Patients', physiotherapists' and other stakeholders' experiences and perceptions about supported home physiotherapy for people with musculoskeletal conditions: a qualitative study.

OBJECTIVES: Exercise, support and advice are the key treatment strategies of musculoskeletal problems. The aims of this study were to determine patients', physiotherapists', and other stakeholders' perspectives about supported home physiotherapy for the management of musculoskeletal problems and to identify the barriers and facilitators to rolling out this model of physiotherapy service delivery. METHODS: This study was conducted as part of a process evaluation run alongside a large trial designed to determine whether supported home physiotherapy is as good or better than a course of in-person physiotherapy. Forty interviews were conducted with 20 trial participants, 15 physiotherapists, and 5 other stakeholders. The interviews were semi-structured and based on interview guides. Each interview was transcribed and a three-tiered coding tree was developed. RESULTS: Six key themes were identified. Supported home physiotherapy (i) is convenient for some patients, (ii) does not always align with patients' and therapists' expectations about treatment (iii) is suitable for some but not all, (iv) can reduce personal connection and accountability, (v) has implications for physiotherapists' workloads, and (vi) has barriers and facilitators to future implementation. CONCLUSIONS: Findings suggest that patients are far more accepting of supported home physiotherapy than physiotherapists assume. This model of service delivery could be rolled out to improve access to physiotherapy and to provide a convenient and effective way of delivering physiotherapy to some patients with musculoskeletal conditions if our trial results indicate that supported home physiotherapy is as good or better than in-person physiotherapy. CLINICAL TRIAL REGISTRY NUMBER: ACTRN12619000065190 CONTRIBUTIONS OF THIS PAPER.

Remotely delivered physiotherapy is as effective as face-to-face physiotherapy for musculoskeletal conditions (REFORM): a randomised trial.

QUESTION: Is remotely delivered physiotherapy as good or better than face-to-face physiotherapy for the management of musculoskeletal conditions? DESIGN: Randomised controlled, non-inferiority trial with concealed allocation, blinded assessors and intention-to-treat analysis. PARTICIPANTS: A total of 210 adult participants with a musculoskeletal condition who presented for outpatient physiotherapy at five public hospitals in Sydney. INTERVENTION: One group received a remotely delivered physiotherapy program for 6 weeks that consisted of one face-to-face physiotherapy session in conjunction with weekly text messages, phone calls at 2 and 4 weeks, and an individualised home exercise program delivered through an app. The other group received usual face-to-face physiotherapy care in an outpatient setting. OUTCOME MEASURES: The primary outcome was the Patient Specific Functional Scale at 6 weeks with a pre-specified non-inferiority margin of -15 out of 100 points. Secondary outcomes included: the Patient Specific Functional Scale at 26 weeks; kinesiophobia, pain, function/disability, global impression of change and quality of life at 6 and 26 weeks; and satisfaction with service delivery at 6 weeks. RESULTS: The mean between-group difference (95% CI) for the Patient Specific Functional Scale at 6 weeks was 2.7 out of 100 points (-3.5 to 8.8), where a positive score favoured remotely delivered physiotherapy. The lower end of the 95% CI was greater than the non-inferiority margin. Whilst non-inferiority margins were not set for the secondary outcomes, the 95% CI of the mean between-group difference ruled out clinically meaningful differences. CONCLUSION: Remotely delivered physiotherapy with support via phone, text and an app is as good as face-to-face physiotherapy for the management of musculoskeletal conditions. TRIAL REGISTRATION: ACTRN12619000065190.

Protocol for a process evaluation: face-to-face physiotherapy compared with a supported home exercise programme for the management of musculoskeletal conditions: the REFORM trial.

INTRODUCTION: The REFORM (REhabilitation FOR Musculoskeletal conditions) trial is a non-inferiority randomised controlled trial (n=210) designed to determine whether a supported home exercise programme is as good or better than a course of face-to-face physiotherapy for the management of some musculoskeletal conditions. The trial is currently being conducted across Sydney government hospitals in Australia. This process evaluation will run alongside the REFORM trial. It combines qualitative and quantitative data to help explain the trial results and determine the feasibility of rolling out supported home exercise programmes in settings similar to the REFORM trial. METHODS AND ANALYSIS: Two theoretical frameworks underpin our process evaluation methodology: the Realist framework (context, mechanism, outcomes) considers the causal assumptions as to why a supported home exercise programme may be as good or better than face-to-face physiotherapy in terms of the context, mechanisms and outcomes of the trial. The RE-AIM framework describes the Reach, Effectiveness, Adoption, Implementation and Maintenance of the intervention. These two frameworks will be broadly used to guide this process evaluation using a mixed-methods approach. For example, qualitative data will be derived from interviews with patients, healthcare professionals and stakeholders, and quantitative data will be collected to determine the cost and feasibility of providing supported home exercise programmes. These data will be analysed iteratively before the analysis of the trial results and will be triangulated with the results of the primary and secondary outcomes. ETHICS AND DISSEMINATION: This trial will be conducted in accordance with the National Health and Medical Research Council National Statement on Ethical Conduct in Human Research (2018) and the Note for Good Clinical Practice (CPMP/ICH-135/95). Ethical approval was obtained on 17 March 2017 from the Northern Sydney Local Health District Human Research Ethics Committee (trial number: HREC/16HAWKE/431-RESP/16/287) with an amendment for the process evaluation approved on 4 February 2020. The results of the process evaluation will be disseminated through publications in peer-reviewed journals and presentations at scientific conferences. TRIAL REGISTRATION NUMBER: ACTRN12619000065190.

Face-to-face physiotherapy compared with a supported home exercise programme for the management of musculoskeletal conditions: protocol of a multicentre, randomised controlled trial-the REFORM trial.

INTRODUCTION: Exercise, support and advice are considered core components of management for most musculoskeletal conditions and are typically provided by physiotherapists through regular face-to-face treatments. However, exercise can be provided remotely as part of a home exercise programme, while support and advice can be provided over the telephone. There is initial evidence from trials and systematic reviews to suggest that remotely provided physiotherapy can be used to manage a variety of musculoskeletal conditions safely and effectively. METHODS AND ANALYSIS: The aim of this single-blind randomised controlled non-inferiority trial is to determine whether a supported home exercise programme is as good as or better than face-to-face physiotherapy for the treatment of musculoskeletal conditions. Two hundred and ten participants will be recruited from five public hospitals in Sydney, Australia. Participants will be randomised to either the supported home exercise group or the face-to-face physiotherapy group. Participants allocated to the supported home exercise group will initially receive one face-to-face session with the trial physiotherapist and will then be managed remotely for the next 6 weeks. Participants allocated to the face-to-face physiotherapy group will receive a course of physiotherapy as typically provided in Sydney government hospitals. The primary outcome is function measured by the Patient Specific Functional Scale at 6 weeks. There will be nine secondary outcomes measured at 6 and 26 weeks. Separate analyses will be conducted on each outcome, and all analyses will be conducted on an intention-to-treat basis. A health economic evaluation will be conducted from a health funder plus patient perspective. ETHICS AND DISSEMINATION: Ethical approval was obtained on the 17 March 2017 from the Northern Sydney Local Health District HREC, trial number HREC/16HAWKE/431-RESP/16/287. The results of this study will be submitted for publication to peer-reviewed journals and be presented at national and international conferences. Recruitment commenced in March 2019, and it is anticipated that the trial will be completed by December 2021. This trial will investigate two different models of physiotherapy care for people with musculoskeletal conditions. TRIAL REGISTRATION NUMBER: CPMP/ICH-135/95. PROTOCOL VERSION: The most recent version of the protocol is V.1.2 dated November 2019.

Randomized trial of simple versus complex drug-eluting stenting for bifurcation lesions: the British Bifurcation Coronary Study: old, new, and evolving strategies.

BACKGROUND: The optimal strategy for treating coronary bifurcation lesions remains a subject of debate. With bare-metal stents, single-stent approaches appear to be superior to systematic 2-stent strategies. Drug-eluting stents, however, have low rates of restenosis and might offer improved outcomes with complex stenting techniques. METHODS AND RESULTS: Patients with significant coronary bifurcation lesions were randomized to either a simple or complex stenting strategy with drug-eluting stents. In the simple strategy, the main vessel was stented, followed by optional kissing balloon dilatation/T-stent. In the complex strategy, both vessels were systematically stented (culotte or crush techniques) with mandatory kissing balloon dilatation. Five hundred patients 64+/-10 years old were randomized; 77% were male. Eighty-two percent of lesions were true bifurcations (>50% narrowing in both vessels). In the simple group (n=250), 66 patients (26%) had kissing balloons in addition to main-vessel stenting, and 7 (3%) had T stenting. In the complex group (n=250), 89% of culotte (n=75) and 72% of crush (n=169) cases were completed successfully with final kissing balloon inflations. The primary end point (a composite at 9 months of death, myocardial infarction, and target-vessel failure) occurred in 8.0% of the simple group versus 15.2% of the complex group (hazard ratio 2.02, 95% confidence interval 1.17 to 3.47, P=0.009). Myocardial infarction occurred in 3.6% versus 11.2%, respectively (P=0.001), and in-hospital major adverse cardiovascular events occurred in 2.0% versus 8.0% (P=0.002), respectively. Procedure duration and x-ray dose favored the simple approach. CONCLUSIONS: When coronary bifurcation lesions are treated, a systematic 2-stent technique results in higher rates of in-hospital and 9-month major adverse cardiovascular events. This difference is largely driven by periprocedural myocardial infarction. Procedure duration is longer, and x-ray dose is higher. The provisional technique should remain the preferred strategy in the majority of cases. Clinical Trial Registration Information- URL: http://www.clinicaltrials.gov. Unique identifier: NCT 00351260.

Hospital and operator variations in drug-eluting stent use: a multi-level analysis of 5967 consecutive patients in Scotland.

OBJECTIVE: To determine whether drug-eluting stent (DES) use varies among Scottish hospitals, and the extent to which any variations are explained by differences between operators, patients and lesions. METHODS: Multi-level analysis of consecutive patients treated with percutaneous coronary intervention (PCI) between April 2005 and March 2006 in Scotland, using the Scottish Coronary Revascularization Registry. RESULTS: A total of 38 operators performed 5967 PCI procedures on 8489 lesions. Crude level of DES use was 47.6%, and the results varied among hospitals (range 30.6-61.8%, chi(2) = 341.6, P < 0.0001). There was significant between-operator variation in the null model. This was attenuated by the addition of hospital as a fixed effect. Nonetheless, the final model demonstrated significant between-operator variability [sigma(2) = 0.486 (0.249-0.971)] and between-hospital variation, after case-mix adjustment. CONCLUSIONS: Within Scotland, marked variation existed among hospitals in the use of DES. Operator was the most important factor at patient level, and hospital of treatment, rather than case-mix, was the most important modifier of between-operator variation. Patient selection for DES is complex and may contribute to much of the variations demonstrated. Consensus criteria would provide more detail than is included in current guidance, may aid decision-making for individual patients, reduce opportunity costs and ensure equity of access.

Drug-eluting stents versus bare-metal stents for off-label indications: a propensity score-matched outcome study.

BACKGROUND: The US Food and Drug Administration recently concluded that data on off-label drug-eluting stent (DES) safety are limited. However, in actual clinical practice, DES are often used for off-label indications, and observational studies demonstrate that complications are higher when compared with on-label use. We aimed to determine whether clinical outcomes differ after DES and bare-metal stent implantation in a patient cohort defined by DES off-label indications. METHODS AND RESULTS: We used the national revascularization registry in Scotland to identify patients who underwent coronary stenting for an off-label indication between January 2003 and September 2005. Individual-level linkage to comprehensive national admission and death databases was used to ascertain the end points of death, myocardial infarction, and target-vessel revascularization. We calculated propensity scores on the basis of clinical, demographic, and angiographic variables and matched DES to bare-metal stents on a 1:1 basis. The final study population consisted of 1642 patients, well matched for important covariables at baseline. Event-free survival was calculated over 24 months with the Kaplan-Meier method. All-cause death was more common after bare-metal stent implantation during follow-up (7.7% versus 6.6%; hazard ratio 0.63; 95% confidence interval, 0.40 to 0.99; P=0.04). No difference in the rates of myocardial infarction were noted (7.3% versus 7.5%; hazard ratio 1.02; 95% confidence interval, 0.69 to 1.54; P=0.92). Target-vessel revascularization was reduced in patients treated with DES (13.9% versus 10.7%; hazard ratio 0.67; 95% confidence interval, 0.49 to 0.93; P=0.02). CONCLUSIONS: At 24 months, patients treated with DES for off-label indications had lower rates of death and target-vessel revascularization and similar rates of myocardial infarction, as compared with patients treated with bare-metal stents.

Reduced vascular complications and length of stay with transradial rescue angioplasty for acute myocardial infarction.

OBJECTIVES: The aim of this study was to compare clinical outcomes for transradial and transfemoral percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction undergoing rescue angioplasty. BACKGROUND: Transfemoral percutaneous coronary intervention in patients with acute myocardial infarction treated with systemic thrombolysis is associated with a significant risk of vascular complications. A transradial approach may reduce vascular complications, improve mobilization and facilitate earlier discharge. METHODS: In a retrospective analysis, clinical outcomes for 287 consecutive patients undergoing rescue angioplasty for acute myocardial infarction were determined. Data were recorded using a standardized proforma and analyzed using SPSS. RESULTS: Procedural success was similar for the transradial and transfemoral routes (98% vs. 93%; P = 0.3). There was a reduction in vascular complications (0 (0%) vs. 32 (13%); P < 0.01) and post-procedural length of stay (7.0 +/- 7.9 vs. 7.9 +/- 5.6 days; P < 0.005) in the radial group when compared with the femoral group. There were no differences in procedural or in-hospital mortality, procedure duration, or radiation dose between the two groups. CONCLUSION: Rescue angioplasty performed via the radial artery is safe, effective, and associated with a reduction in vascular complications and length of hospital stay when compared with the femoral approach. These findings suggest that where facilities and experience allow rescue angioplasty in patients with acute myocardial infarction should be performed via the radial artery.

Effects of sumatriptan and eletriptan on diseased epicardial coronary arteries.

BACKGROUND: Triptans are contraindicated in patients with known or suspected coronary artery disease (CAD); however, few studies have evaluated triptans in patients with obstructive CAD to quantify the vasoconstrictive effect on diseased coronary vessels. METHODS: Patients undergoing percutaneous transluminal coronary angioplasty for symptomatic single-vessel CAD were randomised to one of three parallel cohorts to receive (1) 6 mg intravenously (IV) infused eletriptan plus subcutaneous (SC) placebo, (2) IV infused placebo plus 6 mg SC sumatriptan or (3) IV infused placebo plus SC placebo, as simultaneous administrations in a double-blind manner. Serial arteriograms, hemodynamic indices, electrocardiography and triptan plasma concentrations were obtained. RESULTS: . Fifteen minutes after triptan challenge, median (95% confidence interval) changes in coronary artery diameter (CADM) at the focal point of the stenosed segment were: dilation of 2.6% (-5.0, 11.4), eletriptan 6 mg IV (n = 18); constriction of 6.8% (-12.6, 0.4), sumatriptan 6 mg SC (n = 17), and constriction of 4.5% (-7.0, 7.9), placebo (n = 10). One patient had angiographic evidence of a new thrombus at the stenosis site, necessitating termination of study infusion and successful stenting of the lesion. There was no correlation between effects on CADM and triptan concentration, or between hemodynamic or electrocardiograph changes and the presence (n = 13) or absence (n = 33) of chest pain. CONCLUSIONS: Triptans had very little effect on diseased epicardial coronary arteries in a small group of angina sufferers with established CAD. Results should be interpreted cautiously since there may be instances where even modest triptan-associated epicardial constriction is sufficient to precipitate myocardial ischemia in patients with severe obstructive CAD.

Randomized, controlled study of long-acting local anesthetic (levobupivacaine) in femoral artery sheath management during and after percutaneous coronary intervention.

OBJECTIVE: To assess the effect of long-acting local anesthetic (levobupivacaine) in addition to lidocaine for the management of femoral artery sheaths during and after percutaneous coronary intervention (PCI). BACKGROUND: Femoral artery sheaths are commonly used during PCI. Sheath removal is often delayed after the procedure by which time short-acting local anesthetic agents may no longer be effective. METHODS: Sixty patients were randomized to either usual care or the administration of local levobupivacaine after PCI. Patients were asked to report their pain experienced on a visual analogue score. RESULTS: Thirty patients received additional levobupivacaine (0.5%) and 30 received standard care. There were no procedural differences between the groups, except that more patients in the control group received intravenous (IV) morphine at the time of sheath removal. There was no difference between the control group and levobupivacaine group in pain scores at the time of sheath insertion. (2.0 +/- 0.4 versus 1.8 +/- 0.3; p = 0.80). Both groups recorded low pain scores while waiting for sheath removal, and the score was slightly (but not significantly) lower in the levobupivacaine group (1.3 +/- 0.2 versus 0.8 +/- 0.2; p = 0.09). Pain scores were lower in the levobupivacaine group during sheath removal 2.2 +/- 0.4 versus 1.1 +/- 0.2; p = 0.02). There were no differences in terms of blood pressure between the groups at any time point. CONCLUSIONS: Levobupivacaine reduced the need for IV opiate and provided better analgesia than lidocaine alone in patients undergoing PCI.

Structure-based drug design targeting an inactive RNA conformation: exploiting the flexibility of HIV-1 TAR RNA.

The targeting of RNA for the design of novel anti-viral compounds represents an area of vast potential. We have used NMR and computational methods to model the interaction of a series of synthetic inhibitors of the in vitro RNA binding activities of a peptide derived from the transcriptional activator protein, Tat, from human immunodeficiency virus type 1. Inhibition has been measured through the monitering of fluorescence resonance energy transfer between fluorescently labeled peptide and RNA components. A series of compounds containing a bi-aryl heterocycle as one of the three substituents on a benzylic scaffold, induce a novel, inactive TAR conformation by stacking between base-pairs at the site of a three-base bulge within TAR. The development of this series resulted in an enhancement in potency (with Ki < 100 nM in an in vitro assay) and the removal of problematic guanidinium moieties. Ligands from this series can act as inhibitors of Tat-induced transcription in a cell-free system. This study validates the drug design strategy of using a ligand to target the RNA receptor in a non-functional conformation.

Rational design of inhibitors of HIV-1 TAR RNA through the stabilisation of electrostatic "hot spots".

The targeting of RNA for the design of novel anti-viral compounds has until now proceeded largely without incorporating direct input from structure-based design methodology, partly because of lack of structural data, and complications arising from substrate flexibility. We propose a paradigm to explain the physical mechanism for ligand-induced refolding of trans-activation response element (TAR RNA) from human immunodeficiency virus 1 (HIV-1). Based upon Poisson-Boltzmann analysis of the TAR structure, as bound by a peptide derived from the transcriptional activator protein, Tat, our hypothesis shows that two specific electrostatic interactions are necessary to stabilise the conformation. This result contradicts the belief that a single argininamide residue is responsible for stabilising the TAR fold, as well as the conventional wisdom that electrostatic interactions with RNA are non-specific or dominated by phosphates. We test this hypothesis by using NMR and computational methods to model the interaction of a series of novel inhibitors of the in vitro RNA-binding activities for a peptide derived from Tat. A subset of inhibitors, including the bis-guanidine compound rbt203 and its analogues, induce a conformation in TAR similar to that brought about by the protein. Comparison of the interactions of two of these ligands with the RNA and structure-activity relationships observed within the compound series, confirm the importance of the two specific electrostatic interactions in the stabilisation of the Tat-bound RNA conformation. This work illustrates how the use of medicinal chemistry and structural analysis can provide a rational basis for prediction of ligand-induced conformational change, a necessary step towards the application of structure-based methods in the design of novel RNA or protein-binding drugs.

An evaluation of Superthumb and the Kneeshaw device as manual therapy tools.

This research evaluated two hand-held tools (Superthumb and Kneeshaw device) that have been developed in order to reduce hand pain associated with the performance of manual therapy. Two studies were conducted: one evaluated the ability to perceive elastic stiffness with the devices and the other evaluated physiotherapist and patient comfort when the devices were used to apply a mobilisation to the lumbar spine. In the first study we found that the two tools and the pisiform grip provided equivalent ability to detect small differences in elastic stiffness, however the tools introduced a bias so that the stiffness stimuli felt stiffer than when assessed with the pisiform grip. In the second study we found that the two tools were substantially less comfortable than the pisiform grip, for both patient and therapist, when a therapist applied a Grade III mobilisation to the lumbar spine. The results suggest that neither tool, in its current form, is suitable for clinical practice.