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.

Impact of antibiotic prophylaxis on catheter-associated urinary tract infections during atrial fibrillation ablation.

PURPOSE: Urinary catheter placement is common during atrial fibrillation (AF) ablation when performed under general anesthesia. Whether patients undergoing AF ablation would benefit from prophylactic antibiotics is unknown. METHODS: Patients undergoing AF ablation in a single center from December 2011 until June 2016 were included. All patients received urinary catheters and general anesthesia. After June 2014, patients received antibiotic prophylaxis with a single dose of oral nitrofurantoin and a catheter insertion checklist performed prior to urinary catheter placement. The intervention group (group B) was compared to the pre-intervention group (group A) for development of the primary outcome. A multivariable logistic regression was performed to determine if any of the covariates were associated with catheter-associated urinary tract infection (CAUTI) development. RESULTS: There were 452 patients who underwent AF ablation during the analysis period (212 in group A and 240 in group B). The average patient age was 60 years (range 23-85) and 70% of the patients were male. Utilizing an intention to treat approach, there was a significantly lower incidence of CAUTI in the intervention group compared to controls (4.7 vs. 0.83%; OR 0.18, p = 0.029). There were no significant differences between the groups with respect to urinary tract infection risk factors or catheter duration. CONCLUSION: An intervention consisting of a single dose of nitrofurantoin in addition to performance of a catheter insertion checklist prior to urinary catheter insertion decreased CAUTI by 80% in patients undergoing AF ablation. Such interventions may be beneficial to reduce CAUTI in this group of patients.

Feasibility of ultrasound-guided vascular access during cardiac implantable device placement.

PURPOSE: Ultrasound (US)-guided access for venous catheter placement has previously been shown to improve success rates and decrease access-related complications. The purpose of this study was to determine the feasibility of US-guided versus traditional vascular access approaches during implantation of cardiac implantable electronic devices (CIEDs). METHODS: We evaluated outcomes for 816 consecutive patients undergoing new CIED implantation between May 2013 and April 2016 at a single institution with respect to use of US guidance for vascular access (137 with US guidance versus 679 with traditional access techniques). The primary outcome was a composite of procedural complications including deep vein thrombosis, pneumothorax, or hematoma. RESULTS: There was no cross-over between US guidance and traditional access. The overall complication rate was 3.6% (2.2% in US, 3.8% in non-US). The use of US was associated with a decrease in fluoroscopy time (r = -0.17, p < 0.01) but not the primary outcome (r = 0.03, p = 0.34). In models adjusted for age and number of leads, use of US was non-significantly associated with a change in fluoroscopy time (beta = -0.20, p = 0.7). In logistic models adjusted for age and number of leads, use of US was associated with a trend toward reduced major complications (OR = 0.57, 95% CI 0.17-1.91, p = 0.36). CONCLUSIONS: US-guided vascular access for CIED implantation is safe and effective compared to traditional approaches with a non-significant reduction in both fluoroscopy time and procedural complications.

Injectable loop recorder implantation in an ambulatory setting by advanced practice providers: Analysis of outcomes.

INTRODUCTION: Implantable loop recorder (ILR) insertion has historically been performed in a surgical environment such as the electrophysiology (EP) lab. The newest generation loop recorder (Medtronic Reveal LINQ™, Minneapolis, MN, USA) is injectable with potential for implantation in a non-EP lab setting by advanced practice providers (APPs) facilitating improved workflow and resource utilization. We report the safety and efficacy of injectable ILR placement in the ambulatory care setting by APPs. METHODS: A retrospective review was performed including all patients referred for injectable ILR placement from March 2014 to November 2015. All device placement procedures were performed in an ambulatory care setting using the standard manufacturer deployment kit with sterile technique and local anesthetic following a single dose of intravenous antibiotics. Acute procedural success and complication rates following injectable ILR placement in the ambulatory setting were reviewed. RESULTS: During the study period, 125 injectable ILRs were implanted. Acute procedural success with adequate sensing (R-waves ≥ 0.2 mV) occurred in 100% of patients. There were no acute procedural complications. Subacute complications occurred in two patients (1.6% of implantations), including one possible infection treated with oral antibiotics and one device removal due to pain at the implant site. CONCLUSION: In this retrospective single-center study, implantation of injectable ILR in an ambulatory care setting by APPs following a single dose of intravenous antibiotics and standard manufacturer technique yielded a low complication rate with high acute procedural success. Use of this implantation strategy may improve EP lab workflow while providing a safe and effective technique for device placement.

Inpatient hospitalization of oncology patients: are we missing an opportunity for end-of-life care?

INTRODUCTION: Despite advances in the care of patients with cancer over the last 10 years, cancer remains the second leading cause of death in the United States. Many patients receive aggressive, in-hospital end-of-life care at high cost. There are few data on outcomes after unplanned hospitalization of patients with metastatic cancer. METHODS: In 2000 and 2010, data were collected on admissions, interventions, and survival for patients admitted to an academic inpatient medical oncology service. RESULTS: The 2000 survey included 191 admissions of 151 unique patients. The 2010 survey assessed 149 admissions of 119 patients. Lung, GI, and breast cancers were the most common cancer diagnoses. In the 2010 assessment, pain was the most common chief complaint, accounting for 28%. Although symptoms were the dominant reason for admission in 2010, procedures and imaging were common in both surveys. The median survival of patients after discharge was 4.7 months in 2000 and 3.4 months in 2010. Despite poor survival in this patient population, hospice was recommended in only 23% and 24% of patients in 2000 and 2010, respectively. Seventy percent of patients were discharged home without additional services. CONCLUSION: On the basis of our data, an unscheduled hospitalization for a patient with advanced cancer strongly predicts a median survival of fewer than 6 months. We believe that hospital admission represents an opportunity to commence and/or consolidate appropriate palliative care services and end-of-life care.

Is discharge knee range of motion a useful and relevant clinical indicator after total knee replacement? Part 1.

OBJECTIVES: Knee range of motion (ROM) at the point of discharge from acute care is used as a clinical indicator to benchmark performance between hospital services after total knee replacement (TKR). The utility of the current benchmark, including whether discharge ROM varies between hospitals, is unknown. This study aimed to determine whether the benchmark [≥80 degrees flexion and ≤5 degrees fixed flexion (extension)] is realistic and whether the service provider is a predictor of knee ROM. METHODS: A prospective, observational cohort study was conducted involving 176 TKR patients from four hospitals. Knee ROM was photographically assessed preoperatively and at discharge. 'Hospital', typical patient demographic data and preoperative ROM were identified a priori as potential predictors of knee ROM. RESULTS: Overall, 2% [95% CI (confidence interval) 1-6] of patients attained the ROM benchmark. Individual hospital attainment of the benchmark ranged 0-7% with a significant difference (P = 0.047) evident between the best performer and the remaining hospitals. The overall rates of attainment of the individual flexion (25%, 95% CI 19-32) and extension (15%, 95% CI 10-21) components were similarly low, although the scatter between hospitals was large [flexion (2-47%); extension (8-44%)]. Preoperative flexion and hospital were significant (P = 0.002) predictors of discharge flexion, explaining 21% of the variance. Similarly, hospital and preoperative extension together with gender were significant (P < 0.001) predictors of discharge extension, explaining 26% of the variance. CONCLUSIONS: A small minority of patients attained the knee ROM benchmark, indicating the existing standard is unrealistic. Nevertheless, that 'hospital' is an important predictor confirms the potential of ROM for benchmarking purposes. Differences in physiotherapy practices may contribute to inter-hospital variation in discharge knee ROM together with other undefined factors. The causal relationships explaining the variation and the relationship between discharge ROM and longer-term outcome are avenues for future exploration which will help define the clinical relevance of the indicator.

Is discharge knee range of motion a useful and relevant clinical indicator after total knee replacement? Part 2.

OBJECTIVE: Knee range of motion (ROM) at discharge from acute care is used as a clinical indicator following total knee replacement (TKR) surgery. This study aimed to assess the clinical relevance of this indicator by determining whether discharge knee ROM predicts longer-term knee ROM and patient-reported knee pain and function. METHODS: A total of 176 TKR recipients were prospectively followed after discharge from acute care. Outcomes assessed included knee ROM and Oxford knee score post rehabilitation and 1 year post surgery. Discharge ROM and other patient factors were identified a priori as potential predictors in multiple linear regression modelling. RESULTS: A total of 133 (76%) and 141 (80%) patients were available for follow-up post rehabilitation [mean postoperative week 8.1 (SD 2.7)] and at 1 year [mean postoperative month 12.1 (SD 1.4)], respectively. Greater discharge knee flexion was a significant (P < 0.001) predictor of greater post-rehabilitation flexion but not 1-year knee flexion (P < 0.083). Better discharge knee extension was a significant predictor of better post-rehabilitation (P = 0.001) and 1-year knee extension (P = 0.013). Preoperative Oxford score and post-rehabilitation knee flexion independently predicted post-rehabilitation Oxford score, and gender predicted 1-year Oxford score. Discharge ROM did not significantly predict Oxford score in either model. CONCLUSION: The finding that early knee range predicts longer-term range provides clinical evidence favouring the relevance of discharge knee ROM as a clinical indicator. Although longer-term patient-reported knee pain and function were not directly associated with discharge knee ROM, they were associated with ROM when measured concurrently in the sub-acute phase. No causal effect has been demonstrated, but the findings suggest it may be important for physiotherapists to maximize range in the early and sub-acute periods.

Quantitative sizing of nano/microparticles with a tunable elastomeric pore sensor.

The use of a "size-tunable" polyurethane resistive pulse sensor for quantitative sizing of nano- and microparticles is presented. A linear relationship, as first suggested by Maxwell, between particle volume and change in electric resistance across the pore was observed. Particle sizes were quantified for a given size-tunable membrane, by first creating a linear calibration curve to a series of monodisperse carboxylated polystyrene particles of various diameters and then applying this curve to calculate the size of "unknown" nanoparticles. The diameters of a selection of synthetic and biological particles, being PMMA and nonfunctionalized polystyrene particles, along with biological nanoparticles (adenovirus) were calculated using this methodology. Calculated particle diameters and coefficients of variation were shown to be in good agreement with both transmission electron microscopy and dynamic light scattering results.

Haemotoxicity of busulphan, doxorubicin, cisplatin and cyclophosphamide in the female BALB/c mouse using a brief regimen of drug administration.

Many anticancer drugs are myelotoxic and cause bone marrow depression; however, generally, the marrow/blood returns to normal after treatment. Nevertheless, after the administration of some anti-neoplastic agents (e.g. busulphan, BU) under conditions as yet undefined, the marrow may begin a return towards normal, but normality may not be achieved, and late-stage/residual marrow injury may be evident. The present studies were conducted to develop a short-term mouse model (a 'screen') to identify late-stage/residual marrow injury using a brief regimen of drug administration. Female BALB/c mice were treated with BU, doxorubicin (DOX), cisplatin (CISPLAT) or cyclophosphamide (CYCLOPHOS) on days 1, 3 and 5. In 'preliminary studies', a maximum tolerated dose (MTD) for each drug was determined for use in 'main studies'. In main studies, mice were treated with vehicle (control), low and high (the MTD) dose levels of each agent. Necropsies were performed, and blood parameters and femoral/humeral nucleated marrow cell counts (FNCC/HNCC) were assessed on six occasions (from days 1 to 60/61 post-dosing). Late-stage/residual changes were apparent in BU-treated mice at day 61 post-dosing: RBC, Hb and haematocrit were reduced, mean cell volume/mean cell haemoglobin were increased and platelet and FNCC counts were decreased. Mice given DOX, CISPLAT and CYCLOPHOS, in general, showed no clear late-stage/residual effects (day 60/61). It was concluded that a brief regimen of drug administration, at an MTD, with assessment at day 60/61 post-dosing was a suitable short-term method/screen in the mouse for detecting late-stage/residual marrow injury for BU, a drug shown to exhibit these effects in man.

Modeling of the SPR resolution enhancement for conventional and nanoparticle inclusive sensors by using statistical hypothesis testing.

This paper describes a statistical approach that improves the detection accuracy in simulated experimental surface plasmon resonance (SPR) systems operated in a conventional angular readout scheme. Two SPR system have been investigated: a conventional one and a second one, containing absorbing metallic nanoparticles within the sensing layer. The modified Maxwell-Garnett model that optimally describes the experimental literature results was applied to modeling of the nanoparticle-inclusive sensor. Statistical hypothesis testing was then used to determine the limit of detection of the analyte and nanoparticles. Analyte concentrations as low as 1 pM, corresponding to the refractive index change of 4x10(-8) have been detected with optimized metal layers operated close to the nanoparticle absorption maximum. This is about one order of magnitude smaller than the values obtained in conventional SPR systems with nanoparticles and comparable to the phase-sensitive surface plasmon resonance detection.

Red blood cells do not attenuate the SPCE fluorescence in surface assays.

We describe the positive effect of surface plasmon-coupled fluorescence emission (SPCE) on the detection of a signal from a surface immunoassay in highly absorbing or/and scattering samples. A model immunoassay using fluorescently labeled anti-rabbit antibodies that bind to rabbit immunoglobulin on a silver surface was performed, and the signal was detected in the presence of various highly absorbing and/or scattering solutions or suspensions, such as hemoglobin solution, plastic beads, and red blood cells. The results showed that a highly absorbing solution consisting of small molecules (dye, hemoglobin) attenuates the SPCE signal approximately 2-3-fold. In contrast, suspensions with the same absorption containing large particles (large beads, red blood cell suspension) attenuate the SPCE signal only slightly, approximately 5-10%. Also, a suspension of large undyed, highly scattering beads does not reduce the SPCE signal. The effects on the immunoassay signal of the sample background absorption and scattering, the size of the background particles, and the geometry of the experimental set-up are discussed. We believe that SPCE is a promising technique in the development of biosensors utilized for surface-based assays, as well as any assays performed directly in highly absorbing and/or scattering solutions without washing or separation procedures. Figure Red blood cells (unlike hemoglobin) do not attenuate the SPCE fluorescence in surface assays.

Metal particle-enhanced fluorescent immunoassays on metal mirrors.

We present fluoroimmunoassays on plain metal-coated surfaces (metal mirrors) enhanced by metal nanoparticles (silver island films [SIFs]). Metal mirrors (aluminum, gold, or silver protected with a thin silica layer) were coated with SIFs, and an immunoassay (model assay for rabbit immunoglobulin G or myoglobin immunoassay) was performed on this surface using fluorescently labeled antibodies. Our results showed that SIFs alone (on glass surface not coated with metal) enhance the immunoassay signal approximately 3- to 10-fold. Using a metal mirror instead of glass as support for SIFs results in up to 50-fold signal enhancement.

Elevated factor VII as a risk factor for recurrent fetal loss. Relationship to factor VII gene polymorphisms.

Haemostatic abnormalities can be detected in a portion of the women who have recurrent fetal loss. We measured factor VII coagulant activity (FVII:C) in 65 women with 3 or more fetal losses (recurrent cases), 31 women with one 2nd or 3rd trimester loss (late loss cases), and 81 women with only live births (controls). FVII:C was greater than 2 standard deviations above the mean for controls in 9 recurrent cases (13.8%) and 2 controls (2.5%) for an odds ratio of 6.35 (95% CI 1.32-30.52, p=0.012). In recurrent cases, mean levels were significantly higher than controls for FVII:C (p=0.003), FVII antigen (p=0.024), and FVIIa (p=0.001). Late loss cases had an odds ratio of 4.23 (95% CI 0.67-26.67, p=0.098) with FVII:C, FVII antigen, and FVIIa not significantly different from the controls. DNA was examined for the presence of mutations or polymorphisms in the promoter region of the FVII gene, using denaturing HPLC. Abnormal patterns were confirmed with direct sequencing. A previously reported polymorphism, -402 G>A, was found to be present in 11/14 subjects with elevated FVII:C (79%) and 43% of those with normal levels (p=0.029). FVII:C, FVII antigen and FVIIa varied significantly with genotype; however, genotype frequencies did not differ between controls and either case group. No other promoter polymorphisms were identified. This is the first report of a significant elevation of FVII in a population with recurrent fetal loss. These data suggest the need for further investigation of this potential risk factor.

Community-based group exercise improves balance and reduces falls in at-risk older people: a randomised controlled trial.

BACKGROUND: recent studies have found that moderate intensity exercise is an effective intervention strategy for preventing falls in older people. However, research is required to determine whether supervised group exercise programmes, conducted in community settings with at-risk older people referred by their health care practitioner are also effective in improving physical functioning and preventing falls in this group. OBJECTIVES: to determine whether participation in a weekly group exercise programme with ancillary home exercises over one year improves balance, muscle strength, reaction time, physical functioning, health status and prevents falls in at-risk community-dwelling older people. METHODS: the sample comprised 163 people aged over 65 years identified as at risk of falling using a standardised assessment screen by their general practitioner or hospital-based physiotherapist, residing in South Western Sydney, Australia. Subjects were randomised into either an exercise intervention group or a control group. Physical performance and general health measures were assessed at baseline and repeated 6-months into the trial. Falls were measured over a 12-month follow-up period using monthly postal surveys. RESULTS: at baseline both groups were well matched in their physical performance, health and activity levels. The intervention subjects attended a median of 23 exercise classes over the year, and most undertook the home exercise sessions at least weekly. At retest, the exercise group performed significantly better than the controls in three of six balance measures; postural sway on the floor with eyes open and eyes closed and coordinated stability. The groups did not differ at retest in measures of strength, reaction time and walking speed or on Short-Form 36, Physical Activity Scale for the Elderly or fear of falling scales. Within the 12-month trial period, the rate of falls in the intervention group was 40% lower than that of the control group (IRR=0.60, 95% CI 0.36-0.99). CONCLUSIONS: these findings indicate that participation in a weekly group exercise programme with ancillary home exercises can improve balance and reduce the rate of falling in at-risk community dwelling older people.

A controlled trial of behavioural education to promote exercise among physiotherapy outpatients.

This pilot study aimed to test a behavioural intervention by outpatient physiotherapists to promote moderate physical activity among their clients for general health reasons. A quasi-experimental study was conducted with 204 subjects. The intervention consisted of behavioural counselling, information brochures and a physical activity diary. Self-reported physical activity was measured at baseline and at six weeks follow-up. At follow-up, the improvements in total minutes of physical activity using the preceding week as the recall period were substantial in both the control and intervention groups, but not significantly different. In the average weekly physical activity reported by subjects for the preceding six months, intervention subjects were significantly more likely to report a 60min/wk improvement than controls (adjusted odds ratio 2.97, 95% confidence interval [CI] 1.36-6.46). However, this was the only significant difference evident between the groups in the average weekly physical activity measures. Pre- and post-surveys completed by participating physiotherapists showed marked improvements in their knowledge and confidence regarding physical activity promotion. While the capacity of outpatient physiotherapists to educate clients about physical activity for non-therapeutic reasons can be improved, the most effective intervention model for clients in this setting remains unclear.