Osteoarthritis year in review 2018: rehabilitation and outcomes.

OBJECTIVE: Conduct a systematic review of systematic reviews and randomised controlled trials (RCTs) from the past year evaluating rehabilitation for people with osteoarthritis, and provide narrative synthesis of findings focused on core recommended treatments for osteoarthritis (exercise, education, biomechanical interventions, weight loss). DESIGN: A comprehensive search strategy was used to search PubMed, EMBASE and Cochrane databases (16th May 2017 to 22nd March 2018). Search terms included 'osteoarthritis', 'rehabilitation', 'systematic review', and 'randomised controlled trial'. Inclusion criteria were: (1) RCT, or systematic review of randomised clinical trials (RCTs); (2) human participants with osteoarthritis (any joint); (3) evaluation of rehabilitation intervention; and (4) at least one patient-reported measure. Methodological quality was evaluated using the Assessment of Multiple Systematic Reviews (AMSTAR) tool (systematic reviews) and PEDro rating scale (RCTs). Narrative synthesis mapped findings to core recommendations from existing osteoarthritis clinical guidelines. RESULTS: From 1994 records, 13 systematic reviews and 36 RCTs were included. 73% of these evaluated knee osteoarthritis (36 studies). The remaining studies evaluated hand osteoarthritis (6 studies), hip, hip/knee and general osteoarthritis (each 2 studies), and neck osteoarthritis (1 study). Exercise was the most common intervention evaluated (31%). Updated recommendations for exercise prescription and preliminary guidance for psychological interventions are provided. CONCLUSION: Level 1 and 2 osteoarthritis rehabilitation literature continues to be dominated by knee osteoarthritis studies. Consistent with current clinical guidelines, exercise should be a core treatment for osteoarthritis, but future studies should ensure that exercise programs follow published dose guidelines. There is a clear need for research on rehabilitation for hip, hand, foot/ankle, shoulder and spine osteoarthritis.

Relation of meniscus pathology to prevalence and worsening of patellofemoral joint osteoarthritis: the Multicenter Osteoarthritis Study.

OBJECTIVE: To determine the relationship of meniscal damage to magnetic resonance imaging (MRI) features of compartment-specific patellofemoral joint (PFJ) osteoarthritis (OA) at baseline and 2 years later. METHOD: Individuals from a prospective cohort of individuals aged 50-79 with or at risk of knee OA were included. At the 60-month and 84-month study visit, Whole-Organ MRI Score (WORMS) was used to assess meniscal tears and extrusions as well as cartilage damage and bone marrow lesions (BMLs) in the medial and lateral patella and trochlea. Worsening of structural features was defined as any increase in WORMS score from 60 to 84 months. Logistic regression was used to determine the cross-sectional and longitudinal relation of meniscus damage to features of compartment-specific PFJ OA. RESULTS: Relative to knees without lateral meniscal pathology at baseline, those with grades 3-4 lateral meniscal tear and extrusion had greater risk of worsening of cartilage damage in the lateral PFJ 2 years later (Risk ratio: 1.7 [95% CI: 1.1-2.7) and (1.7 [1.2-2.5]), respectively. Relative to those without medial meniscal pathology at baseline, those with grades 1-2 (0.6 [0.4-0.9]) and 3-4 (0.7 [0.5-1.0]) medial meniscal tears had lower risk of worsening of BMLs in the medial PFJ 2 years later. CONCLUSION: Meniscal tear and extrusion are associated with increased risk of medial and lateral PFJ OA and more severe meniscal pathology is associated with worsening of PFJ OA 2 years later. Lateral meniscal pathology appears to be more detrimental to the lateral PFJ.

Altered fear processing in adolescents with a history of severe childhood maltreatment: an fMRI study.

BACKGROUND: Children with a history of maltreatment suffer from altered emotion processing but the neural basis of this phenomenon is unknown. This pioneering functional magnetic resonance imaging (fMRI) study investigated the effects of severe childhood maltreatment on emotion processing while controlling for psychiatric conditions, medication and substance abuse. METHOD: Twenty medication-naive, substance abuse-free adolescents with a history of childhood abuse, 20 psychiatric control adolescents matched on psychiatric diagnoses but with no maltreatment and 27 healthy controls underwent a fMRI emotion discrimination task comprising fearful, angry, sad happy and neutral dynamic facial expressions. RESULTS: Maltreated participants responded faster to fearful expressions and demonstrated hyper-activation compared to healthy controls of classical fear-processing regions of ventromedial prefrontal cortex (vmPFC) and anterior cingulate cortex, which survived at a more lenient threshold relative to psychiatric controls. Functional connectivity analysis, furthermore, demonstrated reduced connectivity between left vmPFC and insula for fear in maltreated participants compared to both healthy and psychiatric controls. CONCLUSIONS: The findings show that people who have experienced childhood maltreatment have enhanced fear perception, both at the behavioural and neurofunctional levels, associated with enhanced fear-related ventromedial fronto-cingulate activation and altered functional connectivity with associated limbic regions. Furthermore, the connectivity adaptations were specific to the maltreatment rather than to the developing psychiatric conditions, whilst the functional changes were only evident at trend level when compared to psychiatric controls, suggesting a continuum. The neurofunctional hypersensitivity of fear-processing networks may be due to childhood over-exposure to fear in people who have been abused.

Grey matter volume and thickness abnormalities in young people with a history of childhood abuse.

BACKGROUND: Childhood abuse is associated with abnormalities in brain structure and function. Few studies have investigated abuse-related brain abnormalities in medication-naïve, drug-free youth that also controlled for psychiatric comorbidities by inclusion of a psychiatric control group, which is crucial to disentangle the effects of abuse from those associated with the psychiatric conditions. METHODS: Cortical volume (CV), cortical thickness (CT) and surface area (SA) were measured in 22 age- and gender-matched medication-naïve youth (aged 13-20) exposed to childhood abuse, 19 psychiatric controls matched for psychiatric diagnoses and 27 healthy controls. Both region-of-interest (ROI) and whole-brain analyses were conducted. RESULTS: For the ROI analysis, the childhood abuse group compared with healthy controls only, had significantly reduced CV in bilateral cerebellum and reduced CT in left insula and right lateral orbitofrontal cortex (OFC). At the whole-brain level, relative to healthy controls, the childhood abuse group showed significantly reduced CV in left lingual, pericalcarine, precuneus and superior parietal gyri, and reduced CT in left pre-/postcentral and paracentral regions, which furthermore correlated with greater abuse severity. They also had increased CV in left inferior and middle temporal gyri relative to healthy controls. Abnormalities in the precuneus, temporal and precentral regions were abuse-specific relative to psychiatric controls, albeit at a more lenient level. Groups did not differ in SA. CONCLUSIONS: Childhood abuse is associated with widespread structural abnormalities in OFC-insular, cerebellar, occipital, parietal and temporal regions, which likely underlie the abnormal affective, motivational and cognitive functions typically observed in this population.

Bikeshare Use in Urban Communities: Individual and Neighborhood Factors.

Objective: Bicycling is an affordable way to increase access to employment, schooling, and services and an effective measure against obesity. Bikeshare programs can make bicycling accessible to diverse populations, but little evidence exists on their adoption in low-resource neighborhoods. Our study examined factors associated with bikeshare use in a metropolitan area in the southern United States. Methods: We performed a retrospective cross-sectional analysis of a database of clients (N=815) who rented a bicycle from Zyp Bikeshare in Birmingham, Alabama between October 2015 and November 2016. Individual-level variables included bike use frequency, average speed, total miles traveled, total minutes ridden, bike type (traditional vs electricity-assisted pedelec), membership type, sex, and age. Area-level data aggregated to Census tracts, proxies for neighborhoods, were obtained from the 2010 US Census after geocoding clients' billing addresses. Using exploratory factor analysis, a neighborhood socioeconomic disadvantage index (SDI) was constructed. Bikeshare station presence in a tract was included as a covariate. Multivariate linear regression models, adjusted for clustering on Census tracts, were estimated to determine predictors of bikeshare use. Results: In a multivariate regression model of individual and neighborhood characteristics adjusted for clustering, each decile increase in the SDI was associated with a 9% increase in bikeshare use (P<.001). Bikeshare use was also positively associated with speed (.1, P<.001), total miles (.008, P<.001), and pedelec use (1.02, P<.01). Conclusion: Higher neighborhood socioeconomic disadvantage is associated with higher bikeshare use. Bikeshare is a viable transportation option in low-resource neighborhoods and may be an effective tool to improve the connectivity, livability, and health of urban communities.

Extreme-Ultraviolet-Initated High-Order Harmonic Generation: Driving Inner-Valence Electrons Using Below-Threshold-Energy Extreme-Ultraviolet Light.

We propose a novel scheme for resolving the contribution of inner- and outer-valence electrons in extreme-ultraviolet (XUV)-initiated high-harmonic generation in neon. By probing the atom with a low-energy (below the 2s ionization threshold) ultrashort XUV pulse, the 2p electron is steered away from the core, while the 2s electron is enabled to describe recollision trajectories. By selectively suppressing the 2p recollision trajectories, we can resolve the contribution of the 2s electron to the high-harmonic spectrum. We apply the classical trajectory model to account for the contribution of the 2s electron, which allows for an intuitive understanding of the process.

The effects of a varus unloader brace for lateral tibiofemoral osteoarthritis and valgus malalignment after anterior cruciate ligament reconstruction: a single case study.

We investigated the immediate effects of a varus knee brace on knee symptoms and knee-joint biomechanics in an individual with predominant lateral tibiofemoral joint osteoarthritis (TFJOA) and valgus malalignment after anterior cruciate ligament (ACL) reconstruction. A varus unloader brace was prescribed to a 48-year-old male with predominant lateral radiographic and symptomatic TFJOA and valgus malalignment eight-years following ACL reconstruction. During a step-down task, the participant rated knee pain, task-difficulty, knee-stability and knee-confidence on four separate visual analogue scales. Quantitative gait analysis was conducted during self-selected walking trials under three test conditions in a randomized order: (i) no brace; (ii) brace without frontal plane adjustment (no varus re-alignment); and (ii) brace with frontal plane adjustment (varus re-alignment). Post-processing of gait data involved calculation of knee kinematics and net joint moments for the reconstructed limb. The participant reported improved pain (3%), task difficulty (41%), stability (46%) and confidence (49%) when performing the step-down task with the brace. The varus brace resulted in immediate reductions in knee abduction angle (24%) and internal rotation angle (56%), and increased knee adduction moment (18%). These findings provide preliminary evidence for potentially beneficial effects of bracing on knee-symptoms and biomechanics in individuals with lateral TFJOA after reconstruction.

Quadriceps volumes are reduced in people with patellofemoral joint osteoarthritis.

OBJECTIVES: This study aimed to (1) compare the volumes of vastus medialis (VM), vastus lateralis (VL), vastus intermedius and rectus femoris and the ratio of VM/VL volumes between asymptomatic controls and patellofemoral joint osteoarthritis (PFJ OA) participants; and (2) assess the relationships between cross-sectional area (CSA) and volumes of the VM and VL in individuals with and without PFJ OA. METHODS: Twenty-two participants with PFJ OA and 11 controls aged ≥ 40 years were recruited from the community and practitioner referrals. Muscle volumes of individual quadriceps components were measured from thigh magnetic resonance (MR) images. The CSA of the VM and lateralis were measured at 10 equally distributed levels (femoral condyles to lesser femoral trochanter). RESULTS: PFJ OA individuals had smaller normalized VM (mean difference 0.90 cm(3) · kg(-1), α = 0.011), VL (1.50 cm(3) · kg(-1), α = 0.012) and rectus femoris (0.71 cm(3) · kg(-1), α = 0.009) volumes than controls. No differences in the VM/VL ratio were observed. The CSA at the third level (controls) and fourth level (PFJ OA) above the femoral condyles best predicted VM volume, whereas the VL volume was best predicted by the CSA at the seventh level (controls) and sixth level (PFJ OA) above the femoral condyles. CONCLUSION: Reduced quadriceps muscle volume was a feature of PFJ OA. Muscle volume could be predicted from CSA measurements at specific levels in PFJ OA patients and controls.

Interference between competing pathways in atomic harmonic generation.

We investigate the influence of the autoionizing 3s3p(6)nℓ resonances on the fifth harmonic generated by 200-240 nm laser fields interacting with Ar. To determine the influence of a multielectron response we develop the capability within time-dependent R-matrix theory to determine the harmonic spectra generated. The fifth harmonic is affected by interference between the response of a 3s electron and the response of a 3p electron, as demonstrated by the asymmetric profiles in the harmonic yields as functions of wavelength.

Virus safety of plasma products using 20 nm instead of 15 nm filtration as virus removing step.

During the manufacture of human plasma derivatives, a series of complementary measures are undertaken to prevent transmission of blood-borne viruses. Virus filtration using 15 nm (Planova15N) filters has successfully been implemented in manufacturing processes for various plasma derivatives primarily because virus filtration is a technique, mild for proteins, that can effectively remove even small non-lipid-enveloped viruses, such as HAV and parvovirus B19. However, the use of 15 nm filters has limitations with regard to protein capacity of the filters and the process flow, resulting in an expensive manufacturing step. Therefore, studies were performed to test whether the use of 20 nm (Planova20N) filters, having different characteristics compared to 15 nm filters, can be an alternative for the use of 15 nm filters. It is shown that 20 nm filtration can be an alternative for 15 nm filtration. However, the virus removal capacity of the 20 nm filters depends on the plasma product that is filtered. Therefore, an optimisation study must be performed with regard to process parameters such as pressure, pH and protein concentration for each plasma product. In this study, using optimised conditions, the virus removal capacity of 20 nm filters appears to be comparable or even better when compared to that of 15 nm filters.

[Important alteration of the Dutch treatment algorithm in patients with type 2 diabetes mellitus]. / Belangrijke wijziging van behandelrichtlijn 'Diabetes mellitus type 2'.

Recent trials of two classes of glucose-lowering drugs (SGLT2 inhibitors and GLP1RAs) have shown consistent cardiovascular and renal benefits that appear independent of glycaemic control. These results have prompted the Dutch College of General Practitioners (NHG) together with the Dutch Society of Internal Medicine (NIV) to update the treatment algorithm in patients with type 2 diabetes mellitus (T2D) at very high CVD risk. The use of SGLT2 inhibitors or GLP1RAs is now recommended in 3 groups of people with T2D. 1. patients with established CVD; 2. Patients with chronic kidney disease and a moderately to high CVD risk according to KDIGO; 3. patients with heart failure with reduced ejection fraction (HFrEF). Treatment algorithms differ for drug-naïve and drug-treated patients with T2D. In both drug-naïve and drug-treated patients the use of a SGLT2 inhibitor respectively as monotherapy or add-on is recommended as first step. If HbA1c is above the individual target, metformin will be added in drug-naive patients whereas GLP1-RAs could be considered in drug-treated patients. GLP1-RAs should also be considered when SGLT2-inhibitors are contraindicated.

Two-photon inner-shell ionization in the extreme ultraviolet.

We have observed the simultaneous inner-shell absorption of two extreme-ultraviolet photons by a Xe atom in an experiment performed at the short-wavelength free electron laser facility FLASH. Photoelectron spectroscopy permitted us to unambiguously identify a feature resulting from the ionization of a single electron of the 4d subshell of Xe by two photons each of energy (93±1) eV. The feature's intensity has a quadratic dependence on the pulse energy. The results are discussed and interpreted within the framework of recent results of ion spectroscopy experiments of Xe obtained at ultrahigh irradiance in the extreme-ultraviolet regime.

Very heavy solar cosmic rays: energy spectrum and implications for lunar erosion.

The energy spectrum of solar cosmic-ray particles of the iron group has been determined for the first time over the energy range from 1 to 100 million electron volts per nucleon by the use of glass removed from the Surveyor 3 spacecraft. The difference between the observed (energy)(-3) spectrum and the limiting spectrum derived previously from tracks in lunar rocks gives an erosion rate of 0 to 2 angstroms per year. High-energy fission of lead, induced by galactic cosmicray protons and alpha particles, has also been observed.

Particle track identification: application of a new technique to apollo helmets.

The Apollo helmets are being used to record the dose of heavy particles to which astronauts are exposed on space missions. An improved method for examining and identifying the etched tracks of heavy charged particles consists of replicating tracks and measuring the etching rate as a function of position along the track. Tracks have been observed in Apollo helmets that correspond to ionized atoms heavier than iron.

Cosmic-ray tracks in plastics: the apollo helmet dosimetry experiment.

Counts of tracks from heavy cosmic-ray nuclei in helmets from Apollo missions 8 and 12 show variations caused by solar modulation of the galactic cosmic-ray flux. Specific estimates of the biological damage to certain nonreplaceable cells by track-forming particles during these space missions indicate that the fraction of deactivated cells could range from a lower limit of 3 x 10(-7) to an upper limit of 1.4 x 10(-4).

Apollo 14 and apollo 16 heavy-particle dosimetry experiments.

Doses of heavy particles at positions inside the command modules of Apollo missions 8, 12, 14, and 16 correlate well with the calculated effects of solar modulation of the primary cosmic radiation. Differences in doses at different stowage positions indicate that the redistribution of mass within the spacecraft could enhance safety from the biological damage that would otherwise be expected on manned, deep-space missions.

Particle Track, X-ray, Thermal, and Mass Spectrometric Studies of Lunar Material.

Particle tracks in Apollo 11 samples are dominantly of cosmic ray and solar origin: primary galactic and solar flare particles, likely spallation recoil tracks, and possible solar-wind heavy particles. The energy spectrum of irongroup nuclei is inferred from track density gradients in surface layers, and a limit of << 10(-7) centimeter per year is deduced for the surface erosion rate. From cosmic ray tracks in rock and core samples it is clear that the lunar soil is stirred often during each few million years. X-rays reveal augite, anorthite, olivine, ilmenite, troilite, nonmeteoritic iron, and assorted glasses, but no major structural damage. Hydrogen, helium, and other gases in the fines are compatible with expected solar wind ratios.

Risk and management of pre-diabetes.

Type 2 diabetes mellitus (T2DM) is associated with a two- to four-fold increased risk of developing cardiovascular disease (CVD) and microvascular complications, which may already be present before diagnosis. It is, therefore, important to detect people with an increased risk of T2DM at an early stage. In order to identify individuals with so-called 'pre-diabetes', comprising impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), current guidelines have developed definitions based on fasting plasma glucose, two-hour glucose concentrations and haemoglobin A1c. Subjects with pre-diabetes are at an increased risk of developing T2DM and CVD. This elevated risk seems similar according to the different criteria used to define pre-diabetes. The risk of progression to T2DM or CVD does, however, depend on other risk factors such as sex, body mass index and ethnicity. Based on the risk factors to develop T2DM, many risk assessment models have been developed to identify those at highest risk. These models perform well to identify those at risk and could be used to initiate preventive interventions. Many studies have shown that lifestyle modification and metformin are effective in preventing the development of T2DM, although lifestyle modification seems to have a more sustainable effect. In addition, lifestyle modification seems more effective in those with IGT than those with IFG. In this review, we will describe the different definitions used to define pre-diabetes, progression from pre-diabetes to T2DM or other vascular complications, risk factors associated with progressions and the management of progression to T2DM, ending with clinical recommendations.

Randomized, placebo-controlled trial of the angiotensin-converting enzyme inhibitor, ramipril, in patients with coronary or other occlusive arterial disease. PART-2 Collaborative Research Group. Prevention of Atherosclerosis with Ramipril.

OBJECTIVES: The primary objective of this study was to investigate the effects of the angiotensin-converting enzyme (ACE) inhibitor, ramipril, on carotid atherosclerosis in patients with coronary, cerebrovascular or peripheral vascular disease. BACKGROUND: Angiotensin-converting enzyme inhibitors have been shown to reduce the risk of coronary events in various patient groups and to prevent the development of atherosclerosis in animal models. It has been hypothesized that the clinical benefits of ACE inhibitors may, therefore, be mediated by effects on atherosclerosis. METHODS: Six hundred seventeen patients were randomized in equal proportions to ramipril (5-10 mg daily) or placebo. At baseline, two years and four years, carotid atherosclerosis was assessed by B-mode ultrasound, and left ventricular mass was assessed by M-mode echocardiography. RESULTS: Blood pressure (BP) was reduced by a mean of 6 mm Hg systolic and 4 mm Hg diastolic in the ramipril group compared with the placebo group (p<0.001). There was no difference between groups in the changes in common carotid artery wall thickness (p = 0.58) or in carotid plaque (p = 0.93). Left ventricular mass index decreased by 3.8 g/m2 (4%) in the ramipril group compared with the placebo group (2p = 0.04). CONCLUSIONS: The results provide no support for the hypothesis that reduced atherosclerosis is responsible for the beneficial effects of ACE inhibitors on major coronary events. It is more likely that the benefits are due to lower BP, reduced left ventricular mass or other factors such as reversal of endothelial dysfunction.

Effects of early captopril administration after thrombolysis on regional wall motion in relation to infarct artery blood flow.

OBJECTIVES: To determine whether early administration of captopril lessens infarct zone regional wall motion abnormalities when infarct artery blood flow is abnormal. BACKGROUND: The interaction between angiotensin-converting enzyme (ACE) inhibitor therapy, ventricular function and infarct artery blood flow has not been well described. METHODS: A total of 493 patients aged < or = 75 years with first infarctions, presenting within 4 h of symptom onset, were randomized to receive 6.25 mg captopril, increasing to 50 mg t.d.s. or a matching placebo 2.1+/-0.4 h after commencing intravenous streptokinase (1.5 x 10(6) U over 30 to 60 min). Trial therapy was stopped 48 h prior to angiography at 3 weeks, to determine regional wall motion and infarct artery flow. RESULTS: There were no differences in ejection fractions or end-systolic volumes between patients randomized to receive captopril and those randomized to receive a placebo. Among patients with anterior infarction (n = 216), randomization to captopril resulted in fewer hypokinetic chords (40+/-13; vs. 44+/-13; p=0.028) and a trend toward fewer chords >2 SD below normal (26+/-17 vs. 30+/-17; p=0.052) in the infarct zone. In patients randomized to receive captopril who had anterior infarction and Thrombolysis in Myocardial Infarction (TIMI) 0-2, flow there were fewer hypokinetic chords (44+/-12 vs. 50+/-9; p=0.043) and a trend toward fewer chords >2 SD below normal (33+/-15 vs. 39+/-13; p=0.057). Patients receiving captopril who had anterior infarction and corrected TIMI frame counts > 27 had fewer hypokinetic chords (42+/-13 vs. 46+/-12; p=0.015) and fewer chords >2 SD below normal (27+/-17 vs. 32+/-17; p= 0.047). Captopril had no effect in patients with inferior infarction. There were 20 late cardiac deaths (median follow-up 4 years) in the captopril group and 35 in the placebo group (p=0.036). CONCLUSIONS: Randomization to receive captopril 2 h after streptokinase improved regional wall motion at 3 weeks. The greatest benefit was seen in patients with anterior infarction particularly when infarct artery blood flow is reduced.