OBJECTIVES: To assess the effectiveness of systematic preconception genetic risk assessment to enable autonomous reproductive choice and to improve reproductive outcomes in women and their partners who are both identified as carriers of thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease in healthcare settings when compared to usual care.
SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Registers. Date of latest search of the registers: 04 August 2021. In addition, we searched for all relevant trials from 1970 (or the date at which the database was first available if after 1970) to date using electronic databases (MEDLINE, Embase, CINAHL, PsycINFO), clinical trial databases (National Institutes of Health, Clinical Trials Search portal of the World Health Organization, metaRegister of controlled clinical trials), and hand searching of key journals and conference abstract books from 1998 to date (European Journal of Human Genetics, Genetics in Medicine, Journal of Community Genetics). We also searched the reference lists of relevant articles, reviews and guidelines and also contacted subject experts in the field to request any unpublished or other published trials. Date of latest search of all these sources: 25 June 2021. SELECTION CRITERIA: Any randomised controlled trials (RCTs) or quasi-RCTs (published or unpublished) comparing reproductive outcomes of systematic preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease when compared to usual care.
DATA COLLECTION AND ANALYSIS: We identified 37 papers, describing 22 unique trials which were potentially eligible for inclusion in the review. However, after assessment, we found no RCTs of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease.
MAIN RESULTS: No RCTs of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease are included. A trial identified earlier has published its results and has subsequently been listed as excluded in this review.
AUTHORS' CONCLUSIONS: As there are no RCTs of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis, or Tay-Sachs disease included in either the earlier or current versions of this review, we recommend considering potential non-RCTs studies (for example prospective cohorts or before-and-after studies) for future reviews. While RCTs are desirable to inform evidence-based practice and robust recommendations, the ethical, legal and social implications associated with using this trial design to evaluate the implementation of preconception genetic risk assessment involving carrier testing and reproductive autonomy must also be considered. In addition, rather than focusing on single gene-by-gene carrier testing for specific autosomal-recessive conditions as the intervention being evaluated, preconception expanded genetic screening should also be included in future searches as this has received much attention in recent years as a more pragmatic strategy. The research evidence for current international policy recommendations is limited to non-randomised studies.
DESIGN: Following the PRISMA-ScR guidelines, three electronic databases were searched (Pubmed, Scopus and Web of Science).
RESULTS: A total of twelve studies were included in the final review that reported on small-animal (rats, guinea pigs, rabbits) and large-animal (dogs and goats) models. Based on the grafting biomaterials, eight papers used cell-free scaffolds, four articles utilised cell-based scaffolds. The timing protocol for the initiation of OTM employed in the studies ranged from immediate to 6 months after surgical grafting. Only four studies included autologous bone graft (gold standard) as positive control. Most papers reported positive results with regards to the rate of OTM and bone augmentation effects while only a few reported side effects such as root resorptions. Overall, the included articles showed a massive heterogeneity in terms of the animal bone defect model characteristics, scaffold materials, study designs, parameters of OTM and methods of analysis.
CONCLUSION: Since there was inadequate evidence to identify the optimal protocol of OTM, optimization of animal bone defect models and outcome measurements is needed to improve the translational ability of future studies.
METHODS: Three sets of fake braces and one control were dissembled to only their brackets and archwires and immersed separately in SBF. They were placed in an incubator shaker at a temperature of 37 °C at 50 rpm. A 3.0 ml measurement of SBF was taken out from the sample containers at days 7, 14 and 28 and kept at - 20 °C for further analysis. Data were analysed using SPSS version 26.0 (IBM, Armonk, USA) (P
METHODS: The Q methodology was used where 37 opinion statements were ranked in order of importance in a unimodal shaped grid. Results were explored using the Centroids factor extraction and Varimax rotation.
RESULTS: Four-three persons living with haemodialysis, mean age± SD= 56.58 ± 10.22 years, participated in the study. Five-factors were identified: living in the present, family preference, self preservation, power vs. control and autonomy in decision making, loaded by eleven, four, four, three and three participants with 16 individuals not loading significantly and two were confounded. Preferences for remaining positive in the face of illness through a healthy lifestyle and preserving relationships and autonomy were demonstrated.
CONCLUSIONS: End-of-life discussions are potentially inhibited by preferences to live for the present which should be explored in future studies.
PRACTICE IMPLICATION: Statement sets may be used to help facilitate end-of-life discussions through identification of opinion groups. Establishing preferences may guide identification of those willing to initiate discussions.
RESULTS: The FI in China increased rapidly from about 5 kg ha-1 in 1961 to the highest value of 282 kg ha-1 in 2014, then decreased to about 231 kg ha-1 in 2018. Although the fertilizer allocation efficiency (FAE) showed a slight downward trend, slight upward trend was observed for the fertilizer integrated efficiency (FIE). FIs in India, Iran and Turkey continuously rose from5 kg ha-1 in 1961to 116, 49(148 in 2006),120kg ha-1 in 2018, respectively, while FAEs showed a significant fluctuation around horizontal direction or downward trends and their FIEs showed a slight fluctuation downward. FIs of Britain, Germany and France except USA, increased rapidly from about 200-400 kg ha-1 in 1960s to peaks of 430-530 kg ha-1 in 1980s, then dropped to 150-340 kg ha-1 around 2010, and then up to current level of 200-350 kg ha-1 , while FAEs and FIEs increased rapidly.
CONCLUSION: France and Germany were found to have moderate chemical fertilizer input and the highest FIE. Thus, their experiences of ecological agricultures in both countries could provide good examples for the developing countries to follow. In short, models of FAE and FIE were easier way to reflect the fertilizer efficiencies in developed and developing countries. This article is protected by copyright. All rights reserved.
METHODS: RAINBOW-Asia was a randomised, double-blind, placebo-controlled, phase 3 trial done at 32 centres in China, Malaysia, the Philippines, and Thailand. Adult patients (≥18 years) with metastatic or locally advanced, unresectable gastric or GEJ adenocarcinoma who previously received fluoropyrimidine-platinum-based chemotherapy were randomly assigned with a centralised interactive web response system in a 2:1 ratio to receive ramucirumab 8 mg/kg or placebo intravenously on days 1 and 15 plus paclitaxel 80 mg/m2 intravenously on days 1, 8, and 15 of every 28-day cycle. Randomisation was stratified by Eastern Cooperative Oncology Group performance status and presence of peritoneal metastases. The co-primary endpoints were progression-free survival and overall survival. Efficacy analyses were done in the intention-to-treat population, and safety analysis included patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, NCT02898077, and has been completed.
FINDINGS: Between March 2, 2017, and June 30, 2020, 440 patients were randomly assigned to receive ramucirumab plus paclitaxel (n=294) or placebo plus paclitaxel (n=146). Median progression-free survival was 4·14 months (95% CI 3·71-4·30) in the ramucirumab plus paclitaxel group compared with 3·15 months (2·83-4·14) in the placebo plus paclitaxel group (hazard ratio [HR] 0·765, 95% CI 0·613-0·955, p=0·0184). Median overall survival was 8·71 months (95% CI 7·98-9·49) in the ramucirumab plus paclitaxel group and 7·92 months (6·31-9·10) in the placebo plus paclitaxel group (HR 0·963, 95% CI 0·771-1·203, p=0·7426). The most common grade 3 or worse treatment-emergent adverse events were decreased neutrophil count (159 [54%] of 293 patients in the ramucirumab plus paclitaxel group vs 56 [39%] of 145 in the placebo plus paclitaxel group), decreased white blood cell count (127 [43%] vs 42 [29%]), anaemia (46 [16%] vs 24 [17%]), hypertension (21 [7%] vs nine [6%]), and febrile neutropenia (18 [6%] vs one [<1%]).
INTERPRETATION: These findings, along with the results from RAINBOW, support the use of ramucirumab plus paclitaxel as second-line therapy in a predominantly Chinese population with advanced gastric or GEJ adenocarcinoma.
FUNDING: Eli Lilly and Company, USA.
TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.
DESIGN AND METHODS: This is a retrospective study. We reviewed medical records of six patients diagnosed with CACT and CPT2 deficiencies. They were identified from a selective high-risk screening of 50,579 patients from January 2010 until Jun 2020.
RESULTS: All six patients had either elevation of the long chain acylcarnitines and/or an elevated (C16 + C18:1)/C2 acylcarnitine ratio. SLC25A20 gene sequencing of patient 1 and 6 showed a homozygous splice site mutation at c.199-10 T > G in intron 2. Two novel mutations at c.109C > T p. (Arg37*) in exon 2 and at c.706C > T p. (Arg236*) in exon 7 of SLC25A20 gene were found in patient 2. Patient 3 and 4 (siblings) exhibited a compound heterozygous mutation at c.638A > G p. (Asp213Gly) and novel mutation c.1073 T > G p. (Leu358Arg) in exon 4 of CPT2 gene. A significant combined prevalence at 0.01% of CACT and CPT2 deficiencies was found in the symptomatic Malaysian patients.
CONCLUSIONS: The use of the (C16 + C18:1)/C2 acylcarnitine ratio in dried blood spot in our experience improves the diagnostic specificity for CACT/CPT2 deficiencies over long chain acylcarnitine (C16 and C18:1) alone. DNA sequencing for both genes aids in confirming the diagnosis.
OBJECTIVE: This study explored use of the frontoparietal (FP) placement for reducing retrograde memory side effects with ECT. We hypothesised that superior retrograde memory outcomes would occur with FP compared to temporoparietal (TP) placement and with ultrabrief (UB: 0.3 ms) compared to brief pulse (BP: 1.0 ms) width ECT.
METHODS: In this randomised cross-over, double-blinded study, participants received a single treatment of BP TP, BP FP, UB TP and UB FP ECT. Neuropsychological testing was conducted prior to and immediately following each treatment. Computational modelling was conducted to explore associations between E-fields in regions-of-interest associated with memory.
RESULTS: Nine participants completed the study. The FP placement was not superior to TP for retrograde memory outcomes. For both electrode placements UB pulse width was associated with significantly better visual retrograde memory compared to BP (p
METHODS: Cross-sectional study at the University of Malaya Medical Centre, Kuala Lumpur. Subjects underwent subjective refraction, then automated refraction, and finally Netra smartphone-based refraction. All results were converted to power vectors (M, J0 and J45) and were analysed using repeated-measures ANOVA and Bland-Altman plots. Sensitivity and specificity were determined. The best cut-off points were determined from ROC curve analysis. P .05), but those between automated and subjective refraction were (0.06 vs 0.11 and 0.07 vs -0.02, p = .004 and p