Sampling and measurement methods for a study of childhood refractive error in a UK population

International audienceBackground There is a paucity of data describing the prevalence of childhood refractive error in the United Kingdom. The Northern Ireland Childhood Errors of Refraction study, along with its sister study the Aston Eye Study, are the first population-based surveys of children using both random cluster sampling and cycloplegic autorefraction to quantify levels of refractive error in the United Kingdom. Methods Children aged 6-7 years and 12-13 years were recruited from a stratified random sample of primary and post-primary schools, representative of the population of Northern Ireland as a whole. Measurements included assessment of visual acuity, oculomotor balance, ocular biometry and cycloplegic binocular open-field autorefraction. Questionnaires were used to identify putative risk factors for refractive error. Results 399 (57%) of 6-7 years and 669 (60%) of 12-13 years participated. School participation rates did not vary statistically significantly with the size of the school, whether the school is urban or rural, or whether it is in a deprived/non-deprived area. The gender balance, ethnicity and type of schooling of participants are reflective of the Northern Ireland population. Conclusions The study design, sample size and methodology will ensure accurate measures of the prevalence of refractive errors in the target population and will facilitate comparisons with other population-based refractive data

Do healthcare professionals and young adults know about the National Chlamydia Screening Programme? Findings from two cross-sectional surveys

The extent to which healthcare professionals (HCPs) and young people (YP) are aware of, and adhere to, National Chlamydia Screening Programme (NCSP) recommendations on testing frequency is unclear. To address this two cross-sectional surveys in 2015-2016: one among genitourinary medicine (GUM) and non-GUM HCPs (n = 109) and the other among YP attending a GUM clinic in England (n = 195). For both, questions were designed to measure awareness of NCSP guidance and whether respondents acted on that knowledge. This included questions about YP's most recent test(s) (if ever) and the time since first and last sex with their most recent partners. Knowledge of NCSP testing guidelines varied among both GUM and non-GUM HCP respondents. However, lack of knowledge of the guidelines did not preclude HCPs from recommending testing in line with NCSP recommendations in practice. While most YP were not aware of NCSP recommendations, around two-thirds had tested for Chlamydia at least once in the last year. However, testing seldom appeared to coincide with partnership change. There is a knowledge gap and a discord between testing recommendations and practice. Interventions are needed to encourage appropriate testing patterns to maximise the individual and public health benefits of testing

The association of APOE genotype and cognitive decline in interaction with risk factors in a 65–69 year old community sample

<p>Abstract</p> <p>Background</p> <p>While the evidence of an association between the apolipoprotein E (<it>APOE</it>) <it>*E4 </it>allele and Alzheimer's disease is very strong, the effect of the <it>*E4 </it>allele on cognitive decline in the general population is more equivocal. A cross-sectional study on the lifespan effects of the <it>*E4 </it>allele <abbrgrp><abbr bid="B1">1</abbr></abbrgrp> failed to find any effect of the <it>*E4 </it>allele on cognitive performance at ages 20–24, 40–44 or 60–64 years.</p> <p>Methods</p> <p>In this four year follow-up study, we reexamine the effect of <it>*E4 </it>in the sample of 2,021 individuals, now aged 65–69 years.</p> <p>Results</p> <p>Performance on the Mini-Mental State Examination (MMSE) was significantly poorer for <it>*E4 </it>homozygotes than heterozygotes or non-carriers. The effects of the <it>*E4 </it>genotype on cognitive decline over four years were found on the MMSE and Symbol-Digit Modalities test but only when controlling for risk factors such as head injury and education. Analyses were repeated with the exclusion of participants diagnosed with a mild cognitive disorder, with little change.</p> <p>Conclusion</p> <p>It is possible that <it>*E4 </it>carriers become vulnerable to greater cognitive decline in the presence of other risk factors at 65–69 years of age.</p

Concurrent administration of Docetaxel and Stealth® liposomal doxorubicin with radiotherapy in non-small cell lung cancer : excellent tolerance using subcutaneous amifostine for cytoprotection

The substantial augmentation of the radiation sequelae during chemo–radiotherapy with novel drugs masks the real potential of such regimens. In this study we examined whether subcutaneous administration of amifostine can reduce the toxicity of a highly aggressive chemo–radiotherapy scheme with Stealth® liposomal doxorubicin (Caelyx®) and Docetaxel (Taxotere®) in non-small cell lung cancer. Twenty-five patients with stage IIIb non-small cell lung cancer were recruited in a phase I/II dose escalation trial. The starting dose of Taxotere® was 20 mg m−2 week and of Caelyx® was 15 mg m−2 every two weeks, during conventionally fractionated radiotherapy (total dose of 64 Gy). The dose of Taxotere®/Caelyx® was, thereafter, increased to 20/25 (five patients) and 30/25 mg m−2 (15 patients). Amifostine 500 mg was given subcutaneously before each radiotherapy fraction, while an i.v. amifostine dose of 1000 mg preceded the infusion of docetaxel. The ‘in-field’ radiation toxicity was low. Grade 3 esophagitis occurred in 9 out of 25 (36%) patients. Apart from a marked reduction of the lymphocyte counts, the regimen was deprived from any haematological toxicity higher than grade 1. No other systemic toxicity was noted. The CR and CR/PR rates in 15 patients treated at the highest dose level was 40% (6 out of 15) and 87% (13 out of 15) respectively. It is concluded that the subcutaneous administration of amifostine during high dose Taxotere®/Caelyx® chemo–radiotherapy is a simple and effective way to render this aggressive regimen perfectly well tolerated, by reducing the systemic and the ‘in-field’ toxicity to the levels expected from simple conventional radiotherapy. The impressive tolerance and the high CR rate obtained encourages the conduct of a relevant randomized trial to assess an eventual survival benefit in patients with non-small cell lung cancer

Preparing for PrEP: estimating the size of the population eligible for HIV pre-exposure prophylaxis among men who have sex with men in England

OBJECTIVES: The size of the population of men who have sex with men (MSM) who may be eligible for HIV pre-exposure prophylaxis (HIV-PrEP) in England remains unknown. To plan for a national PrEP implementation trial, we estimated the number of MSM attending sexual health clinics (SHCs) that may be eligible for HIV-PrEP in England. METHODS: Sexually transmitted infection (STI) surveillance data from 2010 to 2015 from the GUMCAD surveillance system were used to estimate the annual number of HIV-negative MSM who may be eligible for HIV-PrEP in England. Based on national eligibility criteria, we identified HIV-negative MSM attending SHCs with a HIV-negative test in the past year and used diagnosed bacterial STI (past year) in this group as a proxy for condomless sex and eligibility for HIV-PrEP. We estimated HIV incidence per 100 person-years (py) in these groups in 2014. RESULTS: During 2010-2015, the number of HIV-negative MSM attending SHCs with a HIV-negative test in the past year doubled from 14 643 to 29 023, and HIV incidence in this group was 1.9 (95% CI 1.6 to 2.2) per 100 py in 2014. In the same period, the subgroup with a bacterial STI diagnosis (past year), and therefore considered potentially eligible for HIV-PrEP in this analysis, increased from 4365 (30%) to 10 276 (35%). HIV incidence in this subgroup was 3.3 (95% CI 2.7 to 4.0) per 100 py in 2014. CONCLUSIONS: In 2015, approximately 10 000 HIV-negative MSM were considered potentially eligible for HIV-PrEP based on clinic history in GUMCAD. These data were used to inform the initial recruitment target for the PrEP Impact Trial and will inform future evaluations at a population level

Expression of oestrogen receptors, ERα, ERβ, and ERβ variants, in endometrial cancers and evidence that prostaglandin F may play a role in regulating expression of ERα

<p>Abstract</p> <p>Background</p> <p>Endometrial cancer is the most common gynaecological malignancy; risk factors include exposure to oestrogens and high body mass index. Expression of enzymes involved in biosynthesis of oestrogens and prostaglandins (PG) is often higher in endometrial cancers when compared with levels detected in normal endometrium. Oestrogens bind one of two receptors (ERα and ERβ) encoded by separate genes. The full-length receptors function as ligand-activated transcription factors; splice variant isoforms of ERβ lacking a ligand-binding domain have also been described. PGs act in an autocrine or paracrine manner by binding to specific G-protein coupled receptors.</p> <p>Methods</p> <p>We compared expression of ERs, progesterone receptor (PR) and cyclooxygenase-2 (COX-2) in stage 1 endometrial adenocarcinomas graded as well (G1), moderately (G2) or poorly (G3) differentiated (n ≥ 10 each group) using qRTPCR, single and double immunohistochemistry. We used endometrial adenocarcinoma cell lines to investigate the impact of PGF2α on expression of ERs and PR.</p> <p>Results</p> <p>Full length ERβ (ERβ1) and two ERβ variants (ERβ2, ERβ5) were expressed in endometrial cancers regardless of grade and the proteins were immunolocalised to the nuclei of cells in both epithelial and stromal compartments. Immunoexpression of COX-2 was most intense in cells that were ERα^neg/low. Expression of PR in endometrial adenocarcinoma (Ishikawa) cell lines and tissues broadly paralleled that of ERα. Treatment of adenocarcinoma cells with PGF2α reduced expression of ERα but had no impact on ERβ1. Cells incubated with PGF2α were unable to increase expression of PR mRNA when they were incubated with E2.</p> <p>Conclusion</p> <p>We have demonstrated that ERβ5 protein is expressed in stage 1 endometrial adenocarcinomas. Expression of three ERβ variants, including the full-length protein is not grade-dependent and most cells in poorly differentiated cancers are ERβ^pos/ERα^neg. We found evidence of a link between COX-2, its product PGF2α, and expression of ERα and PR that sheds new light on the cross talk between steroid and PG signalling pathways in this disease.</p

Recommendations for a core outcome set for measuring standing balance in adult populations: a consensus-based approach

Standing balance is imperative for mobility and avoiding falls. Use of an excessive number of standing balance measures has limited the synthesis of balance intervention data and hampered consistent clinical practice.To develop recommendations for a core outcome set (COS) of standing balance measures for research and practice among adults.A combination of scoping reviews, literature appraisal, anonymous voting and face-to-face meetings with fourteen invited experts from a range of disciplines with international recognition in balance measurement and falls prevention. Consensus was sought over three rounds using pre-established criteria.The scoping review identified 56 existing standing balance measures validated in adult populations with evidence of use in the past five years, and these were considered for inclusion in the COS.Fifteen measures were excluded after the first round of scoring and a further 36 after round two. Five measures were considered in round three. Two measures reached consensus for recommendation, and the expert panel recommended that at a minimum, either the Berg Balance Scale or Mini Balance Evaluation Systems Test be used when measuring standing balance in adult populations.Inclusion of two measures in the COS may increase the feasibility of potential uptake, but poses challenges for data synthesis. Adoption of the standing balance COS does not constitute a comprehensive balance assessment for any population, and users should include additional validated measures as appropriate.The absence of a gold standard for measuring standing balance has contributed to the proliferation of outcome measures. These recommendations represent an important first step towards greater standardization in the assessment and measurement of this critical skill and will inform clinical research and practice internationally

Refractive Status at Birth: Its Relation to Newborn Physical Parameters at Birth and Gestational Age

Refractive status at birth is related to gestational age. Preterm babies have myopia which decreases as gestational age increases and term babies are known to be hypermetropic. This study looked at the correlation of refractive status with birth weight in term and preterm babies, and with physical indicators of intra-uterine growth such as the head circumference and length of the baby at birth.All babies delivered at St. Stephens Hospital and admitted in the nursery were eligible for the study. Refraction was performed within the first week of life. 0.8% tropicamide with 0.5% phenylephrine was used to achieve cycloplegia and paralysis of accommodation. 599 newborn babies participated in the study. Data pertaining to the right eye is utilized for all the analyses except that for anisometropia where the two eyes were compared. Growth parameters were measured soon after birth. Simple linear regression analysis was performed to see the association of refractive status, (mean spherical equivalent (MSE), astigmatism and anisometropia) with each of the study variables, namely gestation, length, weight and head circumference. Subsequently, multiple linear regression was carried out to identify the independent predictors for each of the outcome parameters.Simple linear regression showed a significant relation between all 4 study variables and refractive error but in multiple regression only gestational age and weight were related to refractive error. The partial correlation of weight with MSE adjusted for gestation was 0.28 and that of gestation with MSE adjusted for weight was 0.10. Birth weight had a higher correlation to MSE than gestational age.This is the first study to look at refractive error against all these growth parameters, in preterm and term babies at birth. It would appear from this study that birth weight rather than gestation should be used as criteria for screening for refractive error, especially in developing countries where the incidence of intrauterine malnutrition is higher