Activity-related pain and sensitization predict within- and between-person pain experience in people with knee osteoarthritis: An ecological momentary assessment study.

BACKGROUND AND OBJECTIVES: Knee Osteoarthritis (OA) is a prevalent musculoskeletal condition that often results in pain and disability. Determining factors predicting variability in pain experience is critical to improving clinical outcomes. Underlying pain sensitization and its clinical manifestations, such as activity-related pain, may better predict the knee OA pain experience. This study aimed to determine whether Quantitative Sensory Testing (QST) derived sensitization measures and activity-related pain predict knee OA pain experiences collected via smartphone ecological momentary assessment (EMA). DESIGN: Individuals with knee OA were recruited from an urban community in New Zealand. Those eligible to participate underwent baseline QST with clinical measures of activity-related pain also being collected. The knee OA pain experience was collected via smartphone EMA three times daily for two weeks. Mixed effects location scale models were developed using a multilevel modelling approach. RESULTS: Eighty-six participants with knee OA participated in the study. Mean age was 67.3 years, with most of the participants being female (64%) and New Zealand European (90.6%). Activity-related pain predicted worse and more variable pain intensity, pain interference, and bothersomeness outcomes within and between individuals with knee OA. Widespread cold hyperalgesia and local mechanical hyperalgesia were shown to predict higher within-person variability in pain intensity and pain interference respectively, while mechanical temporal summation predicted less within-person variability in pain intensity and interference. DISCUSSION: Those demonstrating activity-related pain and sensitization could be at risk of experiencing worse and more variable knee OA pain in the subsequent weeks. Testing for sensitization in clinical practice could therefore identify those at greatest risk of higher and more variable knee OA pain experiences and in greatest need of treatment. Larger validation studies are required, which include individuals with more severe knee OA

Understanding the biopsychosocial knee osteoarthritis pain experience: an ecological momentary assessment.

INTRODUCTION: Psychological, social, and lifestyle factors contribute to the knee osteoarthritis (OA) pain experience. These factors could be measured more accurately using smartphone ecological momentary assessment (EMA). OBJECTIVES: The objective of this study was to characterise the pain experiences of those with knee OA by a smartphone EMA survey and explain how momentary psychological and social states influence knee OA pain experiences. METHODS: A smartphone EMA survey was designed and piloted. Eligible participants completed smartphone EMA assessing the knee OA pain experience 3 times daily for 2 weeks. Descriptive statistics were used to characterise factors involved in knee OA pain followed by the development of mixed-effects location scale models to explore heterogeneity and relationships between symptoms involved in the knee OA pain experience. RESULTS: Eighty-six community-dwelling volunteers with knee OA were recruited. Pain, psychosocial, and lifestyle factors involved in knee OA pain experience were heterogeneous and variable. Those with greater variability in pain, fatigue, negative affect, and stress had worse levels of these symptoms overall. In addition, fatigue, negative affect, stress, anxiety, loneliness, and joint stiffness demonstrated within-person relationships with knee OA pain outcomes. CONCLUSIONS: Knee OA pain is a heterogeneous biopsychosocial condition. Momentary experiences of psychological, social, fatigue, and joint stiffness explain individual and between-individual differences in momentary knee OA pain experiences. Addressing these momentary factors could improve pain and functional outcomes in those with knee OA. Validation studies, including individuals with more severe knee OA presentations, are required to support findings and guide clinical interventions to improve outcomes for those with knee OA

Snout Shape in Extant Ruminants

Copyright: © 2014 Tennant, MacLeod. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. [4.0 license]. The attached file is the published version of the article

Mutual Mate Choice: When it Pays Both Sexes to Avoid Inbreeding

Theoretical models of sexual selection predict that both males and females of many species should benefit by selecting their mating partners. However, empirical evidence testing and validating this prediction is scarce. In particular, whereas inbreeding avoidance is expected to induce sexual conflicts, in some cases both partners could benefit by acting in concert and exerting mutual mate choice for non-assortative pairings. We tested this prediction with the gregarious cockroach Blattella germanica (L.). We demonstrated that males and females base their mate choice on different criteria and that choice occurs at different steps during the mating sequence. Males assess their relatedness to females through antennal contacts before deciding to court preferentially non-siblings. Conversely, females biased their choice towards the most vigorously courting males that happened to be non-siblings. This study is the first to demonstrate mutual mate choice leading to close inbreeding avoidance. The fact that outbred pairs were more fertile than inbred pairs strongly supports the adaptive value of this mating system, which includes no “best phenotype” as the quality of two mating partners is primarily linked to their relatedness. We discuss the implications of our results in the light of inbreeding conflict models

Impaired contractile function of the supraspinatus in the acute period following a rotator cuff tear

Background: Rotator cuff (RTC) tears are a common clinical problem resulting in adverse changes to the muscle, but there is limited information comparing histopathology to contractile function. This study assessed supraspinatus force and susceptibility to injury in the rat model of RTC tear, and compared these functional changes to histopathology of the muscle. Methods: Unilateral RTC tears were induced in male rats via tenotomy of the supraspinatus and infraspinatus. Maximal tetanic force and susceptibility to injury of the supraspinatus muscle were measured in vivo at day 2 and day 15 after tenotomy. Supraspinatus muscles were weighed and harvested for histologic analysis of the neuromuscular junction (NMJ), intramuscular lipid, and collagen. Results: Tenotomy resulted in eventual atrophy and weakness. Despite no loss in muscle mass at day 2 there was a 30% reduction in contractile force, and a decrease in NMJ continuity and size. Reduced force persisted at day 15, a time point when muscle atrophy was evident but NMJ morphology was restored. At day 15, torn muscles had decreased collagen-packing density and were also more susceptible to contraction-induced injury. Conclusion: Muscle size and histopathology are not direct indicators of overall RTC contractile health. Changes in NMJ morphology and collagen organization were associated with changes in contractile function and thus may play a role in response to injury. Although our findings are limited to the acute phase after a RTC tear, the most salient finding is that RTC tenotomy results in increased susceptibility to injury of the supraspinatus

Effect of a 2-week interruption in methotrexate treatment on COVID-19 vaccine response in people with immune-mediated inflammatory diseases (VROOM study): a randomised, open label, superiority trial

Background: Methotrexate is the first-line treatment for immune-mediated inflammatory diseases and reduces vaccine-induced immunity. We evaluated if a 2-week interruption of methotrexate treatment immediately after COVID-19 booster vaccination improved antibody response against the S1 receptor binding domain (S1-RBD) of the SARS-CoV-2 spike protein and live SARS-CoV-2 neutralisation compared with uninterrupted treatment in patients with immune-mediated inflammatory diseases. Method: We did a multicentre, open-label, parallel-group, randomised, superiority trial in secondary-care rheumatology and dermatology clinics in 26 hospitals in the UK. Adults (aged ≥18 years) with immune-mediated inflammatory diseases taking methotrexate (≤25 mg per week) for at least 3 months, who had received two primary vaccine doses from the UK COVID-19 vaccination programme were eligible. Participants were randomly assigned (1:1) using a centralised validated computer program, to temporarily suspend methotrexate treatment for 2 weeks immediately after COVID-19 booster vaccination or continue treatment as usual. The primary outcome was S1-RBD antibody titres 4 weeks after COVID-19 booster vaccination and was assessed masked to group assignment. All randomly assigned patients were included in primary and safety analyses. This trial is registered with ISRCTN, ISRCTN11442263; following a pre-planned interim analysis, recruitment was stopped early. Finding: Between Sept 30, 2021, and March 7, 2022, we screened 685 individuals, of whom 383 were randomly assigned: to either suspend methotrexate (n=191; mean age 58·8 years [SD 12·5], 118 [62%] women and 73 [38%] men) or to continue methotrexate (n=192; mean age 59·3 years [11·9], 117 [61%] women and 75 [39%] men). At 4 weeks, the geometric mean S1-RBD antibody titre was 25 413 U/mL (95% CI 22 227–29 056) in the suspend methotrexate group and 12 326 U/mL (10 538–14 418) in the continue methotrexate group with a geometric mean ratio (GMR) of 2·08 (95% CI 1·59–2·70; p<0·0001). No intervention-related serious adverse events occurred. Interpretation: 2-week interruption of methotrexate treatment in people with immune-mediated inflammatory diseases enhanced antibody responses after COVID-19 booster vaccination that were sustained at 12 weeks and 26 weeks. There was a temporary increase in inflammatory disease flares, mostly self-managed. The choice to suspend methotrexate should be individualised based on disease status and vulnerability to severe outcomes from COVID-19. Funding: National Institute for Health and Care Research

Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012

OBJECTIVE: To provide an update to the "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," last published in 2008. DESIGN: A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. METHODS: The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Recommendations were classified into three groups: (1) those directly targeting severe sepsis; (2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and (3) pediatric considerations. RESULTS: Key recommendations and suggestions, listed by category, include: early quantitative resuscitation of the septic patient during the first 6 h after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 h of the recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de-escalation, when appropriate (1B); infection source control with attention to the balance of risks and benefits of the chosen method within 12 h of diagnosis (1C); initial fluid resuscitation with crystalloid (1B) and consideration of the addition of albumin in patients who continue to require substantial amounts of crystalloid to maintain adequate mean arterial pressure (2C) and the avoidance of hetastarch formulations (1B); initial fluid challenge in patients with sepsis-induced tissue hypoperfusion and suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (more rapid administration and greater amounts of fluid may be needed in some patients (1C); fluid challenge technique continued as long as hemodynamic improvement is based on either dynamic or static variables (UG); norepinephrine as the first-choice vasopressor to maintain mean arterial pressure ≥65 mmHg (1B); epinephrine when an additional agent is needed to maintain adequate blood pressure (2B); vasopressin (0.03 U/min) can be added to norepinephrine to either raise mean arterial pressure to target or to decrease norepinephrine dose but should not be used as the initial vasopressor (UG); dopamine is not recommended except in highly selected circumstances (2C); dobutamine infusion administered or added to vasopressor in the presence of (a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or (b) ongoing signs of hypoperfusion despite achieving adequate intravascular volume and adequate mean arterial pressure (1C); avoiding use of intravenous hydrocortisone in adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (2C); hemoglobin target of 7-9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage (1B); low tidal volume (1A) and limitation of inspiratory plateau pressure (1B) for acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure (PEEP) in ARDS (1B); higher rather than lower level of PEEP for patients with sepsis-induced moderate or severe ARDS (2C); recruitment maneuvers in sepsis patients with severe refractory hypoxemia due to ARDS (2C); prone positioning in sepsis-induced ARDS patients with a PaO (2)/FiO (2) ratio of ≤100 mm Hg in facilities that have experience with such practices (2C); head-of-bed elevation in mechanically ventilated patients unless contraindicated (1B); a conservative fluid strategy for patients with established ARDS who do not have evidence of tissue hypoperfusion (1C); protocols for weaning and sedation (1A); minimizing use of either intermittent bolus sedation or continuous infusion sedation targeting specific titration endpoints (1B); avoidance of neuromuscular blockers if possible in the septic patient without ARDS (1C); a short course of neuromuscular blocker (no longer than 48 h) for patients with early ARDS and a PaO (2)/FI O (2) 180 mg/dL, targeting an upper blood glucose ≤180 mg/dL (1A); equivalency of continuous veno-venous hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1B); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding in patients with bleeding risk factors (1B); oral or enteral (if necessary) feedings, as tolerated, rather than either complete fasting or provision of only intravenous glucose within the first 48 h after a diagnosis of severe sepsis/septic shock (2C); and addressing goals of care, including treatment plans and end-of-life planning (as appropriate) (1B), as early as feasible, but within 72 h of intensive care unit admission (2C). Recommendations specific to pediatric severe sepsis include: therapy with face mask oxygen, high flow nasal cannula oxygen, or nasopharyngeal continuous PEEP in the presence of respiratory distress and hypoxemia (2C), use of physical examination therapeutic endpoints such as capillary refill (2C); for septic shock associated with hypovolemia, the use of crystalloids or albumin to deliver a bolus of 20 mL/kg of crystalloids (or albumin equivalent) over 5-10 min (2C); more common use of inotropes and vasodilators for low cardiac output septic shock associated with elevated systemic vascular resistance (2C); and use of hydrocortisone only in children with suspected or proven "absolute"' adrenal insufficiency (2C). CONCLUSIONS: Strong agreement existed among a large cohort of international experts regarding many level 1 recommendations for the best care of patients with severe sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for this important group of critically ill patients