Accuracy of Time to Treatment Initiation Data in Musculoskeletal Soft Tissue Sarcoma.

Background: Time to treatment initiation (TTI) is a quality metric in cancer care. The purpose of this study is to determine the accuracy of TTI data from a single cancer center registry that reports to the National Cancer Database (NCDB) for sarcoma diagnoses. Methods: A retrospective analysis of a single Commission on Cancer (CoC)-accredited cancer center's tumor registry between 2006 and 2016 identified 402 patients who underwent treatment of a musculoskeletal soft tissue sarcoma and had TTI data available. Registry-reported TTI was extracted from the tumor registry. Effective TTI was manually calculated by medical record review as the number of days from the date of tissue diagnosis to initiation of first effective treatment. Effective treatment was defined as oncologic surgical excision or initiation of radiation therapy or chemotherapy. Registry-reported TTI and effective TTI values were compared for concordance in all patients. Results: In the entire cohort, 25% (99/402) of patients had TTI data discordance, all related to surgical treatment definition. For patients with a registry-reported value of TTI = 0 days, 74% (87/118) had a diagnostic surgical procedure coded as their first treatment event, with 73 unplanned incomplete excision procedures and 14 incisional biopsies. In these patients, effective TTI was on average 59 days (P < 0.001). For patients with a registry-reported value of TTI >0 days, only 4% (12/284) had discordant TTI values. Conclusions: Nearly three-fourths of patients with a registry-reported value of TTI = 0 days in a large, CoC-accredited cancer center registry had a diagnostic procedure coded as their first treatment event, though their effective treatment had not yet started. These data suggest that TTI is likely longer than what is reported to the NCDB. Redefinition of what constitutes surgical treatment should be considered to improve the accuracy of data used in measuring TTI in sarcoma.

Preoperative Magnetic Resonance Imaging Offers Questionable Clinical Utility, Delays Time to Hip Arthroscopy, and Lacks Cost-Effectiveness in Patients Aged ≤40 Years With Femoroacetabular Impingement Syndrome: A Retrospective 5-Year Analysis.

PURPOSE: To assess the clinical utility of preoperative magnetic resonance imaging (MRI) and quantify the delay in surgical care for patients aged ≤40 years undergoing primary hip arthroscopy with history, physical examination, and radiographs concordant with femoroacetabular impingement syndrome (FAIS). METHODS: From August 2015 to December 2020, 1,786 consecutive patients were reviewed from the practice of 1 fellowship-trained hip arthroscopist. Inclusion criteria were FAIS, primary surgery, and age ≤40 years. Exclusion criteria were MRI contraindication, reattempt of conservative management, or concomitant periacetabular osteotomy. After nonoperative treatment options were exhausted and a surgical plan was established, patients were stratified by those who presented with versus without MRI. Those without existing MRI received one, and any deviations from the surgical plan were noted. All preoperative MRIs were compared with office evaluation and intraoperative findings to assess agreement. Demographic data, Hip Disability and Osteoarthritis Outcome Score (HOOS)-Pain, and time from office to MRI or arthroscopy were recorded. RESULTS: Of the patients indicated by history, physical examination, and radiographs alone (70% female, body mass index 24.8 kg/m2, age 25.9 years), 198 patients presented without MRI and 934 with MRI. None of the 198 had surgical plans altered after MRI. Patients in both groups had MRI findings demonstrating anterosuperior labral tears that were visualized and repaired intraoperatively. Mean time from office to arthroscopy for patients without MRI versus those with was 107.0 ± 67 and 85.0 ± 53 days, respectively (P < .001). Time to MRI was 22.8 days. No difference between groups was observed among the 85% of patients who surpassed the HOOS-Pain minimal clinically important difference (MCID). CONCLUSION: Once indicated for surgery based on history, physical examination, and radiographs, preoperative MRI did not alter the surgical plan for patients aged ≤40 years with FAIS undergoing primary hip arthroscopy. Moreover, preoperative MRI delayed time to arthroscopy. The necessity of routine preoperative MRI in the young primary FAIS population should be challenged.

Interrater Agreement of an Arthroscopic Anterior Cruciate Ligament Tear Classification System.

BACKGROUND: Anterior cruciate ligament (ACL) rupture is the most common ligament injury treated surgically by orthopaedic surgeons. The gold standard for the treatment of the majority of primary ACL tears is ACL reconstruction. However, novel methods of repair, such as bridge-enhanced ACL repair (BEAR), are currently being investigated as alternatives to reconstruction. To assess patients for midsubstance repair suitability, clarify the prognostic implications of injury location and damage, and evaluate the results of a repair technique, it is important to have a baseline classification system or grading scale that is reproducible across surgeons, particularly for multicenter collaboration. Currently, no such system or scale exists. PURPOSE: To develop an arthroscopic ACL tear classification system and to evaluate its interobserver reliability. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 3. METHODS: Eleven fellowship-trained orthopaedic surgeon investigators reviewed 75 video clips containing arthroscopic evaluation of a torn ACL and then completed the 6-question ACL Pathology Evaluation Form. Agreement statistics including exact agreement, Fleiss κ, Gwet agreement coefficient 1 (AC1), and Gwet AC2 were then calculated to assess interobserver reliability. RESULTS: In aggregate, the multiple assessments of observer reproducibility revealed that surgeon participants in this study, when evaluating the same injury, agreed roughly 80% of the time on whether (1) at least 50% of the tibial footprint remained, (2) the remaining tibial stump was ≥10 mm, and (3) the injury was therefore reparable using the BEAR procedure. Participants also agreed roughly 60% of the time on exactly how many suturable bundles were available. These characteristics are believed to be most important, among those studied, in determining whether a torn ACL is amenable to midsubstance repair. CONCLUSION: This study is the first of its kind to demonstrate the interobserver reliability of arthroscopic classification of ACL tears. We have demonstrated that this classification system, though not ideally reproducible, is reliable enough across surgeons at multiple institutions for use in multicenter studies. REGISTRATION: NCT03776162 (ClinicalTrials.gov identifier).

Predicting the Need for Surgical Intervention Prior to First Encounter for Individuals With Knee Complaints: A Novel Approach.

BACKGROUND: Orthopaedic complaints, particularly those relating to the knee, are some of the most common conditions that bring patients to the hospital. Many patients bypass their primary care physician to seek the care of an orthopaedic surgeon without referral, leaving the surgeon to manage an increasingly large number of patients, many of whom will never require surgery. PURPOSE: To develop a brief questionnaire that can be administered via phone/web at the time of appointment request to predict an individual patient's probability of requiring surgical intervention. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: All patients (N = 1307) seeking an appointment for a new knee-related complaint completed a branching-logic questionnaire. A retrospective chart review was conducted following the conclusion of each patient's episode of care to determine whether surgery was recommended. Logistic regression models were used to predict the risk of surgery based on triage question responses, basic demographics (age, sex), and laterality (unilateral vs bilateral). The ability of the models to discriminate between those who did and did not receive a surgical recommendation was measured with a concordance index. RESULTS: The model provided a high level of discrimination between surgical and nonsurgical cases (concordance index, 0.69). Recent injury with inability to walk and no recent injury with no pain were both associated with an increased probability of receiving a recommendation of surgical intervention as compared with patients who reported pain without recent injury (odds ratio [OR]: 3.51 [P < .001] and 2.78 [P = .008], respectively). A unilateral complaint was associated with needing surgical intervention (OR, 4.52 [P < .001]). Age had a significant nonlinear relationship with odds of needing of surgery, with middle-aged patients (range, 20-50 years) having the greatest odds. CONCLUSION: The current model, which utilizes demographic questions and portions of a routine history alone, was able to accurately identify individuals who are most likely (up to 65% probability) and least likely (<5% probability) to need knee surgery. This model can quickly and easily conduct triage at the time of appointment request to ensure that patients with the highest likelihood of receiving a recommendation for surgical intervention are seen by surgical providers, while those who are unlikely to receive such a recommendation can be seen by nonsurgical providers.

Arthroplasty studies with greater than 1000 participants: analysis of follow-up methods.

BACKGROUND: The use of patient-reported outcome measures (PROMs) has become a mainstay of orthopedic joint arthroplasty research. Large studies with >1000 participants are vital to orthopedic research, as they allow for comprehensive multivariable analysis. Achieving high follow-up rates minimizes potential response bias. Maintaining adequate follow-up rates becomes more challenging as sample size increases. We aimed to systematically review the present literature to determine the follow-up rates of large cohorts/registries of total joint arthroplasty patients and to identify factors associated with successful collection of PROMs. METHODS: A comprehensive literature search of PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Inclusion criteria were: ≥1000 participants, ≥6 months of postoperative follow-up, and use of validated PROMs postoperatively. RESULTS: Of 720 abstracts screened, 21 studies met inclusion criteria. Only 2 studies reported achieving a PROM follow-up rate ≥80%, but neither collected PROMs preoperatively. The median rate of follow-up was 70%, and the median number of patients was 2970. Only 38% (8 of 21) of studies collected baseline PROMs prior to surgery. CONCLUSIONS: Very few studies in the present literature have collected validated PROMs on ≥1000 patients with ≥80% follow-up; these parameters are conducive to comprehensive multivariable analysis, while maintaining study validity and avoiding follow-up bias. Federal funding and a central coordinating site may be helpful in achieving follow-up in studies of this magnitude. LEVEL OF EVIDENCE: Level III, systematic review of studies with Level of Evidence I-III.

A smart decision: smartphone use for operative data collection in arthroscopic shoulder instability surgery.

OBJECTIVE: This study tested validity, accuracy, and efficiency of the Orthopaedic Minimal Data Set Episode of Care (OME) compared with traditional operative report in arthroscopic surgery for shoulder instability. As of November 2017, OME had successfully captured baseline data on 97% of 18 700 eligible cases. MATERIALS AND METHODS: This study analyzes 100 cases entered into OME through smartphones by 12 surgeons at an institution from February to October 2015. A blinded reviewer extracted the same variables from operative report into a separate database. Completion rates and agreement were compared. They were assessed using raw percentages and McNemar's test (with continuity correction). Agreement between nominal variables was assessed by unweighted Cohen's kappa and a concordance correlation coefficient measured agreement between continuous variables. Efficiency was assessed by median time to complete. RESULTS: Of 37 variables, OME demonstrated equal or higher completion rates for all but 1 and had significantly higher capture rates for 49% (n = 18; P < .05). Of 33 nominal variables, raw proportional agreement was ≥0.90 for 76% (n = 25). Raw proportional agreement was perfect for 15% (n = 5); no agreement statistic could be calculated due to a single variable in operative note and OME. Calculated agreement statistic was substantial or better (κ > 0.61) for 51% (n = 17) for the 33 nominal variables. All continuous variables assessed (n = 4) demonstrated poor agreement (concordance correlation coefficient <0.90). Median time for completing OME was 103.5 (interquartile range, 80.5-151) seconds. CONCLUSIONS: The OME smartphone data capture system routinely captured more data than operative report and demonstrated acceptable agreement for nearly all nominal variables, yet took <2 minutes to complete on average.

Prospective Evaluation of the Patient Acceptable Symptom State to Identify Clinically Successful Anterior Cruciate Ligament Reconstruction.

BACKGROUND: The length of most patient-reported outcome measures creates significant response burden, which hampers follow-up rates. The Patient Acceptable Symptom State (PASS) is a single-item, patient-reported outcome measure that asks patients to consider all aspects of life to determine whether the state of their joint is satisfactory; this measure may be viable for tracking outcomes on a large scale. HYPOTHESIS: The PASS question would identify clinically successful anterior cruciate ligament reconstruction (ACLR) at 1-year follow-up with high sensitivity and moderate specificity. We defined "clinically successful" ACLR as changes in preoperative to postoperative scores on the Knee injury and Osteoarthritis Outcome Score (KOOS) pain subscale and the KOOS knee-related quality of life subscale in excess of minimal clinically important difference or final KOOS pain or knee-related quality of life subscale scores in excess of previously defined PASS thresholds. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 2. METHODS: Patients enrolled in a prospective longitudinal cohort completed patient-reported outcome measures immediately before primary ACLR. At 1-year follow-up, patients completed the same patient-reported outcome measures and answered the PASS question: "Taking into account all the activity you have during your daily life, your level of pain, and also your activity limitations and participation restrictions, do you consider the current state of your knee satisfactory?" RESULTS: A total of 555 patients enrolled in our cohort; 464 were eligible for this study. Of these, 300 patients (64.7%) completed 1-year follow-up, of whom 83.3% reported satisfaction with their knee after surgery. The PASS question demonstrated high sensitivity to identify clinically successful ACLR (92.6%; 95% CI, 88.4%-95.6%). The specificity of the question was 47.1% (95% CI, 35.1%-59.5%). The overall agreement between the PASS and our KOOS-based criteria for clinically successful intervention was 81.9%, and the kappa value indicated moderate agreement between the two methods (κ = 0.44). CONCLUSION: The PASS question identifies individuals who have experienced clinically successful ACLR with high sensitivity. The limitation of the PASS is its low specificity, which we calculated to be 47.1%. Answering "no" to the PASS question meant that a patient neither improved after surgery nor achieved an acceptable final state of knee health. The brevity, interpretability, and correlation of the PASS question with significant improvements on various KOOS subscales make it a viable option in tracking ACLR outcomes on a national or global scale.

Development of the KOOSglobal Platform to Measure Patient-Reported Outcomes After Anterior Cruciate Ligament Reconstruction.

BACKGROUND: The Knee injury and Osteoarthritis Outcome Score (KOOS) has demonstrated inferior psychometric properties when compared with the International Knee Documentation Committee (IKDC) subjective knee form when assessing outcomes after anterior cruciate ligament (ACL) reconstruction. The KOOS, Joint Replacement (KOOS, JR) is a validated short-form instrument to assess patient-reported outcomes (PROs) after knee arthroplasty, and the purpose of this study was to determine if augmenting the KOOS, JR with additional KOOS items would allow for the creation of a short-form KOOS-based global knee score for patients undergoing ACL reconstruction, with psychometric properties similar to those of the IKDC. HYPOTHESIS: An augmented version of the KOOS, JR could be created that would demonstrate convergent validity with the IKDC but avoid the ceiling effects and limitations previously noted with several of the KOOS subscales. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 2. METHODS: Based on preoperative and 2-year postoperative responses to the KOOS questionnaires from a sample of 1904 patients undergoing ACL reconstruction, an aggregate score combining the KOOS, JR and the 4 KOOS Quality of Life subscale questions, termed the KOOSglobal, was developed. Psychometric properties of the KOOSglobal were then compared with those of the IKDC subjective score. Convergent validity between the KOOSglobal and IKDC was assessed with a Spearman correlation (ρ). Responsiveness of the 2 instruments was assessed by calculating the pre- to postoperative effect size and relative efficiency. Finally, the presence of a preoperative floor or postoperative ceiling effect was defined with the threshold of 15% of patients reporting either the worst possible (0 for KOOSglobal and IKDC) or the best possible (100 for KOOSglobal and IKDC) scores, respectively. RESULTS: The newly developed KOOSglobal was responsive after ACL reconstruction and demonstrated convergent validity with the IKDC. The KOOSglobal significantly correlated with the IKDC scores (ρ = 0.91, P < .001), explained 83% of the variability in IKDC scores, and was similarly responsive (relative efficiency = 0.63). While there was a higher rate of perfect postoperative scores with the KOOSglobal (213 of 1904, 11%) than with the IKDC (6%), the KOOSglobal was still below the 15% ceiling effect threshold. CONCLUSION: The large ceiling effects limit the ability to use several of the KOOS subscales with the younger, more active ACL population. However, by creating an aggregate score from the KOOS, JR and 4 KOOS Quality of Life subscale questions, the 11-item KOOSglobal offers a responsive PRO tool after ACL reconstruction that converges with the information captured with the IKDC. Also, by offering the ability to calculate multiple scores from a single questionnaire, the KOOSglobal may provide the orthopaedic community a single PRO platform to be used across knee-related subspecialties. Registration: NCT00478894 ( ClinicalTrials.gov identifier).

To MOON and Back: Lessons Learned and Experience Gained Along the Way.

This article highlights the Multicenter Orthopedic Outcomes Network (MOON) study of anterior cruciate ligament reconstruction, from its inception in 1991 to the follow-on studies in progress currently. Lessons learned throughout the process are emphasized.

An in vitro Model to Mimic Selection of Replication-Competent HIV-1 Intersubtype Recombination in Dual or Superinfected Patients.

The low frequency of HIV-1 recombinants within entire viral populations in both individual patients and culture-based infection models impedes investigation of the underlying factors contributing to either the occurrence of recombinants or the survival of recombinants once they are formed. So far, most of the related studies have no consideration of recombinants' functionality. Here, we established a functional recombinant production (FRP) system to produce pure and functional HIV-1 intersubtype Env recombinants and utilized 454 pyrosequencing to investigate the distribution of over 4000 functional and non-functional recombination breakpoints from either the FRP system or dual infection cultures. The results revealed that most of the breakpoints converged in gp41 (62%) and C1 (25.3%) domains of gp120, which has strong correlation with the similarity between the two recombining sequences. Yet, the breakpoints also appeared in C2 (5.2%) and C5 (4.6%) domains not correlated with the recombining sequence similarity. Interestingly, none of the intersubtype gp120 recombinants recombined between C1 and gp41 regions either from the FRP system or from the dual infection culture, and very few from the HIV epidemic were functional. The present study suggests that the selection of functional Env recombinants is one of the reasons for the predominance of C1 and gp41 Env recombinants in the HIV epidemic, and it provides an in vitro model to mimic the selection of replication-competent HIV-1 intersubtype recombination in dual or superinfected patients.

Functional bottlenecks for generation of HIV-1 intersubtype Env recombinants.

BACKGROUND: Intersubtype recombination is a powerful driving force for HIV evolution, impacting both HIV-1 diversity within an infected individual and within the global epidemic. This study examines if viral protein function/fitness is the major constraint shaping selection of recombination hotspots in replication-competent HIV-1 progeny. A better understanding of the interplay between viral protein structure-function and recombination may provide insights into both vaccine design and drug development. RESULTS: In vitro HIV-1 dual infections were used to recombine subtypes A and D isolates and examine breakpoints in the Env glycoproteins. The entire env genes of 21 A/D recombinants with breakpoints in gp120 were non-functional when cloned into the laboratory strain, NL4-3. Likewise, cloning of A/D gp120 coding regions also produced dead viruses with non-functional Envs. 4/9 replication-competent viruses with functional Env's were obtained when just the V1-V5 regions of these same A/D recombinants (i.e. same A/D breakpoints as above) were cloned into NL4-3. CONCLUSION: These findings on functional A/D Env recombinants combined with structural models of Env suggest a conserved interplay between the C1 domain with C5 domain of gp120 and extracellular domain of gp41. Models also reveal a co-evolution within C1, C5, and ecto-gp41 domains which might explain the paucity of intersubtype recombination in the gp120 V1-V5 regions, despite their hypervariability. At least HIV-1 A/D intersubtype recombination in gp120 may result in a C1 from one subtype incompatible with a C5/gp41 from another subtype.

Factores de riesgo genéticos y no genéticos asociados con la esquizofrenia / Genetic and Nongenetic Risk Factors Associated with Schizophrenia

Introducción: la esquizofrenia se encuentra entre las enfermedades psiquiátricas más severas, su prevalencia media en la población adulta con independencia de la raza o el país de origen se sitúa en torno al 1%. El municipio de Holguín presenta un número importante de pacientes. Objetivo: determinar si existe agregación de la enfermedad al identificar la contribución de factores genéticos y describir el comportamiento de factores ambientales: antecedentes prenatales y perinatales, el nivel socio-económico y el funcionamiento familiar, asociados con la esquizofrenia. Métodos: se realizó un estudio de 30 casos y 60 controles para determinar si existe agregación familiar en la esquizofrenia. El universo de estudio estuvo constituido por el total de individuos en el área de salud con el diagnóstico de esquizofrenia y antecedentes patológicos familiares de esta enfermedad. La información se recogió por medio de la entrevista. Resultados: se evidenció que existe agregación familiar de la enfermedad en las familias estudiadas; los familiares de primer grado constituyeron los más afectados. Predominó el antecedente de desnutrición materna (22 casos para el 50,0% y 26 controles para el 38,2%) así como, el bajo peso al nacer (con 17 casos para el 30,8% y 18 para el 26,4% en los controles), que es significativo. El nivel socio-económico no fue significativo. Se demostró una fuerte asociación entre este factor de riesgo y la enfermedad en las familias disfuncionales que fueron las más frecuentes (19 en los casos para el 63,3%). Conclusiones: la contribución de los factores genéticos fue determinante al predominar en las familias de primer grado afectadas, también es importante la influencia de los factores no genéticos y todo ello demuestra la necesidad de crear estrategias dirigidas al asesoramiento de las familias en riesgo de padecer esta enfermedad.

Introduction: Schizophrenia is among the most severe psychiatric disorders, the mean disease prevalence in the adult population is around 1%, without considering the race or country of study. The municipality of Holguín reports a significant number of patients. Objective: to determine whether aggregation of the disease when identifying the genetic factors as well as to describe the behavior of environmental factors (prenatal and perinatal history, socio-economic level and family functioning) associated with schizophrenia. Methods: an analytical study of 30 cases and 60 control patients to determine whether familial aggregation for schizophrenia. The study group consisted of the total number of individuals in the health area with a diagnosis of schizophrenia and pathological family history of this disease. The information was collected through an interview. Results: the results showed that there was familial aggregation of the disease in the studied families, the first-degree relatives were the most affected ones. There was a predominance of maternal malnutrition history (22 cases for 50.0% and 26 controls for 38.2%) and the low birth weight with 17 cases for 30.8% and 18 of them for 26.4% in). The socioeconomic level was not significant. The results showed the strong association between this risk factor and the disease in dysfunctional families (19 cases to 63.3%). Conclusiones: the genetic factors was determinant and nongenetic factors showed the need for strategies aimed at counseling families at risk for this disease.

Factores de riesgo genéticos y no genéticos asociados con la esquizofrenia / Genetic and Nongenetic Risk F actors Associated with S chizophrenia

Introducción : la esquizofrenia se encuentra entre las enfermedades psiquiátricas más severas, su prevalencia media en la población adulta con independencia de la raza o el país de origen se sitúa en torno al 1 por ciento. El municipio de Holguín presenta un número importante de pacientes.Objetivo : determinar si existe agregación de la e nfermedad al identificar la contribución de factores genéticos y describir el comportamiento de factores ambientales:antecedentes prenatales y perinatales, el nivel socio - económico y el funcionamiento familiar, asociados con la esquizofrenia. Métodos : se realizó un estudio de 30 casos y 60 controles para determinar si existe agregación familiar en la esquizofrenia. El universo de estudio estuvo constituido por el total de individuos en el área de salud con el diagnóstico de e squizofrenia y antecedentes patológicos familiares de esta enfermedad . La información se recogió por medio de la entrevista. Resultados : se evidenció que existe agregación familiar de la enfermedad en las familias estudiadas; los familiares de primer grado constituyeron los más afectados . Predominó el antecedente de desnutrición materna 22 casos para el 50,0 por ciento y 26 controles para el 38,2 por ciento así como, el bajo peso al nacer con 17 casos para el 30,8 por ciento y 18 para el 26,4 por ciento en los controles, que es significativo. El nivel socio - económico no fue significativo. Se demostró un a fuerte asociación entre este factor de riesgo y la enfermedad en las familias disfuncionales que fueron las más frecuentes 19 en los casos para el 63,3 por ciento(AU)

Introduction : Schizophrenia is among the most severe psychiatric disorders, the mean disease prevalence in the adult population is around ,1 percent, without considering the race or country of study. The municipality of Holguín reports a significant number of patients.Objective : to determine whether aggregation of the disease when identify ing the genetic factors as well as to describe the behavior of environmental factors prenatal and perinatal history, socio - economic level and family functioning associate d with schizophrenia.Methods : a n analytical s tudy of ,30, cases and ,60, control patients to determine whether familial aggregation for schizophren ia. The study group consisted of the total number of individuals in the health area with a diagnosis of schizophrenia and pathological family history of this disease. The information was collected through an interview.Results : the results showed that ther e was familial aggregation of the disease in the studied families, the first - degree relatives were the most affected ones. There was a predominance of maternal malnutrition history 22 ca ses for ,50.0 percent, and ,26, controls for,3 8.2 percent, and the low birth weight with ,17, cases for ,30.8 percent, and ,18, of them for ,26.4 percent,in. The socioeconomic level was not significant. The results showed the strong association between this risk factor and the disease in dysfunctional families,19, cases to ,63.3 percent,Conclusions : the genetic facto rs was determinant and nonge netic factors showed the need for strategies aimed at counseling families at risk for this disease(AU)