High-Resolution Magnetic Resonance Imaging Can Reliably Detect Orbital Tumor Recurrence after Enucleation in Children with Retinoblastoma.

PURPOSE: Orbital tumor recurrence is a rare but serious complication in children with retinoblastoma, leading to a high risk of metastasis and death. Therefore, we assume that these recurrences have to be detected and treated as early as possible. Preliminary studies used magnetic resonance imaging (MRI) to evaluate postsurgical findings in the orbit. In this study, we assessed the diagnostic accuracy of high-resolution MRI to detect orbital tumor recurrence in children with retinoblastoma in a large study cohort. DESIGN: Consecutive retrospective study (2007-2013) assessing MRI findings after enucleation. PARTICIPANTS: A total of 103 MRI examinations of 55 orbits (50 children, 27 male/23 female, mean age 16.3±12.4 months) with a median time of 8 months (range, 0-93) after enucleation for retinoblastoma. METHODS: High-resolution MRI using orbital surface coils was performed on 1.5 Tesla MRI systems to assess abnormal orbital findings. MAIN OUTCOME MEASURES: Five European experts in retinoblastoma imaging evaluated the MRI examinations regarding the presence of abnormal orbital gadolinium enhancement and judged them as "definitive tumor," "suspicious of tumor," "postsurgical condition/scar formation," or "without pathologic findings." The findings were correlated to histopathology (if available), MRI, and clinical follow-up. RESULTS: Abnormal orbital enhancement was a common finding after enucleation (100% in the first 3 months after enucleation, 64.3% >3 years after enucleation). All histopathologically confirmed tumor recurrences (3 of 55 orbits, 5.5%) were correctly judged as "definitive tumor" in MRI. Two orbits from 2 children rated as "suspicious of tumor" received intravenous chemotherapy without histopathologic confirmation; further follow-up (67 and 47 months) revealed no sign of tumor recurrence. In 90.2%, no tumor was suspected on MRI, which was clinically confirmed during follow-up (median follow-up after enucleation, 45 months; range, 8-126). CONCLUSIONS: High-resolution MRI with orbital surface coils may reliably distinguish between common postsurgical contrast enhancement and orbital tumor recurrence, and therefore may be a useful tool to evaluate orbital tumor recurrence after enucleation in children with retinoblastoma. We recommend high-resolution MRI as a potential screening tool for the orbit in children with retinoblastoma to exclude tumor recurrence, especially in high-risk patients within the critical first 2 years after enucleation.

Polyphenol intake and mortality risk: a re-analysis of the PREDIMED trial

Background: Polyphenols may lower the risk of cardiovascular disease (CVD) and other chronic diseases due to their antioxidant and anti-inflammatory properties, as well as their beneficial effects on blood pressure, lipids and insulin resistance. However, no previous epidemiological studies have evaluated the relationship between the intake of total polyphenols intake and polyphenol subclasses with overall mortality. Our aim was to evaluate whether polyphenol intake is associated with all-cause mortality in subjects at high cardiovascular risk. Methods: We used data from the PREDIMED study, a 7,447-participant, parallel-group, randomized, multicenter, controlled five-year feeding trial aimed at assessing the effects of the Mediterranean Diet in primary prevention of cardiovascular disease. Polyphenol intake was calculated by matching food consumption data from repeated food frequency questionnaires (FFQ) with the Phenol-Explorer database on the polyphenol content of each reported food. Hazard ratios (HR) and 95% confidence intervals (CI) between polyphenol intake and mortality were estimated using time-dependent Cox proportional hazard models. Results: Over an average of 4.8 years of follow-up, we observed 327 deaths. After multivariate adjustment, we found a 37% relative reduction in all-cause mortality comparing the highest versus the lowest quintiles of total polyphenol intake (hazard ratio (HR) = 0.63; 95% CI 0.41 to 0.97; P for trend = 0.12). Among the polyphenol subclasses, stilbenes and lignans were significantly associated with reduced all-cause mortality (HR =0.48; 95% CI 0.25 to 0.91; P for trend = 0.04 and HR = 0.60; 95% CI 0.37 to 0.97; P for trend = 0.03, respectively), with no significant associations apparent in the rest (flavonoids or phenolic acids). Conclusions: Among high-risk subjects, those who reported a high polyphenol intake, especially of stilbenes and lignans, showed a reduced risk of overall mortality compared to those with lower intakes. These results may be useful to determine optimal polyphenol intake or specific food sources of polyphenols that may reduce the risk of all-cause mortality.

Improving interMediAte Risk management. MARK study

Background: Cardiovascular risk functions fail to identify more than 50% of patients who develop cardiovascular disease. This is especially evident in the intermediate-risk patients in which clinical management becomes difficult. Our purpose is to analyze if ankle-brachial index (ABI), measures of arterial stiffness, postprandial glucose, glycosylated hemoglobin, self-measured blood pressure and presence of comorbidity are independently associated to incidence of vascular events and whether they can improve the predictive capacity of current risk equations in the intermediate-risk population. Methods/Design: This project involves 3 groups belonging to REDIAPP (RETICS RD06/0018) from 3 Spanish regions. We will recruit a multicenter cohort of 2688 patients at intermediate risk (coronary risk between 5 and 15% or vascular death risk between 3-5% over 10 years) and no history of atherosclerotic disease, selected at random. We will record socio-demographic data, information on diet, physical activity, comorbidity and intermittent claudication. We will measure ABI, pulse wave velocity and cardio ankle vascular index at rest and after a light intensity exercise. Blood pressure and anthropometric data will be also recorded. We will also quantify lipids, glucose and glycosylated hemoglobin in a fasting blood sample and postprandial capillary glucose. Eighteen months after the recruitment, patients will be followed up to determine the incidence of vascular events (later follow-ups are planned at 5 and 10 years). We will analyze whether the new proposed risk factors contribute to improve the risk functions based on classic risk factors. Discussion: Primary prevention of cardiovascular diseases is a priority in public health policy of developed and developing countries. The fundamental strategy consists in identifying people in a high risk situation in which preventive measures are effective and efficient. Improvement of these predictions in our country will have an immediate, clinical and welfare impact and a short term public health effect

Assessment of total cardiovascular risk in hypertensive subjects

Valtimotautiriskin arviointi verenpainepotilailla Valtimotaudit ovat yleisin kuolinsyy koko maailmassa. Väestön elintapojen muuttuminen ja ikääntyminen uhkaavat edelleen lisätä valtimotautien esiintyvyyttä. Kokemäenjokilaakson valtimotautien ehkäisyprojektin tavoitteena oli löytää 45–70-vuotiaasta väestöstä henkilöt, joilla on kohonnut riski sairastua valtimotauteihin. Kaksivaiheisen seulontamenetelmän avulla voitiin terveydenhoitajan antama elintapaneuvonta kohdistaa riskihenkilöihin ja rajoittaa lääkärin vastaanoton tarve niihin potilaisiin, jotka todennäköisesti hyötyvät ennaltaehkäisevästä lääkityksestä. Suomalainen tyypin 2 diabeteksen sairastumisriskin arviointikaavake ja hoitajan toteama kohonnut verenpaine osoittautuivat käytännöllisiksi menetelmiksi seuloa väestöstä riskihenkilöitä. Valtimotautien ehkäisyprojektissa Harjavallassa ja Kokemäellä todettiin verenpainetauti 1 106 henkilöllä, jotka eivät sairastaneet valtimotautia tai aiemmin todettua diabetesta. Heidän tutkimustulostensa avulla voidaan arvioida kohonneen verenpaineen vaikutusta sokeriaineenvaihduntaan ja verenpaineen aiheuttamiin kohde-elinvaurioihin. Sokeriaineenvaihdunnan häiriöt ovat verenpainetautia sairastavilla yleisempiä kuin väestössä muutoin. Käyttämällä metabolisen oireyhtymän kriteerejä sokerirasituskokeen suorittamisen edellytyksenä voidaan tutkimusten määrää vähentää kolmanneksella ja silti löytää lähes kaikki diabetesta tai sen esiastetta sairastavat verenpainepotilaat. Verenpainepotilaista etenkin metabolista oireyhtymää sairastavilla naisilla on suurentunut munuaisten vajaatoiminnan riski. Jos verenpainepotilaan munuaisten toimintaa arvioidaan pelkästään plasman kreatiniini -arvon perusteella, kolme neljästä munuaisten vajaatoimintaa potevasta jää toteamatta verrattuna laskennallisen glomerulusten suodattumisnopeuden määritykseen seulontamenetelmänä. Joka kolmannella verenpainetautia sairastavalla voidaan todeta alaraajavaltimoiden kovettumista; useammin niillä, joiden ylä- ja alaverenpaineen erotus, pulssipaine on yli 65 mmHg. Verenpainetauti on itsenäinen perifeerisen valtimotaudin vaaratekijä. Tutkimuksessa käytetty menetelmä nilkka-olkavarsipainesuhteen määrittämiseksi soveltunee hyvin perusterveydenhuollon käyttöön riskihenkilöiden löytämiseksi. Valtimotautien kokonaisriskin arviointimenetelmät tai uuden riskitekijän, herkän C-reaktiivisen proteiinin määritys eivät voi korvata kohde-elinvaurioiden mittaamista verenpainepotilaan valtimotautiriskin huolellisessa arvioinnissa.

TCDI vs TCD for stroke risk prevention in children with sickle cell anemia: a cross-sectional study

Children with sickle cell anemia (SCA) are at increased risk of stroke. Elevated blood-flow velocities in the middle cerebral artery detected by Transcranial Doppler (TCD) are a good predictor of stroke risk in these children. Velocities obtained by TCD are measured by using a specific parameter, the time-averaged mean of the maximum velocity (TAMM). Children with TAMM velocities ≥200 cm/sec are at high risk of stroke, and transfusions as primary prevention might be done. Transcranial Doppler-imaging (TCDI) is now widely available and it allows the visualization of intracranial vessels.Few studies have compared the TAMM in TCD and TCDI, and no studies have established a cutoff point for TAMM in TCDI equivalent to the STOP criteria of “normal”, “conditional” and “abnormal”, which could predict a high risk of stroke in children with SCAObjectives: To compare the TAMM velocity obtained by TCDI with the TAMM velocity obtained with TCD in the middle cerebral artery, and to determine a cutoff point for TAMM in TCDI that could predict a high risk of stroke in children with SCAMethods: This study is a cross-sectional study of a diagnostic test. 78 children with sickle cell anemia between 2 to 16 years will be evaluated with both TCD and TCDI in order to determinate the TAMM with the two devices. Velocities obtained with both Doppler techniques will be compared using an intraclass correlation coefficient

An analysis of the risk of cocoa moniliasis occurrence in Brazil as the result of climate change

The aim of this study was to evaluate the potential risk of moniliasis occurrence and the impacts of climate change on this disease in the coming decades, should this pathogen be introduced in Brazil. To this end, climate favorability maps were devised for the occurrence of moniliasis, both for the present and future time. The future scenarios (A2 and B2) focused on the decades of 2020, 2050 and 2080. These scenarios were obtained from six global climate models (GCMs) made available by the third assessment report of Intergovernmental Panel on Climate Change (IPCC). Currently, there are large areas with favorable climate conditions for moniliasis in Brazil, especially in regions at high risk of introduction of that pathogen. Considering the global warming scenarios provided by the IPCC, the potential risk of moniliasis occurrence in Brazil will be reduced. This decrease is predicted for both future scenarios, but will occur more sharply in scenario A2. However, there will still be areas with favorable climate conditions for the development of the disease, particularly in Brazil's main producing regions. Moreover, pathogen and host alike may undergo alterations due to climate change, which will affect the extent of their impacts on this pathosystem.

Potential impact of the global climate changes on the spatial distribution of areas of risk for the occurrence of eucalyptus rust in Brazil

Rust, caused by Puccinia psidii, is one of the most important diseases affecting eucalyptus in Brazil. This pathogen causes disease in mini-clonal garden and in young plants in the field, especially in leaves and juvenile shoots. Favorable climate conditions for infection by this pathogen in eucalyptus include temperature between 18 and 25 ºC, together with at least 6-hour leaf wetness periods, for 5 to 7 consecutive days. Considering the interaction between the environment and the pathogen, this study aimed to evaluate the potential impact of global climate changes on the spatial distribution of areas of risk for the occurrence of eucalyptus rust in Brazil. Thus, monthly maps of the areas of risk for the occurrence of this disease were elaborated, considering the current climate conditions, based on a historic series between 1961 and 1990, and the future scenarios A2 and B2, predicted by IPCC. The climate conditions were classified into three categories, according to the potential risk for the disease occurrence, considering temperature (T) and air relative humidity (RH): i) high risk (18 < T < 25 ºC and RH > 90%); ii) medium risk (18 < T < 25 ºC and RH < 90%; T< 18 or T > 25 ºC and RH > 90%); and iii) low risk (T < 18 or T > 25 ºC and RH < 90%). Data about the future climate scenarios were supplied by GCM Change Fields. In this study, the simulation model Hadley Centers for Climate Prediction and Research (HadCm3) was adopted, using the software Idrisi 32. The obtained results led to the conclusion that there will be a reduction in the area favorable to eucalyptus rust occurrence, and such a reduction will be gradual for the decades of 2020, 2050 and 2080 but more marked in scenario A2 than in B2. However, it is important to point out that extensive areas will still be favorable to the disease development, especially in the coldest months of the year, i.e., June and July. Therefore, the zoning of areas and periods of higher occurrence risk, considering the global climate changes, becomes important knowledge for the elaboration of predicting models and an alert for the integrated management of this disease.

Comparative study of the different degrees of risk of gastrointestinal stromal tumor

OBJECTIVE: To evaluate the applicability of the main categories of risk and morphological factors in the prognosis of gastrointestinal stromal tumors. METHODS: we retrospectively studied fifty-four cases of GIST, assessing the main prognostic factors of this neoplasis: risk levels, topography, size, mitotic index, necrosis, histological subtype and immunophenotype. We also verified their association and the reduction of overall survival. RESULTS: Univariate analysis showed that tumors with mitoses number greater than 5 per 50CGA (high-power fields), the presence of necrosis and a high risk for both the systems proposed by Fletcher and Miettinen had a significant association with reduced survival (p = 0.00001, 0.0056, 0.03 and 0.009, respectively). The remaining analyzed factors (size, histological subtype, topography and immunophenotype) had no such association. Multivariate analysis (Jacard index) showed that the Miettinen degree of risk was the one that best correlated with prognosis. CONCLUSION: the risk criteria of Fletcher and Miettinen are important in assessing the prognosis of patients with gastrointestinal stromal tumors, especially the latter, which adds to the mitotic index and the presence of tumor necrosis.

Cardiovascular risk in middle-aged breast cancer survivors: a comparison between two risk models

PURPOSE: It was to assess the risk of cardiovascular disease (CVD) in breast cancer survivors (BCS).METHODS: This cross-sectional study analyzed 67 BCS, aged 45 -65 years, who underwent complete oncological treatment, but had not received hormone therapy, tamoxifen or aromatase inhibitors during the previous 6 months. Lipid profile and CVD risk were evaluated, the latter using the Framingham and Systematic COronary Risk Evaluation (SCORE) models. The agreement between cardiovascular risk models was analyzed by calculating a kappa coefficient and its 95% confidence interval (CI).RESULTS: Mean subject age was 53.2±6.0 years, with rates of obesity, hypertension, and dyslipidemia of 25, 34 and 90%, respectively. The most frequent lipid abnormalities were high total cholesterol (70%), high LDL-C (51%) and high non-HDL-C (48%) concentrations. Based on the Framingham score, 22% of the participants had a high risk for coronary artery disease. According to the SCORE model, 100 and 93% of the participants were at low risk for fatal CVD in populations at low and high risk, respectively, for CVD. The agreement between the Framingham and SCORE risk models was poor (kappa: 0.1; 95%CI 0.01 -0.2) for populations at high risk for CVD.CONCLUSIONS: These findings indicate the need to include lipid profile and CVD risk assessment in the follow-up of BCS, focusing on adequate control of serum lipid concentrations.

Fibronectin in the ascitic fluid of cirrhotic patients: correlation with biochemical risk factors for the development of spontaneous bacterial peritonitis

Cirrhotic patients (23 with alcoholic cirrhosis, 5 with posthepatitic cirrhosis and 2 with cryptogenic cirrhosis) with ascites and portal hypertension were studied and divided into two groups corresponding to high or low risk to develop spontaneous bacterial peritonitis (SBP) related to the concentration of total protein in the ascitic fluid (A-TP): group I (high risk): A-TP£1.5 g/dl and group II (low risk): A-TP>1.5 g/dl. Fibronectin (FN), C3 and C4 concentrations were measured by radial immunodiffusion while total protein was measured by the biuret method. The mean values (group I vs group II) of C3 (12.59 ± 4.72 vs 24.53 ± 15.58 mg/dl), C4 (4.26 ± 3.87 vs 7.26 ± 4.14 mg/dl) and FN (50.47 ± 12.49 vs 75.89 ± 24.70 mg/dl) in the ascitic fluid were significantly lower (P<0.05) in the group considered to be at high risk for SBP. No significant difference was observed in the plasma/ascites fibronectin ratio (3.91 ± 1.21 vs 3.80 ± 1.26) or gradient (131.46 ± 64.01 vs 196.96 ± 57.38) between groups. Fibronectin in ascites was significantly correlated to C3 (r = 0.76), C4 (r = 0.58), total protein (r = 0.73) and plasma FN (r = 0.58) (P<0.05). The data suggest that the FN concentration in ascites is related to the opsonic capacity of this fluid, and that its concentration in the ascitic fluid may be a biochemical risk factor indicator for the development of spontaneous bacterial peritonitis

Prevalence and risk factors for HBV, HCV and HDV infections among injecting drug users from Rio de Janeiro, Brazil

Viral hepatitis constitutes a major health issue, with high prevalence among injecting drug users (IDUs). The present study assessed the prevalence and risk determinants for hepatitis B, C and D viruses (HBV, HCV and HDV) infections among 102 IDUs from Rio de Janeiro, Brazil. Serological markers and HCV-RNA were detected by enzyme immunoassay and nested PCR, respectively. HCV genotyping was determined by restriction fragment length polymorphism analysis (RFLP). HBsAg, anti-HBc and anti-HBs were found in 7.8, 55.8 and 24.7% of IDUs, respectively. In the final logistic regression, HBV infection was independently associated with male homosexual intercourse within the last 5 years (odds ratio (OR) 3.1; 95% confidence interval (CI) 1.1-8.8). No subject presented anti-delta (anti-HD). Anti-HCV was detected in 69.6% of subjects, and was found to be independently associated with needle sharing in the last 6 months (OR 3.4; 95% CI 1.3-9.2) and with longer duration of iv drug use (OR 3.1; 95% CI 1.1-8.7). These data demonstrate that this population is at high risk for both HBV and HCV infection. Among IDUs from Rio de Janeiro, unprotected sexual intercourse seems to be more closely associated with HBV infection, whereas HCV is positively correlated with high risk injecting behavior. Comprehensive public health interventions targeting this population and their sexual partners must be encouraged.

Prevalence of antibodies to human herpesvirus-8 in populations with and without risk for infection in São Paulo State

Human herpesvirus 8 (HHV-8) is a newly described herpesvirus that is etiologically associated with all forms of Kaposi's sarcoma (KS). Seroepidemiological studies have shown high prevalence rates of HHV-8 antibodies among men who have sex with men (MSM) and AIDS patients, African children, Brazilian Amerindians, and elderly individuals in certain regions of Europe. The aim of the present study was to determine the prevalence of HHV-8 antibodies in healthy children and young adults from different cities in São Paulo State, and in a population at high risk for HHV-8 infection: HIV-negative MSM, and AIDS patients with and without KS. Antibodies to HHV-8 latency-associated nuclear antigen and lytic-phase antigens were detected by immunofluorescence assays. In 643 healthy children and young adults from the general population attending a vaccination program for yellow fever in ten different cities in São Paulo State, the prevalence of HHV-8 antibodies detected by the presence of latent or lytic antigens ranged from 1.0 to 4.1% in the different age groups (mean = 2.5%). In the MSM group, the prevalence was 31/95 (32.6%). In the group of patients with AIDS, the prevalence was 39.2% (51/130) for non-KS patients and 98.7% (77/78) for AIDS patients with the diagnosis of KS confirmed by histopathological examination. We conclude that HHV-8 has a restricted circulation among healthy children and young adults in the general population of São Paulo State and a high prevalence among MSM and AIDS patients.

Impairment of cytomegalovirus-specific cellular immune response as a risk factor for cytomegalovirus disease in transplant recipients

Human cytomegalovirus (CMV) infection is common in most people but nearly asymptomatic in immunocompetent individuals. After primary infection the virus persists throughout life in a latent form in a variety of tissues, particularly in precursor cells of the monocytic lineage. CMV reinfection and occurrence of disease are associated with immunosuppressive conditions. Solid organ and bone marrow transplant patients are at high risk for CMV disease as they undergo immunosuppression. Antiviral treatment is effective in controlling viremia, but 10-15% of infected patients can experience CMV disease by the time the drug is withdrawn. In addition, long-term antiviral treatment leads to bone marrow ablation and renal toxicity. Furthermore, control of chronic CMV infection in transplant recipients appears to be dependent on the proper recovery of cellular immunity. Recent advances in the characterization of T-cell functions and identification of distinct functional signatures of T-cell viral responses have opened new perspectives for monitoring transplant individuals at risk of developing CMV disease.

High HTLV-1 proviral load, a marker for HTLV-1 associated myelopathy/tropical spastic paraparesis, is also detected in patients with infective dermatitis associated with HTLV-1

Salvador (BA, Brazil) is an endemic area for human T-cell lymphotrophic virus type 1 (HTLV-1). The overall prevalence of HTLV-1 infection in the general population has been estimated to be 1.76%. HTLV-1 carriers may develop a variety of diseases such as adult T-cell leukemia/lymphoma, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and infective dermatitis associated with HTLV-1 (IDH). IDH is a chronic and severe form of childhood exudative and infective dermatitis involving mainly the scalp, neck and ears. It has recently been observed that 30% of patients with IDH develop juvenile HAM/TSP. The replication of HTLV-1 has been reported to be greater in adult HAM/TSP patients than in asymptomatic HTLV-1 carriers. In the current study, the proviral load of 28 children and adolescents with IDH not associated with HAM/TSP was determined and the results were compared to those obtained in 28 HTLV-1 adult carriers and 28 adult patients with HAM/TSP. The proviral load in IDH patients was similar to that of patients with HAM/TSP and much higher than that found in HTLV-1 carriers. The high levels of proviral load in IDH patients were not associated with age, duration of illness, duration of breast-feeding, or activity status of the skin disease. Since proviral load is associated with neurological disability, these data support the view that IDH patients are at high risk of developing HAM/TSP.

Early detection and intervention for infants at risk of autism spectrum disorders

Autism is a developmental disorder that is characterized by abnonnal social interactions and communications as well as repetitive and restricted activities and interests. There is evidence of a genetic component, as 5% of younger siblings are diagnosed if their older sibling has been diagnosed. Autism is generally not diagnosed until age 3 at the earliest, yet it has been shown that early intervention for children with autism can greatly increase their functioning. Because of this, it is important that symptoms of autism are identified as early as possible so that diagnosis can occur as soon as possible to allow these children the earliest intervention. This thesis was divided into two parts. The first looked at the psychometrics of two proposed measures, the Parent Observation Checklist (POC), administered monthly, and the Infant Behavior Summary Evaluation (mSE), administered bimonthly, to see if they can be used with the infant population to identify autistic symptoms in infants who are at high risk for autism or related problems because they have an older sibling with autism. Study 1 reported acceptable psychometric properties of both the POC and IBSE in terms of test-retest reliability, internal consistency, construct validity and predictive validity. These results provide preliminary evidence that parent report measures can help to detect early symptoms of ASD in infants. The POC was shown to differentiate infants who were diagnosed from a matched group that was not diagnosed by 3 years of age. The second part of this thesis involved a telephone interview of parents who reported developmental and/or behavior problems in their high-risk infants that may be early signs of Autism Spectrum Disorder (ASD). During the interview, a service questionnaire was administered to see what interventions (including strategies recommended by the researchers) their at risk infants and affected older siblings were receiving, how satisfied the parents were with them and how effective they felt the interventions were. 3 Study 2 also yielded promising results. Parents utilized a variety of services for at risk infants and children with ASD. The interventions included empirically validated early intervention (e.g., ABA) to non-empirically validated treatments (e.g., diet therapy). The large number of nonempirically validated treatments parents used was surprising, yet parents reported being involved and satisfied, and thought that the services were effective. Parents' perceptions of their stress levels went down slightly and feelings of competence rose when they accessed services for their infants. Overall, the results of this thesis provide new evidence that parent-report methods hold promise as early detection instruments for ASD in at-risk infants. More research is needed to further validate these instruments as well as to understand the variables related to the parents' choice of early intervention for their at risk and affected children.