Nuclear cataract shows significant familial aggregation in an older population after adjustment for possible shared environmental factors.

PURPOSE: To quantify the association between siblings in age-related nuclear cataract, after adjusting for known environmental and personal risk factors. METHODS: All participants (probands) in the Salisbury Eye Evaluation (SEE) project and their locally resident siblings underwent digital slit lamp photography and were administered a questionnaire to assess risk factors for cataract including: age, gender, lifetime sun exposure, smoking and diabetes history, and use of alcohol and medications such as estrogens and steroids. In addition, blood pressure, body mass index, and serum antioxidants were measured in all participants. Lens photographs were graded by trained observers masked to the subjects' identity, using the Wilmer Cataract Grading System. The odds ratio for siblings for affectedness with nuclear cataract and the sibling correlation of nuclear cataract grade, after adjusting for covariates, were estimated with generalized estimating equations. RESULTS: Among 307 probands (mean age, 77.6 +/- 4.5 years) and 434 full siblings (mean age, 72.4 +/- 7.4 years), the average sibship size was 2.7 per family. After adjustment for covariates, the probability of development of nuclear cataract was significantly increased (odds ratio [OR] = 2.07, 95% confidence interval [CI], 1.30-3.30) among individuals with a sibling with nuclear cataract (nuclear grade > or = 3.0). The final fitted model indicated a magnitude of heritability for nuclear cataract of 35.6% (95% CI: 21.0%-50.3%) after adjustment for the covariates. CONCLUSIONS: Findings in this study are consistent with a genetic effect for age-related nuclear cataract, a common and clinically significant form of lens opacity.

Cataract surgery and subtype in a defined, older population: the SEECAT Project

AIM:

To describe the distribution of cataract subtypes present before surgery among a defined population of older, bilaterally pseudophakic individuals.

METHODS:

This was a cohort study of bilaterally pseudophakic individuals participating in the Salisbury Eye Evaluation (SEE), and their locally resident siblings. Subjects underwent slit lamp and retroillumination photography and grading using the Wilmer Cataract Grading System. For all individuals determined to be bilaterally pseudophakic, an attempt was made to determine for each eye the type(s) of cataract present before surgery, based on previous SEE photographs (for SEE participants) and/or medical records obtained from the operating ophthalmologist (for both SEE participants and their siblings).

RESULTS:

The mean age of 223 participants providing data in this study was 78.7 (SD 5.2) years, 19.3% of subjects were black and 60.1% female. The most common surgically removed cataract subtype in this population was pure nuclear (43.5%), followed by nuclear combined with posterior subcapsular cataract (PSC) (20.6%), and nuclear combined with cortical (13.9%); less common types were pure cortical (4.9%), pure PSC (4.5%), and PSC combined with cortical (2.7%). Factors such as sex and source of lens data (study photograph versus clinical record) did not significantly affect the distribution of lens opacity types, while PSC was significantly (p = 0.01) more common among younger people and nuclear cataract was significantly (p = 0.001) more common among white compared to black people.

CONCLUSION:

Epidemiological studies have suggested that the different subtypes of cataract are associated with different risk factors. As studies begin to identify new prevention strategies for cataract, it would appear likely that different strategies will be efficacious against different types of cataract. In this setting, it will be helpful to know which cataract types are most frequently associated with surgery. Among this older, majority white population, nuclear cataract showed a clear predominance among individuals having undergone surgery in both eyes. This may be contrasted with both clinic and population based studies of younger people, which have generally found PSC cataract to predominate.

Cortical, but not posterior subcapsular, cataract shows significant familial aggregation in an older population after adjustment for possible shared environmental factors.

PURPOSE:

To quantify the risk for age-related cortical cataract and posterior subcapsular cataract (PSC) associated with having an affected sibling after adjusting for known environmental and personal risk factors.

DESIGN:

Sibling cohort study.

PARTICIPANTS:

Participants in the ongoing Salisbury Eye Evaluation (SEE) study (n = 321; mean age, 78.1+/-4.2 years) and their locally resident siblings (n = 453; mean age, 72.6+/-7.4 years) were recruited at the time of Rounds 3 and 4 of the SEE study. INTERVENTION/TESTING METHODS: Retroillumination photographs of the lens were graded for the presence of cortical cataract and PSC with the Wilmer grading system. The residual correlation between siblings' cataract grades was estimated after adjustment for a number of factors (age; gender; race; lifetime exposure to ultraviolet-B light; cigarette, alcohol, estrogen, and steroid use; serum antioxidants; history of diabetes; blood pressure; and body mass index) suspected to be associated with the presence of cataract.

RESULTS:

The average sibship size was 2.7 per family. Multivariate analysis revealed the magnitude of heritability (h(2)) for cortical cataract to be 24% (95% CI, 6%-42%), whereas that for PSC was not statistically significant (h(2) 4%; 95% CI, 0%-11%) after adjustment for the covariates. The model revealed that increasing age, female gender, a history of diabetes, and black race increased the odds of cortical cataract, whereas higher levels of provitamin A were protective. A history of diabetes and steroid use increased the odds for PSC.

CONCLUSIONS:

This study is consistent with a significant genetic effect for age-related cortical cataract but not PSC.

The association between myopia and various subtypes of lens opacity: SEE (Salisbury Eye Evaluation) project.

PURPOSE: To establish the relationship between myopia and lens opacity. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Two thousand five hundred twenty participants from the Salisbury Eye Evaluation aged 65 to 84 years. METHODS: Participants filled out questionnaires regarding medical history, social habits, and a detailed history of distance spectacle wear. They underwent a full ocular examination. Lens photographs were taken for assessment of lens opacity using the Wilmer grading system. Multivariate logistic regression models using generalized estimating equations were used to analyze the relationship between lens opacity type and degree of myopia, while accounting for potential confounders. MAIN OUTCOME MEASURES: Presence of posterior subcapsular opacity, cortical opacity, or nuclear opacity. RESULTS: Significant associations were found between myopia and both nuclear and posterior subcapsular opacities. For nuclear opacity, the odds ratios (ORs) were 2.25 for myopia between -0.50 diopters (D) and -1.99 D (P<0.001), 3.65 for myopia between -2.00 D and -3.99 D (P<0.001), 4.54 for myopia between -4.00 D and -5.99 D (P<0.001), and 3.61 for myopia -6.00 D or more (P = 0.002). For posterior subcapsular cataracts, ORs were 1.59 for myopia between -0.50 D and -1.99 D (P = 0.11), 3.22 for myopia between -2.00 D and -3.99 D (P = 0.002), 5.36 for myopia between -4.00 D and -5.99 D (P<0.001), and 12.34 for myopia -6.00 D or more (P<0.001). No association was found between myopia and cortical opacity. The association between posterior subcapsular opacity and myopia was equally strong for those wearing glasses by age 21 years and for those without glasses; for nuclear opacity, significantly higher ORs were found for myopes who started wearing glasses after age 21. CONCLUSIONS: These results confirm the previously reported association between myopia, posterior subcapsular opacity, and nuclear opacity. Furthermore, the strong association between early spectacle wear and posterior subcapsular opacity among myopes, absent for nuclear opacity, suggests that myopia may precede opacity in the case of posterior subcapsular opacity, but not nuclear opacity. Measures of association between posterior subcapsular opacity and myopia were stronger in the current study than have previously been found. Longitudinal studies to confirm the association are warranted.

Impact of posterior subcapsular opacification on vision and visual function among subjects undergoing cataract surgery in rural China: Study of Cataract Outcomes and Up-Take of Services (SCOUTS) in the Caring is Hip Project, report 5.

AIM: To study the effect of posterior capsular opacification (PCO) on vision and visual function in patients undergoing cataract surgery in rural China, and to compare this with the effect of refractive error. METHODS: Patients undergoing cataract surgery in at least one eye by local surgeons in a rural setting between 8 August and 31 December 2005 were examined with slit lamp grading of PCO 10-14 months after surgery. Subjects with any PCO associated with best-corrected visual acuity of 6/7.5 or worse, or with grade 2+ or worse PCO without visual decrement, were offered YAG laser capsulotomy. Vision and self-reported visual function were assessed, and various demographic and clinical factors potentially associated with PCO were recorded. RESULTS: Of 313 patients operated on within the study window, 239 (76%) could be contacted by telephone; study examinations were performed on 176 (74%). Examined subjects had a mean (SD) age of 69.4 (10.5) years, 116 (67%) were female, and 149 (86%) had been blind (presenting visual acuity < or = 6/60) in the operated eye before surgery. PCO of grade 1 or above was present in 34 of 204 operated eyes (16.7%). Those with PCO had significantly worse presenting vision (p = 0.007) but not visual function (p>0.3) than those without PCO. Women had a significantly higher prevalence of PCO (20.9%) than did men (8.6%, p<0.05). Of 19 eyes undergoing capsulotomy with best-corrected visual acuity measured the next day, 13 (68%) improved by one or more lines, and seven (37%) improved by two or more lines. Despite a higher uptake of capsulotomy (95%) as opposed to refraction (35%) in this cohort, the yield in terms of eyes with poor presenting visual acuity (< 6/18) that could be improved was higher for refraction (26% = 9/35) than for capsulotomy (9% = 3/35). CONCLUSION: The prevalence of PCO and impact on vision and visual function in this cohort was modest 1 year after surgery. However, PCO prevalence increases with time. Follow-up of this cohort is underway to determine the effectiveness of this early intervention in identifying and treating subjects who will eventually experience clinically significant PCO.

The prevalence of caries in patients referred for orthodontic assessment in Northern Ireland – A retrospective study

Objectives: To determine the prevalence of untreated carious lesions in permanent teeth in patients (under the age of 18) referred for an orthodontic assessment in specialist practice. In addition, the figures shall be compared with national data for Northern Ireland (as outlined in the recent Child Dental Health Survey 2013)
The Gold standard would be that 100% of patients would be caries free upon presentation.

Methods: The clinical records and radiographs (OPT of quality grading 1 or 2) of 337 patients were reviewed. This encompassed patients who had an orthodontic assessment carried out in specialist practice over a 6 month period (following referral from their general dental practitioner)

Results: A total of 337 patient records were examined. Of these, 149 were male (44.2%) and 188 were female (55.8%), with an age range of 7-17 years at the time of new patient assessment. It was found that 36 patients (10.7%) had evidence (clinical and/or radiographic) of active and untreated dental caries. Of those affected, 14 were male and 22 were female.
Breaking the data down in terms of age, we can also get some indication as to how this cohort compares with national data for Northern Ireland :⃰

7-10 years (Mean = 9.3) = 14.3% caries (versus NI average of 6% for 8 year olds)
11-13 years (Mean = 12.1) = 10.1% caries, (versus NI average of 16% for 12 year olds)
14-17 years (Mean = 15.2) = 9.1% caries (versus NI average of 15% for 15 year olds)

⃰using the diagnostic threshold “Decay into dentine (visual dentine caries excluded)”


Conclusion: In this sample group, a total of 10.7% of patients (9.4% of males, 11.7% of females) presented with evidence of undiagnosed caries upon being assessed as a new patient in specialist orthodontic practice. Hence, the gold standard was not met.

c-Met inhibition in a HOXA9/Meis1 model of CN-AML

BACKGROUND: Hematopoiesis is a paradigm for developmental processes, hierarchically organized, with stem cells at its origin. Hematopoietic stem cells (HSCs) replenish progenitor and precursor cells of multiple lineages, which normally differentiate into short-lived mature circulating cells. Hematopoiesis has provided insight into the molecular basis of tissue homeostasis and malignancy. Malignant hematopoiesis, in particular acute myeloid leukemia (AML), results from impaired development or differentiation of HSCs and progenitors. Co-overexpression of HOX and TALE genes, particularly the HOXA cluster and MEIS1, is associated with AML. Clinically relevant models of AML are required to advance drug development for an aging patient cohort.

RESULTS: Molecular analysis identified altered gene, microRNA, and protein expression in HOXA9/Meis1 leukemic bone marrow compared to normal controls. A candidate drug screen identified the c-Met inhibitor SU11274 for further analysis. Altered cell cycle status, apoptosis, differentiation, and impaired colony formation were shown for SU11274 in AML cell lines and primary leukemic bone marrow.

CONCLUSIONS: The clonal HOXA9/Meis1 AML model is amenable to drug screening analysis. The data presented indicate that human AML cells respond in a similar manner to the HOXA9/Meis1 cells, indicating pre-clinical relevance of the mouse model.

Physical rehabilitation interventions for adult patients during critical illness: an overview of systematic reviews

Background Physical rehabilitation interventions aim to ameliorate the effects of critical illness-associated muscle dysfunction in survivors. We conducted an overview of systematic reviews (SR) evaluating the effect of these interventions across the continuum of recovery.

Methods Six electronic databases (Cochrane Library, CENTRAL, DARE, Medline, Embase, and Cinahl) were searched. Two review authors independently screened articles for eligibility and conducted data extraction and quality appraisal. Reporting quality was assessed and the Grading of Recommendations Assessment, Development and Evaluation approach applied to summarise overall quality of evidence.

Results Five eligible SR were included in this overview, of which three included meta-analyses. Reporting quality of the reviews was judged as medium to high. Two reviews reported moderate-to-high quality evidence of the beneficial effects of physical therapy commencing during intensive care unit (ICU) admission in improving critical illness polyneuropathy/myopathy, quality of life, mortality and healthcare utilisation. These interventions included early mobilisation, cycle ergometry and electrical muscle stimulation. Two reviews reported very low to low quality evidence of the beneficial effects of electrical muscle stimulation delivered in the ICU for improving muscle strength, muscle structure and critical illness polyneuropathy/myopathy. One review reported that due to a lack of good quality randomised controlled trials and inconsistency in measuring outcomes, there was insufficient evidence to support beneficial effects from physical rehabilitation delivered post-ICU discharge.

Conclusions Patients derive short-term benefits from physical rehabilitation delivered during ICU admission. Further robust trials of electrical muscle stimulation in the ICU and rehabilitation delivered following ICU discharge are needed to determine the long-term impact on patient care. This overview provides recommendations for design of future interventional trials and SR.