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Purpose: Pitch variations (tone productions) have been reported as a measure to differentiate Cantonese-speaking children with and without childhood apraxia of speech (CAS). This study aims to examine fundamental frequency (F0) changes within syllables and the effects of syllable structure, lexical status, and syllable positions on F0 in Cantonese-speaking preschool children with and without CAS. Method: Six children with CAS, six children with non-CAS speech sound disorder plus language disorder (S&LD), 22 children with speech sound disorder only (SSD), and 63 children with typical speech-language development (TD) performed the tone sequencing task (TST). Growth curve analysis was employed to analyze and compare the F0 values within syllables with three Cantonese tones (high level, high rising, and low falling). The analysis considered the effects of syllable structure (vowel and consonant–vowel), lexical status (word and nonword), and syllable position (initial, medial, and final) on F0, as well as comparisons within and between groups. Results: Within each group, the effects of syllable structure and position on F0 values were found with different patterns. Between-group comparisons showed that the CAS group had reduced F0 contrasts. The CAS group could be differentiated from the control groups based on interactions of F0 with syllable structure and position, but not lexical status. The dissimilarity of F0 values detected between the CAS and SSD/TD groups was more prominent than that observed between the CAS and S&LD groups. Conclusions: This study demonstrated that Cantonese-speaking children with CAS had difficulty in varying F0 within syllables as compared to those without CAS, suggesting pitch variation difficulty and language-specific impairment profiles in CAS. Future investigations of objective measures for identifying Cantonese speakers with CAS and cross-linguistic investigations using growth curve analysis and the TST are suggested. [ABSTRACT FROM AUTHOR]

We use an ensemble Monte Carlo transport approach to calculate and compare the impact ionization and avalanche photodiode excess noise characteristics in three materials—a band-engineered InAlAs/InAsSb type-II superlattice, bulk InAs, and HgCdTe—all with an identical bandgap of 370 meV at 250 K. The electronic band structures and energy–momentum conservation conditions are used to calculate the impact ionization rates, carrier histories, multiplication gains, and excess noise characteristics. The calculated impact ionization coefficients and excess noise factors indicate a single carrier species multiplication in all three materials under low applied electric fields. We find the ratio of impact ionization coefficients to be k = 7 × 10 − 4 for InAs and 3 × 10 − 4 for HgCdTe under an applied field of 50 kV/cm, and the superlattice to be k < 10 − 6 at fields up to 400 kV/cm. The bulk materials experience avalanche breakdown as the applied field increases, transitioning to Geiger mode behavior at gains above 10 3 for InAs and 10 4 for HgCdTe. However, this breakdown is absent from the superlattice at the highest fields considered in this study due to hole confinement, indicating superior performance compared to the bulk materials. Our results demonstrate the role of superlattice band engineering in designing quality avalanche photodiode materials. [ABSTRACT FROM AUTHOR]

Children and adolescents are among the most vulnerable to developing posttraumatic stress in the aftermath of a disaster. This study investigated posttraumatic stress among students attending surrounding primary and secondary schools following the 2014 Hazelwood mine fire in the Latrobe Valley region of Australia. Posttraumatic stress levels of students (n = 323) attending smoke-exposed schools (n = 20) were assessed 16–21 months after the event using the Children's Revised Impact of Events Scale (CRIES). The mean CRIES total score of students attending these schools was 17.22, suggesting an overall moderate level of posttraumatic stress associated with the mine fire. Across the sample, 22% of the students (n = 23) had a CRIES score of ≥30, indicative of posttraumatic stress at a level warranting clinical concern. Students attending schools located closer to the mine (Morwell Schools) experienced significantly greater levels of posttraumatic stress (CRIES M = 21.63) compared with students attending schools located further away (Non-Morwell Schools; CRIES M = 14.70). This difference appeared to have been primarily driven by higher scoring among Morwell students on the Arousal symptom domain of the CRIES. The mean CRIES score of primary school students (M = 23.18) was over double that of secondary school students (M = 10.30) regardless of the proximity of their school to the smoke event; however, this difference did not reach statistical significance. These findings highlight the need for public health responses following disasters that include targeted mental health support for child and adolescent age-groups. [ABSTRACT FROM AUTHOR]

Summary: Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) is endemic to parts of Asia and overexpression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α are common in NPC. Anti-vascular agents have known clinical activity in patients with recurrent/ metastatic NPC and in this study, we investigated the anti-tumor effect of BI 836880, a humanized bispecific nanobody against VEGF and angiopoietin-2 (Ang2), in preclinical models of EBV-positive and EBV-negative NPC. The efficacy of BI 836880 was also compared with bevacizumab, a recombinant humanized monoclonal antibody against VEGF. We found that BI 836880 could exert growth-inhibitory effect on endothelial cells (HUVEC-C) and the EBV-negative NPC cell line (HK1), but to a lesser extent in the EBV-positive NPC cell lines, C17C and C666-1. In patients-derived xenograft (PDX) models of NPC - Xeno-2117 and Xeno-666, BI 836880 could suppress tumor growth and Ki67, as well as induce tumor necrosis and reduce microvessel density. Moreover, treatment with BI 836880 increased the level of macrophage infiltration in both PDX tumor models of NPC, suggesting that BI 836880 may exert immunomodulatory effect on the NPC immune microenvironment. When compared with bevacizumab, BI 836880 appeared to show at least comparable activity as bevacizumab in terms of its anti-proliferative and anti-angiogenic effects. This study showed that BI 836880 has anti-proliferative, anti-angiogenic and possibly immunomodulatory effect in clinical models of NPC, therefore the dual targeting of VEGF and Ang2 signaling in NPC should be further investigated. [ABSTRACT FROM AUTHOR]

Simple Summary: Instead of extensive conventional surgical resection, early-stage colorectal cancers are now often primarily treated using specialized local resection techniques, such as the endoscopic submucosal dissection (ESD). Sometimes after ESD a regular surgical resection is still needed. However, the impact of ESD on this surgery has not been well studied yet. This study aimed to investigate if ESD affected the safety and outcome of completion surgery. Outcomes of two groups of patients were compared: one consisting of patients who only had an upfront surgical resection and another consisting of patients who had an ESD followed by a surgical resection. Results showed that safety and outcome of surgery were similar in both groups. This means that ESD does not significantly increase negative outcomes of surgery. This knowledge empowers doctors to perform ESD as a first treatment option for early-stage colorectal cancers. T1 colorectal cancers (T1CRC) are increasingly being treated by endoscopic submucosal dissection (ESD). After ESD of a T1CRC, completion surgery is indicated in a subgroup of patients. Currently, the influence of ESD on surgical morbidity and mortality is unknown. The aim of this study was to compare 90-day morbidity and mortality of completion surgery after ESD to primary surgery. The completion surgery group consisted of suspected T1CRC patients from a multicenter prospective ESD database (2014–2020). The primary surgery group consisted of pT1CRC patients from a nationwide surgical registry (2017–2019). Patients with rectal or sigmoidal cancers were selected. Patients receiving neoadjuvant therapy were excluded. Propensity score adjustment was used to correct for confounders. In total, 411 patients were included: 54 in the completion surgery group (39 pT1, 15 pT2) and 357 in the primary surgery group with pT1CRC. Adverse event rate was 24.1% after completion surgery and 21.3% after primary surgery. After completion surgery 90-day mortality did not occur, though one patient died in the primary surgery group. After propensity score adjustment, lymph node yield did not differ significantly between the groups. Among other morbidity-related outcomes, stoma rate (OR 1.298 95%-CI 0.587-2.872, p = 0.519) and adverse event rate (OR 1.162; 95%-CI 0.570-2.370, p = 0.679) also did not differ significantly. A subgroup analysis was performed in patients undergoing rectal surgery. In this subgroup (37 completion and 136 primary surgery), these morbidity outcomes also did not differ significantly. In conclusion, this study suggests that ESD does not compromise morbidity or 90-day mortality of completion surgery. [ABSTRACT FROM AUTHOR]

(1) Background: Percutaneous microwave ablation (MWA) is an accepted treatment of non-operative liver cancer. This study compares the ablation zones of four commercially available 2.45 GHz MWA systems (Emprint, Eco, Neuwave, and Solero) in an ex vivo porcine liver model. (2) Methods: Ex vivo porcine livers (n = 85) were obtained. Two ablation time setting protocols were evaluated, the manufacturer's recommended maximum time and a 3 min time, performed at the manufacturer-recommended maximum power setting. A total of 236 ablation samples were created with 32 (13.6%) samples rejected. A total of 204 samples were included in the statistical analysis. (3) Results: For single-probe protocols, Emprint achieved ablation zones with the largest SAD. Significant differences were found in all comparisons for the 3 min time setting and for all comparisons at the 10 min time setting except versus Neuwave LK15 and Eco. Emprint produced ablation zones that were also significantly more spherical (highest SI) than the single-probe ablations from all other manufacturers. No statistical differences were found for ablation shape or SAD between the single-probe protocols for Emprint and the three-probe protocols for Neuwave. (4) Conclusions: The new Emprint HP system achieved large and spherical ablation zones relative to other 2.45 GHz MWA systems. [ABSTRACT FROM AUTHOR]

Renin–angiotensin–aldosterone system inhibitors (RAASi) are associated with improved survival outcomes in patients receiving immune checkpoint inhibitors (ICIs), but the data on the response to treatment and tumour-based endpoints across different tumour types are unknown. We carried out a retrospective study at two tertiary referral centres in Taiwan. All adult patients treated with ICIs between January 2015 and December 2021 were included. The primary outcome was overall survival and the secondary outcomes were progression-free survival (PFS) and clinical benefit rates. In total, 734 patients were enrolled in our study, of which 171 were RAASi users and 563 were non-users. Compared with non-users, RAASi users had a longer median overall survival [26.8 (interquartile range 11.3–not reached) versus 15.2 (interquartile range 5.1–58.4) months, P < 0.001] and PFS [12.2 (interquartile range 3.9–34.5) versus 5.0 (interquartile range 2.2–15.2) months, P < 0.001]. In univariate Cox proportional hazard analyses, the use of RAASi was associated with a 40% reduction in the risk of mortality [hazard ratio 0.58 (95% confidence interval 0.44–0.76), P < 0.001] and disease progression [hazard ratio 0.62 (95% confidence interval 0.50–0.77), P < 0.001]. The association remained significant after adjusting for underlying comorbidities and cancer therapy in multivariate Cox analyses. A similar trend was observed for PFS. Furthermore, RAASi users experienced a greater clinical benefit rate than non-users (69% versus 57%, P = 0.006). Importantly, the use of RAASi before ICI initiation was not associated with improved overall survival and PFS. RAASi were not associated with an increased risk of adverse events. The use of RAASi is associated with improved survival outcomes, treatment response and tumour-based endpoints in patients undergoing immunotherapy. • RAASi were associated with improved clinical outcomes across a broad range of cancer patients receiving ICI. • Subgroup analysis showed that ARB were associated with improved clinical outcomes in patients undergoing immunotherapy. • The use of RAASi before immune checkpoint blockade was not associated with improved survival. • RAASi were not associated with increased risk of adverse events among cancer patients receiving ICI. [ABSTRACT FROM AUTHOR]

Research on dementia literacy in Chinese societies is still emerging, and this is especially the case among racially minoritized groups. The present study explored the knowledge, causal beliefs, and help-seeking behaviors of South Asian migrants in Hong Kong about dementia. It also investigated existing community barriers related to dementia knowledge and help-seeking. We conducted a qualitative study from a purposive sample of 38 older people and family caregivers from India, Pakistan, and Nepal who lived in Hong Kong. Focus groups and individual in-depth interviews were used to gather information, while thematic analysis was employed to analyze the data. Five main themes were identified: normalization with stigmatization of dementia; spiritual and psychosocial attributions of dementia; familial responsibility despite potential caregiving burden; uncertainties versus openness to professional care; and barriers and opportunities in dementia literacy. Ethnic minorities recognized dementia as a disease of normal aging or a mental disorder. They also perceived spiritual and psychosocial factors as their main causes. While participants recognized the potential burden of dementia caregiving, families were their first point of help-seeking, as many of them expressed contrasting feelings of confidence or doubt toward professional services. Utilization of health education strategies, together with collaboration with community leaders, could address the barriers to dementia literacy. This is the first study to explore how ethnic minorities in Asia perceive dementia and its related help-seeking behaviors in their communities. South Asian migrants in Hong Kong have a limited understanding of dementia and may experience delays in obtaining relevant community services. While culture influenced their knowledge, health education may address their misperceptions and help-seeking behaviors toward dementia. Culture- and language-specific programs could also improve dementia knowledge and health service access. [ABSTRACT FROM AUTHOR]

Childhood apraxia of speech (CAS) is a paediatric motor speech disorder. We investigated the lexical tone perception and production abilities of children with CAS and the relationships between the two. Three children with CAS, aged between 3;7 and 5;8, were given the Cantonese Tone Identification Test (CANTIT) and the Hong Kong Cantonese Articulation Test (HKCAT) for assessment of tone perception and production, respectively. Accuracy and error patterns were investigated based on their performance on the two tests. Correlation analysis was performed on children's perception and production scores. Two children scored at the lowest rank on the CANTIT, while one child obtained a Z score of 0. All children scored three standard deviations below the mean on the HKCAT. No statistical differences were found among the six tones with respect to perception accuracy, H(5) = 3.731, p = 0.589. Error analysis showed that children with CAS demonstrated more confusion on perceiving tones compared with TD peers. There were no main effects for task (F(1,2) = 0.040, p = 0.859) or tone (F(5,10 = 0.997, p = 0.467); nor were there task or tone interaction effects on perception versus production accuracy (F(5,10) = 1.772, p = 0.206). Tone perception and production accuracy were not significantly correlated (r2 = 0.181, p = 0.078). Tone perception deficits were evident in two out of three children with CAS, while all children had lexical tone production difficulties. In this small sample, tone production was more universally affected than tone perception. [ABSTRACT FROM AUTHOR]

This study aims to determine the relationship between intracranial pressure (ICP) and intraocular pressure (IOP) in patients with normal-tension glaucoma (NTG) who were already on anti-glaucoma treatment using an estimated ICP (estICP) and translaminar pressure difference (estTPD) formula. A cross-sectional comparative study consisted of 66 subjects (66 eyes) who were divided into NTG (n=33) and normal (n=33) group was conducted from 1st November 2017 until 31st May 2020 at a tertiary hospital in Malaysia. After obtaining consent from subjects, ocular and systemic data including IOP, visual field testing, axial length, central corneal thickness (CCT), peripapillary and macular retinal nerve fibre layer evaluation as well as blood pressure (BP) and body mass index (BMI) were collected. The estICP (mm Hg) was calculated as 0.44 x BMI (kg/m2) + 0.16 x diastolic blood pressure (mmHg) - 0.18 x age (years) - 1.91. The estTPD was derived from this calculated value, where estTPD (mm Hg) = IOP -- estICP. Analysis showed there was no significant difference in estimated ICP between NTG and normal subjects [mean difference (95% CI): 0.37 (-1.39, 2.12), p=0.679]. The difference in estTPD between NTG and normal subjects were found to be statistically insignificant too [mean difference (95% CI): -1.24 (-2.95, 0.47), p=0.149]. The variables significant in multivariate model included best corrected visual acuity (p=0.028), retinal nerve fiber layer (RNFL) (p=0.003), average macular (p=0.002) and estTPD (p=0.008). The EstTPD was found to be protective towards NTG, which the unit increased in estTPD will decreased the odds of having NTG by 26.5% [Adj. OR (95% CI): 0.735 (0.586, 0.922), p=0.008]. In conclusion, ICP was correlated in increased in IOP. A higher TPD may be associated with a lower chance of developing NTG. [ABSTRACT FROM AUTHOR]

The extant literature explains autocratization either through domestically or internationally-driven explanations. The former focuses on studying autocratic strongmen's executive aggrandizement or promissory coups from a domestic perspective, while the latter highlights the critical role of autocratic powers in promoting autocratic practices to neighboring countries from an international perspective. Transcending such a dichotomous approach, this study endeavors to explore the coupling of domestic and international drivers in causing autocratization in the context of Asia through a comparative analysis of Cambodia, the Philippines, Myanmar and Thailand. The comparative analysis indicates that domestic politics spearheads autocratization (that is, the role of autocratic strongmen in spearheading autocratization through executive aggrandizement or promissory coups), while international politics consolidates such autocratization (that is, the role of autocratic powers in consolidating autocratization pathway through their exporting influence). With the rising rivalry between democratic and autocratic powers, there are more pressing needs than ever to integrate domestic and international perspectives in autocratization studies. [ABSTRACT FROM AUTHOR]

In this work, we used a combination of photoluminescence (PL), high resolution X-ray diffraction (XRD), and Rutherford backscattering spectrometry (RBS) techniques to investigate material quality and structural properties of MBE-grown InGaAsBi samples (with and without an InGaAs cap layer) with targeted bismuth composition in the 3%–4% range. XRD data showed that the InGaAsBi layers are more homogeneous in the uncapped samples. For the capped samples, the growth of the InGaAs capped layer at higher temperature affects the quality of the InGaAsBi layer and bismuth distribution in the growth direction. Low-temperature PL exhibited multiple emission peaks; the peak energies, widths, and relative intensities were used for comparative analysis of the data in line with the XRD and RBS results. RBS data at a random orientation together with channeled measurements allowed both an estimation of the bismuth composition and analysis of the structural properties. The RBS channeling showed evidence of higher strain due to possible antisite defects in the capped samples grown at a higher temperature. It is also suggested that the growth of the capped layer at high temperature causes deterioration of the bismuth-layer quality. The RBS analysis demonstrated evidence of a reduction of homogeneity of uncapped InGaAsBi layers with increasing bismuth concentration. The uncapped higher bismuth concentration sample showed less defined channeling dips suggesting poorer crystal quality and clustering of bismuth on the sample surface. [ABSTRACT FROM AUTHOR]

Background: Childhood apraxia of speech (CAS) is a motor-based speech sound disorder (SSD) with a core impairment in the planning and programming of spatiotemporal parameters of speech movement sequences. CAS may cause deficits in both segmental and suprasegmental components of speech, and it can severely affect children's ability to speak intelligibly and communicate effectively and impact their quality of life. Assessment tasks, such as the maximum performance tasks (MPT) and Syllable Repetition Task (SRT), examine children's segmental sequencing skills to assist with the diagnosis of CAS. In Hong Kong, although the MPT and SRT have been used clinically to diagnose CAS in Cantonese-speaking children, their validity has not been reported. There is an urgent need for such investigations. Suprasegmentally, lexical stress errors have been reported as a consensual feature and to aid in the diagnosis of CAS. However, there are challenges in diagnosing CAS in children who speak tonal languages like Cantonese. A recent study has reported lexical tone errors in Cantonese-speaking children with CAS. Furthermore, deficits in pitch-variation skills were found in Cantonese-speaking children with CAS using a tone sequencing task (TST). It is hypothesized that there is a universal deficit in pitch-variation skills among tonal and nontonal language speakers with CAS. Further investigations of pitch-variation skills using the TST in Cantonese-speaking children with CAS may shed light on suprasegmental deficits in tonal languages and contribute to the development of a valid diagnostic tool for CAS in children who speak other tonal languages, such as Vietnamese, Thai, and Mandarin. Objective: This study aims to examine the diagnostic potential of the MPT, SRT, and TST in diagnosing Cantonese-speaking children with CAS and to investigate pitch-variation skills in Cantonese-speaking children with and without CAS. Methods: A total of 25 children with CAS and 3 groups of age- and gender-matched controls (non-CAS SSD only group, non-CAS SSD co-occurring with language impairment group, and typical development group) will be recruited. All participants will perform the MPT, SRT, and TST measures. Their performances on these tools will be perceptually judged and acoustically measured. Results: Data collection will last from January 1, 2022, to October 30, 2023. As of August 2022, the project has recruited 4 children in the CAS group, 21 children in the non-CAS SSD group, 4 children in the speech and language impairment group, and 53 children in the typical development group. Conclusions: It is anticipated that Cantonese-speaking children with CAS will have poorer pitch-variation skills than the control groups and that the MPT, SRT, and TST will be appropriate diagnostic tools for identifying CAS in Cantonese-speaking children. The project will benefit the field of speech-language pathology locally and internationally, with short- and long-term impacts. [ABSTRACT FROM AUTHOR]

In this research, we report on a comparative study of the corro-erosive properties of TaC and HfC individual coatings and (Ta70-Hf30-C) and (Ta30-Hf70-C) coatings. These were subjected to different impact angles of abrasive particles, corresponding with angles of 30°, 60° and 90°. It was determined that at 90°, a higher structural damage of the coatings obtained was presented. In addition, for all the systems, it was possible to conclude that the coating formed by (Ta30-Hf70-C) presented a roughness of approximately 7.11 nm, which influenced corrosive properties such as the corrosion potential and corrosion rate. Finally, it was possible to conclude that the (Ta30-Hf70-C) coating presented a higher resistance against corro-erosive environments. This was attributed to structural and mainly superficial factors, making this coating the best option to be implemented as a protective coating against highly aggressive environments in industry. [ABSTRACT FROM AUTHOR]

In recent years, there has been an emerging theory of "student identity politics," which focuses on student activism based on race, gender, and sexual identity. Thus far, scholars have not yet systematically extended the analysis of student identity politics to those student activism relating to territorial identity. The student-led territorial identity movement that began in Hong Kong in 2015, which has transformed the center-autonomy relations between Beijing and Hong Kong, offers a case study that enriches the theory of student identity politics by bringing in the notion of territorial identity and opening the door for future comparative studies of territorial identity movements worldwide. [ABSTRACT FROM AUTHOR]

The retrospective pragmatic real‐world data (RWD) study compared the healing outcomes of diabetic foot ulcers (DFUs) treated with either ovine forestomach matrix (OFM) (n = 1150) or collagen/oxidised regenerated cellulose (ORC) (n = 1072) in out‐patient wound care centres. Median time to wound closure was significantly (P =.0015) faster in the OFM group (14.6 ± 0.5 weeks) relative to the collagen/ORC group (16.4 ± 0.7). A sub‐group analysis was performed to understand the relative efficacy in DFUs requiring longer periods of treatment and showed that DFUs treated with OFM healed up to 5.3 weeks faster in these challenging wounds. The percentage of wounds closed at 36 weeks was significantly improved in OFM treated DFUs relative to the collagen/ORC. A Cox proportional hazards analysis showed OFM‐treated wounds had a 18% greater probability of healing versus wounds managed with collagen/ORC, and the probability increased to 21% when the analysis was adjusted for multiple variables. This study represents the first large retrospective RWD analysis comparing OFM and collagen/ORC and supports the clinical efficacy of OFM in the treatment of DFUs. [ABSTRACT FROM AUTHOR]

Objective: To compare the preoperative detection of endometriosis using transvaginal sonography (TVS) supplemented by transabdominal sonography (TAS) with surgical assessment of disease, using the #Enzian classification for endometriosis.Methods: This was a prospective multicenter diagnostic accuracy study of women undergoing TVS/TAS and radical surgery for deep endometriosis (DE) at different tertiary referral centers. The localization and grade of severity of the endometriotic lesions and adhesions were described according to the criteria of the #Enzian classification, both at preoperative ultrasound examination and during surgery. According to the #Enzian classification, the small pelvis is divided into three compartments for DE: A (rectovaginal septum and vagina); B (uterosacral and cardinal ligaments, parametrium and pelvic sidewalls); and C (rectum). In addition, further locations (F) are classified as adenomyosis (FA), urinary bladder involvement (FB) and ureteric involvement with signs of obstruction (FU). Other intestinal locations (FI) and other extragenital locations (FO) are also included. Ovarian endometriosis and adhesions at the level of the tubo-ovarian unit are listed as O and T, respectively. The #Enzian grade of severity (Grade 1-3) was determined for #Enzian compartments O, T, A, B and C based on the size of the lesion or the severity of the adhesions. Concordance between preoperative assessment using TVS/TAS and evaluation at surgery was assessed. The sensitivity, specificity, positive and negative predictive values and accuracy of TVS/TAS in the detection of endometriotic lesions/adhesions in the different #Enzian compartments were calculated.Results: In total, 745 women were included in the analysis. Preoperative TVS/TAS and surgical findings showed a concordance rate ranging between 86% and 99% for the presence or absence of endometriotic lesions/adhesions, depending on the evaluated #Enzian compartment. The concordance rate between TVS and surgery ranged between 71% and 92% for different severity grades, in #Enzian compartments O, T, A, B and C. Determining the presence or absence of adhesions at the level of the tubo-ovarian unit and classifying them accurately as Grade 1, 2 or 3 on TVS was more difficult than determining the presence and severity of endometriotic lesions in #Enzian compartments O, A, B and C. The sensitivity of TVS/TAS for the detection of endometriotic lesions ranged from 50% (#Enzian compartment FI) to 95% (#Enzian compartment A), specificity from 86% (#Enzian compartment Tleft ) to 99% (#Enzian compartment FI) and 100% (#Enzian compartments FB, FU and FO), positive predictive value from 90% (#Enzian compartment Tright ) to 100% (#Enzian compartment FO), negative predictive value from 74% (#Enzian compartment Bleft ) to 99% (#Enzian compartments FB and FU) and accuracy from 88% (#Enzian compartment Bright ) to 99% (#Enzian compartment FB).Conclusions: The localization and severity of endometriotic lesions/adhesions, as described and classified according to the #Enzian classification, can be diagnosed accurately and non-invasively using TVS/TAS. The #Enzian classification provides a uniform classification system for describing endometriotic lesions, which can be used both at TVS/TAS and during surgical evaluation. © 2021 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Study Question: Is a single endometrial scratch prior to the second fresh IVF/ICSI treatment cost-effective compared to no scratch, when evaluated over a 12-month follow-up period?Summary Answer: The incremental cost-effectiveness ratio (ICER) for an endometrial scratch was €6524 per additional live birth, but due to uncertainty regarding the increase in live birth rate this has to be interpreted with caution.What Is Known Already: Endometrial scratching is thought to improve the chances of success in couples with previously failed embryo implantation in IVF/ICSI treatment. It has been widely implemented in daily practice, despite the lack of conclusive evidence of its effectiveness and without investigating whether scratching allows for a cost-effective method to reduce the number of IVF/ICSI cycles needed to achieve a live birth.Study Design, Size, Duration: This economic evaluation is based on a multicentre randomized controlled trial carried out in the Netherlands (SCRaTCH trial) that compared a single scratch prior to the second IVF/ICSI treatment with no scratch in couples with a failed full first IVF/ICSI cycle. Follow-up was 12 months after randomization.Economic evaluation was performed from a healthcare and societal perspective by taking both direct medical costs and lost productivity costs into account. It was performed for the primary outcome of biochemical pregnancy leading to live birth after 12 months of follow-up as well as the secondary outcome of live birth after the second fresh IVF/ICSI treatment (i.e. the first after randomization). To allow for worldwide interpretation of the data, cost level scenario analysis and sensitivity analysis was performed.Participants/materials, Setting, Methods: From January 2016 until July 2018, 933 women with a failed first IVF/ICSI cycle were included in the trial. Data on treatment and pregnancy were recorded up until 12 months after randomization, and the resulting live birth outcomes (even if after 12 months) were also recorded.Total costs were calculated for the second fresh IVF/ICSI treatment and for the full 12 month period for each participant. We included costs of all treatments, medication, complications and lost productivity costs. Cost-effectiveness analysis was carried out by calculating ICERs for scratch compared to control. Bootstrap resampling was used to estimate the uncertainty around cost and effect differences and ICERs. In the sensitivity and scenario analyses, various unit costs for a single scratch were introduced, amongst them, unit costs as they apply for the United Kingdom (UK).Main Results and the Role Of Chance: More live births occurred in the scratch group, but this also came with increased costs over a 12-month period. The estimated chance of a live birth after 12 months of follow-up was 44.1% in the scratch group compared to 39.3% in the control group (risk difference 4.8%, 95% CI -1.6% to +11.2%). The mean costs were on average €283 (95% CI: -€299 to €810) higher in the scratch group so that the point average ICER was €5846 per additional live birth. The ICER estimate was surrounded with a high level of uncertainty, as indicated by the fact that the cost-effectiveness acceptability curve (CEAC) showed that there is an 80% chance that endometrial scratching is cost-effective if society is willing to pay ∼€17 500 for each additional live birth.Limitations, Reasons For Caution: There was a high uncertainty surrounding the effects, mainly in the clinical effect, i.e. the difference in the chance of live birth, which meant that a single straightforward conclusion could not be ascertained as for now.Wider Implications Of the Findings: This is the first formal cost-effectiveness analysis of endometrial scratching in women undergoing IVF/ICSI treatment. The results presented in this manuscript cannot provide a clear-cut expenditure for one additional birth, but they do allow for estimating costs per additional live birth in different scenarios once the clinical effectiveness of scratching is known. As the SCRaTCH trial was the only trial with a follow-up of 12 months, it allows for the most complete estimation of costs to date.Study Funding/competing Interest(s): This study was funded by ZonMW, the Dutch organization for funding healthcare research. A.E.P.C., F.J.M.B., E.R.G. and C.B. L. reported having received fees or grants during, but outside of, this trial.Trial Registration Number: Netherlands Trial Register (NL5193/NTR 5342). [ABSTRACT FROM AUTHOR]

Study Question: Is there an increased risk of breast cancer among women after ART treatment including ovarian hormone stimulation?Summary Answer: The risk of breast cancer was slightly increased among women after ART treatment compared to age-matched, untreated women in the background population, and the risk was further increased among women initiating ART treatment when aged 40+ years.What Is Known Already: The majority of breast cancer cases are sensitive to oestrogen, and ovarian hormone stimulation has been suggested to increase the risk of breast cancer by influencing endogenous oestrogen levels. Previous studies on ART treatment and breast cancer have varied in their findings, but several studies have small sample sizes or lack follow-up time and/or confounder adjustment. Recent childbirth, nulliparity and higher socio-economic status are breast cancer risk factors and the latter two are also associated with initiating ART treatment.Study Design, Size, Duration: The Danish National ART-Couple II (DANAC II) cohort includes women treated with ART at public and private fertility clinics in 1994-2016.Participants/materials, Setting, Methods: Women with no cancer prior to ART treatment were included (n = 61 579). Women from the background population with similar age and no prior history of ART treatment were randomly selected as comparisons (n = 579 760). The baseline mean age was 33.1 years (range 18-46 years). Results are presented as hazard ratios (HRs) with corresponding CIs.Main Results and the Role Of Chance: During follow-up (median 9.69 years among ART-treated and 9.28 years among untreated), 5861 women were diagnosed with breast cancer, 695 among ART-treated and 5166 among untreated women (1.1% versus 0.9%, P < 0.0001). Using Cox regression analyses adjusted for nulliparity, educational level, partnership status, year, maternal breast cancer and age, the risk of breast cancer was slightly increased among women treated with ART (HR 1.14, 95% CI 1.12-1.16). All causes of infertility were slightly associated with breast cancer risk after ART treatment. The risk of breast cancer increased with higher age at ART treatment initiation and was highest among women initiating treatment at age 40+ years (HR 1.37, 95% CI 1.29-1.45). When comparing women with a first birth at age 40+ years with or without ART treatment, the increased risk among women treated with ART persisted (HR 1.51, 95% CI 1.09-2.08).Limitations, Reasons For Caution: Although this study is based on a large, national cohort of women, more research with sufficient power and confounder adjustment is needed, particularly in cohorts with a broad age representation.Wider Implications Of the Findings: An increased risk of breast cancer associated with a higher age at ART treatment initiation has been shown. Ovarian stimulation may increase the risk of breast cancer among women initiating ART treatment when aged 40+ years. Age-related vulnerability to hormone exposure or higher hormone doses during ART treatment may explain the increased risk.Study Funding/competing Interest(s): This work was supported by a PhD grant to D.V. from the Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Funding for establishing the DANAC II cohort was received from the Ebba Rosa Hansen Foundation. The authors report no conflict of interest.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Objective: In this study, the authors investigated the longitudinal effect of the recovery attributes of peer support workers (PSWs) on users of mental health services in Hong Kong over a 9-month period.Methods: Recovery attributes were measured among PSWs (N=26) employed by four local nongovernmental organizations before their commencement of service. The recovery-related outcomes of regular service users (N=181) were measured every 3 months for 9 months. Multilevel mixed-effects linear regression analyses with restricted maximum likelihood were used to analyze the possible association of PSWs' qualities on service users' recovery outcomes. The Holm-Bonferroni method was used to adjust for p values to account for multiple comparisons.Results: Results showed that levels of hope and self-esteem among PSWs were statistically significantly associated with improvements in hope and empowerment among service users over time.Conclusions: PSWs' recovery attributes may benefit service users' personal recovery. Future exploration on the specific pathways of recovery attributes of PSWs on service users' recovery is suggested. [ABSTRACT FROM AUTHOR]

Background: While well-conducted systematic reviews (SRs) can provide the best evidence on the potential effectiveness of acupuncture, limitations on the methodological rigour of SRs may impact the trustworthiness of their conclusions. This cross-sectional study aimed to evaluate the methodological quality of a representative sample of SRs on acupuncture effectiveness.Methods: Cochrane Database of Systematic Reviews, MEDLINE, and EMBASE were searched for SRs focusing on the treatment effect of manual acupuncture or electro-acupuncture published during January 2018 and March 2020. Eligible SRs must contain at least one meta-analysis and be published in English language. Two independent reviewers extracted the bibliographical characteristics of the included SRs with a pre-designed questionnaire and appraised the methodological quality of the studies with the validated AMSTAR 2 (A MeaSurement Tool to Assess systematic Reviews 2). The associations between bibliographical characteristics and methodological quality ratings were explored using Kruskal-Wallis rank tests and Spearman's rank correlation coefficients.Results: A total of 106 SRs were appraised. Only one (0.9%) SR was of high overall methodological quality, zero (0%) was of moderate-quality, six (5.7%) and 99 (93.4%) were of low-quality and critically low-quality respectively. Among appraised SRs, only ten (9.4%) provided an a priori protocol, four (3.8%) conducted a comprehensive literature search, five (4.7%) provided a list of excluded studies, and six (5.7%) performed meta-analysis appropriately. Cochrane SRs, updated SRs, and SRs that did not search non-English databases had relatively higher overall quality.Conclusions: Methodological quality of SRs on acupuncture is unsatisfactory. Future reviewers should improve critical methodological aspects of publishing protocols, performing comprehensive search, providing a list of excluded studies with justifications for exclusion, and conducting appropriate meta-analyses. These recommendations can be implemented via enhancing the technical competency of reviewers in SR methodology through established education approaches as well as quality gatekeeping by journal editors and reviewers. Finally, for evidence users, skills in SR critical appraisal remain to be essential as relevant evidence may not be available in pre-appraised formats. [ABSTRACT FROM AUTHOR]

Background: Standard screening of endometrial cancer (EC) for Lynch syndrome (LS) is gaining traction; however, the prognostic impact of an underlying hereditary etiology is unknown. We established the prevalence, prognosis, and subsequent primary cancer incidence of patients with LS-associated EC in relation to sporadic mismatch repair deficient (MMRd)-EC in the large combined Post Operative Radiation Therapy in Endometrial Carcinoma-1, -2, and -3 trial cohort.Methods: After MMR-immunohistochemistry, MLH1-promoter methylation testing, and next-generation sequencing, tumors were classified into 3 groups according to the molecular cause of their MMRd-EC. Kaplan-Meier method, log-rank test, and Cox model were used for survival analysis. Competing risk analysis was used to estimate the subsequent cancer probability. All statistical tests were 2-sided.Results: Among the 1336 ECs, 410 (30.7%) were MMRd. A total of 380 (92.7%) were fully triaged: 275 (72.4%) were MLH1-hypermethylated MMRd-ECs; 36 (9.5%) LS MMRd-ECs, and 69 (18.2%) MMRd-ECs due to other causes. Limiting screening of EC patients to 60 years or younger or to 70 years or younger would have resulted in missing 18 (50.0%) and 6 (16.7%) LS diagnoses, respectively. Five-year recurrence-free survival was 91.7% (95% confidence interval [CI] = 83.1% to 100%; hazard ratio = 0.45, 95% CI = 0.16 to 1.24, P = .12) for LS, 95.5% (95% CI = 90.7% to 100%; hazard ratio = 0.17, 95% CI = 0.05 to 0.55, P = .003) for "other" vs 78.6% (95% CI = 73.8% to 83.7%) for MLH1-hypermethylated MMRd-EC. The probability of subsequent LS-associated cancer at 10 years was 11.6% (95% CI = 0.0% to 24.7%), 1.5% (95% CI = 0.0% to 4.3%), and 7.0% (95% CI = 3.0% to 10.9%) within the LS, "other," and MLH1-hypermethylated MMRd-EC groups, respectively.Conclusions: The LS prevalence in the Post Operative Radiation Therapy in Endometrial Carcinoma trial population was 2.8% and among MMRd-ECs was 9.5%. Patients with LS-associated ECs showed a trend towards better recurrence-free survival and higher risk for second cancers compared with patients with MLH1-hypermethylated MMRd-EC. [ABSTRACT FROM AUTHOR]

To establish an ideal microenvironment for regenerating maxillofacial defects, recent research interests have concentrated on developing scaffolds with intricate configurations and manipulating the stiffness of extracellular matrix toward osteogenesis. Herein, we propose to infuse a degradable RGD-functionalized alginate matrix (RAM) with osteoid-like stiffness, as an artificial extracellular matrix, to a rigid 3D-printed hydroxyapatite scaffold for maxillofacial regeneration. The 3D-printed hydroxyapatite scaffold was produced by microextrusion technology and showed good dimensional stability with consistent microporous detail. RAM was crosslinked by calcium sulfate to manipulate the stiffness, and its degradation was accelerated by partial oxidation using sodium periodate. The results revealed that viability of bone marrow stem cells was significantly improved on the RAM and was promoted on the oxidized RAM. In addition, the migration and osteogenic differentiation of bone marrow stem cells were promoted on the RAM with osteoid-like stiffness, specifically on the oxidized RAM. The in vivo evidence revealed that nonoxidized RAM with osteoid-like stiffness upregulated osteogenic genes but prevented ingrowth of newly formed bone, leading to limited regeneration. Oxidized RAM with osteoid-like stiffness facilitated collagen synthesis, angiogenesis, and osteogenesis and induced robust bone formation, thereby significantly promoting maxillofacial regeneration. Overall, this study supported that in the stabilized microenvironment, oxidized RAM with osteoid-like stiffness offered requisite mechanical cues for osteogenesis and an appropriate degradation profile to facilitate bone formation. Combining the 3D-printed hydroxyapatite scaffold and oxidized RAM with osteoid-like stiffness may be an advantageous approach for maxillofacial regeneration. [ABSTRACT FROM AUTHOR]

Traditionally, budgetary scholars focus on deficit politics in Western democracies, emphasizing budgetary conflicts among budgetary actors over different strategies to balance budgets. While most countries are facing budget deficits, some countries and regions are experiencing budget surpluses. However, surplus politics, and its comparison with deficit politics, remains underexplored. This study is a pioneer attempt to compare the similarities and differences between deficit politics and surplus politics, using Hong Kong and Singapore as binary cases. [ABSTRACT FROM AUTHOR]

Study Question: Is fertility treatment with clomiphene citrate associated with an increased risk of childhood epilepsy, including specific subtypes of epilepsy?Summary Answer: Fertility treatment with clomiphene citrate may be associated with a small increased risk of idiopathic generalized epilepsy and focal epilepsy in childhood.What Is Known Already: Clomiphene citrate is among the most commonly prescribed drugs for fertility treatment. However, concerns have been raised as to whether the treatment may harm the developing fetus.Study Design, Size, Duration: This nationwide cohort study included all pregnancies in Denmark from 1 July 1995 resulting in a live-born singleton child before 31 December 2013. The children were followed until 31 December 2016.Participants/materials, Setting, Methods: Children conceived after fertility treatment with clomiphene citrate were identified from the Danish National Prescription Registry. The primary outcomes were childhood epilepsy, idiopathic generalized epilepsy, and focal epilepsy identified from the Danish National Patient Register and from antiepileptic drug prescriptions in the Danish National Prescription Registry. All analyses were conducted using Cox proportional hazards regression.Main Results and the Role Of Chance: A total of 1 081 291 pregnancies were included; 12 644 children (1.2%) developed epilepsy. Fertility treatment with clomiphene citrate was associated with a small increased risk of childhood epilepsy (hazard ratio [HR]: 1.10; 95% CI: 1.00-1.22), idiopathic generalized epilepsy (HR: 1.41; 95% CI: 1.16-1.72), and focal epilepsy (HR: 1.26; 95% CI: 1.04-1.53).Limitations, Reasons For Caution: The increased risk of idiopathic generalized epilepsy may be due to confounding from time stable parental characteristics related to treatment with clomiphene citrate, since the association was strongest with the lowest administered dosage of clomiphene citrate prior to conception, and the association disappeared in a sibling analysis.Wider Implications Of the Findings: The increased risk of focal epilepsy may be related to the hormonal treatment, since the association tended to increase with increasing cumulative dosage of clomiphene citrate prior to conception, and the association persisted in a sibling analysis. This finding may be of clinical importance, since alternative hormones are available for fertility treatment.Study Funding/competing Interest(s): Financial support from Aarhus University and the Aase and Ejnar Danielsen Foundation. U.S.K. received personal teaching fees from Merck, outside the submitted work.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Importance: Cytisine is more effective than placebo and nicotine replacement therapy for smoking cessation. However, cytisine has not been tested against the most effective smoking cessation medication, varenicline, which is associated with adverse events known to lead to discontinuation of therapy.Objective: To examine whether standard cytisine treatment (25 days) was at least as effective as standard varenicline treatment (84 days) for smoking cessation.Design, Setting, and Participants: This noninferiority, open-label randomized clinical trial with allocation concealment and blinded outcome assessment was undertaken in Australia from November 2017 through May 2019; follow-up was completed in January 2020. A total of 1452 Australian adult daily smokers willing to make a quit attempt were included. Data collection was conducted primarily by computer-assisted telephone interview, but there was an in-person visit to validate the primary outcome.Interventions: Treatments were provided in accordance with the manufacturers' recommended dosage: cytisine (n = 725), 1.5-mg capsules taken 6 times daily initially then gradually reduced over the 25-day course; varenicline (n = 727), 0.5-mg tablets titrated to 1 mg twice daily for 84 days (12 weeks). All participants were offered referral to standard telephone behavioral support.Main Outcomes and Measures: The primary outcome was 6-month continuous abstinence verified using a carbon monoxide breath test at 7-month follow-up. The noninferiority margin was set at 5% and the 1-sided significance threshold was set at .025.Results: Among 1452 participants who were randomized (mean [SD] age, 42.9 [12.7] years; 742 [51.1%] women), 1108 (76.3%) completed the trial. Verified 6-month continuous abstinence rates were 11.7% for the cytisine group and 13.3% for the varenicline group (risk difference, -1.62% [1-sided 97.5% CI, -5.02% to ∞]; P = .03 for noninferiority). Self-reported adverse events occurred less frequently in the cytisine group (997 events among 482 participants) compared with the varenicline group (1206 events among 510 participants) and the incident rate ratio was 0.88 (95% CI, 0.81 to 0.95; P = .002).Conclusions and Relevance: Among daily smokers willing to quit, cytisine treatment for 25 days, compared with varenicline treatment for 84 days, failed to demonstrate noninferiority regarding smoking cessation.Trial Registration: anzctr.org.au Identifier: ACTRN12616001654448. [ABSTRACT FROM AUTHOR]

Study Question: What is the transcriptome signature associated with poor performance of rescue IVM (rIVM) oocytes and how can we rejuvenate them?Summary Answer: The GATA-1/CREB1/WNT signalling axis was repressed in rIVM oocytes, particularly those of poor quality; restoration of this axis may produce more usable rIVM oocytes.What Is Known Already: rIVM aims to produce mature oocytes (MII) for IVF through IVM of immature oocytes collected from stimulated ovaries. It is not popular due to limited success rate in infertility treatment. Genetic aberrations, cellular stress and the absence of cumulus cell support in oocytes could account for the failure of rIVM.Study Design, Size, Duration: We applied single-cell RNA sequencing (scRNA-seq) to capture the transcriptomes of human in vivo oocytes (IVO) (n = 10) from 7 donors and rIVM oocytes (n = 10) from 10 donors. The effects of maternal age and ovarian responses on rIVM oocyte transcriptomes were also studied. In parallel, we studied the effect of gallic acid on the maturation rate of mouse oocytes cultured in IVM medium with (n = 84) and without (n = 85) gallic acid.Participants/materials, Setting, Methods: Human oocytes were collected from donors aged 28-41 years with a body mass index of <30. RNA extraction, cDNA generation, library construction and sequencing were performed in one preparation. scRNA-seq data were then processed and analysed. Selected genes in the rIVM versus IVO comparison were validated by quantitative real-time PCR. For the gallic acid study, we collected immature oocytes from 5-month-old mice and studied the effect of 10-μM gallic acid on their maturation rate.Main Results and the Role Of Chance: The transcriptome profiles of rIVM/IVO oocytes showed distinctive differences. A total of 1559 differentially expressed genes (DEGs, genes with at least 2-fold change and adjusted P < 0.05) were found to be enriched in metabolic processes, biosynthesis and oxidative phosphorylation. Among these DEGs, we identified a repression of WNT/β-catenin signalling in rIVM when compared with IVO oocytes. We found that oestradiol levels exhibited a significant age-independent correlation with the IVO mature oocyte ratio (MII ratio) for each donor. rIVM oocytes from women with a high MII ratio were found to have over-represented cellular processes such as anti-apoptosis. To further identify targets that contribute to the poor clinical outcomes of rIVM, we compared oocytes collected from young donors with a high MII ratio with oocytes from donors of advanced maternal age and lower MII ratio, and revealed that CREB1 is an important regulator. Thus, our study identified that GATA-1/CREB1/WNT signalling was repressed in both rIVM oocytes versus IVO oocytes and in rIVM oocytes of lower versus higher quality. Consequently we investigated gallic acid, as a potential antioxidant substrate in human rIVM medium, and found that it increased the mouse oocyte maturation rate by 31.1%.Large Scale Data: Raw data from this study can be accessed through GSE158539.Limitations, Reasons For Caution: In the rIVM oocytes of the high- and low-quality comparison, the number of samples was limited after data filtering with stringent selection criteria. For the oocyte stage identification, we were unable to predict the presence of oocyte spindle, so polar body extrusion was the only indicator.Wider Implications Of the Findings: This study showed that GATA-1/CREB1/WNT signalling was repressed in rIVM oocytes compared with IVO oocytes and was further downregulated in low-quality rIVM oocytes, providing us the foundation of subsequent follow-up research on human oocytes and raising safety concerns about the clinical use of rescued oocytes.Study Funding/competing Interest(s): This work was supported by the Collaborative Research Fund, Research Grants Council, C4054-16G, and Research Committee Funding (Research Sustainability of Major RGC Funding Schemes), The Chinese University of Hong Kong. The authors have no conflicts of interest to declare. [ABSTRACT FROM AUTHOR]

Background: Epidemiological studies and meta-analyses show an association between statin use and a reduced incidence of colorectal cancer (CRC). We have shown that statins act on CRC through bone morphogenetic protein (BMP) signalling, but the exact cellular targets and underlying mechanism of statin action remain elusive. In this study, we set out to assess the influence of statins on global cancer cell signalling by performing an array-based kinase assay using immobilised kinase substrates spanning the entire human kinome.Methods: CRC cells with or without Lovastatin treatment were used for kinome analysis. Findings on kinome arrays were further confirmed by immunoblotting with activity-specific antibodies. Experiments in different CRC cell lines using immunoblotting, siRNA-mediated knockdown and treatment with specific BMP inhibitor Noggin were performed. The relevance of in vitro findings was confirmed in xenografts and in CRC patients treated with Simvastatin.Results: Kinome analysis can distinguish between non-specific, toxic effects caused by 10 µM of Lovastatin and specific effects on cell signalling caused by 2 µM Lovastatin. Statins induce upregulation of PTEN activity leading to downregulation of the PI3K/Akt/mTOR signalling. Treatment of cells with the specific BMP inhibitor Noggin as well as PTEN knockdown and transfection of cells with a constitutively active form of AKT abolishes the effect of Lovastatin on mTOR phosphorylation. Experiments in xenografts and in patients treated with Simvastatin confirm statin-mediated BMP pathway activation, activation of PTEN and downregulation of mTOR signalling.Conclusions: Statins induce BMP-specific activation of PTEN and inhibition of PI3K/Akt/mTOR signalling in CRC. [ABSTRACT FROM AUTHOR]

Objective: To evaluate potential MRI-defined effect modifiers of amoxicillin treatment in patients with chronic low back pain and type 1 or 2 Modic changes (MCs) at the level of a previous lumbar disc herniation (index level).Methods: In a prospective trial (AIM), 180 patients (25-64 years; mean age 45; 105 women) were randomised to receive amoxicillin or placebo for 3 months. Primary outcome was the Roland-Morris Disability Questionnaire (RMDQ) score (0-24 scale) at 1 year. Mean RMDQ score difference between the groups at 1 year defined the treatment effect; 4 RMDQ points defined the minimal clinically important effect. Predefined baseline MRI features of MCs at the index level(s) were investigated as potential effect modifiers. The predefined primary hypothesis was a better effect of amoxicillin when short tau inversion recovery (STIR) shows more MC-related high signal. To evaluate this hypothesis, we pre-constructed a composite variable with three categories (STIR1/2/3). STIR3 implied MC-related STIR signal increases with volume ≥ 25% and height > 50% of vertebral body and maximum intensity increase ≥ 25% and presence on both sides of the disc. As pre-planned, interaction with treatment was analysed using ANCOVA in the per protocol population (n = 155).Results: The STIR3 composite group (n = 41) and STIR signal volume ≥ 25% alone (n = 45) modified the treatment effect of amoxicillin. As hypothesised, STIR3 patients reported the largest effect (- 5.1 RMDQ points; 95% CI - 8.2 to - 1.9; p for interaction = 0.008).Conclusions: Predefined subgroups with abundant MC-related index-level oedema on STIR modified the effect of amoxicillin. This finding needs replication and further support.Key Points: • In the primary analysis of the AIM trial, the effect of amoxicillin in patients with chronic low back pain and type 1 or 2 MCs did not reach the predefined cut-off for clinical importance. • In the present MRI subgroup analysis of AIM, predefined subgroups with abundant MC-related oedema on STIR reported an effect of amoxicillin. • This finding requires replication and further support. [ABSTRACT FROM AUTHOR]

Objectives: Long-term care facilities (LTCFs) may act as a reservoir of ESBL-producing Enterobacterales (ESBL-E) and carbapenemase-producing Enterobacterales (CPE) for hospitals and the general population. In this study, we estimated the prevalence and molecular epidemiology of rectal carriage with ESBL-E and CPE in residents of Dutch LTCFs between March 2018 and December 2018.Methods: LTCFs were geographically selected across the country. For each LTCF, a random sample of residents were tested for ESBL-E and CPE in 2018. To identify risk factors for high carriage prevalence and/or individual carriage, characteristics of LTCFs and of a subset of the tested residents were collected. WGS was conducted on isolates from LTCFs with an ESBL-E prevalence of >10% and all CPE isolates to identify institutional clonal transmission.Results: A total of 4420 residents of 159 LTCFs were included. The weighted mean ESBL-E prevalence was 8.3% (95% CI: 6.8-10.0) and no CPE were found. In 53 LTCFs (33%), where ESBL-E prevalence was >10%, MLST using WGS (wgMLST) was performed. This included 264 isolates, the majority being Escherichia coli (n = 224) followed by Klebsiella pneumoniae (n = 30). Genetic clusters were identified in more than half (30/53; 57%) of high ESBL-positive LTCFs. Among the E. coli isolates, blaCTX-M-15 (92/224; 41%) and blaCTX-M-27 (40/224; 18%) were the most prevalent ESBL-encoding genes. For K. pneumoniae isolates, the most common was blaCTX-M-15 (23/30; 80%).Conclusions: The estimated prevalence of ESBL-E rectal carriage in Dutch LTCFs is 8.3% and resistance is observed mainly in E. coli with predominance of blaCTX-M-15 and blaCTX-M-27. ESBL-E prevalence in LTCFs seems comparable to previously reported prevalence in hospitals and the general population. [ABSTRACT FROM AUTHOR]

Objective: To analyse the Na content of bread by comparing the amount of salt and Na among the label, laboratory analysis and international guidelines.Design: Ten selected bakeries provided 3239 randomly selected samples of bread, which were weighed on-site. Triplicate samples were retrieved from each bakery (thirty samples) for analysis. Bread production was observed, and ingredient labels were queried to determine salt weights, which were used for comparison with the laboratory analysis. Flame photometry and the method for chlorides were utilised for analysing Na. Laboratory findings were compared to nine different international nutritional guidelines for Na consumption.Setting: Florianopolis, south of Brazil.Participants: Ninety independent bakeries locally producing Portuguese rolls were queried; rolls from ten conveniently selected bakeries were retrieved for further analysis.Results: The average weight of the rolls was 50·2 ± 5·3 g. The average amount of salt (g) per roll, by laboratory and label analyses, was 0·69 ± 0·0 and 0·62 ± 0·1 g, respectively. The mean level of Na (mg) reported on nutrient labels (478·2 ± 93·4/100 g) was significantly lower than by laboratory analysis (618·2 ± 73·8/100 g), P < 0·001. There was a difference for Na in rolls produced in the bakeries considering the unit weight of rolls (P ≤ 0·001) per 100 g (P = 0·026) and the mode of production. The consumption of two averaged units of rolls was equivalent to 51·7 % of the Brazilian guideline daily amount for Na for children and 31 % for adults.Conclusions: The nutrient labels underreported Na values. This study strengthens the importance of monitoring Na of breads in Brazil. [ABSTRACT FROM AUTHOR]

Background: We investigated whether associations between prevalent diabetes and cancer risk are pertinent to older adults and whether associations differ across subgroups of age, body weight status or levels of physical activity.Methods: We harmonised data from seven prospective cohort studies of older individuals in Europe and the United States participating in the CHANCES consortium. Cox proportional hazard regression was used to estimate the associations of prevalent diabetes with cancer risk (all cancers combined, and for colorectum, prostate and breast). We calculated summary risk estimates across cohorts using pooled analysis and random-effects meta-analysis.Results: A total of 667,916 individuals were included with an overall median (P25-P75) age at recruitment of 62.3 (57-67) years. During a median follow-up time of 10.5 years, 114,404 total cancer cases were ascertained. Diabetes was not associated with the risk of all cancers combined (hazard ratio (HR) = 0.94; 95% confidence interval (CI): 0.86-1.04; I2 = 63.3%). Diabetes was positively associated with colorectal cancer risk in men (HR = 1.17; 95% CI: 1.08-1.26; I2 = 0%) and a similar HR in women (1.13; 95% CI: 0.82-1.56; I2 = 46%), but with a confidence interval including the null. Diabetes was inversely associated with prostate cancer risk (HR = 0.81; 95% CI: 0.77-0.85; I2 = 0%), but not with postmenopausal breast cancer (HR = 0.96; 95% CI: 0.89-1.03; I2 = 0%). In exploratory subgroup analyses, diabetes was inversely associated with prostate cancer risk only in men with overweight or obesity.Conclusions: Prevalent diabetes was positively associated with colorectal cancer risk and inversely associated with prostate cancer risk in older Europeans and Americans. [ABSTRACT FROM AUTHOR]

Study Question: Do genetic variations in the DNA damage response pathway modify the adverse effect of alkylating agents on ovarian function in female childhood cancer survivors (CCS)?Summary Answer: Female CCS carrying a common BR serine/threonine kinase 1 (BRSK1) gene variant appear to be at 2.5-fold increased odds of reduced ovarian function after treatment with high doses of alkylating chemotherapy.What Is Known Already: Female CCS show large inter-individual variability in the impact of DNA-damaging alkylating chemotherapy, given as treatment of childhood cancer, on adult ovarian function. Genetic variants in DNA repair genes affecting ovarian function might explain this variability.Study Design, Size, Duration: CCS for the discovery cohort were identified from the Dutch Childhood Oncology Group (DCOG) LATER VEVO-study, a multi-centre retrospective cohort study evaluating fertility, ovarian reserve and risk of premature menopause among adult female 5-year survivors of childhood cancer. Female 5-year CCS, diagnosed with cancer and treated with chemotherapy before the age of 25 years, and aged 18 years or older at time of study were enrolled in the current study. Results from the discovery Dutch DCOG-LATER VEVO cohort (n = 285) were validated in the pan-European PanCareLIFE (n = 465) and the USA-based St. Jude Lifetime Cohort (n = 391).Participants/materials, Setting, Methods: To evaluate ovarian function, anti-Müllerian hormone (AMH) levels were assessed in both the discovery cohort and the replication cohorts. Using additive genetic models in linear and logistic regression, five genetic variants involved in DNA damage response were analysed in relation to cyclophosphamide equivalent dose (CED) score and their impact on ovarian function. Results were then examined using fixed-effect meta-analysis.Main Results and the Role Of Chance: Meta-analysis across the three independent cohorts showed a significant interaction effect (P = 3.0 × 10-4) between rs11668344 of BRSK1 (allele frequency = 0.34) among CCS treated with high-dose alkylating agents (CED score ≥8000 mg/m2), resulting in a 2.5-fold increased odds of a reduced ovarian function (lowest AMH tertile) for CCS carrying one G allele compared to CCS without this allele (odds ratio genotype AA: 2.01 vs AG: 5.00).Limitations, Reasons For Caution: While low AMH levels can also identify poor responders in assisted reproductive technology, it needs to be emphasized that AMH remains a surrogate marker of ovarian function.Wider Implications Of the Findings: Further research, validating our findings and identifying additional risk-contributing genetic variants, may enable individualized counselling regarding treatment-related risks and necessity of fertility preservation procedures in girls with cancer.Study Funding/competing Interest(s): This work was supported by the PanCareLIFE project that has received funding from the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement no 602030. In addition, the DCOG-LATER VEVO study was funded by the Dutch Cancer Society (Grant no. VU 2006-3622) and by the Children Cancer Free Foundation (Project no. 20) and the St Jude Lifetime cohort study by NCI U01 CA195547. The authors declare no competing interests.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Background: Granulocyte colony-stimulating factors (G-CSFs), which are used for the prevention of complications from chemotherapy-related neutropenia, are linked to the risk of developing second primary myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). The objective of this study was to examine the correlation between using a specific G-CSF agent and the risk of MDS/AML among older patients with non-Hodgkin lymphoma (NHL).Methods: This was a retrospective cohort study of adults aged >65 years who were diagnosed with first primary NHL between 2001 and 2011. With data from the Surveillance, Epidemiology, and End Results-Medicare-linked database, adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for the risk of MDS/AML associated with the receipt of G-CSF(filgrastim and pegfilgrastim) in Cox proportional-hazards models, which were stratified according to treatment accounting for confounding by indication.Results: Among 18,245 patients with NHL patients who had a median follow-up of 3.5 years, 56% received chemotherapy and/or immunotherapy, and G-CSF was most commonly used in those who received rituximab plus multiple chemotherapy regimens (77%). Subsequent MDS/AML diagnoses were identified in 666 patients (3.7%). A modest increased risk of MDS/AML was observed with the receipt of G-CSF (HR, 1.28; 95% CI, 1.01-1.62) and a trend was observed with increasing doses (Ptrend < .01). When specific agents were analyzed, an increased risk of MDS/AML was consistently observed with filgrastim (≥10 doses: HR, 1.67; 95% CI, 1.25-2.23), but not with pegfilgrastim (≥10 + doses: HR, 1.11; 95% CI, 0.84-1.45).Conclusions: A higher of MDS/AML was observed in patients with NHL risk among those who received G-CSF that was specific to the use of filgrastim (≥10 doses), but not pegfilgrastim. Neutropenia prophylaxis is an essential component of highly effective NHL treatment regimens. The differential risk related to the types of G-CSF agents used warrants further study given their increasing use and newly available, US Food and Drug Administration-approved, biosimilar products. [ABSTRACT FROM AUTHOR]

Study Question: Does endometrial scratching in women with one failed IVF/ICSI treatment affect the chance of a live birth of the subsequent fresh IVF/ICSI cycle?Summary Answer: In this study, 4.6% more live births were observed in the scratch group, with a likely certainty range between -0.7% and +9.9%.What Is Known Already: Since the first suggestion that endometrial scratching might improve embryo implantation during IVF/ICSI, many clinical trials have been conducted. However, due to limitations in sample size and study quality, it remains unclear whether endometrial scratching improves IVF/ICSI outcomes.Study Design, Size, Duration: The SCRaTCH trial was a non-blinded randomised controlled trial in women with one unsuccessful IVF/ICSI cycle and assessed whether a single endometrial scratch using an endometrial biopsy catheter would lead to a higher live birth rate after the subsequent IVF/ICSI treatment compared to no scratch. The study took place in 8 academic and 24 general hospitals. Participants were randomised between January 2016 and July 2018 by a web-based randomisation programme. Secondary outcomes included cumulative 12-month ongoing pregnancy leading to live birth rate.Participants/materials, Setting, Methods: Women with one previous failed IVF/ICSI treatment and planning a second fresh IVF/ICSI treatment were eligible. In total, 933 participants out of 1065 eligibles were included (participation rate 88%).Main Results and the Role Of Chance: After the fresh transfer, 4.6% more live births were observed in the scratch compared to control group (110/465 versus 88/461, respectively, risk ratio (RR) 1.24 [95% CI 0.96-1.59]). These data are consistent with a true difference of between -0.7% and +9.9% (95% CI), indicating that while the largest proportion of the 95% CI is positive, scratching could have no or even a small negative effect. Biochemical pregnancy loss and miscarriage rate did not differ between the two groups: in the scratch group 27/153 biochemical pregnancy losses and 14/126 miscarriages occurred, while this was 19/130 and 17/111 for the control group (RR 1.21 (95% CI 0.71-2.07) and RR 0.73 (95% CI 0.38-1.40), respectively). After 12 months of follow-up, 5.1% more live births were observed in the scratch group (202/467 versus 178/466), of which the true difference most likely lies between -1.2% and +11.4% (95% CI).Limitations, Reasons For Caution: This study was not blinded. Knowledge of allocation may have been an incentive for participants allocated to the scratch group to continue treatment in situations where they may otherwise have cancelled or stopped. In addition, this study was powered to detect a difference in live birth rate of 9%.Wider Implications Of the Findings: The results of this study are an incentive for further assessment of the efficacy and clinical implications of endometrial scratching. If a true effect exists, it may be smaller than previously anticipated or may be limited to specific groups of women undergoing IVF/ICSI. Studying this will require larger sample sizes, which will be provided by the ongoing international individual participant data-analysis (PROSPERO CRD42017079120). At present, endometrial scratching should not be performed outside of clinical trials.Study Funding/competing Interest(s): This study was funded by ZonMW, the Dutch organisation for funding healthcare research. J.S.E. Laven reports grants and personal fees from AnshLabs (Webster, Tx, USA), Ferring (Hoofddorp, The Netherlands) and Ministry of Health (CIBG, The Hague, The Netherlands) outside the submitted work. A.E.P. Cantineau reports 'other' from Ferring BV, personal fees from Up to date Hyperthecosis, 'other' from Theramex BV, outside the submitted work. E.R. Groenewoud reports grants from Titus Health Care during the conduct of the study. A.M. van Heusden reports personal fees from Merck Serono, personal fees from Ferring, personal fees from Goodlife, outside the submitted work. F.J.M. Broekmans reports personal fees as Member of the external advisory board for Ferring BV, The Netherlands, personal fees as Member of the external advisory board for Merck Serono, The Netherlands, personal fees as Member of the external advisory for Gedeon Richter, Belgium, personal fees from Educational activities for Ferring BV, The Netherlands, grants from Research support grant Merck Serono, grants from Research support grant Ferring, personal fees from Advisory and consultancy work Roche, outside the submitted work. C.B. Lambalk reports grants from Ferring, grants from Merck, grants from Guerbet, outside the submitted work.Trial Registration Number: Registered in the Netherlands Trial Register (NL5193/NTR 5342).Trial Registration Date: 31 July 2015.Date Of First Patient’s Enrolment: 26 January 2016. [ABSTRACT FROM AUTHOR]

Background: Neurobiological feedback in surgical training could translate to better educational outcomes such as measures of learning curve. This work examined the variation in brain activation of medical students when performing laparoscopic tasks before and after a training workshop, using functional near-infrared spectroscopy (fNIRS).Methods and Procedures: This single blind randomised controlled trial examined the prefrontal cortex activity (PFCA) differences in two groups of novice medical students during the acquisition of four laparoscopic tasks. Both groups were shown a basic tutorial video, with the "Trained-group" receiving an additional standardised one-to-one training on the tasks. The PFCA was measured pre- and post-intervention using a portable fNIRS device and reported as mean total oxygenated hemoglobin (HbOµm). Primary outcome of the study is the difference in HbOµm between post- and pre-intervention readings for each of the four laparoscopic tasks. The pre- and post-intervention laparoscopic tasks were recorded and assessed by two blinded individual assessors for objective scores of the performance.Results: 16 Trained and 16 Untrained, right-handed medical students with an equal sex distribution and comparable age distribution were recruited. Trained group had an attenuated left PFCA in the "Precision cutting" (p = 0.007) task compared to the Untrained group. Subgroup analysis by sex revealed attenuation in left PFCA in Trained females compared to Untrained females across two laparoscopic tasks: "Peg transfer" (p = 0.005) and "Precision cutting" (p = 0.003). No significant PFCA attenuation was found in male students who underwent training compared to Untrained males.Conclusion: A standardised laparoscopic training workshop promoted greater PFCA attenuation in female medical students compared to males. This suggests that female and male students respond differently to the same instructional approach. Implications include a greater focus on one-to-one surgical training for female students and use of PFCA attenuation as a form of neurobiological feedback in surgical training. [ABSTRACT FROM AUTHOR]

Purpose: Two innovative reinforced biologic materials were studied in a non-human primate hernia repair model. The test articles, which combine layers of ovine decellularized extracellular matrix with minimal amounts of synthetic polymer, were evaluated for their biologic performance as measured by inflammatory response, healing kinetics, integration, and remodeling into functional host tissue. For comparison, seven clinically used biologic and synthetic meshes were also studied. Methods: Animals were implanted with test articles in surgically created full-thickness midline abdominal wall defects, and evaluated macroscopically and histologically at 4, 12, and 24 weeks. Results: Macroscopically, biologics resorbed and remodeled into naturally appearing tissue; the reinforced biologics appeared similar, but remodeled earlier and were less prone to stretch. Synthetics developed a layer of reactive tissue above and separate from the contracted mesh structure. At early time points, the collagen networks of biologics and reinforced biologics were infiltrated by host cells primarily as a peripheral layer on the biologics. As early as 12 weeks, the collagen networks associated with the reinforced biologics remodeled into organized host collagen. By 24 weeks, both reinforced biologics and biologics had low levels of inflammation. In contrast, a foreign body response persisted at 24 weeks with the synthetics, which had developed less organized collagen, separate in space from the actual mesh. Conclusions: The current study shows a favorable response to reinforced biologics, which were associated with an initial inflammatory response, resolving by later time points, followed by active remodeling, and the formation of new morphologically functional collagen. [ABSTRACT FROM AUTHOR]

The presence of age-related neuropathology characteristic of Alzheimer's disease (AD) in people with Down syndrome (DS) is well-established. However, the early symptoms of dementia may be atypical and appear related to dysfunction of prefrontal circuitry.Objective: To characterize the initial informant reported age-related neuropsychiatric symptoms of dementia in people with DS, and their relationship to AD and frontal lobe function.Methods: Non-amnestic informant reported symptoms (disinhibition, apathy, and executive dysfunction) and amnestic symptoms from the CAMDEX-DS informant interview were analyzed in a cross-sectional cohort of 162 participants with DS over 30 years of age, divided into three groups: stable cognition, prodromal dementia, and AD. To investigate age-related symptoms prior to evidence of prodromal dementia we stratified the stable cognition group by age.Results: Amnestic and non-amnestic symptoms were present before evidence of informant-reported cognitive decline. In those who received the diagnosis of AD, symptoms tended to be more marked. Memory impairments were more marked in the prodromal dementia than the stable cognition group (OR = 35.07; P < .001), as was executive dysfunction (OR = 7.16; P < .001). Disinhibition was greater in the AD than in the prodromal dementia group (OR = 3.54; P = .04). Apathy was more pronounced in the AD than in the stable cognition group (OR = 34.18; P < .001).Conclusion: Premorbid amnestic and non-amnestic symptoms as reported by informants increase with the progression to AD. For the formal diagnosis of AD in DS this progression of symptoms needs to be taken into account. An understanding of the unique clinical presentation of DS in AD should inform treatment options. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the associations of regular glucosamine use with all-cause and cause-specific mortality in a large prospective cohort.Methods: This population-based prospective cohort study included 495 077 women and men (mean (SD) age, 56.6 (8.1) years) from the UK Biobank study. Participants were recruited from 2006 to 2010 and were followed up through 2018. We evaluated all-cause mortality and mortality due to cardiovascular disease (CVD), cancer, respiratory and digestive disease. HRs and 95% CIs for all-cause and cause-specific mortality were calculated using Cox proportional hazards models with adjustment for potential confounding variables.Results: At baseline, 19.1% of the participants reported regular use of glucosamine supplements. During a median follow-up of 8.9 years (IQR 8.3-9.7 years), 19 882 all-cause deaths were recorded, including 3802 CVD deaths, 8090 cancer deaths, 3380 respiratory disease deaths and 1061 digestive disease deaths. In multivariable adjusted analyses, the HRs associated with glucosamine use were 0.85 (95% CI 0.82 to 0.89) for all-cause mortality, 0.82 (95% CI 0.74 to 0.90) for CVD mortality, 0.94 (95% CI 0.88 to 0.99) for cancer mortality, 0.73 (95% CI 0.66 to 0.81) for respiratory mortality and 0.74 (95% CI 0.62 to 0.90) for digestive mortality. The inverse associations of glucosamine use with all-cause mortality seemed to be somewhat stronger among current than non-current smokers (p for interaction=0.00080).Conclusions: Regular glucosamine supplementation was associated with lower mortality due to all causes, cancer, CVD, respiratory and digestive diseases. [ABSTRACT FROM AUTHOR]

Background: To explore and compare safety, efficiency, and health-related quality of telephone triage in out-of-hours primary care (OOH-PC) services performed by general practitioners (GPs), nurses using a computerised decision support system (CDSS), or physicians with different medical specialities. Methods: Natural quasi-experimental cross-sectional study conducted in November and December 2016. We randomly selected 1294 audio-recorded telephone triage calls from two Danish OOH-PC services triaged by GPs (n = 423), nurses using CDSS (n = 430), or physicians with different medical specialities (n = 441). An assessment panel of 24 physicians used a validated assessment tool (Assessment of Quality in Telephone Triage - AQTT) to assess all telephone triage calls and measured health-related quality, safety, and efficiency of triage. Results: The relative risk (RR) of poor quality was significantly lower for nurses compared to GPs in four out of ten items regarding identifying and uncovering of problems. For most items, the quality tended to be lowest for physicians with different medical specialities. Compared to calls triaged by GPs (reference), the risk of clinically relevant undertriage was significantly lower for nurses, while physicians with different medical specialties had a similar risk (GP: 7.3%, nurse: 3.7%, physician: 6.1%). The risk of clinically relevant overtriage was significantly higher for nurses (9.1%) and physicians with different medical specialities (8.2%) compared to GPs (4.3%). GPs had significantly shorter calls (mean: 2 min 57 s, SD: 105 s) than nurses (mean: 4 min 44 s, SD: 168 s). Conclusions: Our explorative study indicated that nurses using CDSS performed better than GPs in telephone triage on a large number of health-related items, had a lower level of clinically relevant undertriage, but were perceived less efficient. Calls triaged by physicians with different medical specialities were perceived less safe and less efficient compared to GPs. Differences in the organisation of telephone triage may influence the distribution of workload in primary and secondary OOH services. Future research could compare the long-term outcomes following a telephone call to OOH-PC related to safety and efficiency. [ABSTRACT FROM AUTHOR]

Background: Owing to recent advances in cancer therapy, updated data are required for clinicians counselling patients on treatment of spinal metastases.Objective: To analyse the outcomes of surgical treatments of spinal metastases.Methods: Prospective and multicentric study that included consecutively patients operated on for spinal metastases between January 2016 and January 2017. Overall survival was calculated with the Kaplan-Meier method. Cox proportional hazard model was used to calculate hazard ratio (HR) analysing mortality risk according to preoperative Karnofsky performance status (KPS), mobility level and neurological status.Results: A total of 252 patients were included (145 males, 107 females) aged a mean 63.3 years. Median survival was 450 days. Primary cancer sites were lung (21%) and breast (19%). Multiple spinal metastases involved 122 patients (48%). Concomitant skeletal and visceral metastases were noted in 90 patients (36%). Main procedure was laminectomy and posterior fixation (57%). Overall, pain and mobility level were improved postoperatively. Most patients had normal preoperative motor function (50%) and remained so postoperatively. Patients "bedbound" on admission were the less likely to recover. In-hospital death rate was 2.4% (three disease progression, one septic shock, one pneumonia, one pulmonary embolism). Complication rate was 33%, deep wound infection was the most frequent aetiology. Higher mortality was observed in patients with poorest preoperative KPS (KPS 0-40%, HR = 3.1, p < 0.001) and mobility level ("bedbound", HR = 2.16, p < 0.001). Survival seemed also to be linked to preoperative neurological function.Conclusion: Surgical treatments helped maintain reasonable condition for patients with spinal metastases. Intervention should be offered before patients' condition worsen to ensure better outcomes. [ABSTRACT FROM AUTHOR]

Background: Iron deficiency anemia affects hundreds of millions of women and children worldwide and is associated with impaired infant outcomes. Small-quantity lipid-based nutrient supplement (LNS) have been found to reduce the prevalence of anemia and iron deficiency in some trials.Objectives: We evaluated the effectiveness of daily LNS supplementation on child anemia and micronutrient status in Madagascar within the context of an existing, scaled-up nutrition program.Methods: We cluster-randomized 125 communities to (T0) a routine program with monthly growth monitoring and nutrition education; (T1) T0 + home visits for intensive nutrition counselling; (T2) T1 + LNS for children aged 6-18 mo; (T3) T2 + LNS for pregnant/lactating women; or (T4) T1 + parenting messages. Pregnant women and infants aged <12 mo were enrolled in 2014 and followed for 2 y. Child outcome measures included hemoglobin and anemia assessed using the HemoCue 301 system (n = 3561), and serum ferritin and soluble transferrin receptor as markers of iron status, retinol-binding protein as a marker of vitamin A status, and C-reactive protein and α-1 acid glycoprotein from a finger stick blood draw among a subsample (n = 387). We estimated mean difference using linear regression and prevalence ratios using modified Poisson regression accounting for the clustered design. All analyses were intention-to-treat.Results: Children in the LNS groups (T2 and T3) had ∼40% lower prevalence of anemia and iron deficiency anemia and 25% lower prevalence of iron deficiency than children in the control group (T0) (P < 0.05 for all). There were no differences in any of the biomarkers when comparing children in the T4 group with those in T0; nor were there differences between T3 and T2.Conclusions: Our findings suggest the provision of LNS in the context of a large-scale program offers significant benefits on anemia and iron status in young children.This trial was registered at www.isrctn.com as ISRCTN14393738. [ABSTRACT FROM AUTHOR]

Rationale: Non-cystic fibrosis bronchiectasis is characterized by airway mucus accumulation and sputum production, but the role of mucus concentration in the pathogenesis of these abnormalities has not been characterized.Objectives: This study was designed to: 1) measure mucus concentration and biophysical properties of bronchiectasis mucus; 2) identify the secreted mucins contained in bronchiectasis mucus; 3) relate mucus properties to airway epithelial mucin RNA/protein expression; and 4) explore relationships between mucus hyperconcentration and disease severity.Methods: Sputum samples were collected from subjects with bronchiectasis, with and without chronic erythromycin administration, and healthy control subjects. Sputum percent solid concentrations, total and individual mucin concentrations, osmotic pressures, rheological properties, and inflammatory mediators were measured. Intracellular mucins were measured in endobronchial biopsies by immunohistochemistry and gene expression. MUC5B (mucin 5B) polymorphisms were identified by quantitative PCR. In a replication bronchiectasis cohort, spontaneously expectorated and hypertonic saline-induced sputa were collected, and mucus/mucin concentrations were measured.Measurements and Main Results: Bronchiectasis sputum exhibited increased percent solids, total and individual (MUC5B and MUC5AC) mucin concentrations, osmotic pressure, and elastic and viscous moduli compared with healthy sputum. Within subjects with bronchiectasis, sputum percent solids correlated inversely with FEV1 and positively with bronchiectasis extent, as measured by high-resolution computed tomography, and inflammatory mediators. No difference was detected in MUC5B rs35705950 SNP allele frequency between bronchiectasis and healthy individuals. Hypertonic saline inhalation acutely reduced non-cystic fibrosis bronchiectasis mucus concentration by 5%.Conclusions: Hyperconcentrated airway mucus is characteristic of subjects with bronchiectasis, likely contributes to disease pathophysiology, and may be a target for pharmacotherapy. [ABSTRACT FROM AUTHOR]

Purpose: Ventral hernia repair with concurrent panniculectomy (VHR-PAN) is associated with high wound complication rates despite reported increased patient satisfaction. Some surgeons believe negative-pressure therapy after primary closure of the surgical incision (ciNPT) may lower wound complications in high-risk abdominal wounds. This study aims to evaluate if ciNPT improves outcomes in patients undergoing VHR-PAN.Methods: An 8-year retrospective cohort study was performed on patients who underwent VHR-PAN. Patients were divided into two groups: those who received closed-incision negative-pressure therapy ("ciNPT") and those who received standard sterile dressings ("SSD"). The primary outcome of interest was the rate of postoperative complications between these groups. Complications were subdivided into surgical site occurrences (which included surgical site occurrences that required an intervention), return to the operating room, and hernia recurrence.Results: A total of 104 patients were analyzed: 62 in the ciNPT group and 42 in the SSD group. Median follow-up duration was similar between both groups (182 days vs 195 days, p = 0.624). Patients in the ciNPT group had fewer total complications (57% vs. 83%, p = 0.004) and fewer SSO (47% vs. 69%, p = 0.025). However, no differences were noted when comparing individual complications (SSI, wound dehiscence, skin necrosis, chronic wound, seroma, and hematoma). There was no difference in return to the operating room (27% vs. 26%, p = 0.890) or hernia recurrence (21% vs 19%, p = 0.811). Multivariate analysis showed that ciNPT decreased the risk of SSOPI nearly fourfold (odds ratio 0.28, 95% CI = 0.09-0.87, p = 0.027).Conclusions: This study showed that closed-incision negative-pressure therapy in ventral hernia repair with concurrent panniculectomy may decrease the rate of wound complications in this high-risk population. [ABSTRACT FROM AUTHOR]

In the aftermath of a large Q fever (QF) epidemic in the Netherlands during 2007-2010, new chronic QF (CQF) patients continue to be detected. We developed a health-economic decision model to evaluate the cost-effectiveness of a 1-time screening program for CQF 7 years after the epidemic. The model was parameterized with spatial data on QF notifications for the Netherlands, prevalence data from targeted screening studies, and clinical data from the national QF database. The cost-effectiveness of screening varied substantially among subpopulations and geographic areas. Screening that focused on cardiovascular risk patients in areas with high QF incidence during the epidemic ranged from cost-saving to €31,373 per quality-adjusted life year gained, depending on the method to estimate the prevalence of CQF. The cost per quality-adjusted life year of mass screening of all older adults was €70,000 in the most optimistic scenario. [ABSTRACT FROM AUTHOR]

The Mid-Atlantic Twin Registry (MATR) is a population-based registry of more than 60,000 twins primarily born or living in Virginia, North Carolina and South Carolina. Researchers may utilize the MATR for administration of research services, including study recruitment, data or sample (e.g., DNA) collection, archival dataset creation, as well as data collection through mailed, phone or online surveys. In addition, the MATR houses the MATR Repository, with over 1700 DNA samples primarily from whole blood available for researchers interested in DNA genotyping. For over 40 years MATR twins have participated in research studies with investigators from a range of scientific disciplines and institutions. These studies, which have resulted in numerous publications, explored diverse topics, including substance use, smoking behaviors, developmental psychopathology, bullying, children's health, cardiovascular disease, cancer, the human microbiome, epigenetics of aging, children of twins and sleep homeostasis. Researchers interested in utilizing twins are encouraged to contact the MATR to discuss potential research opportunities. [ABSTRACT FROM AUTHOR]

Background: Acute mesenteric ischaemia (AMI) is a life-threatening surgical emergency resulting from thromboembolic occlusion of the mesenteric vasculature. Traditional management of AMI has been open revascularisation with or without bowel resection—a procedure which carries considerable morbidity and mortality in an already unwell, compromised patient. Endovascular and more minimally invasive management approaches to AMI have been reported. Proponents of endovascular management suggest this approach may be associated with reduced morbidity and mortality compared with open surgery. Objectives: To assess the impact of endovascular approach for AMI on mortality and need for subsequent laparotomy and/or bowel resection. Data Sources: The search bodies PubMed and Medline were interrogated. Eligibility Criteria, Participants and Interventions: All studies in English with greater than 10 patients examining outcomes for patients undergoing endovascular intervention for acute mesenteric ischaemia were included. All patients over 18 years presenting with a diagnosis of acute mesenteric ischaemia secondary to an arterial thromboembolic source were included. Studies examining endovascular intervention alone or endovascular and open intervention were selected. Results: The 30-day mortality for endovascular approach from all 13 studies was 16–42%. Of the 7 comparative studies including results of open revascularisation, the 30-day mortality for patient treated with an endovascular approach was 15–39% versus 33–50% for open revascularisation. Laparotomy rates post-initial endovascular intervention ranged from 13 to 73%. Bowel resection post-endovascular therapy ranged from 14 to 40% among studies. Concerning 7 comparative studies for open versus endovascular revascularisation, the rate of bowel resection in the endovascular group ranged 14–28% and 33–63% in the open cohort. Endovascular intervention also demonstrated lower median length (s) of bowel resected. Limitations: Heterogeneity of studies and patient populations studied including selection bias. Conclusions and implications of findings: Endovascular management may be associated with reduced mortality and need for/length of bowel resection compared with the traditional open approach, but there remains a paucity of robust data to support this. The available literature illustrates that a subgroup of patients without haemodynamic compromise and more insidious onset may garner benefit from endovascular intervention. [ABSTRACT FROM AUTHOR]

Aims: To describe the nature and causes of patient safety incidents relating to care at home for children with enteral feeding devices.Methods: We analysed incident data relating to paediatric nasogastric, gastrostomy or jejunostomy feeding at home from England and Wales' National Reporting and Learning System between August 2012 and July 2017. Manual screening by two authors identified 274 incidents which met the inclusion criteria. Each report was descriptively analysed to identify the problems in the delivery of care, the contributory factors and the patient outcome.Results: The most common problems in care related to equipment and devices (n=98, 28%), procedures and treatments (n=86, 24%), information, training and support needs of families (n=54, 15%), feeds (n=52, 15%) and discharge from hospital (n=31, 9%). There was a clearly stated harm to the child in 52 incidents (19%). Contributory factors included staff/service availability, communication between services and the circumstances of the family carer.Conclusions: There are increasing numbers of children who require specialist medical care at home, yet little is known about safety in this context. This study identifies a range of safety concerns relating to enteral feeding which need further investigation and action. Priorities for improvement are handovers between hospital and community services, the training of family carers, the provision and expertise of services in the community, and the availability and reliability of equipment. Incident reports capture a tiny subset of the total number of adverse events occurring, meaning the scale of problems will be greater than the numbers suggest. [ABSTRACT FROM AUTHOR]

Objective: To systematically review the literature and assess the diagnostic value of biomarkers in detection of late-onset left ventricular (LV) dysfunction in childhood cancer survivors (CCS) treated with anthracyclines.Methods: We systematically searched the literature for studies that evaluated the use of biomarkers for detection of LV dysfunction in CCS treated with anthracyclines more than 1 year since childhood cancer diagnosis. LV dysfunction definitions were accepted as an ejection fraction <50% or <55% and/or a fractional shortening <28%, <29% or <30%. Contingency tables were created to assess diagnostic accuracies of biomarkers for diagnosing LV dysfunction.Results: Of 1362 original studies screened, eight heterogeneous studies evaluating four different biomarkers in mostly asymptomatic CCS were included. In four studies, an abnormal N-terminal pro-B-type natriuretic peptide (NT-proBNP, cut-off range 63-125 ng/L) had low sensitivity (maximally 22%) and a specificity of up to 97% for detection of LV dysfunction. For troponin levels, in five studies one patient had an abnormal troponin value as well as LV dysfunction, while in total 127 patients had LV dysfunction without troponin elevations above cut-off values (lowest 0.01 ng/mL). Two studies that evaluated brain natriuretic peptide and nitric oxide were underpowered to draw conclusions.Conclusions: In individual studies, the diagnostic value of NT-proBNP for detection of LV dysfunction in CCS is limited. Troponins have no role in detecting late-onset LV dysfunction with cut-off values as low as 0.01 ng/mL. Further study on optimal NT-proBNP cut-off values for rule out or rule in of LV dysfunction is warranted. [ABSTRACT FROM AUTHOR]

Background: Methylglyoxal (MGO) is the most potent precursor of advanced glycation end products (AGEs). MGO and AGEs have been associated with diabetes, its complications, and other age-related diseases. Experimental studies have shown that the flavonoids quercetin and epicatechin are able to scavenge MGO and lower AGE formation.Objective: Data on the effects of these flavonoids on MGO and AGE concentrations in humans are not yet available. We therefore investigated the effect of quercetin and epicatechin on the concentrations of MGO and AGEs in a post hoc analysis.Methods: Thirty-seven apparently healthy, nonsmoking adults with a systolic blood pressure between 125 and 160 mm Hg at screening were included in a randomized, double-blind, placebo-controlled crossover trial. Participants ingested (-)-epicatechin (100 mg/d), quercetin 3-glucoside (160 mg/d), or placebo capsules for periods of 4 wk separated by 4-wk washout periods. Fasting blood samples were collected at the start and end of each intervention period. Liquid chromatography-tandem mass spectrometry was used to determine plasma concentrations of the dicarbonyl compounds MGO, glyoxal (GO), and 3-deoxyglucosone (3-DG) and free and protein-bound AGEs. Gene expression of glyoxalase 1 (GLO1), the enzyme involved in the degradation of MGO, was determined by either microarray or quantitative reverse transcriptase-polymerase chain reaction.Results: The treatment effect (Δtreatment - Δplacebo) of quercetin on MGO was -40.2 nmol/L (95% CI: -73.6, -6.8 nmol/L; P = 0.019), a decrease of 11% from baseline values, whereas GO, 3-DG, and free and protein-bound AGEs did not change significantly. Epicatechin did not affect the concentrations of dicarbonyls and free and protein-bound AGEs. We did not find a significant change in expression of GLO1.Conclusions: In apparently healthy (pre)hypertensive men and women, quercetin but not epicatechin decreased plasma MGO concentrations. Quercetin may potentially form a new treatment strategy for diseases in which MGO plays a pivotal role. This study was registered at clinicaltrials.gov as NCT01691404. [ABSTRACT FROM AUTHOR]