA. Out of these, 298 mink samples from 16  farms tested positive for anti-SARS-CoV-2 antibodies . Only 4 p = 0.3171).At the time of sampling, the number of minks on the 19 serologically tested farms ranged from 1,025 to 79,300. The average number of minks on the antibody-positive farms was 14,992 and 7,298 on the antibody-negative farms . Data abp < 0.0001) higher than the proportion of viral RNA-positive farms.The proportion of mink farms with anti-SARS-CoV-2 antibodies was significantly   . The ince cases) .p < 0.0001) mink farms than the SARS-CoV-2 RNA. SARS-CoV-2 infection was likely detected in different stages at various farms. For instance, 11 out of 16 antibody-positive mink farms tested negative by real-time RT-PCR, but most of them had a high proportion of antibody-positive samples, suggesting a long presence of SARS-CoV-2 infection in the farms. Furthermore, all pooled dead mink samples from farms No. 1 and 2 tested positive for viral RNA, but less than half of the tested mink blood samples had anti-SARS-CoV-2 antibodies, suggesting an earlier infection phase  mink farm, tested positive by real-time RT-PCR in this study. The low number of positive environmental samples detected in our study could be due to the collection technique because swabs used in our study covered much less surface area than dust cloths used in Dutch and Greek studies , 24. The5.This study showed a lack of detection of SARS-CoV-2 in Lithuanian mink farms by passive surveillance. However, it remains unclear if it was caused by improper reporting or limited increase of mortality and/or morbidity of SARS-CoV-2 infected mink. The unexpected widespread exposure of mink farms  to the virus suggests that passive surveillance is ineffective for early detection of SARS-CoV-2 in mink. Further studies are needed to reveal the present status in previously infected Lithuanian mink farms.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.Ethical review and approval was not required for the animal study because no experimental procedures were performed on animals. All animal samples were taken by official veterinarians for a compulsory animal health surveillance program. Therefore, no ethical approval was required.MM, VP, PB, and AM contributed to conception and design of the study. SP and JB performed the laboratory analysis. SŽ performed the data analysis and wrote the first draft of the manuscript. AM wrote sections of the manuscript. All authors contributed to the article and approved the submitted version.The collection and testing of samples were done by implementing disease control services of Lithuanian State Food and Veterinary Services and was partly supported by the Lithuanian Ministry of Agriculture.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The success of training computer-vision models heavily relies on the support of large-scale, real-world images with annotations. Yet such an annotation-ready dataset is difficult to curate in pathology due to the privacy protection and excessive annotation burden. To aid in computational pathology, synthetic data generation, curation, and annotation present a cost-effective means to quickly enable data diversity that is required to boost model performance at different stages. In this study, we introduce a large-scale synthetic pathological image dataset paired with the annotation for nuclei semantic segmentation, termed as Synthetic Nuclei and annOtation Wizard (SNOW). The proposed SNOW is developed via a standardized workflow by applying the off-the-shelf image generator and nuclei annotator. The dataset contains overall 20k image tiles and 1,448,522 annotated nuclei with the CC-BY license. We show that SNOW can be used in both supervised and semi-supervised training scenarios. Extensive results suggest that synthetic-data-trained models are competitive under a variety of model training settings, expanding the scope of better using synthetic images for enhancing downstream data-driven clinical tasks. Whole slide images (WSIs) offer an efficient tool to assess the disease visual status ranging from staging, metastasis, to prognosis3. Especially high-resolution WSI can capture diverse tissue appearance and cell morphology to inform clinical decision making. To advance diagnosis of breast cancer, nuclei identification plays a key role because its characteristics are strongly associated with patient outcomes4. For instance, aggressive breast cancers often include vesicular nuclei and prominent nucleoli5. Building a quantitative pipeline of nuclei analysis is thus crucial for understanding cancer microenvironment. Growing deep-learning approaches4 are developed to automate WSI-based nuclei segmentation, however, the model performance is contingent on the quality and quantity of real-world training samples.Breast cancer is the most prevalent type of cancer in women with 2.3 million new cases annually6, and fine-tune the model until convergence9. Yet, pathological data curation faces daunting challenges in the healthcare system due to privacy protection and excessive annotation burden11. Annotating tissue characteristics from a complex WSI can take on average 1.8 hours12, thus scaling human-level WSI annotation is increasingly challenging. To date, real-world breast cancer-related nuclei data sets . To address this limitation, in cancer pathology, researchers apply mask-defined approaches29 to generate synthetic images for improving cell semantic segmentation . These approaches usually begin with proposing predefined masks to locate nuclei positions. Examples include random-, distributional-generated masks29 and human-annotated masks29. Under such a mask-constrained setting, the use of GANs is prone to generate only shape-predefined nuclei samples. For instance, a predefined mask focusing on capturing fully-separated nuclei is unlikely to include the clumped nuclei, which is commonly observed in real-world tissue images. As a result, this predefined setting becomes a hurdle to training robust models for segmenting challenging cells  have been a key computational tool for producing high-quality synthetic imagessynthetic nuclei and annotation wizard (SNOW)  Fig. , which a35. SNOW could also facilitate breast-cancer-specific pretraining and finetuning tasks. SNOW provides an alternative set of samples for the model training for the downstream task . In addition, SNOW dataset could be used as the source data for training adversarial attack detection models to recognize malicious attacks in medical image analysis. Despite showing appealing characteristics of SNOW, we limit our focus on breast carcinoma in this report. A broader range of exploration on multiple cancers is the natural next step. Our study is built upon the power of off-the-shelf models with a proven utility on pathological images36, while diffusion models37 are not considered due to their high computational costs . To sum up, the release of SNOW makes an important step towards curating synthetic data sets compared to the current machine-training workflows using real-world pathological data . The NA is designed to generate weak nuclei annotation  without adding fine-tuning procedures of nuclei annotator. Instead of pretraining on a large-scale, out-domain dataset , SIG and NA here is trained from scratch using in-domain public datasets given their differential characteristics on image resolution and annotation availability  regularization38, which is used for estimating the quality of latent space interpolations and correlating with consistency and stability of shapes. Further, StyleGAN2 applies a truncation operation38 to add more diversity for image generation by avoiding the generated image converging to the ‘mean’ representation of the training dataset. These components make StyleGAN2 to produce the required synthetic images in our task.Synthetic image quality is evaluated by measuring the similarity between synthetic data to real-world data, including the nuclei shape and tissue morphology. Further, the nuclei statistics, such as the number of nuclei in each synthetic image, also reflect the quality of synthetic image. To satisfy these criteria, we choose StyleGAN239. Standard data augmentation is helpful to alleviate the overfitting39, yet noisy augmentation inputs must be well handled. To address these issues, we use an adaptive discriminator augmentation (ADA) scheme in our SIG without changing the loss function or network architecture of StyleGAN2. The ADA scheme39 controls the augmentation strength by using a threshold p ∈  dynamically based on the degree of potential overfitting. The augmentation is applied with probability p or skipped with probability 1 - p). Inspired by RandAugment40, eighteen diverse transformations are included in the augmentation. The ADA scheme adjusts theshold p by evaluating the relevance between the StyleGAN2’s output on the original training samples and the generated images. Further, ADA evaluates the overfitting degree by estimating the portion of the training samples to get positive discriminator outputs. Without a large-scale out-domain pretraining , the use of ADA is proven to be helpful in a data-limited training environment39.To ensure the quality of image generation from StyleGAN2, data generation efficiency is a crucial factor in the domain of pathological image analysis. Considering a small-scale training data set, the discriminator of StyleGAN2 can overfit training samples, where the feedback to the generator of StyleGAN2 becomes less meaningful and training starts to diverge15. As opposed to using human annotation to scale up, we initialize NA module by leveraging public datasets with prior human knowledge of nuclei inputs. We selected HoVer-Net6 as the nuclei annotator in our study because of its reliable performance in multiple baselines of segmenting challenging nuclei examples15. In HoVer-Net, the feature extraction component is inspired by a pre-activated residual network with 50 layers (Preact-ResNet50)41. Compared to the standard Preact-ResNet50, HoVer-Net reduces the total down-sampling factor from 32 to 8 by using a stride of 1 in the first convolution and removing the subsequent maxpooling operation. These modifications reduce immediate loss of information and ensure the quality of segmentation6. HoVer-Net utilizes the nearest neighbour up-sampling via distinct functional branches, including nuclei pixel (NP) and HoVer branch. The NP branch predicts pixel membership to the nuclei or background, while the HoVer branch predicts the horizontal and vertical distances of nuclear pixels to their centres of mass6.We define the nuclei annotator (NA) as a label-efficient expert to automatically accomplish nuclei annotation in synthetic images. Instead of pursuing fine-grained annotations, NA module only produces a set of weak nuclei annotations that perform reasonably good to train segmentation models without adding human correction. Currently, the routine workflow of nuclei semantic segmentation heavily depends on human annotation, which explains the restricted scale of nuclei dataset in the literatureθ is trained on the training set lBCE and dice loss lDICE. Further, we select the best model θ* for model evaluation from the validation set, where n is the number of the training set.For supervised training scheme, we use all of the available images and the corresponding annotations for model training. The model 42, we use the mix of labeled and unlabeled data to train the model. First, we train a teacher model θteacher on the labeled training set lBCE and dice loss lDICE. Moreover, we select the best teacher model For semi-supervised training scheme, we utilize a self-training strategy to enable a better exploration of the in-depth information hidden in the images. Inspired byThen, we use the selected teacher model θstudent on the labeled and pseudo-labeled data to minimize the combined loss. The student model has a same architecture and size as the teacher model.We then train a student model Further, the best student model is selected by measuring the performance from validation set. The selected student model 13 includes 162 breast tissue tiles with point location for each nuclei. As BreCaHAD data set does not provide the semantic segmentation mask of entire nuclei , we utilize PanNuke data set15 for training nuclei annotator, which contains both images and corresponding annotation masks . To date, PanNuke data set15 is the largest nuclei segmentation data set . Under the proposed pipeline, SNOW produces 20k synthetic breast cancer tissue patches paired with nuclei shape annotations.The creation of our synthetic dataset is associated with two real-world data sets. Table 43) and GitHub (https://github.com/Cassie07/SNOW-Dataset).Image folder All synthetic images are in SNOW_Image.zip folder.Mask folders Due to the large size of the nuclei segmentation mask, we split all masks into four folders . In each zip folder, we include three sub-folders: json, mat, and overlay. We only use mat folders to save nuclei segmentation mask for each synthetic image.Datasheets for Datasets To help users understand details of the dataset and possible extensive use, we prepared datasheets44 for our data set. The detailed responses are related to the following factors, including study motivation, composition, collection process, preprocessing/cleaning/labeling information, distributions, and data maintenance.All data records are included in Zenodo , we evaluate the segmentation performance on the independent, real-world dataset of Triple Negative Breast Cancer (TNBC) data set16. For all experiments in our study, the batch size is 64, the optimizer is Adam48, and the learning rate is 1e-4. We used four Tesla V100 SXM2 GPUs for our experiments. To evaluate nuclei semantic segmentation performance, we use the DICE score, Jaccard index ), and average hausdorff distance (aHD).We apply nuclei semantic segmentation to evaluate the performance of the proposed synthetic dataset. To rigorously avoid data confusion, we did not use additional data augmentation during the training of segmentation models. Our major focus here is placed on diagnosing data utility, which differs from the majority of studies towards tuning model parameters for optimizing segmentation performance. In our experiment, we consider standard ResNet34https://github.com/NVlabs/stylegan2-ada-pytorch. The model weights are obtained by training StyleGAN2-ADA from scratch on BreCaHAD dataset. The batch size is 64, the optimizer is Adam, and the learning rate is 2.5e-3. Each image of BreCaHAD is cropped into patches with the resolution of 512 × 512 for model training. We choose BreCaHAD as a choice for generator input because of its key focus on nuclei assessment, where each image patch includes reasonable amounts of nuclei  for model training. This is in contrast with The Cancer Genome Atlas (TCGA) database49 containing WSIs without selection and annotation of nuclei, stromal cells, lymphocytes, and other tissue contents. For the design of image annotator, we use the PanNuke-trained HoVerNet model. The model weights are obtained from https://github.com/vqdang/hover_net. During the training process, the batch size is 8, the optimizer is Adam, and an initial learning rate of 1e-4 and then reduced it to 1e-5 after 25 epochs.Regarding the synthetic image generator, we use the model of BreCaHAD-trained StyleGAN2-ADA. The model weights are released by real-world data set . Finally, the finetuned model will be tested on the remained real-world data TNBC (20%). In this pipeline, the in-domain pretraining is under either supervised and semi-supervised training strategy, while the finetuning is under supervised training mode. We choose a full-model weights trainable finetuning to update the model weights on TNBC training set. Under the above setting, we also report baseline results regarding whether or not using out-domain real-world data for model encoder initialization.To assess the extensible utility of SNOW, we evaluate a joint segmentation performance using synthetic and real-world data 16 and CoNSeP dataset6). In Table We extend to assess the reliability performance of the nuclei annotator on the unseen data sets. We use the trained annotator to annotate multiple public nuclei segmentation data sets and comparing the results with the associated ground-truth annotations provided by human experts. First, we report the internal nuclei annotator capability by annotating PanNuke data set because the nuclei annotator is trained and evaluated by the same data set. Second, we assess the ability of nuclei annotator by evaluating on unseen data sets (e.g., TNBCIn Fig. 42 applied on the natural image dataset.In Fig. We use CC-BY license and complete attribution metadata.Supplementary information