Causes Of Colon Cancer Symptoms

>> thank you for joining us, andgood afternoon or good evening or good morning,depending on when and from where you're joining us. i'm dr. phoebe thorpe, andit's my pleasure to welcome you to cdc's public healthgrand rounds for november, 2016. "improving the lives of peoplewith sickle cell disease". we have an exciting session,so let's get started, but first a few housekeepingslides. we do have continuingeducation credits available

for physicians, nurses,pharmacists, veterinarians, and health educators, anda couple other groups. please see our publichealth grand rounds website for more information. this is our disclosurefor this session. in addition to our website,we're also available on all your favoritesocial media sites, and we are live tweetingtoday, so please use #cdcgrandrounds, for allyour tweeting needs.

we also feature a videosegment, "beyond the data", which is posted afterthis session. this month's segmentfeatures my interview with dr. hassell. we also partnered with thecdc public health library and information center to feature scientific articlesrelated to sickle cell disease. please see cdc.gov/scienceclipsfor more details. here is a preview

of the upcoming publichealth grand round sessions. in addition to today's speakers,i'd like to take a moment to thank the individualslisted here. thank you. and now, for a few words fromcdc's director, dr. frieden. >> sickle cell is aninherited disorder that causes lifelong healthchallenges, with the potential for sudden and devastatingconsequences. sickle cell diseasedisproportionately affects

minorities in the u.s.,especially african american and hispanic communities. in 1973, the averagelifespan of a person with sickle cell disease, inthe u.s., was only 14 years. today, the averagelifespan is 42 years. these numbers demonstrateboth how far we've come and how far we have to go. i've personally caredfor many patients with sickle cell disease,and i appreciate how painful

and difficult it can be. the progress we've made results from collaboration among manypartners, clinical research, public health, patientadvocacy groups, and the broader sicklecell community. clinical research has advancedour understanding of treatments that prevent acutecrises and strokes, which are the majorcauses of morbidity in sickle cell disease.

preventing pneumococcaldisease through vaccination and newborn screening that identifies affectedinfants are some of the ways publichealth has contributed to reducing early mortality. we have much more to doto prevent sickle cell, either through counselingapproaches, or, in the future, new modalities. in the u.s., more than90 percent of children

with sickle celllive to adulthood, but there are still importantgaps in care and areas for improvement, especiallyfor teenagers and young adults with sickle cell disease. figuring out how toclose these gaps requires that we know what works and accurately evaluatehow well it works. past cdc efforts, some ofwhich you'll hear about today, were among the first todevelop population-based

surveillance systems. current cdc efforts, includingthe sickle cell data collection program, build on these effortsby collecting information about healthcare and outcomesthroughout the entire lifespan of people with sicklecell disease. this data will support basicand clinical science advances, healthcare system changes,and patient, provider, and health systemscentered policy solutions. as you'll hear today, we've madeprogress treating sickle cell

disease and the complicationsof it over the past fourdecades through. continued collaboration, we canbetter understand the disease and its treatment, and improvethe quality of life and outcomes for people living withsickle cell disease. >> and now for ourfirst speaker, dr. mary hulihan. >> so, good afternoon, everyone! and thank you for joining usto learn more about using data

to understand gapsin care and outcomes for sickle cell disease. the term sickle cell disease,or scd, describes a group of inherited redblood cell disorders. people with scd have abnormalhemoglobin, called hemoglobin s, or sickle hemoglobin, intheir red blood cells. sickle hemoglobin, seen here onthe left, can form stiff rods within the red cell, changing it into a crescent ora sickle shape.

these red blood cells arenot flexible and can stick to the vessel wallscausing a blockage that slows or stops blood flow. when this happens, oxygencan't reach nearby tissues. for comparison, on the rightside, are red blood cells with normal hemoglobinthat are diff shaped. in all forms of scd,at least one of the two abnormal hemoglobingenes causes a person's body to make hemoglobins. hemoglobin s/s,

also called sickle cellanemia, is the most common form of sickle cell disease in theu.s., and the most severe. hemoglobin s/c disease andhemoglobin beta thalassemia, are other common formsof sickle cell disease. people who inheritonly a single copy of hemoglobin s havesickle cell trait. people with sickle celltrait usually do not have any of the symptoms of scd,but they can pass the trait onto their children.

two parents with trait need togo through genetic counseling, including awarenessof their trait status, which is important. globally, there areapproximately 300,000 annual births with sickle cell anemia. almost 80 percent ofthese births occur in sub-saharan africa. unlike the united states, wheremore than 95 percent of patients with sickle cell diseasewill live past the age of 18,

the under 5 mortality ratefor children born in low and middle income countriesmay be as high as 90 percent. improved access to publichealth infrastructures and specific medicalinterventions are necessary in order to lower globalsickle cell disease mortality. a diagnosis of sickle celldisease is often associated with multiple comorbidities. the lack of tissue oxygen caused by sickle hemoglobin can causeattacks of sudden, severe pain,

called pain crises, whichare the clinical hallmarks of sickle cell disease. the red cell sickling and pooroxygen delivery can also cause organ damage. over a lifetime, scd can harma person's brain, spleen, eyes, lungs, liver, and multipleother organs and organ systems. these chronic complicationsmay lead to early mortality. individuals with the most severeform of scd have a lifespan that is 2 to 3 decades shorterthan those without sickle cell.

and while the u.s. hasmade tremendous strides in improving outcomes forchildren, as you can see here, beginning in the mid-teen years,there's a striking discrepancy between mortality ratesfor patients with scd, shown as light blue columns, compared to the generalafrican american population, shown as dark blue columns,and the total u.s. population, shown as green columns. this difference in death ratescontinues throughout most

of adulthood. universal newborn screening forsickle cell disease is required in all 50 states, andthe district of columbia, and is one strategy that hasimproved outcomes for children. however, there are no long-termfollow up programs, registries, or data collection systems. so the exact number of peopleliving with sickle cell disease in the u.s. is unknown. it is - it is estimated

to affect approximately100,000 americans. the map shown here showsthe estimated prevalence of sickle cell disease by state. as you can see, whileflorida and new york have more than 7,000 sickle cellpatients each, many of states in the northwest mayhave less than 500. through an interagency agreementwith the nih's national heart, lung, and blood institute,and led by cdc's division of blood disorders,

a population-based monitoringsystem, called the registry and surveillance system forhemoglobinopathies project, or rush, was initiated in 2010 in the seven statesseen here in red. this project helpeddesign the framework for statewide surveillanceof sickle cell disease by using existing data sourcesto identify patients with scd, and then using thesesame data sources to understand the healthcare utilization patterns

of this population. in 2012, the public healthresearch, epidemiology, and surveillance forhemoglobinopathies project, or phresh, was launchedto evaluate and validate the rush methods, and to begin disseminatingfindings from this monitoring systemto various stakeholders, including patients and families,healthcare providers, and local, state, and nationalpolicymakers.

phresh was conducted in twoof the original rush states, california and georgia, and italso included a third state, mississippi, to assessthe feasibility of expanding thesurveillance work to additional statesat a reduced cost. in 2015, we began workingon the most recent iteration of state-based surveillance, the sickle cell datacollection program, or scdc. building on the knowledgegained during rush and phresh,

the program willcollect, synthesize, and disseminate multisource,population-based, longitudinal data forindividuals with scd. there are four mainobjectives for scdc. the first, and most basic, is that it will establisha health profile of the scd population. it will also track changesin scd outcomes over time, ensure credible, scientific -scientifically-sound information

to inform standards ofcare, and inform policy and health care practices. all of this together, we hope,will result in improved quality of life, life expectancy, and health amongthose living with scd. although we are currentlyworking with only two states, we will be able to includeabout 10,000 patients with sickle cell disease,or about 10 percent of the u.s. populationin this project.

to begin, scdc willinclude surveillance data from 2004 through 2014. and additional years will beadded as they become available. this system will includeindividual-level information from these data sources,at a minimum. newborn screening, hospitaldischarge, medicaid claims, emergency department,and death records. additionally, there will becase reports from a number of clinical centers throughoutthe participating states.

at this time, agreements for all of the source dataare being finalized, and the master casefile infrastructure is under construction. initial data analysesare beginning, and plans for dissemination of the results arebeing formulated. our hope is to buildupon these experiences and develop a trainingcurriculum

to educate additionalstates about the process for developing apopulation-based surveillance system for sickle cell disease. this training institute willestablish goals and benchmarks for the participatingstates, and those successful in meeting these measureswill be incorporated into the complete system. and so i would liketo thank those of you who are direct participantsin scdc,

the california rare diseasesurveillance program, and the georgia health policycenter, as well as our partners who continue to supportour efforts. as we develop and expand thescdc program, we will continue to heavily rely upon thecouncil, advice, and expertise of these groups,especially the patients with sickle cell disease andtheir families who continue to educate us on the needs,challenges, and barriers that remain, improvingtheir help.

thank you so much for yourattention, and i now would like to introducedr. kim smith-whitley. [ applause ] >> good afternoon, and thank youfor inviting me to participate in this cdc publichealth grand rounds. my discussion today will focuson advances and challenges in pediatric cell in thesickle cell community. sickle cell disease, as youhave heard, is characterized by accelerated destructionof red cells, or hemolysis,

vascular occlusion, and unpredictable clinicalcomplications, such as pain, life-threateninginfection, stroke, and acute chest syndrome. despite the fact that the firstpatient that had been described in 1910, and the firstdiagnostic test was developed in 1949, by the late 1960's,sickle cell related morbidity and mortality were still high. based on concerns forequitable care, in 1971,

the sickle cell diseaseassociation of america formed. this organization embodiedmultiple community-based organizations throughoutthe u.s. with the goal of improving the qualityof life of those living with sickle celland finding a cure. a year later, the nationalsickle cell anemia control act passed. this legislation putin place resources to support sicklecell disease research

and the infrastructurefor clinical care. one of the first clinicalresearch trials that came under the umbrella of support,instituted by the control act, addressed early childhoodmortality, specifically pneumococcalsepsis. in a 1986 study thatwas halted early, oral penicillin was proven toprevent pneumococcal infections and sepsis in young children. this study recommended

that prophylaxis startat 4 months of age. this led to the quandary ofidentifying infants early enough to benefit from thispreventive treatment. the oral penicillin prophylaxisstudy largely provided the basis to advocate for newbornscreening although the ability todiagnose sickle cell disease in newborns had beenavailable since 1972, there was not evidence that detecting the diseaseearlier could alter the

clinical outcomes. although many states had alreadyadopted newborn screening in 1987, it had not beenwidely adopted, therefore, the nih consensusconference recommended that all states adoptuniversal screening of newborns newborn screening, along withinfection prevention programs that started penicillinin infancy and specialized vaccinations,reduced the mortality associated with pneumococcal infections.

another devastating complicationof sickle cell disease in children is stroke. historically, scd wasthe most common cause of stroke in children. infarctive strokes,where oxygen supply to the brain tissue wascomprised, occurs in 15 percent of young children withsickle cell disease type ss. in children withsickle cell disease, these infarctive strokes aredue to damaged, narrowed,

or stenotic blood vessels. in 1992, using a noninvasivetechnique to estimate the flow of blood through thebrain, researchers found that they could predictwhich children with sickle cell diseasewould develop stroke by using transcranialdoppler ultrasound. since we knew thatchronic transfusions, or regular bloodtransfusions every 3 to 5 weeks could preventrecurrent strokes,

researchers asked,was it possible that chronic transfusion therapycould prevent first strokes in children with sicklecell disease identified at high risk by tcd? 130 children participated inthis randomized control trial. more strokes occurredon the observation arm than the transfusion arm, demonstrating a 92 percentreduction in stroke risk with chronic transfusiontherapy.

another breakthroughhas been hydroxyurea. hydroxyurea is achemotherapeutic agent, that when used at low doses, hasa tolerable side effect profile, and increases the productionof fetal hemoglobin. a 1995 multicenteredtrial in adults with sickle cell diseaseasked the question, whether hydroxyurea coulddecrease sickle cell disease related complications? this study demonstratedfewer painful episodes,

acute chest syndrome, and theneed for transfusion therapy in the group randomizedhydroxyurea. lastly, bone marrowtransplantation is a cure this 1996 study followed22 patients with sickle cell diseasewho had a brother or sister, without sickle cell, who wasan eligible bone marrow donor. this study demonstratedexcellent results with 73 percent event-freesurvival. however, one of the greatlimitations is having an

appropriate donor. in 20 years, only 1,000transplants have been performed in this patient population. for children withsickle cell disease, great advances have been made to prevent complicationsbefore they occur or prevent complicationrecurrences. recent research hasadvanced clinical care, but more is needed asdisease-related morbidity

and mortality remain high. there are no mechanisms inplace to track the care provided to those with sicklecell disease. moreover, there are fewdisease-modifying therapies, or treatments toshorten the course of acute and chronic pain. finally, there is no universalcure accessible to all in addition, providing thisimproved care for children and adults with sickle celldisease have been challenging.

we don't know where children andadults are living in the u.s., nor whether they are gettingthe healthcare that they need. advocacy organizations, suchas the sickle cell disease association of america,or scdaa, remain concerned about ways to bestaddress these issues. in 2003, the sickle cell diseasetreatment act supported increase health services for children andadults with sickle cell disease, but an update of thisact is still waiting to be authorized in 2016.

in 2014, in order to addressthese continued challenges in the sickle cell diseasecommunity, we adopted, at scdaa, a new agenda to encourageone voice to support sickle cell diseasethrough advocacy initiatives. increased access to high-qualityhealthcare across the lifespan, drug development, therapies,andprograms to improve quality of life, and to also decreasedisease-related complications, and then a cure accessible forall with sickle cell disease. as one way to begin toaccomplish these goals,

scdaa developed get connected,an information-sharing, patient-powered registry. this is a database and networkof multiple stakeholders in the sickle cell community. children and adults with sicklecell disease, their families, their communities, primarilycommunity-based organizations, healthcare providers,government, and private industrystakeholders. this web-based platform is

where all participants canreceive information important to the sickle cell community. one focus has been toincrease the number of patients with sickle cell disease whoreceive care in a medical home and increase awarenessof hydroxyurea therapy. through a hrsa grant, 35 community health workerswere trained to find children and adults with sicklecell disease, connect them to a healthcare team, andenroll them in get connected

to ensure follow up andaccess to resources. in 15 states, inless than a year, 3,152 individuals have beenenrolled, challenging one of the largest prospectivecohorts only to have been raised through the cooperativestudy of sickle cell disease. in summary, we have madeadvances in pediatrics, but few have been madeacross the lifespan. a lack of data is impactingour ability to develop and steer futurehealth policies.

we hope get connected and thesickle cell data collection projects will helpwith this gap. lastly, we need more accessto healthcare professionals with expertise in sickle celldisease, not just for children, but also for adultswith sickle cell. we have a relativelyhigh rate of deaths in the young adult age groupand decreased overall survival. we are all working towardshealthier lives for children and adults with sicklecell disease.

and the acknowledgements, ihave to acknowledge the scdaa, newborn screening program cbo's, because they trulykeep the light shining. and with that, i thankyou for your attention, and i'd now like tointroduce dr. kathy hassell. >> i would like to add mythanks for the opportunity to participate ingrand rounds today, and to present my perspectiveas an academic hematologist who has worked for, more than20 years now, with adults living

using population surveillance to better understand theadult sickle cell disease, particularly prematuredeath and the growing burden of chronic organ damage maypermit the identification of opportunities forprevention and intervention, both in childhood and adulthood. it is also important tounderstand the impact of healthcare access andutilization on the course of the disease and on thesuccessive implementations

of interventions. although the majority ofchildren with all forms of sickle cell diseasesurvive into adulthood, premature death has beenrecognized in consented cohorts, such as the cooperativestudy of sickle cell disease in the jamaican sickle cellpopulation, and in a cohort of patients followedfor more than 40 years at a single institutionin los angeles. death occurs earlier with themost severe form of the disease,

hemoglobin ss, ascompared to those with the milder hemoglobinsc disease, and race-matched individualswithout sickle cell disease. as depicted in the greenbars on this graph, population surveillancedata from the phresh program, that you heard outlinedby dr. hulihan, identifies more individualsand captured by other cdc mortalitydatabases, as depicted in the blue bars.

this demonstrates the potential,for example, to find survivors into later adulthoodthat appear to be missed by using other sources. unfortunately, the averagesurvival still appears to be around 42 years, similarto the cohort data that we just reviewed. recognizing the distribution,or shifts in the age of death, potentially permits assessment of interventionson a population.

as an example, the blue lineon the graph demonstrates that in 1979, part of the population diedin early childhood. subsequent introduction ofearly childhood interventions, as described bydr. smith-whitley, including newborn screening,prophylactic penicillin, and pneumococcal vaccinations, appeared to temporallybe associated with the disappearance

of observed childhooddeaths in 2006 and 2014. while important informationis gleaned from the whole populationdata, caution is warranted when interpreting results. the sickle cell data collectionprogram does not yet distinguish between different typesof sickle cell disease. as noted, there aresignificant differences in expected prematuredeath between types of sickle cell disease,

so determining an overallpopulation average may overestimate the lifespan forthose more severely affected, and underestimate thelifespan for those with milder typesof the disease. in addition, not allinterventions are applied to all types of sicklecell disease. for example, hydroxyurea is aproven benefit, as you heard from dr. smith-whitley, insickle cell anemia, or ss, and s beta thalassemia.

but 40 percent ofindividuals have other types of sickle cell disease andwould not routinely be given this intervention. assessment of thepopulation as a whole, without distinguishingtype of disease, may miss important gains within a given subsetof the population. another important aspect of adult sickle celldisease is the burden

of chronic organ damage. a study of autopsies from more than 20 years ago revealedinjury in targeted organs, including the lung, thekidneys, and the brain, with secondary injury inthe liver and the heart, and noted that chronic organdamage was the second-leading cause of death after infection. in a single institution cohort,followed for more than 40 years of follow up, 73 percentdeveloped chronic organ damage.

although this earlierdata suggested that infection was animportant cause of death, more contemporary data indicate that chronic organ damagemay now be the leading cause of death. a study of cdc deathcertificates suggested that cardiopulmonary and renaldisease are common causes of death, and death due toinfection is now less common. only 20 percent of this cohortdied during acute crisis.

and comorbidities thataffect individuals without sickle celldisease, like heart disease and hypertension and pneumonia,were also noted to be present. discerning the presenceof both sickle cell and potentially non sicklecell related organ damage is important in planningprevention and intervention. understanding theonset and progression of complicationsis also critical when planning strategiesfor prevention,

early detection,and intervention. this slide depicts medicaid data from five states demonstratingan increase in the development of any complication, indicatedby the red line, pain indicated by the blue line, and the onset of pulmonary complicationsindicated by the pink line, all of which appear toincrease in mid-adolescence. population surveillance canalso characterize the use of interventions in aneffort to understand impact.

as an example, these medicaiddata suggested there's a falloff in the use of transfusiontherapy, beginning in mid-adolescence. seeming to correspond with thatrise in complication and pain, although hydroxyurea use appearsto remain stable into adulthood. interesting data tostimulate both speculation and the need forfurther analysis. another marker of increaseddisease activity may be the use of the emergency department,which may be necessary

for acute complicationsand acute, severe pain. use of the ed has also beeninterpreted as an indicator of a lack of access toadequate, routine healthcare. note that this increase begins in mid-adolescence,at around age 16. thus, the planned sicklecell data collection program has the potential to clarifythe course of the disease, and factors thatimpact that course. longitudinal trackingcan identify the onset

and progression ofcomplications, and determine theutilization and impact of both complication-specificand disease-modifying therapies. as previously noted,however, the inability to distinguish the type of sickle cell disease mayconfound interpretation of findings. as the rate and severityof the complications varies between different typesof sickle cell disease,

and disease-modifyingtherapies are not always applied to all patients. a final key area is access toand utilization of healthcare by adults living withsickle cell disease. the oft-stated assumptionis that all children with sickle cell disease receivecomprehensive sickle care from experts in sicklecell disease itself. data from the maryland medicaidprogram suggests, however, that this may not be the case,indicating that 38 percent

of children had not yet seen ahematologist by the age of 2. so it seems a carefulexamination of the pediatriclandscape is warranted. adult sickle cell care ismost usually characterized as nonexistent, due to lackof knowledge of providers, or inaccessible, dueto a loss of insurance, or rendered by providers withoutany knowledge or interest. to date, i would submitthat this is based on anecdotal experiencerather than data.

the increase in complications,ed utilization to mortality in early adulthood issaid to be evidence for the lack of adulthealthcare. but the data we justreviewed suggested that these changes begin inmid-adolescence before transfer to an adult care providerhas even been considered. with regard to the nonexistenceof adult sickle cell providers, this map depicts thenumber and location by state of adult hematologistsor other physicians

and advanced practiceproviders who indicate that they see adult sicklecell patients in the, so-called find a hematologistservice of the american society of hematology, orwho participate in the sickle celladult provider network, which is an organizationwhich promotes collaboration, research, and educationalactivities amongst adult providers. it should be noted that someof the most prominent members

of the sickle cell providercommunity are not hematologists, but include internal medicine,primary care, and other types of providers who havedeveloped considerable expertise in the management ofsickle cell disease. so a surveillance system whichcaptures sites of care and types of providers is likely to identify unrecognized cellsof adult care, as well as pediatric care. while most adults with sicklecell disease, at any given time,

appear to have healthcareinsurance of some type, most usually medicaidand/or medicare, their plans may not covernecessary services or access to expert providers, andhigh deductibles might preclude utilization. there may also beintermittent loss of coverage when they lose a job thatprovided insurance or, ironically, when they gain a jobthat gives them too much income to make them eligible forsome of these programs.

an often overlooked aspect of the adult health careutilization is the role of self-determination. adolescents, and especiallynewly-autonomous young adults may have access to knowledgeableproviders, but elect to opt out of the healthcare system. as an example, thisstudy demonstrated that 8 of 22 patients died within5 years of a referral into an established adultsickle cell program.

all 8 had declined to continuetheir disease-modifying chronic transfusion therapy. in this area, the opportunity of the sickle cell datacollection program is to understand where adolescents and young adults receive healthcare, and observe the course of the disease whilestill in pediatric care, which in some programsextends into the early 20's. this may permit recognitionof the changes in the biology

of the disease and/orto understand the impact on the level of patientengagement. unfortunately, thesystem will not be able to capture many effortsto provide care, including referrals, transfers,and scheduled appointments that were not kept as data for services actually renderedare captured in the new system. given this, the lack of utilization cannot be simplyequated with a lack of access.

nonetheless, and despitethese limitations, the sickle cell data collectionprogram will provide important population-level data aboutpremature death, disease course, the impact of interventions,and healthcare utilization, and, i believe, identifyproviders and sites of care, informing the developmentof strategies for prevention and interventions that willhelp to lessen the burden and now i'd like to introducemy colleague, dr. jean raphael, to discuss implicationsfor health care policies.

>> great, thank youfor having me here. so, again, my goal for today is to really discuss thepolicy implications of what's been discussed so far. so i'll do that throughthree objectives. so, one, i'll talk about thecurrent guiding principles in healthcare policy andhealthcare policy initiatives. the second objective is to identify policychallenges currently occurring

and then, lastly, i'lloutline a policy agenda for sickle cell diseaseto improve care. so, increasingly, health policymakers have advocated the triple aim as a model forimproving population health. so the triple aim hasthree core aspects. so the first is reducing cost. and, more specifically, thatmeans eliminating overuse or misuse of diagnostictests or therapies. it also means ensuring therearen't redundancies in care

that occur with differentpatients, either with sickle cell diseaseor other chronic conditions. the second core principle of the triple aim isimproving population health. and so there aretwo aspects to this. so the first is identifyingsystemic variations in care outcomes, being ableto look across a population, take that data, and then to beable to apply that knowledge to developed policiesfor improvement.

the third aspect of the tripleaim is enhancing patient experience, and i thinkyou've all heard a lot about patient experience lately,and so there are two parts to that, is that, one, you wantto actively survey patients about their experiencesin the healthcare system, whether they be inthe outpatient setting or the inpatient setting, andthen you want to take that data, then translate it into howyou do system redesign. and as a fundamental part ofsystem redesign, you're going

to involve those samepatients and families, and able to make improvements. so those are the coreaspects of the triple aim for population health. so with the triple aimas the goal, researchers and policy makers mustarticulate a path towards achieving these aims. and in doing so, what you have to do is a comprehensiveapproach

where you go all the way fromthe basic biomedical sciences, all the way to improvingpopulation health and establishing policy. so how does that work? so it starts off withtesting what care works. so this could be clinicalefficacy research, and then, from there, you moveon to the next step. and the next step istesting who benefits from - from promising care.

so that can involveoutcomes, research, that can involve comparativeeffectiveness research where you compare differentevidence-based solutions or strategies ormedications to see which ones work betterfor populations. and then also health servicesresearch, where you look at sort of the how of healthcare andwhat that means for patients. and then the nextstep is testing how to deliver high-quality carereliably and in all settings.

so what does thatpractically mean? that means, is ensuringthat all these solutions and strategies you'vecome up with at this point can actuallywork in real environments, in urban environments, inrural environments, as well. so it's really seeingwhat practically works. and if you can achieveall of that, then you get to this outcome ofimproving population health and really havingan impact on policy.

so while there have been efforts to make sickle celldisease a bigger part of health policy initiatives, these efforts have beenconsistently undermined by insufficient data, aswe've talked about before. so here's a great example. so, look at healthy people2020, hemoglobinopathies, of which sickle cell is one,were well-representative -- well-represented inhealthy people 2020.

so, one, there was a focus ontreatment, sort of screening for complications anddisease-modifying therapies, and there was a second focuson access to a medical home, community resources,educational support. so this was a great opportunityto really affect the care of sickle cell disease, butwhat happened, over time, is they actually had toretire these objectives because there wasinsufficient data systems to actually assess them.

so, again, a greatlost opportunity here where there was agreat initiative, but then it could not succeed, because we didn't have thenecessary data to do it. so in order to assess what arethe different types of policies that we can enact to improvecare for sickle cell disease, we have to look at both theadvances in sickle cell disease, as well as some ofthe challenges. so here outlining some ofthe advances, as we've talked

about throughout these talks. so one is hydroxyurea as adisease-modifying therapy. the second is transcranialdoppler screening to assess stroke risk. also chronic diseasetransfusions to reduce stroke riskamong individuals and you take thataltogether with a number of other innovations, whatyou have is an extended life expectancy.

so in 1973, where yourtypical individual with sickle cell disease wouldlive to about 14 years of age, in 2008, life expectancyhas exceeded - had exceeded 42 years of age. and you see those incrementalimprovements over time. so those are theadvances in care. so now it's necessaryto also talk about the challengesthat remain. so one is just persistentlyhigh resource utilization.

so we see that in the numbersof emergency care visits, hospitalizations whichcontribute to significant and substantial medicalexpenditures. a second aspect is the high riskof mortality at early adulthood. so we see, in thattransition from pediatric care to adult care, you seean increase in morbidity and mortality as childrenmake that transition. so that's anotherarea of concern. the next thing, we just havea poorly-studied population.

a lot of that is due topoor funding and organizing that we see, so we havemajor advancements, by the sickle celldisease association, as was outlined earlier, but,overall, these are just efforts that could use moresupport over time. other challenges also include,again, as we've talked about, lack of data sources withadequate numbers of people with sickle cell disease,or a sufficient amount of clinical data to reallymake some appropriate changes

in care. and then despite the fact of having new evidence-basedguidelines come out in 2014, even with those guidelines,there were limitations in how much evidence weactually have for what we do, with respect to sicklecell disease management. and then the last thing, as dr.smith-whitley had pointed out, there's just a limited numberof clinical providers willing to take on this patientpopulation, particularly

in the adult world,particularly for people who are - for hematologists. so those are thechallenges that we have. so as we outline an agendafor sickle cell disease, here are the things that iwant you to consider today. first is population healthand bigdata are essential. we've talked about, through allour talks, it's so important to get the type of data where wecan really look at what's going on systematically,and then be able

to make the policychanges to improve care. another piece on the agendais comparative effectiveness, research of differenttreatments. so it could be clinicalmanagement, it could be medications, it could be approachesto care as well. and then the nextthing, and this is going to sound counterintuitive,is really starting to look at technology-basedinterventions.

so despite the factthat individuals with sickle celldisease tend to come from underserved populations,there is substantial data out there now thatactually shows that these individuals havegreat access to technology, and this could mean cellphones, other mobile technology, text messaging, and,in some cases, underserved populationshave greater access than the majority population.

again, it's counterintuitive,but it allows you to know that this is a place wecan take advantage of, because this is somewhere that people actuallywant intervention. so this could be health apps,it could be online programs, people have also done some workin terms of gaming, video games, avatars, so all ofthis has the potential to really meet patientswhere they are, at their own convenience,where they don't have to go

for in-person interventions,they could do it all in which the way thatmakes sense to them. another thing is developmentof new funding strategies, whether it be looking at bigdata or whether it be looking at how technology couldactually impact this population. looking back at someof the clinical areas for priorities is buildingmedical neighborhoods. so we hear about medical homes, but then there's this largercontext of medical neighborhoods

where primary care providersand specialists collaborate to take care of these patients. and from a policyperspective, what we want to do is decrease the barriersfor these collaborations and really allow thesepeople to meet together in a multi disciplinearea fashion where people can reallymanage patients over time. another aspect is supportingadult providers with expertise. so some of you may haveheard of the echo program.

so this is a model of care where you have these virtuallearning networks of providers, where providers inrural settings or underserved settings canreally leverage the expertise of specialists, and thiscould be in, sort of, virtual case conferences, wherepeople from rural settings or underserved settings,can present their patients, some of their clinicalconundrums, and get, you know, really great accessto these experts

who can help themmanage these cases. so that's just a way justto increase the amount of resources availableto these providers. another thing we could do ismodify an existing reimbursement model, such that providers,specifically hematologists and primary care providers whoare taking care of individuals with sickle celldisease, get reimbursed for care coordination, becausethat is such a fundamental part of what needs to happen withthis patient population.

and the last thing is addressingthe social determinants of health. so we've talked about thisbeing an underserved population, a high number of these patientsbeing on public insurance, so we can't justfocus on what's going on in the healthcaresector, we actually have to go more proximal interms of upstream factors to really address how tomore effectively engage these patients in their care,and to address some

of the barriers they facein their daily lives. so what do we do now? so one thing is we've talkedabout all these phenomenal, basic, and clinical signs, innovations in sicklecell disease, so now we need the healthpolicy strategies in place to really align what'sbeen going on, and really to make surethat the patients are able to reap the benefits ofall these innovations.

the second thing is thesestrategies really have to align with the current prioritiesin healthcare, so, again, we talked about the tripleaim, reducing healthcare cost, improving population- population health, and then enhancingpatient experience. that's where people arereally thinking about, and that's how providersare being incentivized, so our strategies really haveto align with that model. the last thing is to make sure

that these policy solutionsare patient-centered, provider-centered, and,lastly, health system oriented. so as you've look at allour talks for the last hour, i think there are a numberof themes that have come out. so i just want to summarize themthere before we start talking about specific questions. so, one is that we need to continue the progressand advance in care. so, again, i showed you thatmodel of care, that roadmap,

starting from the basicsciences going all the way to population health. we really need to moreeffectively translate all the great research intotreatment and practice. the next thing is to use the -use data to identify the gaps in care, and this iswhere population health and having access to bigdata is so important. so, reducing the variability indisease course and management, the availability, use,and access to care,

and then really focusing on thattransition piece from pediatric to adult care, because that'swhere we're seeing this concern in terms of increasedmorbidity and mortality. and the last thing iswe need more support to meet the healthcareneeds of individuals with sickle cell disease,so connecting individuals to the right care, understanding which care is betterfor the individual. so although our main focusis on population health,

we have to also balance that with personalizedmedicine as well. and the last thing is justoverall developing better systems of care to providepatient-centered care. so, with that, i thinkwe'll go to the moderating in questions and answers. >> wonderful! thank you so muchfor being here today. we are going to open up thequestion and answer session,

and i didn't know if there wereany questions from online or...? >> we do have questions fromonline, but i would also like to take this opportunityto ask our online audiences, please do submit yourquestions and take advantage of the opportunity to getanswers from this expert panel. from our twitter audience,how useful is d-dimer test in distinguishing vasoocclusivecause of pain from other causes in the patient withsickle cell disease? >> i'm certainly going to pass

that to the cliniciansin the room. >> alright, so this is kathyhassell, for online audience. i happen to be aclotter, most of my time, when not doing sicklecell care in colorado. so the d-dimer is anextraordinarily nonspecific test, and while elevationshave been correlated, roughly, with course of disease,there are no biologic markers of whether or not anindividual's experiencing a vasoocclusive crisis.

it remains a source offrustration for everyone, that we can't simply drawblood test and say, yes, you're in crisisor, no, you're not. it calls for believingthe patient and what they're experiencing. >> great. anybody wantto add to that or...? wonderful. thank you dr. hassell. any other questions from online?

>> not yet, but we hopethey're coming in soon. >> okay, great! well, we can open it up toanybody here in the room today. there are microphones inthe middle of the room, in the aisle, if anybodyhas anything that they would like to ask, please do so! >> i'll go aheadand ask the panel, i'm particularly interestedin this troubling time between adolescence andadulthood, and the study

which showed that someof these deaths were because the patients themselvesdecided to stop treatment. so i could imaginethis being true for many chronic diseasemanagement issues. what do we know about how tohelp adolescents get ready for that transition, mentally,emotionally, you know, through this system, andtry to get them into a place where we know what theirbarriers are going to be and we can help themmake that transition?

>> so, excellent question. and, really, just torestate it, just briefly, is really what do we knowin the sickle cell community about this emerging adultpopulation, you know, between really 16and 23 years of age? and the answer to thatis really not much that is sickle cell specific. what we have done isadopted the american academy of pediatrics approachto really try

to develop systematic processfor transition from pediatric to adult-focused care. and now what we'retrying to do is to see what bestpractices exist, i think throughout the u.s., so that we can gathermore information, and also there is arecent grant funding through patient-centeredoutcomes research institute that is going to look,

as a comparative effectivenessanalysis, of the different types of transition projects, andi think that we'll get a lot of meaningful informationthrough that project. but i think thatwe need more data on what individuals actuallyexperience in transition, not only from a personal level,but a health systems level, and a healthcare providerlevel, which, i think, dr. hassell nicely framed. we need information fromthose stakeholders involved

in the process before weunderstand what we need to do to make a tailoredsystematic approach to sickle cell transition. >> so i'll add the adultprovider perspective. i think an important,from my perspective, an important first step is to separate transferand transition. 20-year-olds don't go to thechildren's hospital any more or less than they go to theadult hospital if they've been,

you know, selected to grow up and leave the children'shospital. transition is a phase oflife, not a site of care. and i think until weunderstand what it takes to care for a 20-year-old,whether they're still at the balloon boy hospitalor across the street, at the, you know, the grownuphospital, there are needs that 18, 20, 22 year olds have. i have two blessedly well sonsmyself, i know about this,

they are invincible, they don'twant to be told, and they, not maliciously opt out, thereare more important things to do, and if we continue to varyour efforts in the transfer to the adult provider who saidno after the fourth no-show, we'll not get to the coreissue of what young people need to assume responsibilityfor their health care, and so far as they'rerequired to do so by law, by age of majority, i think- so it was a long way of saying i think we have

to separate transferfrom transition. and figure out whata 20-year-old needs, not matter who'staking care of them. and as i alluded to, ithink the opportunity of - the data collection that wehave here, is i can assert that i know the no-show rateisn't so good in colorado at the children's hospital fora 20-year-old, but it'd be nice to see what the data show. because i have a biasabout that, clearly,

strongly-willed in that regard. but maybe the data willshow something different, but we need to understandwhere care is being rendered, and to what extent it's beingengaged, sort of regardless of the site of care, asone of the key pieces in addressing thispopulation's need. >> and i was going to add,also, just about, again, about this need for research. and so i think in termsof sickle cell disease,

there's been a ton ofqualitative research done out there about, you know, families having difficultyseparating from the pediatricenvironment, the pediatrician or the pediatric hematologisthaving difficulty separating from the family, and so youhave all those barriers there, but it's just - what'sbeen lacking is that quantitative data. and, again, when you think

about sickle cell diseasebeing a fairly rare condition, so at each individual site,it's hard to get those numbers to really look at whatworks effectively in terms of a transition ora transfer program. and so there aredifferent programs going on at different individualinstitutions, but, again, these are numbers with30 patients, 50 patients, it's really difficult to putthat together and say, okay, this is now an evidence-basedstrategy moving forward.

and as dr. smith-whitleypointed out, that's why the pcorigrant that is out there will be so important in termsof really being able to pull different centerstogether, pulling their data to say, okay, now,in large numbers, we can say what effectivelyworks for transition. >> thank you so much! so i'll turn back toany online questions. >> the writer wants to know

if the clinicians use extendedphenotype-matched blood for patients requiringchronic transfusion therapy? >> so that's a very interestingquestion, and i think that one of the things that we've spokenabout today are data gaps. and really trying toinform health policy on what evidence is there whenthere's very limited evidence. we have data to suggest that extended antigen-matchedblood may lead to the lower development ofred cell antibodies, making -

finding appropriate redcell units that match that individual uncomplicated, and also possibly patient -placing that individual at risk for delayed hemolytictransfusion reactions. but just as we have found thatdata, we have found other data to suggest just the opposite. so, what we really needis an organized approach to a deeper dive inunderstanding the situation in which the individualreceives the transfusion,

because that might havesomething to do with development of these antibodies, if theindividual is an healthy state as opposed to a sick state. where that donor blood is comingfrom, what is - what are some of the characteristicsof the individual? and then dive into more thebasic science information about genotype/phenotypeof the blood. and getting a large cohorttogether to work this out nationwide is one ofthe challenges that we face.

>> so, you know, themisfortune on this panel of having myself coming fromuniversity of colorado, where, for more than 30 years, we arethe only place in the world that does extended phenotypefor 17-plus minor antigens. and so, for us, alloimmunizationdoes occur, the demosaic, these variations of rh, thatwe see the occasional anti-u antibody, which, evenas a hematologist, i had learned about before this. so i think i'm convincedit's great, it's wonderful

in a population withfew african americans, and yet 30 people receivingchronic exchange transfusion with 100 units a month, we can,in fact, sustain that in little, old colorado, but i completelyagree with dr. smith-whitley. if we could understand who isgoing to form alloantibodies, we could apply that ina more targeted fashion. we can do it only because it waslong established for 30 years and our regional blood centerhas that work, the setup, the very expensive part of thatprogram done for a long time.

so i do think much work needsto be done to understand how to target the veryintensive matching strategies and who will be less likelyto form those antibodies. and from an adultprovider perspective, it's not just delay transfusionreactions, but hemolytic disease of the newborn is a reality,and that is something that, on top of everything else, wehate to pile on a young woman with sickle cell disease whohas three alloantibodies, two of which could cross theplacenta and hurt her baby.

so it's not - it hasimpacts, certainly beyond and in the adultworld, that we face. >> and i just want to brieflyadd too, just to make sure that, you know, everybodythen can also know that there are evidence-basedguidelines that the expert panel reportthrough, nhlbi is out there, and many of us have contributedto that body of work, and we really do believein antigen matching. the question's just becomeabout, how much, when, and how?

>> and then i'll just throwin from cdc's perspective. we do have, separate fromwhat we spoke about today, but a project that wefund looking specifically at transfusion complicationsfor hemoglobinopathies and way to reduce - ways toreduce those complications. so that is work that's goingon that, to some extent, is very much addressing thequestions and the points that were brought up here today. >> one more questionfrom online.

>> from twitter. since people with sicklecell disease make people with sickle cell trait, wheredoes sickle cell trait fit into the surveillance agenda? [ laughter ] >> so, i would say that werecognize the importance of sickle cell trait from theissues of family planning, issues of reproductivecounseling, genetic counseling. i will say that, atthis time, our resources

at cdc are very limited, and so we are focusingour surveillance efforts on sickle cell disease. that is not to say thatwe do not have many ideas and projects sitting inthe pipeline waiting to put into action as soonas we are able to. so it's a great question, it'ssomething that's very important, and an individual's knowledge of their own personal sicklecell trait status is something

that we certainlyrecommend, and something that we hope is in practice. >> and then i'd just like to add that the get connectedinformation-sharing, patient-powered registrywill also incorporate sickle cell trait. so we're hoping that whenthe funding is in place for our researchproject to get underway, that that will be aneasily tappable resource.

>> so we have onequestion from the audience. >> dr. smith-whitley, if you would -- would you maybe talk talk about how the younglady presented ...at the national -- youremember what she spoke about? so, if you would, saysomething about that, because i don't thinkthat's known a lot, how that - she was very upset. >> one of the things that i think has beenmiscommunicated throughout the

community is the experienceof the individual living with sickle cell trait. and many individuals living with sickle cell trait mayhave been told at some point that this was anasymptomatic condition. and we do know that there aresome symptoms that individuals with sickle celltrait experience. one of the things that has beenbrought to light is, you know, blood in the urine, orhematuria, that can occur

in individuals livingwith sickle cell trait, and actually lead to somesignificant outcomes, if not addressed. and then embedded in thatis individuals who present with blood in theirurine that then go on to have renalmedullary carcinoma. and we don't really understandthe relationship fully of sickle cell traitin the context of renal medullary carcinoma,but we know it's something

that we have to be attentiveto and look for, particularly in those individualswith hematuria. many of us believe thatthere are other things going on in other genes thatthen have an effect and maybe have a moresignificant effect and role in those with sickle celltrait, but i think you bring up a very important point inthat we really need to look at individuals livingwith sickle cell trait, and their experiences,and really get good data

through research projects about the complicationsthat they experience. >> can i just addone other comment? so in denver, gosh, it's beenprobably a decade ago now, we had a young man, in histeenage years, succumb to - to renal medullary carcinoma. and i think his parents,understandably, were upset and concerned, andactually, you know, advocated that anyone living

with sickle trait should haveannual ultrasounds from the age of 2, and they were hoping to- to catch - catch it early, and there's - we need to learnmore about why it occurs, it's such a rare thing. but the other point iwanted to make in terms of the broader picture is theywere caucasian, and discounted by many of the sicklecell community, because i must not beright, it can't be true, and i think there aremany different persons

of different colors, andincluding caucasian individuals who may be affectedby trait or disease, and while there's anappropriate focus, i think, on the predominantly affectedcommunity, it was illustrative, right, to see this young mansuccumbs to a rare complication of trait when he was disbelieved that he could evenhave had that scenario. so it was reallyjust eye-opening on many levels, i think.

>> that's all we have time for. thank you so much forjoining me, and, please, thank our speakers for anexcellent presentation. and also, if you have afew minutes, stop on - down one floor, at the library, they have put togetheran excellent sickle cell anemia display. thank you again for joiningus, and see you next month!