A questionnaire to identify patellofemoral pain in the community: an exploration of measurement properties

Background Community-based studies of patellofemoral pain (PFP) need a questionnaire tool that discriminates between those with and those without the condition. To overcome these issues, we have designed a self-report questionnaire which aims to identify people with PFP in the community. Methods Study designs: comparative study and cross-sectional study. Study population: comparative study: PFP patients, soft-tissue injury patients and adults without knee problems. Cross-sectional study: adults attending a science festival. Intervention: comparative study participants completed the questionnaire at baseline and two weeks later. Cross-sectional study participants completed the questionnaire once. The optimal scoring system and threshold was explored using receiver operating characteristic curves, test-retest reliability using Cohen’s kappa and measurement error using Bland-Altman plots and standard error of measurement. Known-group validity was explored by comparing PFP prevalence between genders and age groups. Results Eighty-four participants were recruited to the comparative study. The receiver operating characteristic curves suggested limiting the questionnaire to the clinical features and knee pain map sections (AUC 0.97 95 % CI 0.94 to 1.00). This combination had high sensitivity and specificity (over 90 %). Measurement error was less than the mean difference between the groups. Test–retest reliability estimates suggest good agreement (N = 51, k = 0.74, 95 % CI 0.52–0.91). The cross-sectional study (N = 110) showed expected differences between genders and age groups but these were not statistically significant. Conclusion A shortened version of the questionnaire, based on clinical features and a knee pain map, has good measurement properties. Further work is needed to validate the questionnaire in community samples

Weight management interventions in adults with intellectual disabilities and obesity: a systematic review of the evidence

o evaluate the clinical effectiveness of weight management interventions in adults with intellectual disabilities (ID) and obesity using recommendations from current clinical guidelines for the first line management of obesity in adults. Full papers on lifestyle modification interventions published between 1982 to 2011 were sought by searching the Medline, Embase, PsycINFO and CINAHL databases. Studies were evaluated based on 1) intervention components, 2) methodology, 3) attrition rate 4) reported weight loss and 5) duration of follow up. Twenty two studies met the inclusion criteria. The interventions were classified according to inclusion of the following components: behaviour change alone, behaviour change plus physical activity, dietary advice or physical activity alone, dietary plus physical activity advice and multi-component (all three components). The majority of the studies had the same methodological limitations: no sample size justification, small heterogeneous samples, no information on randomisation methodologies. Eight studies were classified as multi-component interventions, of which one study used a 600 kilocalorie (2510 kilojoule) daily energy deficit diet. Study durations were mostly below the duration recommended in clinical guidelines and varied widely. No study included an exercise program promoting 225–300 minutes or more of moderate intensity physical activity per week but the majority of the studies used the same behaviour change techniques. Three studies reported clinically significant weight loss (≥ 5%) at six months post intervention. Current data indicate weight management interventions in those with ID differ from recommended practice and further studies to examine the effectiveness of multi-component weight management interventions for adults with ID and obesity are justified

Extensive DNA End Processing by Exo1 and Sgs1 Inhibits Break-Induced Replication

Homology-dependent repair of DNA double-strand breaks (DSBs) by gene conversion involves short tracts of DNA synthesis and limited loss of heterozygosity (LOH). For DSBs that present only one end, repair occurs by invasion into a homologous sequence followed by replication to the end of the chromosome resulting in extensive LOH, a process called break-induced replication (BIR). We developed a BIR assay in Saccharomyces cerevisiae consisting of a plasmid with a telomere seeding sequence separated from sequence homologous to chromosome III by an I-SceI endonuclease recognition site. Following cleavage of the plasmid by I-SceI in vivo, de novo telomere synthesis occurs at one end of the vector, and the other end invades at the homologous sequence on chromosome III and initiates replication to the end of the chromosome to generate a stable chromosome fragment (CF). BIR was infrequent in wild-type cells due to degradation of the linearized vector. However, in the exo1Δ sgs1Δ mutant, which is defective in the 5′-3′ resection of DSBs, the frequency of BIR was increased by 39-fold. Extension of the invading end of the plasmid was detected by physical analysis two hours after induction of the I-SceI endonuclease in the wild-type exo1Δ, sgs1Δ, and exo1Δ sgs1Δ mutants, but fully repaired products were only visible in the exo1Δ sgs1Δ mutant. The inhibitory effect of resection was less in a plasmid-chromosome gene conversion assay, compared to BIR, and products were detected by physical assay in the wild-type strain. The rare chromosome rearrangements due to BIR template switching at repeated sequences were increased in the exo1Δ sgs1Δ mutant, suggesting that reduced resection can decrease the fidelity of homologous recombination

Heritability of the dimensions, compliance and distensibility of the human internal jugular vein wall

AIMS: The elasticity of the internal jugular vein (IJV) is a major determinant of cerebral venous drainage and right atrium venous return. However, the level of genetic determination of IJV dimensions, compliance and distensibility has not been studied yet. METHODS: 170 adult Caucasian twins (43 monozygotic [MZ] and 42 dizygotic [DZ] pairs) were involved from the Italian twin registry. Anteroposterior and mediolateral diameters of the IJV were measured bilaterally by ultrasonography. Measurements were made both in the sitting and supine positions, with or without Valsalva maneuver. Univariate quantitative genetic modeling was performed. RESULTS: Genetic factors are responsible for 30-70% of the measured properties of IJV at higher venous pressure even after adjustment for age and gender. The highest level of inheritance was found in the supine position regarding compliance (62%) and venous diameter during Valsalva (69%). Environmental and measurement-related factors instead are more important in the sitting position, when the venous pressure is low and the venous lumen is almost collapsed. The range of capacity changes between the lowest and highest intraluminal venous pressure (full distension range) are mainly determined by genetic factors (58%). CONCLUSIONS: Our study has shown substantial heritability of IJV biomechanics at higher venous pressures even after adjustment for age and gender. These findings yield an important insight to what degree the geometric and elastic properties of the vascular wall are formed by genetic and by environmental factors in humans

Association between ultrasound-detected synovitis and knee pain: a population-based case-control study with both cross-sectional and follow-up data

Background: Recently an important role for synovial pathology in the initiation and progression of knee osteoarthritis (OA) has been emphasised. This study aimed to examine whether ultrasonographydetected synovial changes (USSCs) associate with knee pain (KP) in a community population. Methods: A case-control study was conducted to compare people with early KP (n=298), established KP (n=100) or no KP (n=94) at baseline. Multinomial logistic regression was used to estimate odds ratio (OR) and 95% confidence interval (CI) between groups adjusted for radiographic osteoarthritis (ROA) severity and other confounding factors. After one year 255 participants with early and established KP completed the followup questionnaire for changes in KP. Logistic regression with adjustment was used to determine predictors of KP worsening. Results: At baseline, effusion was associated with early (OR 2.64, 95%CI 1.57 to 4.45) and established KP (OR 5.07, 95%CI 2.74 to 9.38). Synovial hypertrophy was also associated with early (OR 5.43, 95%CI 2.12 to 13.92) and established KP (OR 13.27, 95%CI 4.97 to 35.43). The association with effusion diminished when adjusted for ROA. Power Doppler signal was uncommon (early KP 3%, established KP 2%, controls 0%). Baseline effusion predicted worsening of knee pain at one year (OR 1.95, 95% CI 1.05 to 3.64). However, after adjusting for ROA, the prediction was insignificant (aORs 0.95, 95%CI 0.44 to 2.02). Conclusion: US effusion and synovial hypertrophy are associated with KP, but only effusion predicts KP worsening. However, the association/prediction are not independent from ROA. Power Doppler signal is uncommon in people with KP. Further study is needed to understand whether synovitis is directly involved in different types of KP

The use of CAM and conventional treatments among primary care consulters with chronic musculoskeletal pain

Chronic musculoskeletal pain is the single most cited reason for use of complementary and alternative medicine (CAM). Primary care is the most frequent conventional medical service used by patients with pain in the UK. We are unaware, however, of a direct evidence of the extent of CAM use by primary care patients, and how successful they perceive it to be. Methods Aims and objectives To determine CAM use among patients with chronic musculoskeletal pain who have consulted about their pain in primary care. Study design Face-to-face interview-based survey. Setting Three general practices in North Staffordshire. Participants Respondents to a population pain survey who had reported having musculoskeletal pain in the survey and who had consulted about their pain in primary care in the previous 12 months as well as consenting to further research and agreeing to an interview. Information was gathered about their pain and the use of all treatments for pain, including CAM, in the previous year. Results 138 interviews were completed. 116 participants (84%) had used at least one CAM treatment for pain in the previous year. 65% were current users of CAM. The ratio of over-the-counter CAM use to care from a CAM provider was 3:2. 111 participants (80%) had used conventional treatment. 95 (69%) were using a combination of CAM and conventional treatment. Glucosamine and fish oil were the most commonly used CAM treatments (38%, 35% respectively). Most CAM treatments were scored on average as being helpful, and users indicated that they intended to use again 87% of the CAM treatments they had already used. Conclusion We provide direct evidence that most primary care consulters with chronic musculoskeletal pain have used CAM in the previous year, usually in combination with conventional treatments. The high prevalence and wide range of users experiences of benefit and harm from CAM strengthen the argument for more research into this type of medicine to quantify benefit and assess safety. The observation that most users of conventional medicine also used CAM suggests a continuing need for more investigation of effective pain management in primary care

Competitive Repair by Naturally Dispersed Repetitive DNA during Non-Allelic Homologous Recombination

Genome rearrangements often result from non-allelic homologous recombination (NAHR) between repetitive DNA elements dispersed throughout the genome. Here we systematically analyze NAHR between Ty retrotransposons using a genome-wide approach that exploits unique features of Saccharomyces cerevisiae purebred and Saccharomyces cerevisiae/Saccharomyces bayanus hybrid diploids. We find that DNA double-strand breaks (DSBs) induce NAHR–dependent rearrangements using Ty elements located 12 to 48 kilobases distal to the break site. This break-distal recombination (BDR) occurs frequently, even when allelic recombination can repair the break using the homolog. Robust BDR–dependent NAHR demonstrates that sequences very distal to DSBs can effectively compete with proximal sequences for repair of the break. In addition, our analysis of NAHR partner choice between Ty repeats shows that intrachromosomal Ty partners are preferred despite the abundance of potential interchromosomal Ty partners that share higher sequence identity. This competitive advantage of intrachromosomal Tys results from the relative efficiencies of different NAHR repair pathways. Finally, NAHR generates deleterious rearrangements more frequently when DSBs occur outside rather than within a Ty repeat. These findings yield insights into mechanisms of repeat-mediated genome rearrangements associated with evolution and cancer

The Baker's Yeast Diploid Genome Is Remarkably Stable in Vegetative Growth and Meiosis

Accurate estimates of mutation rates provide critical information to analyze genome evolution and organism fitness. We used whole-genome DNA sequencing, pulse-field gel electrophoresis, and comparative genome hybridization to determine mutation rates in diploid vegetative and meiotic mutation accumulation lines of Saccharomyces cerevisiae. The vegetative lines underwent only mitotic divisions while the meiotic lines underwent a meiotic cycle every ∼20 vegetative divisions. Similar base substitution rates were estimated for both lines. Given our experimental design, these measures indicated that the meiotic mutation rate is within the range of being equal to zero to being 55-fold higher than the vegetative rate. Mutations detected in vegetative lines were all heterozygous while those in meiotic lines were homozygous. A quantitative analysis of intra-tetrad mating events in the meiotic lines showed that inter-spore mating is primarily responsible for rapidly fixing mutations to homozygosity as well as for removing mutations. We did not observe 1–2 nt insertion/deletion (in-del) mutations in any of the sequenced lines and only one structural variant in a non-telomeric location was found. However, a large number of structural variations in subtelomeric sequences were seen in both vegetative and meiotic lines that did not affect viability. Our results indicate that the diploid yeast nuclear genome is remarkably stable during the vegetative and meiotic cell cycles and support the hypothesis that peripheral regions of chromosomes are more dynamic than gene-rich central sections where structural rearrangements could be deleterious. This work also provides an improved estimate for the mutational load carried by diploid organisms

Morbidity and mortality after anaesthesia in early life: results of the European prospective multicentre observational study, neonate and children audit of anaesthesia practice in Europe (NECTARINE)

BACKGROUND: Neonates and infants requiring anaesthesia are at risk of physiological instability and complications, but triggers for peri-anaesthetic interventions and associations with subsequent outcome are unknown. METHODS: This prospective, observational study recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. The primary aim was to identify thresholds of pre-determined physiological variables that triggered a medical intervention. The secondary aims were to evaluate morbidities, mortality at 30 and 90 days, or both, and associations with critical events. RESULTS: Infants (n=5609) born at mean (standard deviation [sd]) 36.2 (4.4) weeks postmenstrual age (35.7% preterm) underwent 6542 procedures within 63 (48) days of birth. Critical event(s) requiring intervention occurred in 35.2% of cases, mainly hypotension (>30% decrease in blood pressure) or reduced oxygenation (SpO2 <85%). Postmenstrual age influenced the incidence and thresholds for intervention. Risk of critical events was increased by prior neonatal medical conditions, congenital anomalies, or both (relative risk [RR]=1.16; 95% confidence interval [CI], 1.04–1.28) and in those requiring preoperative intensive support (RR=1.27; 95% CI, 1.15–1.41). Additional complications occurred in 16.3% of patients by 30 days, and overall 90-day mortality was 3.2% (95% CI, 2.7–3.7%). Co-occurrence of intraoperative hypotension, hypoxaemia, and anaemia was associated with increased risk of morbidity (RR=3.56; 95% CI, 1.64–7.71) and mortality (RR=19.80; 95% CI, 5.87–66.7). CONCLUSIONS: Variability in physiological thresholds that triggered an intervention, and the impact of poor tissue oxygenation on patient's outcome, highlight the need for more standardised perioperative management guidelines for neonates and infants