Autism is a heritable developmental disorder of communication and socialization that has not been well studied in Hispanic populations. Therefore, we are collecting and evaluating all possible cases of autism from a population isolate in the Central Valley of Costa Rica (CVCR) for a clinical and genetic study.We are assessing all subjects and parents, as appropriate, using the newly translated Spanish versions of the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS) as well as tests of intelligence and adaptive behavior. Detailed obstetric and family medical/psychiatric histories are taken. All cases are tested for Fragile X and will be extensively evaluated for cytogenetic abnormalities.To date we have obtained clinical evaluations on over 76 cases of possible autism referred to our study and report data for the initial 35 complete cases. The mean age of the probands is 6.7 years, and 31 of the 35 cases are male. Twenty-one of the cases have IQs <50 and only 6 cases have IQs ≥ 70. Over half of the mothers had complications during pregnancy and/or delivery. No cases have tested positively for Fragile X or PKU. Chromosomal G-banding is not yet complete for all cases.Diagnostic data gathered on cases of autism in the CVCR using Spanish versions of the ADI-R and ADOS look similar to that generated by studies of English-speaking cases. However, only 17% of our cases have IQs within the normal range, compared to the figure of 25% seen in most studies. This result reflects an ascertainment bias in that only severe cases of autism come to treatment in the CVCR because there are no government-sponsored support programs or early intervention programs providing an incentive to diagnose autism. The severity of mental retardation seen in most of our cases may also be exaggerated by the lack of early intervention programs and the use of IQ tests without Costa Rican norms. Still, we must formally train healthcare providers and teachers to recognize and refer autistic cases with normal or near normal IQs that are not seen in treatment. Neuroligin 3 gene on Xq13 has been identified in a sibship where one brother has autism and the other has Asperger's [Autism MIM 209850) is a heritable neurodevelopmental disorder characterized by delayed language acquisition, impaired socialization, and repetitive or stereotyped behaviors. Frequent associated features include sensory abnormalities and lack of motor coordination. The recurrence risk for siblings is approximately 30 times that of the general population, and twin studies have documented a higher concordance rate in monozygotic 60–91%) than in dizygotic twins (0–6%) [% than in09850 is perger's . This muMultiple genes and environmental factors likely contribute to the etiology of autism, making it difficult to isolate disease genes. There is a substantial fall-off in risk of autism for second- and third-degree relatives of autistic probands , and somTwo principle strategies have been used to try to limit the genetic heterogeneity underlying such complex phenotypes. One proven method is to identify more genetically homogeneous subphenotypes. With respect to autism, language delay and obsessive compulsive behaviors are traits that segregate within both affected and unaffected members of a family ,13. In pAnother, albeit less successful, means of reducing genetic heterogeneity is to study these disorders in isolated founder populations. These populations are derived from a small number of original founders and then grow exponentially, in isolation, such that the small number of disease alleles introduced by the founders will be widely distributed in the present day. For instance, genes for Hirschprung's disease have been identified in the genetically isolated population of the old order Mennonites, although some degree of heterogeneity was present even in this population .The CVCR is another well known founder population widely studied by geneticists interested in neuropsychiatric disorders and other complex traits like asthma . The CVCPreviously, genetic studies of autism were not undertaken in the CVCR because the Autism Diagnostic Interview-Revised (ADI-R)  and the According to the National Census Register of Costa Rica, the CVCR harbors approximately 250,000 children between 0–4 years, another 250,000 between 5–9 years, and a total of one million individuals under the age of 20, with a slight preponderance of males in all age groups. . Assuming that published prevalence estimates in other countries apply to Costa Rica, as has been documented for Tourette's Syndrome and Bipolar Disorder , and takWith the appropriate instruments and research-trained bilingual clinicians, we have begun recruiting autistic subjects and their parents from the CVCR for a genetic study. The first stage of the genetic study will be to perform highthroughput cytogenetic screening using a microarray-based Comparative Genomic Hybridization assay specially designed to detect microdeletions and duplications (microdels/dups), including sub-telomeric abnormalities, too small to be identified by standard karyotyping. Should we have a suitable sample size of cytogenetically normal cases after this evaluation, possibly augmented by samples from the genetically related population in Antioquia, we intend to perform a genome-wide single nucleotide polymorphism (SNP) screen to identify autism susceptibility genes. We also intend to use our samples to perform fine-mapping of autism loci identified by other investigators. Here we report complete clinical data gathered on a representative 35 cases recently assessed in the CVCR. Although this is a preliminary assessment, our findings related to the problems of IQ testing and recruitment in this population may be helpful to other Latin American investigators planning similar studies.This project was approved under the guidelines of the Ministry of Health of Costa Rica, the Ethical committee of the National Children's Hospital in San Jose, and the Institutional Review Board at Mount Sinai School of Medicine. These approvals remain active. All adult participants provided written informed consent. Parents of participating minors provided written informed consent; minors who were capable also provided signed assent.Dr. Valeria Nanclares completed a preliminary translation of the ADOS. She is the Autism Program Coordinator at the Pediatric Developmental Center, Advocate Illinois Masonic Medical Center, and also the translator of the ADI-R. Next, two professional translators read the document separately in English and Spanish and documented instances where the translation was weak or ambiguous. This approach avoids the introduction of synonyms and colloquialisms and is thus preferable to simple back-translation. Subsequently, native Spanish-speaking clinical experts from Latin America and Spain reviewed the document for content and accuracy of clinical terminology and achieved a final consensus with the original translator. The Latin American expert is Dr. Elina R. Manghi (ERM), who is also the lead best-estimator for this study. She is a clinical psychologist and the Clinical Service Director for the Family Clinic, Department of Disability and Human Development at the University of Illinois at Chicago. She has over 20 years of experience in the field of psychological testing and for the last 10 years has worked with developmental disorders, including autism. She is a certified off-site trainer for both the English and Spanish versions of the ADI-R and is certified for the research use of the ADOS in the United States. The expert from Spain was Dr. Amaia Hervas, who has worked extensively with Dr. Michael Rutter's group on various autism research projects.The Hospital Nacional de Ninos (HNN) is located in San Jose, the capital city of Costa Rica, and is the only major hospital for children in the CVCR. The HNN has an inpatient Neurodevelopmental Unit and recently added a small special education school providing services for children with mental retardation (MR) and developmental delay but not specifically autism. All four child psychiatrists serving the CVCR are also at the HNN. The leading clinician on our study, Dr. Patricia Jimenez Gonzalez (PJG), is Chief of the inpatient Neurodevelopmental Unit at the HNN and has an extensive private practice. She also has an active relationship with the Autism Parents' Association of Costa Rica, a group that is highly motivated to participate in research and promote community education. PJG has passed Dr. Catherine Lord's certification course for research use of the ADI-R and ADOS.A recent study showed that the number of autism and autism spectrum disorder (ASD) cases being diagnosed in the United States increased precipitously following the introduction of Federal special education laws that included autism spectrum disorders as a disability category in 1991 . The diaFamilies of individuals with possible autism contact us, or are contacted by us after expressing interest in the study, and are formally asked to participate using established informed consent criteria. They are first screened by PJG using an abbreviated version of the ADI-R (Autism Screening Questionnaire) for the presence of symptoms consistent with a developmental disorder, as well as for pertinent medical information. All interviews and exams take place in the Neurodevelopmental Unit of the HNN. Possibly affected individuals and their parents are interviewed by PJG or Dr. Marietha Fallas Delgado (a pediatrician under her supervision) using the ADI-R. Either PJG or Sylvia Monge Monge, M.A., who has a master's degree in psychoeducation, administers the ADOS. Both of these assessments are videotaped for independent scoring by the best estimators.An IQ score and an adaptive behavior score are required for the diagnosis of MR. Intelligence is assessed using age and developmentally appropriate instruments available in Spanish and currently in use in Costa Rica. However, a major problem with these IQ tests is that there are often no norms specific for individual Latin American countries. A few IQ tests have norms derived in Spain and Mexico, yet, according to Domingo Campos, Director, Instituto de Investigaciones Psicologicas de la Universidad de Costa Rica , Costa Rica has no internal data of its own to assess potential scoring biases that might be introduced using foreign norms. The tests we use include the Bayley Scales of Infant Development II (1993)   and hypomelanosis of Ito, as these disorders are strongly associated with autistic symptomatology. . Probands with gastrointestinal problems are sent to Internal Medicine for evaluation as at least one study has shown that an unusual complement-mediated lymphocytic colitis may be unique to severely affected autistic subjects . All proPlease see the Clinical History form see  for compIn both the immediate and extended family we also specifically ask about the presence of language delay and learning deficits, which could be manifestations of the broader autism phenotype. We also ask about autoimmune disorders, as data suggests that at least some of the autistic phenotype may be induced by autoimmune mechanisms operating during pregnancy .Don Eduardo Fournier is a Costa Rican historian with extensive experience in tracing genealogies who collaborates on a majority of the genetic studies in Costa Rica. He screens the Civil Registry and, if necessary, birth, marriage, and death records in churches and civic centers to determine the birthplace of all grandparents and great-grandparents. Previous genetic studies in the CVCR have shown that probands whose great-grandparents were born in the CVCR will most probably be descendants of the original Spanish founder population. We require that cases have six of eight great grandparents born in the CVCR for inclusion in the study.The ADI-R and ADOS are independently scored by our bilingual best-estimators, ERM or Pamela Bondy, M.S./CCC-L (PB). PB is a bilingual speech and language therapist with over 10 years of experience in the field of developmental disabilities. She was trained in the use of the ADI-R and ADOS by ERM. Discrepancies, if any, were resolved and final diagnoses reached after review of collateral historical information, clinical exam, and laboratory testing, according to standard best-estimate diagnostic procedure .MECP2 gene. The Moebius syndrome case offers fascinating insights into the etiological basis of autism and will be reported in detail in a subsequent publication. Extrapolating from the entire data set of 70 cases, the male to female ratio appears to be ~6:1. Our goal is to collect over 200 trios, with no major or minor cytogenetic abnormalities, suitable for genetic mapping.To date we have ascertained 76 subjects and enrolled 70 families in our study. One family later declined to participate because of the mother's health, two cases have been excluded by genealogy, one case was too retarded to determine a diagnosis, one case has RETT syndrome (AU043), and the other excluded case is an autistic child with Moebius syndrome (AU044). We are screening the RETT syndrome case for mutations in the As the diagnostic evaluation takes two to three appointments, we have only complete best-estimated data on 35 cases to date. Karyotypes ordered for cases AU025, AU031, and AU040, with family histories of MR, and for case AU001, who has a cleft palate, were all negative at ≥ 550 bands. Interestingly, case AU025 and case AU031 are related to each other by a distance of seven generations, and a connection with case AU040 has not been ruled out. Case AU008, suspected of Angelman's syndrome, had one normal karyotype, and testing for a chromosomal 15q11-q13 abnormality will be performed. The rest of the karyotypes are pending.Table The Family History of Medical Disorders chart is available in the supplementary data see . AU033 dWe have obtained extensive obstetric data on our cases and will be reporting it in full in a subsequent publication. In brief, although only 4 of the mothers were older than 35, 21 of them had obstetric complications and/or the infant had an APGAR score less than 6 at one minute. Fully twenty of the cases were the product of difficult labor, resulting in fetal distress and a caesarean section in eight instances.On the whole, our first cases have mean ADI-R scores comparable in severity to those of other autism genetic studies, including a sample from the Autism Genetic Resource Exchange (AGRE) (N = 364 cases from 212 sibships) . IQ and Eighty-three percent of our cases are mentally retarded, while 60% have IQs <50. In contrast, epidemiological data from a range of countries, although none of them Latin American, estimate that 75% of autistic individuals have IQs <70 and 40% have IQs <50 . HoweverWe must also consider the possibility that the IQs of our cases are underestimated due to the use of psychometric tests without Costa Rican norms. A recent study done in Argentina illustrates the effects of low socioeconomic status and lack of internal norms on IQ testing results. This group set out to perform a longitudinal study of the effects of poverty and malnutrition on the psychological development of children in a province of Buenos Aires . The stuAt the first evaluation, the malnourished children did have significantly lower developmental quotients than the well nourished group, the majority of which had normal ratings. However, at time point 2, after which the malnourished children had been treated, there was no difference between groups, but both were lower than the standard. At time point 3, when the children were ~10 years of age, there was again no difference in IQ between groups, but ~50% of both groups had IQs = 70. The authors of the study drew two major conclusions from these results. The first was that poverty and lack of early intellectual stimulation had profound effects on IQ, even without malnutrition, and that these effects became more prominent with time. The second conclusion concerned the use of IQ tests without norms reflecting the general population of Argentina. The raters felt that the IQ scores of both groups were probably somewhat underestimated because the norms they were comparing them to were derived from children with much higher socioeconomic status. The raters were very experienced in administration of the IQ tests, which were commonly used at universities and elsewhere in Argentina, so misuse of the tests was not an issue. Unfortunately, Latin American governments do not invest in psychological research, and the corporations that sell tests in the United States don't see Latin America as a strong market and thus put no money into norming translated tests. As further evidence of problems with IQ testing, and perhaps ascertainment bias, in the CVCR, we note that in genetic studies of Tourette's Syndrome and ADHD ongoing in the CVCR, 20–25% of cases evaluated for either phenotype have been excluded because of MR . In contrast, 3.9 % of children with Tourette's Syndrome (TS) had MR (range 1–14%) in a large-scale analysis of this disorder in 22 countries (no specific data for Spanish-speaking countries) . AdditioAccurate assessment of IQ is important, as data suggests that that there may be different genetic and environmental determinants for autism based on level of cognition, although cases of autism with low IQ may still have a strong genetic basis. For instance, Baird & August  observedWe do note frequent obstetric complications in our sample and are researching the rates of these complications in the CVCR hospitals for comparison. We are also looking at factors such as geographic distance from a hospital, which might contribute to suboptimal labor and delivery. However, recent data suggests that these complications are commonly associated with autism and ASD. A large-scale epidemiological study of autism in Western Australia found that cases diagnosed with autism, as well as their unaffected siblings, had more obstetric complications than a control group . The autThere are many possible underlying cytogenetic or other medical disorders that may be accompanied by autistic behavior, and the presence of severe MR can make those cases suspect even if karyotypes are normal. Disturbingly, a group of investigators recently reported that they found microdups/dels, as well as other genetic abnormalities, in 272 cases from the Paris Autism Research International Sibpair (PARIS) sample that had already been included in genetic linkage and association studies . These iWe have successfully used the Spanish versions of the ADI-R and ADOS to diagnose autism for genetic study in the CVCR. The majority of the cases reported here have IQ <50. This reflects an ascertainment bias, yet it is also possible that these scores are artificially low. Nevertheless, we are most likely missing cases of autism with normal or near normal IQ due to a lack of government-sponsored services. Therefore, we are implementing a strategy, used successfully by one of our clinical experts to find both English-speaking and Spanish-speaking higher functioning autistic subjects in the United States, to ascertain these cases. We believe that similar problems with IQ testing and the need for specific strategies to find high functioning autism cases will be important issues to address for studies of autism planned or ongoing in other Latin American countries.The author(s) declare that they have no competing interests.LAM secured the funding for the study, played a major role in designing the study, contributed to the data analysis, and wrote the manuscript.PJG is the leading clinician in Costa Rica and performed the majority of the diagnostic interviews using the ADI-R and ADOS, as well as the neurological and medical evaluations. She contributed to the study design and to the data analysis and ensures compliance with the Bioethics Committee at the HNN.ME coordinated the study in Costa Rica and contributed to the data analysis. She administered informed consents and IQ tests, arranged appointments with subjects.ERM is the lead best estimator for our study and performed the majority of data evaluations. She trained the Costa Rican team in the use of current psychological instruments. She also contributed to the manuscript.MFD performed diagnostic interviews using the ADI-R and contributed to the data analysis.SSM assisted PJG in performing the ADOS and contributed to the data analysis.EF traced the genealogies of the probands and is responsible for establishing familial relationships between the cases as well as providing population data for the CVCR essential to the manuscript.PB performed best-estimate data evaluations and contributed to the data analysis.KC coordinated the study in the USA, entered diagnostic information into a database for future statistical analysis, contributed to the manuscript and ensured compliance with the Institutional Review Board at Mount Sinai School of Medicine.All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:Formulario de historia clinica This is the clinical history form that we designed in Spanish. The table begins with parental occupational and educational history followed by family neuropsychiatric history, obstetric data, including APGAR scores, the developmental and medical history of the proband, education the proband has received and results of the physical exam and laboratory testing.Click here for fileResults of Diagnostic Evaluations for Autism This table contains scores for the individual scores subdomains of the ADI-R, the ADOS scores, the IQ scores and information regarding the parents' occupations and education.Click here for fileFamily History of Medical Disorders This table contains details of the family and personal medical history for each proband. We specifically asked about the presence of autism, language delay, learning deficits, MR, epilepsy or other neurological abnormality, cerebral palsy, major psychiatric disorders and deafness. For instance, if a first cousin on the maternal side had epilepsy, we typed 'M first cousin' in the appropriate box. The letters 'M' or 'P' indicate whether the relative is on the maternal or paternal side, respectively. If the mother had a complication during pregnancy such as bleeding or a urinary tract infection, this is noted with an x in the appropriate box. APGAR scores are recorded, as well as the presence of any congenital defects in the proband.Click here for file


Exercise therapy (ET) is the main conservative and proven effective treatment of patients with intermittent claudication. Currently, the most frequent exercise prescription is a single 'go home and walk' advise, without supervision or follow-up. There is no evidence to support the efficacy of this advise and compliance is known to be low. Therefore, a systematic approach was used to guarantee quality and standardisation of treatment, optimal guideline adherence and improved of inter-professional communication between vascular surgeons and physiotherapists. In this preliminary report we would like to outline the steps taken for the development and implementation of the Network Exercise Therapy ParkstadIn October 2003 all 59 regional physiotherapy practices were invited to attend a symposium regarding ET in a physiotherapeutic setting. Attending physiotherapists interested in providing ET and willing to follow a certified course on ET, were asked to register. Three tastkgroups were formed to accomplish the set targets: Exercise therapy education, Exercise therapy implementation and continuity, and Inter-professional communication in the Parkstad region.In total 27 physiotherapists, from 22 different practices followed the educational program and are now trained and accredited to provide ET according to the guideline of the Royal Dutch Society for Physiotherapy. A web-based database wasdesigned to contain information on disease specific items provided by the vascular surgery department, and aspects with respect to ET registered by the physiotherapist. The information is regularly updated and available online. Access tothe database is restricted to vascular surgeons and physiotherapists in the network. The secondary purpose of the database is to register essential benchmark data for future analysis of ET in a physiotherapeutic setting in the Netherlands and to enable physiotherapists continuous feedback on patient performance. A triage system was developed to detect patients with a compromised cardiac history. This group receives ET at the in-hospital department of revalidation with the possibility of immediate consultation of a cardiologist in case of cardiac complications or even CPR.The Network Exercise Therapy Parkstad of supervised ET is the first initiative in the Netherlands to provide ET close to the patient's home environment. With the implementation of supervised ET in an outpatient physiotherapeutic setting for all eligible patients with symptomatic PAD, the access to care has been improved. A web-based communication system provides physiotherapists and vascular surgeons with all the necessary and continues updated patient information. Future research, currently in progress, will investigate the therapeutic benefits and cost-effectiveness of exercise therapy in a physiotherapeutic setting. Patients with peripheral arterial disease (PAD), with intermittent claudicationas the predominant clinical symptom, experience muscle aching or cramp during walking, secondary to muscle ischemia in the calf, thigh or buttocks. PAD is a manifestation of systemic atherosclerosis. The treatment of patients with PAD stage II (according to Fontaine) consists of vascular risk factor management, smoking cessation and exercise therapy (ET).ET is the main conservative treatment for patients with intermittent claudication and proven effective. The psycCurrently, the most frequent exercise prescription for patients with PAD in theNetherlands, and considered best practice according to the Dutch general practitioners and vascular surgeons claudication intermittens guidelines, is a single'go home and walk' advise, without supervision or follow-up. A leaflet on unsupervised ET provided by the Vascular Patients Society is available. There is no evidence to support the efficacy of this advise and compliance is known to be low. ,6 In stuThe first national physiotherapeutic guideline on ET was issued in December 2003 by the Royal Dutch Society for Physiotherapy. This guiTherefore, a systematic approach was used to guarantee quality and standardisation of treatment, optimal guideline adherence and improved inter-professional communication between vascular surgeons and physiotherapists.To improve the current care for patients with intermittent claudication, we setthe following goals:• Optimalisation of the current knowledge and skills of the physiotherapists• Improve the screening of patients allegeable for ET and to provide a safety-net for patients with a high cardiovascular risk• ET should be accessible close to the patients home address• Implementation of a continues monitoring and exchange of inter-professional patient information systemTo achieve these goals, the so-called Network Exercise Therapy Parkstad steering committee was founded in October 2003. This steering committee consisted of avascular surgeon, three nurse practitioners of the vascular surgery department, an epidemiologist, five physiotherapists and a research fellow of the vascular surgery department. To our knowledge this concept is innovative for the Netherlands and abroad. Before future research will commence, we would like to outlinethe steps taken for the development and implementation of the Network ExerciseTherapy ParkstadIn October 2003 all 59 regional physiotherapy practices were invited to attend a symposium regarding ET in a physiotherapeutic setting. The symposium covered topics on the theoretical background, therapeutic benefits, and an introductionto the new Royal Dutch Society for Physiotherapy guideline on ET. An important issue of the symposium was an open discussion on the formation of the Network Exercise Therapy Parkstad to facilitate supervised ET for patients referred by vascular surgeons from the Atrium Medical Centre. At the end of the symposium, attending physiotherapists interested in providing ET, and in the possession of, or the willingness to acquire, a treadmill, and willing to follow a certified course on ET, were asked to register. From this group of physiotherapists we planned to invite five physiotherapists to join the aforementioned steering committee. Our aim was to obtain both physiotherapists from the Department of Revalidation in our hospital as well as regional physiotherapists.Three taskgroups within the steering committee were formed to accomplish the set targets:• Exercise therapy education• Exercise therapy implementation and continuity• Inter-professional communication in the Parkstad regionTo overcome the noted knowledge deficiencies of ET, this taskgroup organised anaccredited two-day 'in-hospital' educational program on ET provided by the Royal Dutch Society for Physiotherapy and the Dutch Paramedic Institute. This course had already been developed, and provides the necessary knowledge and skills to give professional supervised ET. The course covered the necessary theoreticalbackground, and practical skills to provide ET. Three months later, this coursewas followed by a one day follow-up training. This training took place to exchange practical experiences, and to pay extra attention to the use of clinimetrics, standardisation and optimisation of the protocol, as well as getting an introductory session on the use of the electronic patient file in the web-based database.In some patients with PAD, ET in an outpatient physiotherapeutic setting interferes with the present high cardiovascular risk. To provide ET for patients witha compromised cardiac history in a relatively safe environment, the second taskgroup developed a triage system to filter these patients prior to the ET prescription. In close collaboration with the department of cardiology, a decision tree has been developed.Figure  This enaThe aforementioned leaflet on unsupervised ET of the Vascular Patients Society, which has been used throughout the Netherlands for over 10 years, needed revision. The Vascular Patients Society gave us the opportunity to suggest some alterations in this leaflet to make it compliant with the possibility of supervised ET. In this revised version attention was given to the new insights on PAD, risk factor management and supervised as well as unsupervised ET.ET requires a life-long adaptation of the patient's life-style, in which a continuation of daily walking plays an essential role. ET in a physiotherapeutic setting is only covered by medical insurance in the Netherlands for the durationof one year. To support the patient with the necessary life-style changes, the 'Regional Exercise Therapy Walking group Parkstad' has been formed for patientsto enrol after the termination of the supervised ET after a year.The last taskgroup tried to solve the so far absent or at least insufficient communication between the department of vascular surgery and physiotherapy practices. In close collaboration with the University of Maastricht, department of epidemiology, a web-based database was developed. The purpose of this database was twofold. The primary purpose was to facilitate adequate information exchange between vascular surgeons/nurse-practitioners and physiotherapists. The database was designed to contain information on disease specific items like the extentof PAD, present risk factor and co-morbidity provided by the vascular surgery department. The physiotherapist registered aspects with respect to the ET, like therapy progress and difficulties as well as patient compliance. The information is regularly updated and online available. The secondary purpose of the database is to register essential data for future analysis of ET in a physiotherapeutic setting and to enable physiotherapists to receive continuous feedback (benchmark data) on their performance. Furthermore, this database has been designed to be implemented nationwide, and when accomplished, a substantial and important level of evidence on the value of physiotherapy will be available. Similar databases are currently being developed for other therapies in a physiotherapeutic setting.64 physiotherapists attended the symposium on the future of ET in the Parkstad region from 45 regional physiotherapy practices. Five physiotherapists, two from the Department of Rehabilitation, Atrium medical centre, and three regional physiotherapists joined the steering committee. In total 27 physiotherapists, from 22 different practices followed the educational program and are now trained and accredited to provide ET according to the guideline.Patients with a serious cardiac medical history receive ET in a hospital setting, but the vast majority is referred to a local physiotherapist. Figure  TherevisThe web based database provides vascular surgeons and physiotherapists with essential information. Before the patients are scheduled for a repetitive appointment at the hospital the nurse practitioner has access to all therapy related information. The same principle applies to the physiotherapist who receives all the medical updates. With this information the physiotherapist is better equipped to make an adequate judgement on the exercise capacity of the patient and thevascular surgeon can, based on therapy progress and compliance, make an adequate judgement on the necessity of a vascular intervention. Access to the databaseis restricted to vascular surgeons and physiotherapists in the network.In June 2004 the Network Exercise Therapy Parkstad has started. It is the firstnational network to provide supervised ET in a physiotherapeutic setting close to the patients home. All patients with symptomatic PAD (Fontaine stage II) presented at the vascular surgery outpatient clinic who are considered for maximalnon-invasive treatment, are now primarily referred to one of the physiotherapists in the Network Exercise Therapy Parkstad for supervised ET.In the 1998 report of the Dutch Heart Foundation on obstacles in vascular care, the inadequate ET facilities and infrastructure was noted. RecommenLess than half (49%) of the physiotherapists that attended the symposium, eventually jointed the network. This seems disappointing, but taken into account that only 30% of the Dutch practices is in the possession of the required treadmill, the results were better than expected. Furthermore, the majority of practices are already specialised in for instance, cardiac rehabilitation, pulmonary diseases, sport-physiotherapy or neurological disorders, leaving little room for an additional (and time consuming) speciality. The 22 practices that were capable to meet the set requirements, cover the region well and are highly motivated.ET in a physiotherapeutic setting is more expensive than the 'go home and walk' advise. However, besides the increase in maximal walking distance, the prognosis of general health  may improve. Potential differences in costs are likely to result from less morbidity and medical consumption related to PAD complications, vascular surgery, and associated cardiovascular diseases. It is expected that these savings will exceed the costs of ET in a physiotherapeutic setting. However, a true cost-effectiveness analysis should answer this question. On the other hand, ET in hospitals or rehabilitation clinics, as have been practiced abroad, is more costly. The availability of ET close to the patient's home address is one ofthe advantages of the Network Exercise Therapy Parkstad and is most likely to substantially improve therapy participation and compliance. The group that has not the benefit of supervised ET 'around the corner', is the 'safety-net group' for patients with a high cardiovascular risk. In the previous situation, these patients would not be engaged in ET or suffer an increased risk during unsupervised ET. Providing ET in a hospitalised setting enables patients to slowly reclaim their health in a protective environment. The developed decision tree (which has been incorporated in the web-based database), enables also vascular nursepractitioners to identify these high-risk patients.The Network Exercise Therapy Parkstad requires a different way of working and an intensified manner of communication between the department of vascular surgery and the participating physiotherapists. Working with the web-based database is, compared to the old situation, a new way of working and relatively time consuming. Future research will show the impact and consequences of this database.This preliminary report describes the development and implementation of the Network Exercise Therapy Parkstad. The main goal of this regional network was to improve the access to care, and the communication between the different care providers. Future research, currently in progress, will investigate the therapeutic benefits and the cost-effectiveness of exercise therapy in a physiotherapeutic setting. The Network Exercise Therapy Parkstad is now operational and general practitioners have been invited to join and refer patients from the primary care setting. To guide other interested regions in similar projects an extensive implementation guideline is available.The author(s) declare that they have no competing interests.EW concept development and implementation of network and writing of the manuscript. BB management and implementation of network, preparation of manuscript. CB development and implementation of cardiac decision tree. RW concept implementation and critical review of manuscript. MP participated in the design of the concept and draft of manuscript. RB development of database, concept implementation and critical review of manuscript. JT primary concept development and implementation of network and writing of the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


Coalescent simulations are playing a large role in interpreting large scale intra-specific sequence or polymorphism surveys and for planning and evaluating association studies. Coalescent simulations of data sets under different models can be compared to the actual data to test the importance of different evolutionary factors and thus get insight into these.We have created the CoaSim application as a flexible environment for Monte Carlo simulation of various types of genetic data under equilibrium and non-equilibrium coalescent processes for a variety of applications. Interaction with the tool is through the Guile version of the Scheme scripting language. Scheme scripts for many standard and advanced applications are provided and these can easily be modified by the user for a much wider range of applications. A graphical user interface with less functionality and flexibility is also included. It is primarily intended as an exploratory and educational toolCoaSim is a powerful tool because of its flexibility and ease of use. This is illustrated through very varied uses of the application, e.g. evaluation of association mapping methods, parametric bootstrapping, and design and choice of markers for specific questions These years witness popularity of coalescent based inference of evolutionary parameters, either through exact or approximate methods in order to understand within-species, and in particular human, evolution. This is fuelled by large scale efforts to collect data from different human populations, e.g. the HapMap  and ENCOThe coalescent models are good null models to test specific hypotheses against, and therefore it is often useful to simulate genetic data under different coalescent models.Coalescent simulation of data sets and subsequent calculation of some summary statistics on the data set can be used to obtain the distribution of this summary statistic under a given scenario, and this can be compared to the value of the summary statistic calculated from real data. Parametric bootstrapping can be done by estimating parameters from data under a given  model, apply coalescent simulations under some model using the observed value of the parameters and see if the value observed is compatible with the simulation model. The efficiency of new methods can also be evaluated: Methods for inference of recombination rate and its variation, the importance of gene conversion versus recombination, as well as methods for association mapping under different genetic models have to rely on some heuristic approximations of the full likelihood models which are generally too computationally complex. Validating these approximations and inferring the importance of misspecification of the model of analysis employed is usually done using some variant of coalescent simulations.Various applications for the simulation of the coalescent process are already available e.g. -6). The . The 6]), where instructions for the installation are also provided. CoaSim is written in C++ and is available as source code and in a binary version for Linux operating system as rpm-files.CoaSim can be obtained at An introduction to the simulator is provided as a "getting started" manual, where also the GUI version is described. The GUI is an intuitive interface to the simulator, allowing novice users to immediately start the simulations of sequences. Markers are added manually and the simulation stages can be monitored  can be specified in the scheme script.K of states for a given position.For an introduction to coalescent theory, see for example . BasicalThere are three kinds of built-in markers:(1) Trait markers are binary polymorphisms  with a simple mutation model: after simulating the ARG, a mutation is placed uniformly at random on the tree local to the marker position, nodes below the mutation will have the mutant allele while all others will have the wild-type allele. A range of accepted mutant-frequencies can be specified and a simple rejection-sampling scheme is used to ensure it: if, after placing the mutation, the number of mutant leaves is not within the range, the ARG is rejected and the simulation restarted. This insures an unbiased collection of ARGs with a binary marker within a given frequency range.(2) SNP markers resemble trait markers in that they are binary polymorphisms, and use the same mutation model as the trait-markers. They differ from the trait-markers in how the mutant-frequency is ensured: If, after the mutation has been placed, the number of mutant leaves does not fall within the accepted range, the mutation is re-placed, but the ARG is not rejected and re-simulated. This places a bias on the markers, but one that resembles the ascertainment bias seen in association studies, where SNPs are chosen to have frequencies in certain ranges. An unbiased sampling of mutations within the required frequency range can be obtained by constructing a new ARG and repeating the simulation process, until the required frequencies are attained.k, and a different mutation model than traits and SNPs. For microsatellite markers, each edge in the local tree at the marker is considered in turn and, with the likelihood of mutation being an exponential distribution that depends on the specified mutation rate and the length of the edge. If mutation occurs, a randomly chosen allele from 0 to k-1 is placed on the child node; if no mutation occurs, the child node gets a copy of the allele at the parent node.(3) Microsatellite markers have a specified number of alleles, In addition to the built-in marker types, Scheme scripting allows specification of most conceivable mutation models, the stepwise mutation model for microsatellites is included as an example.Trait markers can be marked as being involved in disease susceptibility under a specified, but arbitrary model of disease risk as a function of biallelic variants at a number of sites specified a priori. A multidimensional matrix specifies disease risk for any combination of variants. Thus, from the simulated data and the disease model, case-control data of any size can be generated. Diploid data with known or unknown phase can be easily generated by calling the relevant function from the Scheme script as specified in the manual.Splitting the sequences into cases and controls based solely on the allele at a trait marker or combination of alleles in a more complex disease determination is not always appropriate since it assumes full penetrance. However, in many complex diseases, penetrance is incomplete and dependent on environmental factors and general genetic background, and the same disease phenotypically can be caused by a different genetic pathway. Hence, it is possible to control the likelihood of a given individual belonging to the case or control group by specifying the probabilities given the possible genotypes.Population size changes, bottlenecks, merging of populations (splitting of populations when viewed forward in time) and migration between sub-populations can vary arbitrarily as specified through the definitions of epochs in the Scheme script controlling the simulation  but with various rates of heterogeneity and penetrance. The data with disease causing mutation removed was then directly piped into the GeneRecon program 9, 10] that attempts to infer the disease marker position from all the simulated markers. This allowed us to investigate the effect of marker density, penetrance, heterogeneity, number of cases/controls etc  data sets. These data sets were then used as input to programs aimed at estimating the recombination rate, allowing us to estimate the variance in effect on data that a single recombination event can have and relate this to number of markers, population growth etc .The CoaSim software package was designed for flexibility and with adaptations and extensions of the various Scheme scripts provided and the user manual, a wide range of situations can be accommodated. It provides the user with a much wider range of demographical models, of marker types and disease models without much loss of user friendliness compared to competing software.Project name: CoaSim 4.0Project home page: Source codes for Guile and GUI versions are supplied [see Additional files]Operating system(s): Linux Fedora 1–4, Redhat 9, and MacOSXProgramming language: C++ and schemeOther requirements: Guile Scheme version 1.6. The GUI requires QT version 3.3License: GNUTM, MHS, CNSP, JNM, LS, planned the project. TM, JNM and PJMM wrote the software, TM wrote the documentation. LS and TM tested the software. MHS, TM, LS and CNSP wrote the paper. All authors read and approved the final manuscript.Click here for fileClick here for fileClick here for fileClick here for file


The recent proliferation of health care report cards, especially in cardiac care, has occurred in the absence of an ethical framework to guide in their development and implementation. An ethical framework is a consistent and comprehensive theoretical foundation in ethics, and is formed by integrating ethical theories, relevant literature, and other critical information (such as the views of stakeholders). An ethical framework in the context of cardiac care provides guidance for developing cardiac report cards (CRCs) that are relevant and legitimate to all stakeholders. The purpose of this study is to develop an ethical framework for CRCs.Delphi technique – 13 panelists: 2 administrators, 2 cardiac nurses, 5 cardiac patients, 2 cardiologists, 1 member of the media, and 1 outcomes researcher. Panelists' views regarding the ethics of CRCs were analyzed and organized into themes.We have organized panelists' views into ten principles that emerged from the data: 1) improving quality of care, 2) informed understanding, 3) public accountability, 4) transparency, 5) equity, 6) access to information 7) quality of information, 8) multi-stakeholder collaboration, 9) legitimacy, and 10) evaluation and continuous quality improvement.We have developed a framework to guide the development and dissemination of CRCs. This ethical framework can provide necessary guidance for those generating CRCs and may help them avoid a number of difficult issues associated with existing ones. A growing number of health care report cards are now available, and they are increasingly being used to increase the profiles of high performing hospitals amongst consumers -3. HowevHealth care report cards are most well developed in cardiac care. An ethical framework would provide necessary guidance for those generating cardiac report cards (CRCs) and may help them avoid a number of difficult issues associated with existing report cards. 'Gaming' and uncertainty about the quality of report card data have been cited as impediments to reliable outcomes measures and a reason to limit the public release of report card data ,6. UncerAn ethical framework can identify points of ethical concern for practitioners, patients, policy makers and researchers. And it can aid in the development, implementation and improvement of future generations of CRCs.The purpose of this study is to develop an ethical framework for CRCs.Forming this ethical framework has been a three step process. First, we analyzed the relevant ethical issues in an earlier article . A summaThe Delphi method allows a panel of stakeholders to generate ideas on a given topic and to reach a consensus on the relative importance of those ideas ,14. ThisParticipants were selected from two previous studies conducted by this research team. The first study described the views of cardiac care administrators, cardiac surgeons, cardiac nurses, cardiac patients, cardiologists, members of the media, and outcomes researchers about CRCs . The secWe selected participants for our Delphi panel so that the views and interests of each stakeholder group were represented. Our final panel consisted of 13 panelists: 5 cardiac patients, 2 administrators, 2 cardiac nurses, 2 cardiologists, 1 member of the media, and 1 outcomes researcher. We included a critical mass of patients in order to balance potential or perceived power differentials and enhance the comfort level of participating patients.Ethical issues related to cardiac report cards, identifies ethical issues related to CRCs, and provided panelists with an ethical analysis [Stakeholders' views about cardiac report cards [Patients' views about cardiac report cards, describe stakeholders' views relating to CRCs (a paper on patients' views has been submitted for publication). We asked the panelists to identify key issues that emerged from the papers, and to suggest other issues that may have been missing but were relevant to the ethics of CRCs. We synthesized the feedback from the panelists and organized the items into categories that originated from the panelists' feedback. We combined the items into a draft ethical framework, using the ethical language of the panelists.The Delphi process consisted of three rounds. Round 1 was conducted using electronic communication. We provided three papers based on previous research to each panelist in order to provide background information on the topic. The first paper, analysis . The othrt cards  and PatiRound 2 was conducted as a face-to-face round-table discussion. First, we disseminated the draft ethical framework developed in Round 1 to the panelists by mail and email. Then the panelists came together for a discussion of key issues from the draft ethical framework. The discussion was facilitated by a member of the research team who encouraged panelists to debate the issues amongst themselves and develop a consensus on the key items. Two other members of the research team independently recorded the round table discussion. We used the data gathered at the meeting to refine the framework's key items. After we organized the feedback into their corresponding categories, we integrated new comments into the existing draft framework and examined it to identify any inconsistencies. At the end of Round 2, we had a refined draft ethical framework.Round 3 was conducted electronically, we disseminated the new draft ethical framework by mail and email to the panelists for final refinements. We organized the panelists' feedback according to the refined list of categories from Round 2. We integrated new comments into a refined, ethical framework and re-examined it for inconsistencies. The result of Round 3 was a final ethical framework for CRCs.This study was approved by the Committee on Research with Human Subjects at the University of Toronto. We obtained informed consent from each panelist and kept all data confidential and anonymous to those who were not directly involved in the project.Figure Improving the quality of cardiac care should be the fundamental objective driving the development and implementation of CRCs. In meeting this objective, report cards should also maximize the public good by ensuring equitable quality of care within and between regions. Providing stakeholders with information on the quality of cardiac care may be a necessary and effective impetus for improving the quality of cardiac care. All of the other principles described below should contribute to the overall goal of improving the quality of cardiac care.CRCs should help inform patients about the quality of cardiac care provided within regions, by healthcare organizations, teams and individual health providers. They should provide information that users identify as relevant to their needs and wants. In particular, the information contained within CRCs must be available and comprehensible to the public – i.e. outcome measures should be provided with an adequate amount of relevant context to interpret data. Providing patients with information is a useful end in itself, even if that information is not utilized by patients in making informed choices. For example, a patient can derive comfort from knowing that his/her health care provider meets an acceptable standard of cardiac care. Report cards should contain physician specific qualitative information, such as a description of patient experiences. Valid and reliable qualitative measures as to the quality of cardiac care will have to be developed. However, physician-specific quantitative measures should not be reported within report cards unless data meet reliable criteria, such as originating from a sufficiently large sample size over a sufficient period of time, utilizing commonly accepted risk-adjustment methods, and including a validation process. Further individual physicians should not be ranked based on the outcomes of these measures. Rather physicians should be identified as meeting or not meeting an acceptable standard of care – which will have to be defined.Information that is collected for and presented in CRCs must remain public property, and access to this information must be free. Public ownership of report cards may prevent them from perpetuating disparities in access to information. Panelists saw public ownership of report cards as a way of engaging the public and other relevant stakeholders in improving the quality of cardiac care. There should be two types of report cards: one for health care professionals and policy makers, and one for patients and the public. There are a number of reasons why this is necessary. The two audiences have different interests, which necessitates different content, and different levels of understanding, which necessitates different formats. However both types of report cards should remain public property. Those responsible for CRCs should use multiple dissemination methods that will reach all stakeholders. These methods should include physician-patient discussions, open forums and discussion panels.CRCs should address issues of equity. They should include information on the quality of cardiac care and allocation of resources in different health care institutions and geographic regions. Equity interplays with the principle of access to information. Ineffective dissemination methods may exacerbate existing disparities amongst cardiac patients. Living in rural areas or having limited access to computers and the internet should not prevent patients from having access to CRCs. The principle of equity insists that all cardiac patients have access to the information contained within CRCs.CRCs should be available to the public because they enhance transparency regarding how the cardiac care system functions. By noting strengths and deficiencies within the cardiac care system, CRCs will enable health care professionals and health policy makers to make necessary changes to enhance the quality of cardiac care, and will enhance public accountability for quality cardiac care. Transparency is also necessary for patients to achieve an informed understanding of the quality of cardiac care, by ensuring consistent access to relevant and accurate information. In this way the principles of transparency, informed understanding, access to information, and quality of information are interrelated. Thus transparency is instrumental because it facilitates other desired outcomes.Public accountability refers to the obligation on the part of health care professionals to accept responsibility for the quality of care they provide. Public accountability can be operationalized in two ways: (1) accountability to the public independent of public participation; and (2) accountability to the public enforced through a partnership with patients. CRCs can help signify health care providers' willingness to be accountable for the quality of care they provide and satisfy the public's need for accountability. Transparency and access to information are key aspects of public accountability.Report cards should be developed in collaboration with all stakeholders, including patients. Those who develop and implement CRCs must involve stakeholders early and throughout the process of report card development, and balance the needs of different stakeholders. In their development and implementation, CRCs can foster collaboration and reduce anger and defensiveness. Multi-stakeholder collaboration and transparency are a means of ensuring that CRCs are viewed as legitimate to all relevant stakeholders.Legitimacy, the moral authority of CRCs, must be a key aspect of the development and implementation of CRCs. Patients' views on what is needed in CRCs are necessary to support the principle of legitimacy because patients are at the heart of cardiac care. Patients' views are inherently important, and outcome measures that address patients' wants, such as patient experience measures, should be included in report cards. Traditional quality indicators of morbidity and mortality will be insufficient to meet these needs. Like morbidity and mortality, patient experience measures must also be of high quality, realizing the principle of quality of information. The legitimacy of report cards is also derived from transparency and public ownership of the information contained within them.Report card data must be of high quality. This means that data must be without bias and risk-adjusted and should also be produced and disseminated by an independent and objective third party. Report cards should provide stakeholders with information on matters that can be addressed by the individuals, groups, or organizations which are being evaluated. Similar institutions should be compared to each other – for example, an urban teaching hospital should be compared to a similar urban teaching hospital. This sensitivity to the similarity of institutions should also encompass differences in patients' geographical proximity to institutions. In addition, CRCs must protect patient privacy. The quality of report card data and access to that data are important if report cards are to help initiate changes for improvement in practice sites, or be tied to government funding.CRCs should be useful to stakeholders. Continuous quality improvement and effectiveness monitoring initiatives should be in place to ensure report cards meet their intended goals. The measures contained within CRCs should be constantly reviewed, through multi-stakeholder collaborations, to ensure that they provide a fair assessment of the quality of care being evaluated, which requires transparency of the information gathered. Access to report card data by individuals from each stakeholder group is necessary for continuous quality improvement to be achieved.This study developed an ethical framework to guide the development and implementation of CRCs  declare that they have no competing interests.DKM conceived the study and participated in the data analysis and writing the paper. SAR had primary responsibility for data collection and analysis, and writing the paper. SR participated in data collection and analysis, and writing.The pre-publication history for this paper can be accessed here:


The role of the pediatrician as genetic counselor is ideal because pediatricians have medical knowledge and experience with genetic disorders (e.g. Down syndrome). Moreover, pediatricians can provide comprehensive care in a medical home to patients with genetic disorders. However, changes in the curriculum of the pediatric resident are necessary to address the future challenges of effectively communicating genetic information to patients. The objective of this study was to explore these challenges and make recommendations for training to adequately prepare pediatricians for their future role as genetic counselors.Three reviewers independently searched PubMed, OVID, and Medline databases to identify articles describing the challenges of communicating genetic information to patients, published from 1960 to December 2005. After the publications were identified and reviewed, four major areas of interest were identified in order to categorize the findings.Twenty-five publications were identified during the literature search. From the review, the following categories were selected to organize the findings: (1) Inherent difficulties of communicating and comprehending genetic information; (2) Comprehension of genetic information by pediatricians; (3) Genetics training in residency programs; and (4) The effect of genetic information on the future role of pediatricians and potential legal implications.Pediatricians and residents lack essential knowledge of genetics and communication skills for effective counseling of patients. The review indicated that successful communication of genetic information involves a number of important skills and considerations. It is likely that these skills and considerations are universally required for the communication of most complex specialized medical information. In the past, communication skills have not been considered a priority. Today, these skills have become a demanding professional and even legal obligation. However, the challenges involved in communicating complex medical information cannot be successfully addressed with universal, one-size-fits-all recommendations. Residency training programs require changes to adequately prepare future pediatricians for the growing challenge of communicating genetic information. Four important skills should be considered in the training of residents to improve the communication of complex information to patients. These skills are (1) discriminating, (2) understanding, (3) simplifying, and (4) explaining information. The complete sequencing of the Human Genome Project has brought complexities, promises, and new challenges to the medical profession . UndoubtSeveral medical issues dealing with genetics single out specific ethnic groups , resultiAs genetic information becomes increasingly more important in medicine, many questions remain unanswered regarding the future role of general pediatricians, as well as the growing need to adequately prepare future pediatricians. Some studies have highlighted the importance of effectively communicating genetic information to the patient and the consequences of ineffective communication. To better understand the challenges of effectively communicating genetic information to patients, we conducted a narrative review of the literature. From this review, we discuss recommendations for improving the training of pediatric residents.Three reviewers independently searched PubMed, OVID and Medline databases from 1960 to December 2005 to identify studies describing the challenges of communicating genetic information to patients. The reviewers used the following keywords alone or in combination to search the databases: "Genetics", "Genetic information", "Genetic Education", "Genetic Counseling", "Pediatric Residents", "Pediatrics", "Communication", and "Patient Education." From the three independent reviews of the literature, an inclusive list of candidate publications was compiled for the narrative review. Publications were included in the review if they had primary data that was broadly relevant to the challenges of communicating genetics information to patients. Publications without significant primary data such as commentaries or case reports were excluded. In addition, studies that focused solely on the description of genetic diseases, description of genetic markers, and controlled studies about genetic screening were excluded. Systematic meta-analyses were not performed due to the absence of randomized, controlled trials comparing standard communication processes with the communication of genetic information. After the publications were reviewed, the following major areas of interest were identified in order to categorize the findings: (1) Inherent difficulties of communicating and comprehending genetic information; (2) Comprehension of genetic information by pediatricians; (3) Genetics training in residency programs; and (4) The effect of genetic information on the future role of pediatricians and potential legal implications. For each category, information was organized into a coherent discussion that included the category name, an exploratory question, and a summary statement of findings, followed by the detailed discussion of the findings.Twenty-five publications were identified and reviewed during the literature search. All articles were written in English. The results are presented in the following four sections: (1) Inherent difficulties of communicating and comprehending genetic information; (2) Comprehension of genetic information by pediatricians; (3) Genetics training in residency programs; and (4) The effect of genetic information on the future role of pediatricians and potential legal implications."Why is difficult to communicate and comprehend genetic information?"Difficulties in communicating medical information are common in patient-physician interactions. This interaction is much more complicated when the communication involves more complex or specialized knowledge, such as is in the case of genetic information, when comprehension might involve understanding risks and mathematical calculations (e.g. probabilities). Moreover, the ability to comprehend such information depends on the quality of communication from the physician to patient. In addition, the process of communicating genetic conditions might involve unusual conditions, such as communicating health-related problems to a person that may have no symptoms of a disease . Finally, communicating genetic information must accommodate for issues such as culture, language proficiency, and education.Difficulties in communicating medical information are commonplace in physician-patient interactions and have been subject to extensive discussions . SeveralGenetic information is inherently more difficult to communicate and to comprehend than other medical information. Although medical information is complex, specialized knowledge such as genetic information presents additional challenges during physician-patient communication. For example, communicating genetic information often involves telling a perfectly healthy patient that there is a significant health concern, based on the finding of a genetic test. A physician may need to inform a parent that they carry a lethal gene, or that an infant has the potential for developing a genetic disease. Yet, the absence of disease may make the comprehension of the threat extremely difficult. Consequently, the lack of association between a potentially serious medical condition and the conspicuous good health of a patient or parent can interfere with the ability to comprehend risks and other information about a genetic disease or condition .Communication of information involving life-threatening situations and those in which the diagnosis involves a relative risk for developing a severe disease involves important emotional, social, and cultural considerations. Risk is a difficult concept for most patients of all backgrounds to comprehend. However, a person's education, beliefs, and personal background can affect how the concept of risk is understood. In the medical context, "risk" expresses a probability that is determined by a systematic calculation, based on established factors and conditions. However, an individual's judgment is assumed to be influenced by personal experiences, moral values, and social norms . But wheThe order in which information is chronologically presented – good news first vs. bad news first – must be considered to avoid causing a listener to block out the remainder of a conversation. This is crucial to the interpretation of the diagnosis. Appropriate initial messages are important for effective communication because they form a foundation for comprehension of subsequent messages. Sometimes, the nature of the initial message can lead to misunderstandings that contribute to greater anxiety, feelings of guilt, distorted self-images, and misinformed decisions . RecipieLa Pean et al. found that during the presentation of newborn genetic screening results, pediatric residents delivered an average of 21.5 "bad news" statements before presenting the "good news." In the study, residents did not present good news until 24.8% of the way through the counseling session . The stuThe role of cultural, educational, and differences in language proficiency are extremely important to the process of communicating genetic information. For example, health beliefs and attitudes influence the way people approach new knowledge and learning . Most inIt is challenging for the healthcare consumer to maintain sufficient healthcare literacy during this era of genetics advances and the information age. The capacity for individuals to learn and retain this complex information is inadequate, resulting in confusion. Understanding genetics involves two relevant factors, salience and belief, which are also determinants in translating the genetic information . People'Cultural and language differences need to be considered when communicating genetic information. Some cultures are open to genetic testing (Latino and Chinese) while others (African Americans and White non-Hispanics) are more concerned about the possibility of personal health information being used in health or job discrimination .The lack of a primary care physician's basic knowledge in genetics and the lack of understanding of a patient's needs may cause a stigmatization of the genetic information. This produces diverse psychosocial problems, anxiety, depression, guilt in some families, and survivor's guilt in those patients who did not share the same genetic disease. Genetic information involves not only the patient, but also other family members that may or may not want to have information disclosure. Many communities have been adversely affected by the disclosure of genetic information; for example, the Ashkenazi Jews who have a predisposition for certain cancers and Native Americans who have suffered from stereotypes depicting significant alcohol abuse ."Why is understanding the genetic information important for effective communication?"The amount of information a pediatrician has to provide patients is considerable. In addition, communication barriers may exist and information may vary from extremely simple to very complex. Furthermore, physicians may not thoroughly understand enough information to simplify complex concepts when providing explanations to the patient.Several pediatric residents may lack sufficient comprehension of genetic information to effectively counsel their patients ,25. As sJohnson et al  and Kegl"Why is the pediatric resident training an obstacle to effective communication?"Training in areas of medical communication in the medical field has been considered deficient. The problem is multidimensional and depends on the type of message and the physician and recipient of the message. Each dimension contributes to an increase in complexity.Historically, psychosocial complications have often resulted from misunderstandings about what it means to be affected by or be a carrier of a genetic disease, and misunderstandings have often followed as a result of ineffective communications between the physician and families. Many authors have reported criticism of pediatric residents from families and public health officials due to their lack of communication skills when discussing genetic conditions ,22,26. SIn order to achieve good communication skills in genetics, the physician must have sufficient knowledge of several aspects of genetics. However, pediatric residents lack adequate knowledge of contemporary genetics, and as a result, they lack skills necessary for communicating genetic information . One of "Why is it important to understand the new roles for the future pediatrician to achieve effective communication?"The future of genetic information is very promising and advancements are occurring at a rapid pace. However, perhaps the necessary changes to respond to the needs of learning, understanding, and explaining genetic information are not occurring at the same pace. However, some specialists – including pediatricians – will be required to develop greater skills to communicate information in genetics in order to provide the best service to the patients and their families.The tremendous increase in the use of genetic information is creating fundamental changes to the role of pediatricians, thus introducing significant legal ramifications. The Human Genome Project has generated a staggering amount of new genetic information, leaving genetic specialists overwhelmed by the increased demand for their services. It is estimated that there are only eight genetic counselors per million patients . This diAnother aspect of genetic information with significant legal implications involves informed consent. In order for a patient to provide informed consent, the person must have the capacity to understand the benefits and risks of a medical intervention. Without sufficient comprehension of all the risks, patients are not fully autonomous to make a truly informed decision. Because today's standard medical consent forms do not cover many of the potential genetic issues and because patients typically lack sufficient understanding of genetic information, patients lack true autonomy to make health care decisions. Many authors have noted the necessity to change the standard medical consent process and to develop appropriate communication skills in order to satisfy the requirements of obtaining informed medical consent ,11-14.An effective process for communicating genetic information to parents and patients will be critical to the success of the future pediatrician because of an increasing number of developments in genetic screening and genetic knowledge. These new developments will increase the need for pediatricians to deliver this information, because of a growing shortage of trained professionals to provide genetic counseling ,14,22,28The literature review confirmed many of our suspicions about the inherent difficulties in communication of genetic information. According to some authors, pediatric residents may lack fundamental knowledge of genetics that is crucial to serving the needs of their patients. In addition, good communication skills are an absolute necessity for the accurate communication of this complex information.The review indicated that successful communication of genetic information involves a number of important skills and considerations. Many of these skills and considerations are probably necessary for the communication of most complex specialized medical information. In the past, communication skills were not considered a priority. Today, these skills have become a demanding professional and even legal obligation. However, the challenges involved in health communications cannot be successfully addressed with universal one-size-fits-all recommendations.We observed that when communicating complex specialized information, four important skills are required: (1) discriminating, (2) understanding, (3) simplifying, and (4) explaining. Discriminating the information that will be communicated to the patient in regard to complexity, content, and nature, is basic in the process of communication. However, discriminating between simple and complex information becomes unnatural for the health professional. After many years of technical training, medical information (whether the content is simple or complex) becomes part of day-to-day conversation and health professionals may become incapable of discriminating between the complexity, nature, or content of the information to be communicated. Therefore, health professionals will typically communicate complex information without realizing the complexity of the message. It is absolutely necessary for complex information to be simplified using a multi-level analysis to reduce complex information to the simplest level. However, this process can only occur when the information is completely understood, which might not be possible when the information involves genetic issues.As indicated earlier, evidence suggests that healthcare professionals may lack sufficient knowledge to adequately counsel patients on genetic matters. Not only is it important for the physician to obtain a fundamental command of a medical subject, it is equally important to become familiar with the diversity of the patients to which the physician communicates the medical information. This becomes even more important when the content of the communication includes specialized health information. Therefore, the pediatric resident needs to obtain a fundamental understanding of genetics and an understanding of differences among patients in culture, literacy, and language proficiency, which may affect communication and comprehension.Finally, pediatric residents need to learn how to communicate information utilizing the best available visual, verbal, and/or written arrangement, depending on the subject. Some studies indicated that genetic information is better understood when the information is communicated using visual aids. Matching the best communication style with the patient is dependent on how patients construct images . ChoosinChanges in the curriculum of the pediatric resident must address the future challenges of successfully communicating genetic information to patients. A great advantage of the pediatrician/family doctor as genetic counselor/manager is their knowledge about medicine and experience with genetic disorders (e.g. Down syndrome), and their ability to bring patients with genetic disorders for comprehensive care into a medical home ,30. In aERB conceived and designed the idea, acquired, analyzed, categorized and interpreted data, drafted the manuscript, and approved the final version of the manuscript.PS acquired, analyzed, categorized and interpreted data, drafted the manuscript, and approved the final version to be published.ML acquired data, designed the manuscript content and results, analyzed, categorized and interpreted data, drafted the manuscript, and approved the final version to be published.All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6920/7/17/prepub


Looking out on and being in the green elements of the landscape around us seem to affect health, well-being and feelings of social safety. This article discusses the design of a research program on the effects of green space in the living environment on health, well-being and social safety.The program consists of three projects at three different scales: at a macro scale using data on the Netherlands as a whole, at an intermediate scale looking into the specific effect of green space in the urban environment, and at micro scale investigating the effects of allotment gardens. The projects are observational studies, combining existing data on land use and health interview survey data, and collecting new data through questionnaires and interviews. Multilevel analysis and GIS techniques will be used to analyze the data.Previous  research in environmental psychology has shown that a natural environment has a positive effect on well-being through restoration of stress and attentional fatigue. Descriptive epidemiological research has shown a positive relationship between the amount of green space in the living environment and physical and mental health and longevity.The program has three aims. First, to document the relationship between the amount and type of green space in people's living environment and their health, well-being, and feelings of safety. Second, to investigate the mechanisms behind this relationship. Mechanisms relate to exposure (leading to stress reduction and attention restoration), healthy behavior and social integration, and selection. Third, to translate the results into policy on the crossroads of spatial planning, public health, and safety. Strong points of our program are: we study several interrelated dependent variables, in different ordinary settings , focusing on different target groups, using appropriate multilevel methods. The briefest summary of our program is in its title: Vitamin G, where G stands for the green space around us. Notions of beneficial effects of nearby green space have persisted throughout history . ResearcVitamin G aims to establish the relationship between the amount and type of green space in people's living environment and their health, well-being, and feelings of safety, to study the mechanisms behind this relationship, and to specify the implications for policy making. Our program differs from previous studies in two respects.First of all, field studies will be conducted instead of experimental studies; this is especially important for applied purposes, because it provides a better indication of the relative size of the effects in real-life settings. Field studies also have higher ecological validity, a more direct social relevance, and a focus on long-term rather than on short-term effects . Secondly, the focus is on ordinary settings instead of 'extreme' settings in which people are especially stressed or frustrated , or live in extremely poor or barren circumstances (as in some of the previous studies: -15). ThiIn this article we describe the research questions and background of the program as a whole and the design and methodology of the three separate projects that form the program. Vitamin G started on 1 January 2005 and will run for four years.The general problem formulation of our research program is: what is the direction and strength of the relationship between the amount of green space in people's living environment and their health, well-being and perceived safety, how can this relationship be explained and how can the results be made useful for policy intervention? This general question will be answered in three projects at three different scales: at a macro scale using data on the Netherlands as a whole, at an intermediate scale looking into the specific effect of green space in the urban environment, and at micro scale investigating the effects of allotment gardens. The specific problem formulations for each of these three projects are:1. How strong is the relationship between the amount of green space in people's living environment and their perceived health and well-being, and feelings of safety and is this relationship stronger for specific population segments and/or types of green space? How can this relationship be explained?2. Do urban neighborhoods that differ in the amount and type of green space in the vicinity, also differ in the health, well-being and perceived safety of the people living in these neighborhoods? Have urban neighborhoods that went through a large change in the amount of green space, changed in these respects? If so, which aspects of the green space seem to be the most influential ones?3. Is having an allotment garden related to health, well-being and perceived safety in urban dwellers and how can this relationship be explained?Our approach to answer these questions is based on analyzing the multilevel relationships between environment and people ,17. PeopExposure to green space consists of direct physical exposure and the psychological processes through which exposure influences health and well-being. These psychological processes will be further developed, using theories about stress and restoration [toration . Restoratoration ). In turtoration . Physicatoration .behavioral mechanism will be developed, using sociological theories about life style, combining structural aspects (socio economic status) and opportunities  and choices people make (behavior) [The ehavior) ,20. Natuehavior) . Attractehavior) . Social ehavior) .selection. Selective migration to or retention in particular living environments might explain part of the relationship between green space in people's living environment and their health. Direct selection occurs, when people's well-being influences their chances of living in a favorable environment; indirect selection, when people with certain characteristics, such as a high income, that are related to well-being can afford to live in a favorable environment [Apart from these causal mechanisms, part of the effect may be the result of ironment . Migratiironment . ConsequThe three questions formulated above, will be answered in three projects.The first question will be addressed in a macroscopic project, establishing the strength of the relationships and testing hypotheses about the mechanisms that explain the association between green space and health, well-being, and feelings of safety. Recent epidemiological research by our team has shown a relationship between a green living environment and perceived health indicators in a large population sample . This waThe second project, addressing the second question, zooms in on the urban environment. Green space is scarcer in urban areas and access to it might be more skewed. Several studies have demonstrated positive relationships between the presence of greenery in urban neighborhoods and residents' health, well-being, and social safety ,5-7,26. th century and have known revivals during and after the two world wars to increase supplies of fresh foods [The third project, addressing the third question, focuses on the micro geographic scale. Being also located in an urban environment, it studies people with and without an allotment garden. There is a long history of the use of gardens to improve psychological well-being and physical health . Howeversh foods . Today, sh foods . Beneficsh foods ,32. Sevesh foods ,34. In osh foods . Gardenish foods . But thesh foods . When thsh foods . It has sh foods . Especiash foods .Methods and design will be discussed for each of the three projects that comprise the program separately.Starting point for the analyses is the positive relationship between green space and people's health that was found by De Vries et al. . In the Table GIS techniques will be used to link the individual level data to the land use data and construct the core independent variables . Because spatially clustered data  are involved, multilevel research techniques will be used to take into account the hierarchical structure of the data when estimating parameters -43.We will apply a twofold methodology: a longitudinal study based on existing neighborhood data and a cross-sectional study based on primary data collection. For the longitudinal study, we will compare data of municipal health services (GGD's) collected prior to and after a considerable change in the local green structure of residential areas. The selection of neighborhoods for the longitudinal study will strongly depend upon the availability of GGD-data on health for neighborhoods that experienced a substantial change in their local greenery situation, prior and after this change. The longitudinal analysis will be rather coarse, since only figures at the level of a residential area as a whole will be available. Furthermore, besides the local greenery situation other characteristics may have changed over time.The cross-sectional study is more detailed in nature. About eight large Dutch cities will be selected, having a comparable level of urbanity. Within each of these cities about ten neighborhoods will be selected with (as much as possible) a homogeneous and similar population, to diminish the possibility of strong selection effects and to enable comparison of people with similar social-economic characteristics across local greenery situations. The neighborhoods will have to differ on the set of local greenery characteristics that are considered relevant. Based on a review of the literature the most important aspects of the local greenery for each of the proposed mechanisms will be identified . The inventory of local urban greenery will include site visits and contacts with municipalities of the cities at hand . GIS-analysis will be used to quantify local greenery characteristics.Data will be collected by means of a postal self-administered questionnaire (see table The way questions are posed will be coordinated with those in the other two projects (same phrasing etc.). The same validated measurement scales will be used regarding health as in Vitamin G1. To aid in the identification of green areas, a detailed map will be included in the questionnaire.Given that the data concern observational units at different levels , the data will be analyzed using multilevel techniques -43. AbouThis project focuses on individual residents of deprived urban neighborhoods who spend considerable amounts of time in allotment gardens. The allotment gardeners will be questioned with respect to the same health-related perceptions and behaviors that will be studied in the other two projects. In addition, data will be collected on relevant background variables, such as housing condition and leisure activities. Data will be collected using a mixed methodology of semi-structured face-to-face interviews and the completion of standard weekly diaries over a prolonged period of time  and gardening philosophy . Each gardener will be matched on age, gender, ethnic background and major health risks  to either a neighbor, or a person from the waiting list. This design results in a total sample of 160 respondents, divided in three groups . Assuming that effect sizes will be medium , this design provides a power of over 90% at an alpha of 0.05 for detecting differences between the gardeners and the control groups if the two control groups can be combined, and a power of 72% at an alpha of 0.05 for detecting differences between the gardeners and each of the two control groups separately.An interviewer at home will interview each respondent personally, using a combination of closed and open-ended questions. The formulation of questions will be coordinated with those in the other two projects as much as possible. In as far as possible, validated measurement scales will be used. In addition, gardeners will also be asked to keep a weekly diary for a month. The diary will ask structured questions concerning the gardeners' health and well-being, time spent and activities at the allotment over the previous week, with additional unstructured space in which the respondents are encouraged to discuss events over the week that may have influenced their health, and their thoughts and feelings concerning these events.Urban green space is under strong pressure . Due to The research program Vitamin G aims to fill up these knowledge gaps. Compared to existing studies strong points are:- We study several interrelated aspects of human well-being that until now have been studied separately: self perceived health, physical complaints, mental health, and perceived safety.- We include a large number of different settings so that aspects of well-being can be linked to physical characteristics .- Field studies will be conducted instead of experimental studies; this is especially important for applied purposes, because it provides a better indication of the relative size of the effects in real-life settings.- The focus is on ordinary settings instead of 'extreme' settings in which people are especially stressed or frustrated , or live in extremely poor or barren circumstances.- A focus on different target groups within society increases the policy relevance.- Distinguishing between individuals and environments makes it possible to analyze these two levels with appropriate statistical models .- The use of similar dependent measures in the three projects and the macroscopic to microscopic approach enables the comparison and integration of the outcomes of the different projects.The program also has its weak points.The studies within the program are mainly cross-sectional. As a consequence, selection effects cannot be excluded, although they can be made less probable by appropriate statistical controls. However, longitudinal studies take much more time and are much more expensive. Especially in Vitamin G1 we use datasets that have been collected for other purposes. This means that some variables have not been measured or have been measured in a less appropriate way. An example of a variable that has not been measured in the existing datasets is differential exposure to greenery. However, in the other two projects where primary data will be collected, this will be measured. Especially Vitamin G2 will provide information on the effects of differential exposure.The program focuses on the beneficial effects of being in a green environment. However, undeniably there are also potential negative effects. Experimental research has shown that nature, in particular wild and uncontrolled nature, is a powerful and probably genetically determined source of fear and anxiety ,48. MoreThe program aims to contribute to spatial and health policy-making. Urban green space is under strong pressure . Due to The author(s) declare that they have no competing interests.All authors participated in the design of the program. PG was the principal applicant of the program as whole and drafted the manuscript. RV is responsible for Vitamin G1; SdV for Vitamin G2 and AvdB for Vitamin G3. All authors read the drafts of the manuscript and approved the final version.The pre-publication history for this paper can be accessed here: