Rapid sub-nanomolar protein determination in serum using electropolymerized molecularly imprinted polymers (E-MIPs).

Rapid detection of biologicals is important for a range of applications such as medical screening and diagnostics. Antibodies are typically employed for biosensing with high sensitivity and selectivity but can take months to prepare. Here, we investigate electropolymerized molecularly imprinted polymers (E-MIPs), which are produced in minutes as alternative-antibody rapid biosensors for the selective recognition of model proteins bovine haemoglobin (BHb) and bovine serum albumin (BSA). We evaluated two disposable screen-printed electrodes (SPE) designated AT-Au and BT-Au based on their different annealing temperatures. E-MIPs for BHb demonstrated an imprinting factor of 146 : 1 at 1 nM and 12 : 1 at 0.1 nM, showing high effectiveness of E-MIPs compared to their control non-imprinted polymers. The BHb imprinted E-MIP, when tested against BSA as a non-target protein, gave a selectivity factor of 6 : 1 for BHb. Sensor sensitivity directly depended on the nature of the SPE, with AT-Au SPE demonstrating limits of detection in the sub-micromolar range typically achieved for MIPs, while BT-Au SPE exhibited sensitivity in the sub-nanomolar range for target protein. We attribute this to differences in electrode surface area between AT-Au and BT-Au SPEs. The E-MIPs were also tested in calf serum as a model biological medium. The BT-Au SPE MIPs detected the presence of target protein in <10 min with an LOD of 50 pM and LOQ of 100 pM, suggesting their suitability for protein determination in serum with minimal sample preparation. Using electrochemical impedance spectroscopy, we determine equilibrium dissociation constants (KD) for E-MIPs using the Hill-Langmuir adsorption model. KD of BHb E-MIP was determined to be 0.86 ± 0.11 nM.

Evaluating Osteoarthritis Management Programs: outcome domain recommendations from the OARSI Joint Effort Initiative.

OBJECTIVE: To develop sets of core and optional recommended domains for describing and evaluating Osteoarthritis Management Programs (OAMPs), with a focus on hip and knee Osteoarthritis (OA). DESIGN: We conducted a 3-round modified Delphi survey involving an international group of researchers, health professionals, health administrators and people with OA. In Round 1, participants ranked the importance of 75 outcome and descriptive domains in five categories: patient impacts, implementation outcomes, and characteristics of the OAMP and its participants and clinicians. Domains ranked as "important" or "essential" by ≥80% of participants were retained, and participants could suggest additional domains. In Round 2, participants rated their level of agreement that each domain was essential for evaluating OAMPs: 0 = strongly disagree to 10 = strongly agree. A domain was retained if ≥80% rated it ≥6. In Round 3, participants rated remaining domains using same scale as in Round 2; a domain was recommended as "core" if ≥80% of participants rated it ≥9 and as "optional" if ≥80% rated it ≥7. RESULTS: A total of 178 individuals from 26 countries participated; 85 completed all survey rounds. Only one domain, "ability to participate in daily activities", met criteria for a core domain; 25 domains met criteria for an optional recommendation: 8 Patient Impacts, 5 Implementation Outcomes, 5 Participant Characteristics, 3 OAMP Characteristics and 4 Clinician Characteristics. CONCLUSION: The ability of patients with OA to participate in daily activities should be evaluated in all OAMPs. Teams evaluating OAMPs should consider including domains from the optional recommended set, with representation from all five categories and based on stakeholder priorities in their local context.

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.

Osteoarthritis year in review 2022: rehabilitation.

This year in review presents key highlights from research relating to osteoarthritis (OA) rehabilitation published from the 1st April 2021 to the 18th March 2022. To identify studies for inclusion in the review, an electronic database search was carried out in Medline, Embase and CINAHLplus. Following screening, included studies were grouped according to their predominant topic area, including core OA rehabilitation treatments (education, exercise, weight loss), adjunctive treatments, novel and emerging treatments or research methods, and translation of rehabilitation evidence into practice. Studies of perceived high clinical importance, quality, or controversy in the field were selected for inclusion in the review. Headline findings include: the positive role of technology to support remote delivery of core OA rehabilitation treatments, the importance of delivering educational interventions alongside exercise, the clinical and cost-effectiveness of a stepped approach to exercise, controversy around the potential mechanisms of action of exercise, mixed findings regarding the use of splinting for thumb base OA, increasing research on blood flow restriction training as a potential new intervention for OA, and evidence that the beneficial effects from core OA treatments seen in randomised controlled trials can be seen when implemented in clinical practice. A consistent finding across several recently published systematic reviews is that randomised controlled trials testing OA rehabilitation interventions are often small, with some risk of bias. Whilst future research is warranted, it needs to be large scale and robust, to enable definitive answers to important remaining questions in the field of OA rehabilitation.

How does hip osteoarthritis differ from knee osteoarthritis?

Hip and knee osteoarthritis (OA) are leading causes of global disability. Most research to date has focused on the knee, with results often extrapolated to the hip, and this extends to treatment recommendations in clinical guidelines. Extrapolating results from research on knee OA may limit our understanding of disease characteristics specific to hip OA, thereby constraining development and implementation of effective treatments. This review highlights differences between hip and knee OA with respect to prevalence, prognosis, epigenetics, pathophysiology, anatomical and biomechanical factors, clinical presentation, pain and non-surgical treatment recommendations and management.

Moderators of the effects of therapeutic exercise for people with knee and hip osteoarthritis: A systematic review of sub-group analyses from randomised controlled trials.

Objective: 1) To identify potential moderators of the effect of therapeutic exercise explored in randomised controlled trials (RCTs) of knee and hip osteoarthritis (OA); 2) summarise the extent, strength and quality of evidence reported for moderators. Design: Systematic review (PROSPERO CRD42019148074). Inclusion criteria: a) RCTs with sub-group analyses investigating potential moderator variables; b) participants with knee and/or hip OA; c) therapeutic exercise interventions compared to either no exercise control or alternative exercise intervention(s), and; d) measuring pain or physical function outcomes. Included RCTs' risk of bias and sub-group analysis quality were assessed. Data were extracted on sub-group analyses (methods and potential moderators), outcomes (pain and function) and sub-group findings (associated statistics of potential moderator∗intervention effects). Findings were analysed using narrative synthesis. Results: 14 RCTs were included; 13 knee OA RCTs (n = 2743 participants) explored 23 potential moderators and 1 hip OA RCT (n = 203) explored 6 potential moderators. Sub-group analysis quality was mixed. Knee varus malalignment was the only moderator of therapeutic exercise compared to non-exercise control in 1 RCT (WOMAC-pain adjusted difference 12.7 in the neutral alignment sub-group and 1.8 in the malaligned sub-group, interaction term: p = 0.02). Varus thrust, knee laxity/instability, obesity and cardiac problems all moderated the effect of therapeutic exercise on pain or function compared to different comparison exercise. Conclusions: Therapeutic exercise may be effective for reducing pain in people with knee OA and neutral alignment but not for those with varus malalignment. The exercise moderator literature is limited. More robust evidence is required to inform sub-group exercise selection.

A mixed methods exploration of physiotherapist's approaches to analgesic use among patients with hip osteoarthritis.

OBJECTIVE: To explore how physiotherapists currently address analgesic use among patients with hip osteoarthritis, and their beliefs about the acceptability of prescribing for these patients. METHODS: A cross-sectional questionnaire was mailed to 3126 UK-based physiotherapists. Approaches to analgesic use among patients with hip osteoarthritis were explored using a case vignette. Semi-structured telephone interviews were undertaken with 21 questionnaire responders and analysed thematically. SETTING: UK. PARTICIPANTS: Physiotherapists who had treated a patient with hip osteoarthritis in the previous 6 months. RESULTS: Questionnaire response: 53% (n=1646). One thousand one hundred forty eight physiotherapists reported treating a patient with hip osteoarthritis in the last 6 months (applicable responses), of whom nine (1%) were non-medical prescribers. Nearly all physiotherapists (98%) reported that they would address analgesic use for the patient with hip osteoarthritis, most commonly by signposting them to their GP (83%). Fifty six percent would discuss optimal use of current medication, and 33%, would discuss use of over-the-counter medications. Interviews revealed that variations in physiotherapists' approaches to analgesic use were influenced by personal confidence, patient safety concerns, and their perceived professional remit. Whilst many recognised the benefits of analgesia prescribing for both patients and GP workload, additional responsibility for patient safety was a perceived barrier. CONCLUSIONS: How physiotherapists currently address analgesic use with patients with hip osteoarthritis is variable. Although the potential benefits of independent prescribing were recognised, not all physiotherapist want the additional responsibility. Further guidance supporting optimisation of analgesic use among patients with hip OA may help better align care with best practice guidelines and reduce GP referrals.

Contributions of biogenic material to the atmospheric ice-nucleating particle population in North Western Europe.

A minute fraction of atmospheric particles exert a disproportionate effect on the phase of mixed-phase clouds by acting as ice-nucleating particles (INPs). To understand the effects of these particles on weather and climate, both now and into the future, we must first develop a quantitative understanding of the major INP sources worldwide. Previous work has demonstrated that aerosols such as desert dusts are globally important INPs, but the role of biogenic INPs is unclear, with conflicting evidence for their importance. Here, we show that at a temperate site all INPs active above -18 °C at concentrations >0.1 L-1 are destroyed on heating, consistent with these INPs being of biological origin. Furthermore, we show that a global model of desert dust INPs dramatically underestimates the measured INP concentrations, but is consistent with the thermally-stable component. Notably, the heat sensitive INPs are active at temperatures where shallow cloud layers in Northern Europe are frequently observed to glaciate. Hence, we suggest that biogenic material is important for primary ice production in this region. The prevalence of heat sensitive, most likely biogenic, INPs in this region highlights that, as a community, we need to quantify the sources and transport of these particles as well as determine their atmospheric abundance across the globe and at cloud altitudes.

Current management of pregnancy-related low back pain: a national cross-sectional survey of U.K. physiotherapists.

BACKGROUND: Pregnancy-related low back pain (LBP) is very common. Evidence from a systematic review supports the use of exercise and acupuncture, although little is known about the care received by women with pregnancy-related back pain in the U.K. OBJECTIVE: To describe current acupuncture and standard care management of pregnancy-related LBP by U.K. physiotherapists. DESIGN: Cross-sectional survey of physiotherapists with experience of treating women with pregnancy-related LBP from three professional networks of the Chartered Society of Physiotherapy. METHODS: In total, 1093 physiotherapists were mailed a questionnaire. The questionnaire captured respondents' demographic and practice setting information, and experience of managing women with pregnancy-related back pain, and investigated the reported management of pregnancy-related LBP using a patient case vignette of a specific, 'typical' case. RESULTS: The overall response rate was 58% (629/1093). Four hundred and ninety-nine physiotherapists had experience of treating women with pregnancy-related LBP and were included in the analysis. Most respondents worked wholly or partly in the U.K. National Health Service (78%). Most respondents reported that they treat patients with pregnancy-related LBP in three to four one-to-one treatment sessions over 3 to 6 weeks. The results show that a range of management strategies are employed for pregnancy-related LBP, and multimodal management is common. The most common reported treatment was home exercises (94%), and 24% of physiotherapists reported that they would use acupuncture with the patient described in the vignette. CONCLUSIONS: This study provides the first robust data on the management of pregnancy-related LBP by U.K. physiotherapists. Multimodal management is common, although exercise is the most frequently used treatment for pregnancy-related LBP. Acupuncture is used less often for this patient group.

Is long-term physical activity safe for older adults with knee pain?: a systematic review.

OBJECTIVE: To determine whether long-term physical activity is safe for older adults with knee pain. DESIGN: A comprehensive systematic review and narrative synthesis of existing literature was conducted using multiple electronic databases from inception until May 2013. Two reviewers independently screened, checked data extraction and carried out quality assessment. Inclusion criteria for study designs were randomised controlled trials (RCTs), prospective cohort studies or case control studies, which included adults of mean age over 45 years old with knee pain or osteoarthritis (OA), undertaking physical activity over at least 3 months and which measured a safety related outcome (adverse events, pain, physical functioning, structural OA imaging progression or progression to total knee replacement (TKR)). RESULTS: Of the 8614 unique references identified, 49 studies were included in the review, comprising 48 RCTs and one case control study. RCTs varied in quality and included an array of low impact therapeutic exercise interventions of varying cardiovascular intensity. There was no evidence of serious adverse events, increases in pain, decreases in physical function, progression of structural OA on imaging or increased TKR at group level. The case control study concluded that increasing levels of regular physical activity was associated with lower risk of progression to TKR. CONCLUSIONS: Long-term therapeutic exercise lasting 3 to 30 months is safe for most older adults with knee pain. This evidence supports current clinical guideline recommendations. However, most studies investigated selected, consenting older adults carrying out low impact therapeutic exercise which may affect result generalizability. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2014:CRD42014006913.