Lost futures, doomed timelines and unwanted inheritances: how we are handling painful time in social work.

This article makes the submission that social work is stuck and needs now to find ways to endure its commitments to caring from inside the suspended time that is so characteristic of late capitalism and not from some imaginary place outside of it. When telling this time in the form of history, there is a tendency to want to pass over what is most difficult about it - the inescapable fact of having to live through it - just at the moment when this is the reality most in need of being carefully thought about. Remembering that in talking about social work, we are talking about a labour of care defined, in part, by a sensitive, practical engagement with time that is difficult to live, I look to recent feminist theoretical work on care that can help us to think about how we might handle being stuck in painful time.

Stability of a high-concentration monoclonal antibody solution produced by liquid-liquid phase separation.

Subcutaneous injection of a low volume (<2 mL) high concentration (>100 mg/mL) formulation is an attractive administration strategy for monoclonal antibodies (mAbs) and other biopharmaceutical proteins. Using concentrated solutions may also be beneficial at various stages of bioprocessing. However, concentrating proteins by conventional techniques, such as ultrafiltration, can be time consuming and challenging. Isolation of the dense fraction produced by macroscopic liquid-liquid phase separation (LLPS) has been suggested as a means to produce high-concentration solutions, but practicality of this method, and the stability of the resulting protein solution have not previously been demonstrated. In this proof-of-concept study, we demonstrate that LLPS can be used to concentrate a mAb solution to >170 mg/mL. We show that the structure of the mAb is not altered by LLPS, and unperturbed mAb is recoverable following dilution of the dense fraction, as judged by 1H nuclear magnetic resonance spectroscopy. Finally, we show that the physical properties and stability of a model high concentration protein formulation obtained from the dense fraction can be improved, for example through the addition of the excipient arginine·glutamate. This results in a stable high-concentration protein formulation with reduced viscosity and no further macroscopic LLPS. Concentrating mAb solutions by LLPS represents a simple and effective technique to progress toward producing high-concentration protein formulations for bioprocessing or administration.AbbreviationsArginine·glutamate (Arg·Glu), Carr-Purcell-Meiboom-Gill (CPMG), critical temperature (TC), high-performance size-exclusion chromatography (HPSEC), liquid-liquid phase separation (LLPS), monoclonal antibody (mAb), nuclear magnetic resonance (NMR), transverse relaxation rate (R2).

Comprehensive Assessment of Protein and Excipient Stability in Biopharmaceutical Formulations Using 1H NMR Spectroscopy.

Biopharmaceutical proteins are important drug therapies in the treatment of a range of diseases. Proteins, such as antibodies (Abs) and peptides, are prone to chemical and physical degradation, particularly at the high concentrations currently sought for subcutaneous injections, and so formulation conditions, including buffers and excipients, must be optimized to minimize such instabilities. Therefore, both the protein and small molecule content of biopharmaceutical formulations and their stability are critical to a treatment's success. However, assessing all aspects of protein and small molecule stability currently requires a large number of analytical techniques, most of which involve sample dilution or other manipulations which may themselves distort sample behavior. Here, we demonstrate the application of 1H nuclear magnetic resonance (NMR) spectroscopy to study both protein and small molecule content and stability in situ in high-concentration (100 mg/mL) Ab formulations. We show that protein degradation (aggregation or fragmentation) can be detected as changes in 1D 1H NMR signal intensity, while apparent relaxation rates are specifically sensitive to Ab fragmentation. Simultaneously, relaxation-filtered spectra reveal the presence and degradation of small molecule components such as excipients, as well as changes in general solution properties, such as pH. 1H NMR spectroscopy can thus provide a holistic overview of biopharmaceutical formulation content and stability, providing a preliminary characterization of degradation and acting as a triaging step to guide further analytical techniques.

The politics of staying behind the frontline of coronavirus.

Intended as a contribution to the Waiting in Pandemic Times project Collection in response to COVID-19, this short paper views the coronavirus crisis in terms of its unpredictable effects on the interior life of the National Health Service (NHS) workforce. Based in part on ethnographic observations from the 'frontline' of the NHS during the hours that immediately followed a first suspected case of coronavirus at a general practice in London, it charts the collision of the ensuing crisis with working definitions of the nature of time in its relation to care. It considers what it might mean for healthcare practitioners at this particular moment in the NHS's history to be living through an experience of 'the ordinary' breaking down. The paper also follows hints of new temporal modes of care appearing during this same period when one kind of crisis in the NHS has been put on hold, and another (the crisis of coronavirus) is just getting underway.

Intra-rater reliability, measurement precision, and inter-test correlations of 1RM single-leg leg-press, knee-flexion, and knee-extension in uninjured adult agility-sport athletes: Considerations for right and left unilateral measurements in knee injury control.

OBJECTIVES: Knowledge of single-leg knee strength test reliability for the right and left limb is critical for between-limb clinical decision-making. Knowledge of between-test correlations is essential for understanding whether tests measure similar or different aspects of muscle strength. This study investigated the intra-rater, test-retest reliability and measurement precision of one repetition maximum (1RM) single-leg leg-press (LP), knee-flexion (KF), and knee-extension (KE) for both limbs, and inter-test correlations. DESIGN: Repeated measures; SETTING: University. PARTICIPANTS: Six males, seven females (age 25.6 ±â€¯5.5 yr; height 171.4 ±â€¯8.4 cm; mass 71.8 ±â€¯13.4 kg). MAIN OUTCOME MEASURES: Normalised 1RM (percent body-mass (%BM)), intraclass correlation coefficient (ICC) (2,1), standard error of measurement (SEM; %BM), Pearson's correlation (r), coefficient of determination (r2). RESULTS: Mean 1RM test-retest values were (right, left): LP, 214.2-218.5%BM, 213.5-215.4%BM; KF, 35.9-38.9%BM, 37.7-38.2%BM; KE, 43.3-44.6%BM, 36.2-39.3%BM. The ICCs/SEMs were (right, left): LP, 0.98/7.3%BM, 0.94/14.2%BM; KF, 0.75/4.9%BM, 0.95/1.9%BM; KE, 0.87/3.4%BM, 0.78/4.4%BM. Correlations were significant (P < 0.01), r/r2 values were: LP-KF, 0.60/0.36; LP-KE, 0.59/0.35; KF-KE, 0.50/0.25. CONCLUSIONS: Tests demonstrated good reliability and measurement precision, although ICCs and SEMs were different between limbs. Tests were correlated, but only one-third of the variance was shared between tests. Practitioners should be cognisant of between-limb differences in reliability and include all tests for knee clinical decision-making.

Application of ER Stress Biomarkers to Predict Formulated Monoclonal Antibody Stability.

For a therapeutic monoclonal antibody (mAb) to reach the clinic, the molecule must be produced at an appropriate yield and quality, then formulated to maintain efficacy and stability. The formation of subvisible particles (SVPs) can impact product stability and is monitored during formulation development; however, the potential of a mAb to form such species can be influenced throughout the whole bioprocess. The levels of intracellular endoplasmic reticulum (ER) stress perceived by Chinese hamster ovary (CHO) cell lines, the day of mAb harvest, and the relationship with subsequent product stability of two mAbs (denoted A and B), as determined by the SVP content after accelerated stability studies, are reported here. Here, it is shown that the propensity of mAb A to form SVPs can be predicted by transcript expression of biomarkers of cellular ER stress, heavy/light-chain transcript and polypeptide amounts, and harvest day. Further, mAb A material harvested on day 9 of culture was more stable, in terms of SVP formation, than material harvested on day 13. These data suggest that ER stress perceived by CHO cells can reflect the stability of a mAb, and that biomarkers of such stress could help define culture harvest time as a tool to control SVP formation in formulated mAbs.

Itm2a silencing rescues lamin A mediated inhibition of 3T3-L1 adipocyte differentiation.

Dysregulation of adipose tissue metabolism is associated with multiple metabolic disorders. One such disease, known as Dunnigan-type familial partial lipodystrophy (FPLD2) is characterized by defective fat metabolism and storage. FPLD2 is caused by a specific subset of mutations in the LMNA gene. The mechanisms by which LMNA mutations lead to the adipose specific FPLD2 phenotype have yet to be determined in detail. We used RNA-Seq analysis to assess the effects of wild-type (WT) and mutant (R482W) lamin A on the expression profile of differentiating 3T3-L1 mouse preadipocytes and identified Itm2a as a gene that was upregulated at 36 h post differentiation induction in these cells. In this study we identify Itm2a as a novel modulator of adipogenesis and show that endogenous Itm2a expression is transiently downregulated during induction of 3T3-L1 differentiation. Itm2a overexpression was seen to moderately inhibit differentiation of 3T3-L1 preadipocytes while shRNA mediated knockdown of Itm2a significantly enhanced 3T3-L1 differentiation. Investigation of PPARγ levels indicate that this enhanced adipogenesis is mediated through the stabilization of the PPARγ protein at specific time points during differentiation. Finally, we demonstrate that Itm2a knockdown is sufficient to rescue the inhibitory effects of lamin A WT and R482W mutant overexpression on 3T3-L1 differentiation. This suggests that targeting of Itm2a or its related pathways, including autophagy, may have potential as a therapy for FPLD2.

Chronic Widespread Pain Drawn on a Body Diagram is a Screening Tool for Increased Pain Sensitization, Psycho-Social Load, and Utilization of Pain Management Strategies.

The aim of this study was to investigate the hypothesis that chronic widespread pain, (CWP) drawn by patients on a body diagram, could be used as a screening tool for increased pain sensitization, psycho-social load, and utilization of pain management strategies. The triage questionnaires of 144 adults attending a chronic pain outpatients' clinic were audited and the percentage pain surface area (PPSA) drawn on their body diagrams was calculated using the "rule of nines" (RON) method for burns area assessment. Outcomes were measured using the painDETECT Questionnaire (PD-Q) and other indices and compared using a nonrandomized, case-control method. It was found that significantly more subjects with CWP (defined as a PPSA ≥ 20%) reported high (≥ 19) PD-Q scores (suggesting pain "sensitization" or neuropathic pain) (P = 0.0002), "severe" or "extremely severe" anxiety scores on the Depression, Anxiety and Stress Scale-21 Items Questionnaire (P = 0.0270), ≥ 5 psycho-social stressors (P = 0.0022), ≥ 5 significant life events (P = 0.0098), and used ≥ 7 pain management strategies (PMS) (P < 00001), compared to control subjects with a lower PPSA. A Widespread Pain Index score ≥ 7 (OR = 11.36), PD-Q score ≥ 19 (OR = 4.46) and use of ≥ 7 PMS (OR = 5.49) were independently associated with CWP. This study demonstrates that calculating PPSA on a body diagram (using the RON method) is a valid and convenient "snapshot" screening tool to identify patients with an increased likelihood of pain sensitization, psycho-social load, and utilizing pain management resources.

Spinal pain: current understanding, trends, and the future of care.

This commissioned review paper offers a summary of our current understanding of nonmalignant spinal pain, particularly persistent pain. Spinal pain can be a complex problem, requiring management that addresses both the physical and psychosocial components of the pain experience. We propose a model of care that includes the necessary components of care services that would address the multidimensional nature of spinal pain. Emerging care services that tailor care to the individual person with pain seems to achieve better outcomes and greater consumer satisfaction with care, while most likely containing costs. However, we recommend that any model of care and care framework should be developed on the basis of a multidisciplinary approach to care, with the scaffold being the principles of evidence-based practice. Importantly, we propose that any care services recommended in new models or frameworks be matched with available resources and services - this matching we promote as the fourth principle of evidence-based practice. Ongoing research will be necessary to offer insight into clinical outcomes of complex interventions, while practice-based research would uncover consumer needs and workforce capacity. This kind of research data is essential to inform health care policy and practice.

Implementing evidence-informed policy into practice for health care professionals managing people with low back pain in Australian rural settings: a preliminary prospective single-cohort study.

OBJECTIVE: To provide access to professional development opportunities for health care professionals, especially in rural Australian regions, consistent with recommendations in the Australian National Pain Strategy and state government policy. DESIGN AND SETTING: A preliminary prospective, single-cohort study design, which aligned health policy with evidence-informed clinical practice, evaluated the implementation and effectiveness of an interprofessional, health care provider pain education program (hPEP) for management of nonspecific low back pain (nsLBP) in rural Western Australia. INTERVENTION: The 6.5-hour hPEP intervention was delivered to 60 care providers (caseload nsLBP 19.8% ± 22.5) at four rural WA regions. OUTCOME MEASURES: Outcomes were recorded at baseline and 2 months post-intervention regarding attitudes, beliefs (modified Health Care Providers Pain and Impairment Relationship Scale [HC-PAIRS]), Back Pain Beliefs Questionnaire [BBQ]), and self-reported evidence-based clinical practice (knowledge and skills regarding nsLBP, rated on a 5-point Likert scale with 1 = nil and 5 = excellent). RESULTS: hPEP was feasible to implement. At 2 months post-hPEP, responders' (response rate 53%) improved evidence-based beliefs were indicated by HC-PAIRS scores: baseline mean (SD) [43.2 (9.3)]; mean difference (95% CI) [-5.9 (-8.6 to -3.1)]; and BBQ baseline [34.3 (6.8)]; mean difference [2.1 (0.5 to 3.6)]. Positive shifts were observed for all measures of clinical knowledge and skills (P < 0.001) and increased assistance with planning lifestyle changes (P < 0.001), advice on self-management (P = 0.010), and for decreased referrals for spinal imaging (P = 0.03). CONCLUSIONS: This policy-into-practice educational program is feasible to implement in rural Western Australia (WA). While preliminary data are encouraging, a further randomized controlled trial is recommended.

Consumers' experiences of back pain in rural Western Australia: access to information and services, and self-management behaviours.

BACKGROUND: Coordinated, interdisciplinary services, supported by self-management underpin effective management for chronic low back pain (CLBP). However, a combination of system, provider and consumer-based barriers exist which limit the implementation of such models into practice, particularly in rural areas where unique access issues exist. In order to improve health service delivery for consumers with CLBP, policymakers and service providers require a more in depth understanding of these issues. The objective of this qualitative study was to explore barriers experienced by consumers in rural settings in Western Australia (WA) to accessing information and services and implementing effective self-management behaviours for CLBP. METHODS: Fourteen consumers with a history of CLBP from three rural sites in WA participated. Maximum variation sampling was employed to ensure a range of experiences were captured. An interviewer, blinded to quantitative pain history data, conducted semi-structured telephone interviews using a standardised schedule to explore individuals' access to information and services for CLBP, and self-management behaviours. Interviews were digitally recorded and transcribed verbatim. Inductive analysis techniques were used to derive and refine key themes. RESULTS: Five key themes were identified that affected individuals' experiences of managing CLBP in a rural setting, including: 1) poor access to information and services in rural settings; 2) inadequate knowledge and skills among local practitioners; 3) feelings of isolation and frustration; 4) psychological burden associated with CLBP; and 5) competing lifestyle demands hindering effective self-management for CLBP. CONCLUSIONS: Consumers in rural WA experienced difficulties in knowing where to access relevant information for CLBP and expressed frustration with the lack of service delivery options to access interdisciplinary and specialist services for CLBP. Competing lifestyle demands such as work and family commitments were cited as key barriers to adopting regular self-management practices. Consumer expectations for improved health service coordination and a workforce skilled in pain management are relevant to future service planning, particularly in the contexts of workforce capacity, community health services, and enablers to effective service delivery in primary care.

A policy-into-practice intervention to increase the uptake of evidence-based management of low back pain in primary care: a prospective cohort study.

BACKGROUND: Persistent non-specific low back pain (nsLBP) is poorly understood by the general community, by educators, researchers and health professionals, making effective care problematic. This study evaluated the effectiveness of a policy-into-practice intervention developed for primary care physicians (PCPs). METHODS: To encourage PCPs to adopt practical evidence-based approaches and facilitate time-efficient, integrated management of patients with nsLBP, we developed an interdisciplinary evidence-based, practical pain education program (gPEP) based on a contemporary biopsychosocial framework. One hundred and twenty six PCPs from primary care settings in Western Australia were recruited. PCPs participated in a 6.5-hour gPEP. Self-report measures recorded at baseline and at 2 months post-intervention included PCPs' attitudes, beliefs (modified Health Care Providers Pain and Impairment Relationship Scale (HC-PAIRS), evidence-based clinical practices (knowledge and skills regarding nsLBP management: 5-point Likert scale with 1  =  nil and 5  =  excellent) and practice behaviours (recommendations based on a patient vignette; 5-point Likert scale). RESULTS: Ninety one PCPs participated (attendance rate of 72%; post-intervention response rate 88%). PCP-responders adopted more positive, guideline-consistent beliefs, evidenced by clinically significant HC-PAIRS score differences (mean change  =  -5.6±8.2, p<0.0001; 95% confidence interval: -7.6 to -3.6) and significant positive shifts on all measures of clinical knowledge and skills (p<0.0001 for all questions). Self management strategies were recommended more frequently post-intervention. The majority of responders who were guideline-inconsistent for work and bed rest recommendations (82% and 62% respectively) at pre-intervention, gave guideline-consistent responses at post-intervention. CONCLUSION: An interprofessional pain education program set within a framework that aligns health policy and practice, encourages PCPs to adopt more self-reported evidence-based attitudes, beliefs and clinical behaviours in their management of patients with nsLBP. However, further research is required to determine cost effectiveness of this approach when compared with other modes of educational delivery and to examine PCP behaviours in actual clinical practice.

Engaging consumers living in remote areas of Western Australia in the self-management of back pain: a prospective cohort study.

BACKGROUND: In Western Australia (WA), health policy recommends encouraging the use of active self-management strategies as part of the co-care of consumers with persistent low back pain (LBP). As many areas in WA are geographically isolated and health services are limited, implementing this policy into practice is critical if health outcomes for consumers living in geographically-isolated areas are to be improved. METHODS: In this prospective cohort study, 51 consumers (mean (SD) age 62.3 (± 15.1) years) participated in an evidence-based interdisciplinary pain education program (modified Self Training Educative Pain Sessions: mSTEPS) delivered at three geographically isolated WA sites. Self report measures included LBP beliefs and attitudes (Back Pain Beliefs Questionnaire (BBQ); Fear Avoidance Beliefs Questionnaire (FABQ)), use of active and passive self-management strategies, and health literacy, and global perceived impression of usefulness (GPIU) recorded immediately pre-intervention (n = 51), same day post-intervention (BBQ; GPIU, n = 49) and 3 months post-intervention (n = 25). RESULTS: At baseline, consumers demonstrated adequate health literacy and elements of positive health behaviours, reflected by the use of more active than passive strategies in self-managing their persistent LBP. Immediately post-intervention, there was strong evidence for improvement in consumers' general beliefs about LBP as demonstrated by an increase in BBQ scores (baseline [mean (SD): 25.8 (7.6)] to same day post-intervention [28.8 (7.2); P < 0.005], however this improvement was not sustained at 3 months post-intervention. The majority of consumers (86.4%) reported the intervention as very useful [rated on NRS as 7-10]. CONCLUSIONS: To sustain improved consumer beliefs regarding LBP and encourage the adoption of more positive health behaviours, additional reinforcement strategies for consumers living in remote areas where service access and skilled workforce are limited are recommended. This study highlights the need for aligning health services and skilled workforce to improve the delivery of co-care for consumers living in geographically isolated areas.

Preclinic group education sessions reduce waiting times and costs at public pain medicine units.

OBJECTIVE: To assess the effects of preclinic group education sessions and system redesign on tertiary pain medicine units and patient outcomes. DESIGN: Prospective cohort study. SETTING: Two public hospital multidisciplinary pain medicine units. PATIENTS: People with persistent pain. INTERVENTIONS: A system redesign from a "traditional" model (initial individual medical appointments) to a model that delivers group education sessions prior to individual appointments. Based on Patient Triage Questionnaires patients were scheduled to attend Self-Training Educative Pain Sessions (STEPS), a two day eight hour group education program, followed by optional patient-initiated clinic appointments. OUTCOME MEASURES: Number of patients completing STEPS who subsequently requested individual outpatient clinic appointment(s); wait-times; unit cost per new patient referred; recurrent health care utilization; patient satisfaction; Global Perceived Impression of Change (GPIC); and utilized pain management strategies. RESULTS: Following STEPS 48% of attendees requested individual outpatient appointments. Wait times reduced from 105.6 to 16.1 weeks at one pain unit and 37.3 to 15.2 weeks at the second. Unit cost per new patient appointed reduced from $1,805 Australian Dollars (AUD) to AUD$541 (for STEPS). At 3 months, patients scored their satisfaction with "the treatment received for their pain" more positively than at baseline (change score=0.88; P=0.0003), GPIC improved (change score=0.46; P<0.0001) and mean number of active strategies utilized increased by 4.12 per patient (P=0.0004). CONCLUSIONS: The introduction of STEPS was associated with reduced wait-times and costs at public pain medicine units and increased both the use of active pain management strategies and patient satisfaction.