Cancer of the prostate (CaP) is the leading cancer among men in sub-Saharan Africa (SSA). A substantial proportion of these men with CaP are diagnosed at late  stages, yet little is known about the etiology of CaP in SSA.We established the Men of African Descent and Carcinoma of the Prostate Network, which includes seven SSA centers partnering with five US centers to study the genetics and epidemiology of CaP in SSA. We developed common data elements and instruments, regulatory infrastructure, and biosample collection, processing, and shipping protocols. We tested this infrastructure by collecting epidemiologic, medical record, and genomic data from a total of 311 patients with CaP and 218 matched controls recruited at the seven SSA centers. We extracted genomic DNA from whole blood, buffy coat, or buccal swabs from 265 participants and shipped it to the Center for Inherited Disease Research  and the Centre for Proteomics and Genomics Research , where genotypes were generated using the UK Biobank Axiom Array.We used common instruments for data collection and entered data into the shared database. Double-entered data from pilot participants showed a 95% to 98% concordance rate, suggesting that data can be collected, entered, and stored with a high degree of accuracy. Genotypes were obtained from 95% of tested DNA samples (100% from blood-derived DNA samples) with high concordance across laboratories.We provide approaches that can produce high-quality epidemiologic and genomic data in multicenter studies of cancer in SSA. The United Nations Sustainable Development Goals, adopted in 2015, set specific targets for reducing global premature mortality associated with noncommunicable diseases, including cancer.2In 2015, approximately 460,000 individuals died of cancer in sub-Saharan Africa (SSA).5 and worldwide, men of African descent have higher CaP incidence and mortality than men of other races or ethnicities.6 In SSA, the number of CaP deaths per year is predicted to increase from 39,000 in 2015 to 76,000 by 2035.4 CaP is more frequently diagnosed at a late  stage in SSA than in other parts of the world,10 and little is known about the roles of exposure or genetic susceptibility loci in its etiology. CaP has the highest heritability of the common cancers.12 Many genetic susceptibility loci have been identified in men of European and Asian descent; however, these loci have not generally been validated in men of African descent, underscoring the need for these studies in African-descent populations.Cancer of the prostate (CaP) is the leading noncutaneous cancer in men worldwide,To address those gaps in our knowledge, we developed a multicenter Men of African Descent and Carcinoma of the Prostate (MADCaP) Network. This article describes the scientific principles, research methods, and standardized procedures and protocols developed by MADCaP investigators for our CaP research in SSA. These approaches may serve as a model for other sorely needed cancer research studies in SSA.In this clinic-based case-control study, eligible participants were men older than age 30 years residing in each MADCaP center’s catchment area and self-identifying as black African with no known or self-reported European, Middle Eastern, or Asian ancestry. All participants were required to reside within a prespecified catchment area surrounding the clinical ascertainment sites. Information about town and country of birth and residential location for the past 10 years was queried. As with patients, the lower age limit for controls was 30 years. The lower bound for inclusion was set at age 30 years on the basis of the earliest age of a CaP diagnosis recorded in any of our centers, which occurred before age 40 years. Eligible patients with CaP, ascertained in urology and oncology clinics or through primary referral, must have had a histologically confirmed first primary CaP of any stage, grade, or pathologic classification. Patient status was confirmed by pathologic diagnosis and medical record review using a standardized abstraction form. Only incident patients, whose first diagnosis of CaP occurred no more than 6 months before study contact, were eligible. Men previously diagnosed with cancer at any other center were excluded.Controls were frequency matched to patient cases by age, ascertained through nonurology and nononcology clinics  at participating SSA institutions  residing13 System for Award Management registration ,14 Electronic Research Administration Commons registration, federal conflict of interest statements, and Collaborative Institutional Training Initiative human subjects research training.15 Local  and centralized institutional review boards approve study protocols annually, following local laws, regulations, and guidelines, and study compliance is monitored frequently following the Office for Human Research Protections international compilation of human research standards.16 US Department of State compliance documents were obtained and distributed to ensure proper implementation of current policies and embargoes.17To comply with local, national, and international regulations governing human subjects research and data sharing, we implemented a series of regulatory protocols. Center and study staff certifications were obtained including US-required federal-wide assurances,All participating institutions signed data use agreements and material transfer agreements. Import and export permits were generated enabling biosamples to be shipped to the CPGR in Cape Town, South Africa, where all central processing, biobanking, and genotype screening are conducted. In addition, MADCaP investigators formed a series of oversight working groups.Each of our centers and the overall study obtained approval for the ethical conduct of the research. These approvals are in accordance with both local and international principles. We took a series of steps to ensure the welfare of our research participants. First, the potential harms to the research participant were minimal. These included minor bruising at the phlebotomy site during peripheral-blood collection. The remaining data collection issues were also minimal risk because they involved questionnaires and medical record abstraction. Second, patient information was protected using standards similar to those outlined in the Health Insurance Portability and Accountability Act. Although the Health Insurance Portability and Accountability Act is a US regulation not in effect in African countries, we have based our patient confidentiality and privacy standards on those regulations, accounting for local laws and regulations that may differ by country. Finally, although the risks to the participants were minimal, the individual benefits to the participants were also small; we did not provide the results of our research to the individual participant. All data are presented in aggregate only. However, the potential benefits to African men may be large as we understand and translate our research results to the clinical and public health of the populations being studied.We standardized biosample collection processes to facilitate consumable and reagent sourcing and obtained high-quality DNA selecting Qiagen’s  QIAamp DNA Blood Midi or Mini Kits on the basis of availability, cost effectiveness, DNA quality, and yield. We collected at least 7 mL of blood in EDTA vacutainer tubes from each participant, maintaining them at 4°C while in transit to the local laboratory and subsequently storing them at −30°C before DNA extraction. When a participant did not provide a blood sample, centers could collect a saliva sample using the Oragene OG-500 kit .18 Common quality control (QC) processes have been implemented to ensure that defined QC metrics are obtained. The QC parameters for DNA include A260/A280 ratios between 1.7 and 2.1; A260/A230 ratios ≥ 1.5; and visualization of high-molecular-weight DNA after gel electrophoresis.CPGR staff visited each SSA center providing training videos supporting biosample protocol adoption and local capacity building.DNA was shipped from each SSA center to CPGR at ambient temperature in DNAstable 2D Barcode 96-well Tube Plates  and stored upon receipt at the CPGR at ambient temperature until processed. After sample resuspension and removal of aliquots for QC purposes, DNA was stored at −80°C for long-term storage before downstream processing.None of our centers had serious power supply issues. However, each of our study centers had generator backups and power surge protectors for the freezers in which our samples were stored. Backup generators kicked in within seconds of a power failure. In addition, we stored our DNA samples in DNA-stable plates, which maximizes DNA quality during shipping as well as potentially variable storage conditions.19 to provide identifiable tracking of participant recruitment, and a DatStat Illume database  for deidentified storage of study data that include no personal identifying information other than the patient’s date of birth. Each study participant was assigned a unique study identification number, concatenated with center identification, year of accrual, and patient case or control status. Center staff received remote database training20 via training guides and tutorials. Videos were available for ongoing training and support.18 The Data Coordinating Center (DCC) monitored data collection, ensuring there were no duplicate identifiers, and generated missing data reports.After multiple teleconferences and an in-person meeting (January 2017), we finalized common data elements and study protocols. We created two Web-accessible, password-protected databases, residing on secure servers—a Research Electronic Data Capture databaseA synopsis of the data collection processes is presented in We conducted two pilot studies to evaluate processes and protocols.All SSA study staff were trained in person. Data collection was monitored to evaluate protocol adherence and the capacity of each center to collect and enter high-quality data.260/A230 ratios and partially degraded samples, submitting 1 to 3 µg of DNA in DNAstable plates after the drying down of DNA samples in a laminar flow hood. The 265 biosamples collected in this pilot were evaluated in parallel experiments using the UK Biobank Axiom Array  at CPGR. CIDR tested 234 DNA samples, assessing QC by running e-gels, Picogreen, and/or Nanodrop and the Illumina QC Array . CPGR tested 223 samples using TaqMan OpenArray Genotyping Barcodes . By design, some samples were sent to both CIDR and CPGR to evaluate reproducibility of results. Duplicate samples were included to help determine technical reproducibility within and across genotyping centers and assess the overall minimal sample quality threshold required.We evaluated each center’s ability to collect, process, and ship DNA across Africa and to use the DNAstable plate for stabilization, storage, and shipment of DNA at room temperature to the CIDR and CPGR. Center staff processed both prospectively and retrospectively collected samples (biosamples previously obtained after unstandardized protocols). By studying these retrospectively collected samples, we could evaluate samples collected under a wide variety of conditions in SSA. Centers were encouraged to provide a range of samples with optimal and suboptimal QC metrics, including low AWe developed a study binder consisting of 11 protocols and 15 data collection forms to provide comprehensive guidance to the SSA centers relating to regulatory, ethical, and data collection procedures. The data collected for this study include basic demographic and clinical characteristics, epidemiologic risk factors, and pathology features.www.madcapnetwork.org)21 built on the Alicanto social learning platform  supporting creation of public and private groups, with document sharing, threaded discussion, and videoconferencing using Zoom software (https://zoom.us). We used these communication tools initially to ensure standardization across study centers and continue to use them to facilitate and monitor study progress, share information, and nurture collaboration. In its first year, the Web site had 1,075 unique visitors, 1,875 visitors’ sessions, 29,030 page views, 112 registered users, and 11 groups available to registered users. The MADCaP study enrollment video22 guides the project manager through all enrollment steps. The Web site was recently awarded a Gold Davey award in the Education category by the Academy of Interactive and Visual Arts. We created a communication platform , and material transfer and data use agreements was obtained. Across seven centers, a total of 186 patients and 122 controls were enrolled onto the pilot study . To moniP < .001).For the laboratory pilot, documentation was generated, and the SSA centers successfully transported both retrospectively and prospectively collected biosamples to the CPGR and CIDR. After DNA extraction, centers performed QC analysis and shipped an aliquot of each sample to the CPGR for corroborative QC analysis. Both CIDR and CPGR performed QC analysis including Nanodrop, gel electrophoresis, and/or Picogreen assays to measure the quality, quantity, and integrity of the biosamples. Appendix Average center call rate from the Illumina Infinium QC array was > 99% for blood and buffy coat samples, whereas samples derived from buccal swab had lower call rates (≤ 92%). Similar performance of samples was observed for the OpenArray Genotyping Barcode Panel for 60 single nucleotide polymorphisms. The samples with the lowest success in both pretesting assays were derived from buccal swabs, which showed significant DNA degradation and displayed the poorest QC metrics  and loweOf the samples assayed on the UK Biobank Axiom Array at both CIDR and CPGR, approximately 47% were derived from blood, 23% from buffy coats, and 30% from buccal swabs representing various DNA samples. Samples were included from three different African countries . 23 However, we have now developed a multicenter research network to study CaP in SSA men. The results presented provide strong evidence that each center can ascertain controls and patients and obtain the required data to achieve the study aims, highlighting the importance of the pilot phase in establishing appropriate and adequate study implementation. The MADCaP Network serves as a paradigm for multicenter cancer research in SSA and among researchers and clinicians in SSA centers with US partners. This collaboration is building capacity and sustainability for cancer research in SSA. SSA centers maintain control of their own studies and may publish independently. Contributing SSA principal investigators (PIs) may also use consortium resources and data to address questions of interest. Data sharing with center PI permission and through confidentiality and data use agreements protects investigators and allows free exchange of data and ideas among consortium members.SSA has been greatly under-represented in studies of cancer.This report describes how SSA centers can become equipped to perform participant ascertainment, data and biosample collection, and DNA processing. QC analysis of prospectively collected data and biospecimens indicated that each center could adequately follow the project’s protocols and procedures to generate data and to extract, store, and ship high-quality biosamples. The biosampling pilot study confirmed the suitability of Biomatrica plates for shipping DNA samples from each African center to the CPGR and CIDR at ambient temperature, validating its continued use for shipping samples for the main study and thus eliminating the need for dry ice shipments, an important shipping option in Africa. Moreover, DNAstable, the DNA stabilizing reagent used to coat the plate wells, did not negatively affect the DNA integrity or sample performance on the Axiom assays using the UK Biobank Array.260/A230 ratio. These results indicate that prospective and retrospective samples will produce a high call rate for genotypes using genotyping assays on a variety of platforms. Moving forward, a standard operating procedure for buccal cell collection, preprocessing, storage, and transport will be optimized and universally used for DNA for MADCaP.A high percentage of retrospectively collected buccal samples failed the assay as a result of sample degradation. Blood and buffy coat samples, irrespective of sample age, performed well, with DNA of high molecular weight and little or no degradation. Older samples that had gone through repeat freeze-thaw cycles provided a lower DNA yield, although they still contained sufficient DNA to perform required assays. The genotyping assays used can also tolerate lower than expected QC metrics, in particular with respect to the A25 Successful networks may need to identify incentives, rewards, and recognition for research faculty and staff, modeling a locally appropriate change management approach, and develop easy-to-use platforms that can scale to larger size studies as well as studies of other noncommunicable diseases. The research itself must be developed in terms of achievable goals with realistic timelines. Finally, the network must provide clear expectations and metrics for collaborators’ contributions and communication, including regular calls and bidirectional center visits. We have also used these lessons to identify key overarching goals for the network, including the development of improved research infrastructure considering the needs and setting in SSA.We have identified principles critical to development of a sustainable research network that has clinical and public health impact. Elements required for successful network development include the commitment of a dedicated, well-connected, and influential local PI willing to promote and mentor junior researchers. An academic environment enabling research is also required, particularly to provide dedicated research time, given the clinic loads of most clinician investigators. Appropriate training and academic career ladders may need to be developed or tailored to permit committed individuals to dedicate effort to a research career. Some SSA institutions do not yet provide these pathways.We also identified several challenges in developing our network. We initially had trouble identifying well-trained, experienced technical staff, but we found we could identify and train center staff to meet our research needs. We observed the value of regular, consistent, targeted communication to address the needs of individual centers and keep the project on track. Early in network development, we learned that we needed to identify realistic study goals and timelines to avoid unmet expectations. We had to set common standards and make sure that protocols were consistent with the centers’ previous experiences and expectations. The development of tools for protocol and data harmonization by a consensus helped avoid unnecessary conflict among groups with different past research experiences. Our adoption of Web-based tools and a communications platform, through which each investigator and staff member could readily find documentation on the study protocols and progress, helped avoid confusion or miscommunication. A major challenge for data collection was being able to obtain consistent Internet access. Once this limitation was identified, we switched from a system of online data entry to a protocol allowing local data entry and bulk data upload at centers having difficulty accessing the Internet. On the basis of our experience to date, we have realistic expectations of returns on the substantial investments of money, resources, and time that MADCaP entails, including improved research infrastructure, a trained local workforce, improved research capacity, and potentially important contributions to science.


The misuse and abuse of prescription opioids have become an urgent health issue in North Carolina (NC), particularly among Medicaid patients who suffer high rates of morbidity and mortality due to abuse and overdose. The NC Division of Medical Assistance (DMA) implemented a recipient management lock-in program, which limits identified patients for a 12-month period to 1 prescriber and 1 pharmacy for benzodiazepine, opiate, and certain anxiolytic prescriptions in order to prevent misuse and reduce overutilization of Medicaid benefits.To (a) evaluate pharmacists’ perceptions of the implementation of the NC recipient management lock-in program (MLIP) and (b) determine how the beliefs and attitudes of pharmacists could promote or inhibit its success.We conducted 12 structured phone interviews with NC pharmacists serving lock-in patients. Interview responses were analyzed through construct analysis, which identified themes organized into 3 domains: organization and implementation, perceived effectiveness, and acceptability.Most respondents reported a positive experience with the program but expressed doubt concerning its impact on prescription drug abuse. The program successfully utilized the pharmacist role as a gatekeeper of controlled substances, and the procedures of the program required no active effort on pharmacists’ part. However, respondents suggested that the DMA improve communication and outreach to address pharmacists’ lack of knowledge about the program’s purpose and confusion over remediating problems that arise with lock-in patients. The DMA should also address the ways in which the program can interfere with access to health care and treatment, allow patients to see multiple physicians within the same clinic, and clarify procedures for patients whose complex health issues require multiple specialists.Although possible improvements were identified, the NC MLIP has strong potential for success as it utilizes pharmacists’ medication gate-keeping role, while minimizing the effort required for successful implementation.


The 2016 mid-term review of the Global Measles-Rubella Strategic Plan 2012–20 for achieving measles-rubella elimination concluded that the full potential of strategies and activities to strengthen routine immunization (RI) service delivery had not been met. In December 2017, we contacted WHO and partner agency immunization staff in all six WHO Regions who identified 23 countries working on measles or rubella elimination that have implemented examples of recommended activities to improve RI, adapted to their needs. Among those examples, opportunities to strengthen RI through implementing supplementary immunization activities (SIAs) were reported most frequently, including advocacy for immunization and educational activities targeted at the public and skills training targeted at health professionals. The expansion of cold chain capacity to accommodate supplies required for SIAs facilitated widening RI service delivery to reach more communities, introduce new vaccines, and reduce the risk of vaccine stock-outs. Substantial numbers of under-vaccinated children, according to the national immunization schedule, have been identified during SIAs, but it is not possible to confirm whether these children actually received missing RI doses. Micro-planning exercises for SIAs have generated data that permitted the revision of catchment populations for fixed site and outreach RI services. Some countries reported using the opportunity afforded by measles/rubella elimination to strengthen overall vaccine-preventable disease surveillance and outbreak preparedness and to introduce mandatory school-entry vaccination requirements covering other vaccines in addition to measles and rubella. Unfortunately, we were unable to obtain information regarding the cost, impact or sustainability of these activities. The evaluation of the many other strategies that have been deployed in recent years to strengthen RI systems and raise vaccination coverage was beyond the scope of this survey. We conclude by providing recommendations to encourage more countries to adapt and implement a comprehensive set of RI-strengthening activities in association with the MR elimination goal. Studies show that in countries with strong health systems, the implementation of additional strategies, particularly SIAs, causes little or no disruption to RI service delivery, but where systems are chronically weak, difficulties may arise MR vaccination coverage through RI has stagnated in recent years During 2016, approximately 119 million persons received MCV during 33 supplementary immunization activities (SIAs)Consequently, the 2015 global measles control milestones were not met. With suboptimal MCV coverage, outbreaks continued to occur among susceptible individuals, including school-aged children and young adults. A mid-term review (MTR), conducted in 2016 and subsequently endorsed by the WHO Strategic Advisory Group of Experts on Immunization (SAGE), noted that current measles elimination strategies were sound but that implementation of the strategies needed improvement In response, the present survey was commissioned to document specific national examples from all six WHO Regions where MR elimination activities have contributed to strengthening aspects of RI service delivery. The goal is to encourage National Immunization Programme (NIP) managers to adopt similar strategies, as appropriate for their countries, and implement selected activities to strengthen RI service delivery.2A letter was sent to WHO and partner agency immunization staff requesting them to provide a list of countries where, in their professional opinion, the implementation of activities associated with measles/rubella elimination had strengthened RI. WHO and partner agencies identified 25 countries where suitable examples were located. The same letter was then sent to key informants in those 25 countries, with follow-up by email, telephone and Skype, in order to secure a full description of the activities and, if available, quantitative or qualitative evidence of cost, impact and sustainability.National examples were divided into six categories of recommended opportunities to strengthen RI through MR elimination activities adapted from the WHO Global Routine Immunization Strategic Plan (GRISP) The survey identified a convenience sample of examples of recommended RI-strengthening activities in each WHO Region, but this set of examples should not be considered representative. Therefore, inter-regional and inter-category comparisons could not be made. Further research would be required to document the global scope of RI-strengthening activities associated with MR elimination.3From the 25 countries contacted, 31 examples from 23 countries (92%) from all six WHO Regions were reported in the survey, with supporting documentation . Despite3.1The WHO guidelines for planning, implementing and evaluating measles and measles-rubella SIAs in each WHO Region include guidance on multiple ways to utilize the opportunity of campaigns to identify unvaccinated or under-vaccinated children in order to complete their RI schedules Red Cross volunteers have implemented pre-SIA house-to-house canvassing activities in >100 SIAs in 46 African countries since 2000. Over 50,000 volunteers have been trained and >11 million households (HHs) visited. Red Cross workers observed that in three recent SIAs , although substantial numbers of children missing RI doses were identified, little information was available to confirm whether these children did in fact receive the vaccine doses they needed As in many Member States in the WHO Americas Region, MRCV coverage in Mexico is high enough to permit suspension of the SIA strategy. However, National Health Weeks are conducted three times per year to supplement RI and sustain high coverage. In the course of H2H visits, rapid coverage monitoring (RCM) assessments are conducted and HBRs are routinely screened in order to identify children who missed MRCV and other RI doses 3.2WHO guidelines also recommend using the opportunity of SIAs to expand cold chain capacity and transport fleets, to extend public advocacy and education for RI through social mobilization and house-to-house (H2H) canvassing, and to give refresher training of healthcare workers (HCWs) to implement SIAs and consolidate RI knowledge and skills including vaccine supply and management, vaccination technique, waste disposal, investigation and reporting of adverse events following immunization (AEFIs), VPD surveillance, risk assessments, data management and transmission, and more.In this survey, the most common activity associated with SIAs was the provision of refresher training to HCWs on a wide variety of RI knowledge and skills. This was confirmed by key informants in all WHO Regions, e.g. in AFR , in AMR , in EMR (Pakistan 2014–15), in EUR , in SEAR , in AMR  and in SEAR . Prior to SIAs in Tanzania in 2014, an additional 240 refrigerators and 10,000 vaccine carriers were procured. In Pakistan during the 2014–15 SIAs, an additional 20,000 standard vaccine carriers and 800 cold boxes significantly increased programme capacity in RI service delivery Preparations for SIAs have facilitated the development of micro-plans to more accurately estimate target populations and to validate denominators for monitoring RI performance. In Tanzania in 2011, SIAs micro-plans were used to identify new sites for outreach and mobile services employing the Reaching Every Child approach 3.3Almost all countries have established case-based measles surveillance and monitor WHO-recommended indicators to achieve measles elimination. Many countries have also established case-based rubella surveillance. In most cases, MR surveillance and reporting is integrated into the national disease surveillance system. Some countries have also included the theory and practice of VPD surveillance in the refresher training provided to HCWs and other cadres during preparations for SIAs, e.g. in Ethiopia in 2016 and Pakistan in 2014–15. During pre-SIA preparations, orientation for HCWs and other cadres to consolidate RI knowledge and skills frequently included detailed training on AEFI surveillance including the identification, treatment and reporting of and response to suspected AEFI cases.In addition, some countries have used the opportunity afforded by the establishment of case-based measles or rubella surveillance to strengthen VPD surveillance in general. When measles case-based surveillance was introduced in Pakistan in 2009, reporting tools were modified to record additional epidemiological data on VPD cases including vaccination status and laboratory results, monthly reporting was replaced by weekly reporting, and measles surveillance indicators were extended to all VPDs To comply with WHO European Regional guidance on MR elimination, the Federal Government of Germany updated legislation in 2014 to introduce nationwide case-based rubella surveillance. At the same time, four more VPDs  were made notifiable and subject to case investigation and response In Malaysia, the prevention of nosocomial measles transmission led to revision of hospital infection control guidelines requiring vaccination with MMR and other selected RI antigens  for all staff involved in patient care, food handling and laboratory work In Mexico, the active search for measles and rubella cases in municipalities reporting inadequate MR surveillance sensitivity, especially those located along national borders, those with substantial tourist arrivals, and those with low RI coverage, was extended to include all VPDs 3.4Following the adoption of the MR elimination goal, Cambodia conducted a nationwide series of professional training exercises on measles outbreak preparedness, investigation and response. These courses also served to build capacity for preparedness and response to other VPD and non-VPD outbreaks In Austria, slow progress towards verifying MR elimination provoked the government to implement a series of advocacy and multi-media promotional activities to boost awareness and demand for RI services among health care professionals and the general public. This included strengthening knowledge and skills related to VPD surveillance and outbreak control, particularly related to timeliness and data quality 3.5In France, slow progress towards verifying MR elimination caused primarily by inadequate MCV population immunity provoked the government to enact legislation in 2017 mandating school-entry vaccination for 11 antigens including MRCV Similarly, in the Republic of Korea, after the school entry vaccination requirement was extended to include MCV2, legislation was modified twice to include proof of vaccination with all RI antigens 3.6Government policy in Mexico provides for comprehensive Well Child visits every 2 months, up to the 5th birthday, which require, among other things, that HCWs review every infant’s and child’s immunization status at each visit and complete the RI schedule as necessary 4A robust RI system should assure that all children have access to recommended vaccines; all HCWs are fully trained to determine eligibility for a given immunization and how to administer the vaccine; maintains a record keeping system that permits easy identification of under-vaccinated children at each healthcare contact; deploys a system to remind parents when vaccinations are due or past due; includes educational programmes and outreach to communities to maximize demand for immunization; implements a sensitive surveillance system that detects VPDs and determines the epidemiology and burden of each VPD; determines whether the cases are a result of failure to vaccinate or vaccine failure; and links immunization to provision of other critical health services, such as growth monitoring.Although the strategies and activities defined in the Global MR Strategic Plan 2012–20 for achieving MR elimination include multiple opportunities to strengthen RI systems, the mid-term review (MTR) of progress conducted in 2016 concluded that the full potential of these opportunities had not been met. The MTR noted that further investigation is indicated to better understand the reasons why countries have not always used MR elimination activities to strengthen RI and what steps could be taken to ensure more widespread implementation in the future. The present survey constituted a first step in that direction and revealed that countries in all six WHO Regions have implemented many, but not all, of the recommended activities, adapted to their needs.This survey was designed to solicit positive examples of how a focus on MR elimination could improve the overall routine immunization system. Where RI service delivery is weak, MR elimination activities may have negative impact on the RI system and, going forward, this will be very important to determine to avoid such outcomes. However, the goal of this survey was to find positive examples in hopes of stimulating persons engaged in enhancing activities to reach the regional MR elimination goals to consider adopting similar procedures to strengthen RI and to show that undertaking major interventions, such as SIAs, could have a positive impact on RI.Preparing for SIAs has facilitated a wide range of RI advocacy and educational activities targeted at the public and health professionals, through widespread social mobilization, H2H canvassing and multiple media channels. Furthermore, additional funds have been deployed to expand cold chain capacity to accommodate extra vaccine supplies required for the surge in vaccination over a short period. These additional resources are extremely valuable for expanding RI service delivery to reach more communities, for introducing new vaccines, and for reducing the risk of vaccine stock-outs.In certain lower-income countries (LICs), micro-planning exercises for measles SIAs generated data that permitted the revision of catchment populations in order to fine-tune micro-planning for fixed site and outreach RI services.Furthermore, during SIAs in many countries substantial numbers of under-vaccinated children were identified, but it is not possible to confirm whether these children actually received missing RI doses. Although it was proposed several years ago to earmark specific resources when planning and budgeting SIAs to ensure that children requiring additional RI vaccine doses were followed up and that compliance was monitored High-income countries (HICs), where SIAs have never been implemented or have not been implemented recently, did not report interventions related to SIAs. In many HICs, other RI-strengthening activities have been implemented in association with the pursuit of MR elimination, especially public advocacy and awareness-raising activities, often in association with National Immunization Week initiatives.Almost all countries have now established case-based measles or MR surveillance and monitor standard indicators in accordance with WHO recommendations. However, some countries have used the opportunity to strengthen VPD surveillance in general. A few countries, mainly HICs, reported enhancing case-based surveillance and outbreak preparedness for VPDs in addition to measles and rubella, legislating mandatory school-entry vaccination requirements with vaccines in addition to measles and rubella, and ensuring that during Well Child clinics HCWs always review infants’ and children’s vaccination status and complete the RI schedule as appropriate. However, it appears that mandatory school-entry vaccination requirements have not yet been introduced and enforced in enough countries, especially large LICs and MICs, to make a significant global impact.WHO and partner agencies have advocated strongly with countries to establish second-year-of-life (2YL) platforms to expand infant immunization beyond the first birthday and, taking advantage of the introduction of the MCV2/MRCV2 dose, to raise awareness of and compliance with all booster doses included in the second year of the national immunization schedule Unfortunately, despite requests for data, we were unable to obtain information regarding the cost, impact or sustainability of the activities. With few exceptions, budgets for SIAs do not itemize expenditure on RI-strengthening activities. Furthermore, quantitative data to monitor impact or the overall sustainability of these measures have not been collected. This is an area which will need to be addressed more aggressively in the future, in order to demonstrate value and encourage more countries to adapt and implement a comprehensive set of RI-strengthening activities in association with the MR elimination goal.The focus of this study was on using the opportunity resulting from the pursuit of regional MR elimination goals to strengthen RI. It provided a number of examples of how efforts focused on MR elimination have helped strengthen RI. Our objective was to document examples of practices that other NIP managers can adapt and implement but we were unable to rank them because their respective impact was not quantified. The study shows that we must hold stakeholders at all levels accountable not only for achieving MR elimination but also taking advantage of those activities to strengthen RI sustainably. However, we fully recognize that the establishment and maintenance of strong RI systems clearly require a wider range of measures than those associated with MR elimination.5a.A protocol, including a user-friendly checklist, should be developed to uniformly assess the impact of SIAs on RI and other aspects of national immunization systems so that those responsible for planning SIAs will understand how they will be evaluated.b.National immunization programmes should document if an activity related to MR elimination efforts negatively impacts RI service delivery and document such information to help in determining how to avoid such results in the future.c.Current efforts to strengthen RI through SIAs should be sustained and, where possible, expanded. WHO Regional post-SIA technical report templates should be revised to:(i)include quantitative indicators to monitor RI-strengthening activities, especially those related to identifying children with incomplete RI schedules and following them up in a timely fashion to ensure that their schedules are completed, and(ii)collect quantitative and qualitative information on the cost, impact and sustainability of RI-strengthening activities.d.All SIAs  offer the opportunity to review HBRs and identify unvaccinated and under-vaccinated children. However, specific resources should be included in SIA budgets to ensure that these children are followed up to complete their RI schedules.e.Effective steps to close immunity gaps in the population should be promoted, including requiring school-entry and, where appropriate, other vaccination checks, especially in LICs and MICs with large populations, to increase global impact.f.After finalizing technical guidelines and raising adequate funding, efforts to introduce 2YL platforms, taking advantage of MCV2/MRCV2 introduction to raise awareness of and compliance with RI booster doses scheduled in the second year of life, should be accelerated.None.Manuscript was prepared from country reports, no personal data were accessed, no invasive procedures were performed, and therefore no ethics clearance was required.


Strengthening health research capacity in low- and middle-income countries (LMICs) has been identified as a driver of development and requirement for efficient investment of limited resources. Among the unique challenges that LMICs face when undertaking research for health are a persistent shortage of experienced researchers and competent interdisciplinary research teams, limited research career opportunities , 2, 3, iSince 2007, TDR, the Special Program for Research and Training in Tropical Diseases cosponsored by United Nations Development Programme (UNDP), UNICEF, the World Bank, and WHO; institutions serving as Regional Training Centers (RTCs); and diverse government and regional partner entities synergized efforts towards building project management capacity for health research, especially for neglected tropical diseases (NTDs) . TogetheOur goal in this Viewpoint is to consider unique features of the “Planning for Success” approach to project management training and its regional dissemination model and provide insight into their applicability to other needs for health-research-capacity–strengthening.The cornerstone of the “Planning for Success” initiative is the Skill-Building course on Effective Project Planning and Evaluation (EPPE) that takes participants through each of the phases of project management, i.e., project planning, implementing, monitoring, and evaluating. Embedding of training in project planning and evaluation within an organization lays the cornerstone for institutionalization of this capacity as an organizational practice. Centro Internacional de Entrenamiento e Investigaciones Médicas (CIDEIM) was initially supported for one year by TDR as a reference center for EPPE training in 2007  in orderIn 2002, TDR identified the need for ensuring efficient, timely, and cost-effective conduct of projects and management of grants funded through its Multilateral Initiative on Malaria (MIM), which aimed to “maximize the impact of scientific research against malaria in Africa, through promotion of capacity building activities and facilitating global collaboration and coordination” . The EPPSeveral models of project management training existed when the EPPE course was developed . HoweverThe Skill-Building course developers intentionally tailored the course to the multidisciplinary backgrounds and roles of the diverse professionals involved in health research. Terms, concepts, and learning methods are conveyed through a specific case study example and immediate application to participants’ own research projects. Project management concepts following a results-based management approach including alignment of objectives, definition of roles, coordination of activities and timelines, and effective mechanisms of communication are presented in practical terms, emphasizing the value of the appropriation and application of project planning and evaluation by research teams.Rooted in David Kolb’s experiential learning theory , course The course brings together multidisciplinary teams including investigators, data managers, project coordinators, public health practitioners, administrators, and institutional authorities from different sectors concerned with research for health . ParticiBuilding health research capacity, particularly to address NTDs, requires a critical mass of competent and coordinated research teams. Development of skills in project planning and evaluation connects individual and institutional capacities, empowering research teams. Since CIDEIM’s introduction to the “Planning for Success” initiative in 2007, 511 individuals, including 85 trainers, in 30 institutions in Latin America and the Caribbean have been trained in “Planning for Success” methodology . Overallhttp://www.who.int/tdr/publications/topics/project_planning_training/en/). These standardized materials and system of replication have facilitated propagation in person and through a virtual course (http://www.cideim.org.co/moodle/) while minimizing the risk for inconsistent course quality and divergence from core messages.During piloting of the EPPE Skill-Building course (2002–2003), MIM grantees ratified the value of the training and expressed the desire to train their team members and others. In response, TDR developed the TTT course to facilitate dissemination . The TTTA commitment to a bottom-up leadership and distributed empowerment approach, together with the mutual leveraging of the institutional resources and capacities of CIDEIM, TDR, PAHO, and national partners, has catalyzed the dissemination of the “Planning for Success” initiative and scalable and sustainable research capacity building. CIDEIM initially built upon its established national research partnerships to develop training experience and increase its trainer pool. With the support of PAHO and TDR, CIDEIM expanded EPPE training to the Andean region, Central America, and Jamaica in the Caribbean . ImportaBeyond the Americas, CIDEIM has also introduced “Planning for Success” training capacity to RTCs in Indonesia, Kazakhstan, and Ghana and to the University of Malawi, promoting the parallel dissemination of project management skills in Central and South East Asia and Western and Eastern Africa. Through this process of inter- and intraregional dissemination, the project management course has been adapted to address a broad range of health research needs, to incorporate other project planning and monitoring challenges such as budgeting, and to allow integration into university curricula, thereby responding to participant evaluations and trainer experiences . MoreoveThe beneficial impact and intermediate outcomes of the “Planning for Success” approach to building project management capacity among health research teams are substantiated by its sustained dissemination and appropriation and the incorporation of the methodology into institutional practices and curricula by the RTC and network institutions. The training experience and methodology described in this Viewpoint deliver a valued product to participants, namely a clear, feasible plan for their projects, thereby promoting institutional appropriation of research skill building through active learning and outcome-oriented courses that complement and are readily integrated into academic curricula. The institutional focus, regional leadership and synergistic partnerships established through the “Planning for Success” initiative have provided a foundation for strengthening regional health research.Effective and sustainable research teams need to have the skills to plan the preparation, conduct, and delivery of research , especially to address neglected tropical diseases (NTDs) in resource-constrained low- and middle-income countries (LMICs). These skills are seldom included in the curricula of higher education.Strategic partnerships among institutions in LMICs, UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR), and WHO regional offices have supported the development of human capital by introducing and disseminating project planning and evaluation competencies using a propagable Train-the-Trainer approach. This initiative has contributed to advancing WHO’s Strategy on Research for Health and developing regional collaborative networks.A regional network of experts and a cadre of over 500 professionals with skills in “Planning for Success” in research for health, including 85 trainers in 30 different institutions in Latin America and the Caribbean, have been trained in the methodology. The institutional focus, regional leadership, and synergistic partnerships have provided a foundation for strengthening regional health research capacity.


Of the 254 counties in Texas, 69% are rural, and three out of every four counties are designated as whole or partial Primary Care Health Professional Shortage Areas. Rural counties in Texas have a higher proportion of older adults compared to metropolitan counties, and rural older adults with Alzheimer’s Disease and their caregivers face unique challenges of limited access to healthcare and lower earnings, resulting in more health-related problems. As part of a HRSA Geriatrics Workforce Enhancement Program, an academic medical center, two Area Agencies on Aging in North Texas, and an Alzheimer’s Association Chapter partnered to expand access to evidence-based programs into surrounding rural counties for older adults and caregivers of persons with Alzheimer’s Disease. An interdisciplinary workgroup developed focus group questionnaires for older adults, caregivers, and health care providers in rural areas to identify perceived needs, barriers to accessing services, and strategic partnerships. The North Central Texas Council of Governments conducted 11 focus groups in late 2018 and early 2019. Of these, seven consisted of family members caring for persons with memory loss. Four consisted of professionals who treat persons with memory loss. Transcription and thematic analysis identified key themes of training needs (both providers’ and laypersons’), resource needs, providers’ best practices, barriers to quality care, and other support needs. Practice implications of the findings include cross-sector partners and integrating telehealth platforms for program delivery. Collaboration between academic and community partners can expand access to evidence-based programs for rural and other underserved communities and address areas of need.


Cancer is a leading burden of disease in Australia and worldwide, with incidence rates varying with age, sex and geographic location. As part of the Ageing, Chronic Disease and Injury study, we aimed to map the incidence rates of primary cancer diagnoses across western Victoria and investigate the association of age, accessibility/remoteness index of Australia (ARIA) and area-level socioeconomic status (SES) with cancer incidence.Data on cancer incidence in the study region were extracted from the Victorian Cancer Registry (VCR) for men and women aged 40+ years during 2010–2013, inclusive. The age-adjusted incidence rates , as well as specific incidence for breast, prostate, lung, bowel and melanoma cancers, were calculated for the entire region and for the 21 Local Government Areas (LGA) that make up the whole region. The association of aggregated age, ARIA and SES with cancer incidence rates across LGAs was determined using Poisson regression.p < 0.001).Overall, 15,120 cancer cases were identified; 8218 (54%) men and 6902 women. For men, the age-standardised rate of cancer incidence for the whole region was 182.1 per 10,000 population/year (95% CI 177.7–186.5) and for women, 162.2 (95% CI: 157.9–166.5). The incidence of cancer  increased with increasing age for men and women. Geographical variations in cancer incidence were also observed across the LGAs, with differences identified between men and women. Residents of socioeconomically disadvantaged and less accessible areas had higher cancer incidence (Cancer incidence rates varied by age, sex, across LGAs and with ARIA. These findings not only provide an evidence base for identifying gaps and assessing the need for services and resource allocation across this region, but also informs policy and assists health service planning and implementation of preventative intervention strategies to reduce the incidence of cancer across western Victoria. This study also provides a model for further research across other geographical locations with policy and clinical practice implications, both nationally and internationally. Cancer is a leading burden of disease in Australia and worldwide. According to the Global Burden of Cancer 2013 report, the burden of cancer is increasing globally and has shifted from the third leading cause of death in 1990 to become the second leading cause of death behind cardiovascular disease, with over 8 million deaths caused by cancer in 2013  and among bowel, lung, melanoma, prostate and breast subtypes. Bowel, lung, melanoma, prostate and breast cancers are the five most common cancer subtypes in Victoria, collectively accounting for 57% of all new cancers and half of all cancer deaths  ARIA and SES (IRSAD deciles converted to quintiles) across the LGAs and corresponding cancer incidence rates. Age-adjusted incidence rates were calculated for the region and geocoding (Pitney Bowes Software Pty Ltd) performed to determine SES and ARIA codes. This analysis was performed using Poisson regression after accounting for aggregated data considering LGA as unit of analysis and incidence rate ratios (IRR) were calculated.Minitab  and STATA 14 were used for analyses.From 2010 to 2013 inclusive, 15,120 cancer cases  were identified for 8218 men and 6902 women. The incidence of cancer [overall] increased with advancing age for both men and women across the region  for men and women  varied between men and women across the LGAs. For men, West Wimmera recorded the highest incidence rate of cancer [overall] with the lowest incidence rates occurring in Ararat and Pyrenees., Ararat was the LGA with the highest cancer incidence rate among women. Ararat is one of the most socioeconomically disadvantaged LGAs in the western Victorian region. Low IRSAD scores indicate relatively greater socioeconomic disadvantage and a lack of advantage overall. For example, a low score would be reflective of an area with (among other factors) many households with low incomes, and/or many people in unskilled professions .Results from our study further demonstrated that LGAs with greater socio-economic disadvantage, and LGAs which scored as less accessible and more remote, were associated with higher cancer incidence rates. These results correlate with the current available literature for Australian populations, which demonstrate disparities in cancer incidence between rural and metropolitan regions , 9, 25. . Outcomes of this study can target healthcare utilization and management of disease locally. Importantly, this study can be utilised as a repeatable profiling model in other geographical settings, where a variety of population densities are present to identify targeted interventions to reduce disparities in cancer outcomes in regional and rural communities.The ACDI study aims to describe the pattern of chronic disease and injury and its relationship with age, sex and location for the region of western Victoria. To date, this study has investigated several diseases and injuries including diabetes, fracture and joint replacement , 33–35. Mandatory notification of new cancer diagnoses is provided to the VCR by hospitals, pathology laboratories and cancer screening registers across the whole of Victoria. The VCR initiated in 1982 and is the most comprehensive and reliable cancer registry in the state, thus it is unlikely that any cases have been missed for the years (2010–2013) analysed in this study. We acknowledge that survival rates were not assessed in this study. The LGAs included in this study are highly diverse and include cities as well as regional centres and LGAs with small populations and large areas including agricultural lands. However, no LGAs in this study region were in the “remote” or “very remote” ARIA categories, and this study included the LGA of Hindmarsh, which has the highest ARIA in the state of Victoria. Thus, results may need to be interpreted with caution when addressing this model on highly remote areas. No inferences can be made at an individual level as ARIA and IRSAD were investigated on an area level, and we utilised aggregated data for analysis. Furthermore, ARIA scores do not account for access to oncology services and screening centres. Nevertheless, these data can be utilised to assist health service planning and implementation of targeted preventative and intervention strategies, screening services and treatment, survivorship and palliation procedures to ensure better service provision across western Victoria.In conclusion, results from this study identified that for the region of western Victoria, cancer incidence rates vary among men and women and across LGA and increase with advancing age, greater socio-economic disadvantage and remoteness/lower accessibility. Identifying inequalities in rural and regional health service delivery is important and it is anticipated that these findings will assist in implementing targeted and improved services at all points of the cancer continuum from prevention strategies, screening services, treatment, survivorship and palliation. This study also provides a model for further understanding of geographical locations with national and international implications.


I am honoured to address as the seventh president of the Mycological Society of China. Mycorrhizal research has a long history in China, including taxonomy, diversity, ecology, molecular biology, and application. Particularly in the past four decades, great progress in mycorrhizal field has been made by Chinese mycologists and ecologists. In this paper, through my own experience, I summarised the main and important advance of recent mycorrhizal researches in terms of mycorrhizal fungal diversity, community, responses to global environmental changes, molecular biology, and function in China. Some perspectives are also proposed for future mycorrhizal studies in China. Mycorrhizae are symbiotic structures formed between soil fungi and terrestrial plant roots , ectomycorrhiza (EM), ectendomycorrhiza, orchid mycorrhiza, arbutoid mycorrhiza, monotropoid mycorrhiza, and ericoid mycorrhiza  papers (Web of Science Core Collection) and 2272 papers in Chinese Journals  have been published by Chinese scientists since 1980  . ParticuQuercus liaotungensis and Pinus tabulaeformis in a temperate forest ecosystem using direct internal transcribed spacer (ITS) sequencing of EM root tips  from intermedium (41−80 years) and old (>80 years) forests, and the EM fungal community assembly was significantly structured by environmental selection in the young and intermedium forests, but by environmental selection and dispersal limitation in the old forest in a subtropical ecosystem  plantation affected rhizosphere soil AM fungal ERH density, richness and community composition  density, and richness  and confirmed their function under drought stress. Liu et al. (R. intraradices and soybean mitogen-activated protein kinase (MAPK) transcripts in mycorrhizal soybean roots, indicating the possibility of a molecular dialogue between AM fungus and host plant and suggesting that they might cooperate to improve soybean’s resistance to drought stress. Concurrently, in terms of nutrient absorption, some studies investigated the mycorrhiza-regulated phosphate transporters in host plants Astragalus sinicus , Rhizophagus irregularis and phosphate-solubilising bacterium  reuptake and was required for AM symbiosis  were transferred to the fungus. Moreover, Chinese scientists have made significant progress in terms of mycorrhizal signal transduction, for example, some specific proteins such as DELLA and CERK1, were found to be common components of symbiotic mycorrhizal signalling pathways and to play critical function during the establishment of symbiosis between AM fungi and host plants  could alleviate the side effects induced by fungicide chlorothalonil on upland rice growth  was found to significantly decrease the concentration of organophosphate insecticide named phoxim in shoots and roots of carrot and green onion  and PGPR Bacillus sp. could interact to maximally suppress the root-knot nematode (i.e. Meloidogyne incognita) and tomato disease development. Recently, He et al. (Spodoptera exigua) altered the photosynthesis and plant endogenous hormones of peanut and tomato. Additionally, the application of mycorrhizal inoculation was found to improve carbon sequestration of coalfield soils and thus to be beneficial for the ecological reclamation in mine region  significantly promoted a competitive advantage of Rhus chinensis over both Celtis sinensis and Cinnamomum camphora  significantly promoted a competitive ability of the mid-successional tree Cyclobalanopsis glauca over the pioneer tree Pinus massoniana compared with the uninoculated control treatment  to conduct more wide and deep researches on the mechanism of mycorrhizal fungal diversity maintenance and community assembly, (2) to strengthen the studies on molecular interaction mechanisms between mycorrhizal fungi, host plants, and other organisms, (3) to improve understanding of mycorrhizal fungal response and adaptive mechanisms under global environmental changes, especially to uncover possible alterations of ecological functioning under interactive conditions of multiple global change factors, and (4) to increase the application of mycorrhizae. I believe that, with increasing of joined Chinese young mycorrhizal scientists and financial support by Chinese government, Chinese scientists will make great progress in mycorrhizal field in future.


Over a fifth of all new HIV infections in the United States occur among persons aged 13 24 years, with most of these diagnoses occurring among gay and bisexual males (81%). While the epidemic of HIV in the United States has leveled off for many age groups, the annual number of new HIV diagnoses among young men who have sex with men  remains high. Traditional approaches to continuum improvement for youth have been insufficient, and targeted interventions are urgently needed for young people at risk for or infected with HIV. Interventions delivered through mobile health technology represent a promising approach for improving outcomes in this population. Mobile phones have nearly reached saturation among youth, making mobile technology a particularly promising tool for reaching this population.The University of North Carolina/Emory Center for Innovative Technology (iTech) is a National Institutes of Health cooperative agreement as part of the Adolescent Medicine Trials Network for HIV/AIDS Interventions. iTech aims to impact the HIV epidemic by conducting innovative, interdisciplinary research on technology-based interventions across the HIV prevention and care continuum for adolescents and young adults in the United States, particularly YMSM, by providing the following: (1) evaluation of novel approaches to identifying youth with undiagnosed HIV infections; (2) evaluation of multilevel, combination prevention approaches, particularly relevant to gender- and sexual-minority youth facing co-occurring health risks; (3) evaluation of uptake of and adherence to biomedical prevention modalities; and 4) evaluation of interventions designed to promote or optimize engagement in care and antiretroviral therapy adherence in HIV-positive youth, to optimize viral load suppression.iTech brings together multidisciplinary experts in the fields of adolescent HIV treatment and prevention, development and evaluation of technology-based interventions, HIV surveillance and epidemiology, and intervention design and evaluation. This initiative will support 8 efficacy trials and 2 exploratory projects, each led by 2 principal investigators. Taken together, the studies address all of the key steps of the HIV prevention and care continuum for youth in the United States. Each proposal uses technology in a scientifically rigorous and innovative way to access, engage, and impact at-risk or infected youth. Nine iTech subject recruitment venues are spread across 8 US cities. Three cores  support all iTech activities and form the research network’s infrastructure, facilitating all aspects of study implementation and evaluation.Formative work has already begun on many of the above-mentioned iTech trials. We expect the first randomized controlled trials to begin in mid-2018. Additional details can be found in the individual intervention protocol papers in this issue.Through its comprehensive research portfolio, iTech aims to effectively advance HIV prevention and care for youth through technology-based, youth-relevant interventions that maximize adaptability and sustainability.RR1-10.2196/10365 Over a fifth 22%) of all new HIV infections in the United States occur among persons aged 13‑24 years, with most of these diagnoses occurring among gay and bisexual males (81%) [2% of allAdvances in HIV prevention tools can effectively reduce new HIV infections among youth. Antiretroviral therapy (ART) is a powerful tool and can be used among HIV‑negative youth to reduce susceptibility to infection  or among youth living with HIV infection (in the form of treatment as prevention) to reduce infectiousness -6. The eHIV testing is the critical first component to facilitate entry into HIV prevention and care. Individuals who are aware of their infection can begin treatment, thus reducing the likelihood of onward transmission and improving clinical outcomes . Those iAlthough PrEP has demonstrated high efficacy in clinical studies, uptake has been low among YMSM, especially YMSM of color ,15,16. TFor youth diagnosed with HIV, engagement in care and treatment with ART to achieve viral suppression are critical components for reaching the goals of improved individual health and prevention of onward transmission. In the United States, only approximately 44% of young people aged 13‑24 years diagnosed with HIV have achieved viral suppression .Thus, traditional approaches to continuum improvement for youth have been insufficient. Targeted interventions are urgently needed to improve the knowledge of undiagnosed HIV infection, access to and retention in prevention and care, medication adherence, and long-term viral load outcomes among youth at risk for or infected with HIV. Interventions delivered through mobile health  technology represent a promising approach for improving outcomes among youth at risk for or infected with HIV. Mobile phones have nearly reached saturation among youth, making mobile technology a particularly promising tool to reach this population. As of 2015, 78% of those aged 18-29 years in the United States own a desktop or laptop computer and 98% report having a mobile phone of some kind, and 86% of these devices are smartphones . AlthougAlthough a number of apps related to HIV and other sexually transmitted infections (STIs) are available via commercial sites , there are limited data to support the design of these apps or rigorous evaluations of their impact ,29. Of nTo effectively advance HIV prevention for youth, technology-based, youth-relevant interventions that maximize adaptability and sustainability need to be developed, heeding lessons learned from successes and failures of in-person interventions. A more efficient and potentially more scalable process for developing and testing these interventions would be to collate interventions that share common principles, design elements, data collection, and evaluation approaches. Moving forward, it is imperative that we build upon and enhance successful platforms to develop sustainable technology-based solutions that represent the highest standards of usability, affordability, accessibility, and large-scale dissemination.The University of North Carolina (UNC)/Emory Center for Innovative Technology (iTech) is a National Institutes of Health cooperative agreement as part of the ATN . iTech aims to impact the HIV epidemic by conducting innovative, interdisciplinary research on technology-based interventions across the HIV prevention and care continuum for adolescents and young adults in the United States. The overall goals of iTech seek to decrease the impact of HIV on the lives of adolescents and young adults in the United States, particularly YMSM, by providing the following: (1) evaluation of novel approaches to identifying youth with undiagnosed HIV infection; 2) evaluation of multilevel, combination prevention approaches, particularly relevant to gender and sexual-minority youth facing co-occurring health risks  evaluation of uptake of and adherence to biomedical prevention modalities; and 4) evaluation of interventions designed to promote or optimize engagement in care and ART adherence in HIV-positive youth, to optimize viral load suppression.iTech will support 8 efficacy trials of interventions and 2 exploratory projects, each of which will be led by 2 principal investigators (PIs). Taken together, the studies address all of the key steps of the HIV prevention and care continuum for youth in the United States. Each proposal uses technology in a scientifically rigorous and innovative way to access, engage, and impact at-risk or infected youth. Nine iTech subject recruitment venues (SRVs) are spread across 8 US cities . Three cores  support all iTech activities and form the research network’s infrastructure that supports all aspects of study implementation and evaluation.iTech is composed of three cores  that function in a coordinated and complementary manner to achieve overall objectives . AuthorsManagement Core (MC) provides the organization and structure necessary to maximize the potential of the research projects within iTech. MC provides infrastructure, regulatory, and operational support and ensures communication and collaboration among the research studies within iTech and with the funders. It is responsible for the project management plan and overall and study-specific timelines, ensuring the project remains within cost and scope, and overseeing and monitoring the iTech SRVs.The iTech Analytic Core (AC) provides expertise and data systems for the conduct of formative research, usability testing, pilot studies, randomized controlled trials (RCTs) and economic analyses to support the aims of the iTech and its research protocols. Throughout the development, execution, analysis, and dissemination phases of each iTech study activity, AC provides guidance on implementing cross-site collaborative research, maintaining scientific rigor, and ensuring timely research completion. Activities of AC are supported by data analytic staff at Emory and UNC with skills in 4 primary areas: data management, qualitative data analysis, quantitative data analysis, and costing analyses. Lead statisticians assemble and supervise teams comprising AC data management and analytic staff for each RCT and complete the design and execution of primary analyses for each iTech study. AC also leads efforts to ensure study tools and measures are harmonized wherever possible across iTech studies and the broader ATN to facilitate pooled and large-scale secondary data analyses projects. Network-wide measures encompass 5 domains: demographics or socioeconomic characteristics, sexual behavior and risk, substance use or abuse, HIV-positive cascade, and HIV-negative cascade. In addition, other survey measures specifically for use within iTech were developed: additional demographic or socioeconomic characteristics, technology items , mental health, and social supports. Further details on ATN data harmonization can be found in a companion manuscript in this eCollection (will be cited once available).The Economic analyses are planned for five of iTech’s current studies . Cost data will be collected by input type and activity. Standardized tools and harmonized measures will be used across studies wherever possible. The study staff will develop the inventory of inputs for each activity for each intervention  and standard definitions of each input and unit of measure. Each study site will use a standard data collection instrument that lists all the inputs, the time frame for collection, and the primary source of cost data. We will use activity-based  costing to assess the cost of the respective interventions. Cost data will be collected by site. The average of the site-specific costs will be used, and the variation in site-specific costs will be examined and reported. Total cost results will be presented by cost per participant using the intervention and cost per percent increase in primary study outcome(s) , referent to the control arm.The iTech Technology Core (TC) provides services for technology-related fields, including mobile technologies, Web-based platforms, laboratory monitoring platforms that collect samples through mailed-out testing kits, social media- and Web-based recruitments, and technology-related ethics issues. TC provides a secure, HIPPA -compliant Web-based system for participant management and retention that is used across all SRVs and studies. TC assists with the measurement of paradata, auxiliary data that capture details about the process of interaction with the Web-based intervention, including website and app analytics, and creates an infrastructure to share and disseminate best practices in technology-delivered HIV interventions. To date, paradata have been underexamined and underreported in research among youth at risk for or infected with HIV [with HIV . ParadatThrough a developed and centralized management and analytic framework, iTech supports a network of multidisciplinary scientists, researchers, clinicians, and public health professionals who work collaboratively to support iTech’s diverse research portfolio. The network science team is made up of all research study PIs, SRV PIs, plus members of iTech’s scientific leadership cores. This team meets monthly to talk about cross-cutting issues, brainstorm new concepts, review new scientific research, and leverage cross-protocol opportunities. iTech also supports a collaborative training and educational mission that crosses all cores and disciplines. iTech provides a nurturing environment to foster new junior investigators into adolescent HIV or AIDS research and builds collaborations to create new and innovative research in this area. We have deliberately built mentoring relationships into each of the research studies, pairing junior investigators with more experienced investigators.iTech has purposefully partnered with clinical care sites that have well-established community collaborations, including established youth advisory boards (YABs). We will work closely with each SRV to ensure sustained YAB involvement at each venue and within the larger iTech network. iTech’s leadership will also work closely with YABs and other community stakeholders and advisors to help evaluate tools and programs, ensuring age appropriateness and readability, cultural sensitivity and linguistic appropriateness, gender and sexual orientation sensitivity, and minimal burden of intervention strategies. In addition, iTech has proposed involvement of at least one YAB member from each SRV in monthly Web-based Youth Advisory Council meetings to allow input on local as well as cross-iTech issues.All research conducted within iTech will be centrally reviewed and approved by the institutional review board (IRB) of the University of North Carolina at Chapel Hill, acting as the IRB of record in accord with National Institutes of Health policies . Local IThe iTech scientific agenda is translated through 8 efficacy trials and 2 exploratory projects, all designed to address 4 primary objectives. Each study includes qualitative formative research to develop or adapt the intervention and an RCT of the intervention(s) versus standard of care. Many new or substantially adapted interventions are also conducting technical pilots in which the intervention is tested for a short period of time and qualitative exit interview data are used to finalize the intervention for RCT. This standardization of the research process across iTech studies is a key aspect of the network. Below, we outline each of the 4 objectives and briefly describe the interventions currently in place to address these objectives; note that all iTech interventions address multiple components of the care and prevention cascades and cross-cutting issues . AdditioDespite Centers for Disease Control and Prevention and American Academy of Pediatrics recommendations that high-risk youth receive an HIV test at least annually , many seLYNX: LYNX is a novel mobile app designed to increase HIV or STI testing and support PrEP uptake among YMSM. In this study, the investigators will expand their current mobile app, designed primarily to increase HIV or STI testing, to include components to increase the uptake and linkage to PrEP for YMSM, and then evaluate the feasibility and acceptability of this app in a pilot RCT. The key components addressed by the integrated LYNX app will be information, motivation, and behavioral skill needs [ll needs -38 for iMyChoices: MyChoices is a youth-optimized version of a mobile app designed to increase HIV or STI testing and support PrEP uptake among YMSM [ong YMSM . In thisong YMSM .COMPARE: If either app described above (or both) is shown to be feasible and acceptable, the app(s) will be tested in this follow-on research study to evaluate for efficacy. If both are deemed feasible and acceptable, YMSM in this 3-year study will be randomized to receive either MyChoices or LYNX or standard of care information about HIV testing and PrEP.We Prevent: This project aims to develop and test a relationship skills-focused HIV prevention intervention for YMSM and their partners. The intervention consists of two telemedicine sessions: the first focuses on relationship skills, and the second consists of HIV testing and counseling for couples and prevention planning [planning . Both seStructural factors, such as lack of access to or prior negative experiences with prevention and care services may impede HIV or STI testing and PrEP uptake among YMSM and transgender youth, particularly among youth with co-occurring health risks and comorbidities  -44. It iGet Connected: Get Connected! is a motivationally based, brief Web-based intervention that employs individual and system-level tailoring technology to reduce barriers to linkage into competent prevention care  for YMSM [for YMSM ,46. YMSMTechStep: The rates of HIV infection among transgender youth  are extremely high, particularly among transwomen [answomen ,48 and tanswomen . Furtheranswomen . TechStePrEP provides a strong preventive benefit to youth at risk for HIV infection and there is overwhelming evidence supporting its efficacy ,21,51-53LifeSteps for PrEP for Youth (LSPY): LifeSteps is an evidence-based HIV medication adherence intervention for HIV infected individuals, which was developed by Safren et al [en et al -59 and hen et al -62, inclen et al . It consP3 : P3 is an interactive mobile phone app for HIV-uninfected YMSM. The app utilizes social networking and game-based mechanics, as well as a comprehensive understanding of what constitutes “best practices” in app development to improve PrEP adherence and retention in preventive care. An enhanced arm (P3+) will deliver in-app adherence counseling based on the integrated Next Step Counseling model [ng model ,65. A thePrEP: Rural and periurban areas across the Southeast do not have extensive access to PrEP providers. A tailored approach for rural YMSM, addressing known structural barriers of transportation, access to providers, and privacy, is likely to yield high levels of PrEP initiation and persistence in care. The study will finalize the development of a unified rural telemedicine system with a standalone mobile phone app interface and then conduct an RCT of the ePrEP intervention to determine if there is higher PrEP adherence compared with a control condition, which gives access to a Web-based PrEP locator.Poor adherence among youth is multifactorial and includes medical , logistical , and psychological  barriers ,67. SuffYouTHrive: YouTHrive (pronounced “youth thrive”) is a Web app intervention to improve ART adherence among youth living with HIV that has the following components: (1) enhanced peer-to-peer interaction, (2) engagement SMS text messages, (3) mood and ART adherence self-monitoring, (4) goal setting, and (5) tailored ART and HIV informational content. Gamification techniques  are used to promote sustained engagement.Formative work has already begun on a number of the iTech trials detailed above. We expect the first RCTs to begin in mid-2018. iTech is anticipating preliminary findings from the first randomized control trials (LYNX and MyChoices) to be presented by early 2019. Additional preliminary findings from TechStep and P3 are expected mid to late 2020, with YouTHrive, Get Connected, and ePrEP presenting preliminary RCT findings by late 2021. We expect additional findings as we add new interventions focused within each of our four iTech objectives.iTech brings together multidisciplinary experts in the fields of adolescent HIV treatment and prevention, development and evaluation of technology-based interventions, HIV surveillance and epidemiology, and intervention design and evaluation. Fostered by an MC that prioritizes communication and collaboration, this robust team will work collaboratively to respond to emerging issues and promote continued advancements in the field.Technology-delivered interventions are well-suited for youth given their modality, the common use of technology in the population, the platform’s suitability to deliver tailored content specific to each user’s HIV or AIDS risk behaviors and context, and the platform’s unique capability to diffuse HIV or AIDS prevention programs to large numbers of youth residing in numerous geographic locations. Youth, including YMSM, are receptive to internet- and mobile phone-delivered interventions ,70,71.Using the internet to recruit, engage, and retain youth in interventions is not only possible but also necessary. Youth may lack the social capital or resources to access in-person interventions, may be dependent on adults for money or transportation, or may need permission to attend programs. These barriers are particularly problematic for YMSM who, due to anticipated or actual stigma, are unable or unwilling to talk to adults about their same-sex attractions, behavior, sexual identity, and need to receive prevention and care services -75. Trad


This systematic review assessed the current evidence base of substance use prevention programs for Indigenous adolescents in the USA, Canada, Australia and New Zealand. The authors investigated (a) the outcomes, type, setting and context of prevention programs; (b) the common components of beneficial prevention programs; and (c) the methodological quality of evaluations of included prevention programs. The authors searched eight peer-reviewed and 20 grey literature databases for studies published between 1 January 1990 and 31 August 2017. Data extracted included type of program , the setting , delivery , context  and common components of the programs. Program evaluation methodologies were critically appraised against standardised criteria. This review identified 26 eligible studies. Substance use prevention programs for Indigenous youth led to reductions in substance use frequency and intention to use; improvements in substance-related knowledge, attitudes and resistance strategies; and delay in substance use initiation. Key elements of beneficial programs included substance use education, skills development, cultural knowledge enhancement and community involvement in program development. Five programs were rated as methodologically strong, seven were moderate and fourteen were weak. Prevention programs have the potential to reduce substance use among Indigenous adolescents, especially when they are developed in partnership with Indigenous people. However, more rigorously conducted evaluation trials are required to strengthen the evidence base. Some governments have officially acknowledged and apologised for their roles in the disruption and abuses inflicted upon Indigenous peoples , Canada, Australia and New Zealand have a comparable history of colonisation and dispossession of culture and land by English settlers, resulting in predominantly English-speaking countries in which Indigenous People are a marginalised minority. The centuries following early colonisation have continued to harm Indigenous peoples through This history combined with contemporary issues such as continued policy failures in social services, education and health care systems have resulted in loss of cultural knowledge and language in Indigenous communities and poorer outcomes in many of the social determinants of health compared with the non-Indigenous population, and significant trauma for Indigenous peoples with lasting inter-generational effects Cornell . The impSubstance use prevention strategies have shown to be effective for non-Indigenous adolescents, including school-based, community-based and family-based programs  the outcomes, type , setting  and context  of prevention programs; (b) the common components of beneficial substance use prevention programs; and (c) the methodological quality of evaluations of substance use prevention programs.This systematic review followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines  evaluated a prevention program aiming to reduce substance use and related outcomes, (b) compared an experimental group to a control group and/or assessed changes over time, (c) included participants aged 10 to 19 years, (d) comprised at least 50% of participants who identified as Indigenous and/or there was a specific sub-analysis for Indigenous participants, (e) were published between 1 January 1990 and 31 August 2017, and (f) full text was available to the authors.BL screened all titles and abstracts based on the eligibility criteria, and a random selection of 25% of studies was independently screened by MS to ensure accuracy in the study selection. There was an agreement on 90% of studies, and consultation was held between the two authors to reconcile the disagreements. MS and BL independently assessed the eligibility of 67 full-text articles, with high inter-rater agreement between the two authors for this assessment . Again, consultation was held between the two authors to reconcile differences of opinion.Data relating to the program and the evaluation of the program were extracted from the included studies. Program types were culture-based, culturally adapted or unadapted . Common program components were determined by identifying the components of these programs that showed broader beneficial impacts.The methodological quality of quantitative studies was assessed using the Quality Assessment Tool for Quantitative Studies from the Effective Public Health Practice Project (EPHPP) , followed by tobacco (n = 12) and cannabis (n = 10). Other substances included stimulants (n = 1), inhalants (n = 2) and analgesics (n = 1). Appendix Table Of the 1483 articles screened, 26 publications reporting results of evaluations of substance use prevention programs for Indigenous youth were eligible. Reasons for exclusion are detailed in Fig. Outcomes of the evaluations are listed by substance-related outcome type in Table Keepin’ it REAL program: two were a cultural adaptation of this program called Living in 2 worlds  studies evaluated a culture-based program, ten (38%) studies evaluated a culturally adapted program and one (4%) study evaluated an unadapted program. Cultural adaptation of non-Indigenous programs included translation of concepts into local Indigenous language and concepts, developing cultural images and the adaptation of activities to include cultural activities such as prayer, dancing and circle conversations. Three studies evaluated the CONNECT), a community-based program (CMCA) and a program where CONNECT and CMCA were combined. These studies found the multi-setting programs had a smaller effect on substance use than the school- or community-based program on their own  evaluated programs were school-based, five (19%) were community-based, five (19%) combined school and family, one (4%) combined community and school, two (8%) combined family and community-based programs, and four (15%) were delivered in community, family and school settings. Family involvement in programs was primarily through one-off workshops or pamphlets given to parents and was not specifically evaluated in any study. Two studies evaluated programs that were delivered in a single setting compared to multiple settings: Schinke et al.  comparedIn terms of the context in which prevention programs were implemented, 12 (46%) were implemented in reservation/discrete Indigenous communities where all community members identify as Indigenous, ten (38%) were implemented in an urban setting, two in Indian territory and two in rural communities. Programs implemented in non-Indigenous specific areas still had 100% Indigenous participants in the evaluation study, except for five studies which had between 16 and 90% Indigenous participants and were all school-based  and Indigenous program facilitators (5 programs). Four programs used health education strategies, which included providing healthy alternatives to substance use, incorporating a holistic concept of wellbeing and media campaigns about healthy lifestyles. Three programs included a booster session 3 to 6 months following program implementation and three programs included recreational activities, such as sports, festivals, painting, going out bush and filmmaking.SmokingZine and Boy and Woman Bear. SmokingZine was an adaptation of a non-Indigenous Web site and included educational modules with culturally relevant content and imagery. It was found to reduce intention to use tobacco, reduce positive beliefs about tobacco smoking, and increase likelihood to help others quit smoking  were provided in two of the four (50%) studies  measured four outcomes, whereas beneficial studies  measured three outcomes. While this is not ideal, it was a useful method of narratively summarising outcomes of the included studies. However, as a consequence of this approach, conclusions about effectiveness of drug prevention for Indigenous youth could not be made. Finally, this review included some studies with a small sample size and these findings should be interpreted with caution as they may lack statistical power to show a statistically significant or clinically meaningful result.Overall, the results of this review indicate that substance use prevention programs have the potential to produce beneficial substance-related outcomes for Indigenous adolescents, especially when they are developed with Indigenous people and include components of skill development, cultural knowledge enhancement and substance-related education. However, methodological quality of the included evaluations lacked the rigour required to draw conclusive statements about the effectiveness of substance use prevention programs for Indigenous adolescents. There is an urgent need for more financial and time investment in conducting rigorous evaluations using practical and alternative research designs, such as multiple baseline designs and cluster RCTs, to create a strong evidence base of what works to prevent substance use among Indigenous youth.