Some clinical features of severe COVID-19 represent blood vessel damage induced by activation of host immune responses initiated by the coronavirus SARS-CoV-2. We hypothesized autoantibodies against angiotensin-converting enzyme 2 (ACE2), the SARS-CoV-2 receptor expressed on vascular endothelium, are generated during COVID-19 and are of mechanistic importance.In an opportunity sample of 118 COVID-19 inpatients, autoantibodies recognizing ACE2 were detected by ELISA. Binding properties of anti-ACE2 IgM were analyzed via biolayer interferometry. Effects of anti-ACE2 IgM on complement activation and endothelial function were demonstrated in a tissue-engineered pulmonary microvessel model.P = 0.0009). Anti-ACE2 IgM autoantibodies were rare (2/50) in non-COVID-19 ventilated patients with acute respiratory distress syndrome. Unexpectedly, ACE2-reactive IgM autoantibodies in COVID-19 did not undergo class-switching to IgG and had apparent DK values of 5.6–21.7 nM, indicating they are T cell independent. Anti-ACE2 IgMs activated complement and initiated complement-binding and functional changes in endothelial cells in microvessels, suggesting they contribute to the angiocentric pathology of COVID-19.Anti-ACE2 IgM (not IgG) autoantibodies were associated with severe COVID-19 and found in 18/66 (27.2%) patients with severe disease compared with 2/52 (3.8%) of patients with moderate disease , National Heart, Lung, and Blood Institute R21HL145216, and Division of Intramural Research, National Institute of Allergy and Infectious Diseases; National Science Foundation Graduate Research Fellowship (DGE1746891)  COVID-19 is caused by the novel coronavirus SARS-CoV-2 . Two yeaThere is significant evidence for preexisting IgG autoantibodies against type I IFNs playing a key role in mediating disease severity in COVID-19 , likely P = 0.0084 by Fisher’s exact test; https://doi.org/10.1172/jci.insight.158362DS1). In order to increase sample size and define the stability and kinetics of these antibodies, we assembled additional patients in whom serum was available from multiple laboratory blood draws taken across their hospitalization. This added 52 patients with COVID-19 for serum analysis: 38 in WHO ordinal groups 6 to 8 (31 ventilated and 7 dead) and 14 patients in ordinal group 4 , the host receptor for SARS-CoV-2 entry , could bP = 0.44 by Fisher’s exact test). Only 4/18 (22%) severe patients with anti-ACE2 IgM antibodies were also IgG positive  patients with severe COVID-19 (WHO 6–8) and 6/52 (11.5%) patients with moderate (WHO 3–5) disease    . While population average neutrophil counts (3) than in the anti-ACE2–negative group (4.95 K/mm3), these results did not reach statistical significance (P = 0.10). The elevated temperature observed in anti-ACE2 IgM–positive patients early after admission  In 3 patients , sampling spanned the development of anti-ACE2 IgM . In thesIn T cell–dependent immune responses, IgM levels generally decrease at the time of class-switching to IgG. We therefore examined whether decreasing IgM levels over time were associated with increasing anti-ACE2 IgG levels at later points. In 1 patient (CV-1), both IgG and IgM were present at the earliest point and remained constant over time . In 8 anP < 0.0001 by unpaired t test; P = 0.028; Mann-Whitney test; P = 0.017 by Fisher’s exact test; Multiple groups have noted that high levels of anti–SARS-CoV-2 S protein IgG occurring at the time of hospital admission are associated with more severe disease in COVID-19  to 21.7 nM (CV-134). In contrast, IgM from controls did not approach saturation binding to ACE2 even at the highest tested concentrations (representing the undiluted sample), and the DK values could thus not be determined , they benefit from avidity effects because of their pentameric construction . Patient IgM binding to immobilized ACE2 was saturable , with aptermined . It is itruction .Since hypomorphic ACE2 function has been associated with severity in ARDS, we investigated whether purified IgM from patients with COVID-19 affected the catalytic function of ACE2 against a fluorogenic substrate. Two purified IgMs used above in binding assays had no effect on ACE2 activity ..IgM antibodies are mainly found in the circulation, where they are the most effective antibody isotype in activating the classical complement cascade at surfaces expressing their cognate antigens . We founAutopsy studies have demonstrated prominent findings in the lungs of COVID-19 patients , 23, incP < 0.001)  for CV-1 IgM is about 80 minutes  . A decre minutes , we expeP = 0.0117). A similar increase in barrier function was observed after perfusion with 100 ng/mL of affinity-purified anti-ACE2 IgM (P = 0.008), providing further evidence that the effect on barrier function is mediated by ACE2 binding. It is noteworthy that some long-lived PMEC stimuli  cause an initial tightening of the endothelial barrier, followed by later barrier leakiness mediated through receptor downregulation , multiple signaling pathways can be initiated . These iThe ability of anti-ACE2 IgMs from patients with COVID-19 to bind C1q and induce C3 deposition on PMECs is consistent with their playing a role in inducing the complement pathway activation that is prominent in patients with severe COVID-19 , 21. DirThese IgM-activated pathways are potentially amenable to several readily available treatments applied in the acute inflammatory phase of severe illness, e.g., steroids and IVIG therapy –39, as wThe subset of patients (27%) with severe COVID-19 who developed IgM antibodies against ACE2  are almost certainly not overlapping with the 10% of patients with severe COVID-19 who had preexisting IgG antibodies against type I IFNs  a confirmed diagnosis of COVID-19; (b) survival to death or discharge; and (c) remnant specimens in the Johns Hopkins COVID-19 Remnant Specimen Biorepository, an opportunity sample that includes 59% of Johns Hopkins Hospital patients with COVID-19 and 66% of patients with length of stay ≥ 3 days between April 20, 2020, and May 14, 2020. Diagnosis of COVID-19 was defined as detection of SARS-CoV-2 using any PCR test with an Emergency Use Authorization from the US Food and Drug Administration. Selection and frequency of other laboratory testing were determined by treating physicians. The primary clinical data source was JH-CROWN, a Johns Hopkins Medicine COVID-19 registry that integrates all clinical data for COVID-19 patients, including demographics, medical history, comorbid conditions, symptoms, medications, laboratory results, medical images, and comprehensive bedside flow sheet data, including vital signs, respiratory events, and intravenous medication titration , to hospitalized with mild-moderate disease , hospitalized with severe disease , and 8 = death. For this study we combined adjacent WHO classes, dividing the inpatient population into 2 groups according to maximum WHO severity: patients who did not require mechanical ventilation (WHO classes 3–5) and those who required mechanical ventilation with or without additional support, such as intravenous pressors, continuous renal replacement therapy, and/or ECMO who survived (WHO classes 6–7) or died (WHO class 8). Serum samples were selected for timing within 24 hours of onset of the maximum WHO class; when multiple samples were available, the specimen closest to the WHO class onset was used. The initial analysis used a random sample of 12 to 20 unique patient specimens from each of the 4 classes meeting the criteria above . To determine biomarker trajectory, we analyzed an expanded cohort of patients who had 3 to 4 consecutive sera per patient across the course of their hospitalization. Patient selection was determined solely by specimen availability. Where available, additional serum for anti-ACE2 IgM–positive individuals was requested from the remnant biorepository.n = 25 patients with SLE from the Hopkins Lupus Cohort, (b) sera from n = 13 patients diagnosed with systemic sclerosis after evaluation at the Johns Hopkins Scleroderma Center, and (c) n = 15 patients with necrotizing myopathy defined by a positive anti-HMGCR antibody status evaluated at the Johns Hopkins Myositis Center. Serum from n = 30 patients with influenza diagnosed using the Cepheid Xpert Xpress Flu/RSV assay in the Johns Hopkins emergency departments or inpatient units was studied. Eleven were evaluated in the emergency department and discharged to outpatient care; an additional 19 patients were hospitalized and required oxygen therapy or assisted ventilation  sera from At the initiation of this study, we were struck by the similar clinical presentation of severe COVID-19 to a dermatopulmonary syndrome, characterized by skin rash, rapidly progressive interstitial lung process with frequent progression to a need for ventilatory support, and a unique vasculopathic phenotype including cutaneous ulcers and digital ischemia , 30, 42.ELISA plate wells were coated overnight with 50 ng of purified protein  diluted in PBS. For each serum assayed, duplicate wells were coated with protein, and an adjacent well was incubated overnight with PBS (to determine background specific to each sample). For anti-ACE2 IgM ELISA, wells were washed with PBS plus 0.1% Tween (PBST), then blocked with 3% milk/PBST. Primary antibody incubations were performed by diluting sera 1:200 in 1% milk/PBST . For area under the curve plots , serial Assays were performed as described for anti-ACE2 IgG ELISAs, using sera diluted 1:1200 .The CoronaChek serologic lateral flow assay (Hangzhou Biotest Biotech) detects IgM and IgG antibodies against the S protein and receptor binding domain of SARS-CoV-2. Studies on positive and negative control specimens from Maryland demonstrated sensitivity of 95%  in convalescent plasma donors an average of 50 days after symptom onset; sensitivity of 100%  in PCR-confirmed hospitalized individuals 15 days after symptom onset; specificity of 100%  in pre-pandemic patients infected with rhinoviruses and other coronaviruses.oC) with a mouse monoclonal anti-FLAG antibody  to detect CD9, a rabbit monoclonal anti-TMPRSS2 antibody , or a mouse monoclonal anti-CD81 antibody . Blotted proteins were detected using HRP-labeled secondary antibodies  and chemiluminescence (Pierce). Images were acquired using a Protein Simple Fluorochem-M digital imager. To screen for antibodies against CD9, CD81, and TMPRSS2 in patient sera, immunoblots were performed using lysates made from untransfected cells and from validated transiently transfected cell lysates . The sera were used at 1:1000 dilution , followed by a mixture of HRP-labeled anti-human IgG and anti-human IgM , with detection as described above.Complementary DNAs encoding full-length FLAG-tagged CD9 and TMPRSS2  and CD81 (GenScript OHu19408) were sequence verified. These DNAs were transiently transfected into HEK293T cells (purchased from ATCC) with ExpiFectamin_293 reagent (Thermo Fisher Scientific A14524). After 48 hours, the cells were lysed in buffer A  and a protease inhibitor cocktail. Robust expression of transiently expressed proteins was confirmed by immunoblotting equal protein amounts of lysates electrophoresed on 11% SDS-polyacrylamide gels. After blocking the membranes, primary antibody incubations were performed , and loaded onto the column. The column was washed twice with 5 CV of PBS. Bound IgM was eluted with 5 CV of 0.1 M glycine pH 3, neutralized with 0.5 CV of 1 M Tris-HCl (pH 8), exchanged into PBS, and concentrated to match the original serum volume. The 280 nm absorbance of the purified IgM was measured to calculate the IgM concentration, using the extinction coefficient for pentameric human IgM.We equilibrated 0.5 mL of POROS CaptureSelect IgM Affinity Matrix (Thermo Fisher Scientific) with 10 column volumes (CV) of PBS pH 7.2 in a Poly-Prep chromatography column (Bio-Rad). Patient sera (400 μL) were diluted 1:10 in PBS, filtered via centrifugation at 12,000Affinity purification of anti-ACE2 IgM from COVID-19 patient CV-1 was accomplished as follows. We incubated 3.5 μg biotinylated ACE2  with 50 μL of streptavidin dynabeads (Invitrogen 65305) in 1 mL of buffer A for 25 minutes. After removing unbound ACE2 and washing, the streptavidin dynabead/biotinylated ACE2 mix was added to 7.5 μg purified whole CV-1 IgM (prepared as described above) in 0.4 mL of buffer A. The mixture was rotated for 95 minutes, then washed, and the bound anti-ACE2 IgM was eluted with glycine and neutralized as described above. The eluted anti-ACE2 IgM was buffer exchanged into Endothelial Cell Growth Medium-2  and concentrated. Anti-ACE2 IgM binding activity of the affinity-purified preparation was confirmed by ELISA .BLI was performed using an Octet RED96 instrument (Molecular Devices) to measure the interaction of purified IgM to ACE2. Wells of a black, flat-bottom, polypropylene plate (Corning) were loaded with the following samples: 50 nM biotinylated human ACE2 ; 2-fold dilutions of purified patient IgM; PBSA (PBS pH 7.2 containing 0.1% BSA); and regeneration buffer . All samples and buffers were filtered before use. ACE2 and the IgM samples were diluted in PBSA. ACE2 was loaded onto hydrated streptavidin biosensor tips (Molecular Devices), and baseline measurements were collected in PBSA. Binding kinetics were then measured by submerging the ACE2-coated biosensors in wells containing 2-fold serial dilutions of each patient IgM sample for 300 seconds (association) followed by submerging the biosensor in wells containing only PBSA for 450 seconds (dissociation). Analysis and kinetic curve fitting (assuming a 1:1 binding model) were conducted using Octet Data Analysis HT software version 7.1 (Molecular Devices). Normalized equilibrium binding curves were obtained by plotting the response value after the 300 second association phase for each sample dilution and normalizing to the maximum value. Equilibrium binding curves were fitted to a 4-parameter logistic regression model in GraphPad Prism (v9.0) software.ACE2 activity was measured using a kit from BioVision (K897). Purified IgM (5 μg) or ACE2 inhibitor was preincubated with ACE2 in white 96-well Costar plates , followed by addition of fluorogenic ACE2 substrate per the manufacturer’s protocol. A PBS control was included for each assay. The positive control contained only ACE2 and substrate, and the negative control was ACE2 plus ACE inhibitor and substrate. Fluorescence was measured every 5 minutes after substrate addition in a BMG Labtech FLUOstar Omega plate reader . Fluorescence values for wells containing no ACE2 were subtracted from the readings.Polystyrene plates  were coated overnight with 50 ng/well of ACE2 protein (Abcam ab151852) in PBS or with PBS alone. After washing with PBST, the plates were blocked with 1% gelatin/PBST. Purified IgM (0.5 μg/well) diluted in 1% gelatin/PBST was then added to the wells . After washing with PBST, plates with attached IgM were used for 2 different assays. For C1q binding, human serum  was added as the complement source. After 1 hour at 37°C, wells were washed with PBST, and goat anti-human C1q (Comptech A200) diluted 1:20,000 in PBST was added . HRP-labeled anti-goat IgG (Thermo Fisher Scientific A16005) diluted 1:5000 in PBST was used as secondary antibody. To measure anti-ACE2 IgM, HRP-labeled anti-human IgM  diluted 1:5000 in PBST  was used. Following addition of SureBlue peroxidase reagent (KPL), reactions were stopped with HCl and absorbances (450 nM) were read.6 cells/mL in EC medium and seeded into microchannels under static conditions for 30 minutes to promote cell adhesion. Microchannels were then perfused at 3 dyne/cm2 for 48 hours in EC medium to form confluent pulmonary endothelium. To replicate the inflammatory state, microvessels were perfused with EC medium supplemented with 1000 U/mL recombinant human IFN-α2 (BioLegend) and 50 ng/mL recombinant human IFN-γ (R&D Systems) for 24 hours.PMECs (Lonza) were used to generate 3D pulmonary microvessels. PMECs were cultured in EC medium from passages 6 to 8 using routine procedures. Three-dimensional, 150 μm diameter microvessels were fabricated based on published protocols . Microch2). Microvessels were then washed out in the above medium minus IgM . After washout, microvessels were perfused with 200 μM Lucifer yellow (Thermo Fisher Scientific) or 2 μM fluorescently labeled 10 kDa dextran (Thermo Fisher Scientific) in EC medium supplemented with 10% normal human complement to assess paracellular permeability. Additional experiments were performed with CV-1 IgM at 3.33 μg/mL. Experiments were also performed using 100 ng/mL affinity-purified anti-ACE2 IgM; this concentration matches the low experimental dose  based on a predicted 3% prevalence of anti-ACE2 IgM in total IgM. Epifluorescence and phase contrast images at original magnification 10× were collected on an inverted microscope (Nikon Eclipse Ti-E) maintained at 37°C for 10 minutes before and 30 minutes after dye perfusion, with images collected every 2 minutes. Fluorescence intensity profiles of a region consisting of the microvessel lumen and surrounding ECM were obtained using ImageJ (NIH). Permeability was calculated as P = (d/4)(1/ΔI)(dI/dt), where d is the vessel diameter, ΔI is the initial increase in fluorescence intensity upon luminal filling, and (dI/dt)0 is the rate of increase in fluorescence intensity as solute exits into the gel , microvessels were treated with 100 μg/mL patient IgM in EC medium supplemented with 10% normal human complement (Quidel) for 30 minutes under low-flow conditions  with illumination provided by an MLC 400 monolithic laser combiner (Keysight Technologies). For ACE2 images, background subtractions were performed in ImageJ with the background subtract plugin and rolling ball radius set at 500 pixels.Microvessels were washed with PBS for 5 minutes, fixed with 3.7% paraformaldehyde (MilliporeSigma) for 15 minutes, blocked with 10% goat serum , then incubated with primary antibody . Primary antibodies used were rabbit anti-CD31 , goat anti-ACE2 , and FITC-conjugated anti-C3c complement rabbit polyclonal antibody . After washing with 10% goat serum for 2 hours, the microvessels were incubated  with secondary antibodies . Nuclei were visualized with DAPI (Thermo Fisher Scientific). Microvessel cross sections were reconstructed from confocal Autopsies of 23 patients infected with SARS-CoV-2, documented by PCR on a pre- or postmortem nasopharyngeal swab, were examined. Autopsies were consented for and performed on the clinical service with complete examination of chest organs and in situ sampling of remaining organs and tissues, with histology performed on all sites. Lung paraffin sections from COVID-19 autopsy patients were either stained with hematoxylin and eosin or processed as follows. After deparaffinization and rehydration, the sections were immersed in antigen retrieval solution (DAKO) . For IgM staining, the sections were blocked with goat serum , followed by incubation with HRP-labeled goat anti-human IgM (Jackson ImmunoResearch 109-035-043) diluted 1:500. Visualization was performed with a liquid DAB substrate-chromagen system (DAKO), and the sections were counterstained with hematoxylin.Patient data and autoantibody data will be stored in the JH-CROWN registry, which is housed on the Johns Hopkins Precision Medicine Analytics Platform. Requests for data or materials derived from human samples may be made available, subject to any underlying restrictions on such data and samples, and will require material transfer and data use agreements through Johns Hopkins University.The clinical measures used in this analysis are from the COVID-19 JH-CROWN Registry that is actively curated by a team of clinicians, informaticists, and statisticians to ensure data quality. For repeated measures outcomes , data were checked by making spaghetti plots  and visut test of the null hypothesis that the 2 population means are equal. When we detected a large deviation from Gaussian distribution (for S protein IgG), a nonparametric test (Mann-Whitney U) was used instead.To compare the rates of IgM antibody positivity between 2 subgroups, we estimated the ratio of the odds of positivity for one subgroup versus the other (OR) and 95% CI. Given the small numbers of patients in some comparator groups, we used a Fisher’s exact test of the null hypothesis that the odds were equal (OR = 1). To compare means of continuous variables with roughly Gaussian distributions (determined using a quantile-quantile plot), we estimated the mean difference and its standard error and used an unpaired 2-tailed 2 distribution with 4 degrees of freedom. The analysis was repeated using natural splines with 2 to 4 degrees of freedom to ensure that the findings were not sensitive to these assumptions.To compare the trajectory of clinical outcomes over time between IgM-positive and IgM-negative groups, we used a linear mixed effects model . Variablt test. These results were statistically significant . In this case, the mixed model reduced to ordinary linear regression, and the group effect was highly statistically significant   with a random intercept to account for a possible correlation among repeated observations for each person. The variance of the random intercepts was taken as 0, indicating no correlation among repeated observations. This assumption was confirmed by comparing the means of the permeability values for the 2 COVID-19 patients and the 3 healthy controls using a 2-tailed  < 0.01) .These studies on patients with COVID-19 were approved by the Johns Hopkins University Institutional Review Board (JHU IRB) , with a waiver of consent because all specimens and clinical data were deidentified by the Core for Clinical Research Data Acquisition of the Johns Hopkins Institute for Clinical and Translational Research; the study team had no access to identifiable patient data. Patient numbers per analysis are denoted in the figure legends. Informed consent for studies on various control populations was obtained following protocols approved by the JHU IRB .AR, LCR, SLZ, DRT, FA, JBS, PCS, MD, PMH, ALC, SCR, RER, AP, BTG, CEM, and OL designed research studies. LCR, FA, MITZ, JBS, EKL, NES, JB, SY, RW, AMV, AG, RML, ZG, PCS, JEH, CEM, CAM, OL, LG, LGA, QY, and DH conducted experiments. AR, LCR, DRT, FA, MITZ, JBS, EKL, NES, JB, SY, PCS, SD, LG, LGA, MD, PMH, ALC, SCR, RER, LMS, KZJF, JEH, BTG, CEM, LCS, CAM, and OL acquired data. AR, SLZ, NES, JB, SY, RW, AMV, AG, RML, ZG, PCS, SD, LG, LGA, MD, PMH, ALC, SCR, BTG, and ZW analyzed data. DRT, WAC, ALC, RER, AP, LMS, KZJF, BTG, LCS, and CAM provided data/reagents. AR, LCR, SLZ, DRT, FA, MITZ, JBS, EKL, NES, JB, SY, RW, AMV, AG, RML, ZG, PCS, SD, LG, MD, PMH, WAC, ALC, SCR, RER, AP, LMS, KZJF, JEH, BTG, CEM, LCS, CAM, OL, LGA, QY, and DH wrote/edited the manuscript. SLZ, DRT, and ZW curated data.


A program in Nepal based on the Helping Babies Breathe training curriculum successfully scaled up newborn resuscitation training and skill retention and could serve as an evidence-based model in other resource-constrained settings. The Safa Sunaulo Nepal (SSN) program to scale up newborn resuscitation capacity-building and skill retention was associated with decreased neonatal death within 24 hours and decreased sick newborns discharged from the maternity unit.The program resulted in 43 facility-based trainers cascading resuscitation skills to 425 medical personnel and supporting skill retention over time.Integrating elements of the SSN program—including a facility-based training cascade using the Helping Babies Breathe curriculum followed by practice and mentorship—may improve newborn resuscitation training and skill retention over time and subsequently improve neonatal outcomes. Intrapartum events leading to asphyxia at birth are a leading cause of neonatal morbidity and mortality in Nepal. In response, the Nepal Ministry of Health and Population adopted the Helping Babies Breathe (HBB) training curriculum in 2015 as a tool to improve neonatal resuscitation and outcomes. Although the effectiveness of HBB training has been well documented, challenges remain in maintaining skills over time. Safa Sunaulo Nepal (SSN) designed an evidence-based intervention for scaling up newborn resuscitation training and skill retention. We report on its implementation and the changes in newborn outcomes during the program period.The program empowered facility-based trainers in newborn resuscitation and skill retention at 12 facilities in Gandaki Province. Seven of 14 level I hospitals and 5 of 6 level II hospitals were selected. A single external mentor coached the facility-based trainers, provided general support, and monitored progress. Program evaluation tracked changes in newborn metrics over 21 Nepali months (March 2018–November 2019). All deliveries occurring in the health facilities during the program period were included in the evaluation. We assessed program effectiveness by analyzing time trends of neonatal mortality, morbidity, and stillbirths.P=.044) and newborn morbidities  showed a significantly declining trend.We gathered data on neonatal health outcomes of 33,417 deliveries, including 23,820 vaginal deliveries and 9,597 cesarean deliveries. During the program, 43 facility-based trainers taught resuscitation skills to 425 medical personnel and supported skill retention. Neonatal deaths within 24 hours of birth (incidence rate ratio [IRR]=0.993, Our findings suggest that the SSN program had a substantial influence on critical neonatal outcomes. Future neonatal resuscitation capacity-building and skill retention efforts may benefit from incorporating elements of the program. Globally, approximately 2.4 million neonates die each year within the first 28 days of life, with intrapartum-related complications  as one of the major causes.–In Nepal, significant improvement has been made in reducing the mortality rate for children aged younger than 5 years,,The Nepal Ministry of Health and Population (MOHP) has initiated a series of policies and programs to improve neonatal resuscitation in response to perinatal asphyxia. The Helping Babies Breathe (HBB) training curriculum,–A major challenge in implementation and dissemination efforts for newborn resuscitation has been maintaining resuscitation skills over time. Several HBB follow-up studies have shown a decline in knowledge and skills over time.A major challenge in implementation and dissemination efforts for newborn resuscitation has been maintaining resuscitation skills over time.The newborn resuscitation and retention program was conducted in Gandaki Province, one of the 7 provinces under the new federal structure in Nepal. An overview of the province is provided in NHTC selected 12 health facilities  in the province to implement the SSN newborn resuscitation program. Selection criteria included: (1) handling a significant share of the deliveries in Gandaki province and (2) having HBB training needs as identified by NHTC. All the hospitals provided vaginal delivery , and all except 1 provided cesarean delivery. The labor units in these hospitals were led by physicians and midwives and equipped to provide neonatal resuscitation at birth. Pediatricians led neonatal care units at secondary and tertiary hospitals. In primary hospitals, sick newborns were managed in the pediatric unit, which was led by either medical officers or nurses/midwives. All deliveries occurring in the health facilities during the program period were included in this evaluation and selected for analysis.The program for scaling up and retaining newborn resuscitation skills was sponsored by LDSC and implemented by SSN from March 2018 to November 2019, which corresponds to Chaitra 2074 to Mangsir 2076 on the Nepali calendar. The program components included: (1) clinical equipment and training materials provided to each facility; (2) facility-level scale-up of resuscitation training to all physicians and nurses/midwives; (3) practice sessions, review meetings, and refresher training; (4) on-site coaching; (5) monitoring of key indicators; and (6) liaisons with administration.Before implementation of the program, 43 trainers representing the cohort of 12 hospitals attended a 2-day HBB TOT course on April 23–24, 2017. These trainers completed the standard HBB curriculum, combined with additional facilitator training. NHTC directed and supervised the training and led the selection of both facilities and trainers.Twenty-seven of 43 trainers (63%) were nurses by profession, with the majority (70%) of the trainers working in their profession for more than 5 years. Nearly 40% of the participants were from district hospitals. Twenty-nine trainers (67%) indicated they personally attended up to 25 deliveries in an average month. Thirty-four (79%) trainers stated they resuscitated babies with a bag and mask as part of their current job.The HBB TOT course was facilitated by 9 Nepali trainers and 4 U.S.-based trainers from LDSC. SSN and LDSC provided trainers with print and electronic copies of instructional materials, such as provider guides and testing materials. Training equipment included NeoNatalie manikins, Penguin suction devices, bag and masks, and stethoscopes. Bag and masks and suction devices were sufficient to set up practice corners and for clinical use in the delivery rooms. LDSC and SSN provided training, replacement instructional materials, and clinical equipment throughout the program as needed and after program completion.An HBB-trained medical officer with research experience was recruited to serve as a mentor, trainer, monitor of facility-based indicators, and administrative liaison to implement newborn resuscitation scale-up and retention for all the facilities. The mentor was the initial driver for scaling up newborn resuscitation in the selected facilities through the use of evidence-based methods to build staff capacity. Under the mentor’s supervision, the newly minted facility-based trainers conducted HBB training for physicians, nurses, and midwives in the labor and neonatal care units. Training sessions were subsequently provided for new staff due to staff turnover and task-sharing.The mentor was the initial driver for scaling up newborn resuscitation in the selected facilities through utilization of evidence-based methods to build staff capacity.After the facility-level scale-up, daily practice sessions were strongly encouraged, using low-dose, high-frequencyThe mentor, in coordination with the facility-based trainer and the hospital nursing supervisor, observed the HBB skills of staff using a neonatal simulator during regular and unannounced site visits; reviewed the practice logbook; provided on-site coaching; reviewed the delivery and newborn logbook; and provided refresher training. Other monitoring activities involved regular phone calls between mentor and trainers, encouragement to maintain standardized delivery room records, and feedback to facility-based trainers based on the review of monthly monitoring reports by SSN representatives. Further, the facility-based trainers communicated with the mentor and each other through dedicated social media groups.We evaluated the program with a prospective cohort design to compare outcomes of birth cohorts in 12 hospitals following the implementation of the resuscitation training program. All deliveries occurring in the health facilities during the program period were included in the evaluation. The 21-month program followed the Nepali calendar, consistent with the reporting convention of the Nepali government. The program period began in March 2018 (Chaitra 2074) and ended in November 2019 (Kartik 2078).The primary evaluation outcome included the pre-post difference in (1) the intrapartum/fresh stillbirths and (2) neonatal deaths within the first 24 hours of life. Stillbirths were considered fresh if they were not macerated. Secondary outcomes included neonatal deaths after the first 24 hours of life with hospital discharge as the endpoint and the use of bag-and-mask ventilation on nonbreathing newborns. Secondary outcomes also included the number of sick newborns discharged from the hospital. Sick newborns discharged from the hospital included their transfer from the maternity unit to another unit of the hospital or to another hospital or discharged home before recovery. It was a proxy for all-cause newborn morbidity during the first days of life.Monthly monitoring reports generated by the mentor documented the scale-up and facility support as well as facility-level metrics. The monthly scale-up and facility support included tracking the number of providers trained and retrained; maintenance of an equipped practice corner and low-dose, high-frequency practice logs; completion of self-evaluation forms; review of meetings held; and review of delivery and newborn logs. Monthly facility-level metrics included the number of vaginal deliveries, number of cesarean deliveries, number of intrapartum (fresh) and macerated stillbirths, number of neonatal deaths within and after 24 hours, and the number of sick newborns transferred or discharged from the maternity unit.In private and higher-level public facilities, monthly facility-level data were derived from the health information department, which tabulated and reported MOHP-mandated metrics. In smaller facilities, the mentor gathered data from registers or logs maintained in the labor room and in the maternity ward. Personal data of patients, such as demographic information, were not collected.The monthly scale-up and support measures were largely comprised of qualitative indicators. An account of these is presented in descriptive terms. We used a Poisson regression model to analyze the trend in the adverse birth outcomes following the implementation of the LDSC/SSN program. Clustering for repeated measurements at the facilities was adjusted with generalized estimating equations model specification.The mentor collected data from standard hospital reports and logs into monthly reports, as well as conducted checks for data quality and integrity. The monthly reports were forwarded to SSN and to a U.S.-based research assistant. SSN conducted an initial review and analysis and prepared MOHP-mandated reports. The data were combined into a master file, after which missing variables were clarified with the mentor, variables missing significant data were deleted, and text was changed into appropriate numerical values. A Nepal-based research assistant conducted the analysis using Excel and SPSS.Ethical approval was obtained from the Nepal Health Research Council (registration number 797/2018) for the newborn resuscitation scale-up and retention program, including data collection from all facilities under the program.The evaluation included 12 health facilities, of which 9 were government owned and 3 were nongovernment owned. Government-owned facilities represented 3 types of health service delivery institutions: primary hospital (1), secondary hospital (7), and tertiary hospital (1). Nongovernment health facilities included in the program provided tertiary-level services and were major referral centers in the province.According to the Health Infrastructure Development Standards 2017, primary hospitals in Nepal are mandated to provide normal delivery and comprehensive emergency obstetric and neonatal care. However, in practice, availability of these latter services in the primary hospital was sporadic, depending upon the availability of physicians. Besides comprehensive emergency obstetric and neonatal care services, both secondary and tertiary hospitals have dedicated departments and wards for providing gynecological and obstetric services. In addition, tertiary hospitals have advanced infrastructures and human resources for providing maternal and newborn care, including a higher number of beds, neonatal care units, and pediatricians. Delivery services were supervised by obstetrician-gynecologists in both secondary and tertiary hospitals.During the program period, a total of 33,417 deliveries took place at the hospitals , of which 23,820 were vaginal deliveries and 9,597 were cesarean deliveries. The run chart depicting the trend of intrapartum stillbirth and neonatal mortality within and after the first day of life is shown in P=.044), a 0.7% decrease in neonatal mortality for every unit change in time. The number of sick newborns transferred from the hospital was significantly associated with time , revealing a 0.4% reduction in the number of sick newborns transferred from the hospital for every unit change in time.The scale-up of HBB resulted in 425 providers receiving training during the program period. The new facility-based trainers, with the assistance of the mentor, cascaded the training in their facilities by training existing and new staff during the program and holding refresher training sessions. Most of the initial training of staff (41%) took place in the first 3 months , while oThe new facility-based trainers, with the assistance of the mentor, cascaded the training in their facilities by training existing and new staff during the program and holding refresher training sessions.A detailed review of data contained in the monthly reports revealed consistent attendance by the mentor at resuscitation reviews with staff during the entire program period, averaging 1.4 meetings per month per hospital. Frequent meetings with nursing supervisors, medical superintendents, and other hospital leaders were also consistent throughout the program but with a higher frequency during the first half of the period, averaging at least once every 2 months. The mentor assisted the facility-based trainers both with consistent practice sessions and review discussions with available staff and with training of new staff. In contrast, the utilization of self-evaluation surveys was poor, and practice corners with completion of practice logs were only scaled up to two-thirds of the hospitals by the end of the program. Practice sessions of staff with the mentor or facility-based trainer were more consistent and universal among the facilities than spontaneous practice by providers. All units remained fully equipped during the program, and LDSC provided replacement equipment as needed. All units maintained both maternal and newborn logs during the entire program, though coaching by the mentor on proper completion of the logs was needed.P<.001). Our findings correspond with several previous studies that found significant decreases in neonatal mortality within 24 hours of birth,,The SSN program was implemented in a phase-wise approach in 5 provinces of Nepal. It was implemented first in Western Nepal and subsequently in Gandaki province. The hospitals in this evaluation were in a significantly more developed region in terms of socioeconomic status, access to health care, and hospital infrastructure than in Western Nepal. Different external mentors were recruited in various locations. A significant association of the program with neonatal mortality within 24 hours of birth as we found in this evaluation was also reported after the implementation of the program in Western Nepal.Our findings correspond with several previous studies that found significant decreases in neonatal mortality before 24 hours of birth following the HBB training.Analysis of the run charts indicates fluctuations in the number of deaths within and after 24 hours of birth and in intrapartum stillbirths over the period of program implementation. On the other hand, the number of babies receiving bag-and-mask ventilation increased gradually over time, suggesting a transfer of skills into the clinical setting. Since the program used minimal MOHP-mandated metrics for program monitoring, data collection procedures for neonatal mortality within and after 24 hours of births and fresh stillbirths were already established at the onset of the SSN’s program implementation. However, data collection procedures for data on newborn morbidity, use of bag and mask, facility-level scale-up, and skill retention metrics were initiated at the onset of program implementation. This may have affected the data quality in the early period of the program.Findings from our evaluation revealed a proportionally higher percentage of cesarean deliveries (28.7%). Of 12 health facilities included in the program, 7 were advanced-level facilities where complicated obstetric cases were referred. Thus, the increased need for cesarean deliveries to manage obstetric complications in these health facilities may have resulted in higher percentages of cesarean deliveries. These facilities accounted for nearly 92% (data not shown) of the cesarean deliveries in the program hospitals.The rollout of the newborn resuscitation capacity-building and skill retention program at scale by SSN utilized quality improvement strategies from earlier studies to sustain newly acquired resuscitation skills. A clinical trial in a tertiary-level hospital in 2013 in Nepal used the quality improvement process cycle to demonstrate HBB’s impact on perinatal outcomes.Several recommendations emerge from the review of mentor functions, some of which are consistent with earlier studies but some of which are not. Based on the scale-up experience in Gandaki, a similar program would need at least 6 months to scale up training and institute retention activities in a portfolio of health care facilities. The role of the mentor was critical in training and assisting the hospital-based facilitators during this time, including holding regular meetings with staff, liaising and advocating with hospital leaders, conducting ad hoc practice sessions and discussions, ensuring the training of new staff, and improving the accuracy of log-based documentation. The establishment and spontaneous staff utilization of practice corners had limited success, and post-resuscitation self-evaluation survey completion was widely unsuccessful. Successful transition to an internal mentor depends highly on support from hospital administration, which in turn needs support from local health authorities.The goal of scale-up is to gain effective coverage of the intervention and institutionalize the intervention as a routine practice within the national health system.A notable strength of the program has been the dedicated commitment and leadership of NHTC, under the MOHP, in conducting HBB training. Beginning before the Gandaki TOT course, SSN received guidance and coordination support from NHTC and the MOHP regarding HBB TOT courses. This support included development and endorsement of an HBB learning resource package (based on the American Academy of Pediatrics module), identification of facilities and human resources requiring HBB training through pretraining needs assessment, technical assistance in training sessions, joint monitoring/supervision of HBB TOT sessions and refresher trainings, recordkeeping of the training equipment provided to the health institutions during HBB TOTs, and strategic direction for effective program implementation. This clearly demonstrates the role of country ownership and leadership in successfully implementing newborn resuscitation skills at scale. The role of a dedicated mentor in scale-up and skill retention was also crucial. These observations are not unique to the SSN’s program of scale-up but have been acknowledged in the scale-up of various maternal and child health interventions.The SSN program was a relatively low-cost intervention. A single external mentor design allows diffusion of associated costs among health facilities. The facility-level cascade training approach incurred a low direct cost to SSN by avoiding travel costs and daily subsistence allowance, compared to off-site training. Indirect costs associated with loss of work hours were also markedly reduced as the facility-level providers were trained while they were still on the job.The SSN program was a relatively low-cost intervention because of its single external mentor design, facility-level cascade training approach, and use of on-the-job training.Another strength of the program is that the participating facilities constituted a large proportion of deliveries in the Gandaki province. Further, the facilities included were diverse, ranging from district-level public hospitals to tertiary-level public and private hospitals providing advanced maternal and newborn services.The program faced several challenges. First, many facilities had a low staffing ratio, leading to unavailability of staff for the facility-based training. Second, widespread staff turnover across facilities, particularly during the human resource adjustments by the Government of Nepal toward the end of the program period, led to the transfer of skilled human resources to other areas and an influx of untrained staff into the facilities. This not only affected the overall quality of newborn care but also posed data collection challenges.The third challenge related to the data collection process itself. The program monitored progress by using limited indicators, most of which were tracked by the facilities for routine reporting to the MOHP and, therefore less prone to error—neonatal deaths being one of those metrics. However, even though most of the facilities tracked stillbirths, misclassification and underreporting of fresh stillbirth was widespread. Accordingly, delivery logs had to be reviewed to confirm accuracy in classification of fresh stillbirth. Similarly, since the facilities did not track and report resuscitation data to the MOHP, delivery logs had to be reviewed to obtain such data. Sick newborns discharged from the maternity unit—a proxy indicator for all-cause morbidity—were also not tracked by facilities as part of routine reporting to the MOHP. This necessitated a review of newborn logs to determine the number of sick infants discharged from the units.Due to the design as a skill training and retention program rather than a clinical study, there was no control/comparison group, which restricted the ability to establish the causality of the program on observed perinatal outcomes. We describe the impact of the newborn resuscitation scale-up on perinatal outcomes using routinely collected data, without establishing the causality, as in clinical trials. With this, we are unable to confirm whether the observed outcomes were solely attributable to the newborn resuscitation scale-up and skills retention program or to other changes at the facilities during the period.Various studies have documented seasonality of adverse birth outcomes in Nepal. Seasonal variation in neonatal deaths (highest risk in August and lowest risk in March) and stillbirths (highest risk in February and lowest in October) was observed in a randomized control trial conducted in rural Nepal from 2002 to 2006.HBB refresher training was conducted in one of the health facilities by UNICEF during the implementation period, augmenting the scale-up of training but not contributing to the retention of skills portion of the SSN program. Likewise, the MOHP training on Community-Based Integrated Management of Childhood Illness and the Skilled Birth Attendant In-service Training Packages provided to some facility staff by the Government of Nepal used the basic HBB algorithm but without the practice components usually deemed necessary for skill acquisition. With these and other types of newborn interventions possibly running concurrent to the SSN program, the exact contribution of the SSN model of newborn resuscitation scale-up and retention program to the observed improvements in neonatal outcomes is difficult to quantify.Interestingly, nearly 79% of trainers in the TOT were already resuscitating babies in their current job at the time of training. Yet, neonatal outcomes improved despite most of the trainers having prior knowledge and experience with neonatal resuscitation. This emphasizes that training alone is insufficient to achieve gains in neonatal outcomes and needs to be followed by practice, mentorship, retraining, and monitoring—the main focus of our efforts.Training alone is insufficient to achieve gains in neonatal outcomes and needs to be followed by practice, mentorship, retraining, and monitoring.This report highlights the potential of the SSN program of newborn resuscitation scale-up and retention to improve perinatal outcomes in low-resource settings through building and sustaining in-facility capacity for resuscitation. Minimal resources were utilized to accomplish this. The report also highlights the complexity of implementing and scaling up evidence-based newborn resuscitation interventions.Our evaluation provides plausible evidence that the SSN program of scaling up newborn resuscitation and skill retention was associated with a decline in neonatal mortality within 24 hours, a decline in the number of sick newborns transferred from the maternity unit, and an improvement in clinical practices. This evidence-based approach is a simple program focused on facility-based cascade training of newborn resuscitation skills using the HBB curriculum, followed by practice, mentorship, and other skill retention strategies. The program demonstrated the role of mentorship in effectively scaling up skills, retaining skills, and monitoring, with a single mentor supervising and monitoring multiple facilities. The program could guide future programs to reduce perinatal outcomes for other resource-limited countries striving to meet the Sustainable Development Goal target of reducing neonatal mortality to at least 12 per 1,000 live births.


A large-scale sand liquefaction producing typical and novel surface phenomena was found at the epicenter of Songyuan M5.7 earthquake occurring on May 28, 2018. Field survey and experimental test encompassing boring sampling, standard penetration test (SPT), cone penetration test (CPT), scanning electron microscopy (SEM), X-ray diffraction (XRD), and X-ray fluorescence (XRF) were performed to ascertain the liquefaction damage and site characteristic. Cone penetration test is an excellent assay for the identification of liquefied sand layer and acquisition of physio-mechanical parameter. Moreover, the assay is applicable for in-situ post-earthquake investigation. Factors promoting the formation and controlling the distribution of the sand liquefaction were analyzed. The liquefaction impacted an 80 km2 area, and was primarily embodied as sand boil and water sprout on rice field, despite producing no significant structural damage. Due to the simple profile of local soil layer, ground motion, geomorphic condition, and groundwater level were the main factors governing the distribution of the liquefaction. Majority of the liquefied sand layer was discovered at the depth less than 10 m. However, deep layer liquefaction at the depth greater than 18 m was also discovered, which was demonstrated by the upward movement of liquefied sand towards the upper silty clay layer at the depth of 17 m. Most importantly, we have identified loess liquefaction, a phenomenon which had not been reported previously in Northeast China. Lastly, it is important to highlight the risk of significant liquefaction damage at Songyuan. Hence, investigating the liquefaction risk is potentially beneficial for augmenting planning on earthquake mitigation, engineering reconnaissance, and design project. History has recorded several liquefaction damage promoted by earthquake, such as the liquefaction damage in Niigata , Dagupan City , Chi-Chi , Kocaeli , and Wenchuan . The destructive impact of liquefaction such as landslide promotes the collapse of buildings and thus the failure to achieve the targeted structural service life. Thus, ongoing study has been expanding our understanding on liquefaction, encompassing liquefaction mechanism, evaluation, and mitigationW 5.2, occurred at Songyuan City, Jilin Province, China on 28th May, 2018. The earthquake was felt throughout Jilin Province, part of Heilongjiang Province, and Inner mongolia autonomous region. The epicenter of the earthquake was the Yamutu village, which is located at the alluvial terrace of Songhua River. The sub-surface soil layer is mainly composed of fine sand and the water level is shallow. Thus, the occurrence of earthquake-induced liquefaction is increasing in recent years. In order to investigate the liquefaction distribution and damage, field survey and subsequent experimental test were conducted, involving boring sampling, standard penetration test (SPT), cone penetration test (CPT), scanning electron microscopy (SEM), X-ray diffraction (XRD), and X-ray Fluorescence (XRF). This paper initially provides an overview on the seismic characteristic of Songyuan and preliminary data on the characteristic of M5.7 earthquake. The earthquake history and current ground motion at Songyuan are elaborated. Thereafter, observed phenomena at liquefied and non-liquefied sites are presented. Not only typical liquefaction damages such as sand boil and waterspout were found, interesting novel phenomena such as deep soil liquefaction and special soil liquefaction (i.e. loess liquefaction) were also indicated. Hence, the outcome of experimental series performed to ascertain the novel finding in Northeast China is discussed. Overall, this paper provides a better understanding on the prevention of liquefaction at Songyuan and fundamental understanding for future research.Post-earthquake investigation is an essential research methodology to study the distribution of liquefaction and identify the influencing factors of a liquefaction. There are two main objectives of the investigation: Initially, liquefied and non-liquefied region are determined based on ground damage. Successively, ground motion data are collected and quantitative data for detailed calculation and analysis are obtained by conducting drilling, screening test, standard penetration test, cone penetration test, and wave velocity test. Researchers and earthquake engineers deduce detailed information on the damage due to liquefaction and its related seismic activity by investigating liquefaction macrophenomena.Nevertheless, there are several limitations to previous investigation on liquefied macrophenomena: (1) While liquefied sites were identified during preliminary post-earthquake investigation by the observed surface macrophenomena such as sand boil, deep soil liquefaction with no obvious macrophenomena was frequently neglected. (2) Report on in-situ special soil liquefaction in Northeast China, such as liquefaction of loess, is scarce. An earthquake with a magnitude of M5.7, the moment magnitude is MDajin chorography, a destructive earthquake (Qianguo earthquake) with an estimated magnitude of (insert magnitude here) occurred on February 1119, and is documented as the most devastating earthquake attacking the city. Figure 7. The epicentral intensity was estimated between VIII and IX. Thousands of people died of the generated subsidence, accounting for approximately one-tenth of the combined population of Zhaozhou and Longzhou. The earthquake impacted the surrounding region of Songhua River Basin where Holocene sand layer is abundantly distributed. The shallow sand layer is saturated and loose, thus being susceptible to liquefaction under an earthquake. Despite the regional geomorphic feature, there was no large-scale landslide, ground crack, or other subsidence-related phenomena in the area. It is suggested that the large-scale subsidence was induced by sand liquefaction spanning from Tahu Town to Nongan Town.Songyuan is a city located at the Southern Songliao Basin. It has a complex fault structure and is one of the two cities in Northeast China which is fortified against seismic intensity of VIII. Series of earthquake with the magnitude of M > 5.0 have occurred throughout the city’s history. As mentioned in 9. Several earthquake have happened since 2006, comprising of: (1) Qianan earthquake with a magnitude of M5.0 on 31st March 2006, (2) Qianguo earthquake swarm with a magnitude of M > 5.0 on 2013, (3) Ningjiang earthquake with a magnitude of M4.9 on 23rd July 2017, and (4) Songyuan earthquake with a magnitude of M5.7 on 28th May 2018. It is important to emphasize that the Qianguo earthquake swarm occurred repeatedly with varying intensity, beginning with a magnitude of M > 5.0 on 31st October 2013 and ended with a magnitude of M5.5 at the end of 2014. During the time period, five earthquake with the magnitude of M5.0–5.9 and seven earthquake with the magnitude ofM4.0–4.9 hit the region. The multiple earthquake affected tens of thousands, and caused damage to buildings and farmland. Thus, it is necessary to highlight the severe liquefaction risk at the region around Songyuan, noting the widely distributed shallow sand layer and underground water.In recent years, seismic activity with a magnitude of M4.0–5.0, particularly multiple earthquake swarm, frequently occurs around Songyuan2 area. The long axis of the region experiencing the intensity of VII was distributed along the northeast direction as long as 9.2 km, whilst the short axis was 4.8 km-long. On the other hand, the region experiencing an intensity of VI spanned an 880 km2 area. The long axis was 24 km-long and the short axis was 16 km-long. The intensity distribution was north–south asymmetry, and the decay rate of intensity was greater towards the southwest than the northeast.Focal mechanism solution (FMS) is an excellent tool to analyze the mainshock-aftershock wave forms recorded as seismographs during an earthquake. Focal mechanism solution of seismographs generated during the Songyuan M5.7 earthquake indicated that it was a strike-slip earthquake. It was suggested that Fuyu-Zhaodong fault was the seismogenic fault. Figure 2, documented at Daliba and Fenghua station by China Strong Motion Network Centre. The two stations were located at close proximity to the epicenter. Daliba station is located 16 km away from the epicenter, and recorded horizontal and vertical PGA of 159 and 189 cm/s2 respectively. On the other hand, Fenghua station is located 24 km away from the epicenter, and recorded horizontal and vertical PGA of 189 and 48 cm/s2.The FMS analysis was supplemented by strong motion record. Figure 2 area) with Yamutu Village at Ningjiang District as the center. The liquefaction zone spanned from Songhua river on the east to Langjia Village (Qianguo County) on the west, and Guojia Village (Qianguo County) on the north to Jiangjia Village (Ningjia District) on the south.Field survey identified that large-scale liquefaction was observed at the region affected by the earthquake with a seismic intensity of VII. In addition, few liquefaction sites were found at the region which experienced the seismic intensity of VI. Figure 11. Most liquefaction phenomena together with outcrop evidence have been observed in large earthquakes in terms of magnitude, but it is barely found in low magnitude earthquakes. A comparison among the different curves which show liquefaction occurrence in terms of earthquake magnitude provide by previous authors are presented in Fig. During this earthquake, maximum epicentral distance of the liquefied sites is 8.4 km. The relationship between the maximum epicentral distance of liquefied sites and earthquake magnitude (Mw or Ms) has been studied by many scholars (Kuiribayashi and Tatusuoka (1975), Ambraseys (1988), Papadopoulos and Lefkopoulos (1993), Galli (2000))3. On the other hand, the string beads shape was embodied as a combination of multiple concentric shape, with the maximum length exceeded 20 m. The diameter of liquefied hole ranged from 20 cm to 4 m, with the maximum depth of 4 m.Sand boil and waterspout were the main liquefaction macrophenomena discovered on liquefied sites. Majority of the macrophenomena was observed on rice field, and lesser proportion was found in forest, dry farmland and residential area. The liquefied sites discovered on rice field were the most severe among the discovered liquefied sites. The sites were characterized by long duration of liquefaction, deep liquefied hole, and large-scale eructation. Observed waterspout lasted from several minutes to several hours and irrigation water was still visible on a rice field at Jiangjia Village after four days of the earthquake, indicating that pressure of pore water in underground soil layer had not been fully dissipated Liquefied ejecta accumulated and were embodied as concentric Fig. a and strThere are two main types of the liquefied sand ejected in this earthquake: yellow fine sand and gray fine sand. The yellow fine sand is more widely distributed than the gray fine sand, which mainly includes quartz and feldspar. The buried depth is about 3-7 m below the surface. The gray fine sand contains a certain amount of mica. The buried depth is generally greater than 5 m. The yellow fine sand is covered by the gray fine sand in part of the liquefied sites, this phenomenon is consistent with the buried relationship between the two types of sand. The particle size distribution of the two types liquefied sand are presented in Fig. Despite the appearance of liquefaction macrophenomena, there was no extensive damage to building caused by the liquefaction. There were only two observed occasion on liquefaction-related damage to building: the damage to a village committee office at Jiangjia Fig. a,b and tBased on the finding of field survey elaborated in "2, friction cylinder surface area of 300 cm2, and the cone angle of 60°. The weight of CPT truck was 20 ton. Researchers have been extensively investigating the application of CPT for studying liquefaction, and have obtained satisfactory result from field application15. Based on SPT and CPT data, liquefied soil layer was identified by the cone tip resistance and lateral friction resistance value collected at liquefied sites. While non-liquefied soil layer was characterized by high cone tip resistance and low lateral friction resistance, liquefied soil layer was identified by low cone tip resistance and low lateral friction resistance.Figure Example of finding derived from the analysis of soil collected from a liquefied site, at which sand eruption was observed is presented in Fig. Figure 17 proposed a simplified calculation formula of sand liquefaction cycle stress ratio:Seed and Idriss1,60cs is fines-corrected standard penetration test blow count corrected for overburden,energy and procedural differences.CRR is cyclic resistance ratio. When CSR > CRR, the soil layer is judged to be liquefied; otherwise, it is judged to be non-liquefied. Rauch (1996) proposed a formula to calculate CRR:Seed-Idriss method’s point at liquefaction and non-liquefaction site are presented in Fig. Special soil liquefaction was located at Wangjia Village Fig. . The liqThe soil sample is black grain when saturated with water. After drying, it is earthy yellow and can see some particles.The Liquid-plastic limit test and particle size analysis result are presented in Table Micromorphological characterization of rare liquefied soil collected from ground surface was performed with Hitachi SU8020 field emission scanning electron microscope (accelerating voltage = 3 kV), and is presented in Fig. 2 and Al2O3 were the most abundant elemental oxide, and oxygen was the major element of the soil. The major content of quartz in the liquefied soil was in agreement with the report by Wei that quartz was a major mineral of Chinese loess18. Thus, the mineral composition of liquefied soil was compared with the mineral composition of Malan loess reported by Liu et al. and is presented in Table 2 content of liquefied soil conformed with the reported SiO2 content of Malan loess, so did the Al2O3 content. On the other hand, the discrepancy in Fe2O3 and CaO content was justified by the sampling limitation: the liquefied soil was collected above the ground, thus exposing the sample to oxygen from atmosphere. The exposure induced the oxidation of Fe2+ to Fe3+ thereby producing a higher Fe2O3 content. Meanwhile, carbonate was dissolved, which reduced the CaO content. In addition to the similarity in mineral composition, the similarity in physical appearance (resemblance to silty clay) affirmed that the liquefied soil was liquefied loess, as further reflected by the comparable physical property .Liquefaction was observed at the epicenter, and caused surface damage mainly to rice field. Nonetheless, there was no large-scale damage to building. Due to the simple profile of regional soil layer, the distribution of liquefaction was primarily governed by ground motion, landform, and groundwater level.Deep liquefaction. Most liquefaction was identified at shallow depth: at soil layer with the depth less than 10 m. The liquefaction produced surface damage and was easily discernable by the phenomena such as sand boil and water spout. On the other hand, deep liquefaction is commonly neglected in field investigation. Nonetheless, in this paper the authors reported the upward movement of liquefied sand from the lower sand layer towards the upper clay layer located at the depth between 16 and 17 m, suggesting the occurrence of deep liquefaction at the depth of between 18 and 19 m. This phenomenon is rarely reported by other field investigation. Additionally, the accuracy of existing method to determine the occurrence of deep liquefaction is low, hence requiring further improvement.In-situ determination method of liquefaction. This study reported the occurrence of liquefaction at the sites with no apparent surface macrophenomena (e.g. sand boil and water spout). Unfortunately, existing field investigation method (drilling and SPT) are not practical for identifying such liquefaction occurrence. Hence, alternative method which is more efficient and accurate is necessitated. CPT is a candidate for the alternative method. It requires less time and produces more accurate result than the current drilling and SPT method. Moreover, it is applicable in-situ during post-earthquake investigation for identifying sand liquefaction. Nevertheless, given the recent incorporation of the method into in-situ post-earthquake investigation, more field data are required to improve the reliability of the method.Special soil liquefaction. In addition to the typical sand liquefaction, special soil liquefaction, specifically loess liquefaction, was postulated. This study is the first study which reported the occurrence of loess liquefaction at Northeast China. Nonetheless, further investigation is required to understand the formation mechanism and factors controlling the formation and/or distribution of the loess liquefaction.High risk of liquefaction at Songyuan. Songyuan is one of the only two cities in Northeast China which is fortified against seismic intensity of VIII. The local seismic activity is frequent and characterized by multiple earthquake swarm. The soil layer is constituted by thick loose sand and the groundwater is located at a shallow depth. Overall finding of this study suggests a high risk of liquefaction at Songyuan, contributed by not only typical sand liquefaction but also special soil liquefaction such as the postulated loess liquefaction. Therefore, research dedicated to studying the liquefaction at Songyuan is essential for improving planning on earthquake mitigation and design project.Based on conducted post-earthquake field survey and subsequent analytical procedure  at the epicenter of M5.7 Songyuan earthquake, the following conclusion was drawn:


As in many low-income countries, the treatment gap for developmental disorders in Pakistan is nearly 100%. The World Health Organization (WHO) has developed the mental Health Gap Intervention guide (mhGAP-IG) to train non-specialists in the delivery of evidence-based mental health interventions in low-resource settings. However, a key challenge to scale-up of non-specialist-delivered interventions is designing training programs that promote fidelity at scale in low-resource settings. In this case study, we report the experience of using a tablet device-based application to train non-specialist, female family volunteers in leading a group parent skills training program, culturally adapted from the mhGAP-IG, with fidelity at scale in rural community settings of Pakistan.The implementation evaluation was conducted as a part of the mhGAP-IG implementation in the pilot sub-district of Gujar Khan. Family volunteers used a technology-assisted approach to deliver the parent skills training in 15 rural Union Councils (UCs). We used the Proctor and RE-AIM frameworks in a mixed-methods design to evaluate the volunteers’ competency and fidelity to the intervention. The outcome was measured with the ENhancing Assessment of Common Therapeutic factors (ENACT), during training and program implementation. Data on other implementation outcomes including intervention dosage, acceptability, feasibility, appropriateness, and reach was collected from program trainers, family volunteers, and caregivers of children 6 months post-program implementation. Qualitative and quantitative data were analyzed using the framework and descriptive analysis, respectively.We trained 36 volunteers in delivering the program using technology. All volunteers were female with a mean age of 39 (± 4.38) years. The volunteers delivered the program to 270 caregivers in group sessions with good fidelity (scored 2.5 out of 4 on each domain of the fidelity measure). More than 85% of the caregivers attended 6 or more of 9 sessions. Quantitative analysis showed high levels of acceptability, feasibility, appropriateness, and reach of the program. Qualitative results indicated that the use of tablet device-based applications, and the cultural appropriateness of the adapted intervention content, contributed to the successful implementation of the program. However, barriers faced by family volunteers like community norms and family commitments potentially limited their mobility to deliver the program and impacted the program’ reach.Technology can be used to train non-specialist family volunteers in delivering evidence-based intervention at scale with fidelity in low-resource settings of Pakistan. However, cultural and gender norms should be considered while involving females as volunteer lay health workers for the implementation of mental health programs in low-resource settings.The online version contains supplementary material available at 10.1186/s43058-022-00343-w. Contributions to the literatureThe present study provides an example of using implementation science frameworks to explore the barriers to and facilitators of using technology to train non-specialist family volunteers to implement a parent skills training program and measure program fidelity at scale in a low-resource community setting.This study administers validated implementation science instruments to measure the program acceptability, feasibility, appropriateness, and reach and provides a comprehensive perspective of diverse stakeholders including organizations, providers, and consumers regarding program implementation in real-world settings.The present study suggests that although technology is a feasible and acceptable implementation strategy to train non-specialist female volunteers, several gender-related barriers—notably competing demands in their homes and community norms that potentially limit the ability of women to participate alone outside the home—could reduce the reach of the program.While technology-assisted application was well accepted as a training tool, most of the caregivers refused to consent to video record a live caregiver-child interaction for monitoring, quality assurance, and evaluation purposes. Understanding the use of technology from end-users’ perspectives is critical to the success of scale-up efforts using technology.Prevalence rates of developmental disorders are estimated to be 1 in 162 children globally . A key lThe mhGAP intervention guide offers a holistic, evidence-based package of care including guidelines for the assessment and management of developmental delays and disorders in children . The proPakistan is a low- and middle-income country in South Asia with an estimated population of 220 million . Over 6%Previously, we had converted the mhGAP guidelines into training videos for caregivers of children with developmental disorders and hosted them on a tablet device . We traiOur evaluation was part of a cluster Randomized Controlled Trial (cRCT) of the technology-assisted parent skills training intervention to improve clinical outcomes in children with developmental disorders . The triOur implementation evaluation was informed by Proctor and colleagues’  and the Effectiveness dimension of RE-AIM, measured using a cluster randomized controlled, are published elsewhere [Maintenance dimension of the RE-AIM framework  was not explored.We measured the implementation outcomes and calculated Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) indices  at threelsewhere . As the The program was delivered in 15 rural Union Councils (UCs) of the sub-district Gujar Khan. A UC is the smallest administrative unit within a sub-district and has a Basic Health Unit (BHU) that provides health care to the local population. Each BHU is staffed by a medical doctor, a dispenser, 15–20 Lady Health Workers (LHWs) working under the supervision of a lady health supervisor, a lady health visitor, and a vaccinator. LHWs are trained to provide preventive maternal and child health care and education in the community. Each LHW is responsible for about 100 households in her village.In the present study, children with developmental disorders were identified with the help of LHWs, in two phases. Firstly, the research team along with LHWs conducted a door-to-door survey and screened all children, aged 2–12 years in the LHW’s catchment area for developmental disorders using Ten Questions Screen (TQS). Secondly, children who screened positive were assessed by a trained clinical psychologist following the clinical assessment guidelines  outlined in the mhGAP-IG . A writtThe family volunteers were family members or parents or caregivers of children with developmental disorders. They had at least eight grades of formal education and were voluntarily willing to be trained and supervised to deliver the intervention to 4–5 families in their villages for at least 6 months. The family volunteers were identified during the door-to-door screening survey. A written informed consent from each family volunteer was obtained before their participation in the study.In addition to the family volunteers, the study participants for the implementation evaluation were program organizers and caregivers of children with developmental disorders.Program organizers  were master trainers who had post-graduate education and specialized training in child mental health as well as program trainers who were graduates with master’s degrees in psychology or social sciences and had at least 1 year of experience of delivering psychological interventions in the study settings. They were trained in parent skills training program by master trainers and cascaded down the training to the providers using tablet-based tool.Consumers of the intervention .We adapted the content and delivery of the mhGAP-IG parent skills training guidelines to suit delivery by non-specialist volunteers in low-resource rural Pakistan.The adapted program consists of 9-weekly group sessions and aims to train caregivers to promote communication, socioemotional development, and adaptive behaviors and manage co-morbid conditions and motor difficulties in their children. It also highlights the significance of caregivers’ self-care and teaches coping skills to caregivers to improve their own psychological well-being. A complete description of technology-assisted family volunteers delivered parent skills training program is mentioned elsewhere .https://fansforkids.org/.We converted the adapted program into an application consisting of training videos hosted on an Android tablet device. To help caregivers learn from the lived experiences of families of children with developmental disorders, the key program messages and strategies were converted into real-life narratives of three children with developmental disorders and their caregivers and family members. The narrative script is simple, interactive, and allows intervention providers and caregivers to discuss each scenario in the context of their own lives and develop individualized management plans for their children. To address the challenge of limited internet access in rural areas of Pakistan, we hosted the intervention videos on the tablet to make them accessible offline. The intervention resources are freely available in Urdu  using the following web link: We followed a cascade model of training and supervision  Fig. 2)2). A masThe data on implementation variables was collected during the program implementation and at 6 months post-program implementation at three implementation levels: organization, providers, and consumer Table .Table 2Ineeds improvement, 2 means done partially, and 3 means done well. A mean score of 2 on each domain of ENACT is required to fulfill the fidelity criteria for the program delivery. The tool has been extensively used previously to measure the common factors competence among non-specialist providers delivering mental health services in low-resource settings [We evaluated the fidelity of the program delivery by non-specialist providers by live rating a random sample of 20% sessions delivered by each “provider” on the ENACT tool , adaptedsettings .n = 7) that were specific for one-on-one therapy sessions were excluded in consultation with the developer of ENACT. The final adapted ENACT for parent skills training consisted of a 20-item tool and incorporated a four-tiered response system. A mean score of 2.5 on each domain of adapted ENACT was required to fulfill the fidelity criteria for the program delivery   to measudoes program fit with the male/female culture in your country? were removed from all three versions . The reach sub-scale assesses the reach of mental health services/programs to underprivileged groups, males/females, orphan children, and people in the military office. All such items related to the reach of the program to male/female and military personnel were excluded as these items were contextually and conceptually not relevant.General adaptations: The general adaptations to the AMHR D&I measures included the change of the program’s name, replacing the word “provider” with “family volunteers” and “mental health services” to “services for caregivers of children with developmental disorders.” As the parent skills training program targets the whole family and has been designed for children of both genders with developmental disorders and their caregivers, the items exploring the appropriateness of the program from a gender perspective such as (1) how does their current role, being the providers of mental health program, and help community health providers feel successful in their job; (2) allow them to have job stability; (3) is aligned with their professional goals; and (4) create more opportunities for their career advancement, was excluded in an adapted version of the tool; each item is scored on a 4-point scale ranging from 0 not at all to 3 a lot, with an additional category for do not know/not applicable. We calculated Cronbach’s alpha for each domain of adapted tools to assess the reliability. The values of Cronbach’s alpha ranged from 0.70 to 0.90, except for the domain of “reach” (α = 0.30).At the provider’s level, the intervention-specific examples such as the delivery of the program, monitoring of the child’s progress using tablets, and participation in monthly supervision meetings were included. In the current study, the providers became family volunteers due to altruism and because of their intrinsic needs of helping their community members or helping their own extended family members (baradari) to improve their health outcomes. As all-female family volunteers were delivering the intervention voluntarily, neither any official contract was issued to them by the implementation organization nor they were employed somewhere else during their participation in the study (80% were not currently employed at the time of enrollment); therefore, the whole domain of “individual professionalism” that was designed to evaluate The quantitative data was analyzed using descriptive analysis. To compare the implementation variables across three levels of participants , the mean differences in each domain of AMHR D&I measures were calculated.We conducted 30 in-depth interviews with six groups of participants (see Table if there was any).The data were analyzed using the framework analysis . In the The case study has been reported following the Standards for Reporting Implementation Studies (StaRI) checklist  please .n = 7), competing family commitments (n = 7), having to work (n = 6), or not achieving competency (n = 6).Out of 62 trained providers, 36 delivered the program to caregivers in local villages. Twenty-six providers were not able to deliver the program due to health problems (The mean age of the 36 participating providers was 35 ± 4.38) years. For 61% of the providers, education level was 10 years . Out of 270 caregivers enrolled, 85% (230/270) of the trial participants attended 6 sessions (± 1), and only 166 caregivers participated in the implementation evaluation. The mean age of the consumers was 35 (± 7.6) years. Half of the consumers had less than 5 years of education or no education .Out of 326 potential parent-child dyads in 15 Union Council, 270 parents of children with development disorders who met the eligibility criteria were enrolled in the study . Eighty-five percent (230 /270) of the consumers attended 6 sessions (range from 5 to 7). The average duration of a group session was 102 min (± 15). The average group size was 6 (range from 3 to 7).Over the period of 6 months, 10 program trainers organized 30 group supervision meetings of providers. The average attendance in the group supervision was 75%. In turn, providers conducted 178 group supervision sessions with consumers after initial training of 9 sessions. The attendance in these supervision sessions was 73%.To assess the fidelity of the program, 20% of the sessions (103/504) spread over 36 providers were rated at three time points . Cronbach’s alpha reliability of the adapted version of ENACT for all three-time points ranged between 0.70 and 0.93. The intervention sessions were delivered with good fidelity as all providers scored on an average of 2.5 or more  out of 4 on all items of the adapted ENACT at the three time points.The primary clinical outcome of interest was change in the child’s functioning at 6 months post-intervention implementation. The results of the overall trial have been published elsewhere .The data on implementation outcomes was collected from 166 consumers, 36 providers, and 14 members of the program team including program trainers Table .Table 5Dn = 166) indicated that the program was highly acceptable to them . They reported high satisfaction on receiving the program training from a “family volunteer” (item response a lot 2.77 ± 0.47) as she was perceived to be someone who listens, understands, and addresses their questions or concerns about their child and program (2.74 ± 0.49) and takes interest in their concerns and problems (2.75 ± 0.49). Family volunteers were able to earn the trust of the caregivers of children with developmental disorders (2.77 ± 0.46) as she was perceived as qualified enough to deliver the program (2.77 ± 0.45).Caregivers (n = 36) . They not only liked the program materials (3.90 ± 0.31), but they also felt good while delivering the program to the families (3.70 ± 0.67). They felt the program was an appropriate intervention (3.90 ± 0.31); moreover, the skills they learnt while delivering the program were perceived to be useful for the families (3.90 ± 0.31). They were also satisfied with the amount of the training (3.90 ± 0.31) and supervision (3.60 ± 0.51) they received by the program trainers.The program was perceived as highly acceptable by the providers (The program acceptability at the organization level was very high (17.79 ± 2.45). The organizers felt that the delivery of the program was a source of contentment for the program team and trainers. It was not only helpful and beneficial for the reputation of the organization, but it could also create more opportunities of service delivery for the organization.The caregivers perceived that participating in the parent skills training program was feasible for them (31.29 ± 4.76). However, they reported challenges in taking time out of their daily routine to attend weekly training sessions (1.86 ± 0.90): in managing household responsibilities, in implementing program strategies at home by themselves (2.15 ± 0.82), and in finding childcare for their other children during the time they were attending the session (2.09 ± 1.03). Caregivers reported that community members did talk negative about the families seeking program services for their children (1.80 ± 0.75).an intervention delivery aid) for the duration of the program; being enrolled in the program as community workers positively contributed to enhance their skills and confidence. This finding is consistent with the results of previous studies on evaluating the social impact of doing community work on community healthcare workers in Pakistan. Studies show that even with the minimalistic stipend of rupees 2500 (PKR), the program had a positive impact on their well-being and contributed to women empowerment, perhaps by increasing their access to healthcare resources, enhancing their decision-making skills, and opening employment opportunities [The program was very feasible for providers to deliver (domain score 49.7 ± 5.73). The item-wise analysis showed that they felt skilled enough to deliver the program (3.80 ± 0.422) and had appropriate time to implement all the activities of the program (3.40 ± 0.84) including organizing group, providing training and peer supervision to caregivers in their villages and continuously monitoring child’s progress during program implementation. Although providers in the current study were delivering services on volunteer basis and they were only given a tablet device (tunities .The program trainers perceived that implementing the parent skills training program was feasible for the organization (42.29 ± 5.44). According to them, the organization had sufficient resources including a sufficient pool of trainers (3.86 ± 0.53), sufficient finances (2.75 ± 0.75), an adequate transportation system (3.57 ± 0.75), and the necessary equipment (3.86 ± 0.36) to train non-specialists and implement the program in the study settings. Moreover, program trainers also mentioned that they received adequate administrative support (3.62 ± 0.65) and clinical supervision (3.77 ± 0.43) to provide supervision and support to the providers.As the intervention content was adapted into a training application with “real-life” narratives  both thedifficulties in seeking permission from their own family to deliver program in the community and competing demands on time due to household responsibilities were identified as potential barriers to continue to implement the program through family volunteers. Previous studies conducted in Pakistan on exploring the factors affecting the work experience of community health workers in rural settings of Pakistan show that providing door-to-door healthcare services in the community settings, especially paying visits to the houses of “non-kin” [Providers reported that they were satisfied with their role as a provider of the program, and they will keep implementing the program to the families (3.50 ± 0.85) in their villages under the supervision of the trainers (3.20 ± 1.1). They appreciated the idea of implementing the program through non-specialist, family volunteers; however, non-kin”  is not cnon-kin” –35, and non-kin” . Thus, eThe program trainers perceived that the program was highly appropriate to the needs and cultural values of the consumers . According to the program trainers, as the program content was designed to meet the needs of the consumers, it was likely to be useful to manage the problems of children with developmental disorders and their caregivers. They perceived that the delivery of the program to the families of children with developmental disorders in the study area was aligned with the core values and goals of their organization and implementing this program was a priority for leaders at their organization.Both the program trainers and providers perceived that the reach of the program was high . The item level analysis indicated that according to the providers, the community members were fully aware that the program was being delivered in the community by the family volunteers (3.50 ± 0.70). They also perceived that all those caregivers in their community who might be in need of a parent skills training program, specifically parents from low socio-economic status, would still find this program useful and attend the training (2.40 ± 0.69). However, according to the consumers the reach of the program was comparatively low (6.99 ± 1.98).might be due to program acceptability), however, various barriers, such as family pressure and restricted women’s mobility in the rural settings of Pakistan, can inhibit the scale-up implementation of the program.We also calculated the reach of the program using RE-AIM indices. We successfully established 36 potentially self-sustaining village-based “family networks” led by 36 trained providers working under the supervision of trainers from the local nongovernmental organization. The target population for the program was 270 caregivers and their children who met the eligibility criteria and were enrolled in the program. Out of 270 participants, 85% (230/270) of the population received the program training by 36 providers using the technology platform. Although the reach of the program during the implementation phase was high  or at the house of providers. Intervention delivery in village-based groups was regarded as an acceptable format of parent skills training by a number of respondents. According to participants, sitting together as a group served as a learning platform for them in which they could share their problems with each other. The respondents expressed that having a session in a group helped them to validate and normalize their feelings about their child’s health condition; additionally, they helped to learn from each other through this experience.This case study describes the implementation evaluation of a family volunteer-delivered, technology-assisted parent skills training program for children with developmental disorders in low-income rural communities. The results showed that technology can be used to train female family volunteers in the delivery of parent skills training program at scale with fidelity. The findings of quantitative and qualitative analyses show that the program’s content, mode of delivery using technology, and non-specialist family volunteers as the delivery agent were perceived to be highly acceptable, feasible, and appropriate to consumers, providers, and organizers, and the technology-assisted program had a high reach according to them. The study also illustrated several other important points about scaling up task-shifting interventions in low-resource settings. First, in addition to the tablet platform, adapting materials to make them engaging and readily identifiable as commonly encountered situations in the community was a key factor in the acceptability of the program. Second, measuring the competency at the end of the training was an essential step in assuring fidelity; nearly 10% of family volunteers entering the training could not be deployed to their communities because they did not achieve the required level of skill.While the technology-assisted training and delivery were feasible and well-accepted, other barriers—notably competing demands in their homes faced by the family volunteers and the parents they worked with, plus community norms that potentially limited the ability of women to participate alone outside the home—reduced the reach of the program. The use of task-shifting approaches to deliver psychological interventions at a doorstep via community-based female healthcare workforce has been frequently used previously and found to be an acceptable implementation strategy , 37, 38.In the present study, we trained family volunteers to deliver parent skills training program to the caregivers of children with developmental disorders in their own villages. The findings of qualitative in-depth interviews showed that locally identified family volunteers were highly acceptable as delivery agents. According to the participants, family volunteers exhibited characteristics of trustworthiness and altruism which contributed significantly to increase the program’s acceptability and made it appropriate for the targeted community/population. In Pakistan, as in many other countries, women/mothers are children’s main caretakers. Based on formative work  and to bHowever, one of the frequent concerns regarding the implementation of evidence-based practices by non-specialist at scale is the decrease in program fidelity and its effectiveness  due to tA key hallmark of our study is the use of implementation science frameworks and valid and reliable implementation outcome measures alongside a clinical trial to measure the effectiveness of the intervention , which aThe definitive randomized evaluation of intervention effectiveness demonstrated that the program did not result in statistically significant improvement in the clinical outcomes of children when implemented at scale. This difference in the intervention impact from the exploratory study  could beWhile our study offers detailed insight into the feasibility and acceptability of using technology-assisted task-shifting strategies to bridge the treatment gap for developmental disorders in low-resource settings, it has a number of limitations. Although we used psychometrically strong implementation outcome measures, our study was not powered to evaluate the implementation effectiveness. The study was not designed and powered to evaluate the implementation outcomes  as potential mediators to change clinical outcomes  in caregivers. Moreover, the data on the implementation outcome was collected at only one time point. The data collection at multiple time points can help to explore whether the fidelity, acceptability, feasibility, and appropriateness of the program were sustained over time. In addition to that, the use of implementation science frameworks helped us to systematically plan and execute the implementation of parent skills training program in real-world settings and to unpack implementation processes at the organization, provider, and consumer levels which are often poorly understood and missing in a traditional randomized evaluation.Technology-enhanced training of volunteers has many positive features, but it needs to be deployed in a culturally congruent way including understanding the way in which the volunteers’ participation potentially challenges their traditional roles in families and communities to improve program implementation and increase its reach. Moreover, context-specific evaluation of the program using implementation outcome measures and frameworks, embedded within the traditional RCTs could be beneficial to identify the priority challenges that need urgent mitigation before further scale up of the program in real-world settings. Such trials are warranted to (a) compile and consolidate implementation data using validated implementation outcome measures that can be used or adapted for a variety of settings and implemented with a range of stakeholders, (b) evaluate the adoption and integration of evidence-based intervention strategies in the healthcare system; (c) evaluate the impact of improved implementation on clinical outcomes, and (d) measure the sustainability of such community-based initiatives over the period of time.Additional file 1. Supplementary information.Additional file 2. Standards for Reporting Implementation Studies: the StaRI checklist.


Today, Antibes is obviously the « Health and Sport city ». Demographic and epidemiological studies reveal problems of ageing and isolation of elderly people; often they are subject to serious health consequences and triggering the loss of autonomy. Precariousness and social isolation also enhance the occurence or deterioration of certain health problems . All these factors lead to a growth of long term illnesses.Following a national law health system modernisation in 2017, the City of Antibes, the Hospital Centre and the Regional Medical and Sport Centre have set up a program called “Pass Form Santé” dedicated to “Prescription Sports”.What does it consist of? Who are the beneficiaries? What are the means implemented?This unique and innovative program in the Alpes Maritimes aims to help people with chronic diseases to improve their health and the way of taking medication. It is to guide them to an adapted physical practice of activity at a regular, secure and progressive way on the recommendation of an attending physician.The City of Antibes has all the resources to enable the implementation of this program: multi-disciplinary local municipal establishments, well trained human resources in different adapted physical activities, and a substantial network of sport and medical-social partners. Since 2017, 135 people have joined the “Pass Form Santé” program. 47% of prescriptions came from liberal or specialist doctors, 31% from hospitals and 22% from the Medical-Sportive Centre of Antibes. The breakdown of pathologies shows a majority cases in cardiology and oncology.Qualitative result on the beneficiaries' health is unequivocal. The program allows them to feel better physically and morally. This “Pass Form Santé” program perfectly meets their expectations and allows them to get closer to an autonomous practice or to join any associative sports network.The city of Antibes, together with its partners, has known how to create this innovative program called “Pass Form Santé” in order to develop prescription sports. It serves as a common link between beneficiaries, the medical professionals and the associative sport networks in order to encourage people with a chronic disease to resume physical activity.