The incidence of major bleeding in adult patients with urogenital and gynecological cancer being treated with direct oral anticoagulants (DOACs): a systematic review.

BACKGROUND: Direct oral anticoagulants (DOACs) are the mainstay of treatment for venous thromboembolism (VTE) and non-valvular atrial fibrillation (AF), with or without an underlying cancer. Patients with cancer have a 2-3-fold increase in risk for bleeding complications compared to non-cancer patients taking anticoagulant therapy, however the incidence of bleeding for urogenital and gynecological cancers on DOACs are uncertain. AIMS: To assess the bleeding risk associated with the use of DOACs in patients with urogenital and/or gynecological cancers. METHOD: We conducted a systematic review of randomized controlled trials (RCTs) and prospective cohort studies to address the safety of DOACs for VTE and AF when used in patients with urogenital and/or gynecological malignancy. The primary outcomes assessed were major and clinically relevant non-major (CRNMB) bleeding, with minor bleeding considered as a secondary outcome. MEDLINE, EMBASE and COCHRANE Central Registry of Controlled Trials were searched up to and including Oct 28, 2022. The study protocol was registered in PROSPERO (CRD42022370981). Studies were independently assessed for inclusion and data extracted in duplicate. RESULT: Seven studies met our inclusion criteria (Fig. 1): 2 RCTs and 5 prospective cohort studies. A total of 676 patients treated with DOACs were included, 628 (92.8%) had VTE and 48 (7.1%) had AF. In patients with VTE treated with DOACs, the pooled major bleeding rate was 2.1%, 95% confidence intervals (CI) 0.9-3.3% (Fig. 2). Pooled estimates could not be determined for AF patients given small event and patient numbers. CONCLUSION: Major bleeding rates in urogenital and/or gynecological cancer patients treated with DOACs are similar to that of the general cancer population.

Natural fixatives alternative to formalin in histopathology: A systematic review.

INTRODUCTION: Since constant long-term exposure to formaldehyde endangers the health of laboratory personnel, sugar-based natural products have become interesting alternative fixatives to formaldehyde because of their preservative and antibacterial properties. However, there are controversial findings on the fixative effects of natural fixatives. This study systematically reviews the evidence comparing natural fixatives' types, dilutions, fixative properties and staining quality in normal tissues and histopathological specimens. MATERIALS AND METHODS: A comprehensive search was performed for studies comparing the natural fixatives- and formaldehyde-fixed tissues using databases from inception to January 2022: PubMed, Ovid Medline and Google Scholar. Two independent reviewers did data extraction. The data were pooled for the type of natural fixatives, their concentrations and fixative qualities compared to formaldehyde. RESULTS: Fifteen studies were included in this systematic review. Nine studies used one natural fixative with different dilutions, while six used several natural fixatives to compare their fixative properties with formaldehyde. The most used natural fixative was honey (n = 12) followed by jaggery (n = 8), sugar (n = 3) and others (n = 1). Honey showed the most promising results in fixation and staining, which are compatible with formalin. Jaggery and sugar also showed the possibility of replacing formaldehyde in tissue fixation and staining in smaller tissue samples. CONCLUSION: Natural fixatives showed promising results in tissue fixation. However, optimising the concentrations and conditions of natural fixatives is difficult because of the different chemical constituents and production steps. More comprehensive studies are necessary for application.

Calcaneal quantitative ultrasound is associated with all-cause and cardiovascular disease mortality independent of hip bone mineral density.

Osteoporosis has been linked with increased risk of cardiovascular disease previously. However, few studies have detailed bone and vascular information. In a prospective study of older women, we demonstrated heel quantitative ultrasound measures were associated with increased cardiovascular and all-cause mortality, independent of established cardiovascular risk factors. INTRODUCTION: Osteoporosis and low bone mineral density (BMD) have been previously linked to cardiovascular disease (CVD) and mortality. Calcaneal quantitative ultrasound (QUS) is used to evaluate bone material properties, especially in older women. However, it is uncertain whether it is related to risk of mortality. This study was aimed to investigate the association between calcaneal QUS measurements and 15-year all-cause and CVD mortality in 1404 older women (mean age 75.2 ± 2.7 years). METHODS: One thousand four hundred four older women, participants of Calcium Intake Fracture Outcome study (CAIFOS), had calcaneal bone measured at baseline (1998) and followed for 15 years. The primary outcomes, any deaths, and deaths attributable to cardiovascular causes ascertained by using linked data were obtained from Western Australia data linkage system. RESULTS: Over the 15 years of follow-up (17,955 person years), 584 of the women died, and 223 from CVD. For every standard deviation (SD), reduction in broadband ultrasound attenuation (BUA) in minimally and multivariable-adjusted model including cardiovascular risk factors increased relative hazards for all-cause (multivariable-adjusted HR 1.15; 95%CI: 1.06-1.26, p = 0.001) and CVD mortality (multivariable-adjusted HR 1.20; 95%CI: 1.04-1.38, p = 0.010). Such relationships also persisted when hip BMD was included in the model (all-cause mortality HR 1.19; 95%CI: 1.07-1.33, p = 0.002; CVD mortality HR 1.28; 95%CI: 1.07-1.53, p = 0.008). CONCLUSION: BUA is associated with all-cause and CVD mortality in older women independent of BMD and established CVD risk factors. Understanding why and how these are related may provide further insights about the bone-vascular nexus as well as therapeutic targets benefiting both systems.

Incidence and Outcomes of Early Cancers After Kidney Transplantation.

Outcomes of early cancers after kidney transplantation are not well-understood. We included recipients of first live and deceased donor kidney transplants who developed de novo cancers in Australia and New Zealand between 1980-2016. We compared the frequency and stage of specific cancer types that developed early (≤12-months) and late (>12-months) post-transplantation. Risk factors for death were evaluated using multivariable Cox regression analyses. Of 2,759 recipients who developed de novo cancer, followed-up for 40,035 person-years, 243 (8.8%) patients were diagnosed with early cancer. Post-transplant lymphoproliferative disease, urinary cancers and melanoma were the most common cancer types (26%, 18%, and 12%) and the majority were either in-situ or locally invasive lesions (55%, 84%, and 86%). Tumors arising early from the gastrointestinal and respiratory systems were uncommon but aggressive, with 40% presenting with metastatic disease at time of diagnosis. Overall, 32% of patients with early cancers died within a median of 4.7 months (IQR:0.6-16) post-diagnosis and 91% were cancer-related deaths. Older recipient and donor age were associated with an increased risk of all-cause death. Early cancers, though infrequent in kidney transplant recipients, are associated with poor outcomes, as nearly 1 in 3 died from cancer-related death; with majority of deaths occurring within 12-months of cancer diagnosis.

Parental control on handphone access and usage among Malaysian children.

INTRODUCTION: Parental control for a child's handphone access is important to ensure online safety. This study was to determine parental control on handphone access and the usage amongst Malaysian children. MATERIALS AND METHODS: A cross-sectional survey was conducted electronically between April 2017 and March 2018 among parents with children above 2 years of age, who owned a handphone. The 10-item questionnaire included questions about rules applied to the use of handphones, education on cybersafety, the characteristics and activities of their youngest children who had full-time access to a handphone, and parental perceptions of their children's usage of handphones. A total of 215 parents were included. RESULTS: From this, 92% controlled their children's handphones use by setting rules. The commonest rules were limiting the time of handphone usage (77%) and being aware of whom the child was communicating with (77%). The majority (94%) educated their children on cybersafety, and the commonest discussed topic was not to communicate with strangers (93%). The children's average age of first handphone ownership was 10.6 (SD: 3.6) years, and the use of the handphone averaged 17.4 (SD: 18.5) hours a week. Despite the rules and education provided, only a quarter of parents were confident of their children's capability to manage their own safety when using handphones (27%). CONCLUSION: In summary, Malaysian parents did control their children's handphone usage.

A Comparison of the P-POSSUM and NELA Risk Score for Patients Undergoing Emergency Laparotomy in Singapore.

BACKGROUND (AIMS, HYPOTHESES, OR OBJECTIVES): Emergency laparotomy (EL) is a high-risk surgical procedure associated with considerable morbidity and mortality around the world. A reliable risk-assessment tool that is specific to patients undergoing EL allows the early identification of high-risk patients and enables appropriate healthcare resource allocation. The objective of this study was to compare the commonly used Portsmouth-physiologic and operative severity score for the enumeration of mortality and morbidity (P-POSSUM) with the recently developed National Emergency Laparotomy Audit (NELA) score in terms of their accuracy for identifying patients at increased risk of 30-day mortality in a predominantly Asian population. METHODS: Physiological and operative data from a prospectively collected audit of adult patients undergoing EL in 2018 and 2019 across two tertiary hospitals in Singapore were used to retrospectively calculate both the P-POSSUM and NELA scores for each patient encounter. This was then compared to actual mortality rates to determine each model's accuracy and precision. RESULTS: 830 patients were included in the study with a 30-day mortality of 5.66%. The area under the receiver operating characteristics curve (AUROC) was similar for both the NELA (0.86, p < 0.001, 95% CI 0.81-0.91) and the P-POSSUM models (0.84, p < 0.001, 95% CI 0.78-0.89). While the models over-predicted mortality, overall O:E ratios showed that the NELA model performance was superior to that of P-POSSUM (0.58 [95% CI 0.43-0.77] compared to 0.34 [95% CI 0.26-0.46]). CONCLUSION: The NELA risk-prediction model accurately predicts 30-day mortality in this large cohort of patients undergoing EL and outperforms the current P-POSSUM model. We recommend that the NELA score should replace the P-POSSUM score as a model to distinguish between high- and low-risk patients undergoing EL.

Molecular correlates of response to capmatinib in advanced non-small-cell lung cancer: clinical and biomarker results from a phase I trial.

BACKGROUND: Dysregulation of receptor tyrosine kinase MET by various mechanisms occurs in 3%-4% of non-small-cell lung cancer (NSCLC) and is associated with unfavorable prognosis. While MET is a validated drug target in lung cancer, the best biomarker strategy for the enrichment of a susceptible patient population still remains to be defined. Towards this end we analyze here primary data from a phase I dose expansion study of the MET inhibitor capmatinib in patients with advanced MET-dysregulated NSCLC. PATIENTS AND METHODS: Eligible patients [≥18 years; Eastern Cooperative Oncology Group (ECOG) performance status ≤2] with MET-dysregulated advanced NSCLC, defined as either (i) MET status by immunohistochemistry (MET IHC) 2+ or 3+ or H-score ≥150, or MET/centromere ratio ≥2.0 or gene copy number (GCN) ≥5, or (ii) epidermal growth factor receptor wild-type (EGFRwt) and centrally assessed MET IHC 3+, received capmatinib at the recommended dose of 400 mg (tablets) or 600 mg (capsules) b.i.d. The primary objective was to determine safety and tolerability; the key secondary objective was to explore antitumor activity. The exploratory end point was the correlation of clinical activity with different biomarker formats. RESULTS: Of 55 patients with advanced MET-dysregulated NSCLC, 40/55 (73%) had received two or more prior systemic therapies. All patients discontinued treatment, primarily due to disease progression (69.1%). The median treatment duration was 10.4 weeks. The overall response rate per RECIST was 20% (95% confidence interval, 10.4-33.0). In patients with MET GCN ≥6 (n = 15), the overall response rate by both the investigator and central assessments was 47%. The median progression-free survival per investigator for patients with MET GCN ≥6 was 9.3 months (95% confidence interval, 3.8-11.9). Tumor responses were observed in all four patients with METex14. The most common toxicities were nausea (42%), peripheral edema (33%), and vomiting (31%). CONCLUSIONS: MET GCN ≥6 and/or METex14 are suited to predict clinical activity of capmatinib in patients with NSCLC (NCT01324479).

Modification of the RANKL-RANK-binding site for the immunotherapeutic treatment of osteoporosis.

Here, we proposed the use of mutated RANKL as an immunogen for active immunization and to induce anti-cytokine antibodies for osteoporosis treatment. INTRODUCTION: Osteoclasts are responsible for bone resorption in bone-related disorders. Anti-cytokine therapeutic antibodies such as denosumab are effective for the treatment of osteoporosis. However, problems with antibody manufacturing and the immunogenicity caused by multiple antibody doses have led to the use of auto-cytokines as immunogens to induce anti-cytokine antibodies. METHODS: RANKL was point-mutated based on the crystal structure of the complex of RANKL and its receptor RANK. RESULTS: As a proof of concept, immunization with RANKL produced high levels of specific antibodies and blocked osteoclast development in vitro and inhibited osteoporosis in RANKL-treated or ovariectomized mouse models. CONCLUSIONS: The results demonstrate the successful use of mutated RANKL as an immunogen for the induction of anti-RANKL immune response. This strategy is useful in general anti-cytokine immunotherapy to avoid toxic side effects of osteoporosis treatment.

Targeting neutrophils using novel drug delivery systems in chronic respiratory diseases.

Neutrophils are essential effector cells of immune system for clearing the extracellular pathogens during inflammation and immune reactions. Neutrophils play a major role in chronic respiratory diseases. In respiratory diseases such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, lung cancer and others, there occurs extreme infiltration and activation of neutrophils followed by a cascade of events like oxidative stress and dysregulated cellular proteins that eventually result in apoptosis and tissue damage. Dysregulation of neutrophil effector functions including delayed neutropil apoptosis, increased neutrophil extracellular traps in the pathogenesis of asthma, and chronic obstructive pulmonary disease enable neutrophils as a potential therapeutic target. Accounting to their role in pathogenesis, neutrophils present as an excellent therapeutic target for the treatment of chronic respiratory diseases. This review highlights the current status and the emerging trends in novel drug delivery systems such as nanoparticles, liposomes, microspheres, and other newer nanosystems that can target neutrophils and their molecular pathways, in the airways against infections, inflammation, and cancer. These drug delivery systems are promising in providing sustained drug delivery, reduced therapeutic dose, improved patient compliance, and reduced drug toxicity. In addition, the review also discusses emerging strategies and the future perspectives in neutrophil-based therapy.

Resistant hypertension during antituberculosis treatment: how is rifampicin implicated?

A 67-year-old mental institute resident was treated for smear-positive pulmonary tuberculosis. His background history included chronic essential hypertension which was well-controlled with amlodipine 10mg daily. However, his blood pressure became suboptimal one week into antitubercular treatment, necessitating escalation of antihypertensive therapy up to six medications. Following completion of antitubercular treatment, his blood pressure improved markedly. The number of antihypertensives was able to be reduced to only two after a month. We postulate that rifampicin has attenuated the therapeutic effect of amlodipine via potent induction of hepatic CYP3A4 but the failure to control the blood pressure even with medications unrelated to cytochrome P450 pathways raises the spectre of an additional interaction.

Andexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors.

BACKGROUND: Andexanet alfa (andexanet) is a recombinant modified human factor Xa decoy protein that has been shown to reverse the inhibition of factor Xa in healthy volunteers. METHODS: In this multicenter, prospective, open-label, single-group study, we evaluated 67 patients who had acute major bleeding within 18 hours after the administration of a factor Xa inhibitor. The patients all received a bolus of andexanet followed by a 2-hour infusion of the drug. Patients were evaluated for changes in measures of anti-factor Xa activity and were assessed for clinical hemostatic efficacy during a 12-hour period. All the patients were subsequently followed for 30 days. The efficacy population of 47 patients had a baseline value for anti-factor Xa activity of at least 75 ng per milliliter (or ≥0.5 IU per milliliter for those receiving enoxaparin) and had confirmed bleeding severity at adjudication. RESULTS: The mean age of the patients was 77 years; most of the patients had substantial cardiovascular disease. Bleeding was predominantly gastrointestinal or intracranial. The mean (±SD) time from emergency department presentation to the administration of the andexanet bolus was 4.8±1.8 hours. After the bolus administration, the median anti-factor Xa activity decreased by 89% (95% confidence interval [CI], 58 to 94) from baseline among patients receiving rivaroxaban and by 93% (95% CI, 87 to 94) among patients receiving apixaban. These levels remained similar during the 2-hour infusion. Four hours after the end of the infusion, there was a relative decrease from baseline of 39% in the measure of anti-factor Xa activity among patients receiving rivaroxaban and of 30% among those receiving apixaban. Twelve hours after the andexanet infusion, clinical hemostasis was adjudicated as excellent or good in 37 of 47 patients in the efficacy analysis (79%; 95% CI, 64 to 89). Thrombotic events occurred in 12 of 67 patients (18%) during the 30-day follow-up. CONCLUSIONS: On the basis of a descriptive preliminary analysis, an initial bolus and subsequent 2-hour infusion of andexanet substantially reduced anti-factor Xa activity in patients with acute major bleeding associated with factor Xa inhibitors, with effective hemostasis occurring in 79%. (Funded by Portola Pharmaceuticals; ANNEXA-4 ClinicalTrials.gov number, NCT02329327 .).

Effects of calcium supplementation on circulating osteocalcin and glycated haemoglobin in older women.

One year of calcium supplementation in older women led to modest reductions in total osteocalcin and undercarboxylated osteocalcin (ucOC), with no changes in muscle or fat mass, or glycated haemoglobin. Future studies should explore whether treatments with more profound effects of suppressing ucOC may lead to impaired glycaemic control. INTRODUCTION: Total osteocalcin (TOC) is a marker of bone turnover, while its undercarboxylated form has beneficial effects on glucose metabolism in mice. This post hoc analysis of a randomised double-blind, placebo-controlled trial examined whether 1 year of calcium supplementation affected circulating TOC, undercarboxylated osteocalcin (ucOC) or glycated haemoglobin (HbA1c) in 1368 older community-dwelling women (mean age 75.2 ± 2.7 years). METHODS: Women enrolled in the Calcium Intake Fracture Outcome Study trial (1998-2003) were supplemented with 1.2 g/d of elemental calcium (in the form of calcium carbonate) or placebo. Circulating TOC, ucOC and HbA1c was measured at 1 year (1999). RESULTS: After 1 year of calcium supplementation, TOC and ucOC levels were 17% and 22% lower compared with placebo (mean 22.7 ± 9.1 vs. 27.3 ± 10.9 µg/L and 11.1 ± 4.9 vs. 13.0 ± 5.7 µg/L, both P < 0.001). Carboxylated osteocalcin/ucOC was 6% lower after calcium supplementation (P < 0.05). Despite this, no differences in HbA1c were observed (calcium, 5.2 ± 0.6 vs. placebo, 5.3 ± 0.8%; P = 0.08). Calcium supplementation did not affect BMI, whole body lean or fat mass. In exploratory analyses, total calcium (dietary and supplemental) was inversely related to TOC and ucOC, indicating calcium intake is an important dietary determinant of osteocalcin levels. CONCLUSION: One year of calcium supplementation in older women led to modest reductions in TOC and ucOC, with no changes in muscle or fat mass, or HbA1c. Future studies should explore whether treatments with more profound effects of suppressing ucOC may lead to impaired glycaemic control.

Transverse technique: complementary approach to measurement of first-trimester uterine artery Doppler.

OBJECTIVES: To define a protocol for the first-trimester assessment of uterine artery pulsatility index (UtA-PI) using the new transverse technique, to evaluate UtA-PI measured using the transverse approach vs that obtained using the conventional sagittal approach and to determine if accelerated onsite training (in both methods) of inexperienced sonographers can achieve reproducible UtA-PI measurements comparable with those obtained by an experienced sonographer. METHODS: This was a prospective observational study of women with a singleton pregnancy attending for routine combined first-trimester screening at 11 to 13 + 6 weeks' gestation. The study consisted of two parts, each conducted at a different center (Part 1 in Calgary, Canada and Part 2 in Hong Kong). In Part 1, UtA-PI measurements were performed using the transverse and sagittal techniques by four sonographers trained in both methods, in 10 cases each, and measurement indices (PI), time required and subjective difficulty in obtaining satisfactory measurements were compared. The one sample t-test and Wilcoxon signed rank test were used when appropriate. Bland-Altman plots were used to assess measurement agreement, and intraclass correlation coefficient (ICC) was used to evaluate measurement reliability. A target plot was used to assess measures of central tendency and dispersion. In Part 2, one experienced and three inexperienced sonographers prospectively measured UtA-PI using both approaches in 42 and 35 women, respectively. Inexperienced sonographers underwent accelerated onsite training by the experienced sonographer. Measurement approach and sonographer order were on a random basis. ICC, Bland-Altman and Passing-Bablok analyses were performed to assess measurement agreement and reliability and effect of accelerated training. RESULTS: In Part 1, no difference was observed between the two techniques in mean time to acquire the measurements (118 s for sagittal vs 106 s for transverse; P = 0.38). The four sonographers reported that the transverse technique was subjectively easier to perform (P = 0.04). Bias and ICC for mean UtA-PI between sagittal and transverse measurements were -0.05 (95% limits of agreement, -0.48 to 0.37) and 0.94, respectively. Measurements obtained using the transverse technique after correcting for gestational age were significantly closer to the expected distribution than those obtained using the sagittal technique. In Part 2, there were no significant differences in median UtA-PI measured using the different approaches for both experienced and inexperienced sonographers (P > 0.05 for all sonographers). Mean UtA-PI measurement reliability between approaches was high for the experienced (ICC = 0.92) and inexperienced (ICC > 0.80) sonographers. UtA-PI measurement approaches did not deviate from linearity, while bias ranged from -0.10 to 0.07. The median time required was similar between the techniques (56.1 s for sagittal vs 49.3 s for transverse; P = 0.054). CONCLUSIONS: This novel transverse approach for the measurement of UtA-PI in the first trimester appears to be comparable with the sagittal approach in terms of reliability, reproducibility and time required, and may be easier to perform. Providing accelerated onsite training can be helpful for improving the reliability of UtA-PI measurements and could potentially facilitate the broad implementation of first-trimester pre-eclampsia screening. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Fatal Leptospirosis and Escherichia coli co-infection in a post-partum woman.

The occurrence of Leptospirosis and Escherichia coli coinfection in the post-partum period is a novel case. This report illustrated a previously well woman from a suburban area presented with acute neurological deterioration following a two days history of fever during her puerperal period. Early interventions with fluids, broad spectrum antibiotics and intensive supportive care were given. Despite that, she deteriorated rapidly and developed pulmonary hemorrhage, disseminated intravascular coagulopathy, and multi-organ failure. She succumbed within 12 hours of admission. The knowledge about such fatal co-infections should be disseminated to medical practitioners encountering Leptospirosis infection and general public.

Breast Cancer and Transplantation.

Breast cancer is an important cancer among solid organ transplant recipients. While the incidence of breast cancer in solid organ transplant recipients is comparable to the age-matched general population, the outcomes are generally poor. Interventions such as cancer screening that preclude the development of late-stage disease through early detection are not well studied, and clinical practice guidelines for cancer screening rely solely on recommendations from the general population. Among patients with a prior breast cancer history, disease recurrence after transplantation is a rare but fearful event. Once disease recurs, the risk of death is high. The focus of this review is to present the epidemiology of breast cancer in solid organ transplant recipients, screening and preventive strategies for those who may be at risk, novel genomic profiling for determining tumor progression, and the newer targeted interventions for recipients who have developed breast cancers after solid organ transplantation.

Randomized controlled trial of S-1 versus docetaxel in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy (East Asia S-1 Trial in Lung Cancer).

BACKGROUND: Chemotherapy remains a viable option for the management of advanced non-small-cell lung cancer (NSCLC) despite recent advances in molecular targeted therapy and immunotherapy. We evaluated the efficacy of oral 5-fluorouracil-based S-1 as second- or third-line therapy compared with standard docetaxel therapy in patients with advanced NSCLC. PATIENTS AND METHODS: Patients with advanced NSCLC previously treated with ≥1 platinum-based therapy were randomized 1 : 1 to docetaxel (60 mg/m2 in Japan, 75 mg/m2 at all other study sites; day 1 in a 3-week cycle) or S-1 (80-120 mg/day, depending on body surface area; days 1-28 in a 6-week cycle). The primary endpoint was overall survival. The non-inferiority margin was a hazard ratio (HR) of 1.2. RESULTS: A total of 1154 patients (577 in each arm) were enrolled, with balanced patient characteristics between the two arms. Median overall survival was 12.75 and 12.52 months in the S-1 and docetaxel arms, respectively [HR 0.945; 95% confidence interval (CI) 0.833-1.073; P = 0.3818]. The upper limit of 95% CI of HR fell below 1.2, confirming non-inferiority of S-1 to docetaxel. Difference in progression-free survival between treatments was not significant (HR 1.033; 95% CI 0.913-1.168; P = 0.6080). Response rate was 8.3% and 9.9% in the S-1 and docetaxel arms, respectively. Significant improvement was observed in the EORTC QLQ-C30 global health status over time points in the S-1 arm. The most common adverse drug reactions were decreased appetite (50.4%), nausea (36.4%), and diarrhea (35.9%) in the S-1 arm, and neutropenia (54.8%), leukocytopenia (43.9%), and alopecia (46.6%) in the docetaxel arm. CONCLUSION: S-1 is equally as efficacious as docetaxel and offers a treatment option for patients with previously treated advanced NSCLC. CLINICAL TRIAL NUMBER: Japan Pharmaceutical Information Center, JapicCTI-101155.

Postnatal height and adiposity gain, childhood blood pressure and prehypertension risk in an Asian birth cohort.

OBJECTIVE: There have been hypotheses that early life adiposity gain may influence blood pressure (BP) later in life. We examined associations between timing of height, body mass index (BMI) and adiposity gains in early life with BP at 48 months in an Asian pregnancy-birth cohort. METHODS: In 719 children, velocities for height, BMI and abdominal circumference (AC) were calculated at five intervals [0-3, 3-12, 12-24, 24-36 and 36-48 months]. Triceps (TS) and subscapular skinfold (SS) velocities were calculated between 0-18, 18-36 and 36-48 months. Systolic (SBP) and diastolic blood pressure (DBP) was measured at 48 months. Growth velocities at later periods were adjusted for growth velocities in preceding intervals, as well as measurements at birth. RESULTS: After adjusting for confounders and child height at BP measurement, each unit z-score gain in BMI, AC, TS and SS velocities at 36-48 months were associated with 2.3 (95% CI:1.6, 3.1), 2.1 (1.3, 2.8), 1.4 (0.6, 2.2) and 1.8 (1, 2.6) mmHg higher SBP respectively, and 0.9 (0.4, 1.4), 0.9 (0.4, 1.3), 0.6 (0.1, 1.1) and 0.8 (0.3, 1.3) mmHg higher DBP respectively. BMI and adiposity velocities (AC, TS or SS) at various intervals in the first 36 months however, were not associated with BP. Faster BMI, AC, TS and SS velocities, but not height, at 36-48 months were associated with 0.22 (0.15, 0.29), 0.17 (0.10, 0.24), 0.11 (0.04, 0.19) and 0.15 (0.08, 0.23) units higher SBP z-score respectively, and OR=1.46 (95% CI: 1.13-1.90), 1.49 (1.17-1.92), 1.45 (1.09-1.92) and 1.43 (1.09, 1.88) times higher risk of prehypertension/hypertension respectively at 48 months. CONCLUSIONS: Our results indicated that faster BMI and adiposity (AC, TS or SS) velocities only at the preceding interval before 48 months (36-48 months), but not at earlier intervals in the first 36 months, are predictive of BP and prehypertension/hypertension at 48 months.

Design and development of the BD Odon DeviceTM : a human factors evaluation process.

OBJECTIVE: To (1) determine how intended users interact with and use the BD Odon Device in simulation, (2) use these findings to alter progressively the design of the BD Odon Device and (3) validate that these changes have improved the ability of practitioners to use the BD Odon Device. DESIGN: Human factors evaluation study. SETTING: Simulation suite designed to mimic delivery room. POPULATION OR SAMPLE: Three hundred and ninety simulated operative births, performed by 100 practising clinicians. METHODS: Simulated operative vaginal births performed using the BD Odon Device and the device Instructions for use were subjected to three formative human factors evaluations and one human factors validation test. Following each evaluation, findings were reviewed and the design of the BD Odon Device and Instructions for use were modified. MAIN OUTCOME MEASURES: Successful performance of an operative vaginal birth using the BD Odon Device in accordance with provided training and Instructions for use. RESULTS: Using version two of the BD Odon Device, and following exposure to face-to-face training and written instructions, 25% of accouchers were able successfully to perform a simulated operative vaginal birth. In the final evaluation, following device design and training material alterations, all accouchers were able successfully to perform a simulated operative vaginal birth using version four of the BD Odon Device. CONCLUSIONS: Human factors evaluations have enabled a multi-professional device and training materials design team to alter the design of the BD Odon Device and the Instructions for use in an evidence-based fashion. This process has resulted in a device which has a predictable and likely safe pattern of use. TWEETABLE ABSTRACT: Human Factors evaluations help make the BD Odon Device safe and usable for clinical practice.

Validity of estimating muscle and fat volume from a single MRI section in older adults with sarcopenia and sarcopenic obesity.

AIM: To determine if there is a correlation between the cross-sectional areas (CSAs) in a single section and the volumes of muscles and fat in the thigh of sarcopenic and sarcopenic obesity (SO) populations using magnetic resonance imaging (MRI), and to assess the correlation between thigh MRI data and patient health status, i.e., normal, obese, sarcopenia, and SO. MATERIALS AND METHODS: One hundred and ninety community-dwelling older adults were recruited and categorised into four subgroups based on Asian established criteria: normal, obese, sarcopenia, and SO. MRI images were acquired and muscles, subcutaneous fat (SF), and intermuscular fat (IMF) were automatically segmented in the thighs. Volumes of muscles and fat were calculated for the middle third of the thigh, while CSAs were assessed using a single section at 50% femur length. RESULTS: Correlation between CSA and volume were significantly high (p<0.001) for all components of muscle (0.907), SF (0.963), and IMF (0.939). Thigh CSA and volume both correlated significantly with a clinical diagnosis of normal, obesity, sarcopenia, and SO (p<0.03). CONCLUSIONS: A single CSA at 50% of femur length yields good estimation of muscle and fat volume in the thighs of older adults and correlates closely with the clinical criteria for sarcopenia and SO. This has the potential to greatly reduce costs, scan time, and post-processing time in clinical practice for the prediction of these conditions.

Prolonged Ischemic Time, Delayed Graft Function, and Graft and Patient Outcomes in Live Donor Kidney Transplant Recipients.

The association between prolonged cold ischemic time (CIT) and graft and patient outcomes in live donor kidney transplant recipients remains unclear. The aims of this study were to examine the association of CIT with delayed graft function and graft loss in live donor kidney transplant recipients and those who participated in the Australian Paired Kidney Exchange program using data from the Australia and New Zealand Dialysis and Transplant (ANZDATA) registry. Of 3717 live donor transplant recipients between 1997 and 2012 who were followed for a median of 6.6 years (25 977 person-years), 224 (25%) experienced CIT >4-8 h. Donor age was an effect modifier between CIT and graft outcomes. In recipients who received kidneys from older donors aged >50 years, every hour of increase in CIT was associated with adjusted odds of 1.28 (95% confidence interval [CI] 1.07-1.53, p = 0.007) for delayed graft function, whereas CIT >4-8 h was associated with adjusted hazards of 1.93 (95% CI 1.21-3.09, p = 0.006) and 1.91 (95% CI 1.05-3.49, p = 0.035) for overall and death-censored graft loss, respectively, compared with CIT of 1-2 h. Attempts to reduce CIT in live donor kidney transplants involving older donor kidneys may lead to improvement of graft outcomes.