Efficacy of neuromuscular exercises to promote movement quality and reduce musculoskeletal injury during initial military training in Royal Navy recruits.

INTRODUCTION: Musculoskeletal injuries (MSKIs) are a significant problem in the Royal Navy, contributing to 48% of all medical discharges from service between 2019 and 2020. The objective of the study was to assess efficacy of implementing a neuromuscular training intervention to improve movement quality and reduce MSKIs in Royal Navy recruits undertaking initial military training. METHODS: Neuromuscular training (pre-activation exercises, focusing on hip control) was integrated into the warm-up exercise regimen preceding physical training during the 10-week initial naval training (recruits) programme (January-March 2020) at HMS Raleigh (intervention group; n=162). A control group comprised (n=90) of recruits entering training from January 2019, who completed the standard warm-up programme prior to physical training. Movement control of the intervention group (intervention) was assessed before and after the 10-week programme using the Hip and Lower-Limb Movement Screen (HLLMS). Injury incidence proportion for both groups was determined retrospectively by review of medical notes. RESULTS: The control group's MSKI incidence proportion was 31%, which was higher (p<0.05) than the 8% reported in the intervention group. The majority of MSKIs were of the lower limb, and were reported in weeks 1, 2 and 5 of the 10-week training programme. Movement control, as assessed by the HLLMS score, improved (pretraining (week 1) and post-training (week 10) HLLMS score (mean (SD) pre: 11.2 (5.6); post: 8.4 (3.9); t=5.829, p<0.001) following the neuromuscular training in the intervention group but was not assessed in the control group. CONCLUSION: A neuromuscular control intervention was successfully implemented during the initial military training in the Royal Navy. The cohort undertaking the intervention demonstrated lower injury incidence compared with an equivalent cohort of recruits who undertook standard training. Movement control improved following the intervention, indicating better movement quality. Continued use of the programme may reduce military training attrition in the Royal Navy.

Unrecognized volatile and semi-volatile organic compounds from brake wear.

Motor vehicles are among the major sources of pollutants and greenhouse gases in urban areas and a transition to "zero emission vehicles" is underway worldwide. However, emissions associated with brake and tire wear will remain. We show here that previously unrecognized volatile and semi-volatile organic compounds, which have a similarity to biomass burning emissions are emitted during braking. These include greenhouse gases or, these classified as Hazardous Air Pollutants, as well as nitrogen-containing organics, nitrogen oxides and ammonia. The distribution and reactivity of these gaseous emissions are such that they can react in air to form ozone and other secondary pollutants with adverse health and climate consequences. Some of the compounds may prove to be unique markers of brake emissions. At higher temperatures, nucleation and growth of nanoparticles is also observed. Regions with high traffic, which are often disadvantaged communities, as well as commuters can be impacted by these emissions even after combustion-powered vehicles are phased out.

A Comparison of Patient Characteristics and Outcomes Between Patients Receiving Flexor Digitorum Superficialis Slip Excision or Isolated A1 Pulley Release for Trigger Finger.

PURPOSE: Resection of the radial or ulnar slip of the flexor digitorum superficialis (FDS) tendon is a known treatment option for persistent trigger finger. Risk factors for undergoing FDS slip excision are unclear. We hypothesized that patients who underwent A1 pulley release with FDS slip excision secondary to persistent triggering would have a higher comorbidity burden compared to those receiving A1 pulley release alone. METHODS: We identified all adult patients who underwent A1 pulley release with FDS slip excision because of persistent triggering either intraoperatively or postoperatively from 2018 to 2023. We selected a 3:1 age- and sex-matched control group who underwent isolated A1 pulley release. Charts were retrospectively reviewed for demographics, selected comorbidities, trigger finger history, and postoperative course. We performed multivariable logistic regression to assess the probability of FDS slip excision after adjusting for several variables that were significant in bivariate comparisons. RESULTS: We identified 48 patients who underwent A1 pulley release with FDS slip excision and 144 controls. Our multivariable model showed that patients with additional trigger fingers and a preoperative proximal interphalangeal (PIP) joint contracture were significantly more likely to undergo FDS slip excision. CONCLUSIONS: Patients who underwent A1 pulley release with FDS slip excision were significantly more likely to have multiple trigger fingers or a preoperative PIP joint contracture. Clinicians should counsel patients with these risk factors regarding the potential for FDS slip excision in addition to A1 pulley release to alleviate triggering of the affected digit. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III.

Routine Postoperative Radiographs Do Not Affect Decision Making Following Carpometacarpal Arthroplasty.

Purpose: Arthritis of the first carpometacarpal (CMC) joint affects up to 15% of the population aged over 30 years and 40% of the population aged over 50 years. Arthroplasty of the first CMC joint is a widely accepted treatment option for these patients, with most patients doing well long term despite radiographic evidence of subsidence. Postoperative treatment protocols vary with no defined gold standard, and the need for routine postoperative radiographs has not been defined. The purpose of this study was to evaluate the use of routine postoperative radiographs following CMC arthroplasty. Methods: A retrospective review of patients who underwent CMC arthroplasty from 2014 to 2019 at our institution was performed. Patients receiving a concomitant trapezoid resection or metacarpophalangeal capsulodesis/arthrodesis were excluded. Demographic data, as well as the frequency and timing of postoperative radiographs, were collected. Radiographs were included if taken up to 6 months from the date of surgery. The primary outcome was a repeated operative intervention. Descriptive statistics were used for the analysis. Results: A total of 155 CMC joints from 129 patients were included in the study. Sixty-one (39.4%) patients had no postoperative radiographs, 76 (49.0%) patients had one postoperative radiographic series, 18 (11.6%) had two, 8 (5.2%) had three, and 1 (0.6%) patient had four postoperative series of radiographs. A radiographic series is defined as multiple views taken at a single time point. Four of 155 (2.6%) patients underwent additional operative intervention. There were no patients who underwent revision CMC arthroplasty. Two had wound infections that underwent irrigation and debridement. Two developed metacarpophalangeal arthritis and underwent arthrodesis. There were no cases where repeat operative intervention was driven by postoperative radiographic findings. Conclusions: Routine postoperative radiographs following CMC arthroplasty do not lead to changes in patient management, specifically further surgery. These data may support forgoing routine radiographs in the postoperative period following CMC arthroplasty. Type of study/level of evidence: Therapeutic IV.

Strategies for expanding patient and public involvement into under-served head and neck cancer communities.

PURPOSE OF REVIEW: In this review, we discuss two case studies in which we summarize the process of expanding patient and public involvement (PPI) representation specific to the head and neck cancer population, highlighting the challenges and successes within each project. The first case study reports on the expansion of HaNC PPI membership, a long-established PPI forum which supports Liverpool Head and Neck Centre research. The second case study describes the establishment of a novel palliative care network in head and neck cancer in the North of England, in which PPI was central to the project's success. RECENT FINDINGS: Whilst recognizing diversity is important, it is imperative to acknowledge the contribution of existing members. Engagement with clinicians to reduce issues of gatekeeping is essential. A central theme is that the development of sustainable relationships is critical. SUMMARY: The case studies highlight the challenge of identifying and accessing such a diverse population, particularly in the context of palliative care. Successful PPI is dependent on building and maintaining relationship with PPI members, ensuring flexibility in terms of timing, platforms and venues. Relationships formation should not be restricted to the academic-PPI representative dyad but should consider both clinical-academic and community partnerships to ensure those who are part of under-served communities are afforded the opportunities to become involved in research.

Following a Surgical Paradigm Shift Through the Adoption of Nerve Transfers Among Board-Eligible and Practicing Plastic Surgeons.

BACKGROUND: Nerve transfers represent a new paradigm in the treatment of nerve injuries. Their current level of adoption among surgeons is unknown. This study evaluates the incidence of nerve transfers on case logs of board-eligible plastic surgeons over the past 14 years and surveys practicing nerve surgeons regarding their use of this technique. METHODS: We queried the American Board of Plastic Surgery case log database for all nerve reconstruction Current Procedural Terminology codes from 2008 to 2021 and assessed trends and relationships between geographic region, examination year, and nerve transfer use. We surveyed nerve surgery professional societies to assess trends in practice, compared with a 2017 survey. RESULTS: A total of 1959 nerve reconstruction cases were logged by 738 candidates from 2008 to 2021. Twelve percent of cases included nerve transfers. The proportion of nerve transfer codes (Z = -11.57; P < .0001) and the proportion of candidates performing nerve transfers (Z = -9.21, P < .0001) increased over the study period. Nerve transfers were associated with geographic region (χ2 = 25.826, P = .0002), with most cases performed in the Midwest (26.4%). A higher proportion of practicing nerve surgeons reported performing nerve transfers in this survey than in our 2017 survey (χ2 = 16.7, P < .001). CONCLUSIONS: There has been an increase in nerve transfers logged in the past 14 years by board-eligible plastic surgeons, as well as increased use among currently practicing nerve surgeons. Although nerve transfer use is increasing among both plastic and orthopedic surgeons, a greater proportion of nerve reconstructions include nerve transfers in the plastic surgery cohort.

Adherence to swallowing recommendations during (chemo)radiotherapy in head and neck cancer survivors: a scoping review.

PURPOSE OF REVIEW: There is a paucity of knowledge regarding patient adherence to dysphagia recommendations. It is recognized that unique barriers and facilitators contribute to poor treatment adherence in head and neck cancer (HNC) survivors. This review aims to identify the key themes and knowledge gaps regarding adherence to swallowing recommendations in HNC survivors during (chemo)radiotherapy (C)RT. RECENT FINDINGS: Seven studies were identified. Six facilitators to adherence were extracted, namely pain relief, behavioural intervention, attendance at multidisciplinary clinic, individualised swallowing therapy, absence of prophylactic percutaneous endoscopic gastronomy (PEG) and positive social control from a spouse. Barriers to adherence included pain, depression and presence of prophylactic PEG. Adherence to swallowing recommendations positively impacted swallowing outcomes in one study. SUMMARY: Little is known about adherence to swallowing recommendations during (C)RT in HNC survivors. Capturing adherence is challenging. Several knowledge gaps were identified. Further research is needed to better understand the barriers and facilitators from the survivors' perspective. This will inform development of best practice regarding how swallowing recommendations are provided to promote adherence and improve outcomes.

Calling on Sponsorship: Analysis of Speaker Gender Representation at Hand Society Meetings.

BACKGROUND: The paucity of leadership diversity in surgical specialties is well documented. Unequal opportunities for participation at scientific meetings may impact future promotions within academic infrastructures. This study evaluated gender representation of surgeon speakers at hand surgery meetings. METHODS: Data were retrieved from the 2010 and 2020 meetings of the American Association for Hand Surgery (AAHS) and American Society for Surgery of the Hand (ASSH). Programs were evaluated for invited and peer-reviewed speakers excluding keynote speakers and poster presentations. Gender was determined from publicly available sources. Bibliometric data (Hirsch index) for invited speakers were analyzed. RESULTS: In 2010 at the AAHS ( n = 142) and ASSH meetings ( n = 180), female surgeons represented 4% of the invited speakers and in 2020 increased to 15% at AAHS ( n = 193) and 19% at ASSH ( n = 439). From 2010 to 2020, female surgeon invited speakers had a 3.75-fold increase at AAHS and 4.75-fold increase at ASSH. Representation of female surgeon peer-reviewed presenters at these meetings was similar (2010 AAHS, 26%; and 2010 ASSH, 22%; 2020 AAHS, 23%; 2020 ASSH, 22%). The academic rank of women speakers was significantly lower ( P < 0.001) than for male speakers. At the assistant professor level, the mean Hirsch index was significantly lower ( P < 0.05) for female invited speakers. CONCLUSIONS: Although there was a significant improvement in gender diversity in invited speakers at the 2020 meetings compared with 2010, female surgeons remain underrepresented. Gender diversity is lacking at national hand surgery meetings, and continued effort and sponsorship of speaker diversity is imperative to curate an inclusive hand society experience.

Decompression with Brachioradialis Tenotomy Improves Pain and Quality of Life in Patients with Radial Sensory Nerve Compression.

BACKGROUND: Decompression of the superficial sensory branch of the radial nerve (SBRN) with complete brachioradialis tenotomy may treat pain in both simple and complex cases of SBRN compression neuropathy. METHODS: A retrospective chart review was performed of consecutive patients undergoing this procedure between 2008 and 2020 including postoperative outcomes within 90 days. Data were collected and analyzed, including patient and injury demographics, pain descriptors, and patient-reported pain questionnaire, including reported pain severity and impact on quality of life using visual analogue scale (VAS) instruments. Within-group presurgical and postsurgical analyses and between-group statistical analyses were performed. RESULTS: Thirty-three of 58 patients met inclusion criteria. Median time from symptom onset to surgery was 300 days, and median postoperative follow-up time was 37 days. Twenty-five percent of patients ( n = 8) underwent isolated SBRN decompression. The remainder had concomitant decompression of another radial [ n = 16 (48%) or peripheral [ n = 12 (36%)] entrapment point. Ten of 33 patients (30%) had resolution of pain at final follow-up ( P = 0.004). Median change in worst pain over the previous week was -4 ( P < 0.001), and average pain over the last month was -2.75 ( P < 0.001) on the VAS. The impact of pain on quality of life showed a median change of -3 ( P < 0.001) on the VAS. CONCLUSION: Decompression of the sensory branch of the radial nerve including a complete brachioradialis tenotomy improves pain and quality-of-life VAS scores in patients with both simple compression neuropathy syndrome and complex nerve compression syndrome. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Dysphagia Advances in Head and Neck Cancer.

Purpose of Review: This review summarises the current literature regarding head and neck cancer-associated dysphagia. Up-to-date evidence for dysphagia outcome measurement for this population is provided, in addition to recent innovations that aim to prevent, reduce or remediate the common and debilitating side effects of treatment. Recent Findings: Both patient-reported outcomes and clinical measures are necessary to capture the multi-dimensional nature of swallowing. A minimally important difference in scores has been calculated for some of these measures, to aid interpretation and powering of clinical trials. The number of dysphagia-related trials has increased, predominantly investigating optimal treatment for oropharyngeal HPV-positive disease, and speech and language pathology interventions using an impairment-based approach. Summary: Although substantial progress has been made, further work is necessary to establish a consensus over outcome measures. Modifying treatments may improve outcomes. Several trials are underway to establish the effectiveness of speech and language pathology dysphagia interventions.

What is Operative? Conceptualizing Neuralgia: Neuroma, Compression Neuropathy, Painful Hyperalgesia, and Phantom Nerve Pain.

Neuralgia, or nerve pain, is a common presenting complaint for the hand surgeon. When the nerve at play is easily localized, and the cause of the pain is clear (eg, carpal tunnel syndrome), the patient may be easily treated with excellent results. However, in more complex cases, the underlying pathophysiology and cause of neuralgia can be more difficult to interpret; if incorrectly managed, this leads to frustration for both the patient and surgeon. Here we offer a way to conceptualize neuralgia into 4 categories-compression neuropathy, neuroma, painful hyperalgesia, and phantom nerve pain-and offer an illustrative clinical vignette and strategies for optimal management of each. Further, we delineate the reasons why compression neuropathy and neuroma are amenable to surgery, while painful hyperalgesia and phantom nerve pain are not.

Use of virtual meeting and survey technology to assess Covid-19-related mental well-being of healthcare workers.

Background and aims: Healthcare workers (HCWs) throughout the world have been exposed to economic and existential stress during the Covid-19 pandemic. The American Medical Association (AMA) has documented that increased healthcare burden correlates with increased stress, burnout, and psychological burden in HCWs. However, limits on personnel, time, and in person interactions make it challenging to assess mental health outcomes during a pandemic. This pilot study used virtual technology to efficiently assess these outcomes. Setting: Data were collected based on voluntary participation in the Coping with Covid-19 for Caregivers Survey created by AMA. The survey was sent out to approximately 300 participants who included local physicians, medical residents, medical students, and allied health professionals and students who attended a virtual Mental Health Summit. Methods: The AMA developed survey included questions about demographics, overall stress, fear of infection and transmission of the virus, perceived anxiety or depression due to Covid-19, work overload, childcare issues, and sense of meaning and purpose. The AMA allows for up to five additional questions to be added to their survey, therefore five questions regarding support service utilization, perseverance, and resilience during the Covid-19 pandemic, and two items to further understand students' areas of medical interest. The survey was administered using an online platform through the AMA. The data were analyzed using descriptive statistics. Results: There were 81 survey respondents. Based on the results of the survey, "high stress" was found in 52 (64%) participants. 66 (81%) were afraid (moderately or to a great extent) of exposure or transmission, 61 (75%) described high levels of anxiety or depression, and 67 (84%) noted work overload. Despite this increase in stress, most respondents (77%) said they were not likely to reduce their devoted hours to clinical care or research in the next 12 months, and 81% answered that they would not leave their practice or research within two years. Conclusion: Covid-19 has negatively affected the well-being of HCWs. This is a similar trend seen during other times of healthcare strain. Mental health support, work modulation, and various provisions should be explored as means to reduce Covid-19-related negative impacts. The use of an online summit and online data collection methods were appropriate for collecting data on the impact of the Covid-19 pandemic on mental health. This pilot study supports the larger scale implementation of this technology for health informatics research.

The Creation of a Novel Undergraduate Nursing Employee/Student Hybrid Role in the COVID-19 Response: An Alberta Experience.

The COVID-19 pandemic impacted nursing education and health care systems alike. Increases in staff absenteeism along with increased hospitalizations have strained health systems across the globe. Postsecondary institutions (PSIs) were required to remove students from clinical placements, thus delaying nursing students' ability to complete their programs, and in turn, contributing to the nursing workforce challenges. Health care organizations and PSIs had to collaborate innovatively to support the health care response to the pandemic while continuing to educate and graduate students to expand the nursing workforce. In Alberta, the collaboration between the health system and PSIs led to the creation of an undergraduate nursing employee/student hybrid (UNE/Hybrid) role. This role was not only a response to the nursing workforce challenges created by the pandemic, but it provided nursing students with positive learning clinical placements ensuring that they completed their program in a timely manner. This role was designed to assist with the fourth wave of the pandemic (omicron variant), which was expected to be the most severe wave in terms of hospitalizations and increased staff absences. The UNE/Hybrid role allowed nursing students to complete the required learning for their final preceptorships and/or complete leadership placements in a paid role while being integrated into the unit culture and becoming part of the team. The initiative's results, including its successes, challenges, and lessons, are discussed.

Beyond the Cubital Tunnel: Use of Adjunctive Procedures in the Management of Cubital Tunnel Syndrome.

BACKGROUND: Our management of cubital tunnel syndrome has expanded to involve multiple adjunctive procedures, including supercharged end-to-side anterior interosseous to ulnar nerve transfer, cross-palm nerve grafts from the median to ulnar nerve, and profundus tenodesis. We also perform intraoperative brief electrical stimulation in patients with severe disease. The aims of this study were to evaluate the impact of adjunctive procedures and electrical stimulation on patient outcomes. METHODS: We performed a retrospective review of 136 patients with cubital tunnel syndrome who underwent operative management from 2013 to 2018. A total of 38 patients underwent adjunctive procedure(s), and 33 received electrical stimulation. A historical cohort of patients who underwent cubital tunnel surgery from 2009 to 2011 (n = 87) was used to evaluate the impact of adjunctive procedures. Study outcomes were postoperative improvements in Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire scores, pinch strength, and patient-reported pain and quality of life. RESULTS: In propensity score-matched samples, patients who underwent adjunctive procedures had an 11.3-point greater improvement in DASH scores than their matched controls (P = .0342). In addition, patients who received electrical stimulation had significantly improved DASH scores relative to baseline (11.7-point improvement, P < .0001), whereas their control group did not. However, when compared between treatment arms, there were no significant differences for any study outcome. CONCLUSIONS: Patients who underwent adjunctive procedures experienced greater improvement in postoperative DASH scores than their matched pairs. Additional studies are needed to evaluate the effects of brief electrical stimulation in compression neuropathy.

Symptom burden, management and treatment goals of people with MS spasticity: Results from SEEN-MSS, a large-scale, self-reported survey.

BACKGROUND: Spasticity occurs frequently in people with multiple sclerosis (PwMS) and may affect non-physical aspects of life. However, there is a paucity of data assessing the full impact of spasticity in PwMS. OBJECTIVE: This survey of PwMS and spasticity (PwMSS) was undertaken to understand the impact of spasticity in physical, functional, emotional, and social domains. METHODS: SEEN-MSS (Symptoms and Emotions Exploration Needed in Multiple Sclerosis Spasticity), an online survey, was developed in collaboration with three US-based MS organizations (conducted February-April 2021). RESULTS: Survey was completed by 1,177 PwMSS, 78% female, mean age 56.8yrs, 16.8yrs from MS diagnosis, 11.5yrs with spasticity. Considering day-to-day goals of treatment, respondents reported that managing symptoms(46%) was nearly as important as slowing disease progression(54%). Most reported spasticity was a constant reminder of their MS. Participants reported that spasticity limited daily activities (92%), caused pain (92%), impaired sleep (89%) and negatively impacted emotional well-being (87%). Spasticity fostered a sense of dependence (61%), isolation (40%), decline in self-confidence (75%), self-image (70%), and social connection (62%). CONCLUSIONS: Spasticity has wide-reaching negative impacts on multiple aspects of life, causing substantial burden for PwMSS. Results emphasize the need to fully understand the burden of spasticity and addressing individual needs of PwMSS.

Posterior Interosseous Nerve Compression in the Forearm, AKA Radial Tunnel Syndrome: A Clinical Diagnosis.

BACKGROUND: Posterior interosseous nerve (PIN) compression in the forearm without motor paralysis is a challenging clinical diagnosis. This retrospective study evaluated the clinical assessment, diagnostic studies, and outcomes following surgical decompression of the PIN in the forearm. METHODS: This study reviewed 182 patients' medical charts following PIN decompression between 2000 and 2020 by a single surgeon. After exclusion of combined nerve entrapments, polyneuropathy, motor palsy, or lateral epicondylitis, the study included 14 patients. Data collected included: clinical presentation and pain drawings, provocative testing, functional outcomes, and Disabilities of the Arm, Shoulder, and Hand (DASH) scores. RESULTS: There were 15 PIN decompressions (14 patients, mean follow-up = 11.9 months). Clinical presentation included pain (n = 14) (proximal dorsal forearm, n = 14; distal forearm over radial sensory nerve, n = 3) and positive clinical tests (sensory collapse test over the radial tunnel, n = 8; pain with forearm pronation and compression over the radial tunnel, n = 10; Tinel sign, n = 5). Postoperatively, there were significant improvements in Visual Analog Scale pain scores (6.7 to 3.3, P = .0006), quality-of-life scores (74.7 to 32.7, P = .0001), and DASH scores (46.3 to 33.6, P = .02). CONCLUSIONS: The PIN compression in the forearm without motor paralysis is a clinical diagnosis supported by pain drawings, pain quality, and provocative tests. Patients with persistent, therapy-resistant dorsal forearm pain should be evaluated for PIN compression. Surgical decompression provides statistically significant quantifiable improvement in pain and quality of life.

Associations among depression, demographic variables, and language impairments in chronic post-stroke aphasia.

INTRODUCTION: Depression may influence treatment participation and outcomes of people with post-stroke aphasia, yet its prevalence and associated characteristics in aphasia are poorly understood. Using retrospective data from an overarching experimental study, we examined depressive symptoms and their relationship to demographic and language characteristics in people with chronic aphasia. As a secondary objective, we compared prevalence of depressive symptoms among the overarching study's included and excluded participants. METHODS: We examined retrospective data from 121 individuals with chronic aphasia including depression scale scores, demographic information (sex, age, time post onset of stroke, education, race/ethnicity, and Veteran status), and scores on assessments of general and modality-specific language impairments. RESULTS: Approximately 50% of participants reported symptoms indicative of depressive disorders: 23% indicative of major depression and 27% indicative of mild depression. Sex (males) and comparatively younger age emerged as statistically significant variables associated with depressive symptoms; naming ability was minimally associated with depressive symptoms. Time post onset of stroke, education level, race/ethnicity, Veteran status, and aphasia severity were not significantly associated with depressive symptoms. Depression-scale scores were significantly higher for individuals excluded from the overarching study compared to those who were included. CONCLUSIONS: The rate of depressive disorders in this sample was higher than rates of depression reported in the general stroke literature. Participant sex, age, and naming ability emerged as factors associated with depressive symptoms, though these links appear complex, especially given variable reports from prior research. Importantly, depressive symptoms do not appear to diminish over time for individuals with chronic aphasia. Given these results and the relatively limited documentation of depression in aphasia literature, depression remains a pressing concern for aphasia research and routine clinical care.

Leveraging a Previously Published Population Pharmacokinetic Model to Predict Rivaroxaban Exposure in Real-World Patients.

Population pharmacokinetic (PK)/pharmacodynamic models are commonly used to inform drug dosing; however, often real-world patients are not well represented in the clinical trial population. We sought to determine how well dosing recommended in the rivaroxaban drug label results in exposure for real-world patients within a reference area under the concentration-time curve (AUC) range. To accomplish this, we assessed the utility of a prior published rivaroxaban population PK model to predict exposure in real-world patients. We used the model to predict rivaroxaban exposure for 230 real-world patients using 3 methods: (1) using patient phenotype information only, (2) using individual post hoc estimates of clearance from the prior model based on single PK samples of rivaroxaban collected at steady state without refitting of the prior model, and (3) using individual post hoc estimates of clearance from the prior model based on PK samples of rivaroxaban collected at steady state after refitting of the prior model. We compared the results across 3 software packages (NONMEM, Phoenix NLME, and Monolix). We found that while the average patient-assigned dosing per the drug label will likely result in the AUC falling within the reference range, AUC for most individual patients will be outside the reference range. When comparing post hoc estimates, the average pairwise percentage differences were all <10% when comparing the software packages, but individual pairwise estimates varied as much as 50%. This study demonstrates the use of a prior published rivaroxaban population PK model to predict exposure in real-world patients.