A Multi-site Case Study of Care Coordination Between Primary Care and Specialty Care.

BACKGROUND: Care coordination is critical for patients with multiple chronic conditions, but fragmentation of care persists. Providers' perspectives of facilitators and barriers to coordination are needed to improve care. OBJECTIVES: We sought to understand providers' perspectives on care coordination for patients having multiple chronic diseases served by multiple providers. RESEARCH DESIGN: Based upon our earlier survey of patients with multiple chronic conditions, we selected 8 medical centers having high and low coordination. We interviewed providers to identify facilitators and barriers to coordination and compare them between patient-rated high sites and low sites and between primary care (PC)-mental health (MH) and PC-medical/surgical specialty care. SUBJECTS: Physicians, nurses and other clinicians in PC, cardiology, and MH (N=102) in 8 Veterans Affairs medical centers. RESULTS: We identified warm handoffs, professional relationships, and physical proximity as facilitators, and service agreements, reporting relationships and staffing as barriers. PC-MH coordination was reported as better than PC-medical/surgical specialty coordination. Facilitators were more prevalent and barriers less prevalent in sites rated high by patients than sites rated low, and between PC-MH than between PC-specialty care. DISCUSSION: We noted that professional relationships were highly related to coordination and both affected other facilitators and barriers and were affected by them. We suggested actions to improve relationships directly, and to address other facilitators and barriers that affect relationships and coordination. Among these is the use of the Primary Care Mental Health Integration model.

A Mixed Methods Study of the Association of Non-Veterans Affairs Care With Veterans' and Clinicians' Experiences of Care Coordination.

BACKGROUND: Poor coordination between the Department of Veterans Affairs (VA) and non-VA care may negatively impact health care quality. Recent legislation is intended to increase Veterans' access to care, in part through increased use of non-VA care. However, a possible consequence may be diminished patient experiences of coordination. OBJECTIVE: The objective of this study was to determine VA patients' and clinicians' experiences of coordination across VA and non-VA settings. DESIGN: Observational mixed methods using patient surveys and clinician interviews. Sampled patients were diagnosed with type 2 diabetes mellitus and either cardiovascular or mental health comorbidities. PARTICIPANTS AND MEASURES: Patient perspectives on coordination were elicited between April and September 2016 through a national survey supplemented with VA administrative records (N=5372). Coordination was measured with the 8-dimension Patient Perceptions of Integrated Care survey. Receipt of non-VA care was measured through patient self-report. Clinician perspectives were elicited through individual interviews (N=100) between May and October 2017. RESULTS: Veterans who received both VA and non-VA care reported significantly worse care coordination experiences than Veterans who only receive care in VA. Clinicians report limited information exchange capabilities, which, combined with bureaucratic and opaque procedures, adversely impact clinical decision-making. CONCLUSIONS: VA is working through a shift in how Veterans receive health care by increasing access to care from non-VA providers. Study findings suggest that VA should prioritize coordination of care in addition to access. This could include requiring monitoring of patient-experienced care coordination, surveys of referring and consulting clinicians, and pilot testing and evaluation of interventions to improve coordination.

Organizational Coordination and Patient Experiences of Specialty Care Integration.

BACKGROUND: Delivering care to patients with complex healthcare needs benefits from coordination among healthcare providers. Greater levels of care coordination have been associated with more favorable patient experiences, cost management, and lower utilization of services. Organizational approaches consider how systems, practices, and relationships influence coordination and associated outcomes. OBJECTIVE: Examine measures of organizational coordination and their association with patient experiences of care coordination involving specialists. DESIGN: Cross-sectional surveys of patients and primary care providers (PCPs). PARTICIPANTS: Final sample included 3183 patients matched to 233 PCPs from the Veterans Health Administration. All patients had a diagnosis of type 2 diabetes mellitus and one of four other conditions: hypertension; congestive heart failure; depression/anxiety; or severe mental illness/posttraumatic stress disorder. MAIN MEASURES: Patients completed a survey assessing perceptions of coordinated care. We examined ratings on three domains: specialist knowledge management; knowledge integration across settings and time; and knowledge fragmentation across settings and time. We created care coordination measures involving the PCP and three specialty provider types. PCPs provided ratings on relational coordination for specialists, feedback coordination, and team coordination. We aligned patient's specialty services used with corresponding PCP ratings of that specialty. KEY RESULTS: Patient ratings were significantly lower on specialist knowledge management and knowledge integration when either PCPs did not use feedback coordination (b = - .20; b = - .17, respectively) or rated feedback coordination lower (b = - .08 for both). Teamwork was significantly related to specialist knowledge management (b = .06), knowledge integration (b = .04); and knowledge fragmentation (b = - .04). Relational coordination was related to coordination between the primary care provider and (i) diabetes specialist (b = .09) and (ii) mental health provider (b = .12). CONCLUSIONS: Practices to improve provider coordination within and across primary care and specialty care services may improve patient experiences of care coordination. Improvements in these areas may improve care efficiency and effectiveness.

Survey of Patient-Centered Coordination of Care for Diabetes with Cardiovascular and Mental Health Comorbidities in the Department of Veterans Affairs.

BACKGROUND: Multiple comorbidities thought to be associated with poor coordination due to the need for shared treatment plans and active involvement of patients, among other factors. Cardiovascular and mental health comorbidities present potential coordination challenges relative to diabetes. OBJECTIVE: To determine how cardiovascular and mental health comorbidities relate to patient-centered coordinated care in the Department of Veterans Affairs. DESIGN: This observational study used a 2 × 2 factorial design to determine how cardiovascular and mental health comorbidities are associated with patient perceptions of coordinated care among patients with type 2 diabetes mellitus as a focal condition. PARTICIPANTS: Five thousand eight hundred six patients attributed to 262 primary care providers, from a national sample of 29 medical centers, who had completed an online survey of patient-centered coordinated care in the Department of Veterans Affairs (VA). MAIN MEASURES: Eight dimensions from the Patient Perceptions of Integrated Care (PPIC) survey, a state-of-the-art measure of patients' perspective on coordinated and patient-centered care. KEY RESULTS: Mental health conditions were associated with significantly lower patient experiences of coordinated care. Hypotheses for disease severity were not supported, with associations in the hypothesized direction for only one dimension. CONCLUSIONS: Results suggest that VA may be adequately addressing coordination needs related to cardiovascular conditions, but more attention could be placed on coordination for mental health conditions. While specialized programs for more severe conditions (e.g., heart failure and serious mental illness) are important, coordination is also needed for more common, less severe conditions (e.g., hypertension, depression, anxiety). Strengthening coordination for common, less severe conditions is particularly important as VA develops alternative models (e.g., community care) that may negatively impact the degree to which care is coordinated.

Organizational predictors of coordination in inpatient medicine.

BACKGROUND: As the care of hospitalized patients becomes more complex, intraprofessional coordination among nurses and among physicians, and interprofessional coordination between these groups are likely to play an increasingly important role in the provision of hospital care. PURPOSE: The purpose of this study was to identify the independent effects of organizational factors on provider ratings of overall coordination in inpatient medicine (OCIM). METHODOLOGY/APPROACH: This was an exploratory cross-sectional, descriptive study. Primary data were collected between June 2010 and September 2011 through surveys of inpatient medicine nurse managers, physicians, and chiefs of medicine at 36 Veterans Health Administration medical centers. Secondary data from the 2011 Veterans Health Administration national survey of nurses were also used. Individual-level data were aggregated and analyzed at the facility level. Multivariate linear regression models were used to assess the relationship between 55 organizational factors and provider ratings of OCIM. FINDINGS: Organizational factors that were common across models and associated with better provider ratings of OCIM included provider perceptions that the goals of senior leadership are aligned with those of the inpatient service and that the facility is committed to the highest quality of patient care, having resources and staff that enable clinicians to do their jobs, and use of strategies that enhance interactions and communication among and between nurses and physicians. PRACTICE IMPLICATIONS: To improve intraprofessional and interprofessional coordination and, consequently, patient care, facilities should consider making patient care quality a more important strategic organizational priority; ensuring that providers have the staffing, training, supplies, and other resources they need to do their jobs; and implementing strategies that improve interprofessional communication and working relationships, such as multidisciplinary rounding.

Impact of provider coordination on nurse and physician perceptions of patient care quality.

The objective of this study was to assess the role of provider coordination on nurse manager and physician perceptions of care quality, while controlling for organizational factors. Findings indicated that nurse-nurse coordination was positively associated with nurse manager perceptions of care quality; neither physician-physician nor physician-nurse coordination was associated with physician perceptions. Organizational factors associated with positive perceptions of care quality included facility support of education for nurses and physicians, and the use of multidisciplinary rounding.

Association between use of clinician performance information and patient experience.

OBJECTIVES: To study the association between the collection and use of clinician performance information in physician practices and patient experience in primary care. STUDY DESIGN: Patient experience scores are calculated from the 2018-2019 Massachusetts Statewide Survey of Adult Patient Experience of Primary Care. Physicians were attributed to physician practices using the Massachusetts Healthcare Quality Provider database. Scores were matched to information on the collection or use of clinician performance information from the National Survey of Healthcare Organizations and Systems using practice name and location. METHODS: We conducted observational multivariant generalized linear regression at the patient level where the dependent variables were 1 of 9 patient experience scores and the independent variables were 1 of 5 domains in the collection or use of performance information of the practice. Patient-level controls included self-reported general health, self-reported mental health, age, sex, education, and race/ethnicity. Practice-level controls include the size of the practice and the availability of weekend and evening hours. RESULTS: Nearly 90% of practices in our sample collect or use clinician performance information. High patient experience scores were associated with whether any information was collected and used, especially with whether the practice shared this information internally to compare. Among practices that used clinician performance information, patient experience was not associated with whether the information was used in more aspects of care. CONCLUSIONS: The collection and use of clinician performance information were associated with better primary care patient experience among physician practices. Deliberate efforts to use clinician performance information in ways that cultivate clinicians' intrinsic motivation may be especially effective for quality improvement.

Patient-provider language concordance and colorectal cancer screening.

BACKGROUND AND OBJECTIVE: Patient-provider language barriers may play a role in health-care disparities, including obtaining colorectal cancer (CRC) screening. Professional interpreters and language-concordant providers may mitigate these disparities. DESIGN, SUBJECTS, AND MAIN MEASURES: We performed a retrospective cohort study of individuals age 50 years and older who were categorized as English-Concordant (spoke English at home, n = 21,594); Other Language-Concordant (did not speak English at home but someone at their provider's office spoke their language, n = 1,463); or Other Language-Discordant (did not speak English at home and no one at their provider's spoke their language, n = 240). Multivariate logistic regression assessed the association of language concordance with colorectal cancer screening. KEY RESULTS: Compared to English speakers, non-English speakers had lower use of colorectal cancer screening (30.7% vs 50.8%; OR, 0.63; 95% CI, 0.51-0.76). Compared to the English-Concordant group, the Language-Discordant group had similar screening (adjusted OR, 0.84; 95% CI, 0.58-1.21), while the Language-Concordant group had lower screening (adjusted OR, 0.57; 95% CI, 0.46-0.71). CONCLUSIONS: Rates of CRC screening are lower in individuals who do not speak English at home compared to those who do. However, the Language-Discordant cohort had similar rates to those with English concordance, while the Language-Concordant cohort had lower rates of CRC screening. This may be due to unmeasured differences among the cohorts in patient, provider, and health care system characteristics. These results suggest that providers should especially promote the importance of CRC screening to non-English speaking patients, but that language barriers do not fully account for CRC screening rate disparities in these populations.

Built spaces and features associated with user satisfaction in maternity waiting homes in Malawi.

OBJECTIVE: To assess satisfaction with maternity waiting home built spaces and features in women who are at risk for underutilizing maternity waiting homes (i.e. residential facilities that temporarily house near-term pregnant mothers close to healthcare facilities that provide obstetrical care). Specifically we wanted to answer the questions: (1) Are built spaces and features associated with maternity waiting home user satisfaction? (2) Can built spaces and features designed to improve hygiene, comfort, privacy and function improve maternity waiting home user satisfaction? And (3) Which built spaces and features are most important for maternity waiting home user satisfaction? DESIGN: A cross-sectional study comparing satisfaction with standard and non-standard maternity waiting home designs. Between December 2016 and February 2017 we surveyed expectant mothers at two maternity waiting homes that differed in their design of built spaces and features. We used bivariate analyses to assess if built spaces and features were associated with satisfaction. We compared ratings of built spaces and features between the two maternity waiting homes using chi-squares and t-tests to assess if design features to improve hygiene, comfort, privacy and function were associated with higher satisfaction. We used exploratory robust regression analysis to examine the relationship between built spaces and features and maternity waiting home satisfaction. SETTING: Two maternity waiting homes in Malawi, one that incorporated non-standardized design features to improve hygiene, comfort, privacy, and function (Kasungu maternity waiting home) and the other that had a standard maternity waiting home design (Dowa maternity waiting home). PARTICIPANTS: 322 expectant mothers at risk for underutilizing maternity waiting homes (i.e. first-time mothers and those with no pregnancy risk factors) who had stayed at the Kasungu or Dowa maternity waiting homes. FINDINGS: There were significant differences in ratings of built spaces and features between the two differently designed maternity waiting homes, with the non-standard design having higher ratings for: adequacy of toilets, and ratings of heating/cooling, air and water quality, sanitation, toilets/showers and kitchen facilities, building maintenance, sleep area, private storage space, comfort level, outdoor spaces and overall satisfaction (p = <.0001 for all). The final regression model showed that built spaces and features that are most important for maternity waiting home user satisfaction are toilets/showers, guardian spaces, safety, building maintenance, sleep area and private storage space (R2 = 0.28). KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: The design of maternity waiting home built spaces and features is associated with user satisfaction in women at risk for underutilizing maternity waiting homes, especially related to toilets/showers, guardian spaces, safety, building maintenance, sleep area and private storage space. Improving maternity waiting home built spaces and features may offer a promising area for improving maternity waiting home satisfaction and reducing barriers to maternity waiting home use.

Development of an Adverse Event Surveillance Model for Outpatient Surgery in the Veterans Health Administration.

OBJECTIVE: Develop and validate a surveillance model to identify outpatient surgical adverse events (AEs) based on previously developed electronic triggers. DATA SOURCES: Veterans Health Administration's Corporate Data Warehouse. STUDY DESIGN: Six surgical AE triggers, including postoperative emergency room visits and hospitalizations, were applied to FY2012-2014 outpatient surgeries (n = 744,355). We randomly sampled trigger-flagged and unflagged cases for nurse chart review to document AEs and measured positive predictive value (PPV) for triggers. Next, we used chart review data to iteratively estimate multilevel logistic regression models to predict the probability of an AE, starting with the six triggers and adding in patient, procedure, and facility characteristics to improve model fit. We validated the final model by applying the coefficients to FY2015 outpatient surgery data (n = 256,690) and reviewing charts for cases at high and moderate probability of an AE. PRINCIPAL FINDINGS: Of 1,730 FY2012-2014 reviewed surgeries, 350 had an AE (20 percent). The final surveillance model c-statistic was 0.81. In FY2015 surgeries with >0.8 predicted probability of an AE (n = 405, 0.15 percent), PPV was 85 percent; in surgeries with a 0.4-0.5 predicted probability of an AE, PPV was 38 percent. CONCLUSIONS: The surveillance model performed well, accurately identifying outpatient surgeries with a high probability of an AE.

Factors Associated with Hospital Admission after Outpatient Surgery in the Veterans Health Administration.

OBJECTIVE: To examine factors associated with 0- to 7-day admission after outpatient surgery in high-volume specialties: general surgery, orthopedics, urology, ear/nose/throat, and podiatry. STUDY DESIGN: We calculated rates and assessed diagnosis codes for 0- to 7-day admission after outpatient surgery for Centers for Medicare and Medicaid Services (CMS) and Veterans Health Administration (VA) dually enrolled patients age 65 and older. We also estimated separate multilevel logistic regression models to compare patient, procedure, and facility characteristics associated with postoperative admission. DATA COLLECTION: 2011-2013 surgical encounter data from the VA Corporate Data Warehouse; geographic data from the Area Health Resources File; CMS enrollment and hospital admission data. PRINCIPAL FINDINGS: Among 63,585 outpatient surgeries in 124 facilities, 0- to 7-day admission rates ranged from 5 percent (podiatry) to 28 percent (urology); nearly 66 percent of the admissions occurred on the day of surgery. Only 97 admissions were detected in the CMS data (1 percent). Surgical complications were diagnosed in 4 percent of admissions. Procedure complexity, measured by relative value units or anesthesia risk score, was associated with admission across all specialties. CONCLUSION: As many as 20 percent of VA outpatient surgeries result in an admission. Complex procedures are more likely to be followed by admission, but more evidence is required to determine how many of these reflect potential safety or quality problems.

"It Keeps Us from Putting Drugs in Pockets": How a Public-Private Partnership for Hospital Management May Help Curb Corruption.

INTRODUCTION: Health care sector corruption diverts resources that could otherwise be used to improve access to health services. Use of private-sector practices such as a public-private partnership (PPP) model for hospital governance and management may reduce corruption. In 2011, a government-run hospital in Lesotho was replaced by a PPP hospital, offering an opportunity to compare hospital systems and practices. OBJECTIVE: To assess whether a PPP model in a hospital can help curb corruption. METHODS: We conducted 36 semistructured interviews with key informants between February 2013 and April 2013. We asked about hospital operations and practices at the government-run and PPP hospitals. We performed content analysis of interview data using a priori codes derived from the Corruption in the Health Sector framework and compared themes related with corruption between the hospitals. RESULTS: Corrupt practices that were described at the government-run hospital (theft, absenteeism, and shirking) were absent in the PPP hospital. In the PPP hospital, anticorruption mechanisms (controls on discretion, transparency, accountability, and detection and enforcement) were described in four management subsystems: human resources, facility and equipment management, drug supply, and security. CONCLUSION: The PPP hospital appeared to reduce corruption by controlling discretion and increasing accountability, transparency, and detection and enforcement. Changes imposed new norms that supported personal responsibility and minimized opportunities, incentives, and pressures to engage in corrupt practices. By implementing private-sector management practices, a PPP model for hospital governance and management may curb corruption. To assess the feasibility of a PPP, administrators should account for cost savings resulting from reduced corruption.

Organizational Factors Associated With Perceived Quality of Patient Care in Closed Intensive Care Units.

BACKGROUND: Improving patient care quality in intensive care units is increasingly important as intensive care unit services account for a growing proportion of hospital services. Organizational factors associated with quality of patient care in such units have been identified; however, most were examined in isolation, making it difficult to assess the relative importance of each. Furthermore, though most intensive care units now use a closed model, little research has been done in this specific context. OBJECTIVES: To examine the relative importance of organizational factors associated with patient care quality in closed intensive care units. METHOD: In a national exploratory, cross-sectional study focused on intensive care units at US Veterans Health Administration acute care hospitals, unit directors were surveyed about nurse and physician staffing, work resources and training, patient care coordination, rounding, and perceptions of patient care quality. Administrative records yielded data on patient volume and facility teaching status. Descriptive statistics, bivariate analyses, and regression modeling were used for data analysis. RESULTS: Sixty-nine completed surveys from directors of closed intensive care units were returned. Regression model results showed that better patient care coordination (ß = 0.43; P = .01) and having adequate work resources (ß = 0.26; P = .02) were significantly associated with higher levels of patient care quality in such units (R2 = 0.22). CONCLUSIONS: Augmenting work resources and/or focusing limited hospital resources on improving patient care coordination may be the most productive ways to improve patient care quality in closed intensive care units.

A Qualitative Study of Participation in Cardiac Rehabilitation Programs in an Integrated Health Care System.

INTRODUCTION: Despite strong incentives to use cardiac rehabilitation (CR), patient participation is low in the Veterans Health Administration (VHA). This is paradoxical given that VHA is an integrated health care system that offers a range of CR programs which should logically reduce barriers to access to CR participation. The purpose of this study was to better understand the contextual factors that influence patient participation in CR and how patients consider factors together when making decisions about CR participation. MATERIALS AND METHODS: Using a qualitative study design we examined patient and provider perceptions of CR across six VHA medical centers with high- and low-enrollment rates between December 2014 and October 2015. We conducted semistructured interviews with CR eligible patients who had both enrolled and not enrolled in CR (n = 16), cardiology providers who could refer patients to CR and CR staff who provided CR services (n = 15). Data were analyzed using grounded thematic techniques. RESULTS: We identified program and patient-specific factors related to CR participation. The four program factors were: program responsiveness to patient needs, CR schedule, specialized CR program equipment, and the CR program social environment. Program factors were primarily discussed by individuals associated with sites that had high CR enrollment rates. The patient-specific factor that promoted participation was patient perceptions of CR benefits. Disincentives to participation included competing conditions or obligations, logistical/cost challenges, convenience, and fear of exercise. CR participation entailed a complex process in which patients balanced factors that reinforced patient perceptions that CR was beneficial against factors that acted as disincentives to participation. CONCLUSIONS: CR participation was influenced by both program and patient factors. Patients weighed factors that fostered perceptions that CR was beneficial against factors that served as disincentives to CR participation when considering CR participation. High-enrollment sites may be better at countering disincentives to participate and/or improve patient perceptions of CR. Actionable ways to improve CR participation include encouraging providers to strongly and frequently endorse CR, educating patients about the importance and benefits of CR, emphasizing how exercises are individualized, supervised and monitored, educating patients about how CR is safe and effective, how CR offers peer support, and structuring CR programs to be responsive to patient needs in terms of duration, frequency, schedule, and location.

Building Systemwide Improvement Capability: Does an Organization's Strategy for Quality Improvement Matter?

OBJECTIVES: Health care organizations have used different strategies to implement quality improvement (QI) programs but with only mixed success in implementing and spreading QI organization-wide. This suggests that certain organizational strategies may be more successful than others in developing an organization's improvement capability. To investigate this, our study examined how the primary focus of grant-funded QI efforts relates to (1) key measures of grant success and (2) organization-level measures of success in QI and organizational learning. METHODS: Using a mixed-methods design, we conducted one-way analyses of variance to relate Veterans Affairs administrative survey data to data collected as part of a 3.5-year evaluation of 29 health care organization grant recipients. We then analyzed qualitative evidence from the evaluation to explain our results. RESULTS: We found that hospitals that focused on developing organizational infrastructure to support QI implementation compared with those that focused on training or conducting projects rated highest (at α = .05) on all 4 evaluation measures of grant success and all 3 systemwide survey measures of QI and organizational learning success. CONCLUSIONS: This study adds to the literature on developing organizational improvement capability and has practical implications for health care leaders. Focusing on either projects or staff training in isolation has limited value. Organizations are more likely to achieve systemwide transformation of improvement capability if their strategy emphasizes developing or strengthening organizational systems, structures, or processes to support direct improvement efforts.

A Public-Private Partnership Improves Clinical Performance In A Hospital Network In Lesotho.

Health care public-private partnerships (PPPs) between a government and the private sector are based on a business model that aims to leverage private-sector expertise to improve clinical performance in hospitals and other health facilities. Although the financial implications of such partnerships have been analyzed, few studies have examined the partnerships' impact on clinical performance outcomes. Using quantitative measures that reflected capacity, utilization, clinical quality, and patient outcomes, we compared a government-managed hospital network in Lesotho, Africa, and the new PPP-managed hospital network that replaced it. In addition, we used key informant interviews to help explain differences in performance. We found that the PPP-managed network delivered more and higher-quality services and achieved significant gains in clinical outcomes, compared to the government-managed network. We conclude that health care public-private partnerships may improve hospital performance in developing countries and that changes in management and leadership practices might account for differences in clinical outcomes.

Hospital Public-Private Partnerships in Low Resource Settings: Perceptions of How the Lesotho PPP Transformed Management Systems and Performance.

Abstract-Public-private partnerships (PPPs) seek to expand access to quality health services in ways that best leverage the capacities and resources of both sectors. There are few examples of PPPs in the hospital sector in developing countries, and little is known about how the involvement of the private sector transforms the delivery of health services in this context. In 2006, the government of Lesotho adopted a PPP approach for the health sector, contracting out to design, build, and operate a hospital network in its capital district. This case study examines differences between a government-run hospital and the PPP-run hospital that replaced it, using in-depth interviews with key informants, observation of management systems, and document review. Key informants emphasized changes in infrastructure, communication, human resource management, and organizational culture that improved quality and demand for services. Important drivers of improved performance included better defined policies and procedures, empowerment and training of managers and staff, and increased accountability. Well-functioning support systems kept the hospital clean and equipment functioning, reduced stock-outs, and allowed staff to do the jobs they were trained to do. The Lesotho PPP model provides insight into the mechanisms by which public-private partnerships may increase access and quality of care.

CFEOM1, the classic familial form of congenital fibrosis of the extraocular muscles, is genetically heterogeneous but does not result from mutations in ARIX.

BACKGROUND: To learn about the molecular etiology of strabismus, we are studying the genetic basis of 'congenital fibrosis of the extraocular muscles' (CFEOM). These syndromes are characterized by congenital restrictive ophthalmoplegia affecting muscles in the oculomotor and trochlear nerve distribution. Individuals with the classic form of CFEOM are born with bilateral ptosis and infraducted globes. When all affected members of a family have classic CFEOM, we classify the family as a CFEOM1 pedigree. We have previously determined that a CFEOM1 gene maps to the FEOM1 locus on chromosome 12cen. We now identify additional pedigrees with CFEOM1 to determine if the disorder is genetically heterogeneous and, if so, if any affected members of CFEOM1 pedigrees or sporadic cases of classic CFEOM harbor mutations in ARIX, the CFEOM2 disease gene. RESULTS: Eleven new CFEOM1 pedigrees were identified. All demonstrated autosomal dominant inheritance, and nine were consistent with linkage to FEOM1. Two small CFEOM1 families were not linked to FEOM1, and both were consistent with linkage to FEOM3. We screened two CFEOM1 families consistent with linkage to FEOM2 and 5 sporadic individuals with classic CFEOM and did not detect ARIX mutations. CONCLUSIONS: The phenotype of two small CFEOM1 families does not map to FEOM1, establishing genetic heterogeneity for this disorder. These two families may harbor mutations in the FEOM3 gene, as their phenotype is consistent with linkage to this locus. Thus far, we have not identified ARIX mutations in any affected members of CFEOM1 pedigrees or in any sporadic cases of classic CFEOM.

Familial unilateral Brown syndrome.

PURPOSE: To report a family in which three siblings have unilateral late-onset Brown syndrome. METHODS: The entire nuclear family underwent ophthalmologic evaluation. Orbital imaging and systemic workup were obtained to rule out local or systemic causes. Historic information was obtained from unavailable family members. The family's Brown syndrome trait was analyzed for linkage to the known congenital fibrosis syndrome loci and the CFEOM2 gene, ARIX, was sequenced in affected individuals. RESULTS: All affected siblings developed left-sided Brown syndrome, worse on awakening, at 12-13 years of age. No evidence of Brown syndrome could be identified in other family members, either by exam or history. No abnormalities of the trochlear-tendon complex could be documented. Haplotype analysis of the Brown syndrome phenotype was consistent with recessive inheritance at the DURS1 locus and dominant inheritance with reduced penetrance at the DURS1, DURS2, and FEOM1 loci. No mutations were detected in CFEOM2 gene, ARIX. CONCLUSIONS: We propose that a genetically determined predisposition to Brown syndrome is likely responsible for the observed manifestations in this family and that late age of onset and intermittent manifestations do not distinguish acquired from hereditary Brown syndrome. The pattern of inheritance of the Brown phenotype in this family could be either autosomal recessive or autosomal dominant with reduced penetrance. Our analysis only permitted the exclusion of the FEOM3 locus and the FEOM2 gene, ARIX. Future genetic studies of additional Brown syndrome families should shed additional light on the genetic basis of this disorder.