HTRA1, an age-related macular degeneration protease, processes extracellular matrix proteins EFEMP1 and TSP1.

High-temperature requirement protein A1 (HTRA1) is a serine protease secreted by a number of tissues including retinal pigment epithelium (RPE). A promoter variant of the gene encoding HTRA1 is part of a mutant allele that causes increased HTRA1 expression and contributed to age-related macular degeneration (AMD) in genomewide association studies. AMD is characterized by pathological development of drusen, extracellular deposits of proteins and lipids on the basal side of RPE. The molecular pathogenesis of AMD is not well understood, and understanding dysregulation of the extracellular matrix may be key. We assess the high-risk genotype at 10q26 by proteomic comparison of protein levels of RPE cells with and without the mutation. We show HTRA1 protein level is increased in high-risk RPE cells along with several extracellular matrix proteins, including known HTRA1 cleavage targets LTBP-1 and clusterin. In addition, two novel targets of HTRA1 have been identified: EFEMP1, an extracellular matrix protein mutated in Doyne honeycomb retinal dystrophy, a genetic eye disease similar to AMD, and thrombospondin 1 (TSP1), an inhibitor of angiogenesis. Our data support the role of RPE extracellular deposition with potential effects in compromised barrier to neovascularization in exudative AMD.

Multimodal Imaging of Central Retinal Disease Progression in a 2-Year Mean Follow-up of Retinitis Pigmentosa.

PURPOSE: To determine the rate of progression and optimal follow-up time in patients with advanced-stage retinitis pigmentosa (RP) comparing the use of fundus autofluorescence imaging and spectral-domain optical coherence tomography. DESIGN: Retrospective analysis of progression rate. METHODS: Longitudinal imaging follow-up in 71 patients with retinitis pigmentosa was studied using the main outcome measurements of hyperautofluoresent ring horizontal diameter and vertical diameter along with ellipsoid zone line width from spectral-domain optical coherence tomography. Test-retest reliability and the rate of progression were calculated. The interaction between the progression rates was tested for sex, age, mode of inheritance, and baseline measurement size. Symmetry of left and right eye progression rate was also tested. RESULTS: Significant progression was observed in >75% of patients during the 2-year mean follow-up. The mean annual progression rates of ellipsoid zone line and hyperautofluorescent ring horizontal diameter and vertical diameter were 0.45 degree (4.9%), 0.51 degree (4.1%), and 0.42 degree (4.0%), respectively. The ellipsoid zone line width and hyperautofluorescent ring horizontal diameter and vertical diameter had low test-retest variabilities of 8.9%, 9.5%, and 9.6%, respectively. This study is the first to demonstrate asymmetrical structural progression rate between right and left eye, which was found in 19% of patients. The rate of progression was significantly slower as the disease approached the fovea, supporting the theory that RP progresses in an exponential fashion. No significant interaction between progression rate and patient age, sex, or mode of inheritance was observed. CONCLUSIONS: Fundus autofluorescence and optical coherence tomography detect progression in patients with RP reliably and with strong correlation. These parameters may be useful alongside functional assessments as the outcome measurements for future therapeutic trials. Follow-up at 1-year intervals should be adequate to efficiently detect progression.

Rod metabolic demand drives progression in retinopathies.

Various factors are thought to cause the development and progression of disease in macular degeneration, diabetic retinopathy, and retinitis pigmentosa. Some of the deleterious processes include oxidative stress, hypoxia, metabolic derangement, genetics, and vasculopathy. In this review, we present a unified theory for the pathophysiology of several retinopathies based on the unique and intense metabolism of rod photoreceptors.

The role of organizational culture in retaining nursing workforce.

PURPOSE OF THE STUDY: We examined how organizational culture in nursing homes affects staff turnover, because culture is a first step to creating satisfactory work environments. DESIGN AND METHODS: Nursing home administrators were asked in 2009 to report on facility culture and staff turnover. We received responses from 419 of 1,056 administrators contacted. Respondents reported the strength of cultural values using scales from a Competing Values Framework and percent of staff leaving annually for Registered Nurse (RN), Licensed Practice Nurse (LPN), and nursing aide (NA) staff. We estimated negative binomial models predicting turnover. RESULTS: Turnover rates are lower than found in past but remain significantly higher among NAs than among RNs or LPNs. Facilities with stronger market values had increased turnover among RNs and LPNs, and among NAs when turnover was adjusted for facilities with few staff. Facilities emphasizing hierarchical internal processes had lower RN turnover. Group and developmental values focusing on staff and innovation only lowered LPN turnover. Finally, effects on NA turnover become insignificant when turnover was adjusted if voluntary turnover was reported. IMPLICATIONS: Organizational culture had differential effects on the turnover of RN, LPN, and NA staff that should be addressed in developing culture-change strategies. More flexible organizational culture values were important for LPN staff only, whereas unexpectedly, greater emphasis on rigid internal rules helped facilities retain RNs. Facilities with a stronger focus on customer needs had higher turnover among all staff.

The Quality Indicator Survey: background, implementation, and widespread change.

The Quality Indicator Survey (QIS) is the most comprehensive regulatory change to the nursing home survey process since the Omnibus Budget Reconciliation Act of 1987 (OBRA-87). In this article we describe the policy evolution that led to the QIS, summarize the QIS method and implementation, and profile the QIS survey results. Following over a decade of development, in 2007 the Centers for Medicare and Medicaid Services (CMS) began the national rollout of QIS. The intent was to improve consistency in the nursing home survey and to render the survey process more resident-centered and aligned with the intent of OBRA-87. We reviewed policy reports and firsthand accounts from the lead developer of the QIS methodology and leader of the national training contract for QIS. Changes in survey findings are profiled based on analysis of the publicly available Nursing Home Compare database from 2004 to 2010. Nineteen states implemented the QIS between 2007 and 2010, with nearly 20% of U.S. nursing homes receiving QIS surveys in 2010. Nursing homes surveyed with the QIS received more survey deficiencies on average than in the traditional survey; however, average numbers of deficiencies across states became more similar over the early implementation of QIS, with lower-than-average geographic areas experiencing increases and higher-than-average geographic areas experiencing decreases in survey deficiencies. The explicit and structured questioning of residents in the QIS is associated with increases in deficiencies related to choice, dignity, dental care, and nurse staffing. We describe ways in which the QIS affected the regulatory agencies, providers, and resident communities, although these effects are difficult to quantify. CMS's implementation of QIS is a significant step toward a more resident-centered, comprehensive, and consistent survey process. Substantial changes, however, are required not only among regulators but also among nursing homes. We argue that these new expectations and norms surrounding quality assessment and quality assurance are an important component of achieving culture change in U.S. nursing homes.

Adherence to Pap test guidelines: variation among Asians in California.

OBJECTIVES: To compare Pap screening in the previous 3 years among subgroups of Asian American women, aged 18 to 65 years. DESIGN: Analysis of data from the 2001 and 2003 California Health Interview Survey (CHIS), a cross-sectional population-based telephone survey. MAIN MEASURES: The survey elicited information from major Asian subgroups, including Chinese, Filipina, Japanese, Korean, South Asian, and Vietnamese. Surveys were administered in several languages, including Mandarin, Cantonese, Korean, and Vietnamese. Employing the Andersen behavioral model of health services utilization, this study fits logistic regression models to identify correlates of Pap screening within and across Asian American subgroups. These analyses use time living in the United States and English proficiency as acculturation measures. RESULTS: There were different independent correlates of Pap test receipt for the six Asian subgroups. English proficiency and income were independently associated with Pap screening among only one subgroup; education, time in the US, and insurance among three; and age and usual source of care among four subgroups. Unmarried women were more likely to report not having a Pap test in the past three years across all six subgroups. CONCLUSIONS: Based on these differences, programs and policies targeting the health of Asian American women should consider tailoring interventions to match the needs of different ethnic groups. Specifically, program materials should strive to be both culturally sensitive and linguistically appropriate for all target populations.

Motivation to change chronic illness care: results from a national evaluation of quality improvement collaboratives.

This article examines the motivation of health care professionals to improve quality of chronic illness care using the Chronic Care Model and Plan-Do-Study-Act cycles. The findings suggest that organizational attempts to redesign care require support of activities initiated by practitioners and managers and an organizational commitment to quality improvement.

Pressure ulcer prevalence in long-term nursing home residents since the implementation of OBRA '87. Omnibus Budget Reconciliation Act.

OBJECTIVES: To evaluate change in pressure ulcer prevalence in long-term nursing home residents since the implementation of the Omnibus Budget Reconciliation Act of 1987 (OBRA '87). DESIGN: Cross-sectional comparison of two time periods. SETTING: Ninety-two nursing homes scheduled for a quality-of-care survey randomly selected from 22 representative states. PARTICIPANTS: Four thousand six hundred seventy-nine residents who had resided in the facility for at least 100 days were evaluated: 2,336 during 1992-1994 and 2,343 during 1997-1998. MEASUREMENTS: Trained registered nurses collected data on pressure ulcer prevalence, stage, and risk factors from medical record review during on-site evaluations. Risk-adjusted differences were estimated using logistic regression. RESULTS: Unadjusted prevalence rates for all stages of pressure ulcers (8.52% vs 8.54%, P =.983) and those rated stage 2 or greater (5.31% vs 5.63%, P =.624) did not differ between the two time periods. After adjustment for urinary incontinence, immobility, poor nutrition, and history of previous pressure ulcers, the relative odds of having a pressure ulcer in 1992/4 versus 1997/8 was 1.06 (95% confidence interval (CI) = 0.84-1.34) for all stages and 1.21 (95% CI = 0.92-1.60) for stages 2 and greater. CONCLUSIONS: No change in pressure ulcer prevalence was demonstrated since implementation of OBRA '87 in this nationally derived sample of long-term nursing home residents.