As in other resource limited settings, the Ministry of Health in Zambia is challenged to make affordable and acceptable PMTCT interventions accessible and available. With a 14.3% HIV prevalence, the MOH estimates over one million people are HIV positive in Zambia. Approximately 500,000 children are born annually in Zambia and 40,000 acquire the infection vertically each year if no intervention is offered. This study sought to review uptake of prevention of mother-to-child (PMTCT) services in a resource-limited setting following the introduction of context-specific interventions.Interventions to improve PMTCT uptake were introduced into 38 sites providing PMTCT services in Zambia in July 2005. Baseline and follow up service data were collected on a monthly basis through September 2008. Data was checked for internal and external consistency using logic built into databases used for data management. Data audits were conducted to determine accuracy and reliability. Trends were analyzed pre- and post- intervention.Uptake among pregnant women increased across the 13 quarters (39 months) of observation, particularly in the case of acceptance of counseling and HIV testing from 45% to 90%  in the first year and 99% by year 3 . Receipt of complete course of antiretroviral (ARV) prophylaxis increased from 29% to 66% (p = 0.00) in the first year and 97% by year 3 . There was also significant improvement in the percentage of HIV positive pregnant women referred for clinical care.Uptake of PMTCT services in resource-limited settings can be improved by utilizing innovative alternatives to mitigate the effects of human resource shortage such as by providing technical assistance and mentorship beyond regular training courses, integrating PMTCT services into existing maternal and child health structures, addressing information gaps, mobilizing traditional and opinion leaders and building strong relationships with the government. These health system based approaches provide a sustainable improvement in the capacity and uptake of services. Effective interventions for prevention of mother-to-child transmission (PMTCT) were discovered in the late 1990s, yet mother-to-child transmission (MTCT) remains the most significant route of HIV infection among children [MTCT transmission rates in the United States and Europe are below 2% due to wide coverage and provision of highly effective ART regimen . In contAs in other resource-limited settings, the Ministry of Health (MoH) in Zambia is challenged to make affordable and acceptable PMTCT interventions accessible and available. With a 14.3% HIV prevalence, the MOH estimates over one million people are HIV positive in Zambia .The steps involved in the provision of core PMTCT programs are often referred to as a cascade. The steps include 1) utilization of antenatal care; 2) receiving pre-test counseling; 3) acceptance of HIV test; and 4) receiving HIV test results & post-test counseling. For seropositive mothers the cascade continues with 5) use of ARV prophylaxis for mother and/or baby; 6) use of labor & delivery services which include specific PMTCT interventions during these periods; and 7) postnatal follow-up of the mother and baby with HIV testing of the exposed infant/child and linkage to care and support. As the term "cascade" suggests, uptake typically decreases at each successive step, which occur as a result of economic, educational, political, social, cultural, and/or health system factors. Ideally, the number of pregnant women seen in the antenatal clinic would be equal to the number of women receiving counseling, testing and received results. Furthermore, the number of pregnant women who test positive for HIV should equal to the number offered a complete course of prophylactic ARVs and also referred for clinic care.This descriptive review describes the approaches that were used to increase the ability of the health system to increase uptake and retain pregnant women from the point of enrollment into antenatal care through labor and delivery.In May 2005, Family Health International's (FHI) Zambia Prevention, Care, and Treatment Partnership (ZPCT), was launched in order to strengthen and expand existing HIV/AIDS services in five provinces. The partnership is a six year cooperative agreement funded by the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) through United States Agency for International Development (USAID); it works in collaboration with the Zambian Ministry of Health (MoH) in five of Zambia's nine provinces: Northern, Luapula, Copperbelt, Central, and North-Western. With the exception of the Copperbelt, the provinces selected have the highest poverty index in Zambia . Within In the first phase, from May 2005 to October 2005, HIV related care and treatment services namely counseling and testing (CT), clinical care, antiretroviral therapy (ART) and PMTCT were initiated in 43 facilities. Out of these 38 offered PMTCT services. The remaining five facilities did not offer PMTCT because they did not have at least two trained healthcare workers as required by national guidelines [Simultaneously, facilities were refurbished to provide adequate space for service provision. Refurbishment also included procurement of laboratory and other minor medical equipment as well as the creation of testing corners.In an effort to improve PMTCT uptake, ZPCT employed a variety of strategies to:• Expand access;• Provide same day routine HIV testing with opt-out strategy;• Build human resource capacity;• Improve facility capacity;• Foster understanding and reduce stigma;• Increase male involvement;• Ensure confidentiality;• Conduct postnatal follow-up of mother-baby pairs; and• Improve commodity management.To ensure equity of access even for those in the most rural areas, ZPCT implemented a universal access approach. As part of this approach, PMTCT services were integrated at all levels of health care, including tertiary hospitals, provincial, district, primary and community health care settings. Additionally, ZPCT broadened PMTCT service entry points by providing them in antenatal care (ANC) facilities, labor and delivery wards, maternal, newborn and child health clinics, and family planning and STI clinics.In Zambia, about 90% of pregnant women will attend antenatal clinic at least once, however less than 50% return to deliver in the health facility . In manyThe 'opt-out' model of HIV testing provides all antenatal care attendees with counseling for HIV testing, with the option to refuse HIV testing. Multiple studies have supported the approach of routine testing (opt-out) for increased uptake of HIV testing among pregnant women -10. EvenHuman resource shortages negatively impacted implementation of PMTCT services at every step. Initiation and strengthening services with "opt out" HIV testing with same day results further increased the need for human resources. ZPCT employed a combination of strategies to build human resource capacity by increasing the number of trained HCWs, improving the skills of existing staff and shifting certain tasks to lay providers. The program did not hire new health care workers but used existing Ministry of Health staff. Non-health care workers (i.e. community motivators and lay counselors) were trained to support and provide some PMTCT services. Non-HCWs were used to provide group motivational talks, which shortened the time required for one-on-one pre-test counseling with trained HCWs. Additionally, some non-HCWs were trained in HIV testing and conducted the tests themselves. ZPCT has also trained people living with HIV/AIDS (PLHWA) and lay counselors to provide psychosocial support, make referrals, and help patients adhere to ART.ZPCT trained and mentored nurses, midwives, doctors and other non-laboratory staff in PMTCT, including rapid HIV testing within the PMTCT context. ZPCT also supported off duty shifts, in which HCWs trained in PMTCT are allowed to work an 'extra shift' and are provided with a transportation reimbursement of US$7 per shift as an incentive which is about 3% of the average monthly salary for nurses . TypicalTesting corners were established by ZPCT in May 2005 when it was identified that over 20% of clients did not return for their HIV results . HIV tesFor sites where it was not possible to assess the immunological status of clients due to a lack of laboratory facilities, ZPCT implemented a laboratory specimen referral system, in which blood samples were sent to referral laboratories for testing instead of clients traveling long distances to testing facilities. Referral sites house hematology, chemistry and CD4 machines. Specific clinic days were designated for blood drawing and specimen referral to facilities providing ART using motorcycles. Test results were sent back to the centers for patient management within a turn around time of one week.A lack of understanding by health care providers and communities are a major barrier to the uptake of HIV testing and use of ARV prophylaxis for the mother and/or baby. Lack of information and misinformation perpetuate stigma, discrimination, and reluctance to take ARV prophylaxis. Uptake of ARV prophylaxis can be increased through health education on MTCT and PMTCT interventions and treatment of HIV/AIDS, as well as through sensitization on the need to deliver at a health facility ,14.In order to improve HIV and PMTCT awareness, ZPCT provided health education at community and facility levels with a focus on information programs to improve the knowledge among both women and men regarding PMTCT services. In all the catchment populations surrounding the health facilities, community mobilization and education has been ongoing under the auspices of Neighborhood Health Committees and community based organizations. Mobilization is intense in the beginning and tapers off when the target population has been reached. To specifically increase the acceptability of HIV testing among pregnant women and reduce stigma, traditional and religious leaders were engaged in community sensitization and mobilization. In Luapula province in particular, HCWs encouraged the involvement of traditional leaders within the community. PMTCT providers from the local hospital first led a series of information campaigns targeting traditional and other opinion leaders. Subsequent community meetings were then led by traditional leaders where all males were encouraged to accompany their spouses for their first ANC clinic and be actively involved in their care.In addition, ZPCT, in partnership with Health Communication Partnership (HCP), worked with male peer groups to mobilize men to participate in ANC and reproductive health (RH) services. Pregnant women who come with their spouses were seen first by the midwife or nurse to promote male involvement in maternal and child health services and PMTCT.Counseling and testing services require a counseling space that ensures auditory and visual privacy and an area for HIV testing and waste disposal. ZPCT often found inadequate space or no auditory and/or visual privacy available in the facilities. Therefore, whenever possible, ZPCT renovated the facilities to address these inadequacies, which included partitioning or extension of existing rooms to create added private space.ZPCT's approach placed a clear emphasis on postnatal follow-up of mother-baby pairs. This step has proved to be necessary in increasing uptake of referrals to clinical care and support for both babies and mothers. Mother-baby pairs were followed up in the maternal and child health (MCH) setting and aided through the development of new tools, such as the Mother-Baby Tracking Tool; HIV exposed babies were initiated on co-trimoxazole prophylaxis. Where accessible, babies were tested at six weeks through polymerase chain reaction (PCR). Where PCR was not available, HIV exposed babies were tested at nine and eighteen months. Babies who tested positive for HIV were linked to care and treatment services and the mother supported to provide appropriate feeding options through infant feeding counseling. Exclusive breast feeding was encouraged up to the first six months. Whilst formula for infant feeding was not offered, women who opted not to breast feed were counseled to ensure replacement feeding was acceptable, feasible, affordable, safe and sustainable.Initially there were commodity stock outs of HIV test kits and supplies. Stock outs resulted in interruptions in service provision. ZPCT supported training for HCWs in commodity and data management to facilitate correct and timely orders.The data was collected from 38 sites providing PMTCT services in five provinces of Zambia by July 2005. This was then followed by the introduction of a set of interventions to improve PMTCT uptake. Baseline and follow up data was collected as part routine service statistics compiled monthly through September 2008. Collected data was checked for internal and external consistency using logic built into the databases that are used for the data management. Additionally, data audits were conducted on a quarterly basis to determine the accuracy and reliability of the already reported data. Trends were analyzed pre- and post- intervention to assess the effect of interventions.Approval: Data was approved for use by Ministry of Health and Zambia Prevention Care and Treatment PartnershipAfter three years of implementation, substantial increases were observed in the proportion and number of women accessing PMTCT services , 9723 pregnant women were counseled about PMTCT, 4630 (45%) were tested for HIV and received their results, 890 tested positive for HIV, 549 seropositive pregnant women were enrolled or referred to clinical care beyond PMTCT, and 258 seropositive pregnant women (29%) received a complete course of ARV prophylaxis. One year later, from July 2006 to September 2006, 7509 pregnant women were counseled about PMTCT, 6758 (90%)  were tested for HIV and received their results, 1057 tested positive for HIV, 967 seropositive pregnant women were enrolled or referred to clinical care beyond PMTCT, and 701 seropositive pregnant women received a complete course of ARV prophylaxis (66%) . The trend is sustained in year 2 and 3 with percentage of pregnant women counseled, tested and receiving results increasing to 99% with those receiving complete course of prophylaxis reaching 100%  allowed same day HIV test results possible in places with limited or no laboratory staff and reduces waiting times. In addition, the use of lay counselors to conduct counseling and testing to complement the efforts of health care workers has contributed to improved uptake. However, these efforts require changes to policy and regulatory framework to make it feasible.Technical assistance, particularly hands-on mentorship, is necessary beyond the regular training courses for services to be implemented well, especially with operationalizing routine HIV testing and ensuring same day results.Next, expanded PMTCT services should be integrated into the existing maternal and child health structure, which requires strengthening the health system management infrastructure and training and mentoring of current health care workers.Information gaps related to PMTCT exist and must be addressed. Misinformation leads to stigmatization, discrimination, and low services uptake. Subsequently, male partners should become integrated into the PMTCT process. Traditional leaders/opinion leaders play an important role in mobilizing communities to access HIV/AIDS services and specifically to increase male involvement in PMTCT services.Finally, a strong relationship with the government at all the levels of the health system is critical. PMTCT programs planning to integrate expand or rapidly scale up must have government support and ownership.The authors declare that they have no competing interests.KT, MK and PK conceived the study, participated in the design and helped draft the manuscript. RD, MB, CT, YDM participated in the design and helped draft the manuscript. MK and RD did the statistical analysis. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6963/10/29/prepub


There is a long and rich history of research and control in the field of schistosomiasis that has resulted in major scientific and public health accomplishments. Examples of such findings and accomplishments include immunologic regulation in chronic infections  We did not develop such an agenda as an attempt to work around or displace other efforts to organize schistosomiasis-related programs . In fact, this agenda was developed with full knowledge and input from some of these existing programs. Nor is this agenda a means to obtain funding or to provide a priority listing of what kind of schistosomiasis research is needed to achieve given, spelled-out objectives, although we hope that the agenda may eventually be used to further both of these goals. Rather, we initiated this effort to help advance schistosomiasis research by enhancing cooperation and communication among the community of investigators interested in this neglected tropical disease, with the eventual goal of making stronger contributions to both biomedical science and public health.The possible development of a comprehensive schistosomiasis research agenda was first discussed in a symposium at the annual meeting of the American Society of Tropical Medicine and Hygiene in Washington, D. C., in December 2005. This symposium actually followed by a month a meeting of the WHO/TDR Scientific Working Group (SWG) on Schistosomiasis, held in Geneva in November 2005. Both coordinators of the current agenda participated fully in the SWG on Schistosomiasis, and we strongly encourage interested readers to read the recently published proceedings from that meeting of 63 investigators and public health officials The final consensus schistosomiasis research agenda is provided in full in Boxes From one perspective, the new agenda may appear to be nothing more than an exhaustive “laundry list” of every type of study needed on schistosomiasis. The agenda also has elements that could be applied to almost any neglected tropical disease. Nevertheless, almost the entire schistosomiasis community participated in its development, trying to make the distinct parts fit a united whole. The agenda is not an attempt to prioritize one discipline of schistosomiasis research over another. We specifically avoided doing this because it is unlikely that any one funding agency would be interested in programs across the entire spectrum. In addition, we believe that attempts to prioritize specific areas of research from this broad agenda would prove to be unproductive and would create unnecessary factions. However, it may be valuable for researchers within one arena—for example, vaccine development or transmission dynamics—to use the agenda to prioritize research needs within their own field. It may also be useful for a group of individuals to take components from different sections of the agenda that fit well together and then approach funding agencies with linked components from the agenda. For example, a group of investigators who wanted to work together on development of a new, more sensitive, robust, field-applicable assay for active infection could merge relevant aspects of the agenda into a plan that spans genomics through field testing, including community acceptability, and then take that plan forward to a funding agency. If the consensus agenda is utilized in developing the proposal, both the group of investigators and the funding agency would be reassured that its foundation arose from the group effort of literally hundreds of experts in the field.PLoS ONE journal (http://www.plosone.org/), in which readers can annotate the literature, start discussion threads, and upload their own editorial commentaries. Through such an interactive process of community interchange, the new schistosomiasis research agenda can be continually commented upon, rearranged, and rewritten, as needs be.The agenda is not intended to be a static document. Rather, if it is to be relevant to the community, topics and approaches must be added and removed as new discoveries are made. The overarching goal of the agenda is to be inclusive of all those aspects of schistosomiasis-related research that are considered by the schistosomiasis community to be worthwhile, from both a basic scientific perspective and, obviously, in relationship to ultimate disease and infection control. We also hope to work with the Public Library of Science (PLoS) to create a schistosomiasis community portal based upon the online functionality in the recently launched A. DrugsOptimization of treatment regimens in different transmission conditionsNumber of dosesDose intervalsMechanisms of action (old and new drugs)Identification of schistosome proteins/pathways that are candidates for drug actionDevelopment and testing of new drugs Development of schistosome cell lines for high-throughput screeningFunctional expression of putative drug targetsRNAi analysis for the detection of target moleculesAssays for standardization of drug qualityDevelopment and standardization of assays and markers for resistance to praziquantelMonitoring the nature and spread of drug resistance, and its effect on schistosomesCombinatorial effects of anti-schistosome therapiesArtemisinin-based combination therapiesCombinations of established anti-schistosome drugs with new drugs as registeredPharmacokineticsEffects of infections and coinfectionsFood intakeIntensity of infection and transmissionImpediments to treatmentAccess to drugsAccess to other health care servicesAccess to appropriate information, education, and communication for infected communitiesHow do real and/or perceived adverse events affect control programs?B. DiagnosticsOptimization and combination of existing tools Assays for worm burdenSensitive, specific, inexpensive, field applicable, using accessible specimensHigh prevalence areasLow prevalence areasAble to distinguish active infection and successful cureInvestigate metabolites and other products as markers of infectionTools for detection of morbidity or pre-morbidityValidation of diagnostic approachesCentral standardizationUniformity of assays among studies and control programsSurveillance tools for control programsDevelopment and standardization of molecular monitoringHumansSnailsAssessment of treatment failuresSociocultural and economic factors influencing the validity of diagnostic testsC. Control and implementationCombined approaches to controlEvaluate integrated use of treatment, sanitation, water supply, molluscicides, health communication, biological and environmental interventions, and eventually vaccines in combinatorial ways, and their community acceptability; develop comprehensive mathematical models incorporating these control measures and their clinical and economic impactEvaluate integrated control programs, their efficacy and effectivenessSchool-basedCommunity-basedCombination of school- and community-based approachesTreatment of special populationsUse during pregnancy and lactation periodsUse during early childhoodSocial aspects of controlHealth communications/education programsEvaluate combinations of content, communication means, participants and institutional settings adapted to local conditionsPerceptions, attitudes, and practices—the knowing and doing gapCommunity involvement in controlSocial dynamics of snail control by environmental modificationsWhat are the incentives and disincentives at individual, household, village, and regional levels for praziquantel treatment and snail habitat modifications?Evaluation to improve sustainability, including areas of low endemnicityControl in health systems and inter-sectorial perspectiveWhat determines the cost-effectiveness of various control measures?Enhancement of water resources development projectsWhat determines whether control is part of an integrated program?Integration of control into community-directed treatment schemesDynamics of control as part of the broader health systems perspective A. HostsHumanGenetic studiesAge effectsReservoir hosts of human speciesSnailsTools to assess cercarial species, presence and releaseTools to identify and distinguish closely related snail speciesQuantification and factors affecting absolute density of infected snailsSurveillance of immigrant snails into new areasAssessment of genetic inbreeding on parasite transmissionConsequences of parasite coinfections in snailsEnvironmental impacts on parasite transmission to snailsEvaluation of new molluscicidesGenetic studies on host–parasite strain interactions and compatibility, including genomics, mathematical models, and population structureComparison of field versus laboratory parasite isolatesB. Fresh waterPositive/negative effects of pollution on snails and transmissionImpact of environmental change Development, implementation, use, and impact of appropriate technologies for water suppliesEnvironmental impact and effectiveness of molluscicide-based controlImpact of natural and exotic species on snails and on transmissionC. Transmission dynamics HumanNatural, non-human hostsUrban transmissionLow transmission areas after control programsSocial determinants of exposure Perceptions, attitudes, and practices—relationship to changes in transmissionD. Public awarenessCampaigns based on realistic DALYs (disability-adjusted life years) and impact of schistosomiasis to increase awareness and need E. Application of geographic information systems/remote sensing and ground verificationTransmission patterns and predictionsGeo-spatial (micro) determinants of riskA. MorbidityAttributable fractionAnemia and mechanisms of anemiaUnder-nutritionOrgan dysfunctionCognitive developmentEconomic costs of infectionAdapt standardized tools for quality of life assessment to schistosomiasisAccurate disability weights, recalibration of DALYsImpact of disease on households, communities, and societiesSchistosoma haematobium and possibly S. japonicum)Carcinogenesis Morbidity following reinfectionEffects on reproductive health and fertility Effects of host geneticsB. ComorbiditiesInteractions of other infections with schistosomiasis Effects of schistosomiasis and its treatment on coinfectionsEffects of coinfections and their treatment on schistosomiasisEffects of schistosomiasis on transmission of coinfections(S. mansoni and S. haematobium)Interactions and impact of dual schistosome infections Interactions of schistosomiasis with noninfectious conditions Effects of schistosomiasis on vaccination programsC. PregnancyInfluence on childMorbidityIn child in utero In child subsequently infectedImmunologyEffect on neonatal vaccinationsIf child subsequently infectedTreatment issuesNeed retrospective and prospective studiesImplementation, policy changesA. VaccinesDiscoveryAntigens and protective responses in model and human systemsHigh-throughput vaccine designEffects on infected or previously treated hosts Vaccine types other than prophylactic Scale-up production (good laboratory/manufacturing practices)Adjuvants/delivery (DNA versus prime boost versus protein)EvaluationModel systemsCloser look at animals that develop “sterile immunity”Rapid assessment of vaccine efficacyNon-human primates In the field B. Immunology and pathologyDuring infection (human and model systems)Resistance versus susceptibility—mechanismsImmunopathologic mechanismsFibrosisAngiogenesisImmunoregulatory mechanismsHost responses to defined antigensImmune evasionEffects on non-immune systems Effects on immune response systemInnate immune alterations/identification of schistosome pathogen-associated molecular patternsAtopic allergy/role of schistosomiasis in “hygiene hypothesis”Autoimmune diseasesSchistosome molecules as adjuvantsRole of host genetic polymorphisms (resistance and morbidity)Effect of treatment on immune responsesSnail responses to infectionC. Genomes and postgenomics Sequencing, annotation, database developmentComparisons of species and strainsProteomicsGlycomicsD. Basic biology of life-cycle stagesAs themselvesMale–female interactionsFemale reproductive development and fecundityAs model systemsLife-cycle stage shifts as developmental biologyS. haematobiumEstablishment of laboratory life cycles of S. japonicumExpanded studies on experimental Fecundity and egg excretionInvestigation of schistosome germ cellsHost–parasite interactionsRole of host molecules in parasite development and life cycleIdentification of parasite molecules that regulate host functionNeurobiology and neuromuscular physiologyE. Biochemistry and molecular studiesMembrane biologyMetabolism using genomics, glycomics, and proteomicsCharacterization and functional roles and uses of schistosome componentsDevelopment of “molecular tool box” for schistosomesSchistosome cell linesRNAi and other gene silencing toolsTransient and stable transgenic schistosome cells or parasitesExpression of schistosome proteins in other eukaryotic systemsImportant functional genesIsolate/investigate individual schistosome organs  or cellsFactors dictating host specificity in vertebrates and snailshttp://www.schisto-resource.org/ and http://www.afbr-bri.com/sr3/); (5) recruitment of trainees; (6) enhanced mentoring of junior schistosome researchers; and (7) assistance in enlisting outside experts into the field of schistosomiasis  more schistosomiasis-focused interdisciplinary networks; (2) the development of standardized protocols for multicenter studies; (3) a higher profile for schistosomiasis within the global health community; (4) the further use of repositories of schistosome-related materials  and eventually better publicize the need for all research on this important disease, which in addition to advancing global public health efforts also has much to offer to fundamental biomedical knowledge. In addition, we hope that this will be an inclusive and living agenda. To make the latter attribute come true we invite readers of


More than 20 key officials from the American Veterinary Medical Association and theAssociation of American Veterinary Medical Colleges met with staff from the Centers forDisease Control and Prevention (CDC) December 5–6, 2002, to discuss theincreasing convergence of issues confronting human and animal health. Among theofficials in attendance were the deans from more than half of all U.S. veterinaryschools.The meeting goals were to increase the veterinary community’s understanding ofCDC programs and the varied roles played by veterinarians throughout the agency; toprovide CDC officials an opportunity to gain insight into current issues in veterinarymedicine as well as the public health perspectives of veterinary leaders; and to providea forum for discussions on ways to increase partnerships between the human andveterinary medical communities to meet critical public health needs. Presentations weremade by James Hughes, Michel Bunning, Patricia Griffin, David Bell, Nina Marano, TraceeTreadwell, Thomas Ksiazek, and Peter Schantz, National Center for Infectious Diseases;Marguerite Pappaioanou, Office of Global Health; Hugh Mainzer, National ImmunizationProgram; Douglas Hamilton, Epidemiology Program Office; and Andrew Dannenberg, NationalCenter for Environmental Health. Many of these speakers are CDC veterinarians, whodescribed their paths from veterinary training to public health.The daily interactions of humans, animals, and the environment have a dramatic impact onpublic health. Current and evolving health threats include infections transmittedthrough animals, insects, food, and water, as well as illnesses resulting fromenvironmental toxins, the misuse of antibiotics, and bioterrorism. Factors affectingthese threats include the international movement of people, animals, and animalproducts; globalization and management of the complex food and fiber system; climate andother environmental changes, including those affecting wildlife populations and theirinteractions; and national and global security. Effectively meeting these challengesrequires strong links between human and animal health clinicians, researchers,laboratorians, and public health officials.Specific topics presented included West Nile virus and other vectorborne diseases,emerging viral and parasitic zoonoses, food safety, antimicrobial resistance,CDC’s role in the 2001 anthrax investigations, and the agency’sbioterrorism preparedness and response program. Presentations highlighted public healthissues such as the need to upgrade containment facilities and to define optimalantibiotic use for farm animals. Efforts needed to further protect the health of humans,companion animals, zoo and exotic animals, and wildlife were also discussed. Theseefforts include improving strategies to reduce the occurrence of intestinal parasites inpets and increasing surveillance among imported animals and products to recognizeinfections not previously seen in the United States.Several presenters emphasized the importance of surveillance systems in enabling promptrecognition of disease occurrences. Examples included two food safety surveillanceprograms: FoodNet, a collaborative project involving nine states, the U.S. Department ofAgriculture, CDC, and the Food and Drug Administration; and PulseNet, a national andinternational network of public health laboratories that subtype foodborne bacteria toenable rapid comparison of DNA patterns through an electronic database. Othersurveillance systems discussed included the National Antimicrobial Resistance MonitoringSystems and the Laboratory Response Network (LRN). LRN is a tiered system oflaboratories with varying diagnostic capabilities, ranging from confirmatory analysis tospecialized identification of agents potentially used in a bioterrorist attack. Thenetwork is supported through funding designated for bioterrorism preparedness andresponse. Meeting participants discussed the need to increase participation ofveterinary clinicians and diagnosticians in these surveillance systems, especially LRN,noting that 80% of the agents classified as “category A”  are zoonotic. Strategies discussed at the conferencetoward this end included adding veterinary and animal health laboratories to LRN as wellas establishing a similar network among such laboratories to collect more comprehensivedata on the occurrence of infections affecting veterinary and human health.CDC veterinarians participating in the meeting described their experiences as well as theroles of other agency veterinarians. Many CDC veterinarians are epidemiologists whojoined the agency as officers in the Epidemic Intelligence Service (EIS),CDC’s 2-year, hands-on comprehensive epidemiology and public health trainingprogram. Of the approximately 75 veterinarians who work at CDC, nearly half are in theNational Center for Infectious Diseases, where they work in laboratory animal researchas well as epidemiology. Discussions at the meeting described the critical roles playedby veterinarians at the local, state, and national levels in responding to the recentWest Nile virus outbreaks. Approximately 42 states currently have state public healthveterinarians.Many discussions focused on ways to increase the number of veterinarians in public healthclinical and laboratory programs. Several CDC veterinarians cited classes in herd healthas stimulating their interest toward public health careers. At the initial level,efforts are needed to ensure that veterinary students are aware of these careeropportunities early in their education. Potential strategies include offeringexternships and public health rotations, such as at CDC or at local and state healthdepartments, as part of veterinary medical school training courses and offering combineddegrees in veterinary medicine and public health —a course ofstudy already offered by several veterinary colleges. Other innovative public healthprograms that could be incorporated by veterinary medical colleges include studies infood safety, environmental toxicology, healthy ecosystems, international diseases, andpopulation medicine.More veterinary EIS Officers are also needed. Approximately one third of veterinariansapplying to EIS are accepted, essentially the same acceptance rate as for otherprofessions. Increased numbers of veterinarian applicants would therefore translate intohigher numbers of accepted veterinarians. EIS recruits at the national AmericanVeterinary Medical Association meeting but could expand its efforts to include schoolsof veterinary medicine. Similarly, efforts are needed to increase the number ofveterinarians and veterinary students applying for other training programs at CDC suchas the Emerging Infectious Diseases Laboratory Fellowships. Through this program,bachelor’s or master’s level scientists are recruited for 1-yearassignments and postdoctoral level scientists for 2-year assignments at state, local,and CDC public health laboratories. More veterinary applicants are also needed for othertraining programs offered by CDC, such as the elective in epidemiology for seniormedical and veterinary students—a 6- to 8-week introductory course inpreventive medicine, public health, and applied epidemiology.The World Health Organization (WHO) will soon be making available on the Internet itsfindings from a study group on the future of veterinary public health . The report describes the increasing emergence and reemergence ofzoonotic diseases in the 1980s and 1990s and their importance for global public health(To effectively meet these challenges, human and animal health issues must be merged intoa new public health agenda. Creating and responding to such an agenda depend on stronginteractions between the human and veterinary clinical, laboratory, and public healthprofessional organizations. These interactions are essential for developing new andstrengthening existing partnerships necessary for implementing effective public healthprograms. This meeting was a step toward this goal.


We used data from a large cohort study of Canadian women to assess the association of meat intake and dietary intake of iron and haem iron with risk of endometrial cancer. Among 34 148 women with an intact uterus at baseline and followed for a mean of 16.4 years, we identified 426 incident endometrial cancer cases. Data from a food frequency questionnaire administered at baseline were used to calculate intake of all meats, red meat, total dietary iron, iron from meat, haem iron, and non-haem iron. Analyses were carried out using Cox proportional hazards models with adjustment for known risk factors and covariates. We found no association of intake of meat or any of the dietary iron-related variables with risk of endometrial cancer. Endometrial cancer is largely a malady of affluent, developed societies, showing a more than 10-fold variation between high- and low-incidence countries , and recA possible association of red meat intake with endometrial cancer risk may reflect a role of haem iron, which derives mainly from red meat and which has greater bioavailability than inorganic iron . Free irGiven that few cohort studies have examined the association of meat intake with risk of endometrial cancer , a randomised controlled trial of screening for breast cancer, which has been described in detail elsewhere  or death, whichever occurred first. During an average of 16.4 years of follow-up of the dietary cohort, we identified 426 incident endometrial cancer cases.Data from the FFQ were used to calculate total dietary iron intake using a database described elsewhere .−2) (continuous); menopausal status ; parity ; age at menarche (continuous); duration of oral contraceptive use ; duration of hormone replacement use ; total caloric intake (continuous); intake of raw vegetables (continuous); alcohol intake (in grams–continuous); physical activity ; and education (three levels). Addition of indicator variables for screening centre (1–15) and randomisation group in the original screening trial  did not affect the risk estimates, and therefore, these variables were omitted. Because an effect of iron or haem iron intake could be confounded by intake of other dietary constituents with which they are correlated, we included important food items  in additional models. Inclusion of these variables did not affect the risk estimates for iron or haem iron, and as a result they are not included in the final models. To test for trends in risk with increasing levels of the exposures of interest, we assigned the median value for each quintile and then fitted the medians as a continuous variable in the risk models. We then evaluated the statistical significance of the corresponding coefficient using the Wald test  were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between meat intake and iron intake and endometrial cancer risk. Quintiles of meat- and iron-related variables were constructed based on their distribution in the total population. All multivariate models included the following covariates: BMI , the patterns were similar to those described above, and no associations or trends were seen with any of the six variables.In both age- and multivariate-adjusted models, none of the meat or iron-related variables was associated with risk of endometrial cancer . For allThere was no association between haem iron intake and endometrial cancer risk within strata of BMI, hormone replacement therapy use (ever or never), or menopausal status . The results for meat-related variables and the other iron-related variables were similar (data not shown).The present analysis showed no association between intake of meat or red meat or dietary intake of iron, haem iron, iron from meat sources, or non- haem iron and risk of endometrial cancer. We also found no association of any of these variables with endometrial cancer risk within strata of BMI or hormone replacement use, the two strongest risk factors in our study, or within strata of menopausal status, which is an important determinant of body iron levels.The few previous studies of meat and red meat intake in relation to endometrial cancer were mainly case–control in type, while a recent systematic review and meta-analysis has examined the available evidence in detail  to permit a conventional analysis (P for trend =0.03). We did not have information on use of iron supplements, which represent an important contributor to total iron intake in users. In a cohort study of New York City women enrolled from 1985 to 1991 (No previous studies have examined dietary iron intake in relation to endometrial cancer risk. However, a case–control study from Sweden (The present study has a number of strengths. We had a relatively large number of incident endometrial cancer cases and were able to control for known risk factors, including BMI, hormone replacement therapy, parity, oral contraceptive use, and physical activity, as well as other covariates, including total caloric intake. In agreement with previous studies, in our data BMI and duration of hormone replacement use showed dose–response relationships with endometrial cancer risk, and parity and duration of oral contraceptive use were inversely associated with risk. Our questionnaire included 22 questions on different types of meat and meat-containing dishes, and we used two different approaches to estimating haem iron intake, both of which yielded similar results. Finally, the results were unchanged when cases diagnosed during the first 3 years of follow-up were excluded from the analysis.A number of limitations should also be mentioned. Only baseline exposure data were available, and dietary and other exposures may have changed over the 16 year average follow-up period, resulting in some degree of non-differential misclassification of exposure, which would reduce the power to detect an effect of the variables under study. Also, we also did not have information on a personal history of diabetes.In summary, in this large prospective cohort study, we found no suggestion of an association of intake of meat, red meat, or dietary intake of iron or haem iron assessed at baseline with risk of subsequent endometrial cancer. Furthermore, we found no associations of any of these variables within strata of established risk factors. Future studies should improve on the assessment of iron and haem intake by using repeated measurements and obtaining information on use of iron-containing supplements and a personal history of metabolic syndrome and diabetes.


The diagnosis of chronic fatigue syndrome (CFS) in research studies requires the exclusion of subjects with medical and psychiatric conditions that could confound the analysis and interpretation of results. This study compares illness parameters between individuals with CFS who have and those who do not have exclusionary conditions.We used a population-based telephone survey of randomly selected individuals, followed by a clinical evaluation in the study metropolitan, urban, and rural counties of Georgia, USA. The medical and psychiatric histories of the subjects were examined and they underwent physical and psychiatric examinations and laboratory screening. We also employed the multidimensional fatigue inventory (MFI), the medical outcomes survey short form-36 (SF-36) and the US Centres for Disease Control and Prevention symptom inventory (SI).Twenty-nine percent  of the 5623 subjects who completed the detailed telephone interview reported exclusionary diagnoses and we diagnosed an exclusionary condition in 36% of 781 clinically evaluated subjects. Both medical and psychiatric exclusionary conditions were more common in women, blacks and participants from rural areas. Subjects with and without exclusions had similar levels of fatigue and impairment as measured by the MFI and SF-36; those with CFS-like illness  were more likely to have an exclusionary diagnosis. After adjusting for demographics, body mass index, fatigue subscales, SF-36 subscales and CFS symptoms, CFS-like illness did not remain significantly associated with having an exclusionary diagnosis.Medical and psychiatric illnesses associated with fatigue are common among the unwell. Those who fulfill CFS-like criteria need to be evaluated for potentially treatable conditions. Those with exclusionary conditions are equally impaired as those without exclusions. The diagnosis of chronic fatigue syndrome (CFS) for research and clinical purposes is based on a clinical definition: persistent or relapsing fatigue of at least 6-months' duration, that is not alleviated by rest and that causes a substantial reduction in activities; a fatigue that cannot be explained by medical or psychiatric conditions and must be accompanied by at least four of the eight case defining symptoms  .Since CFS definitions were originally formulated for research purposes, the exclusion of active medical and psychiatric illnesses or diseases associated with fatigue was considered necessary for two reasons -5. FirstIn addition to its use in research, the definition is widely used for clinical purposes. The clinical application has been hampered because it gives practitioners little guidance on how to determine when a patient is sufficiently impaired or symptomatic to warrant the diagnosis and when to include patients with adequately treated 'exclusionary' diseases who may continue to have symptoms and consequences compatible with CFS. The first issue was partly addressed by the application of empiric methods to the diagnostic process . HoweverThe purpose of this analysis is to describe the prevalence of exclusionary diagnoses identified in a population-based surveillance study of fatigue illnesses and to compare those with and without such conditions in terms of: (1) demographics; (2) specific exclusionary categories; (3) the presence of CFS case-definition criteria; and (4) levels and characteristics of fatigue and impairment. The frequency with which potentially treatable conditions were identified in subjects otherwise meeting research criteria for CFS emphasizes the need for clinicians treating patients presenting with unexplained fatigue to consider these illnesses in the differential diagnosis.This study was approved by the US Centers for Disease Control and Prevention (CDC) Institutional Review Board, as required by Department of Health and Human Services regulations. All participants were volunteers who gave their informed consent. The study was conducted in English. Non-English speaking respondents were excluded.et al. [unwell any household members who had had at least one of the four most common CFS defining symptoms  for ≥ 1 month and as well those who had experienced none of these problems for ≥ 1 month.The study design was described in detail by Reeves et al. . Subjectet al. ,9. A houn = 469), those classified as chronically unwell (n = 505), and the randomly selected well (n = 641) matched to the CFS-like classification on age, sex and geographic area were invited to a 1-day clinic where they were given a physical examination, a psychiatric interview, laboratory screening and completed self-administered questionnaires. Final classification categories include: (1) CFS; (2) insufficient fatigue ; (3) non-fatigued (NF); and (4) subjects who appeared in each category but for an exclusionary diagnosis.All those identified as unwell with fatigue, as well as randomly selected persons identified as well and as unwell without fatigue, were asked to complete a detailed computer assisted telephone interview (CATI). On the basis of the telephone interview respondents were classified as: (1) having a medical or psychiatric condition considered exclusionary; (2) having a CFS-like illness characterized by severe fatigue lasting for 6 months or longer that was not alleviated by rest, that caused a substantial reduction in occupational, educational, social or personal activities and that was accompanied by at least four of the CFS case defining symptoms ; (3) having prolonged (≥ 1 month) or chronic (≥ 6 months) unwellness with or without fatigue, but not meeting criteria for CFS; or (4) being well. All respondents classified as CFS-like  [Demographic data  and past medical and psychiatric history data were obtained via telephone interviews and confirmed at clinic by self-administered questionnaires. Height and weight were measured at the clinic; body mass index (BMI) was calculated as the ratio of weight in kilograms to height in metres squared. To complete the screening for existing, but unidentified, medical and psychiatric conditions, participants reviewed current medications and medical history with clinic personnel and had a complete physical examination with laboratory tests recommended for the evaluation of possible CFS. In addition, a psychiatric interview was conducted using the structured clinical interview for disorders described in the forth edition of the  DSM-IV) . A revieWe used the multidimensional fatigue inventory (MFI)  to assesad hoc comparisons. We used logistic regression to generate odds ratios (OR) as measures of the association between the inclusion/exclusion status and the demographic factors and qualitative health status. A multivariate logistic regression model was used to examine the likelihood of a subject being excluded with the adjustment of all other covariates in the model. All tests of significance were two-sided with the alpha level set at 0.05. The analyses were performed using SAS version 9.1 .General linear models were performed in order to examine the bivariate associations between health outcome measures  and the following covariates: (1) diagnostic subgroups ; (2) exclusion status (included or excluded); (3) demographics such as sex, age, race or geographic stratum; (4) BMI. Tukey-Kramer tests were employed to test significance of The study sample of 5,623 subjects at a CATI evaluation (the detailed interview) were primarily female (64%), white (65%), living in rural or urban areas (80%) with a mean age of 41.6 years (data statistics not shown). Similar distributions were present in the 781 subjects seen in the clinic whose mean age was 43.5 years . However, when adjusted for all other variables in the table, only a lower (worse) vitality score (the score representing fatigue and energy) of the SF-36 was associated with exclusionary diagnoses.As shown in Table The types of specific exclusionary medical and psychiatric conditions detected in clinic were similar for those otherwise classified as CFS, ISF and NF Table ; thyroidP < 0.01; Table P < 0.01 for all; Table P < 0.01; Table Subjects with psychiatric exclusionary conditions were significantly younger than subjects with medical exclusions . In addition, subjects with both types of conditions had significantly lower mean scores for SF-36 subscales measuring physical functioning and role physical. Subjects with only psychiatric exclusionary conditions were significantly less impaired than those with only medical exclusionary conditions for physical functioning and in the physical component summary score (P < 0.01 for both). Overall, the group with both types of exclusionary diagnoses demonstrated greater fatigue, greater impairment and higher symptom scores.Subjects with both medical and psychiatric diagnoses had higher MFI-20 scores (more fatigue) in all dimensions and these differences were statistically significant for physical fatigue, reduced activity and reduced motivation (2) of BMI .Table The study illustrates the complexity that exclusionary conditions introduce into both research and clinical considerations of subjects potentially classified as CFS. The exclusionary diagnoses are common; 28% of subjects in a population-based sample had exclusions identified during a personal history telephone interview. Exclusionary conditions/diseases were subsequently recognized in an additional 36% of subjects undergoing a full clinical examination. It appears that during the telephone interview subjects did not know of or did not remember all of their exclusionary diagnoses. This discrepancy could be due to: (1) greater accuracy and specificity of information obtained by clinical examination compared to telephone interview; (2) variable access to healthcare which, in turn, means variable access to diagnostic means ; (3) asyThe finding that increased BMI was independently associated with having an exclusionary condition among CFS patients, suggests that the condition may be 'silent' as in some correlates of elevated BMI, including metabolic conditions, sleep disorders and hypothyroidism. This interpretation is supported by the finding of exclusionary conditions in 26 people who, in the telephone interview, had considered themselves 'well'.The diagnoses considered exclusionary for CFS were originally selected because they frequently result in symptoms similar, if not identical, to those characteristic of CFS subjects. As might be expected, differences between subjects with and without exclusionary diagnoses were not universally present. For example, general fatigue and reduced activity scores of the MFI and physical function, role physical, social function and role emotional scores of the SF-36 were equivalent. Likewise, CFS and non-CFS symptom scores were not significantly different. Thus, in terms of level of overall 'sickness'  and impaAlthough not emphasizing the differences between subjects who fulfill defined requirements for exclusionary diagnoses and those who do not, previous studies of chronic fatigue and CFS have shown high rates of psychiatric morbidity and functional morbidity and have documented these outcomes as important public health burdens ,19. AnotIn principle, the results of this study, and of previous observations, support the original decision to exclude subjects with fatigue and selected concurrent identifiable illnesses/diseases from the research diagnosis of CFS as the latter shares illness characteristics and consequences with the syndrome . The excIt is equally clear that subjects with exclusionary diagnoses are at least as comparably functionally impaired as the included subjects. The chronically unwell population, identified here with a fatiguing illness, is likely to have a medical disease and/or a psychiatric disease. However, these conditions may go undiagnosed. Since subjects with and without identifiable exclusionary disease processes share many symptoms, clinical management requires careful attention in order to correctly identify and treat the medical and psychiatric illnesses. It is clear that treatment of the underlying diseases will not resolve fatigue and symptoms in all instances and it is possible that illnesses/diseases with chronic fatigue share a common underlying pathophysiologic mechanism. In order to examine this possibility, subjects with exclusionary conditions could be included with CSF cases for comparison.The primary limitation of this study is the inclusion of subjects who have been ill for an average of 6-7 years. The majority of the subjects had experienced a gradual onset of their illness. Thus the exclusion of subjects fulfilling CFS criteria and having medical and/or psychiatric illnesses may be observed more frequently in the population under study than in the younger individuals with an acute onset. Likewise, the levels of impairment may also be more applicable to this population. Replication of these observations will be possible in future follow-up studies.As those with CFS suffer from personal, social, workplace  and obseThis analysis allows three different, but complementary, interpretations of the results that need to be addressed in future studies. First, it substantiates the need for the identification of underlying diagnoses that impact the choice of subjects for epidemiological and mechanistic studies of a specifically described illness construct. Secondly, it suggests that those who would otherwise fulfill the CFS definition, but who have an exclusionary illness or disease, are as impaired as those defined as having CFS. The third interpretation is that CFS, in the population studied here, may reflect underlying medical or psychiatric illnesses or diseases that are not necessarily 'under control'. The data therefore suggest that, in order to substantiate CFS as a specific entity or to identify shared pathophysiological factors, subjects fulfilling the criteria of fatiguing illnesses, but who have exclusionary and non-exclusionary diagnoses, need to be included as comparison case groups in both mechanistic and therapeutic studies. The identification of subjects for CFS studies requires a clinical evaluation; medical and psychiatric histories obtained by telephone interviews are not completely reliable.Diagnostic and statistical manual of mental disorders; DSM-IV: disorders described in the fourth edition of the DSM; ISF: insufficient fatigue; MDDM: major depressive disorder with melancholic features; MFI: Multidimensional Fatigue Inventory; MCS: mental component summary; NF: non-fatigued; OR: odds ratio; PCS: physical component summary; SCID: structured clinical interviews for DSM disorders; SF-36: short form 36; SI: symptom inventory.BMI: body mass index; CATI: computer-assisted telephone interview; CDC: US Centers for Disease Control and Prevention; CFS: chronic fatigue syndrome; DSM: The authors declare that they have no competing interests.JFJ, ERU and WCR were involved in the conception and design. JMSL, EMM, RSB, UMN, ERU, JFJ and WCR were involved in the analysis and interpretation of the data. JFJ. JMSL, EMM, ERU, RSB and WCR drafted the article. JFJ, JMSL, EMM, RSB, UMN, ERU and WCR were responsible for critical revision of the article for intellectual content. JFJ, JMSL, EMM, RSB, UMN, ERU and WCR gave final approval of the article. JMSL, EMM and WCR provided statistical expertise. JMSL, JFJ and WCR were involved in the collection and assembly of the data.The pre-publication history for this paper can be accessed here:


Internal carotid artery (ICA) dissection is responsible for 10–20% of strokes in young and middle-aged patients. Isolated ICA dissection involving the intrapetrous carotid canal is particularly rare, and no case has been reported to describe an association between intrapetrous ICA dissection and essential thrombocythemia. We report a case of ischemic stroke in the presence of intrapetrous right ICA dissection and essential thrombocythemia. The diagnosis of essential thrombocythemia was performed by bone marrow biopsy. The essential thrombocythemia may cause endothelial dysfunction and predispose to vascular damage such as carotid artery dissection. Internal carotid artery (ICA) dissection is responsible for less than 2% of all ischemic strokes, and for 10–20% of strokes in young and middle-aged patients, with a peak incidence in the fifth decade . We repoA 57-year-old woman was admitted to II° Policlinico hospital of Naples after an episode of left arm weakness, dysarthria and mouth deviation at left, occurred one week before admission. The patient had a medical history of paroxysmal supraventricular tachyarrhythmias and smoking. She denied any history of trauma and other cardiovascular risk factors. The patient was normotensive and on physical examination she presented a normal clinical state except for neurological evaluation that showed the persistence of left arm weakness and low facial paralysis with NIH stroke scale  score of 3. Diagnostic evaluation included extensive laboratory blood tests , that were normal except for LDH (lactate dehydrogenase) increase and platelet count , chest roentgenography , 12-lead electrocardiography , transthoracic echocardiography , carotid ultrasound, that revealed a fibrocalcific plaque at the left carotid bulb, without significant haemodynamic changes, brain magnetic resonance, that showed a cerebral ischemic at the posterior-frontal lobe of the right cortical hemisphere, and brain computed tomography (CT)-angiography, disclosing an irregular narrowing and an eccentric filling defect along the petrous portion of the right ICA suggestive of a dissection . The disease usually affects middle aged to elderly individuals, with an average age at diagnosis of 50–60 years. Approximately half of the patients are asymptomatic while the other half have vasomotor, thrombotic or hemorrhagic disturbances. Typical essential thrombocythemia is a Philadelphia bcr-abl negative (Ph1-) CMPD with a good prognosis and overall survival. For a long time, the Polycythemia Vera Study Group (PVSG) criteria for the diagnosis of ET have not included histopathological data. Recently, a new World Health Organization (WHO) classification for CMPD has been developed, incorporating clinical, laboratory and morphologic data along with fresh knowledge and techniques . The cliBCR-ABL gene rearrangement and we excluded causes of reactive thrombocytosis. It is unclear whether there is a relationship between intrapetrous internal carotid artery dissection and essential thrombocythemia. An endothelial damage, due to the activation of leukocytes and the consequent release of elastase and alkaline phosphatase, is observed in essential thrombocythemia and it seems to play a major role about the pathogenesis of the thrombophilic state, including elevated levels of platelet-specific proteins, increased tromboxane generation and expression of activation-dependent epitopes on platelet surface [In our patient we observed a progressive increase of platelet count and various complications, typical of essential thrombocythemia. We performed a bone marrow biopsy and the study of  surface . The ass surface .It is much more likely that thrombocytosis and elevated homocysteine, because they both increase thrombosis, make dissections more likely to be symptomatic, than that they actually predispose to dissection. Probably there are many patients with dissection that is asymptomatic; those with increased thrombosis are more likely to have symptoms and thereby be diagnosed.In summary, this case shows that essential thrombocythemia might predispose to vascular dysfunction and damage such as carotid artery dissection. Whether this association is casual or causal remains a matter of speculation. However, essential thrombocythemia should be excluded in the presence of carotid artery lesions and thrombocytosis.Written informed consent was obtained from the patient for publication of this Case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.CMPD: Philadelphia Chronic myeloproliferative disease; CT: computed tomography; ET: essential thrombocythemia; ICA: internal carotid artery; LDH: lactate dehydrogenase; MR: magnetic resonance; NIHSS: National Institute of Health Stroke Scale; Ph1-: Philadelphia bcr-abl negative; PTCA: percutaneous transluminal coronary angioplasty; PVSG: Polycythemia Vera Study Group; WHO: World Health Organization.The authors declare that they have no competing interests.DD and DDM conceived and designed the study; acquired the data; analyzed and interpreted the data; drafted the manuscript; made critical revision of the manuscript for important intellectual content. GG and MR helped to acquire the data, and made critical revision of the manuscript for important intellectual content. TR, FR, and PA drafted the manuscript; made critical revision of the manuscript for important intellectual content. All authors read and approved the final manuscript.


We ascertained the degree to which language (English versus Spanish), and residence time in the US influence responses to survey questions concerning two topics: self-reported acculturation status, and recent physical activity (PA). This topic is likely to be of general interest because of growing numbers of immigrants in countries worldwide.We carried out qualitative (cognitive) interviews of survey items on acculturation and physical activity on 27 Latino subjects from three groups: (a) In Spanish, of those of low residence time (less than five years living in the U.S.) (n = 9); (b) In Spanish, of those of high residence time (15 or more years in the U.S) (n = 9); and (c) in English, of those of high residence time (n = 9).There were very few language translation problems; general question design defects and socio-cultural challenges to survey responses were more common. Problems were found for both acculturation and PA questions, with distinct problem types for the two question areas. Residence time/language group was weakly associated with overall frequency of problems observed: low residence time/Spanish (86%), high residence time/Spanish (67%), and English speaking groups (62%).Standardized survey questions related to acculturation and physical activity present somewhat different cognitive challenges. For PA related questions, problems with such questions were similar regardless of subject residence time or language preference. For acculturation related questions, residence time/language or education level influenced responses to such questions. These observations should help in the interpretation of survey results for culturally diverse populations. The Latino population is of considerable importance for public health and epidemiological research in the US because of its size and growth rate, and because this population includes a complex mix of people from different countries, of differing economic status, different preferred languages for various social, work, or media related activities, and varied level of acculturation to Non-Latino U.S. society.A 2008 estimate indicates that the US population includes over 46 million Latinos or approximately 15.4% of the total population A key challenge for measuring health behaviors and conducting epidemiological studies in the Latino population is the development of comparable survey instruments capable of eliciting valid and repeatable responses concerning both health behaviors and the psychological and social aspects of the recent immigrants . Such eAcculturation measures have been difficult to develop for health surveys, especially because these are the subject of considerable controversy, as an explanatory variable concerning health status and health behaviors. Some studies document strong correlations between health behaviors and acculturation, as measured by language use or duration of residence in the US -7. In coPopulation-based research and surveillance requires valid instruments for the assessment of lifestyle variables and for demographic and cultural variables that might influence behavior. Of particular concern is the possibility that language and cultural variation in immigrant populations might make it difficult to develop such instruments so as to produce equally valid results for people with different nativities and language skills - or cross-cultural comparability -13. Cognhttp://wwwn.cdc.gov/QBANK/Home.aspx, systematically characterize the types of problems observed in the cognitive pretesting of survey questions into nine specific coding categories: (1) Interviewer Difficulties, (2) Problematic Terms, (3) Ambiguous Concepts, (4) Overly Complex Question, (5) Erroneous Assumption or Double Barrel Question(6) Questionnaire Effects (spanning more than a single item), (7) Recall/Estimation Difficulty, (8) Biased/Sensitive Question, and (9) Inadequate Response Options. Q-BANK codes have been used as part of an interagency Federal effort to characterize the outcomes of cognitive interviews, and as a compendium of the types of flaws commonly exhibited by a range of evaluated survey questions. Similarly, Willis et al have divided such problems into six categories; interviewer difficulty, question wording, question structure, recall and judgment, response selection, and other problems. These include features producing difficulties related to cognitive processing  and problems of cultural adaptation such as the tendency to give open ended responses to some questions (a response selection problem) or generic cognitive problems with questions that occur regardless of language such as recalling the number of times a respondent felt something) . Note aThe selected questions categorized physical activities in terms of intensity and function; e.g., "How often do you do LIGHT OR MODERATE LEISURE-TIME physical activities for AT LEAST 10 MINUTES that cause ONLY LIGHT sweating or a SLIGHT to MODERATE increase in breathing or heart rate?" Questions also asked the respondents to estimate the duration of such activities; e.g. "About how long do you do these light or moderate leisure-time physical activities each time?" Similar questions concerning vigorous activity, leisure walking, and transportation walking were also included in the cognitive test ; grammatical corrections ; less formality in speech ; use of more common language ; and a change in how frequency was asked . The adjudicator also made slight changes to the physical activity questions, consisting of remediating inconsistencies in the language used  and editing wording felt to be awkward .Full text of the physical activity and acculturation questions in English and Spanish and associated initial probes concerning responses to and interpretations of the questions are presented in Additional File Three groups of nine respondents were recruited in the Washington DC suburbs and in Denver, Colorado). In each location, interview candidates were screened, recruited, and interviews were scheduled with volunteers who met study requirements. The study design explicitly included respondents from a range of Latino and Latino national backgrounds Table . RespondStudy procedures and materials were approved by Westat's Internal Review Board (IRB), and determined to be exempt from IRB review at NIH. Two trained bilingual cognitive interviewers (one of Mexican background and one Puerto Rican), conducted the 18 interviews for Spanish-language cognitive interviews. Three additional trained cognitive interviewers conducted the 9 interviews for English-language cognitive interviews. The lead interviewer for all three design conditions had additional qualitative research, survey design, questionnaire translation and cognitive interview analysis skills. The lead interviewer coordinated all interviewing and reporting activities and conducted roughly half of the cognitive interviews.A senior staff member conducted a four-hour study specific training session that reviewed project goals and procedures. Building on Goerman's ,44 guideMost n = 14) of the interviews took place in cognitive laboratory facilities at Westat in Rockville, Maryland, and others took place at community day labor sites in Maryland (n = 10) and in Denver, Colorado (n = 3). Study subjects received $50 compensation for their participation. Interviews lasted approximately 60 minutes and followed a cognitive interview protocol with two main elements. First, interviewers explained the purpose of the project and the structure of the cognitive interview, and assured respondents that all information would be treated as confidential. Interviewers requested permission to audiotape interviews and, when applicable, informed respondents that Westat staff were observing the interview. Interviewers reminded respondents that they could refuse to answer any questions and that they could end the interview at any time; respondents provided written informed consent. The draft questionnaire was administered using concurrent cognitive probing, in which respondents answered the tested questions as the interviewer read them, and interviewers also administered structured probes that assessed how respondents interpreted key questions or phrases and how they selected questionnaire responses. Cognitive interviewers also used spontaneous probe questions (those that were unscripted) at any point in the interview to follow up any observed confusion or difficulties answering the questionnaire items , and, and52]]In one sense, it is fortunate that many of the problems observed were generic in nature, and occurred in multiple groups. At the least, this effect may serve to set a 'level playing field' in which cross-cultural differences are unbiased; although, variation in item interpretation within each group may add overall bias or variability to the set of obtained responses. To revisit one of our initial motivations, this would also suggest that changes in self-reported physical activity associated with changes in self reported acculturation are not likely to be caused by changing interpretation of physical activity questions. Nevertheless, the general U.S. population has difficulty with descriptors of physical activity such as 'intensity'  and therMore optimistically, increased attention to the basic principles of question design  could bFirst, there were only 27 subjects divided across three groups. However, past work on cognitive testing and focus groups suggests that many of the dominant issues with standardized survey questions or topics addressed in focus groups emerge in modest sized groups [Second, and related, is the fact that we cannot compare the responses of different Latino subgroups to questions in the two domains. Cultural differences associated with country or region of origin could influence cognitive responses to survey items. Third, education and residence time/language preference are confounded in this sample; the low residence time/Spanish group has much lower levels of education than the other two groups. It would be interesting to examine cognitive responses of well-educated recent immigrants to these questions. However, this may be a smaller and more difficult to recruit population. Additionally, short term residents who preferred to receive interviews in English are missing from this study. Linguistic isolation can influence participation in health surveys [Fourth, this study sampled residents from two geographic locales, lacking respondents from areas that could be culturally distinct .This study has several major limitations. d groups . Further surveys . Fourth,Our focus is on the US Latino population, but lessons learned from this work are likely applicable to many countries and cultural groups ,58. OverIn summary, the results of this study further complement recent work on the challenges associated with question design in the use of dietary questions in national and regional surveys ,22,23. TThe authors declare that they have no competing interests.DB and GW conceived of the project, analyzed data and drafted the paper. BF, CH, KL and AN, collected data, extracted and analyzed data, reviewed and rewrote sections of the paper. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/10/481/prepubAcculturation and physical activity questions and initial probes. This file contains the questions examined via cognitive testing and the initial probes used in this study in both English and Spanish language versions.Click here for file


Paul Courtright and colleagues argue that the changing patterns of global childhood blindness suggest a need to reassess research, training, and programmatic requirements. Childhood blindness is a priority area for VISION 2020, a global initiative to eliminate avoidable blindness, because blind and visually impaired children have a lifetime of blindness ahead of them.Globally, vitamin A deficiency– and measles-related blindness in children has declined substantially although it persists in some focal settings.With reductions in nutritional and infectious causes of blindness, intra-uterine and genetic causes of blindness  have assumed increased importance and need tertiary care–level interventions and long-term follow-up to achieve good visual rehabilitation.Further research is needed to identify the underlying causes of congenital and developmental cataract and to determine the best strategies for recognition, referral, treatment, and rehabilitation.Changing patterns of global childhood blindness suggest a reassessment of research, training, and programmatic needs.The global initiative—VISION 2020: The Right to Sight—launched in 1999, targeted blindness in children as one of the five priority areas of disease control Blindness can occur through many different pathways and due to many different pathogens or insults. Classifying the causes of childhood blindness has always been quite complicated and WHO adopted both an anatomical and aetiological classification system in an attempt to focus attention on those conditions that can be prevented, those that can be treated, and those with no prevention or treatment strategies available that would need rehabilitation Corneal scarring and phthisis bulbi due to vitamin A deficiency, measles, and infection were the commonest causes of blindness in the early 1990s in much of Asia and Africa Due to the rarity of blindness in children, population-based surveys to determine the prevalence of blindness require very large sample sizes and are very costly. Consequently, in the period 1980–2000, only a few population-based studies Even back in 2000 it was anticipated that “old enemies” like vitamin A-deficiency blindness would be eradicated Regardless of the reductions in vitamin A-related corneal blindness, vitamin A deficiency still contributes to increased mortality in preschool children In most developing countries general economic growth and improved health care planning have resulted in an increasing number of eye care providers, even including doctors doing private practice in rural areas. In the last 20 years Africa has seen a 4–5-fold increase in the number of ophthalmologists with increased distribution of services outside of capital cities. India has increased many fold its primary health care infrastructure in the past four decades and NGO hospitals providing high-quality low-cost eye care have been established across the country. Programmes have been put into place to reduce the use of harmful traditional eye medicines and practice, further decreasing the risk of corneal conditions Refractive errors are a common cause of visual impairment Surveys in schools for the blind and annexes have continued The successful testing of “key informant” (KI) methods to find children who are blind While vitamin A supplementation, immunization, and improved nutrition helped decrease corneal blindness; cataracts, glaucoma, penetrating trauma, and retinoblastoma needed tertiary-level paediatric eye centres for treatment. Surgical services are expensive in terms of equipment, instrumentation, and trained human resources. The WHO recommends that there be one paediatric eye centre per 10 million population With the availability of good quality surgical services has come the recognition that congenital and developmental cataract are important causes of blindness in many developing countries Recent studies from India put untreatable conditions such as anopthalmos and micropthalmos Retinopathy of prematurity (ROP) has been rapidly increasing in many middle-income countries, with reports from Brazil, South Africa, India, and China In least developed countries congenital and developmental cataract, retinal pathology, and congenital anomalies are gaining importance as causes of blindness in children. The relative decline in childhood factors and the corresponding increase in intra-uterine and genetic factors suggest a need for a reassessment of research, training, and programmatic priorities. Reasonable steps to be undertaken in the next 5 years include:Recalculation of global estimates of prevalence, incidence, and cause of childhood blindness.Investment in testing different strategies to recognize, refer, and follow up children needing surgical services.Rational investment in tertiary paediatric eye care facilities along WHO recommended criteria. Coordination and collaboration between NGOs and hospitals is needed.Research on the cause of congenital anomalies  in order to put preventive strategies in place—likely difficult and expensive steps, but nonetheless necessary to address.Development of new training materials on childhood blindness, particularly for primary eye-care and secondary eye-care workers in the least developed countries.Screening of premature and low birth weight babies at risk of ROP, requiring cooperation between neonatal nurses, neonatologists, paediatricians, paediatric ophthalmologists, retina specialists, and even immunization workers.