Clinical Implications of Co-administering Apixaban with Key Interacting Medications.

With many available data sources, clinicians need to consider the benefit-risk profile of individual anticoagulants when balancing the need for anticoagulation, including evaluating the risks in patients with comorbidities and potential drug-drug interactions. This narrative review presents clinical data across multiple phases of drug development for the use of apixaban, a selective factor Xa inhibitor, when taken concomitantly with other agents, and evaluates the benefit-risk profile of apixaban with these interacting medications. Key subgroup analyses from the phase 3 ARISTOTLE trial (NCT00412984) are presented using data from patients who received either concomitant inhibitors or inducers of cytochrome P450 3A4 and/or P­glycoprotein. We also review the available evidence for the use of apixaban in patients with cancer-associated thromboembolism, as well as the use of apixaban in patients with COVID-19.

Discrepancies in recommendations for return to regular activities after cervical spine surgery: A survey study.

Background: The recommended timing for returning to common activities after cervical spine surgery varies widely among physicians based on training background and personal opinion, without clear guidelines or consensus. The purpose of this study was to analyze spine surgeons' responses about the recommended timing for returning to common activities after different cervical spine procedures. Methods: This was a survey study including 91 spine surgeons. The participants were asked to complete an anonymous online survey. Questions regarding their recommended time for returning to regular activities (showering, driving, biking, running, swimming, sedentary work, and nonsedentary work) after anterior cervical decompression and fusion (ACDF), cervical disc replacement (CDR), posterior cervical decompression and fusion (PCDF), and laminoplasty were included. Comparisons of recommended times for return to activities after each surgical procedure were made based on surgeons' years in practice. Results: For ACDF and PCDF, there were no statistically significant differences in recommended times for return to any activity when stratified by years in practice. When considering CDR, return to non-sedentary work differed between surgeons in practice for 10 to 15 years, who recommended return at 3 months, and all other groups of surgeons, who recommended 6 weeks. Laminoplasty surgery yielded the most variability in activity recommendations, with earlier recommended return (6 weeks) to biking, non-sedentary work, and sedentary work in the most experienced surgeon group (>15 years in practice) than in all other surgeon experience groups (3 months). Conclusions: We observed significant variability in surgeon recommendations for return to regular activities after cervical spine surgery.

Deep-learning reconstructed lumbar spine 3D MRI for surgical planning: pedicle screw placement and geometric measurements compared to CT.

PURPOSE: To test equivalency of deep-learning 3D lumbar spine MRI with "CT-like" contrast to CT for virtual pedicle screw planning and geometric measurements in robotic-navigated spinal surgery. METHODS: Between December 2021 and June 2022, 16 patients referred for spinal fusion and decompression surgery with pre-operative CT and 3D MRI were retrospectively assessed. Pedicle screws were virtually placed on lumbar (L1-L5) and sacral (S1) vertebrae by three spine surgeons, and metrics (lateral deviation, axial/sagittal angles) were collected. Vertebral body length/width (VL/VW) and pedicle height/width (PH/PW) were measured at L1-L5 by three radiologists. Analysis included equivalency testing using the 95% confidence interval (CI), a margin of ± 1 mm (± 2.08° for angles), and intra-class correlation coefficients (ICCs). RESULTS: Across all vertebral levels, both combined and separately, equivalency between CT and MRI was proven for all pedicle screw metrics and geometric measurements, except for VL at L1 (mean difference: - 0.64 mm; [95%CI - 1.05, - 0.24]), L2 (- 0.65 mm; [95%CI - 1.11, - 0.20]), and L4 (- 0.78 mm; [95%CI - 1.11, - 0.46]). Inter- and intra-rater ICC for screw metrics across all vertebral levels combined ranged from 0.68 to 0.91 and 0.89-0.98 for CT, and from 0.62 to 0.92 and 0.81-0.97 for MRI, respectively. Inter- and intra-rater ICC for geometric measurements ranged from 0.60 to 0.95 and 0.84-0.97 for CT, and 0.61-0.95 and 0.93-0.98 for MRI, respectively. CONCLUSION: Deep-learning 3D MRI facilitates equivalent virtual pedicle screw placements and geometric assessments for most lumbar vertebrae, with the exception of vertebral body length at L1, L2, and L4, compared to CT for pre-operative planning in patients considered for robotic-navigated spine surgery.

Laser Technology Advancements in the Treatment of Benign Prostatic Hypertrophy.

PURPOSE OF REVIEW: Lasers have had a significant impact on the treatment of benign prostatic hypertrophy. This article attempts to distill the advancements in laser technology for the treatment of benign prostatic hypertrophy (BPH) into key and understandable points to help make this topic more accessible to urologists. RECENT FINDINGS: The holmium:yttrium-aluminum-garnet (YAG) laser, one of the most significant lasers in the field of urology, has recently been improved with pulse modulating technology (Moses™ technology). New thulium:YAG technology allows both pulsed and continuous wave modes. The thulium fiber laser is one of the newer lasers to come to market and has been shown to have effective and safe outcomes. GreenLight™ lasers are predominantly used in photovaporization procedures and have also been studied extensively, although less in recent years. The modern urologist is fortunate to have many high-quality lasers and a wide variety of surgical techniques to choose from when treating BPH. Understanding the basic laser principles and applications will help urologists to select the best treatment options for their patients with BPH.

Health Care Resource Utilization and Total Costs of Care for Adult Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia in the United States: A Retrospective Claims Analysis.

PURPOSE: Although immunotherapies such as blinatumomab and inotuzumab have led to improved outcomes, financial burden and health resource utilization (HRU) have increased for adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). This study assessed real-world HRU and costs of care among adult patients with R/R B-ALL by line of therapy (LoT) in the United States. METHODS: We selected patients from the MarketScanⓇ Database (January 1, 2016 through December 31, 2020) as follows: ≥1 claims of ALL-indicated first-line (1L) therapies, ≥1 diagnosis of ALL before the index date (1L initiation date), 6-month continuous enrollment before the index date, second-line (2L) therapy initiation, ≥18 years old at 2L, no clinical trial enrollment, no diagnosis of other forms of non-Hodgkin's lymphoma, and no claim for daratumumab or nelarabine during the study period. Outcome measures included claim-based time to next treatment (TTNT), all-cause and adverse event (AE)-related HRU, and all-cause and AE-related costs. FINDINGS: The R/R B-ALL cohort (N = 203) was 60% male, median age of 41 years, and median Charlson Comorbidity Index score of 3.0. Mean (SD) follow-up was 17.8 (11.8) months. Of those who received 2L, 55.7% (113/203) required 3L, and 15% (30/203) initiated 4L+. Patients relapsed quickly, with a median TTNT of 170 days, 169 days, and 205 days for 2L, 3L, and 4L+, respectively. Hospitalization rates were high across each LoT (2L, 88%; 3L, 73%; 4L+, 73%), and the mean (SD) inpatient length of stay increased by LoT as follows: 8.6 (6.8) days for 2L, 10.6 (13.3) for 3L, and 11.6 (13.6) for 4L+. Mean (SD) overall costs were substantial within each LoT at $513,279 ($599,209), $340,419 ($333,555), and $390,327 ($332,068) for 2L, 3L, and 4L+, respectively. The mean (SD) overall/per-patient-per-month AE-related costs were $358,676 ($497,998) for 2L, $202,621 ($272,788) for 3L, and $210,539 ($267,814) for 4L+. Among those receiving blinatumomab or inotuzumab within each LoT, the mean (SD) total costs were $566,373 ($621,179), $498,070 ($376,260), and $512,908 ($159,525) for 2L, 3L, and 4L+, respectively. IMPLICATIONS: These findings suggest that adult patients with R/R B-ALL relapse frequently with standard of care and incur a substantial HRU and cost burden with each LoT. Those treated with blinatumomab or inotuzumab incurred higher total costs within each LoT compared with the overall R/R B-ALL cohort. Alternative therapies with longer duration of remission are urgently needed, and HRU should be considered for future studies examining the optimal sequencing of therapy.

Image-based estimation of the left ventricular cavity volume using deep learning and Gaussian process with cardio-mechanical applications.

In this investigation, an image-based method has been developed to estimate the volume of the left ventricular cavity using cardiac magnetic resonance (CMR) imaging data. Deep learning and Gaussian processes have been applied to bring the estimations closer to the cavity volumes manually extracted. CMR data from 339 patients and healthy volunteers have been used to train a stepwise regression model that can estimate the volume of the left ventricular cavity at the beginning and end of diastole. We have decreased the root mean square error (RMSE) of cavity volume estimation approximately from 13 to 8 ml compared to the common practice in the literature. Considering the RMSE of manual measurements is approximately 4 ml on the same dataset, 8 ml of error is notable for a fully automated estimation method, which needs no supervision or user-hours once it has been trained. Additionally, to demonstrate a clinically relevant application of automatically estimated volumes, we inferred the passive material properties of the myocardium given the volume estimates using a well-validated cardiac model. These material properties can be further used for patient treatment planning and diagnosis.

Methods to Mitigate Industry Influence in Industry Sponsored Research.

Medical and surgical research has always had a long-standing relationship with industry-based funding from sources, such as drug and device companies. Concerns exist surrounding the association between funding sources, outcome from studies and publication bias. Studies demonstrating increased odds ratios associated with positive results in industry sponsored studies across medicine have stimulated Cochrane reviews, literature reviews and other articles to examine this relationship further. In spine surgery in particular, studies with positive results have an odds ratio of 3.3 of being published. This article discusses the biases associated with industry sponsorship, possible ways to reduce such biases and ways to improve transparency in research relationships. This article explores the types of bias that can be encountered at different stages of research including previous trials in spine surgery. The means of improving transparency including the Physician Payment Sunshine Act of 2010 and International Committee of Medical Journal Editors (ICJME) accreditation are discussed. We recognize that physicians undertaking industry sponsored research should be protected and not be liable to perverse incentives. We conclude that mitigating bias in industry sponsored research is a multistep process and needs a multifaceted approach. The main beneficiary of research should be patients and as such a collective effort from medical professionals, health care institutions, journals and industry should approach research, and publications with that in mind.

A systematic review of the presentation of scan-negative suspected cauda equina syndrome.

BACKGROUND: A significant proportion of patients presenting with suspected cauda equina syndrome (CES) do not have associated radiological evidence to support the diagnosis, often termed 'scan-negative'. Due to the limited number of studies regarding the matter, there is no clear understanding for this presentation. As a result, no treatment protocol exists for the scan-negative group. The purpose of this review is to assess the potential contributing factors leading to the presentation of suspected CES with normal imaging. METHODS: A systematic review was conducted on PubMed and Cochrane databases. Bibliographies of key articles and Google Scholar were searched for additional results. The search strategy provided 204 results. Of those, 8 had no identifiable causation for suspected CES and were included for systematic review. RESULTS: 6 of 8 studies investigated for a difference in clinical presentation between cohorts that may indicate a normal scan. Studies were either inconclusive and contradictory. Two studies suggest a functional somatic disorder as reasoning for negative MRI, with positive provisional findings. CONCLUSION: A psychogenic hypothesis is plausible and warrants further investigation. The need for additional studies is essential to scheming a potential treatment protocol for the scan-negative population, which currently does not exist.

Trends in the management of fractures of the distal radius in Ireland: did the Distal Radius Acute Fracture Fixation Trial (DRAFFT) change practice?

AIMS: The aim of this study was to examine trends in the management of fractures of the distal radius in Ireland over a ten-year period, and to determine if there were any changes in response to the English Distal Radius Acute Fracture Fixation Trial (DRAFFT). PATIENTS AND METHODS: Data was grouped into annual intervals from 2008 to 2017. All adult inpatient episodes that involved emergency surgery for fractures of the distal radius were included. RESULTS: In 2008 Kirschner-wire (K-wire) fixation accounted for 59% of operations for fractures of the distal radius, and plate fixation for 21%. In 2017, the rate of K-wire fixation had fallen to 30%, and the proportion of patients who underwent plate fixation had risen to 62%. CONCLUSION: There is an increasing trend towards open reduction and internal fixation for fractures of the distal radius in Ireland. This has been accompanied by a decrease in popularity for K-wire fixation. DRAFFT did not appear to influence trends in the management of fractures of the distal radius in Ireland. Cite this article: Bone Joint J 2019;101-B:1550-1556.

Combination treatment for male lower urinary tract symptoms with anticholinergic and alpha-blockers.

PURPOSE OF REVIEW: Although alpha-adrenergic antagonists (α-blockers) are effective for relieving voiding lower urinary tract symptoms (LUTS) in men, storage symptoms often persist. The aim of this manuscript is to evaluate the efficacy and safety of combination therapy with α-blockers and muscarinic receptor antagonists (anticholinergics). RECENT FINDINGS: High-quality evidence confirms that the addition of an anticholinergic improves micturition diary parameters, such as daytime and nocturnal frequency and urgency incontinence episodes, as well as total and storage subset scores on the International Prostate Symptom Score. Most studies demonstrate a statistically significant improvement over α-blocker monotherapy. Both, incidence of urinary retention and study withdrawal because of treatment-related adverse events with combination therapy, are low. Urodynamic indices, such as maximum flow rate and postvoid residual volume, are also minimally impacted by combination therapy. Outcomes on validated questionnaires and quality-of-life (QoL) indices also indicate a significant improvement. SUMMARY: The addition of an anticholinergic to an α-blocker in men with storage and voiding LUTS is an effective practice in reducing both categories of symptoms. The addition of anticholinergic is associated with a low rate of urinary retention and the impact on efficient bladder emptying is minimal. Not unexpectedly, QoL is improved.

Quantitative Analysis of Technological Innovation in Urology.

OBJECTIVE: To assess major areas of technological innovation in urology in the last 20 years using patent and publication data. METHODS: Patent and MEDLINE databases were searched between 1980 and 2012 electronically using the terms urology OR urological OR urologist AND "surgeon" OR "surgical" OR "surgery". The patent codes obtained were grouped in technology clusters, further analyzed with individual searches, and growth curves were plotted. Growth rates and patterns were analyzed, and patents were correlated with publications as a measure of scientific support and of clinical adoption. RESULTS: The initial search revealed 417 patents and 20,314 publications. The top 5 technology clusters in descending order were surgical instruments including urinary catheters, minimally invasive surgery (MIS), lasers, robotic surgery, and image guidance. MIS and robotic surgery were the most emergent clusters in the last 5 years. Publication and patent growth rates were closely correlated (Pearson coefficient 0.78, P <.01), but publication growth rate remained constantly higher than patent growth, suggesting validated scientific support for urologic innovation and adoption into clinical practice. CONCLUSION: Patent metrics identify emergent technological innovations and such trends are valuable to understand progress in the field of urology. New surgical technologies like robotic surgery and MIS showed exponential growth in the last decade with good scientific vigilance.

Day of Surgery Admission in Total Joint Arthroplasty: Why Are Surgeries Cancelled? An Analysis of 3195 Planned Procedures and 114 Cancellations.

Background. Day of surgery admission (DOSA) is becoming standard practice as a means of reducing cost in total joint arthroplasty. Aims. The aim of our study was to audit the use of DOSA in a specialty hospital and identify reasons for cancellation. Methods. A retrospective study of patients presenting for hip or knee arthroplasty between 2008 and 2013 was performed. All patients were assessed at the preoperative assessment clinic (PAC). Results. Of 3195 patients deemed fit for surgery, 114 patients (3.5%) had their surgery cancelled. Ninety-two cancellations (80%) were due to the patient being deemed medically unsuitable for surgery by the anaesthetist. Cardiac disease was the most common reason for cancellation (n = 27), followed by pulmonary disease (n = 22). 77 patients (67.5%) had their operation rescheduled and successfully performed in our institution at a later date. Conclusion. DOSA is associated with a low rate of cancellations on the day of surgery. Patients with cardiorespiratory comorbidities are at greatest risk of cancellation.

Quantitative Analysis of Technological Innovation in Knee Arthroplasty: Using Patent and Publication Metrics to Identify Developments and Trends.

BACKGROUND: Surgery is in a constant continuum of innovation with refinement of technique and instrumentation. Arthroplasty surgery potentially represents an area with highly innovative process. This study highlights key area of innovation in knee arthroplasty over the past 35 years using patent and publication metrics. Growth rates and patterns are analyzed. Patents are correlated to publications as a measure of scientific support. METHODS: Electronic patent and publication databases were searched over the interval 1980-2014 for "knee arthroplasty" OR "knee replacement." The resulting patent codes were allocated into technology clusters. Citation analysis was performed to identify any important developments missed on initial analysis. The technology clusters identified were further analyzed, individual repeat searches performed, and growth curves plotted. RESULTS: The initial search revealed 3574 patents and 16,552 publications. The largest technology clusters identified were Unicompartmental, Patient-Specific Instrumentation (PSI), Navigation, and Robotic knee arthroplasties. The growth in patent activity correlated strongly with publication activity (Pearson correlation value 0.892, P < .01), but was growing at a faster rate suggesting a decline in vigilance. PSI, objectively the fastest growing technology in the last 5 years, is currently in a period of exponential growth that began a decade ago. Established technologies in the study have double s-shaped patent curves. CONCLUSION: Identifying trends in emerging technologies is possible using patent metrics and is useful information for training and regulatory bodies. The decline in ratio of publications to patents and the uninterrupted growth of PSI are developments that may warrant further investigation.

The Effect of Weight Loss on Indigenous Australians with Diabetes: a study of Feasibility, Acceptability and Effectiveness of Laparoscopic Adjustable Gastric Banding.

BACKGROUND/OBJECTIVES: Diabetes and obesity are common and serious health challenges for indigenous people worldwide. The feasibility of achieving substantial weight loss, leading to remission of diabetes, was evaluated in a regional indigenous Australian community. SUBJECTS/METHODS: A prospective cohort study of 30 obese indigenous adults from the Rumbalara Aboriginal Co-operative in Central Victoria was performed. Inclusion criteria included aboriginality, BMI > 30 kg/m(2) and diabetes diagnosed within the last 10 years. Weight loss was achieved using laparoscopic adjustable gastric banding (LAGB). Participants were treated in their community and followed for 2 years. Outcomes were compared with those of non-indigenous Australians from an earlier randomized controlled trial (RCT) using a similar protocol. RESULTS: 30 participants (26 females, mean age 44.6 years; mean BMI 44.3) had LAGB at the regional hospital. Twenty-six participants completed diabetes assessment at 2 years follow-up. They showed diabetes remission (fasting blood glucose < 7.0 mmol/L and haemoglobin A1c (HbA1c) < 6.2 % while off all therapy except metformin) in 20 of the 26 and a mean weight loss (SD) of 26.0 (14) kilograms. Based on intention-to-treat, remission rate was 66 %. Quality of life improved. There was one early event and 12 late adverse events. The outcomes for weight loss and diabetes remission were not different from the LAGB group of the RCT. CONCLUSIONS: For obese indigenous people with diabetes, a regionalized model of care centred on the LAGB is an effective approach to a serious health problem. The model proved feasible and acceptable to the indigenous people. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN 12609000319279).

Availability of accessible and high-quality information on the Internet for patients regarding the diagnosis and management of rotator cuff tears.

BACKGROUND: In the era of informed patient decision-making, educated patients are vital contributors. The Internet provides a vast information source that patients will access. It is imperative that this information be relevant and understandable. Various treatments, each with advantages and disadvantages, are available. We sought to examine the standard of information about the diagnosis and management of rotator cuff tears available to patients on the Internet. METHODS: We identified 125 websites from searching "rotator cuff tear" in the 5 most popular Internet search engines. The websites were examined for readability by measuring the Flesch Reading Ease Score, the Flesch-Kincaid Grade Level, and the Gunning Fog Index. The quality of the websites was measured by the DISCERN instrument, the Journal of the American Medical Association benchmark criteria, and Health on the Net Foundation certification. RESULTS: There were 59 individual URLs analyzed. Overall, the quality was poor, with the average DISCERN score being only 39.47. Furthermore, the mean reading grade level was above 9 (recommended level, 6). Health on the Net Foundation certification did correspond to significantly worse readability scores (P = .004) but did not correlate with improved DISCERN scores. Those that satisfied more of the Journal of the American Medical Association benchmark criteria had significantly better DISCERN scores (P < .001). CONCLUSION: Information about rotator cuff tears is of a low standard and is in many cases written at too high a level for the general population. There are instruments of which we, as surgeons, must be aware to evaluate the resources available and to recommend them to patients to ensure that they understand their condition and treatment options.

Acute bilateral spontaneous forearm compartment syndrome.

Acute spontaneous compartment syndrome of the forearm is rarely reported in the literature. It is typically associated with trauma or thromboembolism in the acute setting and repetitive exertional stress in the chronic setting. However it is rare for it to present bilaterally with no apparent underlying cause. We report the case of a young 31-year-old lady who presented to our Emergency Department with bilateral compartment syndrome of the forearm. Her presenting complaints included acute severe pain and swelling of the forearms bilaterally, with a decreased range of movement of the wrist and fingers. She also complained of numbness in all fingers. She had no history of recent trauma and ultrasound scans showed no evidence of vascular compromise. Past medical history was notable only for idiopathic hypertension and coeliac disease. The patient was taken to theatre urgently where flexor and extensor compartments and carpal tunnel were decompressed. Pronator Teres was found to be dusky initially but turned pink after decompression. All other muscles were normal. An interesting fact of this case was that combination of the high compartment pressures and anaesthetic related hypotension caused the forearm pulses to become impalpable at induction, these returned intra-operatively. The patient has been seen in the outpatient department following discharge. She is well apart from some mildly reduced grip strength in her right hand likely due to carpal tunnel decompression. No cause was found for the scenario after extensive medical investigation.

Analysis of pharmaceutical compounds from glass, fabric, steel, and wood surfaces at atmospheric pressure using spatially resolved, nonresonant femtosecond laser vaporization electrospray mass spectrometry.

Laser electrospray mass spectrometry (LEMS) is demonstrated for pharmaceutical samples at atmospheric pressure. A nonresonant, femtosecond duration laser pulse vaporizes native samples at atmospheric pressure into an electrospray plume for ionization with subsequent transfer into a time-of-flight mass spectrometer. The active ingredients in pharmaceutical tablets were detected in the presence of binders and fillers in intact formulations using LEMS. Mass spectra were also obtained for microgram amounts of the pharmaceutical compounds loratadine, oxycodone, and atenolol deposited on glass, wood, steel, and polyester fabric. The neutral capture efficiency by the electrospray plume for nonresonant laser vaporization of oxycodone and atenolol desorbed from steel is 2.4% +/- 1.5% and 0.25% +/- 0.18%, respectively. LEMS imaging of the spatial distribution of an oxycodone spot on a metal slide with resolution of 250 mum is also presented.

Demand and supply of bone allograft and the role of orthopaedic surgeons.

This study assessed factors responsible for exclusion of patients from bone donation at primary hip arthroplasty in order to improve bone banking. Fifty-five patients underwent screening in preoperative clinics assessing their suitability for femoral head donation. Records at the bone bank were then reviewed post operatively to check whether bone had been harvested from these individuals during surgery. Overall, 95% of the patients screened did not proceed to bone banking. After the initial screening stage 60% of patients were excluded. The majority of exclusions (70%) were unacceptable as donors because of their potential risk of transmission of disease to recipients. Although 40% were consented for donation, femoral heads from only 5% were harvested and sent for storage in the bone bank during hip arthroplasty. Orthopaedic surgeons must take an active part in bone banking and alternative sources of bone grafts require exploration in the future to meet the increasing demand.