Exposure assessment of arsenic speciation in different rice types depending on the cooking mode

Total (As_t), inorganic arsenic (As_i = As(III) + As(V)) and dimethylarsonic acid (DMA) were determined in 37 commercial rice samples collected in France. As_t was measured by inductively coupled plasma-mass spectrometry (ICP-MS) whereas anion-exchange chromatography – ICP-MS was used for As_i and DMA determination. As_t in raw rice varied from 0.041 to 0.535 mg kg⁻¹ whereas As_i varied from 0.025 mg kg⁻¹ (polished Basmati rice) up to 0.471 mg kg⁻¹ (organic rice duo). The daily intake and associated health risk for different population groups as a function of age and gender was also assessed. The intake varied between 0.002 and 0.184 μg kg⁻¹ body weight for As_t and 0.002 and 0.153 μg kg⁻¹ body weight for As_i, which do not pose a chronic toxicity risk. Organic wholegrain rice may entail a risk for children in the case of sole consumption at the expense of polished rice. The impact of rice cooking/boiling in terms of the overall toxicological risk related to As species was also investigated. Pre-rinsing and boiling the raw rice by using an excess of water is the most efficient mode to obtain a significant As_i removal and further reduction of the toxicological risk for children, particularly for white rice varieties.     

The response of breadfruit nutrition to local climate and soil: A review

Breadfruit (Artocarpus altilis) has been promoted as an underutilized crop with tremendous potential to address global hunger and transform agricultural practices in the tropics. While traditionally confined to Oceania, breadfruit has been spread throughout the global tropics in the 250 years, with a significant increase in distribution and production over the last 20–30 years, bringing the crop into a vast array of growing conditions. We apply a systematic protocol to 33 previous studies representing 41 locations to explore the effect of abiotic environmental factors on nutritive aspects of breadfruit in three categories: proximate analyses, micro- and macro-nutrients, and vitamins. In applying linear and multi-variate regressions, data suggests that the abiotic factors play a strong role in the nutritive value of the crop and that each category of nutrition responds differently to the environment. In general, proximate analyses were most responsive to average annual precipitation, while vitamin concentrations respond to both climate and soil parameters; micro- and macro-nutrients show little correlation to climate or soils. We present findings in the context of previous research on abiotic influence of food nutrition.     

Development of a new method for determination of aluminum (Al) in Jordanian foods and drinks: Solid phase extraction and adsorption of Al3+-d-mannitol on carbon nanotubes

In this work, a new method was developed for determination of aluminum (Al) in traditional Jordanian foods (Mansaf, Kofta, Tabboola, Hummous, bread), tea, Arabian coffee and water samples. The method involved solid phase extraction (SPE) of Al³⁺ from the digested samples after complexation with d-mannitol using carbon nanotubes (CNT) as the extractive sorbent. Formation of the Al³⁺-d-mannitol complex was confirmed by infrared spectroscopy. Optimization of the SPE method involved sample pH, d-mannitol-to-Al mole ratio, sample loading and elution flow rates, adsorbent mass, eluent concentration and volume. Based on spiked water samples, the characteristics of the method were as follows: the limit of quantification: 23 μg l⁻¹; sensitivity: 0.0036 (mg l⁻¹)⁻¹; %RSD range: 0.4–1.9%; recovery range: 76.0–93.0%. The equilibrium, thermodynamic and kinetic adsorption studies of Al³⁺-d-mannitol on CNT revealed that adsorption was spontaneous, exothermic, preferred, of physical nature; followed second-order rate kinetics; pore diffusion was not the only rate-controlling step; both Langmuir and Freundlich isotherms represented the data satisfactorily.     

Investigation of heavy metal concentrations in some Turkish wines

Research studies analysing heavy metal or trace elements in Turkish wines is scarce. This study was designed to fill this gap, analysing 43 wines produced in 4 different regions in Turkey. A total of 37 red and 6 white wines produced from various grapes from 2006 to 2008 in Marmara, Aegean, Central Anatolia and Eastern Anatolia regions were studied. Wines were analyzed for Cr, Mn, Fe, Co, Ni, Cu, Zn, Cd and Pb using atomic absorption spectrometer equipped (AAS) with electrothermal atomization unit (ET). Average results for red and white wines, respectively, were: Cr, 38.6 and 29.4 μg/L; Mn, 697 and 101 μg/L; Fe, 1.7 and 0.7 mg/L; Co, 6.3 and 0.5 μg/L; Ni, 134 and 573 μg/L; Cu, 131 and 158 μg/L; Zn, 389 and 2099 μg/L; Cd, 2.8 (red wine; white wine results were under limit of detection); Pb, 6.3 (red wine; white wine results were under limit of detection). These results were interpreted for grape types and regions. Accuracy was tested with standard addition method. Recoveries ranged from 96% to 107% after standard addition. Cr, Fe and Mn in red wines were higher in comparison to white wines, whereas white wines were higher in Ni and Zn. Non-essential Cd and Pb concentrations were very low in both red and white wines. Comparison with literature shows all heavy metal concentrations in the analyzed Turkish wines to be below the limits designated by World Health Organization.     

Study of mercury content in wild edible mushrooms and its contribution to the Provisional Tolerable Weekly Intake in Spain

The study determined total mercury (Hg) content of 10 wild edible mushroom species collected in southern Spain. Results indicated that the highest Hg level corresponded to Boletus aereus with 10.28 ± 2.92 mg/kg DW (dry weight), while the lowest Hg level was found in Terfezia arenaria with 0.09 ± 0.08 mg/kg DW. Regarding the anatomic parts of the mushrooms, caps showed significantly higher Hg concentrations than stems in B. aereus, Amanita caesarea and Macrolepiota procera. The percentage of contribution to the Provisional Tolerable Weekly Intake (PTWI) for Hg was also calculated. Based on consumption data in Spain (0.011 kg/person/week), %PTWI was calculated ranging between 0.06 and 3.5% for mean Hg levels. When a high level of consumption was assumed (0.100 kg/person/week), %PTWI ranged between 0.58 and 31%. Results suggest that wild edible mushrooms in southern Spain could contribute with high Hg levels to the Spanish diet. However, the lack of consumption data for wild edible mushrooms made it difficult to give more definitive conclusions; hence further studies including specific consumption data will be needed.     

我国食品安全现状与风险来源：以餐饮业为例

从我国餐饮业食品安全现状出发,以2001—2012年媒体披露的300起餐饮消费食品安全事件为研究样本,利用内容分析法和描述性统计分析法,从食品安全事件的发生地域、发生季节、食品种类、责任主体、发生原因5个方面,对餐饮业食品安全风险来源进行了分析。结果显示：食品安全事件的发生具有一定的区域性、时间性特征,肉制品的质量、个体经营者和人员环境不卫生是主要的风险来源。根据分析结果,提出了加强我国餐饮服务监管能力建设,加大餐饮行业风险关键点监管力度,完善餐饮单位量化分级管理,创新餐饮服务监管模式等政策建议。     

Heterocyclic aromatic amines in grilled beef: The influence of free amino acids,nitrogenous bases,nucleosides, protein and glucose on HAAs content

The aim of the study was to determine the content and profile of heterocyclic aromatic amines (HAAs) formed during the process of grilling beef under various conditions and involving different cuts of beef meat. 4,8-DiMeIQx was the most prevalent (4.50–7.55 ng g⁻¹) the next were: MeIQx (1.10–7.20 ng g⁻¹), MeIQ (1.70–5.30 ng g⁻¹), and IQ (0.38 2.00 ng g⁻¹). Changes in HAAs content, depending on the chemical composition of beef meat, were investigated; the compounds under analysis included free amino acids, glucose and protein as well as free nitrogenous bases and their nucleosides. It was demonstrated that HAAs formation strongly correlates with the presence of various amino acids in raw beef as well as that of glucose and protein (correlation coefficient 0.84–0.93). It was also demonstrated that free purine bases, pyrimidine bases and their nucleosides, which had never previously been studied in terms of their role as substrates for HAAs synthesis, correlate very strongly with HAA formation in grilled beef (correlation coefficient 0.78–0.99). The influence of thermal processing at high temperatures on the thermal decomposition of aminoimidazoazaarenes has not been corroborated by the present study.     

Levels and daily intake of lead (Pb) and six essential elements in gari samples from Ondo State,Southwest Nigeria: A potential risk factor of health status

Gari, a staple food in most West African countries is a processed product of cassava plant. It supplies about 70% of the daily calorie intake in these countries. In this study, levels of lead (Pb), zinc (Zn), manganese (Mn), cobalt (Co), copper (Cu), calcium (Ca) and iron (Fe) in gari samples that were collected from four major Nigerian cities: Akure, Ondo, Isua and Ore – all located in Ondo State, Southwest, Nigeria were determined. The estimated daily intakes (EDI) of these elements were determined and compared to the recommended dietary intake limits or requirements. The mean concentrations of Pb in gari samples was 0.16 ± 0.09 mg/kg while for essential elements the concentrations were 4.13 ± 0.95, 0.00497 ± 0.00078, 12.98 ± 1.48, 1.01 ± 0.47, 512.6 ± 9.12 and 23.22 ± 2.32 mg/kg for Zn, Mn, Co, Cu, Ca and Fe, respectively. The mean estimated dietary intakes were 0.0333 ± 0.00443, 0.88 ± 0.21, 1.06 ± 0.36, 0.00278 ± 0.00068, 0.22 ± 0.04, 109.7 ± 4.22 and 4.97 ± 1.07 mg/day for Pb, Zn, Mn, Co, Cu, Ca and Fe respectively. The estimated mean Pb dietary intake from gari consumption alone was almost the same as the benchmark dose lower confidence limit (BMDL) for Pb, thus inferring that dietary route is a potential source of Pb contamination for gari consumers in Southwest Nigerian. Also, the data from this study indicated that gari is a good source of some essential elements like Mn, Co, and Cu but not exceptionally rich in Zn, Fe and Ca. It is therefore recommended that gari diets should be complemented with other food substances like beef, vegetables and low fat cheese that are good sources of the deficient elements.     

Paper spray ionization mass spectrometry: Study of a method for fast-screening analysis of pesticides in fruits and vegetables

New faster and simpler methods for determination of pesticides in agricultural products are necessary as requirements for food safety are becoming increasingly stringent. One possibility is to introduce a fast, easy and low-cost screening method before liquid chromatography mass spectrometry analyses. We hereby present a systematic proof of concept study of paper spray mass spectrometry method for pesticide detection as a screening method. Two sampling approaches – wiping the surface with paper and applying the sample homogenate directly on the paper – were used. The wiping method was more extensively studied for imazalil and thiabendazole originally present in oranges. For homogenized samples three matrices – oranges, tomatoes and grapes – and five pesticides of different chemical nature and polarity – thiabendazole, aldicarb, imazalil, methomyl and methiocarb – were chosen. It has been shown that limits of detection below maximum residue levels can be achieved for both methods (e.g. imazalil and thiabendazole detection limits were found to be lower than 5 mg/kg). The methods are therefore suitable for fast screening of samples. Moreover, the wiping method was also applied for 11 samples – oranges, grapefruits, lemons, limes, mandarins, tomatoes, apples, pears, strawberries, grapes and sweet peppers – from the local supermarket to screen for different pesticides. Three positive samples for thiabendazole and imazalil and one positive sample for imazalil were found.     

Determination of zinc concentrations in foods of animal origin,fish and shellfish from Croatia and assessment of their contribution to dietary intake

Zinc concentrations were determined in a total of 121 samples of meat and meat products, fish and fish products and shellfish collected and marketed in Croatia. The concentrations were determined in the following ranges (mg/kg): meat 4.65–64.9, meat products 4.55–51.8, fish 3.12–19.5, fish products 12.3–31.2, mussels 21.1–30.9, oysters 129–431. The highest and lowest mean zinc levels determined were 222 mg/kg in oysters and 6.15 mg/kg in fish. Average zinc recovery of the method used was 100.4% with precision expressed as RSD of 1.5%. Significant differences were found among the tested food items. The estimated mean daily intake (EDI) of zinc in different types of food contributing to the recommended dietary allowance (RDA) for women and men were (%): meat 0.13–1.29 and 0.09–0.94; oysters 0.93 and 0.67, meat products < 0.5, both; fish, fish products and mussels < 0.15, both. The ranges of the average daily intake of zinc of the provisional maximum tolerable daily intakes (PMTDI) were (%): meat and oysters 1.05–10.3; meat products < 5; fish, fish products and mussels < 1. The results found in tested foods items were similar to results from other countries used for comparison.     

A fast and effective method of quantitative analysis of VB1, VB2 and VB6 in B-vitamins complex tablets based on three-dimensional fluorescence spectra

Scattering signals and partial overlapping of target peaks usually appear in fluorescence determination. In this study, the improved wavelet moment method was proposed and applied to the quantitative determination of multiple target components in real B-vitamins complex tablets based on three-dimensional (3D) fluorescence spectra. The correlation coefficients (R) were more than 0.9939, and the correlation coefficients of leave-one-out cross-validation (R_LOO-cv) were more than 0.9376. The inter-day and intra-day variations were less than 5.8% and 6.1%, respectively. The recovery ranged from 97.6% to 109.4%. The limits of detection (LODs) and quantification (LOQs) were less than 0.07 μg mL⁻¹ and 0.13 μg mL⁻¹, respectively. All the statistical parameters indicated that the method was stable and reliable. The application to the practical samples confirmed that wavelet moment method effectively extracted the features of target components in 3D spectra and the proposed method could be applied to the analyses of food or other complex samples.     

A rapid and sensitive method for the determination of dibutyl phthalate in wine by flow-injection chemiluminescence analysis

A sensitive method for the determination of picogram level dibutyl phthalate (DBP) in wine by flow-injection chemiluminescence (FI–CL) analysis is presented for the first time, which was based on the quenching effect of DBP on the luminol–myoglobin (Mb) CL system. The decrement of CL intensity was linearly proportional to the logarithm of DBP concentration in the range of 0.1–100 pg mL⁻¹ with the detection limit of 0.03 pg mL⁻¹ (3σ). At a flow rate of 2.0 mL min⁻¹, a complete determination of DBP including sampling and washing could be accomplished in 0.5 min, giving the maximum sample throughput of 120 h⁻¹. The proposed method was successfully applied to the determination of DBP in wine, human serum and urine samples with the relative standard deviations (RSDs) of less than 3.0% (n = 5). The molecule docking results showed that DBP interacted with the amino acid residues near the heme moiety of Mb. The possible CL mechanism of luminol–Mb–DBP reaction should be that the binding of Mb with DBP forming a 1:1 complex (binding constant K = 1.55 × 10⁴ L mol⁻¹) led to the conformational change of Mb and resulted in the quenching of CL intensity.     

Determination of urocanic acid,a compound implicated in histamine toxicity,and assessment of biogenic amines relative to urocanic acid content in selected fish and fish products

The contents of trans- and cis-urocanic acid (cis-UCA), NaCl and moisture, and pH of sixty-seven fish and shrimp products, including salted anchovy, different types of salted fish, salted shrimp and shrimp paste collected in Malaysia, were examined. Included in the analysis was determination of the contents of nine biogenic amines. The average levels of trans- and cis-UCA in salted anchovy, salted fish, salted shrimp and shrimp paste were 9.67 and 7.25, 14.2 and 11.0, 36.6 and 22.5, 6.96 and 18.7 mg/kg, respectively. In general, the average levels of trans- and cis-UCA were much lower than the histamine levels in fish products. Results showed no strong correlation of pH, salt and moisture contents with trans- and cis-UCA, nor with histamine. Biogenic amines were also detected in processed fish and shrimp products where the most abundant biogenic amine was putrescine with an average level of 227 mg/kg in shrimp paste. Thus, the high rates of cancers in consumers who consume dried salted fish could be indicative of the synergistic effects of biogenic amines and cis-UCA.     

The effects of interventions on quality of life,morbidity and consultation frequency in frequent attenders in primary care: A systematic review

Background: Patients visiting their GPs exceptionally often (frequent attenders, FAs) have high rates of somatic disease, emotional distress, psychiatric illnesses and social problems and require a disproportionate amount of their GPs’ time.

Objectives: To summarize which types of FA have been studied and what the effects of interventions were on quality of life (QoL), symptom severity of underlying illness(es) and consultation frequency. To discover when patients are considered FAs.

Methods: Systematic review of RCTs using a comprehensive search (MEDLINE, PsycINFO, CINAHL and EMBASE, from 1980 to August 2015) and no language restrictions. Two investigators extracted data. Results were summarized qualitatively.

Results: We included 17 RCTs. Heterogeneity at the level of populations, interventions and outcomes precluded statistical pooling. In-depth analysis by GPs assessing a patient’s reasons for frequent attendance decreased consultation frequency by four to six per year. A small effect on symptom severity was noted in depressed FAs, although this finding was not replicated in a recent trial. Multi-component therapy and medication in FAs with medically unexplained symptoms (MUS) improved QoL (SF36 odds ratio: 1.92; 95%CI: 1.08–3.40) and morbidity (CES-D 3.17; 95%CI: 1.27–5.08).

Conclusion: RCTs on intervention effects in frequent attenders to primary care used different patient populations, interventions, comparators and outcome measures. Consistent evidence on the effects of particular interventions in specific patient domains is lacking. A tailored approach based on in-depth analysis among GPs of potential reasons for frequent attendance may decrease consultation frequency. Research involving the screening and treating for FAs with MUS may be useful in future trials.     

Efficacy,immunogenicity, and safety of available vaccines in children on biologics: A systematic review and meta-analysis

Vaccinations are essential for preventing infectious diseases in children with chronic diseases as they have increased risk of infection from frequent use of biologics. Response to immunizations in this group is not well known.ObjectiveA systematic review was performed to evaluate three primary outcomes: efficacy; immunogenicity; and safety of vaccines in children with chronic conditions treated with biologics.MethodsThe protocol for our systematic review and meta-analysis was registered and published with PROSPERO. We searched electronic bibliographic databases for studies published from 2009 to 2019, focusing on vaccinations in children with chronic conditions treated with biologics.ResultsWe retrieved 532 records. Thirty-one full-text articles were selected, and 14 were included in the meta-analysis. No significant publication bias was found. Efficacy: limited data are available regarding the efficacy of vaccination, as most studies have focused on immunogenicity as surrogate outcome for efficacy. Immunogenicity: patients receiving anti-TNF-alpha therapy had a statistically significant risk of poor seroconversion (p = 0.028) and seroprotection by the serotype B influenza vaccine [inflammatory bowel disease (IBD) p = 0.013; juvenile idiopathic arthritis (JIA) p = 0.004]. We found adequate responses with H1N1 and H3N2 serotypes. Few studies existed for pneumococcal, hepatitis A virus, hepatitis B virus, varicella-zoster virus, Measles Mumps Rubella virus, and multiple vaccine administration. Safety: vaccine administration was not associated with serious side effects, but JIA patients on anti-TNF alpha therapy had a statistically significant risk of presenting with myalgia or arthralgia postinfluenza vaccine (p = 0.014).ConclusionsMore evidence concerning efficacy, immunogenicity, and safety of vaccinations is needed to guide physicians in the vaccine decision process for this pediatric population.     

The burden of Respiratory Syncytial Virus (RSV) infection in the Middle East and North Africa (MENA) region across age groups: A systematic review

Respiratory Syncytial Virus (RSV) is a common respiratory virus that generally causes a mild illness in children and adults or severe symptoms with complications in infants and the elderly, particularly in the presence of underlying comorbidities. While epidemiological data about this virus are available globally, data from the Middle East and North Africa (MENA) region are still scarce. For this reason, we conducted a systematic review to determine the burden of RSV disease in the MENA region by searching the available literature up until September 2018. A total of 1242 studies were retrieved of which 90 were included in the review. Most of the included studies were conducted in subjects aged 0–18 years with the majority being in children below 3 years of age, while only 2 studies included exclusively adults above 18 years of age. RSV infection rates varied greatly between different studies on hospitalized subjects and ranged between 4% and 82%, while the range was smaller in studies on outpatient subjects (between 6% and 36%). When calculating the RSV infection rates in the hospitalized subjects with different inclusion criteria, we found that it was 19%, 70%, and 33% among subjects admitted with Acute Respiratory Infections (ARIs), Acute Lower Respiratory Infections (ALRIs), and bronchiolitis, respectively. RSV infections were most common during the winter season. With regards to complications, intensive care unit admissions ranged between 1% and 15%, while the need for mechanical ventilation ranged between 1% and 10%. The overall RSV related mortality rate across all age groups in studies included in our review was 1.9%. This review identifies several limitations in the existing data and under-representation of the adult population. Future studies should be providing more evidence on the RSV burden in adults and children with comorbidities in order to better assess the potential impact of future preventive strategies in the MENA region.     

Neutralizing antibody activity,safety and immunogenicity of human anti-rabies virus monoclonal antibody (Ormutivimab) in Chinese healthy adults: A phase Ⅱb randomized,double-blind,parallel-controlled study

ObjectiveThis study was a randomized, double-blind, parallel-controlled trail to evaluate the rabies virus neutralizing activity（RVNA）, safety and immunogenicity of Ormutivimab + rabies vaccine in Chinese healthy adults.MethodsSubjects were randomly and equally assigned to 4 groups (20 IU/kg Omtv + vaccine, 40 IU/kg Omtv + vaccine, 20 IU/kg HRIG + vaccine, and placebo + vaccine). Subjects received vaccine as the WHO Essen regime combined with Omutivimab、HRIG or placebo on Day 0. The study lasted for 43 days.ResultsA total of 240 subjects were simultaneously assigned to both FAS and SS. Fifty subjects with baseline RVNA > 0.05 IU/ml (detection limit) were excluded, 190 were included into mITT.All the subjects from 40 IU/kg Omtv + vaccine group had a protection level of RNVA (≥0.5 IU/ml, WHO) on Day 14, and those in 20 IU/kg Omtv + vaccine group and placebo + vaccine group converted positive 100 % on Day 28. In contrast to 20 IU/kg HRIG + vaccine and placebo + vaccine, Ormutivimab + vaccine provided a higher RVNA during Days 0 to 7. And RVNA in 40 IU/kg Omtv + vaccine and 20 IU/kg Omtv + vaccine groups were always higher than 20 IU/kg HRIG + vaccine group during the whole study. Although anti-Omtv antibody were detected in some subjects, it did not influence the RVNA. The incidence of adverse reactions was significantly lower in 20 IU/kg Omtv + vaccine group (17.2 %) than in 40 IU/kg Omtv + vaccine (36.7 %) and 20 IU/kg HRIG + vaccine groups (40.3 %).ConclusionCompared with HRIG + vaccine and placebo + vaccine, Omtv + vaccine provided higher RNVA for earlier immune protection. The interference of Ormutivimab on the long-term immune protection induced by rabies vaccine is weaker than HRIG. At the same dose, the adverse reactions of Omtv + vaccine group were less than HRIG + vaccine group.Registration: ClinicalTrials.gov #NCT02559921.     

Safety,tolerability, and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine,followed by sequential PPSV23 vaccination in healthy adults aged ≥50 years: A randomized phase III trial (PNEU-PATH)

BackgroundStreptococcus pneumoniae causes pneumococcal disease, and older adults are at an increased risk. Sequential vaccination of 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) is recommended for broad protection against pneumococcal disease in some countries.MethodsThis phase III trial evaluated the safety, tolerability, and immunogenicity of sequential administration of either V114 (a 15-valent PCV containing serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F) or PCV13, followed 12 months later by PPSV23, in healthy adults aged ≥50 years (NCT03480763). A total of 652 participants were randomized 1:1 to receive either V114 or PCV13, followed by PPSV23.ResultsThe most common solicited adverse events (AEs) following PCV vaccination included injection-site pain and fatigue. Higher proportions of participants with these events were observed in the V114 group following PCV; however, these differences were not clinically significant. Following PPSV23 vaccination, the most common solicited AEs were injection-site pain and injection-site swelling; the proportions of participants with these events were comparable between both groups. Incidence of serious AEs was low in both groups following PCV and PPSV23, and none were related to study vaccines. No deaths occurred during the study. Serum opsonophagocytic activity geometric mean titers and immunoglobulin G geometric mean concentrations were comparable between both groups for all 15 serotypes in V114 following PPSV23. Immune responses elicited by V114 persisted for at least 12 months. Immune responses at 30 days and 12 months post-vaccination with PCV were comparable between both groups for the 13 shared serotypes and higher in the V114 group for the V114-unique serotypes (22F and 33F).ConclusionAdministration of V114 followed by PPSV23 was well tolerated and induced comparable antibody levels to PCV13 followed by PPSV23 in healthy adults aged ≥50 years.