Scoring the EQ-HWB-S: can we do it without value sets? A non-parametric item response theory analysis.

BACKGROUND: Only one pilot value set (UK) is currently available for the EQ Health and Wellbeing Instrument short version (EQ-HWB-S). As an alternative to preference-weighted scoring, we examined whether a level summary score (LSS) is appropriate for the EQ-HWB-S using Mokken scaling analyses. METHODS: Data from patients, carers and the general population collected during the developmental phase of the EQ-HWB-S in Australia, US and UK were used, noting 3 of 9 items have since undergone revision. EQ-HWB-S data fit was examined using R package Mokken scaling's monotone homogeneity model, utilizing the automated item selection procedure (AISP) as well as Loevinger's scaling coefficients for items and the scale (HS). Manifest monotonicity was assessed by examining whether the cumulative probability for responses at or above each response level did not decrease across the summary score. RESULTS: EQ-HWB-S data were available for 3340 respondents: US = 903, Australia = 514 and UK = 1923. Mean age was 50 ± 18 and 1841 (55%) were female. AISP placed all 9 items of the EQ-HWB-S on a single scale when the lower bound was set to < 0.448. Strong scalability (HS = 0.561) was found for the EQ-HWB-S as a single scale. Stronger scales were formed by separating the psychosocial items (n = 6, HS = 0.683) and physical sensation items (n = 3, HS = 0.713). No violations of monotonicity were found except for the items mobility and daily activities for the subgroups with long-term conditions and UK subjects, respectively. DISCUSSION: As EQ-HWB-S items formed a strong scale and subscales based on Mokken analysis, LSS is a promising weighting-free approach to scoring.

Live and Dead Clostridium butyricum GKB7 Diminish Osteoarthritis Pain and Progression in Preclinical Animal Model.

Osteoarthritis (OA) is a degenerative joint disease primarily affecting the elderly. It is characterized by the progressive decline of joint cartilage and alterations in the underlying bone. Several probiotic strains have exhibited immunomodulatory and anti-inflammatory properties. Here, we examined the functions of live and dead Clostridium butyricum GKB7 (GKB7-L and GKB7-D) in a preclinical anterior cruciate ligament transection (ACLT)-enhanced OA procedure. Oral administration of GKB7-L and GKB7-D ameliorated ACLT-induced bone pain as assessed by weight-bearing behavioral testing but did not affect body weight. Micro-computed tomography (CT) results showed that GKB7-L and GKB7-D diminished ACLT-induced bone destruction and loss. GKB7-L and GKB7-D-enriched therapies also reduced ACLT-induced production of the pro-inflammatory cytokines interleukin (IL)-1ß and tumor necrosis factor (TNF)-α, as well as the chondrolytic factor matrix metalloproteinase (MMP)-3, leading to inhibition of aggrecan and collagen type II degradation and thereby blocking cartilage breakdown. We therefore suggest that oral supplementation with GKB7-L or GKB7-D can be beneficial in the prevention and treatment of OA.

Enhanced Recovery After Surgery (ERAS) Pathways for Aesthetic Breast Surgery: A Prospective Cohort Study on Patient-Reported Outcomes.

BACKGROUND: Patients' expectations of an anticipated timeline of recovery and fear of anesthesia in aesthetic breast surgery have not been studied. OBJECTIVE: This study aims to assess patient anxiety, expectations, and satisfaction after Enhanced Recovery after Surgery (ERAS) pathways for aesthetic breast surgery and the progress of postoperative recovery. MATERIALS AND METHODS: All consecutive patients who underwent aesthetic breast surgery between April 2021 and August 2022 were included in this single-center prospective cohort study. The ERAS protocol consists of more than 20 individual measures in the pre-, intra-, and postoperative period. Epidemiological data, expectations, and recovery were systematically assessed with standardized self-assessment questionnaires, including the International Pain Outcome Questionnaire (IPO), the BREAST-Q or BODY-Q, and data collection forms. RESULTS: In total, 48 patients with a median of 30 years of age were included. Patients returned to most daily activities within 5 days. Eighty-eight percent of patients were able to accomplish daily activities sooner than expected. The time of return to normal daily activities was similar across all procedure types. There was no statistically significant difference regarding postoperative satisfaction between patients who recovered slower (12%) and patients who recovered as fast or faster (88%) than anticipated (p=0.180). Patients reporting fear of anesthesia in the form of conscious sedation significantly diminished from 17 to 4% postoperatively (p<0.001). CONCLUSION: Enhanced Recovery after Surgery (ERAS) pathways for aesthetic breast surgery are associated with rapid recovery and high patient satisfaction. This survey study provides valuable insight into patients' concerns and perspectives that may be implemented in patient education and consultations to improve patient satisfaction following aesthetic treatments. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Danger Zones of the Gluteal Anatomy: Improving the Safety Profile of the Gluteal Fat Grafting.

INTRODUCTION: Knowledge of the vascular anatomy is critical to performing safe gluteal surgery. To date, only the course of the main blood vessels within the muscles has been outlined. These findings are based on MRI and CTA images that do not conform to a topographically standardized and normalized probability distribution. OBJECTIVES: The aim of this study was to develop a three-dimensional mapping of the gluteal zones of high vascular density in relation to anatomical landmarks. MATERIALS AND METHODS: This single-center retrospective cohort analysis comprised all consecutive patients who underwent cone-beam computed tomography (CBCT) scans between January 2016 and October 2021. The location of blood vessels in the gluteal region was allometrically normalized in relation to anatomical landmarks. Moreover, the caliber and area of the blood vessels were assessed. RESULTS: CBCT scans of 32 patients with an average age of 64 ± 12 years (range 34-87 years) were included. Fifty-three percent were female. The median [IQR] caliber of the intramuscular gluteal vessels was 1.47 [1.15-1.88] mm, significantly greater than that of the subcutaneous vessels 1.09 [0.72-1.44] mm (p < 0.001). Vascular density was higher intramuscularly, as 4.5% of the area of the muscle was occupied by blood vessels, as opposed to 0.3% in the adipose tissue. CONCLUSION: The analysis of the CBCT scans showed a higher vascular density and larger vessels intramuscularly. We, therefore, recommend the injection of autologous fat merely to the subcutaneous plane. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

TRPV1+ neurons alter Staphylococcus aureus skin infection outcomes by affecting macrophage polarization and neutrophil recruitment.

BACKGROUND: The interaction between the nervous system and the immune system can affect the outcome of a bacterial infection. Staphylococcus aureus skin infection is a common infectious disease, and elucidating the relationship between the nervous system and immune system may help to improve treatment strategies. RESULTS: In this study, we found that the local release of calcitonin gene-related peptide (CGRP) increased during S. aureus skin infection, and S. aureus could promote the release of CGRP from transient receptor potential cation channel subfamily V member 1 (TRPV1+) neurons in vitro. The existence of TRPV1+ neurons inhibited the recruitment of neutrophils to the infected region and regulated the polarization of macrophages toward M2 while inhibiting polarization toward M1. This reduces the level of inflammation in the infected area, which aggravates the local infection. Furthermore, this study demonstrates that TRPV1 may be a target for the treatment of S. aureus skin infections and that botulinum neurotoxin A (BoNT/A) and BIBN4096 may reverse the inhibited inflammatory effect of CGRP, making them potential therapeutics for the treatment of skin infection in S. aureus. CONCLUSIONS: In S. aureus skin infection, TRPV1+ neurons inhibit neutrophil recruitment and regulate macrophage polarization by releasing CGRP. BoNT/A and BIBN4096 may be potential therapeutic agents for S. aureus skin infection.

Predicting complicated appendicitis is possible without the use of sectional imaging-presenting the NoCtApp score.

PURPOSE: Appendicitis is among the most common acute conditions treated by general surgery. While uncomplicated appendicitis (UA) can be treated delayed or even non-operatively, complicated appendicitis (CA) is a serious condition with possible long-term morbidity that should be managed with urgent appendectomy. Distinguishing both conditions is usually done with computed tomography. The goal of this study was to develop a model to reliably predict CA with widespread available clinical and laboratory parameters and without the use of sectional imaging. METHODS: Data from 1132 consecutive patients treated for appendicitis between 2014 and 2021 at a tertiary care hospital were used for analyses. Based on year of treatment, the data was divided into training (n = 696) and validation (n = 436) samples. Using the development sample, candidate predictors for CA-patient age, gender, body mass index (BMI), American Society of Anesthesiologist (ASA) score, duration of symptoms, white blood count (WBC), total bilirubin and C-reactive protein (CRP) on admission and free fluid on ultrasound-were first investigated using univariate logistic regression models and then included in a multivariate model. The final development model was tested on the validation sample. RESULTS: In the univariate analysis age, BMI, ASA score, symptom duration, WBC, bilirubin, CRP, and free fluid each were statistically significant predictors of CA (each p < 0.001) while gender was not (p = 0.199). In the multivariate analysis BMI and bilirubin were not predictive and therefore not included in the final development model which was built from 696 patients. The final development model was significant (x2 = 304.075, p < 0.001) with a sensitivity of 61.7% and a specificity of 92.1%. The positive predictive value (PPV) was 80.4% with a negative predictive value (NPV) of 82.0%. The receiver operator characteristic of the final model had an area under the curve of 0.861 (95% confidence interval 0.830-0.891, p < 0.001. We simplified this model to create the NoCtApp score. Patients with a point value of ≤ 2 had a NPV 95.8% for correctly ruling out CA. CONCLUSIONS: Correctly identifying CA is helpful for optimizing patient treatment when they are diagnosed with appendicitis. Our logistic regression model can aid in correctly distinguishing UA and CA even without utilizing computed tomography.

Enhanced Recovery After Aesthetic Breast Surgery Under Sedation, Intercostal Block and Tumescent Anaesthesia: A Prospective Cohort Study of the Early Postoperative Phase.

BACKGROUND: Comfort and recovery are major concerns of patients seeking aesthetic surgery. This study aimed to assess postoperative pain and recovery after outpatient breast surgery under sedation, intercostal block, and local anaesthesia. METHODS: This prospective cohort study included all consecutive patients who underwent aesthetic breast surgery between April 2021 and August 2022. Epidemiological data, anaesthesia, pain, and patients' satisfaction were systematically assessed with standardized self-assessment questionnaires. RESULTS: Altogether, 48 patients [median (IQR) age: 30 (36-25)] were included. The most frequent surgery was mastopexy. 69% of surgeries involved additional procedures. The mean intercostal block and local anaesthesia time was 15 min. Patients received a median (IQR) of 19 (34-2) mg/kg lidocaine and 2.3 (2.5-2.0) mg/kg ropivacaine. The median (IQR) consumption of propofol and alfentanil was, respectively, 4.89 (5.48-4.26) mg/kg/h and 0.27 (0.39-0.19) µg/kg/min. No conversion to general anaesthesia or unplanned hospital admission occurred. Patients were discharged after a median (IQR) of 2:40 (3:43-1:58) hours. Within the first 24 postoperative hours, 17% required once an antiemetic medication and 38% an opioid. Patients were very satisfied with the anaesthesia and 90% of the patients had not wished more analgesia in the first 24 h. CONCLUSIONS: Aesthetic breast surgery under sedation, intercostal block, and tumescent anaesthesia can safely be performed as an ambulatory procedure and is associated with minimal intra- and postoperative opioid consumption and high patient satisfaction. These data may be used to inform patients and clinicians and improve the overall quality of care. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Definitions of Abnormal Breast Size and Asymmetry: A Cohort Study of 400 Women.

BACKGROUND: Macromastia, micromastia and breast asymmetry have an impact on health and quality of life. However, there is scarce information addressing breast size and asymmetry frequency distribution in reference populations. OBJECTIVE: The current study aims to identify factors that influence breast size and symmetry and classifies abnormal breast sizes and breast asymmetries in an adult German population. METHODS: Breast base dimensions, breast volume, symmetry, and other breast anthropometric parameters of 400 German female patients were determined in a retrospective review of the MRI archives at our institution. Professional medical MRI-segmentation software was used for volume measurement. RESULTS: A total of 400 Patients were retrospectively enrolled. The patients had a mean age of 50 ± 12 years (min: 24; max: 82), mean BMI of 25.0 ± 5.0 (min: 14.7, max: 45.6), and a mean total breast volume of 976 ml (right: 973 ml, min: 64, max: 4777; left: 979 ml, min: 55, max: 4670). The strongest correlation of breast volume was observed with BMI (r = 0.834, p < 0.001), followed by breast base width (r = 0.799, p < 0.001). Smaller breasts have higher breast volume asymmetry ratios (r = - 0.124, p < 0.014). For a BMI between 18.5 and 24.9 kg/m2, micromastia is defined by breast volumes below 250 ml (5th percentile) and macromastia by volumes above 1250 ml (95th percentile). Abnormal breast volume asymmetry (< 5th and > 95th percentile) is equivalent to an absolute difference of approximately 25% relative to the smallest side (bidirectional asymmetry ratio 5th percentile - 19%; 95th percentile 26%). CONCLUSION: This study provides normative data of German women, as well as selected size-for-BMI percentiles and asymmetry ratio percentiles. The normative data may help to establish transparent and objective coverage criteria for health insurances. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Quantification of Breast Volume According to age and BMI: A Three-Dimensional MRI Analysis of 400 Women.

OBJECTIVE: Breast size alteration is the most common aesthetic surgical procedure worldwide. This study aimed to assess the correlation between breast volume and BMI or age. MATERIALS AND METHODS: The analyses were conducted utilizing 400 patients selected by a retrospective review of the archives at our institution. Epidemiological data and medical history were assessed. Adjusting for the age and BMI of patient from previously described cohorts, we calculated mean breast volumes per side and differences from the upper and lower percentiles to the mean volumes. RESULTS: The patients had a median BMI of 23.5 (range: 14.7-45.6) and a median age of 51 (range: 24-82). The average total breast volume increased strongly with BMI (r=0.834, p<0.01) and moderately with age (r=0.305, p<0.01). Within a BMI range of 18-24, breast volumes in the 8th and 18th percentile differ on average by about 50 ml. One BMI unit increase in women with breast sizes in the 10th percentile accounts for a breast volume difference of about 30 ml. CONCLUSION: BMI strongly correlates with breast size. To achieve natural results, preoperative consultation and planning of aesthetic and reconstructive breast surgery must recognize BMI as a major determinant of average breast size. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Combining EQ-5D-5L items into a level summary score: demonstrating feasibility using non-parametric item response theory using an international dataset.

BACKGROUND: The EQ-5D-5L is a well-established health questionnaire that estimates health utilities by applying preference-based weights. Limited work has been done to examine alternative scoring approaches when utility weights are unavailable or inapplicable. We examined whether the Mokken scaling approach can elucidate 1) if the level summary score is appropriate for the EQ-5D-5L and 2) an interpretation of such a score. METHODS: The R package "mokken" was used to assess monotonicity (scaling coefficients H, automated item selection procedure) and manifest invariant item ordering (MIIO: paired item response functions [IRF], HT). We used a rich dataset (the Multiple Instrument Comparison, MIC) which includes EQ-5D-5L data from six Western countries. RESULTS: While all EQ-5D-5L items demonstrated monotonicity, the anxiety/depression (AD) item had weak scalability (Hi = 0.377). Without AD, scalability improved from Hs = 0.559 to Hs = 0.714. MIIO revealed that the 5 items can be ordered, and the ordering is moderately accurate in the MIC data (HT = 0.463). Excluding AD, HT improves to 0.743. Results were largely consistent across disease and country subgroups. DISCUSSION: The 5 items of the EQ-5D-5L form a moderate to strong Mokken scale, enabling persons to be ordered using the level summary score. Item ordering suggests that the lower range of the score represents mainly problems with pain and anxiety/depression, the mid-range indicates additional problems with mobility and usual activities, and middle to higher range of scores reveals additional limitations with self-care. Scalability and item ordering are even stronger when the anxiety/depression item is not included in the scale.

What difference does multiple imputation make in longitudinal modeling of EQ-5D-5L data? Empirical analyses of simulated and observed missing data patterns.

PURPOSE: Although multiple imputation is the state-of-the-art method for managing missing data, mixed models without multiple imputation may be equally valid for longitudinal data. Additionally, it is not clear whether missing values in multi-item instruments should be imputed at item or score-level. We therefore explored the differences in analyzing the scores of a health-related quality of life questionnaire (EQ-5D-5L) using four approaches in two empirical datasets. METHODS: We used simulated (GR dataset) and observed missingness patterns (ABCD dataset) in EQ-5D-5L scores to investigate the following approaches: approach-1) mixed models using respondents with complete cases, approach-2) mixed models using all available data, approach-3) mixed models after multiple imputation of the EQ-5D-5L scores, and approach-4) mixed models after multiple imputation of EQ-5D 5L items. RESULTS: Approach-1 yielded the highest estimates of all approaches (ABCD, GR), increasingly overestimating the EQ-5D-5L score with higher percentages of missing data (GR). Approach-4 produced the lowest scores at follow-up evaluations (ABCD, GR). Standard errors (0.006-0.008) and mean squared errors (0.032-0.035) increased with increasing percentages of simulated missing GR data. Approaches 2 and 3 showed similar results (both datasets). CONCLUSION: Complete cases analyses overestimated the scores and mixed models after multiple imputation by items yielded the lowest scores. As there was no loss of accuracy, mixed models without multiple imputation, when baseline covariates are complete, might be the most parsimonious choice to deal with missing data. However, multiple imputation may be needed when baseline covariates are missing and/or more than two timepoints are considered.

Safety Assessment of HEA-Enriched Cordyceps cicadae Mycelium: A Randomized Clinical Trial.

Objective:Cordyceps cicadae, a medicinal fungus, is assessed as having many functions: anti-cancer, anti-fatigue, anti-aging, immune-boosting, renal and liver protection. Since the industrial production of C. cicadae mycelium consistently manufactures bioactive compounds superior to wild fruiting bodies, there is a need to confirm the toxicity of liquid fermented C. cicadae mycelium. Studies showed the toxicity evaluation of C. cicadae mycelium in animal models, but safety reports in clinical studies are scarce. As such, a safety assessment of oral N6-(2-hydroxyethyl) adenosine (HEA-enriched) C. cicadae mycelium in humans is provided here.Method: After 49 participants ingested granules of 1.05 g of freeze-dried C. cicadae mycelium once a day for 3 months, their blood samples were collected at the beginning and end of the experiment for analysis.Results: There were no significant differences between the initial and final measurements in renal and liver function. Also, there was no influence on blood electrolytes as well as blood lipid levels. In clinical observation, there were also no side effects or adverse feelings mentioned by participants.Conclusion: These results suggested that HEA-enriched C. cicadae mycelium produced by liquid fermentation is safe and can be developed as a functional health food.

Surface-enhanced Raman scattering (SERS) spectroscopy on localized silver nanoparticle-decorated porous silicon substrate.

Surface-enhanced Raman scattering (SERS) spectroscopy is a rapid and non-destructive optical detection method that has been applied in various applications. Recently, three-dimensional (3D) substrate-based silicon nanostructures have been widely used as SERS substrates due to their high detection sensitivity, repeatability, and reusability. This paper uses a simple and low-cost electroless etching deposition process to generate silver nanoparticle-decorated porous silicon (Ag-PS) substrates. We propose a contact deposition process to generate localized Ag-PS (LocAg-PS) for SERS analysis. Due to the hydrophilic LocAg-PS pad on the hydrophobic PS background, the sample droplets self-aligned to the predefined LocAg-PS pads and condensed into a higher local concentration for high sensitivity SERS detection without extensive search for the hot spot. The effects of critical fabrication parameters and SERS analysis on the LocAg-PS surface were evaluated.

Translation and adaptation of the German version of the Veterans Rand-36/12 Item Health Survey.

BACKGROUND: The translated and culturally adapted German version of the Veterans Rand 36 Items Health Survey (VR-36), and its short form, the VR-12 counterpart, were validated in a German sample of orthopedic (n = 399) and psychosomatic (n = 292) inpatient rehabilitation patients. METHODS: The instruments were analyzed regarding their acceptance, distributional properties, validity, responsiveness and ability to discriminate between groups by age, sex and clinically specific groups. Eligible study participants completed the VR-36 (n = 169) and the VR-12 (n = 177). They also completed validated patient-reported outcome measures (PROs) including the Euroqol-5 Dimensions 5 Level (EQ-5D-5L); Depression, Anxiety and Stress Scale (DASS); Hannover Functional Abilities Questionnaire (HFAQ); and CDC Healthy Days. The VR-12 and the VR-36 were compared to the reference instruments MOS Short Form-12 Items Health Survey (SF-12) version 1.0 and MOS Short Form-36 Items Health Survey (SF-36) version 1.0, using percent of completed items, distributional properties, correlation patterns, distribution measures of known groups validity, and effect size measures. RESULTS: Item non-response varied between 1.8%/1.1% (SFVR-36/RESF-36) and 6.5%/8.6% (GHVR-36/GHSF-36). PCS was normally distributed (Kolmogorov-Smirnov tests: p > 0.05) with means, standard deviations and ranges very similar between SF-36 (37.5 ± 11.7 [13.8-66.1]) and VR-36 (38.5 ± 10.1 [11.7-67.8]), SF-12 (36.9 ± 10.9 [15.5-61.6]) and VR-12 (36.2 ± 11.5 [12.7-59.3]). MCS was not normally distributed with slightly differing means and ranges between the instruments (MCSVR-36: 36.2 ± 14.2 [12.9-66.6], MCSSF-36: 39.0 ± 15.6 [2.0-73.2], MCSVR-12: 37.2 ± 13.8 [8.4-70.2], MCSSF-12: 39.0 ± 12.3 [17.6-65.4]). Construct validity was established by comparing correlation patterns of the MCSVR and PCSVR with measures of physical and mental health. For both PCSVR and MCSVR there were moderate (≥ 0.3) to high (≥ 0.5) correlations with convergent (PCSVR: 0.55-0.76, MCSVR: 0.60-0.78) and small correlations (< 0.1) with divergent (PCSVR: < 0.12, MCSVR: < 0.16) self-report measures. Known-groups validity was demonstrated for both VR-12 and VR-36 (MCS and PCS) via comparisons of distribution parameters with significant higher mean PCS and MCS scores in both VR instruments found in younger patients with fewer sick days in the last year and a shorter duration of rehabilitation. CONCLUSIONS: The psychometric analysis confirmed that the German VR is a valid and reliable instrument for use in orthopedic and psychosomatic rehabilitation. Yet further research is needed to evaluate its usefulness in other populations.

Psychometric properties of the EQ-5D-5L: a systematic review of the literature.

PURPOSE: Although the EQ-5D has a long history of use in a wide range of populations, the newer five-level version (EQ-5D-5L) has not yet had such extensive experience. This systematic review summarizes the available published scientific evidence on the psychometric properties of the EQ-5D-5L. METHODS: Pre-determined key words and exclusion criteria were used to systematically search publications from 2011 to 2019. Information on study characteristics and psychometric properties were extracted: specifically, EQ-5D-5L distribution (including ceiling and floor), missing values, reliability (test-retest), validity (convergent, known-groups, discriminate) and responsiveness (distribution, anchor-based). EQ-5D-5L index value means, ceiling and correlation coefficients (convergent validity) were pooled across the studies using random-effects models. RESULTS: Of the 889 identified publications, 99 were included for review, representing 32 countries. Musculoskeletal/orthopedic problems and cancer (n = 8 each) were most often studied. Most papers found missing values (17 of 17 papers) and floor effects (43 of 48 papers) to be unproblematic. While the index was found to be reliable (9 of 9 papers), individual dimensions exhibited instability over time. Index values and dimensions demonstrated moderate to strong correlations with global health measures, other multi-attribute utility instruments, physical/functional health, pain, activities of daily living, and clinical/biological measures. The instrument was not correlated with life satisfaction and cognition/communication measures. Responsiveness was addressed by 15 studies, finding moderate effect sizes when confined to studied subgroups with improvements in health. CONCLUSIONS: The EQ-5D-5L exhibits excellent psychometric properties across a broad range of populations, conditions and settings. Rigorous exploration of its responsiveness is needed.

Multifunctional lipid-based nanocarriers with antibacterial and anti-inflammatory activities for treating MRSA bacteremia in mice.

BACKGROUND: Bacteremia-induced sepsis is a leading cause of mortality in intensive care units. To control a bacterial infection, an immune response is required, but this response might contribute to organ failure. Kidneys are one of the main organs affected by bacteremia. Combination therapies with antibacterial and anti-inflammatory effects may be beneficial in treating bacteremia. This study aimed to develop nanostructured lipid carriers (NLCs) loaded with ciprofloxacin and rolipram that exert a combination of anti-methicillin-resistant Staphylococcus aureus (MRSA) and anti-inflammatory effects. Retinol was incorporated into the nanoparticles to transport retinol-binding protein 4 (RBP4) to the kidneys, which abundantly express RBP receptors. The NLCs were fabricated by high-shear homogenization and sonication, and neutrophils were used as a model to assess their anti-inflammatory effects. Mice were injected with MRSA to establish a model of bacteremia with organ injury. RESULTS: The mean nanoparticle size and zeta potential of the NLCs were 171 nm and - 39 mV, respectively. Ciprofloxacin (0.05%, w/v) and rolipram (0.02%) achieved encapsulation percentages of 88% and 96%, respectively, in the nanosystems. The minimum bactericidal concentration of free ciprofloxacin against MRSA increased from 1.95 to 15.63 µg/ml when combined with rolipram, indicating a possible drug-drug interaction that reduced the antibacterial effect. Nanoparticle inclusion promoted the anti-MRSA activity of ciprofloxacin according to time-kill curves. The NLCs were found to be largely internalized into neutrophils and exhibited superior superoxide anion inhibition than free drugs. Retinol incorporation into the nanocarriers facilitated their efficient targeting to the kidneys. The NLCs significantly mitigated MRSA burden and elastase distribution in the organs of MRSA-infected animals, and the greatest inhibition was observed in the kidneys. Bacterial clearance and neutrophil infiltration suppression attenuated the bacteremia-induced cytokine overexpression, leading to an improvement in the survival rate from 22% to 67%. CONCLUSIONS: The dual role of our NLCs endowed them with greater efficacy in treating MRSA bacteremia than that of free drugs.

Exploring the Internal Structure of the EQ-5D Using Non-Preference-Based Methods.

BACKGROUND: When the EuroQol EQ-5D is applied in settings other than resource allocation, a non-preference-based score may be more appropriate than societal, preference-weighted utility. To develop a psychometric score for the EQ-5D, its structural relationship, ie, how the 5 items/dimensions interrelate, must be understood to inform appropriate methods of summarizing the instrument. OBJECTIVES: To explore psychometrically derived approaches of elucidating the 5-level EQ-5D (EQ-5D-5L) item structure. METHODS: Three measurement models were assessed. All 5 items were modeled as reflective indicators using confirmatory factor analysis. EQ-5D-5L items were conceptualized as formative indicators, and other health scales (eg, the short form 36 health survey) were conceptualized as reflective indicators in Multiple Indicators Multiple Causes models (external MIMIC). The EQ-5D-5L items were modeled as a combination of formative and reflective indicators in internal MIMIC models. Results across 9 data sets from various countries and patient groups were examined to determine their robustness. RESULTS: All items loaded well (0.63-0.96) in the confirmatory factor analysis except for anxiety/depression (0.20-0.66, excluding 1 outlier). The model fit statistics of the external MIMIC models were poor, and the coefficients of the Self-Care dimension were small. The internal MIMIC model with Mobility, Pain/Discomfort, and Anxiety/Depression as formative indicators and Self-Care and Usual Activities as reflective indicators fit best. The model results of the Spanish valuation data set were outliers. CONCLUSIONS: Although there were some variations in results across subgroups, the relationship between the items remained robust. The evidence calls for testing of formative/reflective combination approaches to summarize the EQ-5D-5L.

Riverine Microplastic Pollution in the Pearl River Delta, China: Are Modeled Estimates Accurate?

Plastic pollution has caused increasing global concern. Currently, model estimates of the riverine plastic inputs to the global oceans based on the concept of Mismanaged Plastic Waste (MPW) varied substantially, and no field measurements of riverine inputs were available. We conducted sampling at the eight major river outlets of the Pearl River Delta, South China with rapid economic growth and urbanization to provide field measured data for fine-tuning modeling results. Floating microplastics (MPs) were collected with a Manta net (mesh size of 0.33 mm) five times during 2018. Microplastic particles (0.3-5.0 mm) widely occurred in all sampling sites. The number and mass concentrations of MPs were in the ranges of 0.005-0.7 particles m-3 and 0.004-1.28 mg m-3 and were positively correlated with water discharges. The annual riverine input of MPs from the Pearl River Delta was estimated at 39 billion particles or 66 tons, which converts to 2400-3800 tons of plastic debris based on calculations described in Text S2. These values were substantially below the MPW-based model estimates (91,000-170,000 tons). The large difference between measured and modeling results may have derived from the large uncertainty in the MPW values assigned to the world's countries/regions.

Utility of Contrast-Enhanced Ultrasound for the Assessment of Skeletal Muscle Perfusion in Diabetes Mellitus: A Meta-Analysis.

BACKGROUND This study evaluated the effectiveness of contrast-enhanced ultrasonography for the assessment of skeletal muscle perfusion in diabetes mellites. MATERIAL AND METHODS Electronic databases (Embase, Google Scholar, Ovid, and PubMed) were searched for required articles, and studies were selected by following pre-determined eligibility criteria. Meta-analyses of mean differences or standardized mean differences (SMD) were performed to evaluate the significance of difference in contrast-enhanced ultrasonography measured muscle perfusion indices between patients with diabetes and healthy individuals or between basal and final values of perfusion indices after insulin manipulation or physical exercise in patients with diabetes or healthy individuals. RESULTS There were 15 studies included, with 279 patients with diabetes and 230 healthy individuals in total. The age of the study patients with diabetes mellitus was 55.8 years (95% CI: 49.6 years, 61.9 years) and these patients had disease for 11.4 years (95% CI: 7.7 years, 15.1 years). The percentage of males in group of patients with diabetes was 66% (95% CI: 49%, 84%), body mass index was 29.4 kg/m² (95% CI: 26.5 kg/m², 32.3 kg/m²), hemoglobin A1c was 7.3% (95% CI: 6.7%, 7.9%), and fasting plasma glucose was 149 kg/m² (95% CI: 118 kg/m², 179 kg/m²). Time to peak intensity after provocation was significantly higher in patients with diabetes than in healthy individuals (SMD 1.18 [95% CI: 0.60, 1.76]; P<0.00001). In patients with diabetes, insulin administration did not improve contrast-enhanced ultrasonography measured muscle perfusion indices but exercise improved muscle perfusion but at a level that was statistically non-significant (SMD between basal and post-exercise values (1.03 [95% CI: -0.14, 2.20]; P=0.08). In healthy individuals, lipids in addition to insulin administration was associated with significantly reduced blood volume and blood flow. CONCLUSIONS Our review showed that the use of contrast-enhanced ultrasonography showed that diabetes mellitus was associated with altered muscle perfusion in which insulin-mediated metabolic changes played an important role.

Clinical significance of hyaluronan levels and its pro-osteogenic effect on mesenchymal stromal cells in myelodysplastic syndromes.

BACKGROUND: Hyaluronan (HA), a major component of the extracellular matrix, has been proven to play a crucial role in tumor progression. However, it remains unknown whether HA exerts any effects in myelodysplastic syndromes (MDS). METHODS: A total of 82 patients with MDS and 28 healthy donors were investigated in this study. We firstly examined the bone marrow (BM) serum levels of HA in MDS by radioimmunoassay. Then we determined HA production and hyaluronan synthase (HAS) gene expression in BM mesenchymal stromal cells (MSC) and mononuclear cells derived from MDS patients. Finally, we investigated the effects of HA on osteogenic differentiation of MSC. RESULTS: The BM serum levels of HA was increased in higher-risk MDS patients compared to normal controls. Meanwhile, patients with high BM serum HA levels had significantly shorter median survival than those with low HA levels. Moreover, the HA levels secreted by MSC was elevated in MDS, especially in higher-risk MDS. In addition, HAS-2 mRNA expression was also up-regulated in higher-risk MDS-MSC. Furthermore, we found that MSC derived from MDS patients with high BM serum HA levels had better osteogenic differentiation potential. Moreover, MSC cultured in HA-coated surface presented enhanced osteogenic differentiation ability. CONCLUSIONS: Our results show that elevated levels of BM serum HA are related to adverse clinical outcome in MDS. Better osteogenic differentiation of MSC induced by HA may be implicated in the pathogenesis of MDS.