Complement C3 variant and the risk of age-related macular degeneration

Background: Age-related macular degeneration is the most common cause of blindness in Western populations. Susceptibility is influenced by age and by genetic and environmental factors. Complement activation is implicated in the pathogenesis.Methods: We tested for an association between age-related macular degeneration and 13 single-nucleotide polymorphisms (SNPs) spanning the complement genes C3 and C5 in case subjects and control subjects from the southeastern region of England. All subjects were examined by an ophthalmologist and had independent grading of fundus photographs to confirm their disease status. To test for replication of the most significant findings, we genotyped a set of Scottish cases and controls.Results: The common functional polymorphism rs2230199 (Arg80Gly) in the C3 gene, corresponding to the electrophoretic variants C3S (slow) and C3F (fast), was strongly associated with age-related macular degeneration in both the English group (603 cases and 350 controls, P=5.9 x 10(sup -5)) and the Scottish group (244 cases and 351 controls, P=5.0 x 10(sup -5)). The odds ratio for age-related macular degeneration in C3 S/F heterozygotes as compared with S/S homozygotes was 1.7 (95% confidence interval [CI], 1.3 to 2.1); for F/F homozygotes, the odds ratio was 2.6 (95% CI, 1.6 to 4.1). The estimated population attributable risk for C3F was 22%.Conclusions: Complement C3 is important in the pathogenesis of age-related macular degeneration. This finding further underscores the influence of the complement pathway in the pathogenesis of this disease

The foot posture index, ankle lunge test, Beighton scale and the lower limb assessment score in healthy children: a reliability study

<p>Abstract</p> <p>Background</p> <p>Outcome measures are important when evaluating treatments and physiological progress in paediatric populations. Reliable, relevant measures of foot posture are important for such assessments to be accurate over time. The aim of the study was to assess the intra- and inter-rater reliability of common outcome measures for paediatric foot conditions.</p> <p>Methods</p> <p>A repeated measures, same-subject design assessed the intra- and inter-rater reliability of measures of foot posture, joint hypermobility and ankle range: the Foot Posture Index (FPI-6), the ankle lunge test, the Beighton scale and the lower limb assessment scale (LLAS), used by two examiners in 30 healthy children (aged 7 to 15 years). The Oxford Ankle Foot Questionnaire (OxAFQ-C) was completed by participants and a parent, to assess the extent of foot and ankle problems.</p> <p>Results</p> <p>The OxAFQ-C demonstrated a mean (SD) score of 6 (6) in adults and 7(5) for children, showing good agreement between parents and children, and which indicates mid-range (transient) disability. Intra-rater reliability was good for the FPI-6 (ICC = 0.93 - 0.94), ankle lunge test (ICC = 0.85-0.95), Beighton scale (ICC = 0.96-0.98) and LLAS (ICC = 0.90-0.98). Inter-rater reliability was largely good for each of the: FPI-6 (ICC = 0.79), ankle lunge test (ICC = 0.83), Beighton scale (ICC = 0.73) and LLAS (ICC = 0.78).</p> <p>Conclusion</p> <p>The four measures investigated demonstrated adequate intra-rater and inter-rater reliability in this paediatric sample, which further justifies their use in clinical practice.</p

The paediatric flat foot and general anthropometry in 140 Australian school children aged 7 - 10 years

<p>Abstract</p> <p>Background</p> <p>Many studies have found a positive relationship between increased body weight and flat foot posture in children.</p> <p>Methods</p> <p>From a study population of 140 children aged seven to 10 years, a sample of 31 children with flat feet was identified by screening with the FPI-6. Basic anthropometric measures were compared between subjects with and without flat feet as designated.</p> <p>Results</p> <p>The results of this study, in contrast to many others, question the association of flat feet and heavy children. A significant relationship between foot posture and weight (FPI (L) r = -0.186 (p < 0.05), FPI(R) r = -0.194 (p < 0.05), waist girth (FPI (L) r = -0.213 (p < 0.05), FPI(R) r = -0.228 (p < 0.01) and BMI (FPI (L) r = -0.243 (p < 0.01), FPI(R) r = -0.263 (p < 0.01) was identified, but was both weak and inverse.</p> <p>Conclusions</p> <p>This study presents results which conflict with those of many previous investigations addressing the relationship between children's weight and foot posture. In contrast to previous studies, the implication of these results is that heavy children have less flat feet. Further investigation is warranted using a standardized approach to assessment and a larger sample of children to test this apparent contradiction.</p

Normative values for the Foot Posture Index

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Development and internal validation of a clinical rule to improve antibiotic use in children presenting to primary care with acute respiratory tract infection and cough: a prognostic cohort study

BACKGROUND: Antimicrobial resistance is a serious threat to public health, with most antibiotics prescribed in primary care. General practitioners (GPs) report defensive antibiotic prescribing to mitigate perceived risk of future hospital admission in children with respiratory tract infections. We developed a clinical rule aimed to reduce clinical uncertainty by stratifying risk of future hospital admission. METHODS: 8394 children aged between 3 months and 16 years presenting with acute cough (for ≤28 days) and respiratory tract infection were recruited to a prognostic cohort study from 247 general practitioner practices in England. Exposure variables included demographic characteristics, parent-reported symptoms, and physical examination signs. The outcome was hospital admission for respiratory tract infection within 30 days, collected using a structured, blinded review of medical records. FINDINGS: 8394 (100%) children were included in the analysis, with 78 (0·9%, 95% CI 0·7%-1·2%) admitted to hospital: 15 (19%) were admitted on the day of recruitment (day 1), 33 (42%) on days 2-7; and 30 (39%) on days 8-30. Seven characteristics were independently associated (p<0·01) with hospital admission: age <2 years, current asthma, illness duration of 3 days or less, parent-reported moderate or severe vomiting in the previous 24 h, parent-reported severe fever in the previous 24 h or a body temperature of 37·8°C or more at presentation, clinician-reported intercostal or subcostal recession, and clinician-reported wheeze on auscultation. The area under the receiver operating characteristic (AUROC) curve for the coefficient-based clinical rule was 0·82 (95% CI 0·77-0·87, bootstrap validated 0·81). Assigning one point per characteristic, a points-based clinical rule consisting of short illness, temperature, age, recession, wheeze, asthma, and vomiting (mnemonic STARWAVe; AUROC 0·81, 0·76-0·85) distinguished three hospital admission risk strata: very low (0·3%, 0·2-0·4%) with 1 point or less, normal (1·5%, 1·0-1·9%) with 2 or 3 points, and high (11·8%, 7·3-16·2%) with 4 points or more. INTERPRETATION: Clinical characteristics can distinguish children at very low, normal, and high risk of future hospital admission for respiratory tract infection and could be used to reduce antibiotic prescriptions in primary care for children at very low risk. FUNDING: National Institute for Health Research (NIHR)

Consensus on pre-operative total knee replacement education and prehabilitation recommendations: a UK-based modified Delphi study

Background Over 90,000 total knee replacement (TKR) procedures are performed annually in the United Kingdom (UK). Patients awaiting TKR face long delays whilst enduring severe pain and functional limitations. Almost 20% of patients who undergo TKR are not satisfied post-operatively. Optimising pre-operative TKR education and prehabilitation could help improve patient outcomes pre- and post-operatively; however, current pre-operative TKR care varies widely. Definitive evidence on the optimal content and delivery of pre-operative TKR care is lacking. This study aimed to develop evidence- and consensus-based recommendations on pre-operative TKR education and prehabilitation. Methods A UK-based, three-round, online modified Delphi study was conducted with a 60-member expert panel. All panellists had experience of TKR services as patients (n = 30) or professionals (n = 30). Round 1 included initial recommendations developed from a mixed methods rapid review. Panellists rated the importance of each item on a five-point Likert scale. Panellists could also suggest additional items in Round 1. Rounds 2 and 3 included all items from Round 1, new items suggested in Round 1 and charts summarising panellists’ importance ratings from the preceding round. Free-text responses were analysed using content analysis. Quantitative data were analysed descriptively. All items rated as ‘Important’ or ‘Very important’ by at least 70% of all respondents in Round 3 were included in the final set of recommendations. Results Fifty-five panellists (92%) (patients n = 26; professionals n = 29) completed Round 3. Eighty-six recommendation items were included in Round 1. Fifteen new items were added in Round 2. Rounds 2 and 3 therefore included 101 items. Seventy-seven of these reached consensus in Round 3. Six items reached consensus amongst patient or professional panellists only in Round 3. The final set of recommendations comprises 34 education topics, 18 education delivery approaches, 10 exercise types, 13 exercise delivery approaches and two other treatments. Conclusions This modified Delphi study developed a comprehensive set of recommendations that represent a useful resource for guiding decision-making on the content and delivery of pre-operative TKR education and prehabilitation. The recommendations will need to be interpreted and reviewed periodically in light of emerging evidence

Rearrangement processes and structural variations show evidence of selection in oesophageal adenocarcinomas

Oesophageal adenocarcinoma (OAC) provides an ideal case study to characterize large-scale rearrangements. Using whole genome short-read sequencing of 383 cases, for which 214 had matched whole transcriptomes, we observed structural variations (SV) with a predominance of deletions, tandem duplications and inter-chromosome junctions that could be identified as LINE-1 mobile element (ME) insertions. Complex clusters of rearrangements resembling breakage-fusion-bridge cycles or extrachromosomal circular DNA accounted for 22% of complex SVs affecting known oncogenes. Counting SV events affecting known driver genes substantially increased the recurrence rates of these drivers. After excluding fragile sites, we identified 51 candidate new drivers in genomic regions disrupted by SVs, including ETV5, KAT6B and CLTC. RUNX1 was the most recurrently altered gene (24%), with many deletions inactivating the RUNT domain but preserved the reading frame, suggesting an altered protein product. These findings underscore the importance of identification of SV events in OAC with implications for targeted therapies

Classification of the height and flexibility of the medial longitudinal arch of the foot

<p>Abstract</p> <p>Background</p> <p>The risk of developing injuries during standing work may vary between persons with different foot types. High arched and low arched feet, as well as rigid and flexible feet, are considered to have different injury profiles, while those with normal arches may sustain fewer injuries. However, the cut-off values for maximum values (subtalar position during weight-bearing) and range of motion (ROM) values (difference between subtalar neutral and subtalar resting position in a weight-bearing condition) for the medial longitudinal arch (MLA) are largely unknown. The purpose of this study was to identify cut-off values for maximum values and ROM of the MLA of the foot during static tests and to identify factors influencing foot posture.</p> <p>Methods</p> <p>The participants consisted of 254 volunteers from Central and Northern Denmark (198 m/56 f; age 39.0 ± 11.7 years; BMI 27.3 ± 4.7 kg/m²). Navicular height (NH), longitudinal arch angle (LAA) and Feiss line (FL) were measured for either the left or the right foot in a subtalar neutral position and subtalar resting position. Maximum values and ROM were calculated for each test. The 95% and 68% prediction intervals were used as cut-off limits. Multiple regression analysis was used to detect influencing factors on foot posture.</p> <p>Results</p> <p>The 68% cut-off values for maximum MLA values and MLA ROM for NH were 3.6 to 5.5 cm and 0.6 to 1.8 cm, respectively, without taking into account the influence of other variables. Normal maximum LAA values were between 131 and 152° and normal LAA ROM was between -1 and 13°. Normal maximum FL values were between -2.6 and -1.2 cm and normal FL ROM was between -0.1 and 0.9 cm. Results from the multivariate linear regression revealed an association between foot size with FL, LAA, and navicular drop.</p> <p>Conclusions</p> <p>The cut-off values presented in this study can be used to categorize people performing standing work into groups of different foot arch types. The results of this study are important for investigating a possible link between arch height and arch movement and the development of injuries.</p