While this is good news, these pathogens still retard the development and health of rural communities, especially in Africa. Several NTDs are caused by pathogens transmitted by arthropod vectors, principally mosquitoes, tsetse flies, and ticks. New initiatives bring welcome attention and resources, which may finally lead to the control of diseases like sleeping sickness that were reported to have been controlled during decades of intensive control In a recent article titled “Neglected No Longer: New Progress on NTDs,” Richard Hartfield argues that NTDs are now mainstream because they are on the agenda of three key policy forums―the African Union (AU), the World Health Assembly (WHA), and the Organization of American States (OAS)  Insect ecology and genetics, (2) insect sensory physiology and behaviour (establishing the first electrophysiology laboratory in Africa), (3) insect hormones and chemistry, and (4) biophysics of insects. Five insect species were initially selected because of their critical importance to Africa, three of them—tsetse, ticks, and mosquito vectors of the Yellow Fever Virus—vectors of NTDs. Research capacity was initially developed and strengthened under the leadership of visiting directors of research while mentoring African researchers .http://www.uia.be/s/or/en/1100049901). He received several awards in recognition of his scientific and other achievements, including the African Prize for Leadership for the Sustainable End of Hunger (1987), jointly with the then president of Senegal, Abdou Diouf, from US President Ronald Reagan http://hrst.au.int/en/).TRO's ability to raise funds, negotiate, and organize was further demonstrated by his influence in the formation of the African Academy of Sciences (AAS) in 1985, for which he also served as President from 1986 to 1999, and by helping to set up the African Foundation for Research and Development (AFRAND) (Phenacoccus manihoti) using its exotic natural enemy Epidinocarsis lopezi, for which he received several awards, including the 1995 World Food Prize TRO was succeeded as director-general (DG) in 1994 by Swiss scientist Dr. Hans Rudolf Herren, who led the Centre until 2005. Hans came from the background of having led a campaign to control the cassava mealy bug (Glossina fuscipes fuscipes in East Africa Kobus defassa) were rarely fed on by tsetse. These studies led to the identification of a synthetic tsetse repellent 2-methoxy-4-methylphenol  2 by tsetse flies Research in the field of tsetse flies and trypanosomiasis has been boosted by the publication of the genome of The Biosystematics Support Unit at ICIPE hosts many slide mounts of sandflies (phlebotomine vectors of leishmaniasis), which shows the amount of work that went into surveys to describe sandfly biodiversity and disease epidemiology ICIPE's third DG, Professor Christian Borgemeister (2005–2013), has extended the benefits of the 4-H paradigm by consolidating thematic teams, with the Integrated Vector and Disease Management (IVDM) cluster incorporating Animal and Human Health functions, and by bringing in additional capacities in geospatial sciences. While expanding many research streams, Borgemeister has spearheaded efforts to develop the necessary infrastructure to adequately address arthropod-transmitted viral  and bacterial pathogens, including Rift Valley fever (RVF). The newly established Martin Lüscher Emerging Infectious Diseases Laboratory (MLEID), which has an insectary and a Biosafety Level 3 (BSL3) facility that offer appropriate containment, is the centrepiece for these activities, important for studies of arboviruses vectored by mosquitoes and ticks. The MLEID has also enhanced capacity building through postgraduate-level training and short-term training for students from several countries.http://www.icipe.org/avid/; http://www.icipe.org/cernvec). In 2012, ICIPE was designated as a Food and Agriculture Organization of the United Nations (FAO) Reference Centre for vectors and vector-borne animal diseases  in recognition of ICIPE's “attainment of scientific, technical, and policy standing and its commitment to strengthen capacity development in those areas relevant to FAO's mandate.”Growing ICIPE's research portfolio in this way has allowed the institute to advance knowledge in vector ecology along the path toward developing vector control strategies for reducing the threat and impact of emerging infectious diseases (EIDs). These studies include disease epidemiology www.icipe.org/arppis) is a collaborative programme between ICIPE and African universities, which aims to (1) build capacity on the continent and (2) generate knowledge in innovative insect science, thus contributing to the reduction of poverty and food insecurity. Since its launch in 1983, ARPPIS has trained more than 250 PhD-level scientists and in excess of 300 at the level of MSc by offering fully sponsored fellowships, mostly through the three regional centres: the University of Ghana at Legon, Addis Ababa University, and the University of Zimbabwe in Harare. DRIP complements ARPPIS by enabling students not eligible for ARPPIS fellowships to benefit from ICIPE's research mentorship. This has particularly benefited the researchers from government institutions , who often cannot enrol in full-time study. These training programmes have led to considerable output in terms of theses, publications, and new knowledge and tools. More than 30 doctoral theses on NTDs and more than double this number at the MSc level have been published. It is notable that some of the scholars have taken key leadership positions in their countries . During an interview carried out for an ARPPIS alumni tracer study in 2012, Professor Nyeko observed that the ARPPIS program is particularly useful in building teaching capacity at universities as it “trains PhD candidates who go back to teach others, thereby creating a cycle of knowledge recreation.” He also observed that this is but a small step in alleviating a great sea of need in Africa.ARPPIS Click here for additional data file.


Wohlfahrtia magnifica (Sarcophagidae), and two species of blow flies, Chrysomya bezziana and Cochliomyia hominivorax . The morphology of their first instar larvae is thoroughly and consistently documented here with light microscopy photographs and scanning electron microscopy micrographs. The following morphological structures are documented: pseudocephalon, antennal complex, maxillary palpus, oral ridges, thoracic and abdominal spinulation, spiracular field, posterior spiracles and cephaloskeleton. New diagnostic features drawn from the cephaloskeleton and the spinulation of abdominal segments, including the anal pad, are discovered and extensively described. Earlier descriptions in the literature are revisited, and major discrepancies between these and the results of the current study are discussed. The present results allow clarification, correction and, especially, complementation of information provided by earlier authors. The relatively distant taxonomic position of all three species is evidence that obligatory myiasis has arisen independently, and the extensively similar morphology in the first instar larvae of Chrysomya bezziana, Cochliomyia hominivorax and W. magnifica in comparison to necrophagous species, especially the enhancement of the anterior part of the cephaloskeleton and the segmental spinulation, is therefore best interpreted as homoplasic adaptations to a life strategy as obligate vertebrate parasites. An identification key for first instar larvae of all obligatory traumatic myiasis agents of mammals is provided.There are only three fly species that are obligate agents of traumatic myiasis of humans and livestock: a single species of flesh fly,  Chrysomya bezziana Villeneuve, 1914, Cochliomyia hominivorax  and Wohlfahrtia magnifica  are obligatory parasites, which under natural conditions complete their larval development only in the tissues of living vertebrates  to revise existing data concerning the L1 morphology of the known OTMAs, (2) to expand this knowledge by providing new data and (3) to prepare an easily applied identification key to the L1 of all OTMAs.Chrysomya bezziana and Cochliomyia hominivorax were obtained from laboratory colonies maintained at the Indonesian Research Centre for Veterinary Science, Bogor, Indonesia, and the Mexican-American Commission for the Eradication of Screwworm (COMEXA), Chiapa de Corzo, Mexico, respectively. Larvae of W. magnifica were obtained from gravid females collected from rural surveys around Budapest, Hungary  to extend the pseudocephalon and avoid subsequent deformation when stored in 70 % ethanol .Ten L1 of each species were slide-mounted in Hoyer’s medium , three thoracic segments (t1–t3), seven abdominal segments (a1–a7) and an anal division (ad), which carries the posterior spiracles Fig. . Each thPseudocephalon: Antennal complex with slightly elongated dome, height of basal ring less than length of antennal dome Fig. ; maxillaPseudocephalon: Antennal complex with slightly elongated dome, height of basal ring less than length of antennal dome Fig. ; maxillaChrysomya bezziana, elongated and slightly curved, size of spines decreasing gradually towards the posterior end of body  as well as in some (probably most) species of Miltogramminae  shortening of oral ridges, which terminate medio-laterally on the pseudocephalon; (2) absence of hair-like spines around the spiracular field on the anal division; and (3) peristigmatic tufts with broad and sparsely dichotomous branches.Species of OTMA belong to quite distantly related taxonomic units.


Humeral morphology has been shown to reflect, in part, habitual manipulative behaviors in humans. Among Central European agricultural populations, long-term social change, increasing task specialization, and technological innovation all had the potential to impact patterns of habitual activity and upper limb asymmetry. However, systematic temporal change in the skeletal morphology of agricultural populations in this region has not been well-characterized. This study investigates diachronic patterns in humeral biomechanical properties and lengths among 174 adult Central European agriculturalists through the first ∼5400 years of farming in the region. Greater asymmetry in biomechanical properties was expected to accompany the introduction of metallurgy, particularly in males, while upper limb loading patterns were expected to be more similar between the Bronze and Iron Ages. Results revealed a divergence in the lateralization of upper limb biomechanical properties by sex between the Early/Middle Neolithic and Early/Middle Bronze Age. Neolithic females had significantly more variable properties than males in both humeri, while Bronze Age female properties became homogeneous and very symmetrical relative to the right-biased lateralization of contemporaneous males. The Bronze Age to Iron Age transition was associated with morphological change among females, with a significant increase in right-biased asymmetry and a concomitant reduction in sexual dimorphism. Relative to biomechanical properties, humeral length variation and asymmetry were low though some significant sexual dimorphism and temporal change was found. It was among females that the lateralization of humeral biomechanical properties, and variation within them, changed most profoundly through time. This suggests that the introduction of the ard and plow, metallurgical innovation, task specialization, and socioeconomic change through ∼5400 years of agriculture impacted upper limb loading in Central European women to a greater extent than men. The biomechanics of the human upper limb are complex; largely free from weight bearing activities, the arms can be employed both unilaterally and bilaterally in a wide variety of ways. As the relationships between upper limb morphology, biomechanics, and manipulative behaviors are complex, interpreting morphology in the context of cultural change in the past can be challenging. A single dominant activity has the potential to obscure the influence of multiple less-dominant behaviors Complexity in patterns of bone adaptation within and among agriculturalist groups is also associated with increasing social complexity through time. A comparison of two Italian agricultural populations with similar subsistence activities but different socioeconomic structure (Neolithic (∼6000-5500 BP) versus Iron Age (∼2600-2400 BP)) found marked humeral asymmetry in Iron Age males, associated with the use of weapons, but symmetry in Iron Age females, likely associated with the performance of cereal-processing activities The study of bone adaptation in modern human athletes of known loading regime has greatly facilitated the interpretation of complex behavior patterns in the past from skeletal remains. Many studies of athletes in racquet and throwing sports that produce bilaterally asymmetrical loading patterns have found greater bone mineral content, cortical area, total subperiosteal area, and bending and torsional rigidity in the dominant (loaded) limb relative to the non-dominant limb Expressing an individual's left and right bone biomechanical properties as percent asymmetries allows asymmetry to be more confidently attributed to the local influences of mechanical loading There have been very few studies of asymmetry in humeral biomechanical properties or lengths following the introduction of farming, though see Linearbandkeramik (LBK) culture (∼5500-4900 BC), characterized by its distinctive pottery style, adze-axe stone tools, and timber longhouses alföldi vonaldiszes kerámia, who shared many cultural features with the LBK In Central Europe, the earliest farmers belonged to the Early Neolithic Linear Pottery cultures. In much of the region, this was the Sex differences are evident in the dentition of LBK groups, indicative of dietary differences The many innovations in technology and metallurgy of the Middle/Late Neolithic likely also impacted upper limb loading. Simple ards were used for cutting shallow furrows in the soil, but bilateral manual labor with hoes and other implements would still have been required to first clear the land of brush or cut deeper furrows if required. Plows that actually turned the soil both allowed for more difficult soils to be worked and more land to be exploited Throughout the Bronze Age in Central Europe, in addition to the physical requirements of mining and the production of metal objects, the increased use of weaponry and the great variety of tasks in which individuals would have specialized all had the potential to produce differences in upper limb loading relative to the preceding Neolithic. By the Early Bronze Age  in Central Europe, metallurgy had intensified substantially and continued to do so through the Late Bronze Age , with significant technological and socioeconomic consequences Throughout the Bronze Age, copper metallurgy continued, with the novel addition of tin or arsenic to produce bronze, and the manual activities involved in copper and bronze production would have been similar. Agriculture also remained of primary importance in the Bronze Age, though upper limb loading patterns in the portion of the population involved in farming may have been altered by the use of ards and plows, querns for grinding grain, pounders, sickles, and various other implements at this time The shifting role of metals in society documents a gradual transition between bronze and iron production. In the Early Iron Age (∼800-450 BC) TA) and bending and torsional rigidity  Given the evidence for considerable social and technological change following the introduction of agriculture in Central Europe, it is likely that the type or distribution of habitual manipulative behaviors among members of the population would have been affected. Behavioral change may have altered upper limb loading, and thus may be reflected in humeral morphology. The mechanical performance of limb bones can be quantified by the calculation of cross-sectional geometric (CSG) properties, including estimates of compressive strength  had sufficient preservation of at least one humerus to be included in analyses of variation in length and CSG properties. Of these, 156  had paired elements from which asymmetry in CSG properties could be calculated. In 22 individuals, poor preservation of proximal or distal joint surfaces in one of the paired humeri required the estimation of maximum length from the well-preserved side, leaving 134 pairs of humeri  for inclusion in analyses of humeral length asymmetry.Age was estimated and sexes determined according to the methods outlined in Buikstra and Ubelaker http://rsbweb.nih.gov/ij/). Periosteal mould images do not provide visualization of the endosteal contour; however, periosteally-derived CSG properties (such as those quantified from silicone moulding and laser surface scanning) have shown strong correspondence with true CSG properties CSG properties of left and right humeri were generated using a silicone moulding method TA) and the polar second moment of area (J). TA is highly correlated with cortical area and provides a measure of compressive strength (mm2) J provides an estimate of torsional and (twice) average bending rigidity in any two perpendicular planes through the sum of the second moments of area for those planes, for instance about anteroposterior (xI) and mediolateral (yI) or maximum (maxI) and minimum (minI) planes J was quantified as the sum of maxI and minI. Size-standardization of CSG properties was performed following the method of Ruff TA/estimated body mass and J/(estimated body mass * maximum bone length2). Maximum humeral length parallel to the long axis of the diaphysis was recorded using an osteometric board, and body mass was estimated using an average of left and right femoral head diameters  following the equations for European Holocene populations presented by Ruff and colleagues The CSG properties analyzed in this study are total subperiosteal area : ((right-left)/(average of left and right))*100 TA and J; Auerbach and Ruff TA and J. Variability in maximum length, TA, and J in both left and right humeri by sex was quantified through the calculation of coefficients of variation (CV), calculated as (standard deviation/mean) *100, which provide a size-independent method for the evaluation of relative variation Humeral asymmetries in maximum length and CSG properties were explored through the conversion of lengths and unstandardized TA, and J in each sex between time periods as well as between cemeteries within each time period. Mann-Whitney tests were also used to test for sex differences in asymmetry in humeral length, TA, and J within each time period. A modified Levene's test for homogeneity of mean-adjusted absolute deviation scores was used to test for differences in CVs through time and between the sexes, as these might be indicative of changing task specialization and the range of activities being performed among males and females. The total group mean for each variable was calculated for males and females in each time period. Each individual's value for each variable, for example TA, was then adjusted by his or her group mean using the following equation, where ABS refers to absolute deviation: )/total group mean for TA). The result of this equation was an absolute deviation value for each individual, indicating how far each individual's value was from the group mean for a given variable . One-way analysis of variance (ANOVA) was used to test for temporal change in these absolute deviation scores adjusted for the mean, in each sex as well as between the sexes. If the ANOVA indicated a significant difference between the absolute deviation scores of two groups, variation between the groups was considered to be significantly different.The Kruskal-Wallis test was used examine differences in %DA in maximum length, TA and J in each time period was significantly different from what would be expected by chance, chi-squared tests were used. Due to the need for both humeral elements to be well preserved, sample sizes were reduced for the examination of asymmetry. For this reason, no further statistical analyses were run on percent right-bias data. All statistical analyses were conducted in SPSS v20.To determine whether or not the percentage of right-biased individuals for TA, and J by time period and sex are presented in TA and J increased significantly from the Bronze Age to the Iron Age . Among Bronze Age cemeteries, it was the EBA cemetery of Brno-Tuřany that particularly drove high lateralization in J among males: at this cemetery, males had significantly higher %DA in J (%DA = 19.16%) than males at either Polgár Kenderföld  or Ostojićevo  (p<0.006) and Bronze Age (p<0.004) males .Summary statistics for mean %DAs in humeral length, p<0.024) . Percent4) males . This le Summary statistics for mean percent directional asymmetries (%DA) by time period and sex. Summary statistics for percent directional asymmetries (%DAs) by cemetery and sex.TA and J were calculated and together these provided a consistent picture through time of pervasive right-dominance in humeral strength and rigidity . Neolithic females also had slightly higher CVs for maximum length than males, but not significantly so  in left and right humeral CSG properties and maximum length by time period and sex are presented in TA or J was not significantly different between the sexes in the Early/Middle Neolithic. The range of %DAs among Neolithic males and females exhibited considerable overlap, but Neolithic females had significantly more variable CSG properties in both left and right humeri than males. Thus, results suggest that Neolithic females were loading their upper limbs in a wider variety of ways than males, likely through a broader range of manual activities, and that these activities generated similar patterns of lateralization to males (no significant differences in %DA). Women at the earliest LBK cemetery in Moravia (Czech Republic), Vedrovice, displayed a wide range of humeral %DAs, while mean female %DA values at the two early LBK cemeteries from southwest Germany, Schwetzingen This study explores the impact of agricultural intensification, metallurgy, and social change on habitual manipulative behaviors through ∼5400 years of farming in Central Europe. Mean asymmetry in TA and J was particularly high in males from these cemeteries  relative to the Linear Pottery sites of the Early Neolithic  compared to that of males . The authors attributed this sex-specific pattern of asymmetry in the Early Bronze Age to the performance of domestic labor among females and their decreased participation in intensive agriculture.The most pronounced sex differences in humeral %DA were found in the Early Bronze Age Únětice settlement and burial site of Brno-Tuřany , where male %DA in humeral site see . ArchaeoTA/J, compared to just 65% and 73% of females in the same properties. Humeral CSG properties were consistently right biased in both sexes in all Central European agriculturalists studied, but male values in all time periods fall at the top of the range of modern human values (the high end of reported right-biasing in modern human humeri is ∼90%+) J, while in all females combined (N = 71) the overall right bias was just 73.2%.Sex differences in percent right bias for humeral CSG properties were most pronounced in the Bronze Age , where 9Maximum lengths exhibited much lower variability and asymmetry than CSG properties, though they were consistently more right-biased in females across both the Neolithic and the Bronze Age. This was despite significantly higher %DAs in CSG properties in Bronze Age males relative to females, so asymmetry in bone length in the Central European groups studied does not immediately appear to reflect the influence of manipulative behavior to any large degree. Similarly, Auerbach and Ruff The current study and those of both Auerbach and Ruff TA and J relative to the more symmetrical values in Bronze Age females , but over the 1300+ years between the use of Brno-Tuřany and Brno-Maloměřice (Celtic) TA and J increased by approximately eight-fold (see J), though sample sizes are very small. Decorated bronze artifacts recovered from Brno-Maloměřice have been well-documented Lateralized behaviors were particularly interesting in one small region of Moravia near Brno, Czech Republic: not only did Early Bronze Age males at Brno-Tuřany (Únětice) exhibit the highest %DA in humeral fold see  for J, tSignificant Neolithic and Bronze Age sexual dimorphism in humeral maximum length asymmetry  also declined in the Iron Age, through a significant increase in male length %DAs relative to both preceding periods. It is not likely that this change in length asymmetry reflects major changes in the degree of upper limb loading in Iron Age males relative to previous males, as change in the lateralization of CSG properties would also be expected if this were the case. However, high task specialization among Iron Age males may have reduced the proportion of the population for whom activities would have involved the repetitive and strenuous overhead rotational motion  that may have been influencing length asymmetry in earlier males.Comparisons of humeral cross-sectional geometry among 174 adults spanning ∼5400 years from the onset of agriculture in Central Europe found that the long-term social change, increasing task specialization, and the expansion of copper and bronze metallurgy were associated with little change in upper limb asymmetry and variation among males but considerable change among females. These temporal patterns are suggestive of major changes in the sexual division of labor and the range of manual activities performed by women through the first ∼5400 years of farming in Central Europe. A major divergence in the lateralization of upper limb loading between the sexes occurred in the Early Bronze Age: female activities that loaded the upper limbs became more symmetrical and homogeneous relative to the Neolithic. This may be related to changing agricultural activities among females with the introduction of the ard and plow and/or the increased importance of bilaterally symmetrical tasks such as the grinding of grain, weaving and textile production, and the preparation of ground ores for smelting. Female upper limb loading became significantly more right-biased in the Iron Age, likely associated with the performance of activities involving significant amounts of unilateral loading. In contrast, males through the entire Central European sample exhibited consistent right-biased upper limb lateralization, indicative of the predominance of unilateral upper limb loading. In the Neolithic, habitual behaviors producing this type of loading likely included the use of adzes and axes for woodworking and land clearance, while in the Bronze and Iron Ages, additional male-dominated unilateral activities would have included the mining of metal ores and the smelting and production of metal objects, as well as the use of weapons. In contrast to diaphyseal cross-sectional geometry, asymmetry and variability in bone lengths was minimal and was not clearly associated with mechanical loading.Table S1Sample details and humeral percent directional asymmetries in TA, J, and maximum length for all individuals.(XLSX)Click here for additional data file.Table S2Sample details and size-standardized TA, J, and maximum lengths of the left and right humeri for all individuals.(XLSX)Click here for additional data file.


In 2011, the Division of Cancer Prevention and Control (DCPC), at the United States Centers for Disease Control and Prevention (CDC), released a three-year funding opportunity announcement (FOA) for a competitive, non-research cooperative agreement. The agreement enhanced the capacities of state health departments to promote the application of best practices for evidence-based breast cancer genomics through education, surveillance, and policy activities. The FOA required that applicants focus on activities related to hereditary breast and ovarian cancer (HBOC). The DCPC funded three states: Georgia, Michigan, and Oregon. Georgia was a first-time recipient of cancer genomics funding, whereas Michigan and Oregon had long standing activities in cancer genomics and had received CDC funding in the past. By the end of the funding period, each state had well-functioning and impactful state-based programs in breast cancer genomics. This article highlights the impact of a few key state activities by using CDC’s Science Impact Framework. There were challenges to implementing public health genomics programs, including the need to develop relevant partnerships, the highly technical nature of the subject matter, a lack of genetic services in certain areas, and the difficulty in funding genetic services. Georgia, Michigan, and Oregon have served as models for others interested in initiating or expanding cancer genomics programs, and they helped to determine what works well for promoting and integrating public health genomics into existing systems. Breast Cancer Susceptibility gene (BRCA) mutations are estimated to occur in 1 in 300 to 500 women in the general population ,3,4. BRCTo address this gap, in 2011, the Division of Cancer Prevention and Control (DCPC) at the Centers for Disease Control and Prevention (CDC) released a funding opportunity announcement (FOA) for a competitive, nonresearch cooperative agreement, Enhancing Breast Cancer Genomic Practices Through Education, Surveillance, and Policy. This FOA was intended to enhance the capacities of state health departments to promote best practices for evidence-based breast cancer genomics by using education, surveillance, and policy. Policy and education programs are needed to facilitate the translation of evidence-based genomic applications into practice, to help develop proper evidence for using genomic applications, and to aid health professionals and the public to understand the potential harms and benefits of evidence-based breast cancer genomic applications. In addition, surveillance is needed about the positive and negative uses and outcomes of breast cancer genomic applications.The overall purpose of the cooperative agreement, which was modeled after those previously released by CDC’s Office of Public Health Genomics (OPHG) , was to The FOA required that state health departments conduct policy or systems change activities and either surveillance or education activities. States could also propose to conduct activities in all three areas. The FOA did not require states to undertake specific activities within those three overarching areas, since there are a variety of ways to implement these activities, based on state needs, strengths, and limitations. The funding could not be used for research, fundraising, or clinical services. Application eligibility was limited to state health departments or their bona fide agents. DCPC funded three state health departments—the Michigan Department of Health and Human Services (Michigan), the Oregon Health Authority (Oregon), and the Georgia Department of Public Health (Georgia)—for a three-year period, and each grantee received approximately $ 300,000 per year. Georgia was a first-time recipient of cancer genomics funding and had minimal cancer genomics activities before funding, whereas Michigan and Oregon had long standing activities in cancer genomics and had received CDC funding in the past.Authorization and funding for this cooperative agreement was partially given by a provision of the Patient Protection and Affordable Care Act  . This prAll three grantees proposed education, surveillance, and policy activities in accordance with the FOA and consistent with state-based priorities. Grantees developed or enhanced activities for the promotion of breast cancer genomics. Activities were designed to increase appropriate BRCA 1/2 counseling and testing, increased insurance coverage of BRCA 1/2 and related clinical interventions for appropriate women, and included the development of educational programs to further the public’s and health care providers’ knowledge about family history, risk assessment, and the appropriateness of BRCA1/2 counseling and testing. Next, we briefly describe examples of state-specific activities.Educational activities were directed at the public and health care providers. Health care providers were educated by using in-person conferences, online modules and webinars, and provider newsletters. Both Georgia and Oregon, with CDC and other partners, collaborated with Michigan to create an online educational module for health care providers, which addressed the assessment of cancer family history for genetic risk and appropriate referral to genetic counseling and testing. All grantees included promotion and dissemination of this module in their educational efforts. Patient education activities conducted by the grantees included the development of web pages, lectures, newsletters, displays at health fairs, and information provided at clinician’s offices. Some of these public health activities were intended for high-risk populations, such as young breast cancer survivors and individuals of Ashkenazi-Jewish decent.Many of the surveillance activities used existing infrastructure, such as adding questions to the state’s annual Behavioral Risk Factor and Surveillance Survey (BRFSS) and analyzing state cancer registry data. Michigan and Oregon also used state cancer registry data to identify individuals with cancer diagnoses indicative of possible HBOC, and reported those cases back to the provider and cancer survivor, if possible, along with educational information about genetic counseling and testing . In addition, new surveillance systems were developed with key partners and stakeholders to assess uptake of HBOC genetic counseling, testing, and follow-up services. Michigan and Oregon developed new cancer genetic counseling and testing surveillance programs by partnering with genetics clinics across their respective states to collect data about patients accessing HBOC counseling services, including testing outcomes and follow-up services. Georgia conducted a survey of breast cancer survivors in their state to assess the uptake of genetic counseling, and the state tested and surveyed first and third-year primary care medical residents about their knowledge of HBOC and genetic counseling and testing recommendations. Georgia also collaborated with nine public health clinics across the state to integrate a genetic cancer risk-screening tool into their clinical intake process.®,  Clinical Practice Guidelines In Oncology ). This work was accomplished in a variety of ways depending on the state, but included meeting with health insurance plan medical directors, conducting key informant interviews and focus groups with health plan administrators to assess barriers and facilitators to having evidence-based coverage policies, and developing and disseminating policy guidance documents for insurers. Each state worked collaboratively with their state comprehensive cancer control (CCC) program; genomics objectives and activities were newly incorporated into Georgia’s CCC plans.Policy and systems change activities across all three states were fairly similar. All programs worked with health insurance companies, including private and, where possible, public options in their states, to ensure that coverage policies were consistent with evidence-based recommendations for referral to genetic counseling and testing  Degrees of Impact framework  and was The framework , Table 2Hereditary Breast and Ovarian Cancer: Is Your Patient at High Risk? The development and impact of this activity can be traced as follows.Michigan identified health care provider knowledge gaps by using surveys and other data sources. As one of their key educational activities, a free, online, educational module was developed with attached Continuing Medical Education credits (CMEs) called, BRCA mutations [Michigan developed and implemented a health care provider survey, and results were used to identify knowledge gaps and plan targeted education. Results from the survey showed limited knowledge of basic information about hereditary cancer, management and prevention strategies, and limited use of family history data to determine who to refer for genetic services. For example, only one-third of health care providers correctly identified autosomal dominant as the most common mode of inheritance for most hereditary cancer syndromes; less than one-half collected cancer family history when deciding who to refer to cancer genetics; and less than one-third correctly identified prophylactic oophorectomy as the procedure that most reduces risk of cancer for females aged 40 years with known utations Michigan developed the online CME module, Hereditary Breast and Ovarian Cancer: Is Your Patient at Risk? , with JaAs of February 2015, the site had received many page views (9500 page views from 1800 users in 2200 sessions), but there was limited uptake of CMEs . Most who took the test for CME credit were from Michigan, and an evaluation is ongoing, the results of which will be used to improve the training and dissemination plans. Michigan collaborated with many clinical partners, state organizations, health systems, health plans, advocacy and non-profit groups to promote several educational tools, including the online CME module.i.e., comprehensive cancer control, cancer surveillance, and cancer screening). For example, the DCPC recently developed and hosted a webinar about genomics and risk assessment for the NBCCEDP, given reimbursement changes . This work also informs key DCPC priorities and initiatives . The prBRCA counseling, testing, and related clinical services and gave nonmonetary awards to health plans for having written policies consistent with evidence-based recommendations. Michigan also held focus groups with eight health plan administrators to understand and address barriers and facilitators to the uptake of evidence-based policy by health plans. Michigan also partnered with a state health plan professional organization and sought input from 15 health plan medical directors about BRCA counseling, testing, and clinical services policies.Partnerships with insurance companies may increase the likelihood such companies have written evidence-based policies for their members. As one of their key policy activities, Michigan reviewed health insurance company policies on BRCA Grade B and Grade D Recommendations, informational flyers about the Hereditary Breast and Ovarian Cancer (HBOC): Is Your Patient at Risk? CME online module, samples of exemplary health plan policies for BRCA Clinical Services, relevant clinical guidelines, the Michigan Informed Consent Law Brochure with Model Consent Form, and additional resources from state and national groups.Along with the awards, Michigan also developed and distributed newsletters and packets to health plans to educate administrators about the importance and cost-effectiveness of these services. These packets included the USPSTF Because of Michigan’s educational and policy work with health plans, the state was able to document improvements in coverage for genetic services. There were increases in the number of health plans with written evidence-based policies (from 4 out of 25 in 2008 to 16 out of 25 in 2014) and there was a decrease in reports of inadequate insurance coverage as a barrier to testing . For these efforts, Michigan also was honored with the 2014 Spirit of Collaboration award from their state cancer consortium.As one of their key surveillance and education activities, Georgia incorporated a risk assessment tool, the Breast Cancer Genetics Referral Screening Tool (B-RST), into clinical practice in 9 of 18 public health districts across the state. Each district contains one or more health centers. All of the centers that incorporated the B-RST provided family planning and breast and cervical cancer screening services to low-income, uninsured, and underserved women. Each of nine sites were selected in an attempt to reach high-risk and underserved populations .BRCA-related Cancer: Risk Assessment, Genetic Counseling and Genetic Testing grade B recommendation. This recommendation describes the B-RST as, “one of several screening tools designed to identify a family history that may be associated with an increased risk for potentially harmful mutations in breast cancer susceptibility genes (BRCA1 or BRCA2)” [https://www.breastcancergenescreen.org/ [The B-RST was developed before the cooperative agreement by a key collaborator of the Georgia Department of Public Health ,25. The  BRCA2)” . The screen.org/ , quicklyBecause of the incorporation of B-RST into the clinics, 3636 women were screened by the end of the three-year funding period; 213 (5.9%) had a positive screen and were referred for genetic services; 60% of those with a positive screen (n = 128) were able to be contacted. Among those who received genetic services (n = 127), the 30 people who were appropriate for BRCA testing received testing . Funding for genetic testing was not directly available through these public health clinics; therefore alternative sources of funding had to be identified. Myriad provided free genetic testing for low-income and uninsured women. Underinsured or Medicaid-insured women received testing from a fund developed from the sale of the Georgia Breast Cancer license tag. Georgia’s experience highlights the interest and ability of clinics to incorporate genetic risk assessment tools into busy practices, including those who serve traditionally underserved populations.An article was published describing the implementation of the B-RST and initial results from the screening . All thrCreating Awareness. Starting in 2011, a key collaborator of the Oregon Health Authority chaired and facilitated the Genetic Advisory Council (GAC) to the Health Evidence Review Commission (HERC). The HERC provides coverage guidance and sets priorities for health spending in the Oregon Health Plan and promotes evidence-based medical practice statewide. Oregon and the GAC worked closely to create guidelines and a decision-making algorithm for nonprenatal genetic testing, thus creating awareness among key stakeholders and reflecting acceptance of the concept that genetic services are important. Oregon also worked closely with GAC and the HERC Value-based Benefits Subcommittee to review updated molecular pathology CPT codes and recommended coverage of appropriate tests to ensure that coverage priority was set by using the most current evidence-based genetic information.i.e., to the HERC, the medical director, and managed care directors). These results showed increases in the number of BRCA tests ordered, from 6.7 per 100,000 persons in 2008, to 33.2 per 100,000 persons in 2012, but usage was still lower than expected on the basis of the population covered by Medicaid, indicating underutilization. However, they were unable to determine appropriateness of testing given the incomplete personal and family history data available. These data are paramount as Oregon is one of the few states in which Medicaid covers genetic testing, and these data were used to track progress towards improving coverage for these services. Disseminating Science. Oregon conducted and disseminated results of analyses of Medicaid claims data annually to the Oregon Medicaid program  to promote use of evidence-based genomic tests in multiple ways. The impact of this work can be traced as follows:BRCA counseling were identified, and they and their doctors were notified and received educational materials through the Oregon State Cancer Registry. Oregon identified living patients who were diagnosed with ovarian cancer, breast cancer at a young age (≤ 50 years), and male breast cancer; deceased cancer patients were removed via links with vital records data. These groups of patients were selected because of their increased likelihood of having a hereditable cancer syndrome, which made them likely to be appropriate candidates for referral to genetic counseling and, if indicated after counseling, genetic testing. As one of their key educational and surveillance activities, Oregon implemented bidirectional reporting at the state level. In this case, bidirectional reporting was a process by which cancer survivors who were likely to be appropriate for In 2013, Oregon developed and disseminated targeted public and provider educational materials to 2,801 cancer survivors and 1,253 health care providers and asked them to complete a survivor or provider survey. Results from this study have been presented at state, national, and international conferences ,29. ResuBecause of bidirectional reporting and receipt of education materials, 40% of the cancer survivors who had never received genetic counseling (n = 193) and 47% of cancer survivors who had never received testing (n = 153) reported that a letter prompted them to take action, such as seeing a genetics expert or speaking with family members. Oregon also attempted to determine the impact of bidirectional reporting on health care providers’ behavior. A survey was distributed, but low response rates precluded analyses.he Committee understands that ovarian cancer is expected to claim the lives of more than 14,000 women this year, and there is no test to help identify the disease early when it is most treatable and the chance of survival is greatest. The Committee is pleased that CDC has undertaken pilot efforts in three States to promote breast/ovarian cancer genomics best practices designed to educate women and providers about the BRCA mutation, identify women at high risk, and help ensure appropriate referral for genetic counseling or testing. The Committee encourages CDC to expand these efforts.” [In addition to those specifically mentioned before, other impacts related to the FOA have occurred. Because of the CDC funding, Georgia now has state-wide breast cancer genomic activities where none existed before 2011, including the continuation and expansion of incorporating the B-RST into their breast and cervical cancer screening program and family planning programs. In addition, Congress has seen value in the work conducted through the FOA and encouraged the CDC to expand its cancer genomics efforts. In CDC’s FY 2015 appropriations bill, the state-based cooperative agreements were specifically mentioned in appropriations report language: “Tfforts.” .CDC released a new FOA and round of cancer genomics funding in 2014, which expanded the number of years of funding (from three to five), the number of grantees (three to four), funding amount , and scope . Discussions are underway as to how to integrate genomics into existing programs funded by DCPC, how best to leverage expertise and collaborate across our diverse national programs .The science impact framework is a valuable tool to determine the effect of CDC programmatic funding. By the end of the three-year funding period, all three states had well-functioning and effective state-based programs in breast cancer genomics that included innovative education, surveillance, and policy activities. These states serve as models for others interested in initiating or expanding cancer genomics programs, and their novel activities provide data to determine what works well in the promotion of public health genomics. Public health genomics programs are unique because they require specific and sometimes highly technical expertise in genomics, as well as expertise in the basics of program management and key public health activities . Because of this unique nature, developing strong collaborations and partnerships is key to the success of this work, including collaborations with other CDC-funded programs and with external partners . Other challenges to the implementation of public health genomics include the lack of genetic services in certain areas and the difficulty in funding genetic services. However, despite ongoing challenges, promising activities could be implemented in other states and nationwide. Even public health institutions without dedicated genomics funding could implement some activities, including those described in CDC’s genomic applications toolkit for public health departments . Expandi


Eunice Kennedy Shriver National Institute of Child Health and Human Development’s Global Network research sites.Neonatal deaths account for over 40% of all under-5 year deaths; their reduction is increasingly critical for achieving Millennium Development Goal 4. An estimated 3 million newborns die annually during their first month of life; half of these deaths occur during delivery or within 24 hours. Every year, 6 million babies require help to breathe immediately after birth. Resuscitation training to help babies breathe and prevent/manage birth asphyxia is not routine in low-middle income facility settings. Helping Babies Breathe (HBB), a simulation-training program for babies wherever they are born, was developed for use in low-middle income countries. We evaluated whether HBB training of facility birth attendants reduces perinatal mortality in the We hypothesize that a two-year prospective pre-post study to evaluate the impact of a facility-based training package, including HBB and essential newborn care, will reduce all perinatal mortality  among the Global Network’s Maternal Neonatal Health Registry births ≥1500 grams in the study clusters served by the facilities. We will also evaluate the effectiveness of the HBB training program changing on facility-based perinatal mortality and resuscitation practices. Seventy-one health facilities serving 52 geographically-defined study clusters in Belgaum and Nagpur, India, and Eldoret, Kenya, and 30,000 women will be included. Primary outcome data will be collected by staff not involved in the HBB intervention. Additional data on resuscitations, resuscitation debriefings, death audits, quality monitoring and improvement will be collected. HBB training will include training of MTs, facility level birth attendants, and quality monitoring and improvement activities.Our study will evaluate the effect of a HBB/ENC training and quality monitoring and improvement package on perinatal mortality using a large multicenter design and approach in 71 resource-limited health facilities, leveraging an existing birth registry to provide neonatal outcomes through day 7. The study will provide the evidence base, lessons learned, and best practices that will be essential to guiding future policy and investment in neonatal resuscitation.NCT01681017Trial registration ClinicalTrials.gov Identifier:  Neonatal deaths account for over 40% of the under-5 years old deaths and are increasingly critical for accelerating progress for Millennium Development Goal 4 (MDG4) ,2. NeonaEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Global Network for Women’s and Children’s Health Research  was initiated to conduct sustainable, high-impact research targeted at the major health problems of mothers, infants, and young children in developing countries. The investment in the Global Network sites over 11 years has resulted in uniquely qualified study venues that are suited to successfully carry out studies such as those proposed here [The sed here ,4.Resuscitation training using a standard national program began in the United States with the 1987 publication of the American Academy of Pediatrics (AAP) Neonatal Resuscitation Program . Since tIn the interim between the Global Network’s FIRST BREATH trial and the implementation of the HBB study, the circumstances of birth have changed: the proportion of facility-based deliveries have almost doubled from 40 to 80% in some of the most vulnerable states in India ,10, and Helping Babies Breathe (HBB), a new training program to resuscitate neonates wherever they are born, represents a collaboration between the American Academy of Pediatrics (AAP), NICHD’s Global Network, the Laerdal Medical, and global partners . Pilot tThe HBB package of training materials has not been formally tested in a large study using a common design, materials, and training model. However, a number of studies have evaluated the impact of neonatal care and resuscitation training for physicians, nurses, and other BAs on their skills and knowledge -17. Thesif needed within the first 60 seconds (the Golden Minute) after birth. By focusing on the timely delivery of the essential interventions of drying, warmth, stimulation to breathe and bag and mask ventilation (if required), most babies who are not breathing at birth can be saved. The HBB training materials are of high quality—they use multiple reinforcing modalities ; focus on critical decision points; and give a specific time limit by which ventilation should be established (the Golden Minute). The teaching materials, which include a realistic neonatal simulator , allow trainers to simulate and provide practice in the management of serious birth complications with a model that feels like a depressed newborn versus a fresh stillbirth. This extra practice/training should assist in the maintenance of a high skill level among BAs who have a limited number of deliveries. Quantifying the impact of a program like HBB is challenging, but essential to guide future policy and investment.A crucial component of HBB is training BAs about the importance of intervening with the appropriate resuscitation This two year prospective pre-post study will evaluate the impact of a package of interventions, including HBB and essential newborn care training  and provThe HBB/ENC implementation study will be conducted in three Global Network research units, located in Belgaum and Nagpur, India, and Eldoret, Kenya that have conducted common clinical research for three years under an NICHD cooperative agreement . Data from the MNH Registry, a prospective population-based registry (initiated in 2008) of all pregnancy and neonatal outcomes  in 52 defined geographic clusters with 300–500 births per year, will be used to select the facilities where the HBB training will be conducted.The study will be conducted in a select number of health facilities that represent a substantial portion of facility births in the three research units’ clusters , based on the 2010 MNH Registry data. The facilities must also provide 24-hour coverage for deliveries 7 days/week and have a perinatal mortality rate of 30 per 1,000 deliveries in the pre-study period. Women who reside in and/or deliver in the study clusters will be approached for enrollment in the MNH Registry by separate staff; the primary outcome will be calculated using all delivery data from the MNH Registry during the study period. Addition of other facilities would not have significantly increased the coverage of MNH facility births.The intervention will consist of three major components: selection of the MTs and BAs for training; training; and quality improvement QI and monitoring activities. Details of the components include: (1) selection of MTs, Facilitators and Learners, (2) country-level training of MTs in the HBB/ENC curricula, (3) facility-level training of BAs in the HBB/ENC curricula (4) periodic refresher training and evaluation during the implementation of the training program (5) QI, including regular observation of deliveries in participating study health facilities, unannounced observation of deliveries or HBB skills , resuscitation debriefings, perinatal death audits, daily bag and mask ventilation practice, daily check of cleanliness and availability of resuscitation equipment, and monthly monitoring reports, (6) biweekly calls with research unit HBB coordinator staff, data center, and NICHD staff followed by discussions with facility MTs and BAs.The appropriate selection of MTs and BA is important to ensure fidelity of the intervention/training and the maintenance of resuscitation skills over time. The sites will select the country level MTs and potential new MTs based on criteria outlined in the HBB Implementation Guide . The AAPThree country-level HBB MT workshops will be held, one each in Eldoret, Belgaum, and Nagpur. The country MT teams will include 2 teams of 3 AAP HBB MTs paired with 3 site HBB MTs from Belgaum, Nagpur, and Eldoret, including physicians, midwives, and nurses, to provide a ratio of 6 learners to one MT. Their goal will be to co-lead a 4-day, intense, hands-on workshop to provide a large cohort of new MTs for Nagpur, Belgaum, and Eldoret (at least one MT for every facility), including pre-post training assessment  among births ≥1500 grams across the three participating clusters pre vs. post intervention. The pre-phase is defined as the 12-month period preceding the implementation of the intervention (the HBB facility training will be rolled out at different points in time). The post phase will be the 12-month period after the completion of the initial training of the MTs and BAs in each of the participating facilities. The primary analysis will focus on cluster-level variables, i.e., on measures aggregated at the cluster level for each of the 52 clusters, and the analyses described below will include data from all clusters at all research units.The PMR will be estimated by dividing the sum of ≥1500 gram fresh still births and live births that die within the first 7 days after birth by the total number of ≥1500 grams live births and fresh stillbirths. The PMR will be estimated for each cluster for the pre HBB period and the post HBB period.The primary outcome will be tested using a linear mixed model that incorporates both random cluster effect and fixed effects for time (pre- versus post HBB/ENC training and equipment). The random cluster effect accounts for the correlation between measures across time from the same cluster. The dependent variable will be the cluster-level perinatal mortality rate aggregated separately across the pre and post periods. A dichotomous variable (period) post versus pre HBB/ENC training and equipment implementation will be the fixed treatment effect. A contrast term will be used to test for differences in pre versus post perinatal mortality.Key secondary outcomes include facility measures: (1) difference in the rate of facility-based perinatal mortality among births ≥1500 grams, pre vs. post HBB/ENC implementation, again evaluated at the cluster level; (2) difference in the cluster-level rate of facility-based fresh stillbirths ≥1500 grams, pre vs. post HBB/ENC implementation; and (3) difference in mean number of resuscitations with bag and mask among births ≥1500 grams pre vs. post HBB/ENC implementation. These analyses will evaluate the changes in PNM, FSB and number of bag and mask resuscitations among MNH Registry patients at the facility level .The analysis for all of the secondary mortality outcomes will also be tested using linear mixed models, with a structure comparable to that used for the primary analysis that incorporates both random cluster effect and fixed effects for time (pre versus post HBB/ENC training and equipment).Other secondary outcomes include the difference in mean scores on multiple-choice resuscitation knowledge tests, observed bag and mask skills, and tests of resuscitation management using the Objective Structured Clinical Exams (OSCE) A and B. The hypothesis tested is that the training increases BAs’ skills in adhering to the HBB protocol. A paired t-test will be used to test the hypothesis that the mean difference in score (post minus pre training) is greater than zero. Additionally, secondary analyses will evaluate the cluster and facility results over time.Consistent with the analytic approach proposed for this study, estimates of the power associated with the clusters within the three Global Network sites for the HBB study were generated based on cluster-level analyses of the 2010 data from the MNH Registry for these three sites. The PMR for babies with birth weight of 1500 grams is approximately 25 per 1000 births. A 20% reduction in this case would result in a reduction of approximately 5 deaths per 1000. The standard deviation of PMR between clusters for the subset of babies with a birth weight of ≥1500 is approximately 10 with a correlation across time of about 0.3. The resulting estimate of the standard deviation for the difference in PMR across time in this population is approximately 12. Based on these assumptions, the study has a power of approximately 82% to detect a 20% reduction in PMR among births with a birth weight of ≥1500 grams.The AAP HBB and WHO ENC training programs utilize global standard of care approaches to survival of newborns. The HBB study protocol and informed consents were submitted and approved by the Institutional Review Boards of the participating clinical sites and RTI International, as the data center. The study was also reviewed and approved by the Indian Council of Medical Research for the Belgaum and Nagpur, and the Kenya Institutional Review Board. A written informed consent will be obtained from all learners trained and monitored in HBB and ENC skills.The pregnant women and their neonates will participate in this study as part of the Global Network MNH Registry, which was also reviewed and approved by each site’s IRB. The consent obtained from the pregnant women who consented to be part of the MNH Registry covered all HBB study procedures.The study will evaluate the effect of a HBB/ENC training and a QI and monitoring package on perinatal mortality using a large multicenter common design and approach in 71 resource-limited health facilities, leveraging an existing birth registry to provide neonatal outcome data through day 7. The study will provide the evidence base, lessons learned, and best practices that will be essential to guiding future policy and investment in neonatal resuscitation.The Eunice Kennedy Shriver National Institute of Child Health and Human Development; OSCE: Objective structured clinical evaluations; PMR: Perinatal mortality rate; QI: Quality improvement; TBA: Traditional birth attendants.AAP: American Academy of Pediatrics; ANC: Antenatal care; BMV: Bag and mask ventilation; BA: Birth attendant; DR: Delivery room; ENC: Essential newborn care; GN: Global Network for Women’s and Children’s Health Research; HBB: Helping Babies Breathe; MNH: Maternal and Newborn Health; MT: Master trainer; MCQ: Multiple choice questionnaire; MDG4: Millennium Development Goal 4; MNH: Maternal Newborn Health; NeoNatalie: Realistic neonatal simulator; NICHD: The authors declare that they have no competing interests.AB, LLW and PH wrote the first draft, revised and reviewed the final version; all co-authors provided input into the study protocol and reviewed the final manuscript. SM provided statistical expertise. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2393/14/116/prepubPanel 1. Helping Babies Breathe Trial Quality Improvement and Monitoring Activities. Panel 2. Sample Training Agendas.Click here for file


Pulmonary arterial hypertension (PAH) is a rare disease (15 cases per million) that is characterized by widespread loss of the pulmonary microcirculation and elevated pulmonary vascular resistance leading to pathological right ventricular remodeling and ultimately right heart failure. Regenerative cell therapies  could potentially restore the effective lung microcirculation and provide a curative therapy for PAH. Preclinical evidence suggests that regenerative cell therapy using endothelial progenitor cells or mesenchymal stem cells may be beneficial in the treatment of PAH. These findings have led to the completion of a small number of human clinical trials, albeit with modest effect compared to animal studies. The objective of this systematic review is to compare the efficacy and safety of regenerative cell therapies in preclinical models of PAH as well as assess study quality to inform future clinical studies.We will include preclinical studies of PAH in which a regenerative cell type was administered and outcomes compared to a disease control. The primary outcome will be pulmonary hemodynamics as assessed by measurement of right ventricular systolic pressure and/or mean pulmonary arterial pressure. Secondary outcomes will include mortality, survival, right ventricular remodeling, pulmonary vascular resistance, cardiac output, cardiac index, pulmonary acceleration time, tricuspid annular systolic excursion, and right ventricular wall thickness. Electronic searches of MEDLINE and EMBASE databases will be constructed and reviewed by the Peer Review of Electronic Search Strategies (PRESS) process. Search results will be screened independently in duplicate. Data from eligible studies will be extracted, pooled, and analyzed using random effects models. Risk of bias will be assessed using the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) risk of bias tool, and individual study reporting will be assessed according to an itemized checklist based on the Animal Research: Reporting of In vivo Experiments (ARRIVE) guidelines.This systematic review will examine the efficacy and safety of regenerative cell therapy in preclinical models of PAH. As well, the literature will be assessed for study quality and risk of bias. The results will guide the design of future clinical trials and preclinical animal studies.http://www.dcn.ed.ac.uk/camarades/SyRF/Protocols.htm).CAMARADES (The online version of this article (doi:10.1186/s13643-016-0265-x) contains supplementary material, which is available to authorized users. Pulmonary hypertension is a progressive disease that results from restricted blood flow through the pulmonary circulation and loss of effective pulmonary microvascular area. This leads to increased resistance in the pulmonary vasculature and eventually right heart failure . ClinicaThe current standard of care PAH-specific therapies consists largely of pharmacological vasodilator agents, such as phosphodiesterase-5 inhibitors, prostacyclin analogs, and endothelin antagonists. These have only modest effects on pulmonary hemodynamics, and prognosis remains poor despite introduction of a number of new therapies in the last 5 years . The mosRecent understanding of the role of adult stem and progenitor cells in the maintenance of vascular homeostasis and repair of injury has stimulated interest in the potential for regenerative cell therapies for PAH. Most of the preclinical studies of cell therapy for PAH have used two cell types in particular, early-outgrowth endothelial progenitor cells  and mesenchymal stromal cells  , 9. EPCsIn order to address this knowledge gap, we will conduct a preclinical systematic review of regenerative cell therapy for PAH. In contrast to narrative preclinical reviews of stem cells for PAH treatment, this systematic review will provide additional key evaluations. The meta-analysis will provide an estimation of the cumulative overall effect of stem cell treatment on pulmonary hemodynamics based on currently available data in preclinical studies. This systematic review will also attempt to evaluate the quality of currently available evidence based on risk of bias assessment and completeness of reporting, and the potential for publication bias. This data may impact the design of current preclinical testing of stem cell therapies and potentially influence the design of future clinical trials.In preclinical studies of pulmonary arterial hypertension, do PAH animals receiving regenerative cell therapy exhibit improved pulmonary hemodynamics compared to PAH animals not receiving regenerative cell therapy and is regenerative cell therapy safe?http://www.camarades.info).The protocol was developed by a research team of clinical  and preclinical research scientists , experts in knowledge synthesis and translation . The protocol will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) checklist  that evaluate the efficacy or safety of regenerative cell therapy for PAH.We will include preclinical in vivo models of PAH that reproduce features of the pathophysiology associated and/or etiology of human PAH . SpecifiAnimal models of PH secondary to other causes such as left heart disease, lung disease, or thromboembolism (WHO Groups 3-5)  will notThe intervention group will include animals receiving any regenerative cell therapy . Experiments involving pretreatment of cells, co-treatment, and/or genetic manipulation  will be classified as “cell modifications” for subgroup analysis. Studies using non-stem/progenitor cells  as the therapeutic intervention will be excluded. Studies that do not include the administration of viable cells, for example, studies with only cell-free products derived from stem/progenitor cells such as conditioned media, will also be excluded.The preclinical comparison group will include animals from studies that have had experimentally induced PAH but have not been administered a regenerative cell .Outcomes will be assessed at least 1 week after intervention to exclude the possibility of acute effects of cell administration.The current gold standard for the diagnosis and evaluation of clinical pulmonary hypertension is direct pulmonary hemodynamic measures by right heart catheterization. The primary endpoint will be direct measures of pulmonary hemodynamics  measured after administration of cells Table . The priWe will collect data on all deaths and animal mortality. Right ventricular (RV) remodeling is a forerunner of right heart failure, which is characterized by decreased function and dilatation of the RV and strongly correlates with prognosis and survival in PH patients . We willWe will collect data from other noninvasive measures obtained by echocardiography to evaluate cardiac structure and pulmonary hemodynamics Table . MortaliIn consultation with the review team, electronic search strategies will be developed for each database by an experienced medical information specialist. Ovid MEDLINE®, Ovid MEDLINE® In-Process & Other Non-Indexed Citations, and EMBASE Classic + EMBASE will be searched. The strategy appended was used to search in MEDLINE  and keywords , and parsing will be formatted accordingly to each database. We will use modified animal filters from previously published methods , 17 valiTitles and abstracts of search results will be screened independently by two individuals. Full text of all potentially eligible studies will be reviewed based on our eligibility criteria. Disagreements between reviewers will be resolved by consensus or by a third member of the systematic review team (DJS). Reasons for exclusion of potentially eligible studies will be recorded in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines developed for proper reporting of clinical systematic reviews .https://distillercer.com). Specific data elements collected for this review are listed in Table Data will be extracted independently by two individuals into standardized, electronic pilot-tested forms using DistillerSR software  risk of bias tool. The SYRCLE tool was adapted from the Cochrane Risk of Bias Tool to assess the methodological quality using criteria specific to animal studies Table . Items iThis review will record features that will facilitate judgments of external validity. External validity in preclinical research concerns the extent to which results can be generalized to different experimental measures, settings, and times . These aConstruct validity in preclinical research refers to the ability of a study to generalizable to a clinical scenario . ThreatsWe will assess construct validity based on a pre-defined checklist of factors aimed evaluate how closely the study resembles clinical PAH. The domains assessed will be animal subjects, outcome measures, modeling of disease, administration of intervention, and environment Table . These wWe will apply the Animal Research: Reporting of In vivo Experiments (ARRIVE) guidelines to evaluate the quality of reporting in preclinical studies. The ARRIVE guidelines were developed by the National Centre for the Replacement, Refinement, and Reduction of Animals in Research (NC3Rs) to improve the transparent and comprehensive reporting of research methods and results for in vivo animal experiments .ndeaths/ntotal at defined endpoints and by mean survival in days. Statistical heterogeneity of included studies will be measured using the I2 test with 95 % confidence intervals [Continuous endpoints will be pooled using the ratio of weighted means using the inverse variance random effects method , 23. Deantervals . An evalntervals .Planned subgroup analyses will be examined on the primary endpoint of right heart catheterization hemodynamics (RVSP/mPAP). Heterogeneity will be analyzed for the following: PAH induction method, age, sex, strain, regenerative cell type, tissue origin of cells, timing of administration , follow-up period , route of delivery, cell dose, dose frequency, use of cell pretreatments and other enhancement strategies , and sample sizes of study.The timing of this review is highly relevant, as clinical trials have been completed  , 3 ,26. Systematic reviews should be valuable in stem cell research because of the high degree of heterogeneity of cell products used for therapy. As such, a secondary aim of this study will be to evaluate the relative efficacy between regenerative cell types. Although EPCs and MSCs have both been studied extensively in preclinical models, we anticipate that other cell products such as cells derived from embryonic stem cells or induced pluripotent stem cell may also have in vivo efficacy. Still, guidelines and/or criteria for what constitutes a particular regenerative cell type are ill-defined and when available, they are loosely defined based on an evolving understanding of stem cell biology . In the We anticipate that this comprehensive synthesis will provide valuable information in translating stem cell therapy to the clinic. In addition, this review will have an immediate impact on preclinical research by highlighting knowledge gaps and areas to improve study design for future preclinical investigations of PAH.ALK-1, activin receptor-like kinase 1; ARRIVE, Animal Research, Reporting of In vivo Experiments; BMPR2, bone morphogenetic receptor, type 2; CAMARADES, Collaborative Approach to Meta Analysis and Review of Animal Data from Experimental Studies; CAV1, caveolin 1; ENG, endoglin; EPC, endothelial progenitor cell; KCNK3, potassium channel subfamily K member 3; mPAP, mean pulmonary arterial pressure; MSC, mesenchymal stem cell, marrow stromal cell, or mesenchymal stromal cell; PAH, pulmonary arterial hypertension; PVR, pulmonary vascular resistance; RV, right ventricle; RVSP, right ventricular systolic pressure; SMAD9, mothers against decapentaplegic homolog 9; SYRCLE, Systematic Review Centre for Laboratory animal Experimentation.


We compared antituberculosis treatment (ATT) adherence and outcomes among patients exposed to Photovoice (video of previously cured TB patients sharing experiences about TB treatment) versus those not exposed. The odds of successful outcome  for the 135 patients who watched Photovoice were 3 times greater  than for patients who did not watch Photovoice. The comparison group, on average, missed more doses  than the intervention group who saw Photovoice . Using Photovoice at initiation of ATT has the potential to improve treatment adherence and outcomes. Tuberculosis (TB) requires successful completion of at least six months of antituberculosis treatment (ATT) . UnfortuATT adherence often depends upon the patients' general knowledge of TB, socioeconomic status, and whether they believe in the efficacy of the medication , 7. PhotThe study was conducted at BJGMC, Sassoon General Hospital, Government TB Treatment Centre. BJGMC treats approximately 4,000 tuberculosis patients per year and offers medical service to over 9 million people of the Pune, the second most populous district in Maharashtra state , a 15-miDemographic and clinical variables, number of doses prescribed, number of doses taken during treatment, and treatment outcomes were collected from the TB treatment cards of patients in both the Photovoice and comparison groups. Treatment outcomes were defined as successful or unsuccessful according to national treatment guidelines described elsewhere . Successt-tests were used to compare differences in proportions between successful and unsuccessful outcome among the Photovoice and comparison groups. Odds ratios (OR) were used to measure the association of Photovoice with sputum status at the end of the intensive phase (IP) and with treatment outcomes. All statistical tests were considered to be significant at an alpha of <0.05.Pearson chi-square and independent sample All patients were treated according to national guidelines irrespective of their participation or refusal to take part in the study. All data were safeguarded to protect patient confidentiality and no individual patient identifiers were retained electronically. The study protocol was approved by the International Union Against TB and Lung Disease  and the Institutional Review Board of BJGMC.n = 135; comparison group n = 141) were studied. There were no significant differences in age, HIV status, or clinical presentation between Photovoice and comparison groups  consented to participate. In total, 276 patients  of the Photovoice patients converted sputum at the end of IP compared to 88% in the comparison group . PatientSeveral studies have described factors associated with ATT adherence but few studies describe the impact of interventions leading to behavioral changes that influence treatment outcomes . This stPhotovoice is a simple, inexpensive strategy that might be considered as one of Government of India's Information, Education, and Communications activities to strengthen TB treatment adherence. In combination with other interventions, a Photovoice approach could be an effective tool for reduction of treatment lost to follow-up and other unsuccessful TB treatment outcomes.


FoodNet has provided a foundation for food safety policy and illness prevention since 1996. The Foodborne Diseases Active Surveillance Network (FoodNet) provides a foundation for food safety policy and illness prevention in the United States. FoodNet conducts active, population-based surveillance at 10 US sites for laboratory-confirmed infections of 9 bacterial and parasitic pathogens transmitted commonly through food and for hemolytic uremic syndrome. Through FoodNet, state and federal scientists collaborate to monitor trends in enteric illnesses, identify their sources, and implement special studies. FoodNet’s major contributions include establishment of reliable, active population-based surveillance of enteric diseases; development and implementation of epidemiologic studies to determine risk and protective factors for sporadic enteric infections; population and laboratory surveys that describe the features of gastrointestinal illnesses, medical care–seeking behavior, frequency of eating various foods, and laboratory practices; and development of a surveillance and research platform that can be adapted to address emerging issues. The importance of FoodNet’s ongoing contributions probably will grow as clinical, laboratory, and informatics technologies continue changing rapidly. Escherichia coli O157 caused 732 laboratory-confirmed infections and the deaths of 4 children. After this outbreak, the US Department of Agriculture (USDA) implemented a risk-based meat inspection system. Public health and regulatory officials needed a method to determine whether the changes made by regulatory agencies and the industry were followed by declines in infections. The outbreak had focused attention on the need for reliable data on the incidence of infections caused by enteric pathogens; changes in the incidence over time; and estimates of the actual numbers of illnesses, hospitalizations, and deaths they cause. Therefore, in 1995, with support from Food Safety and Inspection Service (FSIS) of the USDA, CDC established the Foodborne Diseases Active Surveillance Network (FoodNet), an active, population-based sentinel surveillance system. FoodNet monitors changes in the incidence of selected major bacterial and parasitic illnesses transmitted commonly by food, attributes illnesses to sources and settings, and estimates the total numbers of foodborne illnesses in the United States.During the late 1980s and early 1990s, recognizing inconsistencies inherent in passive national surveillance systems, epidemiologists at the Centers for Disease Control and Prevention (CDC) proposed creating a population-based active surveillance system to better measure the frequency of enteric infections and their effects on society. However, resources for these improvements were not available. Then, in late 1992 and early 1993, hamburger patties contaminated with http://www.cdc.gov/FoodNet. The cost of funding for the surveillance sites and CDC, typically <$7 million per year, is dwarfed by the economic impact of the illnesses monitored. Salmonella infections alone cost ≈$3.6 billion each year in direct medical costs, productivity, and years of potential life lost . Over time, the surveillance area has grown to include ≈48 million persons (≈15% of the US population) in Connecticut, Georgia, Maryland, Minnesota, New Mexico, Oregon, and Tennessee and in selected counties in California, Colorado, and New York . More inThe community of multidisciplinary FoodNet scientists collaborates to track infections transmitted commonly by food and to study the sources of infections. FoodNet’s annual report of confirmed infections caused by major pathogens, published within months of the end of each calendar year, is sometimes referred to as the foodborne illness “report card” for the nation. Public health officials, regulatory agencies, and industry use it to gauge progress in food safety and to determine when new policies and prevention efforts are needed  O157 and non-O157, Shigella, Vibrio, and Yersinia and parasitic infection caused by Cryptosporidium and Cyclospora. FoodNet does not track agents for which clinical laboratories do not routinely test . As laboratory practices change, the surveillance system adapts. During the 2000s, culture-independent diagnostic tests (CIDTs) became commercially available to detect Shiga toxin. Recognizing that some laboratories might stop culturing for STEC O157, leading to a perceived decline in infections, FoodNet began surveillance for hemolytic uremic syndrome (HUS) as another way to track STEC O157 infections. Most cases of HUS are caused by STEC O157. As more clinical laboratories began using CIDTs to detect other pathogens, FoodNet responded by gathering data on laboratory practices and on pathogens detected by these tests and by encouraging reflex culturing of specimens that test positive . It is currently conducting a case–control study of non-O157 STEC infections to assess risk factors and correlate virulence factors with symptoms. These studies have yielded rich data of long-term value. When the FDA needed data on sources of S. enterica serotype Enteritidis illnesses before the Egg Rule was implemented, Gu et al. reanalyzed data from an old FoodNet case–control study with a new method and determined that egg-related exposures had the highest attributable fraction , the surveys asked participants how recently they ate selected foods. These data have been used for many analyses. Shiferaw et al. found a higher proportion of men reported eating pink hamburger and runny eggs, whereas a higher proportion of women ate fruits and vegetables  has expanded the impact of both surveillance systems. A FoodNet case–control study linked fluoroquinolone-resistant Campylobacter cases and linking to census tract socioeconomic status (SES) measures, Bemis et al. found the incidence of campylobacteriosis in Connecticut increased as neighborhood SES increased except among children <10 years old, for whom incidence increased as SES decreased  is an obstacle to fully understanding the features of reported infections. FoodNet staff will be engaged in efforts to ensure that national surveillance systems are designed to meet the needs of both states and CDC and that they enable accurate and timely analysis and release of FoodNet data.The widespread growth of electronic health records in the clinical community presents challenges and opportunities for public health. CDC’s Emerging Infections Program is developing informatics capacity to incorporate data streams from electronic health records, electronic laboratory reporting, and other sources of “big data” . FoodNet databases at the sites and CDC are increasingly conforming to national data standards, which will facilitate linking to meaningful use of certified electronic health records technology. Rapid access to clinical data will improve surveillance and epidemiologic studies. Informatics capacity is essential for linking FoodNet surveillance data with geographic information systems and other public health databases . Lessons learned from pilot projects conducted at FoodNet sites could provide an important foundation for developing public health informatics infrastructure nationally. Through multiagency partnership and collaboration, FoodNet has helped improve food safety in the United States in multiple ways. The surveillance network, which began as a project, provides key data for public health analyses and decision-making, and has become an integral part of CDC’s work. FoodNet has matured and transformed over the last 20 years and continues to evolve. Changes in diagnostic practices that affect surveillance and the need for more detailed and precise information about the major sources of infections and how they change over time are just a few of the issues FoodNet will address during the next decade.


Adoption of personalized medicine in practice has been slow, in part due to the lack of evidence of clinical benefit provided by these technologies. Coverage by insurers is a critical step in achieving widespread adoption of personalized medicine. Insurers consider a variety of factors when formulating medical coverage policies for personalized medicine, including the overall strength of evidence for a test, availability of clinical guidelines and health technology assessments by independent organizations. In this study, we reviewed coverage policies of the largest U.S. insurers for genomic (disease-related) and pharmacogenetic (PGx) tests to determine the extent that these tests were covered and the evidence basis for the coverage decisions. We identified 41 coverage policies for 49 unique testing: 22 tests for disease diagnosis, prognosis and risk and 27 PGx tests. Fifty percent (or less) of the tests reviewed were covered by insurers. Lack of evidence of clinical utility appears to be a major factor in decisions of non-coverage. The inclusion of PGx information in drug package inserts appears to be a common theme of PGx tests that are covered. This analysis highlights the variability of coverage determinations and factors considered, suggesting that the adoption of personal medicine will affected by numerous factors, but will continue to be slowed due to lack of demonstrated clinical benefit. The field of personalized medicine is anticipated to significantly impact clinical practice as evidence continues to accumulate for new applications that will lead to greater adoption. The excitement surrounding personalized medicine has, in large part, been due to advances in genome-based technologies to assess variation at the DNA, RNA, protein and metabolite level. Already, a number of genomic applications are clinically available that inform medical decision-making and improve health outcomes. In particular, pharmacogenetic (PGx) testing, or tests to predict risk of adverse drug response or likelihood of response, is on the forefront of the personalized medicine movement. Despite the potential of personalized medicine and continuing development of new clinical tests, adoption of these tools in practice has been relatively slow. The slow uptake is likely due to a combination of factors including lack of physician knowledge, patient interest, insurance coverage and reimbursement and lack of evidence demonstrating clinical utility ,3,4,5,6.In this study, we evaluated medical coverage policies of the largest U.S. insurers for genomic disease-based tests and PGx tests to determine which tests were covered and the evidence basis for the coverage decisions. This snapshot provides a comprehensive overview of insurance coverage policies for these rapidly developing technologies. Overall, we find that insurers generally agree on their coverage policies for genomic tests, but few tests are currently covered. To identify coverage determination policies for genomic and PGx tests, we conducted an online search of the top dozen U.S. insurers (based on U.S. News & World Report listing ). We excCoverage policies for UnitedHealth Group, Aetna, Humana, Independence Blue Cross Group and Cigna are publicly accessible through the company’s website and search engines. We used the following terms to search for genomic and PGx policies: gene, DNA, mutation and genomic. For the Independence Blue Cross Group, all coverage determinations within the category ‘pathology and laboratory’ for genetic and genomic tests were reviewed (no coverage policies were found in the other categories). We defined genetic and genomic tests to include laboratory analysis of DNA, RNA, or protein. Our search was conducted in August 2012.If a drug is specifically indicated for patients with a particular genetic aberration, we excluded the tests required for identifying those patients from our analysis. For examples, testing for KRAS , ALK (anaplastic lymphoma kinase for the drug crizotimib), and Her2/Neu  were excluded from our dataset. For these drugs, coverage of testing is likely to be influenced by pharmacy benefits and use of drug without testing would constitute off-label use.We also reviewed health technology assessments of genomic and PGx tests conducted by two groups: the Centers for Disease Control and Prevention’s Evaluation of Genome Applications in Practice and Prevention (EGAPP) group and the Blue Cross Blue Shield Technology Evaluation Center (BCBS-TEC). For BCBS-TEC, in addition to conducting a text search, we reviewed all assessments in two of the 21 categories listed to identify relevant genomic and PGx assessments: “genetic testing” and “pharmacotherapy/therapy”. For EGAPP, all reports were reviewed. Each coverage policy and assessment was reviewed to identify the specific test, evidence considered (if provided) and the policy decision. In addition, we determined whether the test was cleared or approved by the Food and Drug Administration (FDA). For PGx tests, we also determined whether the package insert had been revised to include information about the impact of genetic variants on risk of adverse response or likelihood to respond and PGx testing.Overview of Coverage Policies. In our search of leading U.S. insurance companies, we identified a total of 41 coverage policies for genomic and PGx testing  to warfarin was not covered by any of the insurers and deemed investigational. The Oncotype Dx is covered by all insurers to assess breast cancer recurrence risk, but considered investigational with respect to colon cancer recurrence. Twelve of the 49 tests were covered by at least one company, with twice as many PGx tests than disease-related tests covered . Nine teBasis for Coverage Decisions. For coverage policies that included background information or reasons for their coverage decision, a review of key clinical studies of the test, clinical guidelines and availability of FDA-approved tests were often included. For several of the tests, while evidence of a strong association between genotype and disease risk or drug effectiveness were noted, the lack of evidence of clinical utility appeared to be the determining factor for coverage. In particular, tests that are not covered tended to lack evidence from prospective, randomized clinical trials. Evidence of cost-effectiveness was not specifically mentioned in any coverage policy. Discordant Coverage Policies. Of the tests reviewed by more than one insurer, five tests had discordant coverage policies: the Allomap test for cardiac allograft rejection risk, the Mammaprint test for breast cancer risk recurrence, CYP2C19 testing for use of clopidogrel, and EGFR and KRAS testing for erlotinib. The AlloMap test and CYP2C19 PGx test for clopidogrel were reviewed by all insurers except United Health. Aetna and Independence Blue Cross provided coverage for these tests, whereas Cigna and Humana considered both tests to be experimental/investigational and therefore, not covered. We compared the coverage policies for discordant coverage decisions. Humana does not provide any background information or rationale for their coverage policies, and therefore, comparisons were not possible. The AlloMap test evaluates expression of 20 genes associated with risk of cardiac allograft rejection following a heart transplant. The test is intended to reduce the number of endomyocardial biopsies performed by identifying patients who are not at risk of rejection, therefore ruling out those patients for biopsy. The BCBS-TEC assessment concluded that the AlloMap test did not meet their criteria for clinical use. Cigna considered a broader range of sources in formulating its policy for AlloMap than other insurers. For example, they commented on four peer-reviewed studies that Aetna did not consider ,12,13,14The CYP2C19 test is used to identify patients not likely to respond to treatment with the anti-platelet drug clopidogrel. The prevalence of loss of function mutations in the CYP2C19 gene ranges from 2%–5% in Caucasians and from 13%–23% in people of Asian ancestry . In 2010Comparison of the differing coverage policies between Cigna and Aetna again shows different data were considered. Cigna analyzed nine peer-reviewed articles on genetic testing in use with clopidogrel; Aetna analyzed only one of these studies in its corresponding review but cited (though not discussed) two other studies evaluated by Cigna. Overall, Aetna considered a smaller data set in formulating its policy, analyzing three peer-reviewed articles and citing four others without discussion. One article was cited by both payers without discussion. Five of the six studies evaluated by Cigna but not Aetna suggest an association between CYP2C19 genotype and response to clopidogrel treatment ,19,20,21One of the important drivers of uptake of genomic tests is insurance coverage. Based on the data collected from a small group of leading insurers, we find that while coverage of genomic and PGx testing is not common, some insurers have been more proactive in this area than others. Overall, 25 percent of the tests reviewed by major insurers are covered, with twice as many PGx tests covered compared to disease-related genomic tests. The variability of review and insurance coverage is consistent with other reports ,8. The let al. [et al. [While FDA test approval does not appear to be a leading factor in coverage decisions, inclusion of PGx information in drug package inserts does appear to be an important factor. Over the past decade, the number of labels with PGx-related information has increased, including some for commonly used drugs ,27. We fet al.  similarl [et al.  reported [et al. . For disGiven that policies are regularly reviewed and updated, we anticipate increased coverage of these tests as evidence is published and physicians become more comfortable ordering such tests, perhaps in response to patient requests, given the high level of interest in PGx testing . As we dAnother approach to increasing the evidence basis of genomic tests is for the Centers for Medicare and Medicaid Services (CMS) to apply the coverage with evidence development (CED) status to promising genomic and PGx tests ,31. ThisThe early adoption of tests is an important factor considered in coverage decisions, particularly in the absence of published evidence of clinical utility . TherefoIn summary, insurance coverage for disease-related genomic and PGx testing is low and variable, though some insurers are willing to provide coverage based on limited evidence of clinical utility. Expanding data collection efforts outside of traditional clinical trial study designs and promoting physician and patient awareness will likely lead to greater review and coverage of these tests.