DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: A cross-sectional analysis of adult (≥ 18 years) current smokers and ex-smokers from 14 countries participating in the ITC Project. Data from the most recent survey questionnaire for each country were included, which spanned the period 2013-17. Countries were categorized into four groups based on regulations governing NVP sales and marketing (allowable or not), and level of enforcement (strict or weak where NVPs are not permitted to be sold): (1) most restrictive policies (MRPs), not legal to be sold or marketed with strict enforcement: Australia, Brazil, Uruguay; (2) restrictive policies (RPs), not approved for sale or marketing with weak enforcement: Canada, Malaysia, Mexico, New Zealand; (3) less restrictive policies (LRPs), legal to be sold and marketed with regulations: England, the Netherlands, Republic of Korea, United States; and (4) no regulatory policies (NRPs), Bangladesh, China, Zambia. Countries were also grouped by World Bank Income Classifications. Country-specific weighted logistic regression models estimated adjusted NVP prevalence estimates for: awareness, ever/current use, and frequency of use (daily versus non-daily).
FINDINGS: NVP awareness and use were lowest in NRP countries. Generally, ever- and current use of NVPs were lower in MRP countries (ever-use = 7.1-48.9%; current use = 0.3-3.5%) relative to LRP countries (ever-use = 38.9-66.6%; current use = 5.5-17.2%) and RP countries (ever-use = 10.0-62.4%; current use = 1.4-15.5%). NVP use was highest among high-income countries, followed by upper-middle-income countries, and then by lower-middle-income countries.
CONCLUSIONS: With a few exceptions, awareness and use of nicotine vaping products varied by the strength of national regulations governing nicotine vaping product sales/marketing, and by country income. In countries with no regulatory policies, use rates were very low, suggesting that there was little availability, marketing and/or interest in nicotine vaping products in these countries where smoking populations are predominantly poorer. The higher awareness and use of nicotine vaping products in high income countries with moderately (e.g. Canada, New Zealand) and less (e.g. England, United States) restrictive policies, is likely due to the greater availability and affordability of nicotine vaping products.
METHODS: A population of 295 consecutive patients undergoing HRM and pH-study for persistent typical or atypical GERD symptoms was prospectively enrolled to build a model and a nomogram that provides a risk score for AET > 6%. Collected HRM data included IEM, EGJ-CI, EGJ type and SLR. A supplemental cohort of patients undergoing HRM and pH-study was also prospectively enrolled in 13 high-volume esophageal function laboratories across the world in order to validate the model. Discrimination and calibration were used to assess model's accuracy. Gastroesophageal reflux disease was defined as acid exposure time >6%.
RESULTS: Out of the analyzed variables, SLR response and EGJ subtype 3 had the highest impact on the score (odd ratio 18.20 and 3.87, respectively). The external validation cohort consisted of 233 patients. In the validation model, the corrected Harrel c-index was 0.90. The model-fitting optimism adjusted calibration slope was 0.93 and the integrated calibration index was 0.07, indicating good calibration.
CONCLUSIONS: A novel HRM score for GERD diagnosis has been created and validated. The MS might be a useful screening tool to stratify the risk and the severity of GERD, allowing a more comprehensive pathophysiologic assessment of the anti-reflux barrier.
TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT05851482).
METHODS: The World Health Organization (WHO) aims to extend UHC to a further 1 billion people by 2023, yet evidence supporting improved emergency care coverage is lacking. In this article, we explore four phases of a research prioritisation setting (RPS) exercise conducted by researchers and stakeholders from South Africa, Egypt, Nepal, Jamaica, Tanzania, Trinidad and Tobago, Tunisia, Colombia, Ethiopia, Iran, Jordan, Malaysia, South Korea and Phillipines, USA and UK as a key step in gathering evidence required by policy makers and practitioners for the strengthening of emergency care systems in limited-resource settings.
RESULTS: The RPS proposed seven priority research questions addressing: identification of context-relevant emergency care indicators, barriers to effective emergency care; accuracy and impact of triage tools; potential quality improvement via registries; characteristics of people seeking emergency care; best practices for staff training and retention; and cost effectiveness of critical care - all within LMICs.
CONCLUSIONS: Convened by WHO and facilitated by the University of Sheffield, the Global Emergency Care Research Network project (GEM-CARN) brought together a coalition of 16 countries to identify research priorities for strengthening emergency care in LMICs. Our article further assesses the quality of the RPS exercise and reviews the current evidence supporting the identified priorities.
METHODS: Biomarkers of internal exposure were measured in red blood cells (collected at baseline) by high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) . In this cross-sectional analysis, four dependent variables were evaluated: HbAA, HbGA, sum of total adducts (HbAA + HbGA), and their ratio (HbGA/HbAA). Simple and multiple regression analyses were used to identify determinants of the four outcome variables. All dependent variables (except HbGA/HbAA) and all independent variables were log-transformed (log2) to improve normality. Median (25th-75th percentile) HbAA and HbGA adduct levels were 41.3 (32.8-53.1) pmol/g Hb and 34.2 (25.4-46.9) pmol/g Hb, respectively.
RESULTS: The main food group determinants of HbAA, HbGA, and HbAA + HbGA were biscuits, crackers, and dry cakes. Alcohol intake and body mass index were identified as the principal determinants of HbGA/HbAA. The total percent variation in HbAA, HbGA, HbAA + HbGA, and HbGA/HbAA explained in this study was 30, 26, 29, and 13 %, respectively.
CONCLUSIONS: Dietary and lifestyle factors explain a moderate proportion of acrylamide adduct variation in non-smoking postmenopausal women from the EPIC cohort.
METHODS: Adult patients with persistent gastroesophageal reflux disease (GERD) symptoms undergoing HRM and pH-impedance or wireless pH study off proton pump inhibitor were prospectively studied between July 2021 and March 2022. After the HRM Chicago 4.0 protocol, patients were requested to elevate 1 leg at 45º for 5 seconds while supine. The SLR maneuver was considered effective when intra-abdominal pressure increased by 50%. IEPs were recorded 5 cm above the lower esophageal sphincter at baseline and during SLR. GERD was defined as AET greater than 6%.
RESULTS: The SLR was effective in 295 patients (81%), 115 (39%) of whom had an AET greater than 6%. Hiatal hernia (EGJ type 2 or 3) was seen in 135 (46%) patients. Compared with patients with an AET less than 6%, peak IEP during SLR was significantly higher in the GERD group (29.7 vs 13.9 mm Hg; P < .001). Using receiver operating characteristic analysis, an increase of 11 mm Hg of peak IEP from baseline during SLR was the optimal cut-off value to predict an AET greater than 6% (area under the receiver operating characteristic curve, 0.84; sensitivity, 79%; and specificity, 85%), regardless of the presence of hiatal hernia. On multivariable analysis, an IEP pressure increase during the SLR maneuver, EGJ contractile integral, EGJ subtype 2, and EGJ subtype 3, were found to be significant predictors of AET greater than 6% CONCLUSIONS: The SLR maneuver can predict abnormal an AET, thereby increasing the diagnostic value of HRM when GERD is suspected.
CLINICALTRIALS: gov ID: NCT04813029.
AIMS: This study aims to investigate the effect of cosmetic products on users' quality of life in eight Arab countries.
METHODS: A cross-sectional study was carried out using an online data collection approach. A validated and specialist instrument tool called BeautyQoL, which consists of five domains and a total of 52 questions, was distributed to a sample of 2219 cosmetic users. Descriptive and inferential statistical analysis was done using SPSS® version 26.0.
RESULTS: The mean age of participants was 34 ± 11.25 years, and more women were represented in the sample (71%) than men. The majority of respondents had oily skin type (39.6%) and tan skin tone (30.4%). QoL through cosmetic use is computed with a mean score of 51 out of 100. The users' mean score satisfaction from cosmetic use is centred on attractiveness (56.1), followed by self-confidence (51.8). Cosmetics have a statistically significant effect on participants who are young adults, women, single, and employed with high income. As the respondents' skin tone deepens from very fair to dark, the mean score for each domain significantly increases, whereas when skin type changes from very oily to dry, the mean score for each domain decreases.
CONCLUSION: The effect of cosmetics on the users' QoL is limited, contrary to the narrative commonly portrayed in cosmetics' advertisements. Therefore, the use of cosmetics among the Arab population should be from an informed perspective of their specific needs instead of conforming to the viral trends pedaled by influencers and bloggers on social media, which might be irrelevant for them.
METHODS AND ANALYSIS: This cross-sectional study uses an online survey to administer a novel COVID Psychosocial Impacts Scale (CPIS) alongside established measures of psychological distress, post-traumatic stress, well-being and post-traumatic growth in the appropriate language. Participants will include adults aged 18 years and above, recruited from Indonesia, Iraq, Iran, Malaysia, Pakistan, Somalia and Turkey, with a pragmatic target sample size of 500 in each country.Data will be analysed descriptively on sociodemographic and study variables. In addition, CPIS will be analysed psychometrically (for reliability and validity) to assess the suitability of use in a given context. Finally, within-subjects and between-subjects analyses will be carried out using multi-level mixed-effect models to examine associations between key sociodemographic and study variables.
ETHICS AND DISSEMINATION: Ethical approval was granted by the Human Ethics Committee, University of Otago, New Zealand (Ref. No. 21/102). In addition, international collaborators obtained local authorisation or ethical approval in their respective host universities before data collection commenced.Participants will give informed consent before taking part. Data will be collected and stored securely on the University of Otago, New Zealand Qualtrics platform using an auto-generated non-identifiable letter-number string. Data will be available on reasonable request. Findings will be disseminated by publications in scientific journals and/or conference presentations.
TRIAL REGISTRATION NUMBER: NCT05052333.
AIMS: We aimed to evaluate the association between 6-thioguanine nucleotide (6-TGN) and anti-TNFα levels and the optimal 6-TGN threshold level associated with higher anti-TNFα levels in combination therapy.
METHODS: We performed a retrospective cross-sectional multicentre study of patients with IBD on combination anti-TNFα and thiopurine maintenance therapy between January 2015 and August 2021. Primary outcomes were infliximab and adalimumab levels. Secondary outcomes were antibodies to infliximab (ATI) or adalimumab (ATA). Univariable and multivariable linear regression were performed to identify variables associated with anti-TNFα levels. Receiver operator characteristic curves were used to define the optimal 6-TGN cut-off levels associated with therapeutic anti-TNFα levels.
RESULTS: The study included 743 paired 6-TGN and anti-TNFα levels (640 infliximab and 103 adalimumab). 6-TGN levels were associated with infliximab levels, but not adalimumab levels, on univariable and multivariable regression. The optimal 6-TGN cut-off associated with therapeutic infliximab levels (≥5 mcg/mL) was 261 pmol/8 × 108 red blood cell (RBC) (area under the curve (AUC) = 0.57) for standard infliximab dosing and 227.5 pmol/8 × 108 RBC (AUC = 0.58) for escalated dosing. For therapeutic adalimumab levels (≥7.5 mcg/mL), the 6-TGN cut-off was 218.5 pmol/8 × 108 RBC (AUC = 0.59) for standard adalimumab dosing and 237.5 pmol/8 × 108 RBC (AUC = 0.63) for escalated dosing.
CONCLUSION: 6-TGN levels were weakly associated with infliximab but not adalimumab levels in combination therapy. 6-TGN levels in the lower end of the therapeutic range (230-260 pmol/8 × 108 RBC) may be adequate to maintain higher infliximab levels, particularly with escalated infliximab dosing.
METHODS: The AVATAR trial randomly assigned patients with severe, asymptomatic AS and LV ejection fraction ≥50% to undergo either early surgical aortic valve replacement (AVR) or conservative treatment with watchful waiting strategy. All patients had negative exercise stress testing. The primary hypothesis was that early AVR will reduce a primary composite endpoint comprising all-cause death, acute myocardial infarction, stroke or unplanned hospitalization for heart failure (HF), as compared to conservative treatment strategy.
RESULTS: A total of 157 low-risk patients (mean age 67 years, 57% men, mean Society of Thoracic Surgeons score 1.7%) were randomly allocated to either early AVR group (n=78) or conservative treatment group (n=79). In an intention-to-treat analysis, after a median follow-up of 63 months, the primary composite endpoint outcome event occurred in 18/78 patients (23.1%) in the early surgery group and in 37/79 patients (46.8%) in the conservative treatment group (hazard ratio [HR] early surgery vs. conservative treatment 0.42; 95% confidence interval [CI] 0.24-0.73, p=0.002). The Kaplan-Meier estimates for individual endpoints of all-cause death and HF hospitalization were significantly lower in the early surgery compared with the conservative group (HR 0.44; 95% CI 0.23-0.85, p=0.012 for all-cause death, and HR 0.21; 95% CI 0.06-0.73, p=0.007 for HF hospitalizations).
CONCLUSIONS: The extended follow-up of the AVATAR trial demonstrates better clinical outcomes with early surgical AVR in truly asymptomatic patients with severe AS and normal LV ejection fraction compared with patients treated with conservative management on watchful waiting.
TRIAL REGISTRATION NUMBER: NCT02436655 (ClinicalTrials.gov).
MATERIALS AND METHODS: These modules included manual semen analysis, sperm morphology and ancillary semen tests (testing for leukocytospermia, sperm vitality, and anti-sperm antibody screening). The virtual format consisted of lecture presentations featuring laboratory protocols with corresponding video demonstrations of routine techniques and best practices. Practical scenarios, troubleshooting, and clinical interpretation of laboratory results were also discussed. At the end of each module, an optional multiple choice question test was held as a prerequisite to obtain certification on the topics presented. Course quality was assessed using participant responses collected via online surveys.
RESULTS: The digital delivery methods used were found to have largely or completely met the participants' expectations for all questions (>85%). The majority (>87%) of the participants either strongly agreed or agreed that the course content was well-structured with appropriate depth, and that their overall expectations of the course had been met.
CONCLUSIONS: This training format appears to be a realistic teaching option to freely share highly specialized expertise and technical knowledge with participants from anywhere in the world with varying levels of competency or experience.
METHODS: Mutation testing was performed on germline DNA (n=15 768) using targeted sequencing panels. The functional impact of missense variants was tested in mouse embryonic stem cell based functional assays.
RESULTS: PTVs in PALB2 were found in 0.73% of breast cancer patients and 0.14% of healthy individuals (OR=5.44; 95% CI 2.85 to 10.39, p<0.0001). In contrast, rare missense variants in PALB2 were not associated with increased risk of breast cancer. Whereas PTVs were associated with later stage of presentation and higher-grade tumours, no significant association was observed with missense variants in PALB2. However, two novel rare missense variants (p.L1027R and p.G1043V) produced unstable proteins and resulted in a decrease in homologous recombination-mediated repair of DNA double-strand breaks.
CONCLUSION: Despite genetic and lifestyle differences between Asian and other populations, the population prevalence of PALB2 PTVs and associated relative risk of breast cancer, are similar to those reported in European populations.