Digital mental health interventions may help middle-aged and older adults with depression overcome barriers to accessing traditional care, but few studies have investigated their use in this population.This pilot study examines the feasibility, acceptability, and potential efficacy of the Meru Health Program, an 8-week mobile app–delivered intervention.A total of 20 community-dwelling middle-aged and older adults  with elevated depressive symptoms participated in a single-arm pilot study investigating the Meru Health Program, an app-delivered intervention supported by remote therapists. The program primarily uses mindfulness and cognitive behavioral skills to target depressive symptoms. A semistructured interview was completed at the baseline to establish current psychiatric diagnoses. Depressive symptoms were measured using the Patient Health Questionnaire and Patient-Reported Outcomes Measurement Information System (PROMIS) depression measures. Anxiety symptoms were measured using the Generalized Anxiety Disorder Scale and the PROMIS Anxiety measure. User experience and acceptability were examined through surveys and qualitative interviews.In total, 90% (18/20) of the participants completed the program, with 75% (15/20) completing at least 7 of the 8 introductory weekly lessons. On average, participants completed 60 minutes of practice and exchanged 5 messages with their therapists every week. The app was rated as helpful by 89% (17/19) participants. Significant decreases in depressive (P=.03) and anxiety symptom measures (P=.01) were found; 45% (9/20) of participants showed clinically significant improvement in either depressive symptoms or anxiety symptoms.The findings suggest that the commercially available Meru Health Program may be feasible, acceptable, and potentially beneficial to middle-aged and older adults. Although larger controlled trials are needed to demonstrate efficacy, these findings suggest that digital health interventions may benefit adults of all ages. Major depressive disorder (MDD) is among the foremost causes of disability worldwide among older adults -3. In adOlder adults face multiple barriers in accessing mental health interventions, including limited transportation and mobility, living distally from treatment settings, and high health care costs, which could be addressed with digital health interventions ,11. As sFew studies have examined mental health–related mobile apps among older users. One group tested an adapted app-based intervention to promote the self-management of chronic conditions alongside peer coaching among middle-aged and older adults with serious mental illness and found it to be feasible, acceptable, and potentially helpful in improving outcomes among the 8 study completers . AnotherThis study investigates the use of an 8-week mobile app–based intervention with remote therapist support called the Meru Health Program (version 2.0), a commercially available digital health program. The Meru app contains video instructional content and guided practices delivered to a group of 5 to 10 individuals who work through the program as a cohort. Videos and practices teach CBT and mindfulness techniques to manage depressive and related symptoms, such as worry. Patients have access to a dedicated therapist via asynchronous within-app messaging or, if needed, a phone call. The therapist provides guidance by (1) responding to patients’ messages, (2) sending unprompted messages to patients and encouraging program adherence, and (3) reviewing responses to practice exercises. The app also includes a moderated discussion where group members can share thoughts and experiences with practices and support other patients by providing limited feedback on their posts.An uncontrolled study of the Meru Health Program in young adults demonstrated feasibility and reduced depressive symptoms . SimilarParticipants were recruited through various announcements describing a mobile app intervention for depression using (1) flyers posted at medical offices and on community boards , (2) web-based advertisements (Craigslist and Facebook), (3) word of mouth, and (4) invitations to previous research participants interested in future research opportunities.The inclusion and exclusion criteria were assessed during the telephone screening. Inclusion criteria were age ≥40 years, elevated depressive symptoms, owning a smartphone, and residing in California because of telehealth laws regarding practicing across state lines. Exclusion criteria included cognitive impairment, suicidal ideation, current participation in psychotherapy, problematic drinking, and psychotic symptoms. Participants taking psychotropic medications must have been on a stable dose (>1 month) to be included.Demographic information and health status, presence of eight major health conditions , and vision and hearing impairment were gathered at baseline via questionnaires.The Mobile Device Proficiency Questionnaire (MDPQ)  examinesThe Patient Health Questionnaire 9-item (PHQ-9)  measuresThe Generalized Anxiety Disorder 7-item (GAD-7) scale  measuresThe Patient-Reported Outcomes Measurement Information System (PROMIS) Depression (short form 8a) and Anxiety (short form 8) scales were used as secondary measures . Total sThe Mini International Neuropsychiatric Interview (MINI 7.0.2)  is a semThe app use data collected included the number of messages sent, duration of use, lessons completed, and the number and types of practices completed.At posttreatment, participants completed a 6-item self-report measure about their experiences and impressions of the program . ParticiAfter treatment, participants completed a semistructured qualitative interview about the program . They weThe study was approved by the Stanford University School of Medicine Institutional Review Board and registered at ClinicalTrials.gov (NCT03652948). The study was conducted between July 2018 and May 2019.several days or more, then the P4 Suicide Risk Screener [Potential participants completed a telephone screen to assess the inclusion and exclusion criteria. The PHQ-9  determinScreener  was admiScreener  identifiScreener  was usedScreener .Eligible participants were invited to an in-person visit, during which the research staff obtained informed consent, followed by administration of the complete MINI and self-report assessments. Participants then received a handout explaining the steps to begin the Meru Health Program. First, study referrals were sent directly to the Meru therapist, who scheduled an introductory call with the participant. Five days before the start of the program, participants received an email with instructions on downloading and logging into the app on their own smartphone.Meru Health is a registered health care provider in multiple states in the United States and Finland. Individuals primarily access the Meru Health Program by selecting health and employee plans. The app is available for download via the App Store (iOS) or Play Store (Android), but patients require a referral and eligibility screen to access the app after download. As described earlier, the program consists of an app, therapist support (via app and weekly emails), and group discussion. The app has five menu options: (1) “today screen” with informational videos and practices to be completed, (2) group discussion page, (3) program timeline, (4) notifications, and (5) asynchronous within-app messaging with the therapist . ParticiMeru Health therapists are licensed practitioners with doctoral or master’s degrees in psychology, counseling, social work, marriage and family therapy, or other related fields. Therapists have formal training in mindfulness, CBT, and manual training (>30 hours), which includes an assessment of skill acquisition to deliver the Meru Health Program. Therapists send weekly emails introducing new content  to be learned within the app each week. Therapists monitor practice completion; send messages to encourage adherence; and review participants’ messages and group discussion posts for possible suicide or homicidal ideation, active substance use, or the presence of psychotic symptoms. The therapist responded to participants exhibiting these symptoms or those who had evidence of worsening mental health within 12 hours. In addition, posts deemed inappropriate or potentially harmful to other group members  were removed.Participants were contacted by researchers during week 5 to complete questionnaires assessing depressive and anxiety symptoms. At the posttreatment assessment, participants completed these questionnaires again and provided feedback about the program via a user experience survey and qualitative interview. Participants received payment only for completion of assessments administered by the research team at baseline, week 5, and week 8/posttreatment . No other payment was provided.To assess the feasibility of the program, we summarized participant flow, inspected retention rates, and calculated the mean use of different app components using the app use data. Acceptability was examined by summarizing responses to the user experience survey.κ>0.70 . Excerpts were discussed among 3 authors , and matrices were created to examine variations in patterns or themes by quantitative ratings consistent with a mixed methods approach [The qualitative interview transcripts were excerpted by the first author (CEG) using Dedoose 8.2.14  web-based software . A codebapproach .Intervention effects on depressive and anxiety symptoms were estimated using linear mixed effects models using SPSS version 24 (IBM) . All parA limited data set that supports the findings of this study is available from the corresponding author upon reasonable request.Participants (N=20) had a mean age of 61.65 years , and most were women  and White and non-Hispanic . Regarding clinically significant improvement, 30% (6/20) participants had improvements in depressive symptoms and 45% (9/20) in anxiety symptoms. All 6 who experienced improvement in depression also showed improvement in anxiety. Age and mobile device proficiency were not significantly associated with change in scores on any outcome measures, but older age was associated with lower mobile device proficiency . Mobile device proficiency total scores ranged from 26.47 to 40, which falls above the average for older adults  in the initial MDPQ validation paper [on paper .Our findings suggest the feasibility and acceptability of an 8-week mobile app–based intervention for depressive and anxiety symptoms in a sample of middle-aged and older adults approximately 30 years older than samples in most mobile intervention research. The low dropout rate (10%) and robust engagement with the app mirrors findings with the Meru Health Program in younger adults ,20 and wOlder adults with depression may benefit from mobile interventions, such as the Meru Health Program, based on significant reductions in depression and anxiety outcomes. This and the finding that 45% (9/20) of individuals achieved a clinically significant reduction in symptoms suggest that the program may be beneficial to some middle-aged and older users. The uncontrolled effect sizes were slightly larger than, but comparable with, those found in a meta-analysis of mobile interventions for depression . Larger pull support where users reach out for help but also incorporated some push-based support . According to the Efficiency Model of Support, the limitations of pull support include underutilization because of concerns about burdening the supporter [The qualitative findings provide an important context to help elucidate specific aspects of the feasibility and acceptability of the program. As expected, the practices were found to be the most helpful component, which is consistent with previous findings regarding guided self-management programs in older adults . The theupporter . Our finGroup support was a unique, yet underutilized, program component. Being part of a group facing similar struggles was helpful to some in promoting understanding and a sense of not being alone. Unfortunately, the limited response options for communicating with other members undermined the use of and interest in this feature. Thus, this component should be considered for modification to increase its utilization. Such future enhancements will need to balance the risks of providing open-ended interactions, including potential breaches in confidentiality.Another potential refinement to the program that might especially benefit older adults is an enhanced program orientation, including an in-person or preview of the app, a handout, instructional videos, or a combination of these. Such an orientation may encourage greater exploration of the app, as older users tend to be hesitant about making errors or pressing incorrect buttons, resulting in less app exploration compared with younger users. Other suggestions for program improvements included greater control over video-delivered information . Program compatibility with tablets could help older users experience dexterity and vision challenges. Including older users in usability testing and research on digital health interventions would ensure that these interventions are optimized for all users. Furthermore, ensuring universal design is an important step before dissemination in health care settings, such as primary care that serves patients across the life span.Conclusions from our findings must consider the limitations of the study. Foremost among these was the lack of a control condition, leaving open the question of whether the intervention was responsible for symptom improvement. Second, most of our sample had at least 16 years of education, which may limit the generalizability of the findings to those with less education. Third, our sample for the pilot study was quite small, with 90% (18/20) of participants completing the intervention. Although the sample included 40% (8/20) non-White individuals, because of the small overall sample size, further research is needed to evaluate the efficacy of this intervention in larger and even more racially and ethnically diverse samples. Fourth, a standardized mobile app rating scale or evidence-based usability measure was not used to assess the acceptability or usability of the Meru Health app. Fifth, mobile device proficiency for the sample was substantially higher than that evidenced in the initial study of the MDPQ ; thus, tIn summary, this study found evidence of feasibility and acceptability of a commercially available app, the Meru Health Program, in a small sample of middle-aged and older users. Furthermore, the findings show that some participants experienced reduced psychiatric symptoms. Although larger, controlled trials are needed to demonstrate efficacy, our findings align with research with younger adults and suggest that digital health interventions may benefit and should be offered to adults of all ages. If future research validates these preliminary findings, mobile mental health interventions could be a valuable tool in addressing unmet treatment needs and reducing the burden of depression among older adults.


IgM monoclonal gammopathy of undetermined significance (IgM MGUS) is an early precursor stage of the rare lymphoma Waldenström Macroglobulinemia (WM). Although comparative gene expression studies on WM, IgM MGUS, and normal B-cells (CTRLs) identified several differentially expressed genes, reliable predictors of progression from IgM MGUS to WM have not yet been identified. We performed a microarray study on CD19+ and CD138+ cells of WM vs. IgM MGUS vs. CTRLs to determine gene signatures for both cell populations. We demonstrated that hematopoietic antigens, cell-adhesion molecules, Wnt-signaling, BCR-signaling, calcium signaling, coagulation cascade, and pathways responsible for cell cycle and proliferation were significantly enriched for genes expressed in B-cells of WM vs. IgM MGUS vs. CTRLs. Interestingly, we showed nine genes which displayed the same expression levels in WM and IgM MGUS compared to CTRLs, suggesting their possible role in the risk of transformation of IgM MGUS to WM.Waldenström Macroglobulinemia (WM) is a B-cell lymphoma characterized by the precursor condition IgM monoclonal gammopathies of undetermined significance (IgM MGUS). We performed a gene expression profiling study to compare the transcriptome signatures of bone marrow (BM) B-cells and plasma cells of 36 WM patients, 13 IgM MGUS cases, and 7 healthy subjects used as controls (CTRLs) by Affymetrix microarray. We determined 2038 differentially expressed genes (DEGs) in CD19+ cells and 29 DEGs genes in CD138+ cells, respectively. The DEGs identified in B-cells were associated with KEGG pathways, mainly involved in hematopoietic cell lineage antigens, cell adhesion/focal adhesion/transmembrane proteins, adherens junctions, Wnt-signaling pathway, BCR-signaling pathway, calcium signaling pathway, complement/coagulation cascade, platelet activation, cytokine-cytokine receptor interactions, and signaling pathways responsible for cell cycle, apoptosis, proliferation and survival. In conclusion, we showed the deregulation of groups of genes belonging to KEGG pathways in the comparison among WM vs. IgM MGUS vs. CTRLs in B-cells. Interestingly, a small set of genes in B-cells displayed a common transcriptome expression profile between WM and IgM MGUS compared to CTRLs, suggesting its possible role in the risk of transformation of IgM MGUS to WM. Waldenström Macroglobulinemia (WM) is a rare malignancy B-cell lymphoma characterized by a lymphoplasmacytic marrow infiltration and an uncontrolled monoclonal IgM production in the bone marrow and other organs. WM has an annual incidence of 3.4 per million among males and 1.7 among the females in United States, while an incidence of 7.3 for males and 4.2 for females occurs in Europe, respectively [MYD88, CXCR4, ARID1A, and CD79B have been found in bone marrow lymphoplasmacytic cells by next-generation sequencing (NGS) in patients with WM [MYD88 gene as an important oncogenic driver [CXCR4 somatic mutations have been observed in more than 40% of WM patients. They do not adversely impact overall survival but play a role in guiding treatment [The disease course starts from asymptomatic WM (smoldering/smWM) form to symptomatic WM (sWM) which can manifest clinical features of lymphoadenopathy, hepatosplenomegaly, thrombocytopenia, pancytopenia, cold agglutinine syndrome, paraprotein-related cryoglobulinemia, peripheral neuropathy, or symptomatic hyperviscosity ,3. WM is with WM . MYD88 L with WM . A previc driver ,13. CXCRreatment . The comIL6 and MAPK signaling pathway were unique to WM [The results provided by gene expression profiling studies (GEP) highlighted differentially expressed genes (DEGs) involved in oncogenesis and B-cell differentiation in the comparison between B-cells and plasma cells of WM vs. multiple myeloma (MM) vs. chronic lymphocytic leukemia (CLL) counterparts, respectively . A compaue to WM .We previously determined the up regulation of JAK/STAT, PI3K/Akt/mTOR, and MAPK signaling pathways between WM and IgM MGUS CD19+ cells whereas immune response and cell activation mainly distinguished WM from IgM MGUS CD138+ cells .A careful multiparametric flow cytometry analysis showed a strong similarity of immunophenotypic expression profile between clonal B-cells of IgM MGUS, smWM, and sWM .A gene expression and mutational study demonstrated that genes involved in the Toll-like receptors (TLR) signaling pathways were up-regulated in symptomatic WM vs. indolent forms . MoreoveDespite the improvement in gene expression signatures and genomic alterations responsible for WM, trustworthy predictors of progression from IgM MGUS to WM have not yet been identified.n = 2038), while we found only 29 significant DEGs in the comparison among plasma cells of WM vs. IgM MGUS vs. CTRLs.In the current study, we selected B-cells and plasma cells of bone marrow of 36 WM patients, 13 IgM MGUS cases, and 7 healthy subjects (CTRLs). Therefore, we performed a wide-transcriptome microarray analysis to determine statistically significant gene expression differences among WM vs. IgM MGUS vs. CTRLs in CD19+ cells and CD138+ cells, respectively. We also investigated the differentially expressed genes using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) to determine candidate genes for the risk of progression of IgM MGUS to WM. Our GEP data identified different patterns of significant DEGs in B-cells  signaling pathway, complement coagulation cascade and platelet activation, cytokine-cytokine receptor interactions/IL-17 signaling pathway, WNT/β catenin signaling pathway, Calcium signaling pathway, JAK/STAT signaling pathway, FOXO signaling pathway, NFKB signaling pathway, and p53 signaling pathway. Finally, we identified nine genes which showed similar expression levels in WM and IgM MGUS with respect to CTRLs, suggesting a candidate gene set signature predictive of the risk of progression of IgM MGUS to WM.The total RNA concentration isolated from 1 million cells (CD19+ or CD138+ cells) was about 1–2 µg and it was measured by Nanodrop .From the comparison among WM, IgM MGUS, and CRTLs of CD19+ cells, we identified 3052 probe-sets corresponding to 2038 unique genes and 584 not annotated probe-sets.GEP analyses among WM, IgM MGUS and CRTLs of CD138+ cells determined 38 probe-sets corresponding to 29 unique genes and six not annotated probe-sets. There were 16 genes in common between the CD19+ and CD138+ cells.https://david.ncifcrf.gov/, 24 July 2020). Complete results are reported in To better characterize the genes selected as differentially expressed, we considered, for all genes that resulted significantly different expressed in at least one of the below listed comparisons, the following patterns of differential expression: p1) WM > IgM MGUS and IgM MGUS > CTRL, p2) WM < IgM MGUS and IgM MGUS < CTRL, p3) WM > IgM MGUS but IgM MGUS < CTRL, p4) WM < IgM MGUS but IgM MGUS > CTRL. We performed a functional annotation clustering and enrichment analysis on each pattern using DAVID 6.8 , 403 unique genes (683 probe-sets of which 135 not annotated), 827 unique genes (1211 probe-sets of which 218 not annotated), and 543 unique genes (781 probe-sets of which 173 not annotated), respectively.n = 20). Among the DEGs, all the genes (encoding transmembrane proteins) shown in PTPRG). These findings suggest that the deregulation of these genes was specific for WM B-cells.Functional clustering has highlighted genes encoding transmembrane proteins (IL2RA (CD25), CD1D, and CD44 were over expressed in WM vs. IgM MGUS and vs. CTRLs (p1). CD4 (helper T cells) was up regulated in IgM MGUS vs. WM and vs. CTRLs (p4).GEP data highlighted eight genes encoding surface hematopoietic cell lineage markers which could determine different cellular stages . Data shHLA-A, HLA-C, HLA-B, HLA-E, and HLA-G which were over expressed in WM vs. IgM MGUS and vs. CTRLs (IGHM (Constant region of the mu heavy chain of IgM), which defines the IgM isotype, was over expressed in WM vs. IgM MGUS and vs. CTRLs, while no differences in expression were noted between IgM MGUS and CTRLs , which are expressed on the surface of B lymphocytes and are involved in the binding with other cells and, in particular, with immune system (T cells), neural system (pre- and post-synaptic neurons), and inflammation processes. The Human leukocyte antigen (HLA) system is a group of proteins that are encoded by the major histocompatibility complex (MHC) genes such as s. CTRLs . None ofnd CTRLs .CD86 (B-cell surface molecule) which regulates T cell responses, was down-regulated in WM vs. IgM MGUS with the fold change (FC = −2.93) and in WM vs. CTRL (FC = −2.02) (Our results showed that = −2.02) .CD58 (plasma membrane protein) and CEACAM1 (CD66a) (angiogenesis) were up regulated in WM vs. IgM MGUS and vs. CTRLs as shown in We found that CDHR3  was over expressed in CTRLs vs. IgM MGUS and vs. WM while no significant expression changes were observed in the comparison between WM and IgM MGUS , CAV1 (Caveolin 1), PTK2 (encoding FAK), and IGF1R (insulin-like growth factor 1 receptor) were under expressed in WM vs. IgM MGUS and vs. CTRLs. On the other hand, RAPGEF1 was over expressed in WM vs. IgM MGUS and vs. CTRLs.We have demonstrated an altered expression of 11 genes which regulate focal adhesion pathway in B-cells . Focal aPTPRJ and PTPN1 in WM vs. IgM MGUS and vs. CTRLs. Both genes encode tyrosine phosphatases which dephosphorilate β-catenin, thus affecting cell-cell adhesion, cell migration, and β-catenin levels. In addition, SSX2IP and TJP1 which regulate the organization of the actin cytoskeleton and the cell migration were down regulated in WM vs. IgM MGUS and vs. CTRLs. The deregulation of expression of both genes was unique to WM B-cells as no differences of expression were found between IgM MGUS and CTRLs.Our GEP data identified some DEGs in adherens junction KEGG pathway . AdherenWNT3 was over expressed in WM vs. IgM MGUS (FC = 2.19) and vs. CTRLs (FC = 2.35)  and vs. IgM MGUS (FC = 2.58) but no significant gene expression differences were noted between WM and IgM MGUS  . LEF1, aIgM MGUS .2+ pathway, we found 4 DEGs. Among them, RYK was up regulated in WM vs. IgM MGUS and vs. CTRLs  and MARCKS  were DEGs in B-cells (Within Wnt/Cas. CTRLs . In addi B-cells .ADRB2 (transmembrane Beta-adrenergic receptor) was over expressed in WM vs. CTRLs (FC = 2.31) and in IgM MGUS vs. CTRLs (FC = 1.8), but no significant expression differences were observed between WM and IgM MGUS B-cells  and vs. CTRLs (FC = 2.64).We revealed the deregulation of 11 genes associated with Calcium signaling pathway which mediate the calcium entry into the cells from the outside through plasma membrane by channels . We have B-cells . We haveTRPC1 in WM vs. IgM MGUS and vs. CTRLs. TRPC1 encodes a membrane protein that can form a non-selective channel permeable to calcium which interacts with ITPR1 and ITPR2 . ITPR1, which mediates the calcium release inside the cells, was under expressed in WM vs. IgM MGUS and vs. CTRLs (MYLK (muscle contraction) was under expressed in WM vs. IgM MGUS and vs. CTRLs , which may play a role in hematopoietic lineage decisions and growth regulation, was over expressed in WM vs. IgM MGUS and vs. CTRLs. Finally, we demonstrated the down regulation of PIK3AP1 in WM and IgM MGUS vs. CTRLs B-cells, but no significant gene expression differences have been found between WM and IgM MGUS , TFPI, and SERPINE1 belonging to the complement and coagulation cascade (hsa04610), were under expressed in WM vs. IgM MGUS but no expression differences were observed between CTRLs and WM as well as CTRLs and IgM MGUS  in WM vs. IgM MGUS and vs. CTRLs with high FC (Among the IL17-like cytokines (KEGG hsa04657), our data showed the over expression of  high FC .BCL2, SOS1, and STAT3 were over expressed in WM vs. IgM MGUS and vs. CTRLs, but no gene expression changes were noted between CTRLs and IgM MGUS.Our GEP data highlighted the deregulation of six crucial genes involved in the JAK/STAT signaling pathway . The actIL4R, IL13RA1, and IL21R were down regulated in WM vs. IgM MGUS and vs. CTRL with high FC  and in WM vs. CTRLs (FC = 2.91). Interestingly, CDKN1B was up regulated in WM vs. IgM MGUS (FC = 1.5) and vs. CTRLs (FC = 1.5), demonstrating the same expression level in IgM MGUS and CTRLs. Our data identified the progressive over expression of RAG1 in WM vs. IgM MGUS vs. CTRLs with high FC   deregulation occurred only in WM B-cells.Our results demonstrated the over expression of GUS (p3) . To be nTP73, CD82, and CHEK1 involved in p53 signaling pathway, were DEGs in B-cells  were deregulated in all the 4 patterns CD19+. We suggest the possible role of ZNF in the transcription regulation and cancer progression in the comparison among the three groups of subjects. Additional studies are needed to confirm these data. Among them, we focused on ZNF804A and ZNF215 which were up regulated in WM vs. IgMGUS and vs. CTRLs with very high FC, while IKZF2 was progressively up regulated from WM to IgM MGUS and CTRLs (Zinc finger proteins (ZNF)  [IgM MGUS . The rol (DLBCL) .Our GEP results highlighted nine genes which displayed a similar expression level between WM and IgM MGUS compared to CTRLs in B-cells, suggesting their possible role in the risk of transformation from IgM MGUS to WM .To better appreciate the trend of expression of these genes, Clustering and principal component analysis applied to the analyzed subjects, considering only the expression signature of the nine candidate genes of the risk of progression of IgM MGUS in WM, highlighted a quite homogeneous cluster of CTRL subjects, whereas WM and IgM MGUS subjects tended to group together. This is consistent with the observation that these nine genes displayed the same expression levels in both WM and IgM MGUS compared to CTRLs . To furtFrom the comparison between WM vs. IgM MGUS vs. CTRLs in the CD138 cells, we found 26 genes deregulated in pattern 2 with high FC ranging up to 6.2, while there were 0, 1 and 2 unique genes in patterns 1, 3 and 4, respectively .ARHGAP32, TJP1 , PARD3 , CADPS2, and SYNM encoding cell junction proteins, were down regulated in WM vs. IgM MGUS and vs. CTRLs with very high FC  and vs. IgM MGUS (FC = 2.92), but no expression differences were observed between WM and IgM MGUS  was progressively up regulated from WM to IgM MGUS and to CTRLs with high FC, respectively  in common between CD19+ cells and CD138+ patterns shown in LAPTM4B, PLA2G2D, KIAA1804, MYLK, ARHGAP32, SYNM, and MARC2 clustered in p2 CD19+ cells as well as in p2 CD138+ cells. TJP1, PPARGC1A, GBA3, and NFIB were down regulated in WM p4 CD19+ and in WM p2 CD138+ cells, respectively. However, these genes were significantly under expressed in WM vs. IgM MGUS.In particular, The current state of the art for genomics and transcriptome knowledge of WM points out the complexity of this disease. The significant degree of clinical and genetic heterogeneity can be attributed mostly to WM tumoral clone compartment which consists of clonal B-cells, clonal plasma cells and a lymphoplasmacytic population ,20. WholTo the best of our knowledge, we report an extensive transcriptome gene expression comparison of B-cells and plasma cells of WM patients vs. IgM MGUS subjects vs. healthy donors in order to identify possible genes and pathways involved in the risk of progression from IgM MGUS to WM. We distinguished IgM MGUS from WM based on the bone marrow infiltrate following the consensus panel recommendations from the second IWWM as described in We have chosen to perform a comparison among the three groups of subjects to investigate an evolutionary pattern associated with transformation. A possible limitation of our approach is that the selected CD19+ cell population of IgM MGUS subjects might include regular non-clonal CD19+ cells which could contribute to the GEP signals. To partially take this eventuality into account, we chose to compare IgM MGUS CD19+ cells vs. normal CD19+ cells to include the gene deregulation referred to normal condition, in order to evaluate the gene expression changes due to the presence of the clonal CD19+ cells.MYD88 and CXCR4 mutation status were not monitored, whereas current literature reports an extreme degree of heterogeneity observed in WM based on MYD88 and CXCR4 mutational status [Another possible limitation of our study is that, at the time of samples collection, the l status ,11,12,13On the contrary, only very few genes, which encoded adherens and gap junction proteins, cell adhesion molecules, p53 signaling pathway and calcium signaling pathway, came from the analysis of CD138+ cells of WM vs. IgM MGUS vs. CTRLs.n = 9) which displayed no significant differences of expression between WM and IgM MGUS B-cells with respect to CTRLs  B-cells compared to non-malignant B-cells and that targeting the endocannabinoid receptors was suggested in the treatment of MCL [Our GEP results demonstrated that transmembrane proteins on B-cells were encoded by DEGs. Among them, t of MCL .IL2RA in B-cells showed by our study is strongly supported by previous authors who have demonstrated that Waldenström’s clone was characterized by CD25 marker [CD1D could play a role as a diagnostic marker in the characterization of B-cell chronic lymphoproliferative disorders (B-CLPDs) [CD1D expression on B-cells was higher in WM vs. IgM MGUS and vs. CTRLs, suggesting its possible role as a marker in WM.Some studies extensively investigated the immunophenotypic features of WM and IgM MGUS B-cells and plasma cells ,23,24. H5 marker . In addiCD44, which encodes a glycoprotein over expressed in cancer stem cells, was up regulated in WM B-cells [CD4 (T-Cell Surface Glycoprotein) was up regulated in IgM MGUS vs. WM and in WM vs. CTRLs B-cells suggesting the presence of this protein on B-cell surface. Its role needs to be further investigated.We found that  B-cells . Some au B-cells . We showAmong the CAMs, some authors identified the higher serum levels HLA-Gs in WM and IgM MGUS compared to CTRLs . In addiCD86 was significantly up regulated in IgM MGUS and CTRLs vs. WM B-cells. Future studies are required to explore the impact of CD86 expression in B-cells of WM and IgM MGUS patients.A previous study on trogocytosis in WM, CLL and MM demonstrated that cells can transfer surface molecules during cell–cell interactions, which can lead to the creation of new cell types with functional changes, as shown in a previous paper . The autCEACAM1 in WM vs. IgM MGUS and vs. CTRLs B-cells, confirming previous investigations which showed the up regulation of CD66a in bone marrow samples of non-Hodgkin lymphoma (NHL) and MM [We have demonstrated the over expression of ) and MM .CNTNAP2 corroborates cell adhesion between Schwann cells and oligodendrocytes. Notably, CNTNAP2 encodes CASPR2 protein which is expressed in central nervous system (CNS) and peripheral nervous system (PNS) playing a role in neurodevelopmental disorders and in the autoimmune disease Sjogren’s syndrome (SS). In addition, previous data showed that CASPR2 and ADAM23 are active in the peripheral neuropathy by controlling the activity of potassium channels in SS [ADAM23 in WM has not yet been found, but the inactivation of this gene is associated with tumorigenesis in human cancers [CNTNAP2 and ADAM23 were deregulated in B-cells of both WM and IgM MGUS. Thus, according to the data shown above, we could speculate the possible role of both genes in WM patients with Sjogren’s syndrome. Based on the possible role of ADAM23 in the peripheral neuropathy, its involvement in IgM MGUS could be supported by some studies which have investigated a large cohort of MGUS patients and found that sensory/motor neuropathies were associated with IgM MGUS patients [As shown in KEGG pathway hsa04514, ls in SS . To the  cancers . We founpatients ,36.ADAM23 up regulation in CTRLs vs. WM and IgM MGUS, but no expression changes between WM and IgM MGUS compared to CTRLs. For this reason, we could assume a possible implication of this gene as a risk of progression from IgM MGUS to WM. However, the deregulation of ADAM23 has a good chance to be implicated in clinical neuropathy presentations in WM as well as in IgM MGUS.Herein, our results have shown the CDHR3 between WM and IgM MGUS; thus, we could suggest its possible role in the risk of progression of IgM MGUS to WM, and even its function still needs to be determined.Moreover, we did not find any expression differences in ITGB5, ITGA2B, ITGB3, THBS1, ACTN1, CAV1, IGF1R, RAPGEF1, VAV3, PTK2, PDGFA) in this pathway which play a role in cell motility (regulation of actin cytoscheleton), differentiation, cell proliferation, and cell survival. In particular, the interaction between membrane receptors  with THBS1, IGF1R with PDGFA, and the plasma membrane protein CAV1 with integrins, activate the Focal adhesion kinase FAK, Src and Shc proteins, to initiate signaling events for the reorganization of the actin cytoskeleton inside the cells (KEGG pathway hsa04510).Among the CAMs, we previously mentioned the integrins, which also take part into the focal adhesion pathway. Our GEP data identified some DEGs  compared to normal LSCs [Previous studies investigated the role of genes involved in the calcium signaling pathway in lymphomas and leukemias as indicated below. The entry of calcium in the cells is due to the presence of an electrochemical gradient across the plasma membrane. A microarray study demonstrated that  B-cells ,44. In amal LSCs .ADRB2 did not show a significant expression difference between WM and IgM MGUS and we could suppose that it might be involved in the progression risk from IgM MGUS to WM  genes by performing RNAseq analysis in mice that lack the TRPC [TRPC belonging to several metabolic pathways such as PI3K-B signaling pathway, cytokine-cytokine receptor interaction, calcium homeostasis, extracellular matrix -receptor, and circadian rhythms in several human diseases. Interestingly, we found a down regulation of TRPC1 in WM vs. IgM MGUS and vs. CTRLs. Thus, we could speculate that the deregulation of TRPC1 gene could play a role in WM. Nevertheless, this needs to be confirmed in future investigations.Recent data showed the possible role of transient receptor potential canonical .The BCR signaling pathway is an integral protein transmembrane complex of B-cells which regulates Ig production, immune response, and autoimmunity and B-cell ontogeny. Antigens link to the BCR antigen receptors such as CD79A, activate the protein tyrosine kinase SYK and a cascade of signals ,49. SYK SYK to promote the survival of MYD88-mutated B-cell lymphoma cells in vitro [PIK3AP1 deletions in acute lymphoblastic leukemia cells [SYK, SOS1, CD79A,PIK3AP1, RASGRP3, and MAP4K1 as DEGs in B-cells. Of note, RASGRP3 and PIK3AP1 did not display any expression differences between WM and IgM MGUS thus, suggesting a possible implication in the risk of progression from IgM MGUS to WM . We have seen the over expression of PF4, PF4V, and PPBP in IgM MGUS and CTRLs vs. WM with high FC, whereas no gene expression differences were pointed out between IgM MGUS and CTRLs, suggesting that the down regulation of these genes was specific for WM B-cells. We could suppose a possible role of these genes in platelet dysfunction in WM because of an interaction between the IgM paraproteins and platelet surface membrane glycoproteins, which can result in the prolongation of the bleeding time and a decrease in platelet adhesion.PF4 and PF4V1 chemiokines bind to CXCR3 receptor and are released during platelet aggregation playing a strong antiangiogenic function. IL17RB in WM patients with MYD88L265P CXCR4WT compared to healthy donors and to WM patients carrying different genotypes [IL17RB in WM vs. IgM MGUS and vs. CTRLs with high FC.Finally, IL17RB takes part in the IL17 signaling pathway as well as in the Cytokine-cytokine receptor interaction pathway. IL17B and IL17E molecules bind to IL17RB in order to control the growth and differentiation of hematopoietic cells through the activation of NF-kappa B signaling pathway. Hunter et al. demonstrated the up regulation of enotypes . AccordiSTAT3) through JAK family genes.The deregulation of JAK/STAT signaling pathway has been largely investigated in the pathogenesis of WM. The JAK/STAT pathway controls several cell processes through signal cascades from the cytoplasm to the nucleus. The cytokine–cytokine receptor interactions, as previously shown, include the binding between growth factors with membrane receptors , which activate STATs genes  were significantly differentially expressed among WM, IgM MGUS and CTRLs B-cells. In line with previous studies, IL6 and FOXO3 were up regulated in WM vs. IgM MGUS. Conversely to a previous study [RAG1 was progressively over expressed in WM vs. IgM MGUS vs. CTRLs and we will further investigate this gene to clarify the disparity shown by our data.Our GEP data highlighted that eight genes  as a mechanism of apoptosis resistance [XIAP in WM vs. IgM MGUS and vs. CTRLs B-cells.Akyurek et al. demonstrated the over expression of sistance . AccordiTP73, CD82 and CHEK1, as significant DEGs in B-cells.P53 signaling pathway is activated by DNA damage, cellular stress, oncogenes, and oxidative processes. We have demonstrated TP73 activation works with a p53 negative feedback whereas CD82 is involved in angiogenesis. CD82 was over expressed in tissue samples of Nodal marginal zone lymphoma patients (NMZL) [CHEK1 (checkpoint kinase 1) is required for checkpoint mediated cell cycle arrest in response to DNA damage or the presence of unreplicated DNA. We have demonstrated that CHEK1 did not show expression differences between WM and IgM MGUS; thus, we could speculate that this gene could be involved in the risk of progression of IgM MGUS to WM  . CHEK1 (US to WM . Our resTJP1 expression in myeloma plasma cells was associated with a better and longer response to protease inhibitors (PI), suggesting this gene as a biomarker in order to identify patients who can benefit from PI-based therapy [TJP1 as progressively over expressed from WM to IgM MGUS to CTRLs with high FC, suggesting its possible role in WM and in IgM MGUS plasma cells which need to be further investigated. As previously shown, we found only very few significant DEGs in the comparison among WM vs. IgM MGUS vs. CTRLs plasma cells, suggesting that this cell population could play a minor role compared to B-cells. However, plasma cells showed the down regulation of genes and pathways mostly involved in cell adhesion, gap and tight junctions in WM vs. IgM MGUS vs. CTRLs with very high FC.Plasma cells represent part of WM tumor cell population. A gene expression profiling study compared WM plasma cells to MM and normal CD138+ cells. The authors identified different expression signatures in plasma cells of WM with respect to MM . Pals et therapy . Our GEPWe collected samples from consenting patients with WM, IgM MGUS, and healthy subjects and written informed consent was obtained from all subjects involved in the study. Among WM patients, 15/36 were asymptomatic, whereas 21/36 were symptomatic. No relapsed WM cases were included in the study. We classified WM and IgM MGUS patients according to the consensus panel recommendations from the second International Workshop on Waldenstrom’s Macroglobulinemia (IWWM) . Regardin = 36) and BM CD138+ (n = 32) cells were isolated from WM, BM CD19+ cells (n = 13) and BM CD138+ (n = 10) cells were selected from IgM MGUS while BM CD19+ cells (n = 7) and BM CD138+ (n = 7) cells were isolated from CTRLs. Baseline patients’ characteristics are shown in We enrolled 36 patients with WM, 13 subjects with IgM MGUS, and 7 healthy subjects used as CTRLs. Among them, BM CD19+ cells  from the BM blood samples  using Ficoll density gradient centrifugation at 800 rpm for 20 min. Immediately after, we selected BM CD19+ cells using Human CD19 MicroBeads; afterward, CD138 cells were positively isolated from the collected CD19− cells using Human CD138 Micro Beads according to the manufacturer’s instructions  .Selected BM CD19+ and BM CD138+ cells were resuspended in 50 μL of RNAlater  and stored at −80 °C until RNA extraction was performed as previously described .Total RNA was isolated from the BM CD19+ and BM CD138+ cells stored in RNAlater using MagMAX 96 Total RNA Isolation Kit (Thermo Fisher Scientific), according to the manufacturer’s instructions. The quality and the yield of the extracted RNA were measured using Nanodrop (Thermo Fisher Scientific).http://dx.doi.org/10.17504/protocols.io.yncfvaw, 19 July 2019). cDNA was hybridized to Affymetrix Human Genome U133 plus 2.0 array using the Gene Chip platform  and signals were scanned by Affymetrix Gene Chip Scanner 3000 according to the manufacturer’s instructions as described in our previous manuscript [We performed microarray experiments on the BM CD19+ and CD138+ cells. cDNA was prepared starting from the previously extracted RNA (50 ng) using Ovation Pico WTA System V2 kit  and Encore Biotin Module Kit (NuGEN) following the manufacturer’s instructions . The boxplots shown in https://cran.r-project.org/, 29 February 2020).The MST in In conclusion, we show that comparative transcriptome profiles of WM vs. IgM MGUS vs. CTRLs allowed to highlight genes and pathways deregulated in B-cells and in plasma cells. Interestingly, we show a common small gene set signature which characterizes WM and IgM MGUS B-cells compared to CTRL B-cells. Based on this gene set signatures, no differences in gene expression were observed between WM and IgM MGUS patients, suggesting new candidate markers in IgM MGUS subjects for the risk of progression to WM.


Childhood poverty is known to be associated with poor health. For youth living in extreme poverty, community-based programs focused on youth development are one strategy to improve health and well-being outcomes. However, very few evaluations of the long-term effectiveness of youth development programs have been conducted.The aim of this study was to assess the long-term effectiveness of a positive youth development program (PYD), serving a segregated housing project with a history of community violence, to improve the health, education, and financial well-being of its alumni.A quasi-experimental causal comparative study design was used to study the effectiveness of the Cabrini-Green Youth Program (CGYP). CGYP alumni (mean: 16.8 +/- 7.4 years after program participation) were surveyed. For comparison, participants from the same housing project who were eligible to participate in the CGYP but did not, were identified.p < .001), less likely to be female , and more likely to have been abused as a child . The majority in both groups reported to be in good to excellent health . After adjusting for comparison group differences, alumni were more likely to have completed college, 24% vs. 12% (adjusted odds ratio (aOR) 2.47, 95% CI, 1.25–4.86), and to end up with some money at the end of the month, 35% vs. 19% .In total, 246/417 (59%) eligible alumni were located. 221 alumni were available to be interviewed; 191/221 (86%) completed the interview survey along with 143 in the comparison group. Both groups self-identified as being Black, African American, and of Other race. Alumni were younger (34.6 vs. 38.1 years, Participation in a PYD program starting at a young age may be associated with reduced poverty in adulthood, possibly aided by higher educational attainment and resultant increased income. PYD may be an effective strategy to supplement evidenced-based poverty reducing policies. This study of a voluntary, community-based PYD program is unique in its up to 33-year follow-up and an outcome assessment that measures more than knowledge change. Child poverty has been associated with poor health throughout the lifespan , 2. PoveIt should be noted at this point that in this paper and for this study, the terms Black and African American are used interchangeably to reflect the self-identified race that program participants identified with most. Latinx is used to denote all people of Hispanic, Latino, or Spanish origin regardless of race. The authors acknowledge that race is a social construct, which is often used to describe visible differences between people but is also used as a means of oppression that largely stems from racism , 22, whiOver the last two decades, the poverty rates for non-Latinx white and Asian youth  have ranged from 10-15%, while rates for non-Latinx Black  and Latinx  youth have ranged from 25% up to 50% or even higher . FamilieYouth who are raised in poor households and communities are at a greater likelihood of living in poverty as adults , 29. DatRacial, residential, economic and social segregation further concentrate the effects of poverty and deprivation . Most BlThe answer most people give for getting youth out of poverty is policy change. However, while government assistance programs and policies to help families move out of poverty have been effective, what is not widely acknowledged is that for the poorest people the current policies, even if they are effective, are insufficient. For instance, in 2019 the Temporary Assistance for Needy Families (TANF), a welfare program, served about 2 million people although that was just 5% of the nearly 40 million people living in poverty. However, that same year only 1.6 million youth received TANF benefits, which translates to only 15% of the 12 million youth living in poverty . WithoutInteragency Working Group on Youth Programs, Positive Youth Development (PYD) is “an intentional, prosocial approach that engages youth within their communities, schools, organizations, peer groups, and families in a manner that is productive and constructive; recognizes, utilizes, and enhances young people’s strengths; and promotes positive outcomes for young people by providing opportunities, fostering positive relationships, and furnishing the support needed to build on their strengths.” [Based on the definition of the engths.” .PYD has its origins in the field of prevention. Prior to the 1990s, intervention programs for youth were primarily focused on preventing problem behaviors before they surfaced, such as teen pregnancy, substance abuse, and juvenile delinquency. In contrast to this traditional approach, which primarily focuses on deficit perspectives about young people, the PYD perspective, which emerged in the early 1990s, applies an asset-based approach that emphasizes “positive development” by focusing on developing assets that enable youth to thrive , 52.As defined, PYD interventions should generally aim to provide youth with education and life skills, opportunities to engage in diverse activities and settings, and positive and sustained relationships with competent caring adults. In the setting of a PYD program, mentoring offers a flexible and adaptive PYD strategy to help youth attain a range of education and life skills. Sustained, supportive and emotionally expressive relationships with non-parental adults have been significantly associated with quality of life since these relationships can impact a range of domains including education, connections to jobs and income as well as physical, mental, and emotional health –55. SociSeveral models and theories to guide and operationalize PYD programs have been suggested and debated. The 5 Cs model defines the competencies that youth need to attain positive development: Competence, Confidence, Connection, Character, and Caring and others have extended this model to 7Cs by including Coping and Control –64. OthePYD has been associated with positive outcomes –70. A reThe aim of this study was to assess the long-term effectiveness of the Cabrini-Green Youth Program (CGYP), a PYD program serving a segregated housing project with a history of community violence, to improve the health, education, and financial well-being of its alumni.This study contributes to the field of youth development in several important ways. This study of the CGYP community-based PYD program showed positive results over 30 years later. The evaluation of a PYD program delivered for over 33 years provides a longer follow-up assessment than most if not all other published long-term evaluations of a PYD program. The findings also highlight return on investment for a program serving Black youth living in a low-income segregated community, which has largely been left out of the PYD literature. A lack of evidence of the long-term effectiveness of PYD programs often prevents continued investment in these important programs.A unique element of the CGYP is that in addition to offering key elements of PYD – skill development, opportunities to engage in diverse activities and settings, and caring relationships with non-parental adults— it provides participants access to a medical home through the CGYP medical clinic. Based on a review of the published literature, no other published descriptions of PYD programs include access to clinical care, and no published evaluation study of a PYD program has included a clinical care component, even though physical health is essential to a child’s ability to attain positive development.This study evaluates the long-term effectiveness of a positive youth development (PYD) program that serves youth from families living in extreme poverty to improve the health, educational, and financial well-being of its participants.The Cabrini Green Youth Program (CGYP) was founded in 1984 to improve the health and life opportunities of youth living in or near the Cabrini-Green Homes, a Chicago Housing Authority (CHA) public housing development. CGYP participants lived in Cabrini-Green until demolition of the housing development in 2011. Many alumni continued to participate in the program even after they moved from the Cabrini-Green Homes; free transportation was provided.CGYP began as a Saturday mentoring program delivered by volunteer Northwestern University medical and law students. During the early 1990’s, CGYP added afterschool tutoring and a medical home in addition to the original Saturday programming. CGYP served children beginning at birth through the CGYP medical clinic, and beginning around age 3 or 4 years, youth participated in age-appropriate reading, tutoring, and recreation programs to meet the needs of the whole child. By linking each of these program elements, the program provided participants with consistent social support.For example, a 6-year-old boy could attend tutoring on Monday, be seen in clinic on Tuesday, participate in a cooking class on Wednesday, and take part in a field trip on Saturday. As the participants matured, educational support included career counseling, college tours, and coaching during college or trade school attendance. Modest college or trade school scholarships up to $3,000 per year were provided. There were no eligibility requirements or cost to participate in this voluntary PYD program. A logic model for CGYP is included as Fig. Alumni were identified from the CGYP administrative data. To be included in the study, alumni had to be born between 1970 and 1995, enrolled in the program at or before age 16 years, and involved for at least two years prior to demolition of the Cabrini-Green Homes in 2011. The alumni were primarily located through referrals from other alumni or staff. In addition, the study team hired a private investigator, used social media, and employed various on-line search engines to identify participants for the study.Using a quasi-experimental causal comparative design, a non-randomized comparison peer group was initially recruited through alumni referral. Each alum was asked to recommend someone about the same age who grew up in Cabrini-Green but did not attend CGYP. Similarly, as comparison participants were identified and interviewed, they were asked to provide names and contact information for additional comparison group members. A few comparison participants were recruited through social media groups that served former Cabrini-Green Home residents. Both former alumni and non-participants were compensated $50. Trained research assistants collected data from both groups between October 2017 and April 2019.The Institutional Review Board of Ann & Robert H. Lurie Children’s Hospital of Chicago approved the study as exempt from ongoing IRB oversight and consent regulations. In accordance with federal regulations 45 CFR 46.104 and 21 CFR 56.104 and institutional review board policies, this study, for which participants were notified that their participation in the survey was voluntary, participants provided informed consent, and participants’ responses were deidentified, was determined to fall under category 2i of the categories of human subject research that are considered exempt from regulatory requirements.Both alumni and comparison participants completed a telephone or electronic survey of previously validated questions. Information about participant years of attendance was extracted from CGYP administrative data.The main outcome measures for this study were self-reported health status, educational attainment, finances, and standard of living relative to their parents at a similar age. Responses were dichotomized for analyses. The first three measures were assessed using questions from the Behavioral Risk Factor Surveillance System (BRFSS) . The staDemographic measures were assessed using questions from the BRFSS, Fragile Families , and theDescriptive statistics summarized demographic and survey variables of interest stratified by program participation. P-values were calculated by a Pearson’s chi-squared test or a Fisher’s exact test in the case of small cell counts. For normally distributed continuous variables, the mean and standard deviation were reported. For continuous, but not normally distributed variables, the median and interquartile range (IQR) were reported. All statistical analysis was performed in R , under an alpha level of 0.05 with no adjustment for multiple hypothesis testing.Logistic regression was used to examine associations between program participation and numerous outcomes. Simple logistic regression models were created for four major outcomes including: health status, college graduation, finances, and standard of living. Each of these outcomes were collapsed into positive and negative responses. The simple regression models included the primary exposure of program participation and the outcome of interest. In addition to the simple logistic regression models, multivariable logistic regression models were constructed to adjust for age, sex, education attainment, incarceration history, and history of physical abuse for the outcomes of health status, finances, and standard of living. For the outcome of college graduation, the adjusted model included all the variables listed above except the educational attainment variable.n = 191). The primary exposure was length of time in the program, treated as a continuous variable. Adjusted logistic regression to control for current age and sex was conducted for the same four outcomes as in the main analysis.Additional analyses were limited to program participants , a relative (N = 26), or a staff member or former volunteer (N = 32) provided contact information for 77% (N = 147) of the alumni who completed the survey. The remaining alumni who completed a survey were located by the following methods: private investigator (N = 11), social media (N = 12), search engines (N = 12), and not specified (N = 9). The majority of the study participants (71%) completed the survey by phone; the other alumni completed the survey online. A total of 171 (41%) former participants were unable to be located despite these extensive search efforts.In total, 191/221 (86%) of available alumni completed the survey : 7.4 years, range 4-33 years). An alum . Among both groups, females were more likely to complete the survey with a higher percentage of comparison group females participating . The alumni also reported experiencing more abuse as a child . Nearly one third (28%) of alumni (N = 54) reported spending time in a correctional facility or on house arrest; 37 (69%) were male. In the comparison group, 19 (13%) experienced incarceration, and among those 16 (84%) were male.Both groups primarily self-identified as Black and African American and reported similar experiences with neighborhood violence while growing up Table . About 8Eighty-three percent of the alumni reported to be in excellent, very good, or good health compared to 74% of the comparison group, odds ratio (OR) 1.73 , 1.02-2.96) , Child Tax Credit (CTC), and Supplemental Nutrition Assistance Program (SNAP) demonstrate the greatest poverty-reducing effects of current major federal assistance programs [The National Academy of Sciences reported in programs . The $1.programs  includedprograms .Ultimately, a key result from this long-term evaluation of the CGYP is the realization that what defines the effectiveness of a PYD intervention may not be as directly related to the program components themselves as much as to how the intervention relates to the structural reality of its participants such that – if nothing in a youth’s environment changes – even if the youth develops assets, will it matter? The limited findings and their implications suggest that the answer is yes. This is a testament not only to the impact that PYD programs like CGYP can make, but to the resilience of the youth themselves.This study is not without limitations. Despite tremendous efforts to track down former participants, these attempts were unsuccessful at obtaining contact information for 40% of the alumni as many were displaced from their homes. However, based on the best available knowledge, the study population included in this study was reflective of the youth who participated in CGYP.Over half (102/171) of the alumni who were unable to be located began the program before there were paid administrative staff, prior to 1993. The pre-1993 attendance data was handwritten and often lacked full names and complete birthdates, which made locating individuals 25 years later from a neighborhood that no longer exists very challenging. By not being able to include these missing alumni’s responses, the results may look more positive than they actually are. However, of the alumni contacted, the survey completion rate was 86%. The efforts required to collect this data were not inconsequential.It also was a challenge to define participation . An alumThis study is also limited by potential selection bias of CGYP participants. Both alumni and non-participants experienced similar amounts of community violence during their youth, but more alumni reported more abuse as a child. On these and other demographic measures, it does not appear that CGYP enrolled only youth who were likely to do well. Any child from the Cabrini-Green area was welcome to join the program, but there may be unmeasured differences between those who joined and those who did not. Thus, alumni were likely to fare better on outcome measures than non-participants with or without the program. Without a randomized controlled trial to evaluate the CGYP intervention, the question of selection bias is not settled. Selection bias in a voluntary attendance program almost certainly exists at some level. CGYP’s impact is likely an interaction of a receptive youth to the intervention of an effective program. Furthermore, due to the observational nature of the study, while associations between CGYP and participant outcomes were identified, these do not imply causal relationships.Future studies to evaluate the long-term outcomes of PYD programs should study the timing of the initiation of PYD programming and the length of service to be able to answer questions such as: What is the minimum length of time a program should be to produce positive outcomes? Future studies also should look more closely at the role of positive non-parental adults to be able to answer questions such as: Who should serve as the adult role models—individuals who are more similar in background to the youth served, different, or both?Recent scientific advances consistently report that exposure to adversity, particularly prolonged and sustained poverty and oppression, including intergenerational transmission, results in “toxic stress” which can affect gene expression and brain development , 138. AsWhile the PYD model has been generally supported by practitioners who develop and lead programs for a range of youth populations, PYD has faced considerable criticism for its primary emphasis on individual level change without a strong emphasis on the contexts that youth live in that can inhibit positive development, especially those most relevant to the lived experiences of Black youth , 141. ThSeveral published papers have stressed the need for PYD to evolve, even in the early years of PYD , 142–146In relation to the evaluation of CGYP, as noted by others the current PYD model limits the examination of the complex social, economic and political forces that impact the lives of Black youth who struggle with poverty and racism . An exteThe findings from this unique long-term study of a 33-year PYD program suggest that participation in CGYP (which has expanded to and continues as the Chicago Youth Programs (CYP)  and is nFor youth living in deep poverty, CGYP may be an effective model of positive youth development, particularly for those who continue to face persistent social inequities. While PYD programs have shifted toward an asset-based approach, this shift has been slower for youth of color and many ongoing efforts still primarily focus on risk-based assessments primarily among programs that include Black youth. Based on the best available knowledge, CGYP was also the first and is still the only PYD program to offer participants access to clinical care. Further studies are needed, and encouraged, to help illuminate the value of PYD for youth of color living in poverty and to reimagine what is possible, perhaps particularly for those youth who routinely experience abuse and witness violence. The hope is that articulating these findings can contribute to interdisciplinary efforts leading to the advancement and necessarily evolution of PYD for Black youth living in poverty who can benefit from them.


Team training interventions to improve team effectiveness within healthcare are widely used. However, in-depth knowledge of how healthcare professionals experience such team training curricula and their implementation processes, as well as how contextual factors impact implementation, is currently missing. The aim of this study is therefore to describe healthcare professionals’ experiences with the implementation of a longitudinal interprofessional team training program in a surgical ward.n = 4), registered nurses (n = 4), and certified nursing assistants (n = 3) was divided into three professionally based focus groups, which were interviewed at three time intervals over a period of 1 year.A descriptive design was applied based on qualitative semi-structured focus group interviews with 11 healthcare professionals. A convenience sample of physicians  was implemented in a surgical ward at a hospital between January 2016 and June 2017. The team training program included three phases: 1) assessment and planning, 2) training and implementation, and 3) sustainment.Healthcare professionals’ experiences with the content of the team training program varied from valuing the different elements of it to seeing the challenges in implementing the elements in clinical practice. A one-day training course was found to be especially beneficial for interprofessional collaboration at the ward. Over time, the nursing staff seemed to maintain their motivation for the implementation of the tools and strategies, while the physicians became less actively involved. Contextual ward factors influenced the adoption and utilization of the tools and strategies of the program both positively and negatively. The healthcare professionals’ experienced the implementation of the team training program as positive for the patient safety culture at the ward in the forms of increased awareness of teamwork and open communication.The study suggests that the implementation of a team training program in a surgical ward is dependent on a set of factors related to content, process, context, and impact. Knowledge on how and why a team training program work supports the transferability to clinical practice in further planning of team training measures.ISRCTN13997367.The study is part of a larger research project with a study protocol that was registered retrospectively on 05.30.17, with the trial registration number The online version contains supplementary material available at 10.1186/s12913-021-06732-6. Interventions to improve team effectiveness within healthcare are widely used . Team trThe current study reports the implementation process of a longitudinal interprofessional team training intervention in a surgical ward based on the Team Strategies and Tools to Enhance Performance and Patient Safety (TeamSTEPPS) program. TeamSTEPPS is an acknowledged, validated, and evidence-based team training program  that hasTeamSTEPPS is designed to improve the quality, safety, and efficiency of health care. A key element in implementing the program is to strengthen the culture of patient safety . PatientA systematic review by Welsch et al. , found tA key question in studying the implementation of team training interventions is whether they are found to be effective or useful in everyday clinical practice by the healthcare personnel who are the main target group for these interventions . QuestioTo our knowledge, this is the first qualitative study in a Norwegian setting that explores how healthcare professionals experience the implementation of the TeamSTEPPS program in a hospital ward. Therefore, the main aim of the study is to describe healthcare professionals’ experiences with the implementation of a longitudinal interprofessional team training program in a surgical ward. The following research question guided the study: How do nurses and physicians in a surgical ward experience the contents of the team training program, the process of implementing the program, the context in which the program is implemented, and the impact of the program on the ward’s patient safety culture? The study is part of a larger research project on teamwork in hospitals , and it The study used a descriptive design based on qualitative semi-structured focus group interviews with healthcare professionals at three time intervals.The implementation of the team training program was carried out in a surgical ward  of a hospital division (200 beds) in a Norwegian hospital trust from May 2016 and June 2017. The surgical ward was selected as the intervention ward due to its motivation for quality improvement and patient safety after recently having experienced several adverse events. The management group consisted of two nurses  and two physicians . The head of the department supported the intervention. The healthcare professionals were organized into two interprofessional teams carrying out patient care. The ward’s bed occupancy rates, patient admissions, and number of full-time equivalent positions are reported in Table n = 4), CNAs (n = 3), and physicians (n = 4). The inclusion criterion was that the healthcare professionals had to have participated in a one-day TeamSTEPPS training course. A total of 41 healthcare professionals participated in the mandatory training. Information about the study and the research team was distributed to all the healthcare professionals, 11 of whom confirmed their participation in the study. The sample consisted of eight women and three men with varying work experiences and employment type within the surgical ward. To ensure the informants’ anonymity, no further background information is provided in the paper.A convenience sample of 11 healthcare professionals (informants) recruited from the surgical ward was divided into three focus groups based on RNs  and 2 hours of high-fidelity simulation, focusing on patient safety and the TeamSTEPPS five key principles. At the end of the course, all healthcare professionals were asked to point out relevant patient safety issues in their clinical practice, and to recommend TeamSTEPPS tools to solve them. After the team training course, a Change Team with a guiding role was assigned and led by the Nurse Unit Manager. The Change Team had members from all ward professions , in addition to the Chair of the surgical department, a former patient, and a researcher serving as a coach. An action plan for the implementation was established, based on the identified patient safety issues at the ward and communicated at unit staff meetings and via email to all employees. Five TeamSTEPPS tools were implemented during the first 6 months of the team training period, launched as “The tool of the month”  were conducted. Three initial focus group interviews were completed with each professional group before the start of the intervention. Four follow-up interviews were conducted after 6 months of the team training program, with three consecutive follow-up interviews being conducted after 12 months. See Table n = 33 min). All the interviews were digitally recorded, transcribed verbatim and anonymized before the analysis.To validate the thematic interview guides, a pilot interview was conducted which generated a new question (experiences related to the TeamSTEPPS refresher courses), resulting in the final version of the guides. Two researchers  conducted the focus group interviews, with one researcher as a moderator and the other as an observer taking notes. All the interviews were conducted in a meeting room at the hospital during the daytime. The interviews started with a clarification of the study’s aims and were conducted as a dialogue in which the informants were encouraged to complete an open-ended collective activity with a reflection on common experiences . The foccontent of the team training program refers to what the informants mean about the specific content of the TeamSTEPPS program, including teamwork skills, tools and strategies. 2) The process of implementing the program refers to how the informants experienced the one-day team training course and the implementation of the program in the surgical ward. 3) The context in which the program was to be implemented refers to where the data were collected and is concerned with the cultural, environmental, or other internal and/or external factors in the surgical ward that influenced the implementation of the intervention. Additionally, 4) the impact of the team training program on achieving a patient safety culture at the ward refers to how the informants experienced the influence of the team training program on patient safety culture in their daily practices.The interviews were analyzed by using a deductive manifest content analysis approach according to Elo, Kyngäs . The fraorganization phase, a structured analysis matrix with columns representing the categories of content, context, process and impact was established. All the data were reviewed for content and were coded according to the four categories first individually by RB and AV. To ensure trustworthiness in the analysis , the patient is just sort of a side scene…and that there is a mistrust towards the healthcare services ingrained in the concept” .The physicians felt that the patients were already included in the team and that they were well informed; this was explained to be part of the surgical work culture. They also pointed to the fact that they themselves learned from the patients.During the program period (six and 12 months after implementation), RNs continued to experience the different components of the program positively. They already knew several of the components from beforehand; however, with designated names given to team training strategies and tools, their care practices were systematized, and their awareness of current team practices increased. During the program period, physicians and CNAs reported that a plethora of the labels on the strategies and tools were confusing, and the CNAs missed the Norwegian terms for the tools. While the CNAs adjusted to the labels over time, the physicians continued to find them difficult to remember. Furthermore, some physicians did not see the training program, with its related strategies and tools, as the appropriate measure for improving patient safety; instead, they referred to an increase in the number of healthcare professionals as the best solution. Related to one of the underlying concepts of the team training program, i.e., “the patient as part of the team”, some of the physicians did not understand the meaning of this in practice, which was expressed by one of them as follows:“When studying medicine, you learn how to do an admission journal, which is in fact quite similar to ISBAR” .The handoff tool was reported to be confusing by RNs and CNAs, which was explained by the fact that the tool was implemented in the last phase of the training program and was therefore not used to its full potential. The debriefing tool was, on the other hand, experienced positively, and the CNAs felt that this tool provided a basis for changes in the ward.Both RNs, CNAs and physicians experienced the team skill of communication as being vital for the training program. The ISBAR and closed loop tools were experienced as essential for improving communication and providing a common way of conducting communication. At the start of the program, RNs had difficulties remembering the ISBAR acronym and what each of the letters referred to. For the physicians, the ISBAR systematics were more common, which was expressed by one of them as follows:The team skill of situational awareness was something that all the participants felt that they already practiced continuously; however, conceptualizing it through the training program helped them become more conscious of it from their own perspective and from a team perspective. The team skill of mutual support was expressed as being especially important by the RNs. They explained that they had always been supportive of each other but that the content of mutual support in the team training program improved their skills in handling positive and negative situations in the ward.As a first step of the implementation process of the team training program, all the participating healthcare professionals experienced the one-day training course as an interprofessional initiative that was seen as very useful for the ward. Throughout the different stages of the process, the nursing staff seemed to maintain their motivation for the implementation of the tools and strategies, while the physicians struggled to keep an overview of the different activities and were less actively involved.Prior to the start of the program, the RNs expressed that by participating, they expected a greater awareness of their own role in teamwork. The physicians felt that they already had good collaboration with the nurses but were humble and acknowledged the fact that there might be issues that they should change to improve. They also expressed a positive attitude towards the simulation-based training.“At the team training course, we learned how to repeat messages, for example, when we answer the phone, but this is something that we already do” .Everyone felt that it was good to come together, and the team training became something that the participants took part in together across professions. An RN stated as follows:“At the team training course, we did not have the attitude that ‘I am the physician doing these tasks, I am the nurse doing these tasks, and I am the CNA so I do these tasks’. It was more a sense of ‘We are in this together, doing it together’" .The RNs were of the opinion that the fact that all of the professionals had an equal starting point regarding the content of the team training program, with no one possessing more knowledge than anyone else, had an impact on the overall climate of collaboration. According to the physicians, this was the first time that they had gathered across professions for a common course. They felt it useful to be together with the RNs and to get to know each other better:“To listen to the nurses and how they perceive the collaboration led to useful reflections on how we do things together, what is good and what can be done differently – that was perhaps the most useful part” .The use of simulation-based team training during the one-day course was well received by both RNs and CNAs. The RNs felt that the simulation-based training stimulated better learning, as it improved their ability to carry out clinical tasks. Many of the physicians had already participated in simulation-based trauma training or other courses either in practice or during their education. However, this was the first time that they conducted simulation-based training together with the nursing staff at the ward. Many had been worried about taking part in these simulations, but as a couple of physicians stated:“Simulation is a challenge if you are doing it for the first time, but eventually, the level of stress is reduced” . “You get emotionally involved quite quickly …and then you are in the situation” .Furthermore, in implementing the team training program in the ward, the RNs felt there were many issues to remember. However, with a focus on a single tool each month (the “tool of the month”), it became easier to internalize the tools and use them in their practices. The Weekly Update, the ward’s digital information channel, was used to focus on the TeamSTEPPS tools and strategies. The physicians expressed that they quickly lost the overview of the implementation of the tools; they felt that the program eventually burned out and that this was unavoidable. Their goal was to catch the basic idea behind the tools. To keep the motivation high, part of the implementation process was to include certain tools at the daily interprofessional patient safety whiteboard meetings:“At the patient safety whiteboard meetings, we use huddling in relation to the redistribution of tasks if someone feels that they have too much to do while others have available capacity… and we use debriefing if there are challenges” .Furthermore, two two-hour refresher courses were held in the ward, in which RNs and CNAs participated and then reported that such courses were important for maintaining knowledge:“The refresher course results in an improved awareness of your actions and how the strategies and tools are labeled in the training program” . “For the knowledge from the team training program to be sustained, you sort of need to work it into your practices so that it becomes routine” .The physicians held a refresher lesson at a morning meeting, but most of the physicians did not have the opportunity to participate.In the follow-up interviews after six and 12 months, the one-day team training course at the start of the implementation was still mentioned as an excellent initiative by both RNs, CNAs and physicians. Some felt that there was too much information included, yet the overall course program was described by the physicians as being concrete and practically oriented and as laying the foundation for fruitful interprofessional discussions. Furthermore, it was seen as positive that the instructors responsible for the course had clinical practice-based work experience at a hospital. The CNAs felt that the training program covered issues they dealt with on a daily basis without personally reflecting on them; thus, the training course contributed to raising their awareness of their own practices with regards to patient safety:The team training program was implemented in a surgical ward in which several contextual factors were registered during the adoption and utilization of the related tools and strategies. These factors were facilitating factors, such as a stable workforce, management support and prior quality improvement efforts, and inhibiting factors, such as high workloads and a lack of coherence with other staff groups and wards. Ward information data from Table “At the start-up of the team training program, it was sort of a leadership-initiated enthusiasm” .The ward had experience with running quality improvement initiatives, and prior to the start-up of the team training program, the ward had implemented patient safety whiteboard meetings and MEWS scoring. The surgical department to which this ward belonged had also started using the Lean methodology a few years ago, with the intention of reducing patient waiting time and improving patient flow and quality. During the team training period, there was a decrease in the number of CNA positions, which was made up for by an increase in the number of RN positions. Ward information data . "By using the handoff tool, you at least have to have enough time to think before writing the report, and that is something that we do not always have, you see" .The RNs were concerned with the time necessary to implement the team training approaches and change their work practices, as these things might be down-prioritized when the ward becomes busy. The physicians also experienced that the summer holidays led to a break in the team training activities and that their overall focus was decreased afterwards. The RNs mentioned the fact that other staff groups, such as ward secretaries, physiotherapists, porters, kitchen and maintenance staff, had not been introduced to the program. The same applied to physicians and healthcare personnel from other wards. They experienced this difference as challenging, i.e., that they as a single ward had received the team training program:“We experience that physicians from other wards who have not participated in the program and learned about the communication tools think that we criticize them when we use the closed-loop tool” .“When a nurse tries for the tenth time to communicate her concern about the patient's pulse being too high and gets the response from a physician from another ward that this is nothing to stress about and refuses to answer the question… then in the end, there is nothing more to do” .During the team training period, changes occurred in the composition of the management group. The head surgeon of the urology section left the position, and the chair of the surgical department moved to another position within the hospital and was replaced by the head surgeon of the gastrointestinal surgery section in 50% of cases, thus reducing the amount of clinical work. The clinical nurse specialist took over the role of leader of the change team since the unit nurse manager was allocated to the position of assistant chair of the surgical department. These changes all affected the management focus of the team training program.All the participants felt that prior to the training program, their teamwork was satisfactory and that the different professions involved knew each other well. The ward had work staff stability, and the physicians felt that the RNs were competent and that proper routines existed for training newly employed nurses. The use of humor when implementing the tools was viewed as positive, and both RNs and physicians described a good atmosphere in the ward during the start of the training program. The implementation of the team training program was management supported, and clear initial messages were given to prioritize participation in the program. One physician commented as follows:ta Table  showed aThe team training program reported experiencing impacts on several properties of the ward’s patient safety culture, specifically those related to team performance, open communication, learning from mistakes, team leadership, and patient-centered care. The impacts on patient safety culture was more prominent among RNs and CNAs than among physicians in the ward.“The team training course opened our eyes about how to communicate with the nursing staff… and what needs to be done to make everyone have a good experience” .However, another physician said:“I do not feel that I got anything in return from the team training course in regard to working in a team, though it might have created an awareness of teamwork among others” .The RNs clearly stated that knowledge regarding teamwork skills and the use of teamwork tools had been useful for promoting patient safety culture at the ward:“As a nurse, I was relieved when ‘my’ mistake was corrected by the use of the closed-loop tool before the patient got hurt” . “With a single tool such as the closed-loop, we have identified miscommunication” .Both RNs and physicians referred to an adverse event that occurred just after the one-day team training course, which concerned an incorrect medication dosage. This event led to a revised procedure based on using tools from the team training program.According to the nurses at the ward, the team training program influenced their clinical practices in a useful manner by externalizing their nonarticulated knowledge regarding teamwork in the care culture. The program created a shared understanding and an awareness of how to work together as a team, thereby creating common work practices. RNs experienced an impact on their awareness of how effective communication influences patient safety, including the ability to set expectations across the professional groups involved. They furthermore experienced that the TeamSTEPPS program contributes to a culture of openness, with an increased focus on mutual support across the professions. The physicians expressed a somewhat different view on open communication and team awareness:The nurse very clearly voiced her opinion about something that was decided against in the procedure, which I as a physician thought was the right thing to do in this case. I then needed to explain the rationale for doing so. In this case, it was legitimate for the nurse to voice her concern in a clear manner” .The CNAs further highlighted the debriefing of the week being conducted at lunch every Friday as a positive contribution to open communication. They reported that it was useful and valuable to talk through the situations they had been through over the course of the week.The physicians experienced that the RNs used the tools from the program in their communication. A physician referred to a situation in which it was clear that a RN disagreed with him, and he reported that this disagreement was communicated in a manner that had been learned from the team training through the use of the two-challenge rule, which was reported as a positive experience:“There are plans for initiatives related to the discharge conversation, where the idea is to get the patient more actively engaged in their information needs, and not focusing solely on the standard letter that everyone receives” .Although the patient safety whiteboard meetings were initiated prior to the team training program, RNs and CNAs reported that the program had contributed positively to the completion of the daily interprofessional meetings, in which tools from the program were used. The RNs experienced that they, as team leaders, received feedback from team members more easily and that morning rounds had become more efficient. Initiatives consisting of dedicated nursing staff being responsible for specific patient rooms, headphones for copatients being provided during physicians bedside rounds, rooms being provided for conversations with patients and their caregivers, and declaration forms being filled out by patients prior to their admission to the hospital had been implemented to involve the patients as part of the team. Other patient initiatives were also in the planning:This study has described healthcare professionals’ experiences with the implementation of a longitudinal interprofessional team training program in a surgical ward at a Norwegian hospital. The study is the first to report qualitative results from implementation of the TeamSTEPPS program in Norway and has therefore had a limited scope and sample. Despite this, the in-depth accounts of healthcare professionals’ experiences with implementation should provide valuable knowledge for the practice field internationally and for the design of future implementation studies on a larger scale. The results according to the content of the training program, the process of implementing the program, the context in which the program was implemented, and the impact of the program on patient safety culture indicate a variety of experiences that provide a comprehensive understanding of the implementation as seen by the nurses and physicians who participated in the program.The findings document that nurses and physicians experienced the ward’s teamwork climate as being good prior to the team training program, which may have been an important factor for the implementation. According to Eddy et al. , the orgDuring the team training program, the nursing staff and physicians were trained together for the first time, and all the healthcare professionals experienced the one-day training course as a successful interprofessional initiative. The reason behind the previous lack of interprofessional training may be the hierarchical structure of healthcare organizations, in which professionalism has traditionally been favored, thereby resulting in professionals working in “silos”  and receThe participants experienced an impact of the team training program on the ward’s patient safety culture in forms of a higher level of awareness about how to work together as a team and openly communicate within and between professional groups. This is also supported by both qualitative  and quanSome issues regarding study limitations should be noted. Data collection dating back to the period of 2016–2017 may affect the timeliness of the results. However, qualitative research on the implementation of team training interventions is mainly missing and we therefore see the study results as a relevant contribution to the evidence base. The limited number of participants and the variation in the focus group sizes may have influenced the results. However, the completion of ten focus group interviews at three time intervals over 1 year combined with contextual ward information provided us with rich data material. Nevertheless, conducting additional partial participant observations could further have strengthened our analysis. The application of a qualitative design restricts the generalization of our study results. However, the results provide an in-depth understanding of health professionals’ experiences with the implementation of a longitudinal team training program that may also offer relevant knowledge for other similar healthcare settings.content of the team training program was experienced as relevant yet complex, more so by nurses than physicians. Furthermore, time and effort were needed for the professionals involved to understand the full range of tools and strategies in the program. The interprofessional focus of the implementation process was experiences as positive, although the nursing staff maintained their motivation throughout the program period better than the physicians did. The context in which the team training program was implemented was characterized by workforce stability and high workloads, the first contributing positively to implementation while the latter caused challenges related to the time and effort needed for successful implementation. Finally, implementation of the team training program was experienced as having an impact on the patient safety culture at the surgical ward through increasing healthcare professionals’ awareness of teamwork and contributing with more open communication among them.According to the experiences of nurses and physicians, the implementation of a team training program in a surgical hospital ward can be described as a comprehensive activity related to the content of the training program, the process of implementation, the context in which implementation takes place, and the impact of the program. The The results highlight how and why a team training program may work supporting the transferability of valuable knowledge to clinical practice in planning team training and supporting sustainability of the training. In supporting sustainability of the team training program we suggest the following actions: Simplification of the team training content to make it easier comprehensible, repetition of team training activities to stimulate motivation throughout the implementation process, and to strive towards workforce stability to secure optimal contextual conditions for the team training program. Furthermore, leadership support and responsibility are vital for the sustainability of the program. To further support transferability and sustainability of the team training program more research is needed.Additional file 1.