Background
It would be helpful for the decision-making process of patients with metastatic bone disease to understand which patients are at risk for worse quality of life (QOL), pain, anxiety, and ...depression. Normative data, and where these stand compared with general population scores, can be useful to compare and interpret results of similar patients or patient groups, but to our knowledge, there are no such robust data.
Questions/Purposes
We wished (1) to assess what factors are independently associated with QOL, pain interference, anxiety, and depression in patients with metastatic bone disease, and (2) to compare these outcomes with general US population values.
Methods
Between November 2011 and February 2015, 859 patients with metastatic bone disease presented to our orthopaedic oncology clinic; 202 (24%) were included as they completed the EuroQOL-5 Dimension (EQ-5D
TM
), PROMIS
®
Pain Interference, PROMIS
®
Anxiety, and PROMIS
®
Depression questionnaires as part of a quality improvement program. We did not record reasons for not responding and found no differences between survey respondents and nonrespondents in terms of age (63 versus 64 years; p = 0.916), gender (51% men versus 47% men; p = 0.228), and race (91% white versus 88% white; p = 0.306), but survey responders were more likely to be married or living with a partner (72%, versus 62%; p = 0.001). We assessed risk factors for QOL, pain interference, anxiety, and depression using multivariable linear regression analysis. We used the one-sample signed rank test to assess whether scores differed from US population averages drawn from earlier large epidemiologic studies.
Results
Younger age (β regression coefficient β, < 0.01; 95% CI, 0.00–0.01; p = 0.041), smoking (β, −0.12; 95% CI, −0.22 to −0.01; p = 0.026), pathologic fracture (β, −0.10; 95% CI, −0.18 to −0.02; p = 0.012), and being unemployed (β, −0.09; 95% CI, −0.17 to −0.02; p = 0.017) were associated with worse QOL. Current smoking status was associated with more pain interference (β, 6.0; 95% CI, 1.6–11; p = 0.008). Poor-prognosis cancers (β, 3.8; 95% CI, 0.37–7.2; p = 0.030), and pathologic fracture (β, 6.3; 95% CI, 2.5–7.2; p = 0.001) were associated with more anxiety. Being single (β, 5.9; 95% CI, 0.83–11; p = 0.023), and pathologic fracture (β, 4.4; 95% CI, 0.8–8.0; p = 0.017) were associated with depression. QOL scores (0.68 versus 0.85; p < 0.001), pain interference scores (65 versus 50; p < 0.001), and anxiety scores (53 versus 50; p = 0.011) were worse for patients with bone metastases compared with general US population values, whereas depression scores were comparable (48 versus 50; p = 0.171).
Conclusions
Impending pathologic fractures should be treated promptly to prevent deterioration in QOL, anxiety, and depression. Our normative data can be used to compare and interpret results of similar patients or patient groups. Future studies could focus on specific cancers metastasizing to the bone, to further understand which patients are at risk for worse patient-reported outcomes.
Level of evidence
Level III, prognostic study.
Statistical models using machine learning (ML) have the potential for more accurate estimates of the probability of binary events than logistic regression. The present study used existing data sets ...from large musculoskeletal trauma trials to address the following study questions: (1) Do ML models produce better probability estimates than logistic regression models? (2) Are ML models influenced by different variables than logistic regression models?
We created ML and logistic regression models that estimated the probability of a specific fracture (posterior malleolar involvement in distal spiral tibial shaft and ankle fractures, scaphoid fracture, and distal radial fracture) or adverse event (subsequent surgery after distal biceps repair or tibial shaft fracture, surgical site infection, and postoperative delirium) using 9 data sets from published musculoskeletal trauma studies. Each data set was split into training (80%) and test (20%) subsets. Fivefold cross-validation of the training set was used to develop the ML models. The best-performing model was then assessed in the independent testing data. Performance was assessed by (1) discrimination (c-statistic), (2) calibration (slope and intercept), and (3) overall performance (Brier score).
The mean c-statistic was 0.01 higher for the logistic regression models compared with the best ML models for each data set (range, -0.01 to 0.06). There were fewer variables strongly associated with variation in the ML models, and many were dissimilar from those in the logistic regression models.
The observation that ML models produce probability estimates comparable with logistic regression models for binary events in musculoskeletal trauma suggests that their benefit may be limited in this context.
We proposed that a test for sensitivity to the adjuvant endocrine therapy component of treatment for patients with stage II-III breast cancer (SET2,3) should measure transcription related to estrogen ...and progesterone receptors (SETER/PR index) adjusted for a baseline prognostic index (BPI) combining clinical tumor and nodal stage with molecular subtype by RNA4 (ESR1, PGR, ERBB2, and AURKA).
Patients with clinically high-risk, hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative (HR+/HER2−) breast cancer received neoadjuvant taxane–anthracycline chemotherapy, surgery with measurement of residual cancer burden (RCB), and then adjuvant endocrine therapy. SET2,3 was measured from pre-treatment tumor biopsies, evaluated first in an MD Anderson Cancer Center (MDACC) cohort (n = 307, 11 years' follow-up, U133A microarrays), cut point was determined, and then independent, blinded evaluation was carried out in the I-SPY2 trial (n = 268, high-risk MammaPrint result, 3.8 years' follow-up, Agilent-44K microarrays, NCI Clinical Trials ID: NCT01042379). Primary outcome measure was distant relapse-free survival. Multivariate Cox regression models tested prognostic independence of SET2,3 relative to RCB and other molecular prognostic signatures, and whether other prognostic signatures could substitute for SETER/PR or RNA4 components of SET2,3.
SET2,3 added independent prognostic information to RCB in the MDACC cohort: SET2,3 hazard ratio (HR) 0.23, P = 0.004 and RCB (HR 1.77, P < 0.001); and the I-SPY2 trial: SET2,3 (HR 0.27, P = 0.031) and RCB (HR 1.68, P = 0.008). SET2,3 provided similar prognostic information irrespective of whether RCB-II or RCB-III after chemotherapy, and in both luminal subtypes. Conversely, RCB was most strongly prognostic in cancers with low SET2,3 status (MDACC P < 0.001, I-SPY2 P < 0.001). Other molecular signatures were not independently prognostic; they could effectively substitute for RNA4 subtype within the BPI component of SET2,3, but they could not effectively substitute for SETER/PR index.
SET2,3 added independent prognostic information to chemotherapy response (RCB) and baseline prognostic score or subtype. Approximately 40% of patients with clinically high-risk HR+/HER2− disease had high SET2,3 and could be considered for clinical trials of neoadjuvant endocrine-based treatment.
•The SET2,3 assay added independent prognostic information to RCB after neoadjuvant chemotherapy.•The SETER/PR index of endocrine transcriptional activity added to contemporary genomic signatures and assays.•SET2,3 was prognostic within both luminal subtypes of breast cancer.•Patients with a high SET2,3 result might be appropriate for clinical trials of neoadjuvant endocrine-based therapy.
Porous carbon nanotube (CNT) mats adsorbed on flat sheet membranes have previously been shown to significantly improve fouling resistance and contaminant removal capabilities. Unfortunately, these ...CNT mats are easily disrupted by backwashing, severely limiting their value in commercial membranes. In this study, we describe how CNT mats, which are stable to backwashing, can be generated on the inner surface of hollow fiber membranes. Mat stability was determined from electron microscopy and by quantifying the mass of CNTs lost during aggressive backwashing, including hydraulic stress and exposure to harsh chemicals. Stable mats were also formed with powder activated carbon, demonstrating that the mat's stability is not a consequence of CNT properties, but rather the nature and directionality of the forces that these mats experience during backwashing. Compared to virgin membranes, CNT-modified membranes exhibited improved fouling resistance which was sustained through multiple backwashing cycles. Moreover, no measureable quantities of CNTs entered the permeate when natural organic matter was filtered through a CNT-modified membrane, indicating that CNTs will not be released into the permeate during filtration. Collectively, these findings indicate that CNT-modified membranes could positively impact the sustainability and performance of hollow fiber membranes being used in water purification.
(Left) Cross-sectional scanning electron microscope (SEM) image and, (Right) schematic representation of a hollow fiber membrane with a stable CNT mat on its inner surface. Display omitted
•Generation of backwashable carbon nanotube mats on the inner surface of polymeric hollow fibers membranes.•Stability of CNT mats to aggressive backwashing.•Improvement of fouling resistance due to CNT mats.
Abstract Background context Spine surgery is usually associated with large amount of blood loss, necessitating blood transfusions. Blood loss-associated morbidity can be because of direct risks, such ...as hypotension and organ damage, or as a result of blood transfusions. The antifibrinolytic, tranexamic acid (TXA), is a lysine analog that inhibits activation of plasminogen and has shown to be beneficial in reducing surgical blood loss. Purpose To consolidate the findings of randomized controlled trials (RCTs) investigating the use of TXA on surgical bleeding in spine surgery. Study design A metaanalysis. Study sample Randomized controlled trials investigating the effectiveness of intravenous TXA in reducing blood loss in spine surgery, compared with a placebo/no treatment group. Methods MEDLINE, Embase, Cochrane controlled trials register, and Google Scholar were used to identify RCTs published before January 2014 that examined the effectiveness of intravenous TXA on reduction of blood loss and blood transfusions, compared with a placebo/no treatment group in spine surgery. Metaanalysis was performed using RevMan 5. Weighted mean difference with 95% confidence intervals was used to summarize the findings across the trials for continuous outcomes. Dichotomous data were expressed as risk ratios with 95% confidence intervals. A p<.05 was considered statistically significant. Results Eleven RCTs were included for TXA (644 total patients). Tranexamic acid reduced intraoperative, postoperative, and total blood loss by an average of 219 mL (−322, −116, p<.05), 119 mL (−141, −98, p<.05), and 202 mL (−299, −105, p<.05), respectively. Tranexamic acid led to a reduction in proportion of patients who received a blood transfusion (risk ratio 0.67 0.54, 0.83, p<.05) relative to placebo. There was one myocardial infarction (MI) in the TXA group and one deep vein thrombosis (DVT) in placebo. Conclusions Tranexamic acid reduces surgical bleeding and transfusion requirements in patients undergoing spine surgery. Tranexamic acid does not appear to be associated with an increased incidence of pulmonary embolism, DVT, or MI.
The Tropospheric Ozone Assessment Report (TOAR) is an activity of the International Global Atmospheric Chemistry Project. This paper is a component of the report, focusing on the present-day ...distribution and trends of tropospheric ozone relevant to climate and global atmospheric chemistry model evaluation. Utilizing the TOAR surface ozone database, several figures present the global distribution and trends of daytime average ozone at 2702 non-urban monitoring sites, highlighting the regions and seasons of the world with the greatest ozone levels. Similarly, ozonesonde and commercial aircraft observations reveal ozone’s distribution throughout the depth of the free troposphere. Long-term surface observations are limited in their global spatial coverage, but data from remote locations indicate that ozone in the 21st century is greater than during the 1970s and 1980s. While some remote sites and many sites in the heavily polluted regions of East Asia show ozone increases since 2000, many others show decreases and there is no clear global pattern for surface ozone changes since 2000. Two new satellite products provide detailed views of ozone in the lower troposphere across East Asia and Europe, revealing the full spatial extent of the spring and summer ozone enhancements across eastern China that cannot be assessed from limited surface observations. Sufficient data are now available (ozonesondes, satellite, aircraft) across the tropics from South America eastwards to the western Pacific Ocean, to indicate a likely tropospheric column ozone increase since the 1990s. The 2014–2016 mean tropospheric ozone burden (TOB) between 60°N–60°S from five satellite products is 300 Tg ± 4%. While this agreement is excellent, the products differ in their quantification of TOB trends and further work is required to reconcile the differences. Satellites can now estimate ozone’s global long-wave radiative effect, but evaluation is difficult due to limited in situ observations where the radiative effect is greatest.
Nuts and vegetable oils are important sources of fat and of a wide variety of micronutrients and phytochemicals. Following their intake, several of their constituents, as well as their derived ...metabolites, are found in blood circulation and in urine. As a consequence, these could be used to assess the compliance to a dietary intervention or to determine habitual intake of nuts and vegetable oils. However, before these metabolites can be widely used as biomarkers of food intake (BFIs), several characteristics have to be considered, including specificity, dose response, time response, stability, and analytical performance. We have, therefore, conducted an extensive literature search to evaluate current knowledge about potential BFIs of nuts and vegetable oils. Once identified, the strengths and weaknesses of the most promising candidate BFIs have been summarized. Results from selected studies have provided a variety of compounds mainly derived from the fatty fraction of these foods, but also other components and derived metabolites related to their nutritional composition. In particular, α-linolenic acid, urolithins, and 5-hydroxyindole-3-acetic acid seem to be the most plausible candidate BFIs for walnuts, whereas for almonds they could be α-tocopherol and some catechin-derived metabolites. Similarly, several studies have reported a strong association between selenium levels and consumption of Brazil nuts. Intake of vegetable oils has been mainly assessed through the measurement of specific fatty acids in different blood fractions, such as oleic acid for olive oil, α-linolenic acid for flaxseed (linseed) and rapeseed (canola) oils, and linoleic acid for sunflower oil. Additionally, hydroxytyrosol and its metabolites were the most promising distinctive BFIs for (extra) virgin olive oil. However, most of these components lack sufficient specificity to serve as BFIs. Therefore, additional studies are necessary to discover new candidate BFIs, as well as to further evaluate the specificity, sensitivity, dose-response relationships, and reproducibility of these candidate biomarkers and to eventually validate them in other populations. For the discovery of new candidate BFIs, an untargeted metabolomics approach may be the most effective strategy, whereas for increasing the specificity of the evaluation of food consumption, this could be a combination of different metabolites.
Postoperative delirium in patients aged 60 years or older with hip fractures adversely affects clinical and functional outcomes. The economic cost of delirium is estimated to be as high as USD 25,000 ...per patient, with a total budgetary impact between USD 6.6 to USD 82.4 billion annually in the United States alone. Forty percent of delirium episodes are preventable, and accurate risk stratification can decrease the incidence and improve clinical outcomes in patients. A previously developed clinical prediction model (the SORG Orthopaedic Research Group hip fracture delirium machine-learning algorithm) is highly accurate on internal validation (in 28,207 patients with hip fractures aged 60 years or older in a US cohort) in identifying at-risk patients, and it can facilitate the best use of preventive interventions; however, it has not been tested in an independent population. For an algorithm to be useful in real life, it must be valid externally, meaning that it must perform well in a patient cohort different from the cohort used to "train" it. With many promising machine-learning prediction models and many promising delirium models, only few have also been externally validated, and even fewer are international validation studies.
Does the SORG hip fracture delirium algorithm, initially trained on a database from the United States, perform well on external validation in patients aged 60 years or older in Australia and New Zealand?
We previously developed a model in 2021 for assessing risk of delirium in hip fracture patients using records of 28,207 patients obtained from the American College of Surgeons National Surgical Quality Improvement Program. Variables included in the original model included age, American Society of Anesthesiologists (ASA) class, functional status (independent or partially or totally dependent for any activities of daily living), preoperative dementia, preoperative delirium, and preoperative need for a mobility aid. To assess whether this model could be applied elsewhere, we used records from an international hip fracture registry. Between June 2017 and December 2018, 6672 patients older than 60 years of age in Australia and New Zealand were treated surgically for a femoral neck, intertrochanteric hip, or subtrochanteric hip fracture and entered into the Australian & New Zealand Hip Fracture Registry. Patients were excluded if they had a pathological hip fracture or septic shock. Of all patients, 6% (402 of 6672) did not meet the inclusion criteria, leaving 94% (6270 of 6672) of patients available for inclusion in this retrospective analysis. Seventy-one percent (4249 of 5986) of patients were aged 80 years or older, after accounting for 5% (284 of 6270) of missing values; 68% (4292 of 6266) were female, after accounting for 0.06% (4 of 6270) of missing values, and 83% (4690 of 5661) of patients were classified as ASA III/IV, after accounting for 10% (609 of 6270) of missing values. Missing data were imputed using the missForest methodology. In total, 39% (2467 of 6270) of patients developed postoperative delirium. The performance of the SORG hip fracture delirium algorithm on the validation cohort was assessed by discrimination, calibration, Brier score, and a decision curve analysis. Discrimination, known as the area under the receiver operating characteristic curves (c-statistic), measures the model's ability to distinguish patients who achieved the outcomes from those who did not and ranges from 0.5 to 1.0, with 1.0 indicating the highest discrimination score and 0.50 the lowest. Calibration plots the predicted versus the observed probabilities, a perfect plot has an intercept of 0 and a slope of 1. The Brier score calculates a composite of discrimination and calibration, with 0 indicating perfect prediction and 1 the poorest.
The SORG hip fracture algorithm, when applied to an external patient cohort, distinguished between patients at low risk and patients at moderate to high risk of developing postoperative delirium. The SORG hip fracture algorithm performed with a c-statistic of 0.74 (95% confidence interval 0.73 to 0.76). The calibration plot showed high accuracy in the lower predicted probabilities (intercept -0.28, slope 0.52) and a Brier score of 0.22 (the null model Brier score was 0.24). The decision curve analysis showed that the model can be beneficial compared with no model or compared with characterizing all patients as at risk for developing delirium.
Algorithms developed with machine learning are a potential tool for refining treatment of at-risk patients. If high-risk patients can be reliably identified, resources can be appropriately directed toward their care. Although the current iteration of SORG should not be relied on for patient care, it suggests potential utility in assessing risk. Further assessment in different populations, made easier by international collaborations and standardization of registries, would be useful in the development of universally valid prediction models. The model can be freely accessed at: https://sorg-apps.shinyapps.io/hipfxdelirium/ .
Level III, therapeutic study.
Purpose
To provide guidelines for all surgical specialists who deal with the open abdomen (OA) or the burst abdomen (BA) in adult patients both on the methods used to close the musculofascial layers ...of the abdominal wall, and regarding possible materials to be used.
Methods
The guidelines were developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach including publications up to January 2017. When RCTs were available, outcomes of interest were quantitatively synthesized by means of a conventional meta-analysis. When only observational studies were available, a meta-analysis of proportions was done. The guidelines were written using the AGREE II instrument.
Results
For many of the Key Questions that were researched, there were no high quality studies available. While some strong recommendations could be made according to GRADE, the guidelines also contain good practice statements and clinical expertise guidance which are distinct from recommendations that have been formally categorized using GRADE.
Recommendations
When considering the OA, dynamic closure techniques should be prioritized over the use of static closure techniques (strong recommendation). However, for techniques including suture closure, mesh reinforcement, component separation techniques and skin grafting, only clinical expertise guidance was provided. Considering the BA, a clinical expertise guidance statement was advised for dynamic closure techniques. Additionally, a clinical expertise guidance statement concerning suture closure and a good practice statement concerning mesh reinforcement during fascial closure were proposed. The role of advanced techniques such as component separation or relaxing incisions is questioned. In addition, the role of the abdominal girdle seems limited to very selected patients.
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