Recommendations for the delivery of therapeutic exercise for people with knee and/or hip osteoarthritis. An international consensus study from the OARSI Rehabilitation Discussion Group.

OBJECTIVE: To develop evidence-informed recommendations to support the delivery of best practice therapeutic exercise for people with knee and/or hip osteoarthritis (OA). DESIGN: A multi-stage, evidence-informed, international multi-disciplinary consensus process that included: 1) a narrative literature review to synthesise existing evidence; 2) generation of evidence-informed proposition statements about delivery of exercise for people with knee and/or hip OA by an international multi-disciplinary expert panel, with statements refined and analysed thematically; 3) an e-Delphi survey with the expert panel to gain consensus on the most important statements; 4) a final round of statement refinement and thematic analysis to group remaining statements into domains. RESULTS: The expert panel included 318 members (academics, health care professionals and exercise providers, patient representatives) from 43 countries. Final recommendations comprised 54 specific proposition statements across 11 broad domains: 1) use an evidence-based approach; 2) consider exercise in the context of living with OA and pain; 3) undertake a comprehensive baseline assessment with follow-up; 4) set goals; 5) consider the type of exercise; 6) consider the dose of exercise; 7) modify and progress exercise; 8) individualise exercise; 9) optimise the delivery of exercise; 10) focus on exercise adherence; and 11) provide education about OA and the role of exercise. CONCLUSION: The breadth of issues identified as important by the international diverse expert panel highlights that delivering therapeutic exercise for OA is multi-dimensional and complex.

Effect of foot orthoses vs sham insoles on first metatarsophalangeal joint osteoarthritis symptoms: a randomized controlled trial.

OBJECTIVES: To compare contoured foot orthoses to sham flat insoles for first MTP joint OA walking pain. DESIGN: This was a participant- and assessor-blinded, sham-controlled, multi-centre randomized clinical trial set in community-based private practices. Eighty-eight adults aged ≥45 years with symptomatic radiographic first MTP joint OA were randomized to receive contoured foot orthoses (n = 47) or sham flat insoles (n = 41), worn at all times when wearing shoes for 12 weeks. Primary outcome was change in first MTP joint walking pain (11-point numerical rating scale (NRS), 0-10) over 12 weeks. Secondary outcomes included additional first MTP joint and foot pain measures, physical function, quality of life and physical activity. Separate linear regression models for primary and secondary outcomes on treatment group were fit, adjusting for the outcome at baseline and podiatrist. Other measures included adverse events. RESULTS: 88 participants were randomized and 87 (99%) completed the 12-week primary outcome. There was no evidence foot orthoses were superior to sham insoles for reducing pain (mean difference -0.3 NRS units (95% CI -1.2 to 0.6), p = 0.53). Similarly, foot orthoses were not superior to sham on any secondary outcomes. Sensitivity analyses yielded similar results. Adverse events were generally minor and transient. CONCLUSION: Contoured foot orthoses are no more effective than flat sham insoles for the clinical management of first MTP joint OA. Given the dearth of evidence on treatments for first MTP joint OA, further research is needed to identify effective management approaches for this common and debilitating condition.

Walking-related knee contact forces and associations with knee pain across people with mild, moderate and severe radiographic knee osteoarthritis: a cross-sectional study.

OBJECTIVE: To investigate knee contact forces (KCFs), and their relationships with knee pain, across grades of radiographic knee osteoarthritis (OA) severity. DESIGN: Cross-sectional exploratory analysis of 164 participants with medial knee OA. Radiographic severity was classified as mild (grade 2), moderate (grade 3) or severe (grade 4) using the Kellgren & Lawrence (KL) scale. Walking knee pain was assessed using an 11-point numerical rating scale. External knee adduction moment (external KAM) and internal muscle forces were used to calculate medial, lateral and total KCFs using a musculoskeletal computational model. Force-time series across stance phase of gait were compared across KL grades using Statistical Parametric Mapping. Associations between KCFs and pain across KL grades were assessed using linear models. RESULTS: Medial KCFs during early and middle stance were higher in participants with KL3 and KL4 compared to those with KL2. In contrast, lateral KCFs were higher in those with KL2 compared to KL3 and KL4 in middle to late stance. The external loading component (i.e., KAM) of the medial KCF during middle to late stance was also greater in participants with KL3 and KL4 compared to those with KL2, whereas the internal (i.e., muscle) component was greater in those with KL3 and KL4 compared to KL3 during early stance. There were no associations between medial KCF and knee pain in any KL grade. CONCLUSIONS: Medial and lateral KCFs differ between mild, moderate and severe radiographic knee OA but are not associated with knee pain severity for any radiographic OA grade.

Can pain flares in knee osteoarthritis be predicted?

Objectives: This study examined whether risk factors for knee osteoarthritis (KOA) pain such as age, gender, body mass index (BMI), baseline pain, and other putative risk factors for knee osteoarthritis pain flares (KOAF) (e.g. knee buckling, injury, mood/stress/social support scores, and footwear) could predict KOAF.Method: People with KOA and previous history of KOAF were selected from a 3 month web-based longitudinal study. KOAF was defined as an increase of ≥ 2 points on a numeric rating scale (compared with background pain) which resolved within 20 days. Predictors assessed at baseline were gender, age, duration of KOA, BMI, pain, knee injury (7 days before), knee buckling (2 days before), Lubben Social Support, Knee Injury and Osteoarthritis Outcome Score, Intermittent and Constant Osteoarthritis Pain score (ICOAP), Positive/Negative Affect Score, and footwear stability/heel height. Outcome was occurrence of any KOAF during the ensuing 30 days. The combined ability of the above variables to predict occurrence of any KOAF was evaluated by multiple logistic regression with a 10-fold cross-validation method to build and internally validate the model. Variables that assessed similar domains were eliminated using receiver operating characteristics curve assessment for best fit.Results: Complete data were available for 313 people (66.6% female, mean ± sd age 62.3 ± 8.2 years, BMI 29.7 ± 6.5 kg/m2). Increasing age, years of osteoarthritis, BMI, background/worst levels of pain, knee injury, knee buckling, ICOAP, and footwear category/heel height significantly predicted the occurrence of KOAF during the following 30 days, with an area under the curve of 0.73 (95% confidence interval 0.67-0.80).Conclusion: A combination of risk factors assessed at baseline, including exposures with potential to vary, successfully predicts the KOAF in the ensuing 30 days.

Association of weather factors with the risk of pain exacerbations in people with hip osteoarthritis.

Objectives: Our objective was to evaluate the association of weather factors with the risk of pain exacerbations in people with symptomatic hip osteoarthritis (OA). Method: Eligible participants with symptomatic hip OA were instructed to log on to the study website and complete questionnaires every 10 days and additionally whenever they considered they were experiencing a pain exacerbation (case period) during the 90 day follow-up. Pain exacerbation was defined as an increase of two points in pain intensity on an 11-point numeric rating scale (0-10) during the follow-up compared with baseline. Each case period was anchored to four control periods within a 35 day interval using a time-stratified approach. Weather data were obtained for both periods from the publicly available meteorological database of the Australian Bureau of Meteorology. We examined the association of weather factors across 72 h before the index date with the risk of pain exacerbation, using conditional logistic regression. Results: Among 252 participants recruited, 129 participants had at least one episode of pain exacerbation and were included in the analysis. A significant dose-response relationship was found between average daily temperature variation in the prior 72 h and risk of pain exacerbations (p = 0.04 for linear trend). There was no significant association between maximum daily temperature, minimum daily temperature, relative humidity, precipitation, or barometric pressure and hip pain exacerbations. Conclusion: The overall results suggest that only daily temperature variation among different weather factors was associated with hip pain exacerbations in people with symptomatic hip OA.

What type of exercise is most effective for people with knee osteoarthritis and co-morbid obesity?: The TARGET randomized controlled trial.

OBJECTIVE: Different exercise types may yield different outcomes in osteoarthritis (OA) subgroups. The objective was to directly compare effectiveness of two exercise programs for people with medial knee OA and co-morbid obesity. DESIGN: We performed a participant- and assessor-blinded randomized controlled trial. 128 people ≥50 years with medial knee OA and body mass index ≥30 kg/m2 were recruited from the community. Interventions were home-based non-weight bearing (NWB) quadriceps strengthening or weight bearing (WB) functional exercise for 12 weeks. Primary outcomes were change in overall knee pain (numeric rating scale, range 0-10) and difficulty with physical function (Western Ontario and McMaster Universities Osteoarthritis Index, 0-68) over 12 weeks. Secondary outcomes included other pain measures, physical function, quality-of-life, global changes, physical performance, and lower-limb muscle strength. RESULTS: 123 (96%) participants were retained. There was no evidence of a between-group difference in change in pain (mean difference 0.73 units (95% confidence intervals (0.05,1.50)) or function (2.80 units (-1.17,6.76)), with both groups reporting improvements. For secondary outcomes, the WB group had greater improvement in quality-of-life (-0.043 units (-0.085,-0.001)) and more participants reporting global improvement (overall: relative risk 1.40 (0.98,2.01); pain 1.47 (0.97,2.24); function 1.43 (1.04,1.98). Although adverse events were minor, more NWB group participants reported ≥1 adverse event (26/66 (39%) vs 14/62 (23%), p = 0.04). CONCLUSIONS: Both exercise types similarly improved primary outcomes of pain and function and can be recommended for people with knee OA and obesity. WB exercise may be preferred given fewer adverse events and potential additional benefits on some secondary outcomes. REGISTRATION: Prospectively registered (Australian New Zealand Clinical Trials Registry #12617001013358, 14/7/2017).

Multistate population and whole genome sequence-based strain surveillance of invasive pneumococci recovered in the USA during 2017.

OBJECTIVES: We aimed to provide population-based and whole-genome sequence (WGS) -based characterization of invasive pneumococcal disease isolates collected from multistate surveillance in the USA during 2017. METHODS: We obtained short-read WGS from 2881 isolates with associated bioinformatics pipeline strain feature predictions. For quality control, capsular serotypes and antimicrobial MICs were also obtained conventionally from 442 isolates. Annotated WGS were provided (inclusive of serotypes, MICs, multilocus sequence types, pilus type(s)) from 2723 isolates. For 158 isolates with suboptimal WGS, antimicrobial MICs were obtained conventionally. RESULTS: There were 127 isolates from children <5 years of age and 2754 isolates from those ≥5 years old in 2017. One of 43 different serotypes was predicted for 2877 of the 2881 isolates. Serotypes in the 13-valent conjugate vaccine together with 6C (PCV13+6C) accounted for 816 (28.3%) isolates, with PCV13 serotype 3 being the most common serotype overall. Non-PCV13-6C- serotypes accounted for 2065 (71.7%) isolates, comprising 96 (75.6%) isolates from children < 5 years old and 1969 (61.4%) isolates from those aged ≥5 years. Of 36 different categories of recently emerged serotype-switch variants, three showed marked increases relative to 2015-2016 in that the number from 2017 surpassed the number from 2015-2016 combined. Two of these included antimicrobial-resistant serotype 11A and 35B serotype-switch variants of the ST156 clonal complex. CONCLUSIONS: PCV13+6C strains are still identified in 2017 but non-PCV13-type strains impose a considerable burden. This well-annotated year 2017 WGS/strain data set will prove useful for a broad variety of analyses and improved our understanding of invasive pneumococcal disease-causing strains in the post-PCV13 era.

The influence of sex and pre-operative obesity on biomechanics two years after total knee arthroplasty: A longitudinal cohort study.

BACKGROUND: Sex and obesity may influence knee biomechanics associated with poor outcomes following primary total knee arthroplasty (TKA) however their long-term impact has not been investigated. RESEARCH QUESTION: Does sex and/or pre-operative obesity influence change in gait biomechanics from pre-TKA to two-years after TKA, and do knee biomechanics return to normal two-years after TKA? METHODS: In this longitudinal study, gait analysis was performed on 78 patients undergoing TKA for knee osteoarthritis prior to surgery (baseline), and on 66 (85 %) of these who returned at the two year follow-up. Gait biomechanics were also collected on a reference sample of 40 asymptomatic participants. Knee variables were analyzed according to time (pre- and post-TKA), sex (men and women), pre-operative obesity (obese vs non-obese), and group (TKA vs reference). Mixed linear regression models were used to examine the effects of TKA, obesity status, gender and all interactions. RESULTS: There were two-year reductions in peak knee frontal plane angle (mean difference -7.21°; 95% confidence intervals -9.37 to -5.05), peak knee adduction moment (KAM) (-17.64Nm; -23.04 to -12.24) and KAM impulse (-9.40Nm.s; -12.04 to -6.77) in males. These and other variables were unchanged in women. At two years, men exhibited a greater varus-valgus thrust excursion (4.9°; 2.7-7.2), and a lower peak knee frontal plane angle (-4.4°; -7.1 to -1.7) and peak KAM (-13.1Nm; -20.9 to -5.4), compared to the reference sample. Biomechanics at two years did not differ between pre-operative obesity subgroups, or between female TKA patients and the reference sample. SIGNIFICANCE: Changes in gait biomechanics two years after TKA are influenced by sex but not obesity. Men but not women showed altered knee biomechanics two years following TKR and compared to a reference sample. It is unknown whether these altered biomechanics in men impact longer term clinical outcomes and satisfaction following surgery.

Prolonged and large outbreak of invasive group A Streptococcus disease within a nursing home: repeated intrafacility transmission of a single strain.

OBJECTIVES: Multiple invasive group A Streptococcus (GAS) infections were reported to public health by a skilled nursing facility (facility A) in Illinois between May 2014 and August 2016. Cases continued despite interventions including antibiotic prophylaxis for all residents and staff. Two other geographically close facilities reported contemporaneous outbreaks of GAS. We investigated potential reasons for ongoing transmission. METHODS: We obtained epidemiologic data from chart review of cases and review of facility and public health records from previous investigations into the outbreak. Infection control practices at facility A were observed and evaluated. Whole genome sequencing followed by phylogenetic analysis was performed on available isolates from the three facilities. RESULTS: From 2014 to 2016, 19 invasive and 60 noninvasive GAS infections were identified at facility A occurring in three clusters. Infection control evaluations during clusters 2 and 3 identified hand hygiene compliance rates of 14% to 25%, appropriate personal protective equipment use in only 33% of observed instances, and deficient wound-care practices. GAS isolates from residents and staff of all three facilities were subtype emm89.0; on phylogenetic analysis, facility A isolates were monophyletic and distinct. CONCLUSIONS: Inadequate infection control and improper wound-care practices likely led to this 28-month-long outbreak of severe infections in a skilled nursing facility. Whole genome sequencing and phylogenetic analysis suggested that intrafacility transmission of a single highly transmissible GAS strain was responsible for the outbreak in facility A. Integration of genomic epidemiology tools with traditional epidemiology and infection control assessments was helpful in investigation of a facility-wide outbreak.

Moderators and mediators of effects of unloading shoes on knee pain in people with knee osteoarthritis: an exploratory analysis of the SHARK randomised controlled trial.

OBJECTIVE: To investigate moderators and biomechanical mediators of effects of unloading shoes on knee pain in people with knee osteoarthritis (OA). METHODS: Exploratory analysis from 164 participants in a clinical trial comparing unloading (ASICS GEL-Melbourne OA) to conventional walking shoes. The primary outcome was 6-month change in knee pain (11-point numerical rating scale (NRS)). Moderators included baseline peak knee adduction moment (KAM), radiographic severity (Kellgren & Lawrence (KL) scale), body mass, foot posture, neuropathic pain and diffuse knee pain. Mediators included change in peak KAM and KAM impulse. RESULTS: Radiographic severity was the only moderator to interact with footwear group (P = 0.02). Participants with KL = 2 experienced greater pain reductions with conventional compared to unloading shoes (mean difference in change in pain -1.64 units, 95% CI -3.07, -0.21), while unloading shoes tended to result in greater pain reductions than conventional shoes in KL = 3 (0.98, 95% CI -0.44, 2.39) and KL = 4 (0.64, 95% CI -0.64, 1.93). No variable showed any significant mediating effect in the entire cohort. However, there was some evidence that unloading shoes may reduce pain through reductions in peak KAM (indirect effect -0.31, 95% CIs -0.65, 0.03; P = 0.07) in people with KL ≥ 3, compared to conventional shoes. CONCLUSION: Unloading shoes conferred additional symptomatic benefits over conventional shoes in people with moderate to severe knee OA. There was some evidence effects may be mediated by a reduction in peak KAM. However, we were underpowered for subgroup analyses. These patients may represent a subgroup to which biomechanical interventions designed to reduce the KAM may be more effectively targeted.

Short-read whole genome sequencing for determination of antimicrobial resistance mechanisms and capsular serotypes of current invasive Streptococcus agalactiae recovered in the USA.

OBJECTIVES: Our objective was to evaluate and exploit a whole genome sequence (WGS) bioinformatics pipeline for predicting antimicrobial resistance and capsular serotypes from invasive group B streptococci (iGBS). METHODS: For 1975 iGBS recovered during 2015 from CDC's Active Bacterial Core surveillance, we compared pipeline predictions with broth dilution testing. Fifty-six isolates from earlier surveillance were included for testing ß-lactams. Conventional serotyping was compared to WGS-based assignments for 302 isolates. RESULTS: All 28 isolates with reduced susceptibility to ß-lactam antibiotics harboured one of 19 rare PBP2x types. Resistances to erythromycin/clindamycin (808/1975 isolates, 41.0%), erythromycin (235/1975, 11.9%) and lincosamide/streptogramin A/pleuromutilins (56/1975, 2.8%) were predicted by the presence of erm-methylase, mef and lsa determinants, respectively (41 of 56 lsa gene-positive isolates also contained lnu, erm and/or mef genes). Presence of both erm and lsa determinants (25 isolates) predicted non-susceptibility to quinupristin/dalfopristin. Most isolates (1680/1975, 85.1%) were tet gene-positive, although 41/1565 (2.6%) tetM-positive isolates were tetracycline-susceptible. All 53 fluoroquinolone-resistant isolates contained ParC and/or GyrA substitutions. Resistances to rifampin (eight isolates), trimethoprim, chloramphenicol and vancomycin (two isolates each) were predicted by the pipeline. Resistance to macrolides/lincosamides without pipeline prediction was rare and correlated to divergent resistance genes or rRNA A2062G substitution. A selection of 267 isolates assigned WGS-based serotypes were also conventionally serotyped. Of these, 246 (92.1%) were in agreement, with the remaining 21 (7.8%) conventionally non-serotypeable. For 32 of 1975 isolates (1.6%), WGS-based serotypes could not be assigned. CONCLUSION: The WGS-based assignment of iGBS resistance features and serotypes is an accurate substitute for phenotypic testing.

Effects of footwear on the knee adduction moment in medial knee osteoarthritis: classification criteria for flat flexible vs stable supportive shoes.

OBJECTIVE: To validate simple criteria that distinguish flat flexible from stable supportive walking shoes by comparing their effects on the knee adduction moment (KAM) in people with medial knee osteoarthritis (OA). DESIGN: This was a cross-sectional biomechanical study. We proposed five criteria to differentiate flat flexible from stable supportive shoes, and selected three pairs of shoes representing each class for biomechanical testing. 28 participants aged ≥50 years with symptomatic medial knee OA underwent gait analysis barefoot and wearing each of the six selected shoes, in random order. Differences in the peak KAM, KAM impulse and peak knee flexion moment (KFM) across test conditions were evaluated with a two-way repeated measures analysis of variance (ANOVA). Immediate changes in walking pain between conditions were also compared. RESULTS: Increases in KAM from barefoot were lower with each of the three flat flexible shoe styles (peak KAM: 6.1-8.9%; KAM impulse: 2.4-5.1%) compared to their stable supportive counterparts (peak KAM: 11.6-15.1%; KAM impulse 10.5-13.2%). There was a significant main effect for footwear class on peak KAM and KAM impulse, whereby stable supportive shoes increased the KAM significantly more than flat flexible shoes (P < 0.001). There were no differences in the KFM or immediate walking pain between footwear classes. CONCLUSIONS: Our proposed criteria can be used by researchers and clinicians to select flat flexible shoes for people with medial knee OA to minimise knee loading. Future research should evaluate whether wearing shoes based on these criteria translates to improvements in knee OA symptoms and/or slows structural disease progression.

The knee adduction moment and knee osteoarthritis symptoms: relationships according to radiographic disease severity.

OBJECTIVE: To investigate relationships between external knee adduction moment parameters (KAM) and osteoarthritis (OA) symptoms according to disease severity. DESIGN: 164 participants with symptomatic medial knee OA were included. Radiographic severity was graded by (1) Kellgren & Lawrence (KL) scale (Grade 2, n = 49; Grade, n = 52; Grade 4, n = 63) and; (2) medial tibiofemoral joint space narrowing (JSN) (Grade 1, n = 47; Grade 2, n = 50; Grade 3, n = 67). KAM-related parameters (peak KAM, KAM impulse and cumulative load) were determined from three-dimensional gait analysis and pedometry. Cumulative load was determined by multiplying KAM impulse by the average number of steps/day recorded over at least 5 days. Symptoms were assessed via numeric rating scale ((NRS), pain) and Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index (pain and physical function). Relationships between KAM parameters (independent variables) and symptoms (dependent variables) were evaluated by radiographic severity using linear models, adjusting for covariates. RESULTS: In mild disease (either KL Grade 2 or JSN Grade 1), there were no associations between KAM and symptoms. In moderate disease of KL Grade 3, higher KAM impulse was associated with greater WOMAC pain. In severe disease (KL Grade 4), higher KAM impulse was associated with less WOMAC pain (KL Grade 4), while higher peak KAM was associated with better function (KL Grade 4). Higher cumulative knee adduction load was associated with less pain on both NRS and WOMAC (JSN Grade 3) as well as better function (both JSN Grade 3 and KL Grade 4). CONCLUSIONS: Relationships between KAM-related parameters and symptoms differ according to underlying radiographic OA severity.

Nonclassicality Criteria in Multiport Interferometry.

Interference lies at the heart of the behavior of classical and quantum light. It is thus crucial to understand the boundaries between which interference patterns can be explained by a classical electromagnetic description of light and which, on the other hand, can only be understood with a proper quantum mechanical approach. While the case of two-mode interference has received a lot of attention, the multimode case has not yet been fully explored. Here we study a general scenario of intensity interferometry: we derive a bound on the average correlations between pairs of output intensities for the classical wavelike model of light, and we show how it can be violated in a quantum framework. As a consequence, this violation acts as a nonclassicality witness, able to detect the presence of sources with sub-Poissonian photon-number statistics. We also develop a criterion that can certify the impossibility of dividing a given interferometer into two independent subblocks.

Evidence for energy conservation during pubertal growth. A 10-year longitudinal study (EarlyBird 71).

BACKGROUND: Diabetes is closely linked to obesity, and obesity rates climb during adolescence for reasons that are not clear. Energy efficiency is important to obesity, and we describe a temporary but substantial fall in absolute energy expenditure, compatible with improved energy efficiency, during the rapid growth phase of puberty. METHODS: In a longitudinal cohort study lasting 10 years, we measured voluntary energy expenditure as physical activity (PA) by accelerometry, involuntary energy expenditure as resting energy expenditure (REE) by oxygen consumption, body mass index (BMI) and body composition by dual energy X-ray absorptiometry annually on 10 occasions from 7 to 16 years in the 347 children of the EarlyBird study. We used mixed effects modelling to analyse the trends in REE and their relationship to BMI, lean mass (LM), fat mass (FM), age, PA and pubertal stage. RESULTS: Relative REE and total PA fell during puberty, as previously described, but the longitudinal data and narrow age-range of the cohort (s.d.±4m) revealed for the first time a substantial fall in absolute REE during the period of maximum growth. The fall became clearer still when adjusted for FM and LM. The fall could not be explained by fasting insulin, adiponectin, leptin, luteinising hormone or follicle stimulating hormone. CONCLUSIONS: There appears to be a temporary but substantial reduction in energy expenditure during puberty, which is unrelated to changes in body composition. If it means higher energy efficiency, the fall in REE could be advantageous in an evolutionary context to delivering the extra energy needed for pubertal growth, but unfavourable to weight gain in a contemporary environment.

The influence of weather on the risk of pain exacerbation in patients with knee osteoarthritis - a case-crossover study.

OBJECTIVE: To quantify the risk of knee pain exacerbation associated with temperature, relative humidity, air pressure and precipitation in persons with knee osteoarthritis. METHOD: A web-based case-crossover study was conducted. Participants with a diagnosis of symptomatic, radiographic knee osteoarthritis were measured at baseline and followed for 3 months. Participants were instructed to log on to the study website if they perceived experiencing knee pain exacerbation (hazard period). Pain exacerbation was defined as an increase of ≥2 on a 0-10 numeric rating scale (NRS) from the participant's mildest pain reported at baseline. A time-stratified case-crossover study was conducted to anchor the corresponding hazard date to four control periods within a particular 35-day interval. Data on maximum and minimum temperature (°C), relative humidity (%), barometric pressure (hPa) and precipitation (mm) were obtained for the hazard and control periods from the publicly available meteorological database of the Australian Bureau of Meteorology. The associations were assessed using conditional logistic regression. RESULTS: Of the 345 participants recruited, 171 participants (women: 64%, mean age: 62 years, mean BMI: 30.2 kg/m2) experienced at least one episode of pain exacerbation, yielding 1,425 observations included in the analyses. There was no apparent association between temperature, relative humidity, air pressure or precipitation and risk of knee pain exacerbation. CONCLUSION: Despite anecdotal reports from patients, change in weather factors does not appear to influence the risk of pain exacerbation in persons with knee osteoarthritis. Additional studies should quantify the association of weather and risk of pain exacerbation in regions with more extreme weather conditions.

Using whole genome sequencing to identify resistance determinants and predict antimicrobial resistance phenotypes for year 2015 invasive pneumococcal disease isolates recovered in the United States.

Our whole genome sequence (WGS) pipeline was assessed for accurate prediction of antimicrobial phenotypes. For 2316 invasive pneumococcal isolates recovered during 2015 we compared WGS pipeline data to broth dilution testing (BDT) for 18 antimicrobials. For 11 antimicrobials categorical discrepancies were assigned when WGS-predicted MICs and BDT MICs predicted different categorizations for susceptibility, intermediate resistance or resistance, ranging from 0.9% (tetracycline) to 2.9% (amoxicillin). For ß-lactam antibiotics, the occurrence of at least four-fold differences in MIC ranged from 0.2% (meropenem) to 1.0% (penicillin), although phenotypic retesting resolved 25%-78% of these discrepancies. Non-susceptibility to penicillin, predicted by penicillin-binding protein types, was 2.7% (non-meningitis criteria) and 23.8% (meningitis criteria). Other common resistance determinants included mef (475 isolates), ermB (191 isolates), ermB + mef (48 isolates), tetM (261 isolates) and cat (51 isolates). Additional accessory resistance genes (tetS, tet32, aphA-3, sat4) were rarely detected (one to three isolates). Rare core genome mutations conferring erythromycin-resistance included a two-codon rplD insertion (rplD69-KG-70) and the 23S rRNA A2061G substitution (six isolates). Intermediate cotrimoxazole-resistance was associated with one or two codon insertions within folP (238 isolates) or the folA I100L substitution (38 isolates), whereas full cotrimoxazole-resistance was attributed to alterations in both genes (172 isolates). The two levofloxacin-resistant isolates contained parC and/or gyrA mutations. Of 11 remaining isolates with moderately elevated MICs to both ciprofloxacin and levofloxacin, seven contained parC or gyrA mutations. The two rifampin-resistant isolates contained rpoB mutations. WGS-based antimicrobial phenotype prediction was an informative alternative to BDT for invasive pneumococci.

Strain features and distributions in pneumococci from children with invasive disease before and after 13-valent conjugate vaccine implementation in the USA.

The effect of second-generation pneumococcal conjugate vaccines on invasive pneumococcal disease (IPD) strain distributions have not yet been well described. We analysed IPD isolates recovered from children aged <5 years through Active Bacterial Core surveillance before (2008-2009; n = 828) and after (2011-2013; n = 600) 13-valent pneumococcal conjugate vaccine (PCV13) implementation. We employed conventional testing, PCR/electrospray ionization mass spectrometry and whole genome sequence (WGS) analysis to identify serotypes, resistance features, genotypes, and pilus types. PCV13, licensed in February 2010, effectively targeted all major 19A and 7F genotypes, and decreased antimicrobial resistance, primarily owing to removal of the 19A/ST320 complex. The strain complex contributing most to the remaining ß-lactam resistance during 2011-2013 was 35B/ST558. Significant emergence of non-vaccine clonal complexes was not evident. Because of the removal of vaccine serotype strains, positivity for one or both pilus types (PI-1 and PI-2) decreased in the post-PCV13 years 2011-2013 relative to 2008-2009 (decreases of 32-55% for PI-1, and >95% for PI-2 and combined PI-1 + PI-2). ß-Lactam susceptibility phenotypes correlated consistently with transpeptidase region sequence combinations of the three major penicillin-binding proteins (PBPs) determined through WGS analysis. Other major resistance features were predictable by DNA signatures from WGS analysis. Multilocus sequence data combined with PBP combinations identified progeny, serotype donors and recipient strains in serotype switch events. PCV13 decreased the frequency of all PCV13 serotype clones and concurrently decreased the frequency of strain subsets with resistance and/or adherence features conducive to successful carriage. Our results serve as a reference describing key features of current paediatric IPD strains in the USA after PCV13 implementation.

Awareness of body weight by mothers and their children: repeated measures in a single cohort (EarlyBird 64).

BACKGROUND: Mothers often do not realize when their child is overweight. We aimed to compare mothers' perceptions of children's weight before and during puberty, and to explore factors at 7 years predicting recognition of overweight at 16 years. METHODS: Mothers of 237 children (136 boys) from the EarlyBird study estimated their own weight category and that of their child aged 7 years and 16 years. The children estimated their own weight category at 16 years. Annual measures: body mass index standard deviation score (BMIsds), per cent fat, physical activity. Pubertal development assessed by age at peak height velocity (APHV). MATERNAL MEASURES: BMI, education, socio-economic status. RESULTS: At 7 years 21% of girls and 16% of boys were overweight or obese, rising to 27% and 22% respectively at 16 years. The accuracy of the mother's perception of her child's weight category improved from 44% at 7 years to 74% at 16 years, but they were less able to judge overweight in sons than daughters. The mothers' level of concern about overweight was greater for girls than boys, and increased for girls (52% mothers of overweight/obese girls were worried at 7 years, 62% at 16 years), but remained static in the boys (42% vs. 39%). Over 80% of the youngsters realized when they were overweight, but 25% normal-weight girls also classed themselves as overweight. Only BMI predicted a mother's ability to correctly perceive her child's weight. Neither her awareness, nor concern, about the child's weight at 7 years had any impact on the trajectory of the child's BMI from 7 years to 16 years. CONCLUSIONS: Parents are central to any successful weight reduction programme in their children, but will not engage while they remain ignorant of the problem. Crucially, any concern mothers may have about their child's excess weight at 7 years appears to have no impact on subsequent weight change.