Appetite stimulation with cannabis-based medicine and methods for assessment of glomerular filtration in older patients with medical illness: A study protocol.

BACKGROUND AND AIM: Malnutrition in older patients is linked to poor appetite. Cannabis-based medicine may have orexigenic properties in older patients, but this has to our knowledge never been investigated. In older patients, uncertainty applies to the accuracy of estimated glomerular filtration rate (eGFR) based on creatinine, which is crucial for medication prescribing. In older patients with poor appetite, the study aims (1) to assess the efficacy of Sativex® (8.1-mg delta-9-tetrahydrocannabinol [THC] and 7.5-mg cannabidiol [CBD]) to stimulate appetite and (2) to compare the performance of various GFR-estimates and measured-GFR (mGFR) for determining gentamicin clearance utilizing population pharmacokinetic (popPK) modelling methods. METHODS AND OBJECTIVES: This study is composed of two substudies. Substudy 1 is an investigator-initiated single-center, double-blinded, randomized, placebo-controlled, superiority, cross-over study. Substudy 1 will recruit 17 older patients with poor appetite, who will also be invited to substudy 2. Substudy 2 is a single-dose pharmacokinetics study and will recruit 55 patients. Participants will receive Sativex® and placebo in substudy 1 and gentamicin with simultaneous measurements of GFR in substudy 2. The primary endpoints are as follows: Substudy 1-the difference in energy intake between Sativex® and placebo conditions; substudy 2- the accuracy of different eGFR equations compared to mGFR. The secondary endpoints include safety parameters, changes in the appetite hormones, total ghrelin and GLP-1 and subjective appetite sensations, and the creation of popPK models of THC, CBD, and gentamicin.

Knee-extensor strength, symptoms, and need for surgery after two, four, or six exercise sessions/week using a home-based one-exercise program: a randomized dose-response trial of knee-extensor resistance exercise in patients eligible for knee replacement (the QUADX-1 trial).

OBJECTIVE: To investigate firstly the efficacy of three different dosages of one home-based, knee-extensor resistance exercise on knee-extensor strength in patients eligible for knee replacement, and secondly, the influence of exercise on symptoms, physical function and decision on surgery. METHOD: One-hundred and forty patients eligible for knee replacement were randomized to three groups: 2, 4 or 6 home-based knee-extensor resistance exercise-sessions per week (group 2, 4 and 6 respectively) for 12 weeks. PRIMARY OUTCOME: isometric knee-extensor strength. SECONDARY OUTCOMES: Oxford Knee Score, Knee injury and Osteoarthritis Outcome Score, average knee pain last week (0-10 numeric rating scale), 6-min walk test, stair climbing test, exercise adherence and "need for surgery". RESULTS: Primary analysis: Intention-to-treat analysis of 140 patients did not find statistically significant differences between the groups from baseline to after 12 weeks of exercise in isometric knee-extensor strength: Group 2 vs 4 (0.003 Nm/kg (0.2%) [95% CI -0.15 to 0.15], P = 0.965) and group 4 vs 6 (-0.04 Nm/kg (-2.7%) [95% CI -0.15 to 0.12], P = 0.628). Secondary analysis: Intention-to-treat analyses showed statistically significant differences between the two and six sessions/week groups in favor of the two sessions/week group for Oxford Knee Score: 4.8 OKS points (15.2%) [1.3 to 8.3], P = 0.008) and avg. knee pain last week (NRS 0-10): -1.3 NRS points (-19.5%) [-2.3 to -0.2], P = 0.018. After the 12-week exercise intervention, data were available for 117 patients (N = 39/group): 38 (32.5%) patients wanted surgery and 79 (67.5%) postponed surgery. This was independent of exercise dosage. CONCLUSION: In patients eligible for knee-replacement we found no between-group differences in isometric knee extensor strength after 2, 4 and 6 knee-extensor resistance exercise sessions per week. We saw no indication of an exercise dose-response relationship for isometric knee-extensor strength and only clinically irrelevant within group changes. For some secondary outcome (e.g., KOOS subscales) we found clinically relevant within group changes, which could help explain why only one in three patients decided to have surgery after the simple home-based exercise intervention. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02931058. Preprint: https://doi.org/10.1101/2021.04.07.21254965.

The relationship between prescribed pre-operative knee-extensor exercise dosage and effect on knee-extensor strength prior to and following total knee arthroplasty: a systematic review and meta-regression analysis of randomized controlled trials.

OBJECTIVE: The aim of this systematic review was to evaluate the relationship between prescribed knee-extensor strength exercise dosage in pre-operative exercise intervention and the effect on knee-extensor muscle strength prior to and following TKA. Additional meta-analyses report the effect of pre-habilitation on outcomes prior to and following TKA. DESIGN: A systematic literature search was performed including RCT's evaluating the effect of pre-operative exercise prior to and following TKA. Meta-regression analysis was performed to evaluate the dose-response relationship between prescribed exercise dose and the pooled effect, measured as standardized mean difference (SMD). The prescribed exercise dose was quantified using a formula accounting for as many exercise descriptors as possible. Risk of bias in the included trials was assessed using the Cochrane Risk of Bias Tool. RESULTS: Twelve trials with 616 patients were included. Meta-regression analysis showed no relationship between prescribed pre-operative knee-extensor exercise dosage and change in knee-extensor strength neither prior to (slope 0.0005 [95%CI -0.007 to 0.008]) or 3 months following TKA (slope 0.0014 [95%CI -0.006 to 0.009]). Prior to TKA, a moderate effect favoring pre-operative exercise for increase in knee-extensor strength was found (SMD 0.50 [95%CI 0.12 to 0.88]), but not at 3 months following TKA (SMD -0.01 [95%CI -0.45 to 0.43]). Risk of bias was generally assessed as unclear. CONCLUSION: Meta-regression analysis of existing trials suggests no relationship between the prescribed pre-operative knee-extensor exercise dosage and the change in knee-extensor strength observed prior to and following TKA. Pre-operative exercise including knee-extensor muscle strength exercise increased knee-extensor strength moderately prior to but not 3 months following TKA. PROTOCOL REGISTRATION: PROSPERO ID (CRD42018076308) (http://www.crd.york.ac.uk/PROSPERO/).

A pilot study to determine the effect of radiographer training on radiostereometric analysis imaging technique.

INTRODUCTION: Producing x-ray images for radiostereometric analysis (RSA) is a demanding technique. Suboptimal examinations result in a high percentage of exposure repetition. The aim of this pilot study was to use an experiential training approach to sharpen the skills of radiographers in acquiring images of an optimal quality. METHODS: A controlled trial using action research strategy was used. The study entailed a two phased approach. Radiographers were purposefully recruited and trained to perform the required investigations. Each phase included 12 examinations of a total knee arthroplasty phantom followed by 10 patient examinations. The quality of all x-ray images performed during the two phases was characterized by measuring the number of visible beads, the center position of the prosthesis (CP) compared to the center of calibration field (CCF). The number of re-exposures used to obtain a usable image during patient examinations was also recorded. RESULTS: The radiographers undergoing the training resulted in a significant improvement in the quality of images produced and visualization of the beads. That is, the ability to move the CP on average 36.1 mm closer to the CCF (p < 0.001), the number of visible beads increased by 3.1 (p < 0.001) and radiographers needed 2.1-2.9 exposures less to obtain RSA images of sufficient qualities during patient examinations in phase 2 (p < 0.001). CONCLUSION: This study illustrates the value of experiential method of teaching and learning with minimal compromise on patient safety but a significant contribution in terms of establishing quality of RSA images.

The effect of personalized versus standard patient protocols for radiostereometric analysis (RSA).

INTRODUCTION: Increasing pressure in the clinic requires a more standardized approach to radiostereometric analysis (RSA) imaging. The aim of this study was to investigate whether implementation of personalized RSA patient protocols could increase image quality and decrease examination time and the number of exposure repetitions. METHODS: Forty patients undergoing primary total hip arthroplasty were equally randomized to either a case or a control group. Radiographers in the case group were assisted by personalized patient protocols containing information about each patient's post-operative RSA imaging. Radiographers in the control group used a standard RSA protocol. RESULTS: At three months, radiographers in the case group significantly reduced (p < 0.001) the number of exposures by 1.6, examination time with 19.2 min, and distance between centrum of prosthesis and centrum of calibration field with 34.1 mm when compared to post-operative (baseline) results. At twelve months, the case group significantly reduced (p < 0.001) number of exposures by two, examination time with 22.5 min, and centrum of prosthesis to centrum of calibration field distance with 43.1 mm when compared to baseline results. No significant improvements were found in the control group at any time point. CONCLUSION: There is strong evidence that personalized RSA patient protocols have a positive effect on image quality and radiation dose savings. Implementation of personal patient protocols as a RSA standard will contribute to the reduction of examination time, thus ensuring a cost benefit for department and patient safety.

Design and evaluation of learning strategies for a group of radiographers in radiostereometric analysis (RSA).

INTRODUCTION: The purpose of this study was to design and evaluate a radiostereometric analysis (RSA) program aimed at radiographers in order to increase their cognitive and practical skills, thereby increasing image quality and minimizing exposure repetition. METHODS AND MATERIALS: Twenty radiographers were randomized into two identically sized study groups. Training consisted of a theoretical and practical workshop using a phantom. Tests were performed to compare the effect of training to nontraining, and the effect of time duration on the maintenance of RSA skills. The effect of training was measured by a written test and three defined parameters influencing image quality. RESULTS: Group A reduced significantly (p < 0.001) by 31.3 mm (21-31%) the distance between the centrum of the prosthesis (CP) and the centrum of the calibration field (CCF) and increased the number of beads (NB) visible by 3.6 (out of 18). A further significant reduction of 5.1 mm (p = 0.023), 1.0 bead more (p < 0.001) and a 2.1 (p = 0.022) point better rotation of the prosthesis (RP) was registered two months later. Group B was tested twice without training and no significant improvement was registered. One month after training group B had experienced overall significant improvement on a par with group A. CONCLUSION: It is realistic to implement an RSA X-ray training program where radiographers significantly improve their theoretical and practical skills in centering the CP closer to the CCF, NB and RP. A duration of up to two months after training does not influence the quality of participants' performance.

Risk factors for post-operative periprosthetic fractures following primary total hip arthroplasty with a proximally coated double-tapered cementless femoral component.

AIMS: The aim of this study was to identify patient- and surgery-related risk factors for sustaining an early periprosthetic fracture following primary total hip arthroplasty (THA) performed using a double-tapered cementless femoral component (Bi-Metric femoral stem; Biomet Inc., Warsaw, Indiana). PATIENTS AND METHODS: A total of 1598 consecutive hips, in 1441 patients receiving primary THA between January 2010 and June 2015, were retrospectively identified. Level of pre-operative osteoarthritis, femoral Dorr type and cortical index were recorded. Varus/valgus placement of the stem and canal fill ratio were recorded post-operatively. Periprosthetic fractures were identified and classified according to the Vancouver classification. Regression analysis was performed to identify risk factors for early periprosthetic fracture. RESULTS: The mean follow-up was 713 days (1 to 2058). A total of 48 periprosthetic fractures (3.0%) were identified during the follow-up and median time until fracture was 16 days, (interquartile range 10 to 31.5). Patients with femoral Dorr type C had a 5.2 times increased risk of post-operative periprosthetic fracture compared with type B, while female patients had a near significant two times increased risk over time for post-operative fracture. CONCLUSION: Dorr type C is an independent risk factor for early periprosthetic fracture, following THA using a double tapered cementless stem such as the Bi-Metric. Surgeons should take bone morphology into consideration when planning for primary THA and consider using cemented femoral components in female patients with poor bone quality. Cite this article: Bone Joint J 2017;99-B:451-7.

Tranexamic acid reduces blood loss in patients with extracapsular fractures of the hip: results of a randomised controlled trial.

AIMS: We chose unstable extra-capsular hip fractures as our study group because these types of fractures suffer the largest blood loss. We hypothesised that tranexamic acid (TXA) would reduce total blood loss (TBL) in extra-capsular fractures of the hip. PATIENTS AND METHODS: A single-centre placebo-controlled double-blinded randomised clinical trial was performed to test the hypothesis on patients undergoing surgery for extra-capsular hip fractures. For reasons outside the control of the investigators, the trial was stopped before reaching the 120 included patients as planned in the protocol. RESULTS: In all 72 patients (51 women, 21 men; 33 patients in the TXA group, 39 in the placebo group) were included in the final analysis, with a significant mean reduction of 570.8 ml (p = 0.029) in TBL from 2100.4 ml (standard deviation (sd) = 1152.6) in the placebo group to 1529.6 ml (sd = 1012.7) in the TXA group. The 90-day mortality was 27.2% (n = 9) in the TXA group and 10.2% (n = 4) in the placebo group (p = 0.07). We were not able to ascertain a reliable cause of death in these patients. DISCUSSION: TXA significantly reduced TBL in extra-capsular hip fractures, but concerns regarding its safety in this patient group must be investigated further before the use of TXA can be recommended. TAKE HOME MESSAGE: We present a randomised clinical trial that is unique in the literature. We evaluate the effect of TXA in very homogenous population - extra-capsular fractures operated with short intramedullary nails. Cite this article: Bone Joint J 2016;98-B:747-53.