Case fatality ratios for serious emergency conditions in the Republic of Ireland: a longitudinal investigation of trends over the period 2002-2014 using joinpoint analysis

Background: In the past decade, the Republic of Ireland has undertaken significant reconfiguration programmes to improve emergency services. During this time the public healthcare system experienced a large real decrease in resources. This study assesses national and regional population outcomes over the period 2002–2014, and whether changes coincide with system reconfiguration and the financial restrictions imposed by the 2008 recession. Methods: Case fatality ratios (CFRs) were constructed for emergency conditions for 2002–2014. Total emergency conditions and individual condition trends were analysed nationally using joinpoint analysis. National results informed the investigation of trends at a regional and county level using an inverse standard error weighted generalised linear model with a log link to construct funnel plots. County-level CFRs were compared for the first and last 3 years of the period to further investigate the changes to county results over the 13 year period, specifically in comparison to the national-level CFR. Results: Nationally, there was an annual fall in CFRs (2.1%). The decline was faster from 2002 to 2007 (annual percentage change = − 3.4; 95% CI-4.4, − 2.4), compared to 2007–2014 (annual percentage change = − 1.2; 95% CI -1.9, − 0.5). The South-East had a lower rate of decrease and the West had a higher rate. Cross sectional analysis of two periods (2002–2004 and 2012–2014) showed high consistency in the counties performance relative to the national CFR in both periods. Conclusion: Change in the national trend coincided with the onset of economic stress on the public health system. Attributing the decline in CFR improvement to economic factors is weakened by the uneven nature of the trend change. No distinct pattern of change was identified among regions which underwent substantial reconfiguration of emergency services

What Can Legacy Patient-Reported Outcome Measures Tell Us About Participation Bias in Patient-Reported Outcomes Measurement Information System Scores Among Lumbar Spine Patients?

Objective Patient-Reported Outcomes Measurement Information System (PROMIS) is a validated tool for assessing patient-reported outcomes in spine surgery. However, PROMIS is vulnerable to nonresponse bias. The purpose of this study is to characterize differences in patient-reported outcome measure scores between patients who do and do not complete PROMIS physical function (PF) surveys following lumbar spine surgery. Methods A prospectively maintained database was retrospectively reviewed for primary, elective lumbar spine procedures from 2015 to 2019. Outcome measures for Patient Health Questionnaire-9 (PHQ-9), visual analogue scale (VAS) back & leg, Oswestry Disability Index (ODI), and 12-item Short Form health survey physical composite summary (SF-12 PCS) were recorded at both preoperative and postoperative (6 weeks, 12 weeks, 6 months, 1 year, 2 years) timepoints. Completion rates for PROMIS PF surveys were recorded and patients were categorized into groups based on completion. Differences in mean scores at each timepoint between groups was determined. Results Eight hundred nine patients were included with an average age of 48.1 years. No significant differences were observed for all outcome measures between PROMIS completion groups preoperatively. Postoperative PHQ-9, VAS back, VAS leg, and ODI scores differed significantly between groups through 1 year (all p < 0.05). SF-12 PCS differed significantly only at 6 weeks (p = 0.003). Conclusion Patients who did not complete PROMIS PF surveys had significantly poorer outcomes than those that did in terms of postoperative depressive symptoms, pain, and disability. This suggests that patients completing PROMIS questionnaires may represent a healthier cohort than the overall lumbar spine population

Effects of Anterior Plating on Achieving Clinically Meaningful Improvement Following Single-Level Anterior Cervical Discectomy and Fusion

Objective The clinical utility of anterior cervical plating for anterior cervical discectomy and fusion (ACDF) procedures remains controversial. This study aims to compare the impact of cervical plating on achievement of minimum clinically important difference (MCID) up to 2 years following ACDF. Methods Patients undergoing primary, single-level ACDF procedures were grouped based on whether their procedure included application of an anterior cervical plate. Demographics, preoperative spinal diagnoses, operative characteristics, and patient-reported outcome measures (PROMs) were compared between plating groups. Achievement of an MCID was assessed using the following previously established thresholds: 12-item Short Form health survey physical component summary (SF-12 PCS) 8.1, visual analogue scale (VAS) neck 2.6, VAS arm 4.1, Neck Disability Index (NDI) 8.5. Rates of MCID achievement were compared between groups. Results The cohort included 192 patients of whom 102 received plating and 90 received no plating. Plating status was significantly associated with Charlson Comorbidity Index and insurance status. Operative duration and estimated blood loss were significantly greater for the plating group. Both groups demonstrated significant improvements at the majority of postoperative timepoints. Significant intergroup differences in PROM improvement were demonstrated for VAS neck and NDI at 6 weeks. Rates of MCID achievement differed significantly between groups for NDI at 6 weeks, and 12 weeks, and SF-12 PCS overall. Conclusion Patients improved significantly in terms of pain, disability and physical function, regardless of plating status, and with the exception of early neck pain and disability, these improvements were similar between groups. Patients that underwent plating as part of their ACDF procedure achieved an MCID for physical function at lower rates overall

Lateral Lumbar Interbody Fusion in the Outpatient Setting with Multimodal Analgesic Protocol: Clinical Case Series

Objective Minimally invasive techniques and multimodal analgesia protocols have made spine surgery in the outpatient setting increasingly feasible. A number of spinal procedures have been documented in the outpatient setting, though the feasibility of lateral lumbar interbody fusion (LLIF) on an ambulatory basis has not been thoroughly assessed. To present a clinical case series of patients undergoing LLIF in the outpatient setting. Methods A prospectively maintained surgical database was retrospectively reviewed to identify patients undergoing outpatient spine procedures with an enhanced multimodal analgesia protocol from October 2016 to February 2021. Patient demographics, medical and spinal diagnoses, procedural characteristics, operative duration, estimated blood loss (EBL), postoperative length of stay (LOS), postoperative pain scores, postoperative narcotic consumption, and incidence of any intra- or postoperative complications were collected. The state’s prescription monitoring program was queried to assess rates of filling narcotic prescriptions >6 weeks following surgery. Results A total of 24 LLIF patients were included. Mean postoperative pain score was 5.8, and mean postoperative narcotic consumption was 26.8 oral morphine equivalents. All patients were discharged on the same day of surgery. No postoperative complications were observed. After the 6-week postoperative timepoint, 16.7% of patients filled a prescription for tramadol, 8.3% for hydrocodone, 4.2% for hydromorphone, 4.2% for cyclobenzaprine, and 4.2% for alprazolam. Conclusion This clinical case series demonstrates that LLIF can be both safe and feasible in the outpatient setting, with minimal narcotic medication dependence in the postoperative period

Do Patient Expectations Represent a More Important Clinical Difference? A Study of Surgical Outcomes in the Cervical Spine

Objective This study aims to compare the impact of achieving an MCID or meeting preoperative expectations on patient satisfaction following cervical spine procedures. Methods A surgical database was retrospectively reviewed for cervical spine surgery patients from 2016 to 2020. Inclusion criteria were primary or revision, single- or multilevel cervical disc arthroplasty or anterior cervical discectomy and fusions (ACDF). Visual analogue scale (VAS) neck and arm pain was assessed preoperatively and postoperatively (6-week, 12-weeks, 6-months, 1-year). Preoperative patient expectation and postoperative satisfaction were recorded. MCID achievement was determined using previously established values. Expectations met and MCID achievement were compared as possible predictors of satisfaction. Results One hundred and six cervical spine patients were included. Both meeting expectations and achieving MCID were significant predictors of satisfaction for arm pain at 6-weeks and 12-weeks (all p≤0.007). Achieving MCID significantly predicted satisfaction for neck pain at all timepoints (all p≤0.007) and meeting expectations predicted satisfaction for neck pain at 6-weeks, 12-weeks, and 1-year (all p≤0.003). Comparison of coefficients revealed no significant difference in effect size between meeting expectations and achievement of MCID as predictors of patient satisfaction (all p>0.050). Conclusion MCID achievement and meeting expectations were significant predictors of satisfaction for neck pain and short-term arm pain. Both measures may be similarly useful for interpretation of patient outcomes and the optimal choice of metric may depend on practice-specific factors

Using Swallowing Quality of Life to Compare Oropharyngeal Dysphagia Following Cervical Disc Arthroplasty or Anterior Cervical Discectomy and Fusion

Objective To evaluate dysphagia outcomes using the swallowing quality of life (SWAL-QOL) questionnaire between patients undergoing cervical disk arthroplasty (CDA) or anterior cervical discectomy and fusion (ACDF). Methods Patient-reported outcome measures (PROMs) were collected using SWAL-QOL, VAS, NDI, and SF-12 PCS. All measures were recorded preoperatively to 6-month postoperatively. Patients were grouped according to cervical procedure and instrumentation used. Differences in PROMs and SWAL-QOL domains were evaluated by t-test and one-way ANOVA with post-hoc testing, respectively. Simple linear regression was employed to evaluate the relationship between number of levels operated on and postoperative outcomes. Results 161 patients were included. CDA patients had significantly worse SWAL-QOL scores at 6-months. Preoperative VAS neck was significantly worse for patients who underwent either an ACDF procedure with a stand-alone cage or CDA as compared to patients who underwent an ACDF with anterior plating. At 6-months postoperatively, CDA patients reported a significantly worse “fatigue” score compared to ACDF patients. At 6-months postoperatively, ACDF patients reported a significantly better “sleep” scores compared to CDA patients with both recipients of an anterior plate and stand-alone cage reporting significantly better scores compared to the CDA cohort (p=0.024; p<0.001). The SWAL-QOL domain of symptom frequency at 6-weeks postoperatively was significantly associated with number of levels operated (p=0.032). Conclusion Patients undergoing either an ACDF or CDA procedure largely did not demonstrate differences in pain, disability, and dysphagia scores. However, at more longitudinal timepoints CDA patients reported worse fatigue and sleep scores compared to ACDF patients

Antimicrobial Stewardship Training for Infectious Diseases Fellows: Program Directors Identify a Curriculum Need

A needs assessment survey of infectious diseases (ID) training program directors identified gaps in educational resources for training and evaluating ID fellows in antimicrobial stewardship. An Infectious Diseases Society of America-sponsored core curriculum was developed to address that need

An Osteoblast-Derived Proteinase Controls Tumor Cell Survival via TGF-beta Activation in the Bone Microenvironment

Breast to bone metastases frequently induce a "vicious cycle" in which osteoclast mediated bone resorption and proteolysis results in the release of bone matrix sequestered factors that drive tumor growth. While osteoclasts express numerous proteinases, analysis of human breast to bone metastases unexpectedly revealed that bone forming osteoblasts were consistently positive for the proteinase, MMP-2. Given the role of MMP-2 in extracellular matrix degradation and growth factor/cytokine processing, we tested whether osteoblast derived MMP-2 contributed to the vicious cycle of tumor progression in the bone microenvironment.To test our hypothesis, we utilized murine models of the osteolytic tumor-bone microenvironment in immunocompetent wild type and MMP-2 null mice. In longitudinal studies, we found that host MMP-2 significantly contributed to tumor progression in bone by protecting against apoptosis and promoting cancer cell survival (caspase-3; immunohistochemistry). Our data also indicate that host MMP-2 contributes to tumor induced osteolysis (μCT, histomorphometry). Further ex vivo/in vitro experiments with wild type and MMP-2 null osteoclast and osteoblast cultures identified that 1) the absence of MMP-2 did not have a deleterious effect on osteoclast function (cd11B isolation, osteoclast differentiation, transwell migration and dentin resorption assay); and 2) that osteoblast derived MMP-2 promoted tumor survival by regulating the bioavailability of TGFβ, a factor critical for cell-cell communication in the bone (ELISA, immunoblot assay, clonal and soft agar assays).Collectively, these studies identify a novel "mini-vicious cycle" between the osteoblast and metastatic cancer cells that is key for initial tumor survival in the bone microenvironment. In conclusion, the findings of our study suggest that the targeted inhibition of MMP-2 and/or TGFβ would be beneficial for the treatment of bone metastases

Waveform Modelling for the Laser Interferometer Space Antenna

LISA, the Laser Interferometer Space Antenna, will usher in a new era in gravitational-wave astronomy. As the first anticipated space-based gravitational-wave detector, it will expand our view to the millihertz gravitational-wave sky, where a spectacular variety of interesting new sources abound: from millions of ultra-compact binaries in our Galaxy, to mergers of massive black holes at cosmological distances; from the beginnings of inspirals that will venture into the ground-based detectors' view to the death spiral of compact objects into massive black holes, and many sources in between. Central to realising LISA's discovery potential are waveform models, the theoretical and phenomenological predictions of the pattern of gravitational waves that these sources emit. This white paper is presented on behalf of the Waveform Working Group for the LISA Consortium. It provides a review of the current state of waveform models for LISA sources, and describes the significant challenges that must yet be overcome.Comment: 239 pages, 11 figures, white paper from the LISA Consortium Waveform Working Group, invited for submission to Living Reviews in Relativity, updated with comments from communit

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease