Choosing appropriate patient-reported outcomes instrument for glaucoma research: a systematic review of vision instruments

PURPOSE: To identify vision Patient-Reported Outcomes instruments relevant to glaucoma and assess their content validity.

METHODS: MEDLINE, MEDLINE in Process, EMBASE and SCOPUS (to January 2009) were systematically searched. Observational studies or randomised controlled trials, published in English, reporting use of vision instruments in glaucoma studies involving adults were included. In addition, reference lists were scanned to identify additional studies describing development and/or validation to ascertain the final version of the instruments. Instruments' content was then mapped onto a theoretical framework, the World Health Organization International Classification of Functioning, Disability and Health. Two reviewers independently evaluated studies for inclusion and quality assessed instrument content.

RESULTS: Thirty-three instruments were identified. Instruments were categorised into thirteen vision status, two vision disability, one vision satisfaction, five glaucoma status, one glaucoma medication related to health status, five glaucoma medication side effects and six glaucoma medication satisfaction measures according to each instruments' content. The National Eye Institute Visual Function Questionnaire-25, Impact of Vision Impairment and Treatment Satisfaction Survey-Intraocular Pressure had the highest number of positive ratings in the content validity assessment.

CONCLUSION: This study provides a descriptive catalogue of vision-specific PRO instruments, to inform the choice of an appropriate measure of patient-reported outcomes in a glaucoma context.

Socio-emotional effects of the transition from sight to blindness,

The research examined the socio-emotional impact of sight loss on a sample of 18 blind and partially sighted adults from the East coast of Scotland (average age 64). The impact of sight loss in four core areas mood, self concept, social connectedness and loss was explored. Data was collected using the mental health and social functioning sub-scales of the National Eye Institute Visual Functioning Questionnaire-25 and semi-structured interviews. Data indicated that participants experienced reduced mental health and decreased social functioning as a result of sight loss. Data also showed that participants shared common socio-emotional issues during transition from sight to blindness, starting with diagnosis, coping with deterioration of sight, experiencing loss, experiencing changed perceptions of self in relation to society, experiencing others in a changed way and experiencing rehabilitation. A theoretical model describing the socio-emotional transition from sight to blindness is proposed. Implications for practice are explored.

Patient-reported outcomes in randomised controlled trials on age-related macular degeneration

BACKGROUND/AIMS: The purpose of this systematic review was to identify the frequency and type of patient-reported outcome measures (PROMs) used in recent randomised controlled trials (RCTs) for age-related macular degeneration (AMD).

METHODS: The authors conducted a systematic search between January 2010 and November 2013 in MEDLINE, EMBASE, Scopus, Cochrane Library (Central) and the clinical trials registries (http://www.controlled-trials.com and http://www.ClinicalTrials.gov) according to defined inclusion criteria (RCTs on AMD in English). Two independent reviewers evaluated studies for inclusion. One reviewer extracted data of included studies, and a second masked reviewer assessed 10% to confirm accuracy in data collection. Reference lists of included papers and appendices of relevant Cochrane systematic reviews were scanned to identify other relevant RCTs. Information collected on extracted outcomes was analysed using descriptive statistics.

RESULTS: Literature and registry search yielded 3816 abstracts of journal articles and 493 records from trial registries. A total of 177 RCTs were deemed to have met inclusion criteria. Of the 858 outcomes reported, 38 outcomes were identified as PROMs (4.4%). Of the 177 RCTs examined, PROMs were used in 25 trials (14.1%). The National Eye Institute Visual Function Questionnaire-25 was the most frequently used PROM instrument (64% of RCTs with PROMs included).

CONCLUSIONS: This review highlights that a small proportion of AMD RCTs included PROMs as outcome measures and that there was a variety in the instruments used.

Self-refraction, ready-made glasses and quality of life among rural myopic Chinese children: a non-inferiority randomized trial.

PURPOSE: To study, for the first time, the effect of wearing ready-made glasses and glasses with power determined by self-refraction on children's quality of life. METHODS: This is a randomized, double-masked non-inferiority trial. Children in grades 7 and 8 (age 12-15 years) in nine Chinese secondary schools, with presenting visual acuity (VA) ≤6/12 improved with refraction to ≥6/7.5 bilaterally, refractive error ≤-1.0 D and <2.0 D of anisometropia and astigmatism bilaterally, were randomized to receive ready-made spectacles (RM) or identical-appearing spectacles with power determined by: subjective cycloplegic retinoscopy by a university optometrist (U), a rural refractionist (R) or non-cycloplegic self-refraction (SR). Main study outcome was global score on the National Eye Institute Refractive Error Quality of Life-42 (NEI-RQL-42) after 2 months of wearing study glasses, comparing other groups with the U group, adjusting for baseline score. RESULTS: Only one child (0.18%) was excluded for anisometropia or astigmatism. A total of 426 eligible subjects (mean age 14.2 years, 84.5% without glasses at baseline) were allocated to U [103 (24.2%)], RM [113 (26.5%)], R [108 (25.4%)] and SR [102 (23.9%)] groups, respectively. Baseline and endline score data were available for 398 (93.4%) of subjects. In multiple regression models adjusting for baseline score, older age (p = 0.003) and baseline spectacle wear (p = 0.016), but not study group assignment, were significantly associated with lower final score. CONCLUSION: Quality of life wearing ready-mades or glasses based on self-refraction did not differ from that with cycloplegic refraction by an experienced optometrist in this non-inferiority trial.

Human Papillomavirus and Oral Cancer: the International Agency for Research on Cancer Multicenter Study

Background: Human papillomavirus (HPV), the causal agent of cervical cancer, appears to be involved in the etiology of cancer of the oral cavity and oropharynx. To investigate these associations, we conducted a multicenter case-control study of cancer of the oral cavity and oropharynx in nine countries. Methods: We recruited 1670 case patients (1415 with cancer of the oral cavity and 255 with cancer of the oropharynx) and 1732 control subjects and obtained an interview, oral exfoliated cells, and blood from all participants and fresh biopsy specimens from case patients. HPV DNA was detected by polymerase chain reaction (PCR). Antibodies against HPV16 L1, E6, and E7 proteins in plasma were detected with enzyme-linked immunosorbent assays. Multivariable models were used for case-control and case-case comparisons. Results: HPV DNA was detected in biopsy specimens of 3.9% (95% confidence interval [CI]=2.5% to 5.3%) of 766 cancers of the oral cavity with valid PCR results and 18.3% (95% CI=12.0% to 24.7%) of 142 cancers of the oropharynx (oropharynx and tonsil combined) with valid PCR results. HPV DNA in cancer biopsy specimens was detected less frequently among tobacco smokers and paan chewers and more frequently among subjects who reported more than one sexual partner or who practiced oral sex. HPV16 DNA was found in 94.7% of HPV DNA-positive case patients. HPV DNA in exfoliated cells was not associated with cancer risk or with HPV DNA detection in biopsy specimens. Antibodies against HPV16 L1 were associated with risk for cancers of the oral cavity (odds ratio [OR]=1.5, 95% CI=1.1 to 2.1) and the oropharynx (OR=3.5, 95% CI=2.1 to 5.9). Antibodies against HPV16 E6 or E7 were also associated with risk for cancers of the oral cavity (OR=2.9, 95% CI=1.7 to 4.8) and the oropharynx (OR=9.2, 95% CI=4.8 to 17.7). Conclusions: HPV appears to play an etiologic role in many cancers of the oropharynx and possibly a small subgroup of cancers of the oral cavity. The most common HPV type in genital cancers (HPV16) was also the most common in these tumors. The mechanism of transmission of HPV to the oral cavity warrants further investigation.

Molecular basis for estrogen receptor alpha deficiency in BRCA1-linked breast cancer

Background BRCA1-mutant breast tumors are typically estrogen receptor alpha (ER alpha) negative, whereas most sporadic tumors express wild-type BRCA1 and are ER alpha positive. We examined a possible mechanism for the observed ER alpha-negative phenotype of BRCA1-mutant tumors.

Methods We used a breast cancer disease-specific microarray to identify transcripts that were differentially expressed between paraffin-embedded samples of 17 BRCA1-mutant and 14 sporadic breast tumors. We measured the mRNA levels of estrogen receptor 1 (ESR1) ( the gene encoding ER alpha), which was differentially expressed in the tumor samples, by quantitative polymerase chain reaction. Regulation of ESR1 mRNA and ER alpha protein expression was assessed in human breast cancer HCC1937 cells that were stably reconstituted with wild-type BRCA1 expression construct and in human breast cancer T47D and MCF-7 cells transiently transfected with BRCA1-specific short-interfering RNA ( siRNA). Chromatin immunoprecipitation assays were performed to determine if BRCA1 binds the ESR1 promoter and to identify other interacting proteins. Sensitivity to the antiestrogen drug fulvestrant was examined in T47D and MCF-7 cells transfected with BRCA1-specific siRNA. All statistical tests were two-sided.

Results Mean ESR1 gene expression was 5.4-fold lower in BRCA1-mutant tumors than in sporadic tumors ( 95% confidence interval [CI]=2.6-fold to 40.1-fold, P =.0019). The transcription factor Oct-1 recruited BRCA1 to the ESR1 promoter, and both BRCA1 and Oct-1 were required for ER alpha expression. BRCA1-depleted breast cancer cells expressing exogenous ER alpha were more sensitive to fulvestrant than BRCA1-depleted cells transfected with empty vector ( T47D cells, the mean concentration of fulvestrant that inhibited the growth of 40% of the cells [IC40] for empty vector versus ER alpha: > 10(-5) versus 8.0 x 10(-9) M [ 95% CI=3.1x10(-10) to 3.2 x 10(-6) M]; MCF-7 cells, mean IC40 for empty vector versus ER alpha : > 10(-5) versus 4.9 x 10(-8) M [ 95% CI=2.0 x 10(-9) to 3.9 x 10(-6) M]).

Conclusions BRCA1 alters the response of breast cancer cells to antiestrogen therapy by directly modulating ER alpha expression.

Risk of Malignant Progression in Barrett’s Esophagus Patients: Results from a Large Population-Based Study

Background: Barrett's esophagus (BE) is a premalignant lesion that predisposes to esophageal adenocarcinoma. However, the reported incidence of esophageal adenocarcinoma in patients with BE varies widely. We examined the risk of malignant progression in patients with BE using data from the Northern Ireland Barrett's esophagus Register (NIBR), one of the largest population-based registries of BE worldwide, which includes every adult diagnosed with BE in Northern Ireland between 1993 and 2005.

Subjects and Methods: We followed 8522 patients with BE, defined as columnar lined epithelium of the esophagus with or without specialized intestinal metaplasia (SIM), until the end of 2008. Patients with incident adenocarcinomas of the esophagus or gastric cardia or with high-grade dysplasia of the esophagus were identified by matching the NIBR with the Northern Ireland Cancer Registry, and deaths were identified by matching with records from the Registrar General's Office. Incidence of cancer outcomes or high-grade dysplasia was calculated as events per 100 person-years (% per year) of follow-up, and Cox proportional hazard models were used to determine incidence by age, sex, length of BE segment, presence of SIM, macroscopic BE, or low-grade dysplasia. All P values were from two-sided tests.

Results: After a mean of 7.0 years of follow-up, 79 patients were diagnosed with esophageal cancer, 16 with cancer of the gastric cardia, and 36 with high-grade dysplasia. In the entire cohort, incidence of esophageal or gastric cardia cancer or high-grade dysplasia combined was 0.22% per year (95% confidence interval [CI] = 0.19% to 0.26%). SIM was found in 46.0% of patients. In patients with SIM, the combined incidence was 0.38% per year (95% CI = 0.31 to 0.46%). The risk of cancer was statistically significantly elevated in patients with vs without SIM at index biopsy (0.38% per year vs 0.07% per year; hazard ratio [HR] = 3.54, 95% CI = 2.09 to 6.00, P <. 001), in men compared with women (0.28% per year vs 0.13% per year; HR = 2.11, 95% CI = 1.41 to 3.16, P <. 001), and in patients with low-grade dysplasia compared with no dysplasia (1.40% per year vs 0.17% per year; HR = 5.67, 95% CI = 3.77 to 8.53, P <. 001).

Conclusion: We found the risk of malignant progression among patients with BE to be lower than previously reported, suggesting that currently recommended surveillance strategies may not be cost-effective. © The Author 2011. Published by Oxford University Press. All rights reserved.

RanGTPase: A Candidate for Myc-Mediated Cancer Progression

BackgroundRas-related nuclear protein (Ran) is required for cancer cell survival in vitro and human cancer progression, but the molecular mechanisms are largely unknown.MethodsWe investigated the effect of the v-myc myelocytomatosis viral oncogene homolog (Myc) on Ran expression by Western blot, chromatin immunoprecipitation, and luciferase reporter assays and the effects of Myc and Ran expression in cancer cells by soft-agar, cell adhesion, and invasion assays. The correlation between Myc and Ran and the association with patient survival were investigated in 14 independent patient cohorts (n = 2430) and analyzed with Spearman's rank correlation and Kaplan-Meier plots coupled with Wilcoxon-Gehan tests, respectively. All statistical tests were two-sided.ResultsMyc binds to the upstream sequence of Ran and transactivates Ran promoter activity. Overexpression of Myc upregulates Ran expression, whereas knockdown of Myc downregulates Ran expression. Myc or Ran overexpression in breast cancer cells is associated with cancer progression and metastasis. Knockdown of Ran reverses the effect induced by Myc overexpression in breast cancer cells. In clinical data, a positive association between Myc and Ran expression was revealed in 288 breast cancer and 102 lung cancer specimens. Moreover, Ran expression levels differentiate better or poorer survival in Myc overexpressing breast (?(2) = 24.1; relative risk [RR] = 9.1, 95% confidence interval [CI] = 3.3 to 24.7, P <.001) and lung (?(2) = 6.04; RR = 2.8, 95% CI = 1.2 to 6.3; P = .01) cancer cohorts.ConclusionsOur results suggest that Ran is required for and is a potential therapeutic target of Myc-driven cancer progression in both breast and lung cancers.