A meta-research study revealed several challenges in obtaining placebos for investigator-initiated drug trials.

OBJECTIVES: To systematically assess the kind of placebos used in investigator-initiated randomized controlled trials (RCTs), from where they are obtained, and the hurdles that exist in obtaining them. STUDY DESIGN AND SETTING: PubMed was searched for recently published noncommercial, placebo-controlled randomized drug trials. Corresponding authors were invited to participate in an online survey. RESULTS: From 423 eligible articles, 109 (26%) corresponding authors (partially) participated. Twenty-one of 102 (21%) authors reported that the placebos used were not matching (correctly labeled in only one publication). The main sources in obtaining placebos were hospital pharmacies (32 of 107; 30%) and the manufacturer of the study drug (28 of 107; 26%). RCTs with a hypothesis in the interest of the manufacturer of the study drug were more likely to have obtained placebos from the drug manufacturer (18 of 49; 37% vs. 5 of 29; 17%). Median costs for placebos and packaging were US$ 58,286 (IQR US$ 2,428- US$ 160,770; n = 24), accounting for a median of 10.3% of the overall trial budget. CONCLUSION: Although using matching placebos is widely accepted as a basic practice in RCTs, there seems to be no standard source to acquire them. Obtaining placebos requires substantial resources, and using nonmatching placebos is common.

Cognitive impairment in a primary healthcare population: a cross-sectional study on the island of Crete, Greece.

OBJECTIVES: Cognitive impairment is known to have a significant impact on the quality of life of individuals and their caregivers, yet it is often underdiagnosed. The objective of this study is to assess the extent of cognitive impairment among elders visiting primary healthcare (PHC) practice settings, to explore associated risk factors and discuss current care challenges for PHC providers. DESIGN: A cross-sectional study was conducted between March 2013 and May 2014. SETTING: Fourteen PHC units located in rural and urban areas of the Heraklion district in Crete, Greece. PARTICIPANTS: Consecutive visitors aged at least 60 years attending selected PHC practices. PRIMARY AND SECONDARY OUTCOME MEASURES: The Mini-Mental State Examination (MMSE) was used to indicate cognitive status. Associations of low MMSE scores (≤23/24, adjusted for education level) with 12 socio-demographic factors, comorbidities and lifestyle factors were assessed. RESULTS: A total of 3140 PHC patients met inclusion criteria (43.2% male; mean age 73.7±7.8 years). The average MMSE score was 26.0±3.8; 26.7±3.5 in male and 25.4±3.9 in female participants (p<0.0001). Low MMSE scores were detected in 20.2% of participants; 25.9% for females vs 12.8% for males; p<0.0001. Female gender (adjusted OR (AOR)=2.72; 95% CI 2.31 to 3.47), age (AOR=1.11; 95% CI 1.10 to 1.13), having received only primary or no formal education (AOR=2.87; 95% CI 2.26 to 3.65), alcohol intake (AOR=1.19; 95% CI 1.03 to 1.37), reporting one or more sleep complaints (AOR 1.63; 95% CI 1.14 to 2.32), dyslipidaemia (AOR=0.80; 95% CI 0.65 to 0.98) and history of depression (AOR=1.90; 95% CI 1.43 to 2.52) were associated with low MMSE scores. CONCLUSIONS: This study identified a relatively high prevalence of low MMSE scores among persons attending PHC practices in a southern European community setting and associations with several known risk factors.

Quality of life in the FOXFIRE, SIRFLOX and FOXFIRE-global randomised trials of selective internal radiotherapy for metastatic colorectal cancer.

Selective internal radiotherapy (SIRT) is a liver-directed treatment involving the injection of yttrium-90 microspheres into the blood supply of liver tumours. There are very few studies assessing health-related quality of life (HRQOL) in patients treated with SIRT. Patients with liver metastases from colorectal cancer (CRC) were randomised in the FOXFIRE (FFr; ISRCTN83867919), SIRFLOX (SF; NCT00724503) and FOXFIRE-Global (FFrG; NCT01721954) trials of first-line oxaliplatin-fluorouracil (FOLFOX) chemotherapy combined with SIRT versus FOLFOX alone. HRQOL was assessed using the three-level EQ-5D, European Organisation for Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) and EORTC Colorectal Liver Metastases cancer module (EORTC QLQ-LMC21) at baseline, ≤3 months, 6 months, 12 months and annually thereafter from randomisation, and at disease progression. Analyses were conducted on an intention-to-treat basis. In total, 554 patients were randomised to SIRT + FOLFOX and 549 patients to FOLFOX alone. HRQOL was statistically significant lower in SIRT + FOLFOX patients ≤3 months after SIRT administration in all three instruments, particularly global health, physical and role functioning and symptoms of fatigue, nausea/vomiting and appetite loss. By accepted thresholds, these differences were deemed not clinically important. Differences between SIRT + FOLFOX and FOLFOX alone over the 2-year follow up and at disease progression were also not clinically important. Although there is some decrease in HRQOL for up to 3 months following SIRT, the addition of SIRT to FOLFOX chemotherapy does not change HRQOL to a clinically important degree in metastatic CRC patients.

Dual Erb B Inhibition in Oesophago-gastric Cancer (DEBIOC): A phase I dose escalating safety study and randomised dose expansion of AZD8931 in combination with oxaliplatin and capecitabine chemotherapy in patients with oesophagogastric adenocarcinoma.

BACKGROUND: AZD8931 has equipotent activity against epidermal growth factor receptor, erbB2, and erbB3. Primary objectives were to determine the recommended phase II dose (RP2D) of AZD8931 + chemotherapy, and subsequently assess safety/preliminary clinical activity in patients with operable oesophagogastric cancer (OGC). METHODS: AZD8931 (20 mg, 40 mg or 60 mg bd) was given with Xelox (oxaliplatin + capecitabine) for eight 21-day cycles, continuously or with intermittent schedule (4 days on/3 off every week; 14 days on/7 off, per cycle) in a rolling-six design. Subsequently, patients with OGC were randomised 2:1 to AZD8931 + Xelox at RP2D or Xelox only for two cycles, followed by radical oesophagogastric surgery. Secondary outcomes were safety, complete resection (R0) rate, six-month progression-free survival (PFS) and overall survival. RESULTS: During escalation, four dose-limiting toxicities were observed among 24 patients: skin rash (1) and failure to deliver 100% of Xelox because of treatment-associated grade III-IV adverse events (AEs) (3: diarrhoea and vomiting; vomiting; fatigue). Serious adverse events (SAE) occurred in 15 of 24 (63%) patients. RP2D was 20-mg bd with the 4/3 schedule. In the expansion phase, 2 of 20 (10%) patients in the Xelox + AZD8931 group and 5/10 (50%) patients in the Xelox group had grade III-IV AEs. Six-month PFS was 85% (90% CI: 66%-94%) in Xelox + AZD8931 and 100% in Xelox alone. Seven deaths (35%) occurred with Xelox + AZD8931 and one (10%) with Xelox. R0 rate was 45% (9/20) with Xelox + AZD8931 and 90% (9/10) with Xelox-alone (P = 0.024). CONCLUSION: Xelox + AZD8931 (20 mg bd 4/3 days) has an acceptable safety profile administered as neoadjuvant therapy in operable patients with OGC. (Trial registration: EudraCT 2011-003169-13, ISRCTN-68093791).

Perifoveal capillary network quantification in young diabetic patients with subclinical or no retinopathy.

OBJECTIVE: To assess the morphology of perifoveal capillary network with quantitative parameters in young patients with diabetes mellitus type I (DM I) using an algorithm. METHODS: Fifty-three images (33 eyes of 33 DM I patients and 20 eyes of 20 non-DM controls) were chosen retrospectively from the University Hospital of Heraklion digital fluorescein angiography database. An additional group consisting of patients with advanced DR abnormalities was included in our analysis to investigate whether our method detects alterations when they are present. The developed algorithm allows the user to manually trace the perifoveal capillary network by selecting with the cursor in a 5° × 5° subimage field of the original image, including the foveal avascular zone (FAZ), and provides measurements of the capillary density, the branch point density, and the FAZ surface in this subarea. RESULTS: The age in the patient group was 19 ± 5 years; age was 21 ± 8 years for the control group. Patients had a history of DM I for 11 ± 5 years. The mapping revealed a perifoveal capillary density of 2.494 ± 0.559 deg-1 in the DM I group versus 2.974 ± 0.442 deg-1 in the control group (p = 0.005). The branch point density was 3.041 ± 0.919 branch points/deg2 and 3.613 ± 1.338 branch points/deg2 in each group, respectively (p = 0.128). The FAZ area was 0.216 ± 0.061 deg2 in the diabetic group and 0.208 ± 0.060 deg2 in the control group (p = 0.672). CONCLUSIONS: The selected quantitative parameters tend to increase or decrease in diabetic patients, in agreement with previous studies. Among the parameters, capillary density may represent the most sensitive metric for the detection of very early diabetic changes. Further improvement of the method could contribute to the development of an automated processing tool for capillary network quantitative assessment.

First-line selective internal radiotherapy plus chemotherapy versus chemotherapy alone in patients with liver metastases from colorectal cancer (FOXFIRE, SIRFLOX, and FOXFIRE-Global): a combined analysis of three multicentre, randomised, phase 3 trials.

BACKGROUND: Data suggest selective internal radiotherapy (SIRT) in third-line or subsequent therapy for metastatic colorectal cancer has clinical benefit in patients with colorectal liver metastases with liver-dominant disease after chemotherapy. The FOXFIRE, SIRFLOX, and FOXFIRE-Global randomised studies evaluated the efficacy of combining first-line chemotherapy with SIRT using yttrium-90 resin microspheres in patients with metastatic colorectal cancer with liver metastases. The studies were designed for combined analysis of overall survival. METHODS: FOXFIRE, SIRFLOX, and FOXFIRE-Global were randomised, phase 3 trials done in hospitals and specialist liver centres in 14 countries worldwide (Australia, Belgium, France, Germany, Israel, Italy, New Zealand, Portugal, South Korea, Singapore, Spain, Taiwan, the UK, and the USA). Chemotherapy-naive patients with metastatic colorectal cancer (WHO performance status 0 or 1) with liver metastases not suitable for curative resection or ablation were randomly assigned (1:1) to either oxaliplatin-based chemotherapy (FOLFOX: leucovorin, fluorouracil, and oxaliplatin) or FOLFOX plus single treatment SIRT concurrent with cycle 1 or 2 of chemotherapy. In FOXFIRE, FOLFOX chemotherapy was OxMdG (oxaliplatin modified de Gramont chemotherapy; 85 mg/m2 oxaliplatin infusion over 2 h, L-leucovorin 175 mg or D,L-leucovorin 350 mg infusion over 2 h, and 400 mg/m2 bolus fluorouracil followed by a 2400 mg/m2 continuous fluorouracil infusion over 46 h). In SIRFLOX and FOXFIRE-Global, FOLFOX chemotherapy was modified FOLFOX6 (85 mg/m2 oxaliplatin infusion over 2 h, 200 mg leucovorin, and 400 mg/m2 bolus fluorouracil followed by a 2400 mg/m2 continuous fluorouracil infusion over 46 h). Randomisation was done by central minimisation with four factors: presence of extrahepatic metastases, tumour involvement of the liver, planned use of a biological agent, and investigational centre. Participants and investigators were not masked to treatment. The primary endpoint was overall survival, analysed in the intention-to-treat population, using a two-stage meta-analysis of pooled individual patient data. All three trials have completed 2 years of follow-up. FOXFIRE is registered with the ISRCTN registry, number ISRCTN83867919. SIRFLOX and FOXFIRE-Global are registered with ClinicalTrials.gov, numbers NCT00724503 (SIRFLOX) and NCT01721954 (FOXFIRE-Global). FINDINGS: Between Oct 11, 2006, and Dec 23, 2014, 549 patients were randomly assigned to FOLFOX alone and 554 patients were assigned FOLFOX plus SIRT. Median follow-up was 43·3 months (IQR 31·6-58·4). There were 411 (75%) deaths in 549 patients in the FOLFOX alone group and 433 (78%) deaths in 554 patients in the FOLFOX plus SIRT group. There was no difference in overall survival (hazard ratio [HR] 1·04, 95% CI 0·90-1·19; p=0·61). The median survival time in the FOLFOX plus SIRT group was 22·6 months (95% CI 21·0-24·5) compared with 23·3 months (21·8-24·7) in the FOLFOX alone group. In the safety population containing patients who received at least one dose of study treatment, as treated, the most common grade 3-4 adverse event was neutropenia (137 [24%] of 571 patients receiving FOLFOX alone vs 186 (37%) of 507 patients receiving FOLFOX plus SIRT). Serious adverse events of any grade occurred in 244 (43%) of 571 patients receiving FOLFOX alone and 274 (54%) of 507 patients receiving FOLFOX plus SIRT. 10 patients in the FOLFOX plus SIRT group and 11 patients in the FOLFOX alone group died due to an adverse event; eight treatment-related deaths occurred in the FOLFOX plus SIRT group and three treatment-related deaths occurred in the FOLFOX alone group. INTERPRETATION: Addition of SIRT to first-line FOLFOX chemotherapy for patients with liver-only and liver-dominant metastatic colorectal cancer did not improve overall survival compared with that for FOLFOX alone. Therefore, early use of SIRT in combination with chemotherapy in unselected patients with metastatic colorectal cancer cannot be recommended. To further define the role of SIRT in metastatic colorectal cancer, careful patient selection and studies investigating the role of SIRT as consolidation therapy after chemotherapy are needed. FUNDING: Bobby Moore Fund of Cancer Research UK, Sirtex Medical.

Protocol for Combined Analysis of FOXFIRE, SIRFLOX, and FOXFIRE-Global Randomized Phase III Trials of Chemotherapy +/- Selective Internal Radiation Therapy as First-Line Treatment for Patients With Metastatic Colorectal Cancer.

BACKGROUND: In colorectal cancer (CRC), unresectable liver metastases are associated with a poor prognosis. The FOXFIRE (an open-label randomized phase III trial of 5-fluorouracil, oxaliplatin, and folinic acid +/- interventional radioembolization as first-line treatment for patients with unresectable liver-only or liver-predominant metastatic colorectal cancer), SIRFLOX (randomized comparative study of FOLFOX6m plus SIR-Spheres microspheres versus FOLFOX6m alone as first-line treatment in patients with nonresectable liver metastases from primary colorectal carcinoma), and FOXFIRE-Global (assessment of overall survival of FOLFOX6m plus SIR-Spheres microspheres versus FOLFOX6m alone as first-line treatment in patients with nonresectable liver metastases from primary colorectal carcinoma in a randomized clinical study) clinical trials were designed to evaluate the efficacy and safety of combining first-line chemotherapy with selective internal radiation therapy (SIRT) using yttrium-90 resin microspheres, also called transarterial radioembolization. OBJECTIVE: The aim of this analysis is to prospectively combine clinical data from 3 trials to allow adequate power to evaluate the impact of chemotherapy with SIRT on overall survival. METHODS: Eligible patients are adults with histologically confirmed CRC and unequivocal evidence of liver metastases which are not treatable by surgical resection or local ablation with curative intent at the time of study entry. Patients may also have limited extrahepatic metastases. Final analysis will take place when all participants have been followed up for a minimum of 2 years. RESULTS: Efficacy and safety estimates derived using individual participant data (IPD) from SIRFLOX, FOXFIRE, and FOXFIRE-Global will be pooled using 2-stage prospective meta-analysis. Secondary outcome measures include progression-free survival (PFS), liver-specific PFS, health-related quality of life, response rate, resection rate, and adverse event profile. The large study population will facilitate comparisons of low frequency adverse events and allow for more robust safety analyses. The potential treatment benefit in those patients who present with disease confined to the liver will be investigated using 1-stage IPD meta-analysis. Efficacy will be analyzed on an intention-to-treat basis. CONCLUSIONS: This analysis will assess the impact of SIRT combined with chemotherapy on overall survival in the first-line treatment of metastatic CRC. If positive, the results will change the standard of care for this disease. TRIAL REGISTRATION: FOXFIRE ISRCTN Registry ISRCTN83867919; http://www.isrctn.com/ISRCTN83867919 (Archived by WebCite at http://www.webcitation.org/6oN7axrvA). SIRFLOX ClinicalTrials.gov NCT00724503; https://clinicaltrials.gov/ ct2/show/NCT00724503 (Archived by WebCite at http://www.webcitation.org/6oN7lEGbD). FOXFIRE-Global ClinicalTrials.gov NCT01721954; https://clinicaltrials.gov/ct2/show/NCT01721954 (Archived by WebCite at http://www.webcitation.org/ 6oN7vvQvG).

Toxoplasmosis in female high school students, pregnant women and ruminants in Cyprus.

BACKGROUND: The protozoan parasite Toxoplasma gondii is important to human and animal health worldwide. This is the first study of prevalence of infection with T. gondii and associated risk factors in human populations and small ruminants in Cyprus. METHODS: A random sample of 18 schools out of 46 participated: 1056 girls aged 16 to 18 years completed a questionnaire and were serologically tested for Toxoplasma between 2008 and 2011 (response rate 30%). In addition, infection with T. gondii laboratory results of 23 076 pregnant women tested between 2009 and 2014 were obtained from hospital records. Finally, 163 (out of 3123) farms were randomly sampled and blood samples from 515 sheep and 581 goats were obtained. RESULTS: Estimated seropositivity prevalence in female students was 6.5% (95% CI 4.3 to 8.7%) and 18% (95% CI 17 to 19%) in pregnant women. Overall, 40.1% of the ruminants tested were seropositive (95% CI 37.2% to 43.0%). Seropositivity differed according to geographical region in all three groups. CONCLUSIONS: Further studies are needed to investigate the differences between regions that lead to differing prevalence levels and patterns between ruminants and humans so that health education policies can be developed to help prevent infection and reduce environmental contamination.

General Practitioners' intention to prescribe and prescribing patterns in selected European settings: The OTCSOCIOMED project.

The aim of this paper is to explore general practitioners' (GPs) prescribing intentions and patterns across different European regions using the Theory of Planned Behavior (TPB). A cross-sectional study was undertaken in selected geographically defined Primary Health Care areas in Cyprus, Czech Republic (CZ), France, Greece, Malta, Sweden and Turkey. Face-to-face interviews were conducted using a TPB-based questionnaire. The number of GP participants ranged from 39 to 145 per country. Possible associations between TPB direct measures (attitudes, subjective norms (SN) and perceived behavioral control (PBC)) and intention to prescribe were assessed by country. On average, GPs thought positively of, and claimed to be in control of, prescribing. Correlations between TPB explanatory measures and prescribing intention were weak, with TPB direct measures explaining about 25% of the variance in intention to prescribe in Malta and CZ but only between 3% and 5% in Greece, Sweden and Turkey. SN appeared influential in GPs from Malta; attitude and PBC were statistically significant in GPs from CZ. GPs' prescribing intentions and patterns differed across participating countries, indicating that country-specific interventions are likely to be appropriate. Irrational prescribing behaviors were more apparent in the countries where an integrated primary care system has still not been fully developed and policies promoting the rational use of medicines are lacking. Demand-side measures aimed at modifying GPs prescribing behavior are deemed necessary.

Does eating family meals and having the television on during dinner correlate with overweight? A sub-study of the PRO GREENS project, looking at children from nine European countries.

OBJECTIVE: Family meals have been negatively associated with overweight in children, while television (TV) viewing during meals has been associated with a poorer diet. The aim of the present study was to assess the association of eating family breakfast and dinner, and having a TV on during dinner, with overweight in nine European countries and whether these associations differed between Northern and Southern & Eastern Europe. DESIGN: Cross-sectional data. Schoolchildren reported family meals and TV viewing. BMI was based on parental reports on height and weight of their children. Cut-off points for overweight by the International Obesity Task Force were used. Logistic regressions were performed adjusted by age, gender and parental education. SETTING: Schools in Northern European (Sweden, the Netherlands, Iceland, Germany and Finland) and Southern & Eastern European (Portugal, Greece, Bulgaria and Slovenia) countries, participating in the PRO GREENS project. SUBJECTS: Children aged 10-12 years in (n 6316). RESULTS: In the sample, 21 % of the children were overweight, from 35 % in Greece to 10 % in the Netherlands. Only a few associations were found between family meals and TV viewing during dinner with overweight in the nine countries. Northern European children, compared with other regions, were significantly more likely to be overweight if they had fewer family breakfasts and more often viewed TV during dinner. CONCLUSIONS: The associations between family meals and TV viewing during dinner with overweight were few and showed significance only in Northern Europe. Differences in foods consumed during family meals and in health-related lifestyles between Northern and Southern & Eastern Europe may explain these discrepancies.

Irrational prescribing of over-the-counter (OTC) medicines in general practice: testing the feasibility of an educational intervention among physicians in five European countries.

BACKGROUND: Irrational prescribing of over-the-counter (OTC) medicines in general practice is common in Southern Europe. Recent findings from a research project funded by the European Commission (FP7), the "OTC SOCIOMED", conducted in seven European countries, indicate that physicians in countries in the Mediterranean Europe region prescribe medicines to a higher degree in comparison to physicians in other participating European countries. In light of these findings, a feasibility study has been designed to explore the acceptance of a pilot educational intervention targeting physicians in general practice in various settings in the Mediterranean Europe region. METHODS: This feasibility study utilized an educational intervention was designed using the Theory of Planned Behaviour (TPB). It took place in geographically-defined primary care areas in Cyprus, France, Greece, Malta, and Turkey. General Practitioners (GPs) were recruited in each country and randomly assigned into two study groups in each of the participating countries. The intervention included a one-day intensive training programme, a poster presentation, and regular visits of trained professionals to the workplaces of participants. Reminder messages and email messages were, also, sent to participants over a 4-week period. A pre- and post-test evaluation study design with quantitative and qualitative data was employed. The primary outcome of this feasibility pilot intervention was to reduce GPs' intention to provide medicines following the educational intervention, and its secondary outcomes included a reduction of prescribed medicines following the intervention, as well as an assessment of its practicality and acceptance by the participating GPs. RESULTS: Median intention scores in the intervention groups were reduced, following the educational intervention, in comparison to the control group. Descriptive analysis of related questions indicated a high overall acceptance and perceived practicality of the intervention programme by GPs, with median scores above 5 on a 7-point Likert scale. CONCLUSIONS: Evidence from this intervention will estimate the parameters required to design a larger study aimed at assessing the effectiveness of such educational interventions. In addition, it could also help inform health policy makers and decision makers regarding the management of behavioural changes in the prescribing patterns of physicians in Mediterranean Europe, particularly in Southern European countries.

Comparison of visual acuity charts in young adults and patients with diabetic retinopathy.

PURPOSE: To compare visual acuity (VA) assessed in healthy eyes and eyes with diabetic retinopathy (DR) using three different logMAR charts: the Sloan letter European-wide chart, the tumbling E chart, and the Landolt C chart. METHODS: Measurements on one eye of 40 volunteers (aged 29 ± 4 years) without visual impairment and 31 DR patients (aged 70 ± 9 years) with mild/moderate visual impairment were included. Visual acuity was assessed, with habitual refractive correction, using each of the three charts. Bland-Altman charts were constructed, and 95% limits of agreement were calculated to measure agreement. RESULTS: Mean VA in the group of young adults was -0.05 ± 0.10 (Sloan letter), -0.02 ± 0.13 (tumbling E), and 0.00 ± 0.12 (Landolt C) logMAR. Average VA estimates differed to a statistically significant extent between all charts. Mean VA in the DR group was 0.46 ± 0.25 (Sloan letter), 0.48 ± 0.26 (tumbling E), and 0.59 ± 0.28 (Landolt C). A statistically significant difference was observed for average Sloan letter versus Landolt C (p < 0.001) and tumbling E versus Landolt C (p < 0.001) acuities. Moreover, in healthy eyes, a moderate correlation (r = -0.38, p = 0.015) was found between the discrepancy in Sloan letter and Landolt C acuity and the mean VA estimate. The 95% limits of agreement were wide (more than approximately 0.2 logMAR for each comparison) and wider in the DR group chart comparisons than in healthy eyes. CONCLUSIONS: Landolt C charts resulted in worse VA estimates compared with letter and tumbling E charts in both young adults and visually impaired subjects with DR. These differences seem more pronounced in DR patients who exhibit worse VAs. The specific study population must be considered in comparing outcomes from different clinical practices.

Effect of blur and subsequent adaptation on visual acuity using letter and Landolt C charts: differences between emmetropes and myopes.

PURPOSE: To compare the effects of defocus induced blur and blur adaptation on visual acuity and to evaluate any differences between emmetropes and myopes using letter and Landolt C logMAR charts. METHODS: The sample consisted of 26 volunteers, with a mean age of 27 ± 3 years, comprising 13 emmetropes (spherical equivalent range: -0.63 to +0.50 D) and 13 myopes (spherical equivalent range: -0.75 to -5.00 D). Monocular visual acuity (VA) was measured in each eye using letter and Landolt C logMAR charts under the following conditions: (1) with the distance refractive correction, (2) immediately after exposure to +2.00 D defocus and (3) following 60 min of binocular adaptation to +2.00 D blur. Objective refraction at the beginning and at the end of the experimental procedure was evaluated. Averaged VA data between the two eyes were used for analysis. RESULTS: Deterioration in VA with +2.00 D defocus was greater in the emmetropes compared to myopes for both charts. The mean difference between the two refractive groups was more pronounced for the Landolt-C (0.17 logMAR) compared to the letter chart (0.10 logMAR). The reduction in VA with blur was related to the amount of the refractive error. Following 60 min of adaptation, a significant improvement in VA was observed in both groups that did not differ between the two charts. The improvement in VA following adaptation using the letter chart was linearly correlated with spherical equivalent refractive correction. CONCLUSIONS: Myopes show higher tolerance to retinal defocus compared to emmetropes, which could be attributed to previous blur experience. The effect of blur on VA is more pronounced using Landolt C optotypes than with letters. Prolonged exposure to blur results in equally improved performance for both refractive groups.

Prospective study of foveal thickness alterations after cataract surgery assessed by optical coherence tomography.

BACKGROUND/AIMS: To evaluate the alterations of mean foveal thickness (MFT) and visual acuity (VA) outcomes after uncomplicated cataract surgery in different groups of patients. METHODS: This study included eyes of consecutive patients who underwent cataract surgery between November 2007 and June 2009. The patients included in the study were divided into 4 groups, as follows: history-free patients, patients with diabetes mellitus without macular involvement at baseline, patients with glaucoma, and patients with epiretinal membrane (ERM). Preoperatively and at 1, 3 and 6 months postoperatively, patients were evaluated for MFT by optical coherence tomography at the central 1-mm macular zone and for logarithm of the minimum angle of resolution best spectacle-corrected VA (BSCVA). RESULTS: A total of 202 eyes were included in the study. MFT values demonstrated a statistically significant increase (p < 0.01) after cataract surgery in all groups at the first and third postoperative month. The history-free (p = 0.09) and glaucoma (p = 0.19) groups did not demonstrate a statistically significant difference in MFT values between the preoperative and 6-month measurements. MFT values 6 months after cataract surgery in the diabetes and ERM groups remained significantly higher (p < 0.01). Despite these findings, VA increased significantly (p < 0.01) in all groups at all postoperative follow-ups. CONCLUSIONS: MFT values increased significantly in all groups at the first and third months after cataract surgery. At 6 months, MFT values returned to preoperative levels in the history-free and glaucoma patients, while they remained significantly higher in the diabetic and ERM patients. Despite these macular alterations, BSCVA improved significantly after cataract surgery in all groups at all postoperative follow-ups.

Choice of analytic approach for eye-specific outcomes: one eye or two?

PURPOSE: To investigate the use of analytic approaches for eye-specific outcomes in ophthalmology publications. DESIGN: A review of analytic approaches used in original research articles published in ophthalmology journals. METHODS: All 161 research articles published in 5 ophthalmology journals in the first 2 months of 2008 were considered. Publications were categorized according to analytic approach: 1 eye selected, both eyes contribute, or per-individual outcome. Studies were considered suboptimal when criteria for eye selection were not provided or when measurements from both eyes were included without interocular correlation being considered. Visual impairment prevalence data were used to illustrate analytic approach choices. RESULTS: Measurements from both eyes were included in 38% of the 112 studies that used statistical inferential techniques. In 31 (74%), there was no mention of possible correlation. Only 7% used statistical methods appropriate for correlated outcomes. In 35 studies (31%), measurements from 1 eye were selected; 31% of these did not provide selection criteria. In 67%, only univariate tests were used. A review of 47 articles published in 2011 produced similar findings. Characteristics of studies were not found to differ according whether the studies were suboptimal. Using a test appropriate for correlated outcomes resulted in a P value 3.5 times that obtained ignoring the correlation. CONCLUSIONS: Between-eye correlation seems not to be assessed commonly in ophthalmology publications, although its knowledge aids the choice of analytic approach when eye-specific variables are of interest. Statistical methods appropriate for correlated ocular outcome data are not being applied widely.

Assessment of macular pigment optical density (MPOD) in patients with unilateral wet age-related macular degeneration (AMD).

PURPOSE: To compare the macular pigment optical density (MPOD) of patients with unilateral wet age-related macular degeneration (AMD) with the MPOD of bilateral dry AMD patients and healthy elderly individuals. METHODS: The MPOD of 34 patients with unilateral wet AMD was measured in their fellow eye that had the dry form of the disease (study group). The MPOD of the study group was compared with the MPOD of 33 patients with bilateral dry AMD (patients' control group) and 35 elderly subjects without any signs of retinal disease (control group). None of the subjects was under carotenoid supplementation. The MPOD was measured with Heterochromatic Flicker Photometry [QuantifEYE™- MPS 9000 (ZeaVision(©))]. The statistical package SPSS v 17.0 was used for the analysis. RESULTS: The overall mean MPOD was 0.52 (SD 0.15). Patients with unilateral wet AMD have significantly higher levels of MPOD in their fellow eye compared with patients with bilateral dry AMD (0.58 versus 0.48, p = 0.026). Mean MPOD of patients with bilateral dry AMD does not differ significantly from that of healthy elderly subjects (0.48 versus 0.50, p = 0.865). In this population sample, no correlation with age was observed, while women have slightly but significantly higher levels of MPOD (0.55 versus 0.49, p = 0.029). CONCLUSION: In the present study, the mean MPOD at the fellow eye of patients with unilateral wet AMD was found to be significantly higher than that of patients with bilateral dry AMD, while no other significant difference emerged between groups. Further investigation is demanded to clarify the role of macular pigment in AMD progression.

In vivo evaluation of blue-light attenuation with tinted and untinted intraocular lenses.

PURPOSE: To evaluate blue-light attenuation in eyes with a tinted intraocular lens (IOL) or an untinted IOL. SETTING: Department of Ophthalmology, University Hospital of Crete, Crete, Greece. DESIGN: Comparative case series. METHODS: Patients had lens extraction and implantation of an Acrysof Natural tinted or Tecnis ZA9003 or Softec III untinted acrylic IOL. The luminance ratio of green (530 nm) and blue (465 nm) light (green:blue ratio) required for isoluminant perception was determined by heterochromatic flicker photometry. Patients were tested preoperatively and 20 days postoperatively. The parafoveal measure of the green:blue ratio, expressed in decibels, is proportional to the blue-light attenuation by the lens. RESULTS: Twenty-two patients received the tinted IOL and 21 the untinted IOL. Preoperatively, age was strongly linearly correlated with the green:blue ratio (r = 0.59, P < .001). The mean postoperative decrease in the green:blue ratio was greater in the untinted IOL group (P = .003). Postoperatively, the tinted IOL group had a significantly higher green:blue ratio than the untinted IOL group (P < .001). In the tinted IOL group, the green:blue ratio was linearly related to IOL dioptric power. CONCLUSION: Less blue light reached the retina with tinted IOLs than with untinted IOLs. The absorption properties of tinted IOLs seemed to resemble those of the aging human crystalline lens, while untinted IOLs resembled the lower levels of blue-light attenuation of younger lenses. Thus, tinted IOLs may protect against the presumed blue-light hazard. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Approaches to breast cancer screening among primary care physicians in rural areas of crete, Greece.

The aim of this study was to assess levels of knowledge regarding breast cancer screening among primary care physicians in rural areas of Crete. A cross-sectional survey of 106 general practitioners and internists and 83 trainee general practitioners (GPs) employed as of October 2004 and practicing at 14 primary health centers in Crete was performed. It was a self-administered survey with 27 items exploring knowledge, attitudes, and behaviors concerning delivery of general preventive and cancer screening services. The main outcome measures were responses to four items on approaches to breast cancer screening practices. Overall response rate was 55% (primary care physicians (PCPs) = 53%; trainee GPs = 60%). Respondents demonstrated a limited awareness of international recommendations for breast cancer screening and exhibited marked variation in their responses to survey items. Agreement with current international guidelines ranged from 31% to 58% for the individual survey items. This survey revealed limited knowledge among PCPs to well-publicized breast cancer screening guidelines and variations in approaches to breast cancer early detection.