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Anand S Iyer,1–3 James M Wells,1,3,4 Surya P Bhatt,1,3 deNay P Kirkpatrick,1,3 Patricia Sawyer,5 Cynthia J Brown,4,5 Richard M Allman,6 Marie A Bakitas,5,7,8 Mark T Dransfield1,3,4 1Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; 2Health Services, Outcomes, and Effectiveness Research Training Program, University of Alabama at Birmingham, Birmingham, AL, USA; 3Department of Medicine, Lung Health Center, University of Alabama at Birmingham, Birmingham, AL, USA; 4Veterans Affairs Medical Center, Birmingham, AL, USA; 5Department of Medicine, Division of Gerontology, Geriatrics, and Palliative Care, University of Alabama at Birmingham, Birmingham, AL, USA; 6Department of Medicine, George Washington University School of Medicine, Washington, DC, USA; 7Department of Medicine, Center for Palliative and Supportive Care, Division of Geriatrics, Gerontology, and Palliative Care Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; 8School of Nursing, University of Alabama at Birmingham, Birmingham, AL, USA Background: Social isolation is a common experience in patients with COPD but is not captured by existing patient-reported outcomes, and its association with clinical outcomes is unknown. Methods: We prospectively enrolled adults with stable COPD who completed the University of Alabama at Birmingham Life Space Assessment (LSA) (range: 0–120, restricted Life-Space mobility: ≤60 and a marker of social isolation in older adults); six-minute walk test (6MWT), and the University of California at San Diego Shortness of Breath Questionnaire, COPD Assessment Test, and Hospital Anxiety and Depression Scale. The occurrence of severe exacerbations (emergency room visit or hospitalization) was recorded by review of the electronic record up to 1 year after enrollment. We determined associations between Life-Space mobility and clinical outcomes using regression analyses. Results: Fifty subjects had a mean ± SD %-predicted FEV1 of 42.9±15.5, and 23 (46%) had restricted Life-Space mobility. After adjusting for age, gender, %-predicted FEV1, comorbidity count, inhaled corticosteroid/long-acting beta2-agonist use, and prior cardiopulmonary rehabilitation, subjects with restricted Life-Space had an increased risk for severe exacerbations (adjusted incidence rate ratio 4.65, 95% CI 1.19–18.23, P=0.03). LSA scores were associated with 6MWD (R=0.50, P

Craig J Brown The Eye Center, Fayetteville, AR, USA Abstract: Cilioretinal artery occlusion is a cause of sudden, often catastrophic loss of central vision. There are no established effective treatments. Recently, a patient presented 24 hours after a cilioretinal artery occlusion, following a cardiac catheterization prior to which her blood thinners had been discontinued. Lacking an effective way to address the severe retinal ischemic oxidative stress, she was offered, under compassionate use, a multivitamin complex designed to address retinal ischemia and oxidative stress. Significant components of this product are l-methylfolate and n-acetyl cysteine. The patient experienced a rapid unexpected improvement in vision and preservation of retinal structure, suggesting that marked improvement in retinal artery occlusions outcomes may be possible as late as 24 hours postocclusion. This is the third reported case of cilioretinal artery occlusion associated with cardiac catheterization. Keywords: retinopathy, MTHFR, homocysteine, l-methylfolate, stroke, NAC

Craig J Brown,1 Faical Akaichi21The Eye Center, Fayetteville, AR, USA; 2Scotland’s Rural College, Edinburgh, UKPurpose: To evaluate risk factors associated with posterior subcapsular cataract (PSC) development and the relationship between vitamin D deficiency and etiology of PSC.Methods: Of 195 consecutive patients from a private ophthalmology practice, diagnosed with PSC, serum vitamin D3 (25-OH D) levels were obtained for 175, and associations among risk factors, comorbidities, and PSC were assessed.Results: In all 175 PSC patients, mean 25-OH D levels were low (24 ng/mL ±11 SD) compared with age/sex-matched standards. Significant differences in 25-OH D levels were noted between PSC subjects taking/not taking calcium supplements, systemic steroids, osteoporosis medications, etc. Alone, smoking status and calcium channel blockers and/or topical steroids use made no significant difference in PSC subjects 25-OH D levels, but two or more of these factors were associated with lowered levels of 25-OH D (P

Background: Inactivation of the maternally or paternally derived X chromosome (XCI) initially occurs in a random manner in early development; however as tissues form, a 'patchiness' will occur in terms of which X is inactivated if cells positioned near each other are clonally descended from a common precursor. Determining the relationship between skewed XCI in different tissues and in different samples from the same tissue provides a molecular assessment of the developmental history of a particular tissue that can then be used to understand how genetic and epigenetic variation arises in development.Methods: XCI skewing was evaluated in and compared between amnion, chorion, trophoblast and mesenchyme using multiple sampling sites from 14 term placentae. XCI was also evaluated in chorionic villus samples obtained at multiple sites and depths from four additional term placentae. The pattern of variation was then compared with methylation variation associated with the H19/IGF2 imprinting control region (ICR); promoter regions of KISS1, PTPN6, CASP8 and APC; and LINE-1 elements.Results: Mean placental level of skewing for amnion and chorion are correlated, consistent with a common developmental origin of at least a component of these membranes from inner cell mass derivatives subsequent to XCI, while trophoblast appears to be derived independently, consistent with its origin from the trophectoderm. Villus samples taken from different depths spanning the fetal to maternal side of the placenta were highly clonally related. Comparing patterns of clonal growth identified through XCI to the distribution of epigenetic variation in other genomic regions suggests that some variation arises early in development (e.g. LINE-1 methylation), whereas other variation arises predominantly after villus tree formation (e.g. methylation at H19/IGF2 ICR).Conclusions: The patterns of XCI skewing are consistent with a model whereby each biopsied site of chorionic villi represents one or a few individual villus trees, each of which is clonally derived from only one or a few precursor cells. Sampling of placentae to evaluate changes associated with clinical pathology should be done with consideration of the tree-to-tree differences. A limitation of this study is the small number of placentas used and therefore placental-specific differences in variation could not be assessed. [ABSTRACT FROM AUTHOR]

Background: In a province-wide audit of patients undergoing treatment for rectal cancer in British Columbia in 1996, the 4-year rate of pelvic recurrence for stage 3 rectal cancer was 27%. The management guidelines were changed in 2002 to include adjuvant short-course preoperative radiation and total mesorectal excision surgical techniques. Education workshops were held to implement the protocol change.Methods: We performed a provincial audit of rectal cancer cases for patients treated in the year after the protocol change, and we compared the pelvic recurrence rates with those from the audit performed in 1996.Results: During a 12-month period beginning Oct. 1, 2003, a total of 367 patients underwent radical resection of rectal cancer with a curative intent. Preoperative adjuvant radiotherapy was used in 54% of cases (197/367). Median follow-up was 34.5 months, and 91% of patients were followed for at least 2 years. Relative to the 1996 cohort, there was a decreasing trend in 2-year overall pelvic recurrence rates in the 2003/04 cohort (9.6% v. 6.9%) and a significant decrease in recurrence among patients with stage 3 cancers (18.2% v. 9.2%; p = 0.020). Use of adjuvant radiation increased significantly (37% v. 65%; p < 0.001), and negative radial margins were achieved in 87% (319/367) of cases.Conclusion: The rates of pelvic recurrence were improved after changes in the management guidelines advocating increased use of total mesorectal excision surgery and preoperative radiation. Knowledge translation with an integrated strategy among surgeons and medical and radiation oncologists was successful in improving population outcomes among patients with rectal cancer. [ABSTRACT FROM AUTHOR]

BACKGROUND: Little is known regarding destinations and distances necessary for independent community ambulation after enactment of the Americans with Disability Act. OBJECTIVE: To qualitatively describe community locations visited by older adults and to determine ambulation distance required to visit these locations. DESIGN: Descriptive study. METHODS: Nineteen subjects, 65 years or older and who were independent with transportation, ambulation, and basic activities of daily living, were recruited from 4 senior centers in urban areas of central Alabama. The study was divided into 2 phases. In part 1, using qualitative methodology, older adults were interviewed to determine locations they visited in the community. In part 2, we visited the types of locations identified in part 1 and measured distances required to conduct business at each location. Obstacles, if any, to reaching these locations were identified. RESULTS: Subjects had a mean age of 76.6 (5.8) years; 80% were women, and 50% lived alone in the community. Locations visited by subjects were identified and measured. Researchers categorized locations as essential, essential to some people, and nonessential. Essential locations included bank, doctor's office, and either a grocery store, pharmacy, and department store or a 'superstore'. A minimum of approximately 200 m was required for community ambulation to most locations, although this distance varied significantly among locations. LIMITATIONS: Geographic location and urban setting may not reflect distances necessary for rural residents. CONCLUSIONS: Physical therapists can use the 200-m distance as a starting point for goal-setting for older adults desiring a return to community independence. [ABSTRACT FROM AUTHOR]

Background: In the mid-1990s, Cochlear Corporation introduced a cochlear implant (CI) to the market that was equipped with hardware that made it possible to record electrically evoked compound action potentials (ECAPs) from CI users of all ages. Over the course of the next decade, many studies were published that compared ECAP thresholds with levels used to program the speech processor of the Nucleus CI. In 2001 Advanced Bionics Corporation introduced the Clarion CII cochlear implant (the Clarion CII internal device is also known as the CII Bionic Ear). This cochlear implant was also equipped with a system that allowed measurement of the ECAP. While a great deal is known about how ECAP thresholds compare with the levels used to program the speech processor of the Nucleus CI, relatively few studies have reported comparisons between ECAP thresholds and the levels used to program the speech processor of the Advanced Bionics CI. Purpose: To explore the relationship between ECAP thresholds and behavioral measures of perceptual dynamic range for the range of stimuli commonly used to program the speech processor of the Advanced Bionics CI. Research Design: This prospective and experimental study uses correlational and descriptive statistics to define the relationship between ECAP thresholds and perceptual dynamic range measures. Study Sample: Twelve postlingually deafened adults participated in this study. All were experienced users of the Advanced Bionics CI system. Data Collection and Analysis: ECAP thresholds were recorded using the commercially available SoundWave software. Perceptual measures of threshold (T-level), most comfortable level (M-level), and maximum comfortable level (C-level) were obtained using both 'tone bursts' and 'speech bursts.' The relationship between these perceptual and electrophysiological variables was defined using paired t-tests as well as correlation and linear regression. Results: ECAP thresholds were significantly correlated with the perceptual dynamic range measures studied; however, correlations were not strong. Analysis of the individual data revealed considerable discrepancy between the contour of ECAP threshold versus electrode function and the behavioral loudness estimates used for programming. Conclusion: ECAP thresholds recorded from Advanced Bionics cochlear implant users always indicated levels where the programming stimulus was audible for the listener. However, the correlation between ECAP thresholds and M-levels (the primary metric used to program the speech processor of the Advanced Bionics CI), while statistically significant, was quite modest. If programming levels are to be determined on the basis of ECAP thresholds, care should be taken to ensure that stimulation is not uncomfortably loud, particularly on the basal electrodes in the array. [ABSTRACT FROM AUTHOR]

Background: Since the early 1990s, it has been possible to measure electrically evoked compound action potentials (ECAPs) from Nucleus cochlear implant users. Recording the ECAP does not require active participation by the subject, and the recordings are not adversely affected by attention or sleep, making this response an ideal tool for monitoring long-term changes. Previous research from our laboratory (Hughes et al, 2001) has shown that ECAP thresholds and slope of the ECAP growth functions are relatively stable over time. However, this conclusion was based on results obtained from a fairly limited number of study participants, each of whom used the Nucleus Cl24M cochlear implant and were followed for less than two years. Purpose: To evaluate the effect of long-term use of a cochlear implant on ECAP thresholds and slope of the ECAP input/output function for both pediatric and adult cochlear implant recipients. Research Design: A longitudinal study that describes how ECAP thresholds and growth functions change over a period of 96 mo following initial activation. Changes over time in ECAP threshold and slope of the ECAP growth function were analyzed, and effects of the subject's age, type of CI (cochlear implant), and stimulating electrode are included in the analysis. Study Sample: 134 Nucleus CI users participated in this study. All were profoundly deaf. This subject pool included 84 individuals (40 adults and 44 children) who used the Nucleus C124M cochlear implant and 50 individuals (21 adults and 29 children) who used the Nucleus C124R cochlear implant. Data Collection and Analysis: Electrodes 5, 10, 15, and 20 were stimulated, and ECAP growth functions were measured for each subject at regular intervals following the initial activation of the device. Results: Small increases in mean ECAP thresholds were observed for both pediatric and adult CI users between an 'early' visit that occurred within 3DS6 mo following hookup and a 'late' visit that occurred 4.8-6 yr later. For adults, the average increase in ECAP threshold was 3.94 CL (clinical programming units for Nucleus CIs). For children, the average increase was 4.16 CL. These differences, while small, were statistically significant. Slope of the ECAP growth functions measured over the same time interval did not change significantly. On average, pediatric CI users had ECAP thresholds that were 4DS5 CL units higher than the adult CI recipients. The most striking outcome from this study, however, was the finding that when compared with postlingually deafened adults, pediatric CI users had ECAP growth functions that were substantially steeper. The differences between the results obtained from children and those obtained from adults were statistically significant and largely independent of device type or stimulating electrode. Conclusion: Results from this study show ECAP thresholds and growth functions to change very little over a 5DS6 yr observation interval suggesting that long-term use of a CI is not likely to have a significant negative impact on the response of the peripheral auditory system. Pediatric CI users were shown to have, on average, higher ECAP thresholds and steeper ECAP growth functions than postlingually deafened adult CI users. This finding suggests potential differences between the two patient populations either in terms of the current fields within the cochlea or the effective distance between the stimulating electrode and the stimulable neural tissue. [ABSTRACT FROM AUTHOR]

Objective: The primary mission of hospital ships is to provide acute medical and surgical services to U.S. forces during military operations. Hospital ships also provide a hospital asset in support of disaster relief and humanitarian assistance (HA) operations. HA missions afford medical care to populations with vastly different sets of medical conditions from combat casualty care, which affects staffing requirements.Methods: Information from a variety of sources was reviewed to better understand hospital ship HA missions. Factors such as time on-site and location shape the mission and underlying goals.Results: Patient encounter data from previous HA missions were used to determine expected patient conditions encountered in various HA operations. These data points were used to project the medical staffing required for future missions.Conclusions: Further data collection, along with goal setting, must be performed to accomplish successful future HA missions. Refining staffing requirements allows deployments to accomplish needed HA and effectively reach underserved areas. [ABSTRACT FROM AUTHOR]