Background: The effects of recurrent exposure to disasters on adolescents’ mental health have rarely been studied. We examined the effects of two earthquake experiences 5 years apart in a longitudinal cohort of Chinese adolescents.Methods: A total of 858 adolescents were assessed in September, 2011  and April, 2013 . Participants’ Wenchuan earthquake experiences and symptoms of post-traumatic stress disorder (PTSD) and depression were assessed at T1, and their Ya’an earthquake experiences, Acute Stress Disorder (ASD), PTSD, and depression were assessed at T2.Results: Structural equation models showed a positive relationship between Ya’an earthquake experiences and symptoms of ASD, PTSD, and depression at T2. T1 PTSD symptoms significantly increased T2 ASD, PTSD, and depression symptoms, and also mediated the relationships between Wenchuan earthquake experiences and T2 ASD, PTSD, and depression symptoms. T1 Depression symptoms also significantly increased T2 ASD, PTSD, and depression symptoms, but only mediated the association between Wenchuan earthquake experiences and T2 depression symptoms. In addition, Wenchuan earthquake experiences moderated the effects of Ya’an earthquake experiences on ASD symptoms and PTSD symptoms but not depression.Conclusion: Repeated to exposure to disasters have adverse additive effects on adolescents’ mental health. Adolescents who experience one disaster may be sensitive to the negative impact of subsequent ones. At 08:02 Beijing Time (00:02UTC) on April 20, 2013, an earthquake with a magnitude of 7.0 on the Richter scale struck the Ya’an County, Sichuan Province, China, the same region devastated by the Wenchuan earthquake on May 12, 2008. The Ya’an earthquake resulted in 196 people dead, 24 missing, at least 11,826 injured with more than 968 seriously injured. A large number of houses and buildings were destroyed, and the estimated direct economic loss was over 85 billion RMB. About 1.5 years before the Ya’an earthquake, a cohort of senior high school students was surveyed to assess long-term psychological sequelae of the Wenchuan earthquake. The occurrence of the Ya’an earthquake thus provided a unique opportunity to examine effects of repeated exposure to disasters on adolescents’ mental status.Major disasters such as earthquake could cause myriad mental health problems , especiaTwo possible response patterns have been documented among individuals repeated exposure to disasters: sensitization  and habiUsing a longitudinal sample of adolescents, we examined psychological reactions to Ya’an earthquake on adolescents exposed to Wenchuan earthquake. Based on previous studies , we hypoFigure 1. In Dujiangyan, the Wenchuan earthquake resulted in 3,069 deaths, 4,388 injuries, and 429 missing. A large number of adolescents were directly exposed to the disaster. In the Ya’an earthquake, only one people was reported dead in Dujiangyan, yet it was strongly felt in this area. When the Ya’an earthquake happened, students of the participating high school were having classes and were evacuated urgently to school playground. The evacuation was rather chaotic and many students showed strong stress reactions.Participants were 858 students  recruited from one high school in Dujiangyan, a city affected by both Wenchuan earthquake and Ya’an earthquake. The geographical location of Dujiangyan in relation to the two earthquake epicenters is depicted in 2 = 5.10, p = 0.28), house damage , property loss other than house , witness or hearing of tragic scenes , PTSD symptoms  and depressive symptoms  at T1 between participants who completed both surveys and those who not. However, females were more likely to drop out than males .In September, 2011 (T1), 3.5 years following the Wenchuan earthquake and 1.5 years before the Ya’an earthquake, a sample of 1,036 students were initially measured to assess the long-term mental health outcomes of the Wenchuan earthquake. All the students in grade 10th were sampled and there was no exclusion criteria. In April, 2013 (T2), about 1 week following the Ya’an earthquake, a total of 858 students participated in the follow-up survey. In this study, data of participants who completed both surveys was reported. There was no statistical differences in death, missing or injury of family members ; house damage ; property loss ; and witness or hearing of tragic scenes . The internal consistency of four items measured by Cronbach alpha was 0.65.The participants’ Ya’an earthquake experiences were measured by four items at T2: (1) How chaotic did you feel about the evacuation when the earthquake happened? “1 = very much, 2 = moderately, 3 = slightly, 4 = not at all”; (2) How panicky or scared did you feel when the earthquake happened or during the evacuation? “1 = very much, 2 = moderately, 3 = slightly, 4 = not at all”; (3) In your opinion, how panicky or scared did your peers feel when the earthquake happened or during the evacuation? “1 = very much, 2 = moderately, 3 = slightly, 4 = not at all”; (4) How often were you worried about the occurrence of another earthquake? “1 = always, 2 = often, 3 = occasionally, 4 = never.” The internal consistency of four items measured by Cronbach alpha was 0.72.The Stanford Acute Stress Reaction Questionnaire (SASRQ) was used to measure acute stress responses to the Ya’an earthquake at T2 . The SASr = 0.87) and internal consistency  among Chinese adolescents  was used to assess depressive symptoms at T1 and T2 . The DSRFigure 2C. Third, the interaction term of the two latent variables created using the Mplus XWITH function was added into the three basic SEMs. Finally, if the interaction term was significant, Mplus model constraint function was used to compare differences between two sexes in the interaction term.In order to examine the study hypotheses, longitudinal structural equation models (SEMs) were performed in Mplus 7.4 . Accordi2), the Comparative Fit Index (CFI), the Tucker-Lewis Index (TLI), and the Root Mean Square Error of Approximation (RMSEA). According to 2, generated by comparing -2log-likelihoods indicates that including the interaction term improved model fit. Wald Test was used to examine differences between sexes in the interaction of two latent variables.The models without interaction term were assessed by Chi square . The mean ages of participants were 11.4, 15.4, and 17.2 (SD = 0.58) years at Wenchuan earthquake, T1 and T2, respectively.The demographics, Wenchuan earthquake experiences and Ya’an earthquake experiences are presented in Table 2. There were significant correlations among most study variables. The correlations of sex with property loss and witness of tragic scenes during Wenchuan earthquake and chaotic evacuation during Ya’an earthquake were not significant. The correlations of death, missing or injury of family members and witness of tragic scenes during Wenchuan earthquake with T2 depression symptoms were not significant.The correlation matrix of study variables are provided in 2 = 131.15, df = 19, CFI = 0.97, TLI = 0.95, RMSEA (95% CI) = 0.08 (0.07–0.09). The factor loadings were above 0.5, except for witness of tragic scenes for Wenchuan earthquake experiences, and the two latent variables were related. The three basic SEMs produced adequate fit to the data: model for T2 ASD symptoms, χ2 = 197.03, df = 37, RMSEA (95% CI) = 0.07 (0.06–0.08), CFI = 0.96, TLI = 0.94; model for T2 PTSD symptoms, χ2 = 211.44, df = 37, RMSEA (95% CI) = 0.07 (0.07–0.08), CFI = 0.96, TLI = 0.93; model for T2 depression symptoms, χ2 = 183.02, df = 37, RMSEA = 0.07 (0.06–0.08), CFI = 0.96, TLI = 0.94. The latent variable interaction models for T2 ASD  and PTSD symptoms  fitted the data well, but not the interaction model for T2 depression . The Wald test of sex differences for T2 ASD  and PTSD  was not significant.The confirmatory factor model for Wenchuan earthquake and Ya’an earthquake experiences was acceptable, χp < 0.01), depression symptoms , and Ya’an earthquake experiences  significantly predicted T2 ASD; Wenchuan earthquake experiences significantly predicted T1 PTSD  and depression , but not T2 ASD ; T1 PTSD  and depression  significantly predicted Ya’an earthquake experiences; Wenchuan earthquake exposure covaried with Ya’an earthquake exposure , T1 PTSD covaried with T1 depression . For T2 PTSD: T1 PTSD  and Ya’an earthquake experiences  significantly predicted T2 PTSD, but T1 depression did not predict T2 PTSD ; Wenchuan earthquake experiences significantly predicted T1 PTSD  and depression , but not T2 PTSD ; T1 PTSD  and depression  significantly predicted Ya’an earthquake experiences; Wenchuan earthquake experiences covaried with Ya’an earthquake experiences , T1 PTSD covaried with T1 depression .The path coefficients of basic models (without interaction) for T2 ASD and PTSD are summarized as follows. For T2 ASD: T1 PTSD  and depression symptoms  and Ya’an earthquake experiences  significantly predicted T2 ASD symptoms. The interaction of Wenchuan earthquake experiences and Ya’an earthquake experiences  also significantly predicted T2 ASD symptoms . There was a significant indirect effect of Wenchuan earthquake experiences on T2 ASD symptoms via T1 PTSD symptoms, but not via T1 depression symptoms.The path coefficients of final models are presented in Figure 2B presents the final model for T2 PTSD symptoms. All variables significantly predicted T2 PTSD symptoms . There was also a significant indirect effect of Wenchuan earthquake experiences on T2 PTSD symptoms via T1 PTSD symptoms, but not via T1 depression symptoms.Figure 2C. As we can see, T1 PTSD  and depression symptoms  and Ya’an earthquake experiences  significantly predicted T2 depressive symptoms. There were significant indirect effects of Wenchuan earthquake experiences on T2 depression symptoms via T1 PTSD and depression symptoms.The model for T2 depression symptoms without latent variable interaction is shown in This study examined mental health outcomes of recurrent experiences of serious natural disasters among Chinese adolescents. The strengths of this study include the longitudinal design, relatively homogenous sample, assessment of the prior disaster-related mental health problems, and analysis of multiple mental health outcomes including ASD, PTSD and depression symptoms. The results demonstrate that repeated experiences of disasters have adverse additive effects on adolescents’ mental health. The findings also provide empirical support for stress sensitization effects – an interaction between Wenchuan and Ya’an earthquake experiences – in liability to ASD and PTSD.Dujiangyan is located 80 km south of Ya’an earthquake epicenter. Despite personnel casualty and economic loss were not very high, the earthquake was strongly felt in this area. Thus, we assessed subjective disaster-related experiences among adolescents. The results showed that over 50% of participants felt very much and moderately scared when the earthquake happened and over 85% worried about the occurrence of another earthquake. Prior research indicated that subjective traumatic experiences played important roles in development of PTSD with effect sizes ranging from medium to large . In the Prior trauma exposure could impact persons’ stress responses and mental adaptation processes to later traumas . In the Consistent with the stress sensitization hypothesis , we founIt is interesting to note that the stress sensitization effects were present for ASD and PTSD but not for depression in this study. This disease–specific relationship may be related to abnormal HPA axis function or changes in specific neural circuitry following disasters . In respIn this study, the effect size of stress sensitive seemed to be small, with the interaction term contributing to approximately 1–2% of the variance of Ya’an earthquake-related ASD and PTSD symptoms. There are two possible explanations. First, Wenchuan earthquake experiences, Wenchuan earthquake-related mental health problems, and Ya’an earthquake experiences were controlled, each of which independently predicted ASD and PTSD symptoms following the Ya’an earthquake. Second, students in the current study experienced slightly objective exposure to the disaster, which may lessen the possible sensitive effect. It should be note that sensitization effects were particularly large among individuals with high level of prior trauma exposure. These individuals may be high risk population of mental health problems. The little increase symptom would be the last straw that overwhelms the camel.Several limitations of the current study should be acknowledged. First, the experiences of the two earthquakes was retrospectively reported, this may introduce biases. We eliminated the possible memory cofounding by using relatively objective items to measure the Wenchuan earthquake experiences and assessing the Ya’an earthquake experiences with short time interval following the earthquake. Second, the Ya’an earthquake experiences and Ya’an earthquake related psychiatric symptoms were assessed at the same time, this also may introduce biases. Third, the data of pre-Wenchuan earthquake psychiatric status and childhood adversities were not available, which may impact the participants’ responses to the two earthquakes. Future studies can examine the additive effects of childhood adversities and disaster exposure on mental health. Fourth, this pre- and post-design study only followed up adolescents one time. One study reported that stress sensitization occurred among adult survivors after 1 year but not 4 years following a disaster . The queFG was involved in data analyses and preparation of the manuscript. FF participated in study design and preparation of the manuscript. YZ and YL commented on and revised the manuscript. All authors read and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Despite these benefits, such services are not universally available. We designed and evaluated a national home-based CR (HBCR) program in the Veterans Health Administration (VHA). The primary aim of the study was to examine barriers and facilitators associated with site-level implementation of HBCRThis study used a convergent parallel mixed-methods design with qualitative data to analyze the process of implementation, quantitative data to determine low and high uptake of the HBCR program, and the integration of the two to determine which facilitators and barriers were associated with adoption. Data were drawn from 16 VHA facilities, and included semi-structured interviews with multiple stakeholders, document analysis, and quantitative analysis of CR program attendance codes. Qualitative data were analyzed using the Consolidated Framework for Implementation Research codes including three years of document analysis and 22 interviews.Comparing high and low uptake programs, readiness for implementation , planning, and engaging champions and opinion leaders were key to success. High uptake sites were more likely to seek information from the external facilitator, compared to low uptake sites. There were few adaptations to the design of the program at individual sites.Consistent and supportive leadership, both clinical and administrative, are critical elements to getting HBCR programs up and running and sustaining programs over time. All sites in this study had external funding to develop their program, but high adopters both made better use of those resources and were able to leverage existing resources in the setting. These data will inform broader policy regarding use of HBCR services. Despi< 0.001) . VHA has< 0.001) , 6, inclTo address access issues and low attendance rates at on-site CR programs, investigators have evaluated home based CR (HBCR) programs. Differences in patient outcomes between home and on-site CR programs are minimal for risk factor modification, mortality, quality of life, clinical events, and costs –11. HoweGiven the evidence of the efficacy of CR, the effectiveness of HBCR programs, and access limitations to on-site programs, we developed, implemented, and evaluated a 12-week telephone/video-delivered HBCR program at the Iowa City Veterans Affairs Health Care System (ICVA). The program was structured to parallel on-site programs, spanning over 12 weeks. It provides patients with exercise prescription, education about their disease, medication compliance and heart healthy diet, assistance with tobacco cessation and psychosocial support. Program staff also relay any concerns or issues directly to the patient’s primary physician or cardiologist. Standardized clinic names and codes and note templates were developed in order to standardize documentation and facilitate retrieval of data for evaluation  framework in this study  . The CFSixteen VAMCs participated in implementation over a 3-year period. We used documents from interaction with the sites to reflect the day-to-day implementation activities, barriers encountered, and discussion of potential solutions. Minutes were maintained for all monthly meetings, and all emails sent to or received by the external facilitator about the HBCR program were saved in electronic files .cfirguide.org). Questions addressed individual, organizational, cultural, and social factors that may influence support for HBCR. Site facilitators identified potential interviewees. Interviews lasted 8 to 92 min (average of 32).To obtain a broader range of perceptions related to workflow processes, barriers, and facilitators to HBCR implementation at the organizational level, semi-structured telephone interviews were conducted with local VHA clinical leadership, providers, and program staff at a sample of nine geographically diverse HBCR sites across a range of uptake. An interview guide was developed using questions derived from the suggested interview questions provided by the CFIR wiki site , including VHA inpatient and outpatient encounter files and Purchased Care files. National VHA files were used to identify all patients with an inpatient diagnosis of acute MI, undergoing PCI, or CABG surgery, the primary indications we used for the HBCR program. To assess CR participation following these qualifying events, we estimated the number of unique patients at each participating site who had an event in the first full fiscal year after the site entered into the study and who underwent one or more CR sessions at or paid for by the same site within 12 months after the qualifying event. Participation was categorized by 1) no participation, or attendance at one or more of the following: 2) VHA on-site CR programs; 3) non-VHA on-site CR programs; or 4) VHA home -based CR program.Domain IV. Characteristics of Individuals as this implementation was focused on the organizational level. We added an additional category under External Setting  to describe communication occurring with outside organizations that may include other VHA facilities. Other modifications were made to the CFIR structure during the coding process. Under Inner Setting we created three sub-codes for this category: Program Characteristics, Organization Characteristics and Program Development. Under “External Change Agent” added “advice codes” to reflect advice sought and provided to implementation sites by the external facilitator. To ensure reliability in data coding, investigators coded the same emails/meeting minute transcripts and then met to examine the extent to which codes overlapped or diverged. The consensus approach was used to determine the final codes for analysis. Coding of interview transcripts was conducted in a similar fashion. Once initial coding was complete, data were then scored according to the influence of each CFIR category on implementation success [All textual data were uploaded in MAXQDA, a qualitative software program for data management and analysis. The unit of analysis was the organizational level. Qualitative data were analyzed using the CFIR coding framework modeled on prior evaluations. A priori, we made the decision to use all CFIR domains except  success , 20 usinn = 2829 (46%) from emails and meeting minutes (excluding the advice segments); n = 1525 (25%) from interviews; and n = 1851 (30%) advice from external facilitator found in emails and meeting minutes.The 16 HBCR implementation sites ranged from small rural facilities to urban tertiary care centers (Table n = 7), medium (n = 4), and low (n = 5) adoption facilities using natural cut points in the data , HBCR participation . Table . We used the influence ratings to provide an estimate of the magnitude (positive or negative) of each construct. Only high and low uptake sites are included in this analysis.Facilities were grouped into high , using it presented challenges.However, low uptake sites did express the helpfulness of the provided information, both from the initial training and information on the SharePoint.Process factors, including Planning, champions and opinion leaders were also more prevalent at high adoption sites. High adoption sites engaged in active program planning. Although low adopters did spend time planning, the process was often much slower at these sites. Opinion leaders at high adopter sites were more engaged with the process of implementation. Low adopter sites encountered difficulty engaging opinion leaders.Finally, high adopter sites typically had local champions to help move implementation forward. At high adoption sites, support from providers, particularly local cardiologists, was key in success. However, low adoption sites often exhibited changes in leadership  that led to a lack of champions. For example, one site had a very supportive Chief of Staff, who initially championed the program. However, after he left, support was not provided.The frequency of Advice codes was also different between high and low uptake sites. In the high uptake sites, requests for advice ranged from 18 to 35 per year (average 24/site/year). In low uptake sites, requests ranged from 9 to 24 per year (average 16/site/year).Comparing high and low uptake programs, readiness for implementation , planning, and engaging champions and opinion leaders were key. Analysis of the external facilitator’s emails also indicated that advice was frequently needed on funding, structural characteristics, using available resources, and access to knowledge and information. High uptake sites were also more likely to seek information from the facilitator, compared to low uptake sites.There were few adaptations to the design of the program at individual sites. All sites used the same electronic medical record and patient program materials. The most common adaptation was the profession of the local site facilitator, e.g., although the external facilitator was an exercise physiologist, some sites chose to use registered nurses or physical therapists. Site facilitators and interview participants were very positive about the design of the program, the helpfulness of the external facilitator, and acknowledged that the program met patient needs for access to care. Because the VHA uses one EMR, sharing note templates and clinic codes across all sites facilitated standardized data entry formats and accessing clinic data for program uptake estimates. Thus, standardized data entry approaches and common clinic codes across the country will facilitate evaluation of data contained in the database.Successful sites demonstrated both strong administrative and clinical leadership, particularly from cardiologists involved in program implementation. These physicians championed the program and communicated with hospital leadership about the importance of the program. Low uptake programs often exhibited inconsistent leadership, i.e., frequent changes in leadership, departure of a supportive physician leader who was then replaced by a less supportive or non-supportive leader. One low adopter site spent the first 10 months in planning activities, and had difficulty implementing the program.High uptake sites appeared to both have greater available resources and were better able to leverage local resources to facilitate program implementation. Successful sites often used existing support staff such as nutritionists, and took advantage of available technology, i.e., secure messaging, to improve efficiency of weekly visits. While space was a potential barrier, high uptake sites developed workarounds to address the space problem. For example, at one site, the lack of space was addressed by allowing HBCR providers to work from home (telework) to implement the program.All sites had access to the SharePoint site for program toolkit materials and were invited to on-site training. While all programs found these sources of information very helpful, low uptake sites had greater difficulty taking advantage of this information. Furthermore, high uptake sites were more likely to seek out additional sources of information, such as professional society websites, to augment program materials, as well as advice and information from the external facilitator.Since these data were collected, the national program has grown to 28 sites, including 9 spoke sites. Hub sites, typically larger sites, provide HBCR program services to patients enrolled at mostly smaller, rural (spoke) sites who do not have a large population of patients for a full HBCR program. A recent analysis of CR within the VHA found that Veterans hospitalized at a facility with a HBCR program were 3 to 4 times more likely to participate in HBCR relative to an on-site VA program or non-VA program respectively . Our iniThere are limitations to the study. The study was conducted within VHA facilities limiting external validity. Outside the VHA, differences in electronic records, human resources, finance, organizational climate, and processes will require “ground up” design and implementation. We do not report clinical outcomes, including adverse events. Grouping of sites by adoption levels may be viewed as arbitrary. Document analysis data were not created for purposes of research and thus are not as rigorous as interviews or focus groups, and important factors may go unmentioned. Although HBCR is more accessible, our program had low referral and enrollment rates, which is a long-standing issue in cardiac rehabilitation programs –26. LastUnderstanding how each VAMC implemented HBCR in their network, the role of facilitation in guiding program development, and local adaptations to program operation provided insight into initial and sustained acceptance of HBCR among a variety of stakeholders. Like other implementation efforts , 28 consMost program implementation in health care settings is driven by a “top-down” (push) approach. This study adds to the implementation literature by examining factors associated with implementation using a “bottom-up” (pull) approach. Thus, these data provide critical information for healthcare institutions to begin to close the gap in access to CR services for patients regardless of where they reside. These data will also inform broader policy regarding use of HBCR services.


N = 1447) of a community-based parenting program, delivered at two levels of intensity  conducted in Victoria, Australia. Individual (parent and family) factors and program factors were assessed by parent report and administrative records, and contextual factors by area-level population statistics. Data were analysed using multilevel logistic or linear regression models. Individual and contextual factors predicted enrolment, while family and program factors were more influential on program retention and parents’ active involvement. Provision of individualised support was important to all forms of engagement, particularly for families experiencing the greatest barriers to participation. These findings indicate that different strategies are required to effectively support families in the processes of enrolling, continuing to attend and actively participating in early intervention programs.Poor participant engagement undermines individual and public health benefits of early intervention programs. This study assessed the extent to which three types of engagement  were influenced by individual, program and contextual factors. Data were from a cluster randomised controlled trial (The online version of this article (10.1007/s11121-018-0897-2) contains supplementary material, which is available to authorized users. Governments in developed countries are investing in early intervention and prevention programs to enhance the life chances of developmentally vulnerable children. Paradoxically, family risk factors that contribute to children’s vulnerability  are also associated with increased likelihood that parents will not enrol, actively participate or remain in prevention programs for their full duration  parent education groups for parents of infants and via facilitated parent-child playgroups for parents of toddlers  or the group program accompanied by six home coaching sessions designed to strengthen the uptake and application of skills within the home .The current study extends this work to investigate the impact of individual, program and community contextual factors on parent engagement with We made the following hypotheses. Firstly, as there was a strong focus throughout program development and staff training on tailoring to the needs of vulnerable families, we expected that parent/family indicators of disadvantage would not influence engagement for those parents who attended. We therefore hypothesised that parent/family factors would be related to poorer initial enrolment as found in previous studies, but would not be associated with poorer retention and involvement. Second, we hypothesised that fewer participation barriers, more favourable program factors and less community-level disadvantage would be associated with greater retention and involvement.Individualised home coaching as an adjunct to the group program provided the opportunity for home coaches to encourage parental participation in the groups. However, this combined group plus home-based approach had not been used before by the services, and they expressed two concerns that this could reduce enrolment due to parents’ reluctance to have someone in their home, and that those who received home visits might not see a need to go to the group as well. We therefore explored whether home coaching had unintended adverse effects on enrolment, attendance and involvement.smalltalk in the MCH service for parents of infants aged 6–12 months (infant RCT) and in the facilitated playgroup service for parents of toddlers aged 12–36 months (toddler RCT). Twenty-two local government areas (LGAs) in the state of Victoria were funded to provide these programs, which were established as new offerings within the LGAs’ suite of early childhood services. LGAs nominated service delivery locations which were then randomly allocated (within LGA) to provide smalltalk group-only, smalltalk plus, or an alternative group program with no smalltalk content. The current paper examines the two smalltalk arms of the trial (i.e. excluding the control group arm). smalltalk programs were delivered at 77 locations across the 22 LGAs: 38 locations provided smalltalk group-only and 39 locations provided smalltalk plus. Most locations employed a single facilitator who ran multiple consecutive groups.Data were collected as part of a government-funded evaluation  and in-home assessment, repeated 10 weeks later after program completion . For the analyses of retention and involvement .For the analyses of enrolment see Fig. , the samenrolment defined as attending at least one group session (yes/no) and retention calculated as the proportion of sessions attended by the parent. Involvement was a summed score derived from facilitator records for each of six parenting strategies of whether the strategy was (i) discussed with the parent (‘exposure’), (ii) rehearsed by the parent in the group (‘application’) or (iii) practiced by the parent at home .Parent engagement was recorded by group facilitators at the end of each group session using a purpose-designed booklet. Weekly attendance records were used to derive measures of Parent and family characteristics were those factors specific to the family that could be assessed prior to commencement of the program and had the potential to impact on engagement. They included demographic factors, adverse life events, parenting self-efficacy, psychological distress and use of other services. These were assessed at baseline via a telephone interview.Table Participation barriers were the parents’ subjective reports of the things that prevented or made it difficult for them to attend the program. These were assessed using a checklist of three types of common barriers , previously found to differentiate high and low attending families  at ± 1 was > 89%. Facilitators also recorded whether they had contact with any family between sessions. Facilitator demographics, knowledge, confidence and preparedness to deliver the program were also conceptualised as program factors. These were assessed by facilitator questionnaires completed before and after training in program delivery. Session quality and facilitator characteristics assessed using these measures have been shown to impact on program outcomes  and the Australian Early Development Census (AEDC sus AEDC .N = 22) was accounted for.Statistical analyses were conducted using Stata version 13.1  were predominantly mothers (98%), and ranged in age from 17 to 62 years . There were similar numbers of male and female children in the sample , with a mean age of 8.0 months (SD = 2.2) in the infant trial and 22.6 months (SD = 7.2) in the toddler trial. Most children were from two-parent families , with Australian-born parents (77%) who had completed year 12 or equivalent (87%). The majority (84%) experienced one or more risk factors for poor development .Parents who completed baseline measures , and the majority spoke English at home (81%). Twenty percent were certificate qualified; 40% had a university degree . Two thirds had previously run playgroups or parenting groups (67%).Fifty-eight staff were trained as n = 568 of 629, 90% in the infant platform; n = 764 of 818, 93% in the toddler platform). Multilevel logistic regression models were used to identify parent/family factors associated with enrolment. Participation barriers and program factors were not included in the models, as parents could only be exposed to these after having attended the program. Unadjusted (univariate) models are available online . A similar trend was evident in the toddler platform . In the infant platform, young parenthood  and receipt of government benefits as the main source of family income  were lower amongst those who enrolled compared to those who did not. There were no significant parent/family predictors of enrolment in the toddler platform.The majority of parents who consented to participate and completed the baseline telephone interview went on to ‘enrol’ as defined by attending at least one group session  and one program factor (greater facilitator contact between sessions).For the For involvement, intraclass correlations (ICC) were high, particularly at the group level (range 0.50 to 0.71), indicating that participants within the same group were highly correlated with respect to their involvement. This contrasts with retention where there were lower levels of clustering within groups (range 0.00–0.04) and facilitators (range 0.04–0.16).p = 0.015) and higher community rates of child language and cognitive vulnerability . Higher enrolment was associated with greater neighbourhood socio-economic advantage . No associations were found between community factors and the measures of parent retention or parent involvement.To examine community-level contextual factors, data were combined across the infant and toddler platforms. Lower enrolment was associated with higher community levels of long-term parent unemployment . These rates compare favourably with other approaches which have reported poorer enrolment . This may offer a ‘softer’ less threatening entry point, allowing parents to feel that they can turn up and see what it is like without necessarily committing to the full program.The lower enrolment by young parents and those on government benefits in the infant platform suggests some unique challenges for these parents that were not evident in the toddler platform. There are several possibilities. This difference could reflect how difficult it is for parents of very young children, despite their best intentions, to attend appointments outside the home. Additionally, the infant smalltalk plus) were more than twice as likely to proceed to enrolment than those allocated to the group-only condition, even though the home coaching had not yet started. smalltalk plus parents had a research assessment conducted by their home coach prior to starting the group; this was conducted by research staff for group-only parents. It is likely this initial contact with the home coach served as an ‘ice breaker’ to program commencement.Families recruited to home coaching programs , logistic  and the program (did not believe child was benefiting) difficulties were associated with lower retention and involvement. This was most evident for retention in the group-only programs (both platforms) and to a lesser extent, involvement. This highlights the compound nature of the multiple challenges facing disadvantaged families and lends weight to the argument that in addition to some families being hard to reach, some programs are hard for families to access  predicted lower levels of active parent involvement. It appears that an older facilitator did not deter parents from attending, but may have made them reluctant to practice skills in the group setting. It is also possible that older facilitators are accustomed to more didactic methods of instruction which allow less opportunity for active parent participation.Previous studies have highlighted the importance of a skilled workforce for engaging families Supplemental Table 2(DOCX 33 kb)Supplemental Table 3(DOCX 34 kb)


With the convergence of various broadcasting systems, the amount of content available in mobile terminals including IPTV has significantly increased. In this paper, we propose a system that enables users to schedule programs considering both section video clips and full video clips based on the user detection method with similar preference. And, since the system constituting the contents can be classified according to the program, the proposed method can store a program desired by the user, and thus create and schedule a kind of individual channel. Experimental results show that the proposed method has a higher prediction accuracy; this is accomplished by comparing existing channel recommendation methods with the program recommendation methods proposed in this paper. With the convergence of broadcasting and communication, the number of broadcasting programs that can be consumed in user TV terminals has significantly increased. In addition, through the provision of various contents such as live TV channels, IPTV services, or TV portals, the amount of program content available to users on TV terminals has greatly increased. One way for users to watch their favorite broadcast program contents is to search for program contents or through automatic recommendation . In the In this paper, we propose an automatic recommendation algorithm based on collaborative filtering. The proposed system consists of offline and online calculation processes.The proposed system understands the user’s tendencies considering the characteristics of real-time and VOD videos of the IPTV, recommends the optimal program to users with similar tendencies, and enables unique program scheduling based on this. Also, it is possible to recommend videos to the user considering both section video clips and full video clips.This paper is structured as follows. In Chapter II, we first examine the content filtering approach and the collaborative filtering approach, which have both been previously studied. In Section III, we propose a new TV program recommendation algorithm. Section IV describes the experimental results and analysis. Section V presents the conclusions of this paper.In this section, we describe the existing research related to this paper. Section A explains the content-based approach and Section B explains the collaborative filtering technique.The content-based approach is a system based on information retrieval technology. It analyzes the similarity between items and user preference by directly analyzing item content and recommending items to the customer based on this analysis –6.In the content-based approach, the past purchase history or profile information of the target is used to determine the preference of the recommendation target. In this case, since such an approach requires only the independent information of the customer, it is a recommendation technique that can be useful even when the information for other users is insufficient. However, if the preference through past purchasing history is required, there must be a sufficient number of item evaluation scores to create the recommendation. If the past purchase history is insufficient, the performance of the recommendation cannot be guaranteed.If the purchase history and the profile information do not exist, the recommendation system of the content-based approach cannot be implemented , 8. In aCollaborative filtering is one of the most commonly used recommendation systems –14. It hCollaborative filtering is a method of predicting the preference based on the similarity between users or items, specifically the premise that ‘customers with similar preferences for a particular item will show similar preferences for other items.’ While the content-based approach predicts estimates depending only on user and item information, the most important difference of collaborative filtering is that user preference is predicted using item evaluation information . It is pCollaborative filtering can be divided into memory-based collaborative filtering and model-based collaborative filtering , 17. MemIn this chapter, we first describe the features of collaborative filtering, and then describe memory-based collaborative filtering and model-based collaborative filtering.The most commonly used method in the Collaborative Filtering (CF) method is Matrix Factorization (MF) , 21. In In collaborative filtering, a user-item matrix is used to predict the preference of the recommendation target customer, and a matrix value indicates the degree of satisfaction of the user with respect to the item. This is illustrated in cold start’. Also, if there is no score as in the ‘Item 4’ column, indicating it has not been purchased yet, it cannot be recommended until someone provides a score. Problems caused by the lack of data are collectively referred to as data sparseness. Various studies have been conducted to solve these problems [In problems –24. As nproblems . In addiproblems .In order to solve the problem of data scarcity, a method that reduces the dimension of the data has been studied. Typically, this involves singular value decomposition (SVD), which removes an insignificant user or item directly from the user- item matrix, thus reducing the dimension of the matrix , 28.Memory-based collaborative filtering techniques can be divided into user-based collaborative filtering and item-based collaborative filtering. User-based collaborative filtering is a method that selects neighboring users who have a similar tendency to other customers by using user preference information, and then recommends common favorites to the selected neighbors . Item-baMemory-based collaborative filtering is considered as ‘Lazy Learning’, meaning that it derives the results via a heuristic technique whenever a recommendation is required without building a model. This has the advantage that the number of parameters that the user has to set is small, but there are also various problems such as data sparsity. Since this problem becomes more serious when applied to real data, much research has been conducted on this issue. In the present study, the benefits of model-based cooperative filtering, which recommends items after utilizing learning data, have been verified. It is possible to supplement the problems of memory-based collaborative filtering by applying machine learning and data mining techniques to both the similarity measurement and the preference prediction of existing memory-based collaborative filtering . RecentlThis section describes the proposed system architecture. The proposed system is shown in The system consists of four modules that perform log analysis, preference detection, similarity analysis, and channel recommendation functions, each fulfilling different roles.log analysis module analyzes logs by device. Through this module, it is possible to analyze the log information of various devices such as smartphones, IPTVs, and PCs in an integrated manner.The preference detection module detects user preference. This module analyzes the tendency of users based on the log information and analyzes information dealing with how much the channels and programs are preferred. For the analysis and clustering of a user’s watching pattern, the preference is analyzed based on the watching frequency, and the formula is as follows. The u's preference p. The total number of broadcasts Np is divided by the number of watching times p′. In u actually watched the program p′ in the total time Lp′ of the program p′ is denoted Wup′ and similarity analysis module analyzes the degree of similarity for each user. Based on the user’s channel and program preference information, this module analyzes whether there is a user who has a similar tendency among each user.The channel recommendation module recommends the channel to the user. This module recommends channels and programs to users with similar tendencies based on the analyzed channels and program preferences and similarity information between users.The In the proposed system, a program is recommended using two pieces of information. When the preference is detected, the real-time preference of the broadcast and the preference of each broadcast section are separately analyzed to store the data. Then, each user is set as a vector, and the similarity between users is obtained by using the preference data. Programs and channels are then recommended based on the similarity.In the proposed system, the user’s program preference is obtained as follows.u preference for a specific program p′ in the proposed system. The weekly statistical data Np. p′. We can confirm that the total program preference is for one week. FLp′ represents the total length (time) of a specific program p′. Lup′ is the time when user u actually watched a specific program p′. The separated data can be divided into real-time programs and VOD programs.In u preference wt is weight value.p′ according to the length of the watching time for each weekday for a week. In the same way, the preference for VOD programs can be calculated. If we want to give weight to specific programs, we can obtain program preference by assigning weight value wt.The similarity of two users is measured based on the preference value of the real-time program and the VOD program obtained by the above equation. At this time, the cosine similarity measure is used to determine the similarity between vectors. The cosine similarity is given as follows.The following describes the channel scheduling system proposed in this paper. In the conventional channel and program classification methods, broadcast contents are broadcasted at predetermined time intervals for each channel so that the user can watch the broadcast only by accessing the corresponding channel at a predetermined time. This is illustrated in In the current TV system, programs are classified according to channels. Therefore, it is impossible to schedule by program. On the other hand, in this paper, we propose a recommendation method for each program and a method for individual scheduling of the program based on this recommendation method. A schematic of the idea is shown in Since the system constituting the contents can be classified according to the program, the proposed method can store a program desired by the user, and thus create and schedule a kind of individual channel.Full Video Clip of the program and the preference for the Section Video Clip of the program. Program p consists of several Section Video Clips as shown in In this paper, we recommend a program to users by considering both the preference for the Section Video Clip is represented by the notation u's preference for Section Video Clips1 of program p. If a program is composed of four Section Video Clips, the preference for the corresponding Section Video Clips can be obtained differently. Therefore, the program can have a preference value based on watching time and a preference value for each Section Video Clip. At this time, since several preference values are generated for the Section Video Clip, an average value needs to be selected to represent each clip.The Section Video Clips as a representative value of the Section Video Clip preference value, which is expressed by In this paper, we use the average value of all preference values of Section Video Clips can be obtained in the same way as in u for program p, and can be expressed as the sum of user u's preference p and average The similarity of Section Video Clip is reflected as the representative value for the calculation, the reliability of the prediction can be increased when a program is recommended.If the program is recommended in this way, it is possible to obtain the preference and similarity for each program. Therefore, it is possible to recommend only a program that cannot be used in the existing channel recommendation method. At this time, since the preference for the The prediction accuracy depends on the weight value that is used when calculating the program preference. We analyzed the difference in degree of prediction for the weighting methods of both the proposed method and the existing weighting method.The existing method is denoted by W1 and the method proposed in this paper is denoted by W1-3. We tested 10, 20, 30, and 40 of the user’s top preference programs using the two methods. The higher the result, the better the performance.When calculating the number of interested watching times, the existing method includes the program in the number of watched times when the actual watching time of the program is more than 10% of the watching time. However, the proposed method reflects the user’s interest more precisely by reflecting the actual watching time between 10% and 30%.In this section, in order to evaluate the validity of the proposed idea, we compared the proposed method against the algorithm used in existing channel recommendation methods.We used a set of real TV watching history data which consists of the watched TV programs by 3,318 TV users for 6 months from Jan. 1, 2015 to June 30, 2015 by a TV watching rate survey agency, Total National Multimedia Statistics (TNMS) Research . CurrentWe compared the prediction accuracy of the proposed algorithm with that of the existing algorithms by using the audience record of each viewer as the training data set. The prediction accuracy is expressed by tp is the number of programs that actually succeeded in recommendation, and fp is the number of failed recommendations.The precision is the percentage of recommended TV programs that have been recommended, and the closer this value is to 1, the higher the accuracy. We used the user-based collaborative filter (UBCF), item-based collaborative filter (IBCF) and RAMDOM (random) method for the evaluation. The results of the experiment are shown in Experimental results exhibit 32.12%, 34.25%, and 29.23% for the prediction accuracy for the UBCF, IBCF, and Random methods, respectively. On the other hand, when the proposed method is used, the result is 39.61%, demonstrating a higher accuracy.Section Video Clip for the preference calculation. To this end, the watching rate is diversified and reflected in the calculation, as well as the watching rate of the Section Video Clip. And, since the system constituting the contents can be classified according to the program, the proposed method can store a program desired by the user, and thus create and schedule a kind of individual channel. Experimental results show that the proposed method has a higher prediction accuracy than existing algorithms in channel preference. Based on this research, we will study the efficiency of the channel scheduling system in future studies.In this paper, we propose a collaborative filtering TV program recommendation system that uses the watching time of each channel and the watching time of each


Patients with primary immunoglobulin deficiency have lower immunoglobulin levels or decreased immunoglobulin function, which makes these patients more susceptible to bacterial infection. Most prevalent are the selective IgA deficiencies , followed by common variable immune deficiency . Agammaglobulinemia is less common  and is characterized by very low or no immunoglobulin production resulting in a more severe disease phenotype. Therapy for patients with agammaglobulinemia mainly relies on prophylactic antibiotics and the use of IgG replacement therapy, which successfully reduces the frequency of invasive bacterial infections. Currently used immunoglobulin preparations contain only IgG. As a result, concurrent IgA and IgM deficiency persist in a large proportion of agammaglobulinemia patients. Especially patients with IgM deficiency remain at risk for recurrent infections at mucosal surfaces, which includes the respiratory tract. IgA and IgM have multiple functions in the protection against bacterial infections at the mucosal surface. Because of their multimeric structure, both IgA and IgM are able to agglutinate bacteria efficiently. Agglutination allows for entrapment of bacteria in mucus that increases clearance from the respiratory tract. IgA is also important for blocking bacterial adhesion by interfering with bacterial adhesion receptors. IgM in its place is very well capable of activating complement, therefore, it is thought to be important in complement-mediated protection at the mucosal surface. The purpose of this Mini Review is to highlight the latest advances regarding IgA- and IgM-enriched immunoglobulin replacement therapy. We describe the different IgA- and IgM-enriched IgG formulations, their possible modes of action and potential to protect against respiratory tract infections in patients with primary immunoglobulin deficiencies. Immunoglobulin production by B-lymphocytes is a sophisticated adaptive immune defense mechanisms evolved in jawed vertebrates . The absImmunoglobulins are with 10–22 g/L a major serum constituent. The majority of serum immunoglobulins are IgG ~75%), followed by IgA (~15%) and IgM (~10%) . IgG can%, followThe different immunoglobulins have specific functions in immunity. Upon binding to their targets, both IgG and IgM are capable of activating complement through binding of C1q. The ability to activate complement for IgG subclasses varies due to differences in C1q binding, which is highest for IgG3, followed by IgG1, IgG2 and is absent for IgG4 , 9. ReceIgA is not able to activate complement directly. There are two subclasses of IgA, IgA1 and IgA2, characterized by differences in their hinge region . WhereasIgA and IgM can be transported to mucosal surfaces through the polymeric immunoglobulin receptor (pIgR) . Only poIgG is not transported by the pIgR, but through the neonatal Fc receptor (FcRn) . FcRn isHaemophilus influenzae serotype B (Hib) conjugate vaccine entered the market, which decreased invasive Hib disease cases substantially in many countries [Streptococcus pneumoniae polysaccharide conjugate vaccines (PCV) has shown to increase capsule-specific IgG antibody levels [S. pneumoniae and H. influenzae in whole blood [A successful strategy to protect healthy individuals from respiratory tract infections is the use of vaccination. In the early 1990s, the ountries –33. Thisountries . Hib vacountries . Vaccinay levels  and confy levels –39. Vaccle blood .The diverse roles of the different immunoglobulin subclasses in protection against infections is illustrated in patients with primary immune deficiencies (PID), as described in more detail below.Selective IgA deficiency (sIgAD) is characterized by serum IgA level of <7 mg/dL, with normal levels of both IgG and IgM in individuals more than 4 years of age . Most paRecurrent respiratory tract infections are the most common disease associated with sIgAD –45. WhenThe European Society for Immunodeficiencies (ESID) Registry defines selective IgM deficiency (sIgMD) as a serum IgM concentration of 2 standard deviations below the normal level, with normal levels of serum IgA and IgG, normal vaccination responses and absence of T cell defects . The immPatients with common variable immune deficiencies (CVID) are characterized by a marked decrease of IgG or IgA with or without low IgM levels, poor specific immunoglobulin responses to vaccination and no profound T-cell deficiency . A monogBtk gene encoding Bruton Tyrosine Kinsase (Btk), which accounts for 85% of agammaglobulinemia patients. IgGRT is recommended for all agammaglobulinemia patients to reduce infections [Patients with agammaglobulinemia have very low or no serum immunoglobulin levels, making these patients highly susceptible to infections . The larfections . Bacterifections –60, likefections , 59.IgG for IgGRT is traditionally collected from the Cohn fraction II after cold methanol precipitation , 62 and IgGRT was first introduced in 1952 by Colonel Ogden Bruton and applied to the first patient with agammaglobulinemia . This paAn advantage for SC-IgGRT is the ability for home treatment, which was shown to be feasible and safe . Home trH. influenzae and S. pneumoniae increased when IV-IgGRT was administered once every 3 weeks as compared to once every 4 weeks [The largest disadvantage of both SC-IgGRT and IM-IgGRT is the limited volume that can be administered per dose. As a result, the patient requires frequent dosing, typically every week. With intravenous IgGRT (IV-IgGRT), larger volumes can be giving, which decreases the frequency of dosing to once in the 3–4 weeks. However, it requires venous access and the incidence of systemic adverse reactions were high in the early years, mainly due to vasomotor and cardiovascular manifestations, which was most likely due to immunoglobulin aggregation and complement activation , 73, 74.Nowadays, both SC-IgGRT and IV-IgGRT are used to prevent infections in patients with PID and are proven to be safe . The choThere are a limited number of IgA- and/or IgM-enriched immunoglobulin preparations used in clinical practice. Here, we summarize studies that have used IgA- and/or IgM-enriched immunoglobulin products, mainly in treatment of acute bacterial infections in general and highlight the studies focused on infections in immunoglobulin deficient patients.Campylobacter jejuni infection were given FFP for 2 or 4 weeks (500 mL twice weekly), which resulted in complete recovery of both patients [Fresh frozen plasma (FFP) was advocated over IM-IgGRT by Richard Stiehm in 1975  and was patients . Plasma patients . Althougin vitro experiments. For instance, Pentaglobin had a greater opsonic activity against Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli, in comparison to IV-IgGRT [S. aureus mouse sepsis model, the number of bacteria in liver and kidney were significantly lower for animals receiving Pentaglobin in comparison to animals receiving IV-IgGRT Intratect [C. jejuni infections [C. jejuni was measured and treatment resulted in the elimination of the C. jejuni infections [C. jejuni infections [C. jejuni [Pentaglobin is an IgA- and IgM-containing immunoglobulin preparation collected from Cohn fraction III, consisting of 72% IgG, 12% IgM, and 16% IgA for intravenous use . PentaglIV-IgGRT , 89. In fections . In thesfections . After tfections . This refections . We have. jejuni  by supplE. coli compared to Pentaglobin [E. coli from the bloodstream [post-hoc analyses supported improved outcome in patients with elevated CRP, reduced IgM, or both. In addition, Trimodulin seemed to prevent secondary bacterial infections because infection-related treatment-emergent adverse events were significantly decreased from 57% in the placebo group to 33% in the Trimodulin-treated patients [Trimodulin  contains twice the amount of IgA (21%) and IgM (23%) in comparison to Pentaglobin. Trimodulin is not treated with ß-propiolactone and showed approximately 10-fold increase in opsonization of taglobin . In a raodstream . Recentlodstream . Althougpatients . Since IIgAbulin is an IgA-enriched IgG preparation, which was shown to prevent necrotizing enterocolitis when administered orally to babies with low birth weight  and has Shigella flexneri-induced intestine epithelial cell damage in an in vitro cell model [Salmonella enterica Typhimurium [S. Typhimurium infection and systemic dissemination in mice [Although not in clinical trials, plasma-derived IgA and IgM containing recombinant secretory component have been tested in animal studies with promising results. It has been shown that plasma-derived IgA and IgM can bind recombinant secretory component to form sIgA and sIgM . Additioll model . sIgA anhimurium . Oral ad in mice . No resuin vitro assays, animal experiments and clinical trials have to be conducted to determine whether IgA and/or IgM-enriched immunoglobulin replacement therapy would prevent bacterial respiratory tract infections in patients with PID.Current IgGRT treatment has not shown to prevent bacterial respiratory tract infections in a selection of PID patients. Based on the clinical presentation of patients with IgA and IgM deficiencies, who mainly present with respiratory tract infections, it is conceivable that IgA- and/or IgM-enriched immunoglobulin replacement therapy with biologically active IgA and/or IgM have the potential to prevent these type of infections. In the near future, pre-clinical JL wrote the initial manuscript. MvdF and MdJ edited and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The Central Appalachian region of the United States is in the midst of a hepatitis C virus epidemic driven by injection of opioids, particularly heroin, with contaminated syringes. In response to this epidemic, several needle exchange programs (NEP) have opened to provide clean needles and other supplies and services to people who inject drugs (PWID). However, no studies have investigated the barriers and facilitators to implementing, operating, and expanding NEPs in less populous areas of the United States.This qualitative case study consisted of interviews with program directors, police chiefs, law enforcement members, and PWID affiliated with two NEPs in the rural state of West Virginia. Interview transcripts were coded inductively and analyzed using qualitative data analysis software. Final common themes related to barriers and facilitators of past program openings, current program operations, and future program plans, were derived through a consensus of two data coders.Both NEPs struggled to find existing model programs, but benefited from broad community support that facilitated implementation. The largest operational barrier was the legal conundrum created by paraphernalia laws that criminalize syringe possession. However, both PWID and law enforcement appreciated the comprehensive services provided by these programs. Program location and transportation difficulties were additional noted barriers. Future program operations are threatened by funding shortages and bans, but necessitated by unexpected program demand.Despite broad community support, program operations are threatened by growing participant volumes, funding shortages, and the federal government’s prohibition on the use of funds to purchase needles. Paraphernalia laws create a legal conundrum in the form of criminal sanctions for the possession of needles, which may inadvertently promote needle sharing and disease transmission. Future studies should examine additional barriers to using clean needles provided by rural NEPs that may blunt the effectiveness of NEPs in preventing disease transmission. Hepatitis C virus (HCV) is a blood-borne infection that is commonly transmitted during injection drug use , 2. HCV Although most countries have seen rates of HCV plateau , incideninjection drug use and used street drugs [The rural state of West Virginia, located entirely in the Appalachian region, has the second-highest rate of incident cases of HCV in the country  and sharet drugs . In respDespite the clear need for NEPs in rural states like West Virginia, there remains a dearth of research documenting the unique context and challenges to operating NEPs in rural areas of the United States that can provide critical information on the barriers and facilitators that impact overall program effectiveness . A mail/A multiple, intrinsic case study approach was selected for the following reasons: 1) each case (NEP) was of interest in and of itself ; 2) the Each case was selected using purposive and snowball sampling strategies . West ViTo answer the central research questions, the lead author (SD) conducted in-depth interviews with the director of each program. At one site, other administrative personnel  also participated in the interview. In-depth interviews were selected to obtain a deeper understanding of these novel programs. Director interviews occurred in March 2016, law enforcement interviews occurred during the summer of 2016, and interviews with program participants occurred during the summer of 2017.from the viewpoint of respondents, each interview was semi-structured, and conversations were allowed to emerge and flow in naturalistic directions that may have departed from the interview guide. Importantly, the specific questions included in the interview guide were also guided by initial discussions with each director and included questions of interest to him or her. Finally, a case study of the first NEP in the United States, Point Defiance [Prior to conducting each interview, a semi-structured interview guide was developed. The structure of the interview guide was focused on the facilitators and barriers encountered during the past program implementation, present ongoing operations, as well as those anticipated to occur in the future. However, due to the interest in obtaining an in-depth understanding of the central research questions Defiance , was alsPrior to starting the interview, interviewees were informed that the discussion was voluntary and could be ended at any time without penalty. Interviewees were also informed that all discussions were confidential and that the specific program would not be identified in any publications or presentations. Therefore, each case has been assigned a pseudonym .Each interview took place in a private conference room or via telephone and lasted approximately 60 minutes. Interviews were recorded using a stereo handheld digital voice recorder . As a baa priori codes for “past”, “present”, and “future”, into which information on “barriers” and “facilitators” corresponding to implementing and opening the program (past time orientation), ongoing program operations (present time orientation), and program growth and expansion (future time orientation) was categorized. Beyond the general descriptions, no other definitions or codes were established a priori. Interpretations were also guided by the primary author’s experience with individuals suffering from addiction and social work training, which embraces the harm reduction model. As suggested by Yin, a cross case synthesis was conducted to denote similarities, differences, and emerging themes between the two cases [Interviews were transcribed by a professional and entered into qualitative data analysis software for analysis . Prior two cases .After initial coding and classification of all transcripts by the primary author, intensive group discussion with a second coder with expertise in qualitative research (DD) with a goal of simple consensus was employed to finalize the categories and overall themes –29. PrioQualitative interviews were conducted with two program directors, a program administrator, a program nurse, two chiefs of police, two law enforcement officers, and eight PWID  who attended the two programs .The Free Clinic was founded by a group of concerned citizens on the premise that healthcare is a universal right that should be available to all citizens regardless of ability to pay. In response to an ever-growing need, the clinic has moved several times, occupying larger quarters each time, and currently occupies a two-story building with ten exam rooms, two waiting rooms, a medication room, conference rooms, offices, and storage areas. The agency has a staff of 21, a volunteer corps of more than 200, and provides more than 28,000 patient encounters and dispenses free medications in the millions to qualified patients every year. In addition to medication assistance, the Free Clinic provides primary health care with a professional staff of physicians, nurse practitioners, physician assistants, registered nurses (RNs), licensed practical nurses (LPNs), medical assistants, social workers, and therapists. Specialty clinics for various diseases  and topics  are also offered. Some dental care and mental health services are provided on a limited basis. All health care, including prevention, health awareness, and chronic disease management, are free of charge to qualified patients and are offered in clinics or in group education.Although Free Clinic personnel were aware that some patients were also PWID, the significant incidence of HCV among this population was not discovered until the Centers for Disease Control (CDC) updated its HCV screening guidelines to recommend testing for all persons between 45 and 64 years of age . The Freth the size of larger cities such as Baltimore, Maryland and Seattle, Washington where many of the first NEPs in the United States opened. Additionally, the Free Clinic NEP serves attendees that travel from surrounding census designated rural counties. Each participant is assigned a unique identification number for tracking purposes during the initial intake. Basic information regarding injection history, including duration and drug of choice, is also collected at this time. Clients are queried regarding whether or not they know their human immunodeficiency virus (HIV) and HCV status, and testing is encouraged. Importantly, all data collected in the context of the NEP is kept entirely separate from clinic medical records. Although not a requirement for participation, clients are encouraged to bring back used needles in a biohazard receptacle given to them by the program. The number of syringes given is based on client need. Need is determined by frequency of reported injections and transportation barriers . There is no cap on syringes, and the program operates year-round. At the time of data collection, 200 unduplicated patients had attended the exchange since its opening.The Free Clinic NEP is open one day each week for less than 5 hours, and makes special arrangements for participants who cannot attend during regularly scheduled hours. No other clinic services are provided during this time period. There are three staff members that are dedicated to the NEP, and students from a nearby university also assist with operations. PWID of all ages are accepted with a very specialized protocol for those under 18 years of age, although no children had yet been seen at the time of the interview. The average age of participants is 33 (range 19–70) with slightly more males than females . All but 3% of participants are White. Although West Virginia is a rural state, the Free Clinic NEP is located in a county not designated as rural by the U.S. Census. However, the overall population size of the entire county is less than 1/6Each participant leaves with approximately 30 to 50 clean needles. Additional drug paraphernalia, including cookers, cotton balls, alcohol swabs, and tourniquets, are also provided. The exchange offers rapid HCV testing as well as serum HIV testing. Participants also have access to a social worker and a nurse practitioner to discuss any health-related issues. Discussions regarding harm reduction, healthcare, treatment, housing, and general case management are common.The Health Department NEP is located within a public health agency that provides a plethora of environmental and epidemiological public health services including environmental services , clinic services  clinics, immunizations, etc.), threat preparedness, and disease investigation. The Health Department NEP is located in a county similar in size to the Free Clinic NEP, and also serves residents from surrounding rural counties.In November 2014, a local Office of Drug Control Policy was created by the mayor of the town in which the health department is located. An investigation by this office into the problem of drug use found an extremely high rate of drug overdose, primarily from heroin. However, most concerning was the observed rising death rate. During this same time period in 2015, Scott County, Indiana was in the midst of an HIV epidemic from injection of illegal drugs with contaminated needles that led to the opening of a NEP to combat the epidemic . These tThe Health Department NEP runs three exchange rooms for at least five hours, one day each week. In contrast to the Free Health Clinic NEP, other health department services are also offered during the same time period. Approximately 15 individuals comprised of seven staff members, pharmacy, nursing, and medical students, and recovery coaches are present during operating hours. Approximately 130 participants use the exchange each week, with a single day high-volume of 144 participants observed. Participants receive a maximum of 40 clean needles, and most participants bring in approximately 30 to 40 used needles to exchange. In addition to exchanging needles, the Health Department NEP provides recovery coaches, STI testing, as well as testing for HCV (serum) and HIV. Participants are also queried regarding their infectious disease status, and are provided access to nurses who can examine their injection sites for potential infection. Teaching regarding safe and clean injection is also provided, and participants with infected sites are seen by a nurse practitioner. The administrative staff described difficulties related to the fact that routine health department services are offered during the times that the NEP is open. For example, many of the NEP participants were smokers who were frequently going outside to smoke, which disrupted other health department clientele.Participants of the Health Department NEP are heterogeneous and contain a range of individuals from PWID who are gainfully employed despite their addictions to one or more substances to those that are unemployed and/or homeless. Although identification is not required by the Health Department NEP, the created ID number assigned to each participant for tracking purposes includes birth year. Gender is split evenly, and 96% of participants are White, which is similar to West Virginia as a whole (94% White) . The aveOverall, the iterative, open coding process yielded 7 general themes: 2 themes related to program implementation and opening (PAST), 4 themes related to ongoing program operations (PRESENT), and 1 theme related to future growth and expansion (FUTURE).One Size Doesn’t Fit All, was identified from NEP directors’ descriptions of difficulties  encountered with locating an existing exchange program to serve as a model for the development of a NEP in their rural communities   see . Law enfNot Just a Needle, included instances where participants described the importance of other supplies and services in addition to clean needles provided by the exchanges  approach to drug use that impacts policing behaviors was a significant barrier to program operations. Despite these challenges, robust community support and the creative leveraging of volunteer resources have facilitated the successful implementation and operation of these programs.In-depth case studies describing the development and implementation of NEPs in the United States are scant. The literature largely consists of brief descriptions of the first NEPs to open in large urban areas of the United States  in the late 1980s and early 1990s in response to the HIV crisis , 36–42. One Size Doesn’t Fit All theme). Rather, many urban programs used the first NEPs that opened in Amsterdam as a guide to program development [Lifepoint NEP case study described the use of qualitative ethnographic methods and systemic community analysis in the design and implementation of a NEP in Milwaukee, Wisconsin [First, as was experienced by both West Virginia programs, there was no readily available model exchange in the United States to guide program design and implementation . In particular, the initial support of the health department was cited several times throughout the Point Defiance NEP case study in Tacoma, Washington [LifePoint NEP involved law enforcement in the planning process, as did both of the West Virginia programs in this case study. Although no participants reported police harassment after the LifePoint NEP implementation, the overall attitude of law enforcement with regard to the program remained largely neutral [Community support was cited as critical to program implementation and continuing operations by a few studies , 40, 43,shington  as a pro neutral .The Legal Conundrum theme) [Point Defiance NEP did not experience many operational barriers, at least initially, primarily because the chief of police made a conscious decision to not arrest the founder for violation of state paraphernalia laws. Additionally, the state Supreme Court later ruled in favor of the exchange finding that public health interests superseded existing drug paraphernalia laws [Most large urban programs have also described difficulties stemming from the existence of paraphernalia laws and associated policing behavior (m theme) , 45, 46.lia laws . Howeverlia laws .Supply and Demand theme). A notable exception to this case is the Point Defiance NEP in Tacoma, Washington where community support minimized financial barriers. Funding from private citizens, in addition to city and county sources, were cited as contributing factors to a program budget that continued to grow [LifePoint NEP case did not report funding difficulties [Funding was a major barrier cited by both West Virginia programs that impacted both current operations and needed expansion plans ( to grow . Similariculties . Howevericulties .(Supply and Demand theme). This expansion involved delivery of needles to participants who did not or could not attend the original fixed site location, which is similar to the expansion plans of the Free Clinic NEP  in this case study, and another study in which NEP participants listed inconvenient location/hours as a barrier to exchange participation [NEP funding difficulties were exacerbated by exponential growth that necessitated the need for geographic expansion cipation . Other ucipation , 40.NEP funding has historically been inextricably intertwined with paraphernalia laws in the United States . In a reLaw enforcement attitudes toward PWID may also impact the approach to drug paraphernalia , 52. AltSome study limitations should be noted. It is possible that responses may have been impacted by social desirability bias given the sensitive topic. However, no names or demographic information were collected or reported to help minimize the impact of this bias and increase the validity of the measurement. Additionally, the experiences of other rural programs in both West Virginia and other locales may be somewhat different than the experiences described in this case study given that the small sample size (n = 2 cases) may have precluded the ability to achieve saturation of opinions, views, and themes. However, it is recommended that no more than 5 cases be selected for a qualitative case study, and some methodologists argue that any case beyond 1 can dilute important case details . Furthershot in the dark and open NEPs in the absence of model programs, adequate funding, and other resources, due to overwhelming need in their small communities. Despite these challenges, such programs have enjoyed robust community support, and have creatively navigated unexpected problems and challenges to effectively implement needle exchange programs in their communities. However, surging participant volumes amidst ongoing funding challenges coupled with location and transportation barriers make the future trajectory of such programs difficult to predict. Additionally, the efficacy of these programs in preventing transmission of blood borne viruses may be compromised from the legal conundrums created by paraphernalia laws and policing behaviors that may promote needle sharing that is the primary risk for acquiring HCV among PWID. Future studies should investigate these potential barriers to using clean needles in people who inject drugs residing in smaller, less populous areas of the United States.Due to overwhelming need, PWID are often in the dark regarding the precise outcomes that will be experienced during their next injection. Will it be the sought-after high or a disappointing low? Will it be a fatal overdose or a ‘near-miss’? Similarly, the two West Virginia needle exchange programs described in this case study have been forced to take a