The data of our study detail the accumulation of the phytochemical composition of biologically active compounds in cranberry samples during the stages of maturity, therefore these data are significant for the assessment of harvest time of cranberry and can be applied to select cranberry cultivars for further cultivation in Lithuanian climatic conditions.In our investigation, we evaluated the content of chlorogenic acid, proanthocyanidins, anthocyanins, flavonols, triterpenoids, and phytosterols in cranberry fruit extracts of the cultivars ‘Baifay’, ‘Early Black’, ‘Howes’, ‘Pilgrim’, ‘Red Star’, and ‘Stevens’ grown in Lithuania, as well as changes in the antioxidant activity in extracts of fruit samples of these cultivars during the period of berry maturation. The highest amount of proanthocyanidins (8.87 ± 0.57 mg EE/g EE) and flavonols (3688.52 ± 22.85 µg/g) was determined in cranberries of the cultivar ‘Howes’ harvested on 12 August. Remarkably, the highest anthocyanins content (9628.62 ± 266 µg/g) was determined in cranberries of the cultivar ‘Howes’ harvested on 22 October. The study showed that the content of phytochemical compounds in cranberries varied between 12 August and 22 October; the content of proanthocyanidins decreased by a factor of about 2, the content of chlorogenic acid decreased by a factor of about 1.3, the content of flavonols decreased by a factor of about 2, and the content of anthocyanins increased by 27 to 450 times. A strong correlation was found between the total proanthocyanidin content of cranberry fruit extracts and their in vitro antiradical and reducing activity (r = 0.781 and 0.726, respectively,  Vaccinium macrocarpon Aiton) belongs to the Ericaceae botanical family [Vaccinium oxycoccus L.), which has resulted in the increasing popularity of the cultivation of large cranberries in the Baltic region [Large cranberry  determining the pharmacological effects in cranberry fruit samples. To this end, research has been carried out and innovative instrumental analytical methodologies have been developed, optimized, and validated to analyze the qualitative and quantitative composition of cranberry fruit samples. Vilkickytė et al. proposed and validated a UPLC-DAD methodology for the analysis of anthocyanins and anthocyanidins in cranberry and other fruit samples . SedbareThe aim of our study was to investigate the phytochemical composition of anthocyanins, flavonols, chlorogenic acid, proanthocyanidins, triterpenoids, and phytosterols in fruit samples of large cranberry cultivars ‘Baifay’, ‘Early Black’, ‘Howes’, ‘Pilgrim’, ‘Red Star’, and ‘Stevens’ grown in Lithuania, in the collection of Vilnius University Botanical Garden, and to evaluate amount changes in these compounds during the ripening period of the fruit. Anthocyanins have been detected in cranberry fruit samples, and have antioxidant ,22 and aAnalysis of anthocyanins and anthocyanidins composition showed that cyanidin-3-O-galactoside, cyanidin-3-O-arabinoside, peonidin-3-O-galactoside, and peonidin-3-O-arabinoside accounted for 93.11% ± 3.4% of the sum of anthocyanins and anthocyanidins in cranberries. The composition of these four predominant glycosidic compounds of the anthocyanin group varied between August 12 and October 22: 36.89% ± 14.66% of cyanidin-3-O-galactoside, 25.84% ± 6.31% of cyanidin-3-O-arabinoside, 21.70% ± 10.78% of peonidin-3-O-galactoside, and 8.68% ± 4.46% of peonidin-3-O-arabinoside . The quaViškelis et al. studied cranberry samples of the cultivars ‘Pilgrim’, ‘Stevens’, ‘Black Veil’, and ‘Ben Lear’ grown in the Lithuanian climate and determined that the content of the major anthocyanins was 33.13% ± 1.15% of peonidin-3-galactoside, 6.21% ± 1.07% of peonidin-3-arabinoside, 21.28% ± 1.05% of cyanidin-3-galactoside, and 17.57% ± 1.05% of cyanidin-3-arabinoside [Our study showed that the lowest total amounts of anthocyanin (10.45 ± 0.7 µg/g–296.49 ± 10 µg/g) were determined in cranberry fruit samples collected on 12 August. The lowest amount of total anthocyanins (10.45 ± 0.7 µg/g) was determined in the cranberry cultivar ‘Baifay’ collected on 12 August and consisted of cyanidin-3-O-galactoside. The sum of anthocyanins in cranberries of the cultivar ‘Early Black’ harvested on 12 August was 28 times higher than that determined in cranberry samples of the ‘Baifay’ cultivar harvested on the same day. In cranberries of the cultivars ‘Baifay’, ‘Early Black’, ‘Howes’, ‘Pilgrim’, ‘Red Star’, and ‘Stevens’ collected on 12 August, the levels of malvidin-3-O-galactoside, malvidin-3-O-arabinoside, and malvidin were below the limit of detection, with a more marked increase in the levels of these compounds starting on 10 September .The highest total amounts of anthocyanin were determined in samples of the tested cranberry cultivars collected on 22 October. The sum of anthocyanins in fruit samples collected on 22 October ranged from 3710.58 ± 89 µg/g to 9628.62 ± 266 µg/g. The lowest amount of total anthocyanins (3710.58 ± 89 µg/g) was determined in samples of the cranberry cultivar ‘Stevens’ collected on 22 October. The highest amount of total anthocyanins (9628.62 ± 266 µg/g) was determined in cranberries of the cultivar ‘Howes’. Cranberries of the cultivar ‘Howes’ harvested on 22 October contained significantly higher levels of delphinidin-3-galactoside, malvidin-3-O-galactoside, malvidin-3-O-arabinoside, malvidin, peonidin, and cyanidin compared to the levels determined in cranberries of the other tested cranberry cultivars harvested on 22 October . The content of anthocyanins and anthocyanidins in cranberries of the cultivars ‘Baifay’, ‘Early Black’, ‘Pilgrim’, ‘Howes’, ‘Red Star’, and ‘Stevens’ grown in Lithuania during the ripening period between 12 August and 22 October increased by 27 to 450 times . During The results of our study show that the cranberry cultivars ‘Howes’, ‘Early Black’, and ‘Pilgrim’ have the highest level of anthocyanins, so these cultivars are promising for growing in Lithuanian climates as a source of anthocyanins. Furthermore, the study revealed an increasing trend in anthocyanin and anthocyanidin content, which provides knowledge on the quantitative changes in individual compounds during the ripening period and allows for selecting the optimum time for cranberry picking when the berries accumulate the highest levels of anthocyanins. Studies on the chemical composition of cranberry fruit samples allow the qualitative and quantitative composition of individual anthocyanins to be assessed and allow for the preparation of useful cranberry raw material with the highest content of anthocyanins, the biologically active compounds that determine the biological effects of cranberries.Flavonols are biologically active compounds with antioxidant, cardioprotective, antibacterial, antiviral, and anticancer activities ,30,31. OWang et. el. determined that quercetin-3-galactoside contains 31–46%, myricetin-3-galactoside contains 19–32%, quercetin-3-α-L-arabinofuranoside contains 7–17%, and quercetin-3-rhamnoside contains 7–14% of the total identified flavonols content in cranberries of different cultivars . These rThe evaluation of flavonols showed that the total flavonol levels in cranberries ranged from 1465.56 ± 31.22 µg/g to 3688.52 ± 22.85 µg/g. The highest total flavonol content (3688.52 ± 22.85 µg/g) was determined in cranberries of the cultivar ‘Howes’ harvested on 12 August, and the lowest total flavonol content (1465.56 ± 31.22 µg/g) was determined in cranberries of the cultivar ‘Howes’ harvested on 22 October.During the ripening period of the fruits from 12 August to 22 October, the sum of the flavonols in cranberries decreased by 1.46 to 2.52 times . VvedensThe flavonol content in cranberries of the cultivar ‘Howes’ decreased throughout the berry picking period. Cranberry cultivars ‘Baifay’, ‘Early Black’, ‘Pilgrim’, ‘Red Star’, and ‘Stevens’ showed a different trend in total flavonol content from that seen in the ‘Howes’ cultivar. In cranberry samples of cultivars ‘Baifay’, ‘Early Black’, ‘Pilgrim’, and ‘Red Star’, an increase in total flavonols by about 1.2 times was observed on 24 September . In fruiThe trends in the changes of the quantitative composition of the compounds myricetin-3-galctoside, quercetine-3-galactoside, and quercetine-3-arabinofuranoside found in the tested cranberry samples were similar to those of the total flavonol content. Between 12 August and 22 October, the amounts of myricetin and quercetin decreased by a factor of 3 and 4, respectively. Quercetin-3-rhamnoside content in fruit samples showed little variation, with a decrease of about 1.1-fold in cranberry samples of cultivars ‘Baifay’, ‘Early Black’, ‘Howes’, ‘Red Star’, and ‘Stevens’, and an increase of about 1.15-fold in cranberry samples of the cultivar ‘Pilgrim’. Wang et al. determined that quercetin-3-galactoside and myricetin-3-galactoside levels varied only slightly during the different stages of maturity in cranberries of the cultivars ‘Howes’, ‘Ben Lear’, ‘Stevens’, Early Black’, ‘Crimson Queen’, ‘Mullica Queen’, ‘Demoranville’, and ‘#35′ .Studies on the phytochemical composition of cranberries allow the determination of flavonols, their quantitative composition, and trends in their content. The highest flavonol levels were found in fruit samples of the cultivars ‘Howes’, ‘Pilgrim’, and ‘Red Star’ taken at different ripening periods, indicating the importance of harvest time. The determination of the content of flavonols is important for assessing the quality of cranberry raw material and for predicting the biological effects of cranberry raw material preparations, which are determined by flavonols.The phenolic carboxylic acids found in cranberry fruit plant material are biologically active compounds. Oszmianski et al. suggested that concentration of phenolic acids, especially of chlorogenic acid is important, as these compounds are the precursors of flavour in cranberry fruit . SantanaIn our study, the analysis of chlorogenic acid content in cranberries showed that chlorogenic acid content varied from 104.73 ± 1 µg/g to 489.70 ± 3 µg/g A. The hiDuring the ripening period from 12 August 2 to 27 August, the chlorogenic acid content in cranberries of cultivars ‘Baifay’, ‘Howes’, ‘Pilgrim’, ‘Early Black’, ‘Red Star’, and ‘Stevens’ decreased, on average, by a factor of 1.33 . During The quantity of chlorogenic acid in cranberries shows little variation during the ripening period of the cranberry fruit, thus the qualitative and quantitative evaluation of chlorogenic acid content can serve as one of the markers for the identification of the cranberry raw material and the assessment of its quality.Escherichia coli [Helicobacter pylori infection [Cranberry fruit raw material was found to contain proanthocyanidin compounds, which are responsible for the antibacterial effect of cranberry preparations. Pérez-López et al. determined that a group of proanthocyanidins inhibit P-fimbriae synthesis and induce a bacterial deformation, on both antibiotic-susceptible and antibiotic-resistant uropathogenic hia coli . Li et anfection . In our During the cranberry ripening period from 12 August to 8 October, a decreasing trend of proanthocyanidin content was observed in cranberry samples of cultivars ‘Baifay’, ‘Howes’, ‘Pilgrim’, ‘Early Black’, ‘Red Star’, and ‘Stevens’, which showed a decrease of about a factor of 2. During the ripening period from 8 October to 22 October, the decrease in proanthocyanidin content in cranberry samples of the tested cultivars either stabilized or there was a 1.1-fold increase. Wang et al. and Vvedenskaya et al. studies confirm our results that the amount of proanthocyanidins decreased most intensively at the beginning of maturity, slightly increased at later stages of maturity ,27. SimiStudies on the amount of proanthocyanidins in cranberry maturity stages are relevant for the preparation of cranberry plant material. The determination of proanthocyanidin content provides an opportunity to prepare cranberries with a known proanthocyanidin content, which can be used for the production of cranberry preparations. Proanthocyanidins in cranberry fruit raw material provide antibacterial effects in the treatment and prevention of urinary tract infections, and the identification of these compounds is therefore important to produce high-quality food supplements and medicinal products of known composition and efficacy ,40.Triterpenoids identified in cranberry fruit are responsible for their anti-inflammatory, antitumor, and anticancer effects . Chen etIn our study, we identified and quantified triterpenoids  and phytosterols (campesterol and β-sitosterol). In cranberry fruit samples collected between August 12 and October 22, ursolic acid accounted for 75.62% ± 2.54%, oleanolic acid—for 19.50% ± 1.42%, corosolic acid—for 2.71% ± 1.95%, maslinic acid—for 0.89% ± 0.78%, α-amyrin—for 0.86% ± 0.45%, and β-amyrin—for 0.42% ± 0.32% of the total triterpenoid content. Klavins et al. confirmed that ursolic acid is the predominant triterpenoid in cranberry fruit [In cranberry fruit samples, β-sitosterol content was higher (98.16% ± 1.84%) than that of campesterol (1.84% ± 0.45%). Wu et al. also indicated that β-sitosterol is the major phytosterol in cranberry fruit . ŠedbarėThe changes in the total amount of triterpene compounds detected in fruit samples of the tested cranberry cultivars between 12 August and 22 October showed a mixed pattern . This vaOszmianski et al. found that the concentration of triterpenoids  in fruits of cranberry cultivars ‘Stevens’ and ‘Pilgrim’ collected from 1 September to 22 September increased by a factor of 1.3 and 1.1, respectively . In our The changes in the amounts of the detected triterpenoids  in cranberries varied. During the ripening period, the quantity of maslinic acid in cranberry fruits of ‘Early Black’ and ‘Howes’ cultivars was significantly higher than that in fruits of ‘Baifay’, ‘Pilgrim’, ‘Red Star’, and ‘Stevens’ cultivars . During The quantity of corosolic acid in cranberries of cultivars ‘Early Black’ and ‘Howes’ was higher than that found in cranberries of cultivars ‘Pilgrim’, ‘Red Star’, and ‘Stevens’ cultivars during ripening . BetweenThe quantity of α-amyrin in fruits of the tested cranberry cultivars increased by up to 40-fold between 12 August and 22 October . The conAnalysis of triterpenoids in cranberry plant material showed that the triterpenoid content in cranberry fruits varied during the ripening period. The high triterpenoids levels during the ripening of cranberry fruits were found in the samples of the ‘Early Black’ cultivar. This is possibly because the cranberries of this cultivar are smaller in size and have a larger surface area of the peel, where triterpenoids accumulate . TriterpThe determination of the phytochemical compounds is important in the preparation of cranberry plant material, as it allows for the preparation of material with known levels of triterpene compounds and phytosterols, which may influence the biological effects of the preparations.Phenolic compounds and triterpenoids found in plant matrices are natural antioxidants ,51. AntiIn our study, the antiradical activity of 100% acetone and 70% ethanol acidified with 1% HCl extracts of cranberries was estimated by the ABTS method, and the reducing activity was tested by applying the FRAP method. The extraction of triterpenoids by aqueous mixtures of organic solvents  is less efficient with a lower polarity organic solvent, and therefore 100% acetone was chosen as the extraction solvent to improve the efficiency of the extraction of triterpenoid compounds from cranberry fruit samples ,56. PhenChanges in the antioxidant activity of cranberry extracts occurring during berry ripening are shown in The antiradical activity of cranberries acetone extracts evaluated by the ABTS method during the ripening of the berries ranged from 3.39 ± 0.38 µmol TE/g to 14.90 ± 2.10 µmol TE/g. The reducing activity of cranberries acetone extracts estimated by the FRAP method ranged from 4.51 ± 0.26 µmol TE/g to 17.61 ± 3.26 µmol TE/g. The acetone extracts of cranberry cultivar ‘Howes’ produced from cranberry samples collected on 12 August showed the strongest antiradical (14.90 ± 2.10 µmol TE/g) and reducing (17.61 ± 3.26 µmol TE/g) activity.Acetone extracts of cranberry cultivars ‘Baifay’, ‘Early Black’, ‘Howes’, ‘Pilgrim’, and ‘Red Star’ made from fruit samples collected on 12 August showed by 2 times stronger antiradical activity and by 1.5 times stronger reducing activity than acetone extracts of cranberry fruit collected on 22 October did. Acetone extracts of fruit samples of the ‘Stevens’ cultivar showed a 1.5-fold decrease in antioxidant activity between 12 August and 24 September, and an approximately 1.5-fold increase between 24 September and 22 October.The antiradical activity of the ethanolic cranberry extracts varied from 95.56 ± 3.74 µmol TE/g to 223.90 ± 16.11 µmol TE/g during the ripening of the berries. The extracts of the ‘Howes’ cranberry fruit samples collected on 12 August demonstrated the strongest antiradical activity (223.90 ± 16.11 µmol TE/g). The weakest antiradical activity (95.56 ± 3.74 µmol TE/g) was determined in cranberry extracts of the ‘Stevens’ cultivar made from cranberry samples collected on 22 October.The antiradical activity of the ethanolic cranberry extracts of the cultivars ‘Early Black’ and ‘Howes’ decreased by a factor of about 1.4 between 12 August and 8 October and increased by a factor of 1.3 between 8 October and 22 October. The strongest antiradical activity of the ethanolic cranberry extracts of cultivars ‘Pilgrim’ and ‘Stevens’ was found in extracts made from cranberries harvested on 10 September. The ethanolic extracts of the cranberry cultivars ‘Baifay’ and ‘Red Star’ showed only a slight variation in antiradical activity during the study.The reducing activity of cranberry ethanolic extracts as assessed by the FRAP method varied from 100.79 ± 13.46 µmol TE/g to 223.60 ± 14.96 µmol TE/g. The strongest reducing activity (223.60 ± 14.96 µmol TE/g) was observed for the ethanolic extracts of cranberry fruit samples of the cultivar ‘Howes’ collected on 27 August. Meanwhile, the ethanolic cranberry extracts of the cultivar ‘Pilgrim’ harvested on 12 August had the weakest antiradical activity (100.79 ± 13.46 µmol TE/g).The reducing activity of the ethanolic cranberry extracts of the cultivars ‘Early Black’, ‘Howes’, and ‘Stevens’ decreased by a factor of about 1.3 between 12 August and 8 October and increased by a factor of about 1.2 between 8 October and 22 October. The strongest reducing activity of the ethanolic extracts of the cranberry cultivars ‘Pilgrim’ and ‘Red Star’ was found in the extracts from cranberries harvested on 27 August. The antiradical activity of the ethanolic fruit extracts of the cranberry cultivar ‘Baifay’ showed only a slight variation during the study.p < 0.001 and r = 0.726, p < 0.001, respectively). Proanthocyanidins identified in cranberry fruit samples contain epicatechin units in their structure, which have exceptionally strong antioxidant properties [We found a linear correlation between antioxidant activity and the levels of anthocyanins, flavonols, chlorogenic acid, proanthocyanidins, triterpene compounds, and phytosterols. The total amount of proanthocyanidins had a strong positive correlation with the antiradical activity determined by the ABTS method and the reducing activity determined by the FRAP method . We found that the total triterpenoid content had a moderate positive correlation with the antiradical activity determined by the ABTS method and the reducing activity estimated by the FRAP method . A moderate correlation was found between the total phytosterol content in cranberry fruit extracts and the in vitro antiradical and reducing activity of their extracts . We found no correlation between the antioxidant activity of the extracts and the anthocyanin or chlorogenic acid content.The total amount of flavonols had a moderate positive correlation with the antiradical activity determined by the ABTS method and the reducing activity estimated by the FRAP method  and flavonols  [p < 0.05) and the FRAP  methods [p < 0.001), and by the ABTS method was r = 0.635 (p < 0.001) [Oszmiański et al. investigated the linear correlation between antioxidant activity and the levels of triterpenoids, anthocyanins, flavonols, and phenolic acids found in cranberry samples of the cultivars ‘Ben Lear’, ‘Franklin’, ‘Howes’, ‘Pilgrim’, ‘Red Star’, and ‘Stevens’ . The aut< 0.001) .Cranberry fruit is a valuable plant material accumulating flavonoids and triterpenoids. In plant materials, it is often not possible to attribute the biological effects to a specific group of compounds or to a specific compound, as the complex of polyphenolic compounds acts synergistically ,64. As tVaccinium macrocarpon Aiton) fruit samples of different cultivars grown in Lithuanian climatic conditions, in the collection of VU Botanical Garden. The variables of meteorological data (precipitation (mm), temperature (°C), and sunshine duration (h)) in the Vilnius region during 2021 are presented in The object of the study was large cranberry . Cranberry fruits were collected during berry ripening six times: on 12 August, 27 August, 10 September, 24 September, 10 October, and 22 October 2021 . The fruit shapes and sizes of the cranberry cultivars ‘Baifay’, ‘Early Black’, ‘Howes’, ‘Pilgrim’, ‘Red Star’, and ‘Stevens’ are shown in The harvested cranberries were crushed and frozen at −20 °C in a freezer. Afterwards, the samples were transferred to a −60 °C freezer . Cranberry samples were freeze-dried by Gudžinskaitė et al. described methodology . Freeze-v/v) ethanol containing 1% hydrochloric acid in ratio 1:20 according to Urbstaite et al. described methodology [Ethanol extracts were prepared for the determination of the content of flavonols, anthocyainis, chlorogenic acid and proanthocyanidins. The freeze-dried powders of each cranberry samples were extracted three times with 70% . The analysis of the composition of anthocyanins, phenolic compounds, triterpenic compounds, and phytosterols in cranberry fruit was performed using a Waters ACQUITY Ultra High-Performance LC system  with a photodiode array detector. The composition of anthocyanins and anthocyanidins in cranberry samples were determined using methodology described by Vilkickyte G. et al. . Determi2 = 0.9994) and expressed as mg/g (–)-epicatechin equivalent (EE) dry weight.The content of proanthocyanidins was performed using the DMCA assay methodology described by the Heil et al.  and modi∙+  antioxidant activity determination was performed using the methodology introduced by Re et al. [2 = 0.999) which was prepared using standard Trolox solutions of 2000–11,000 μmol/L concentration. The ABTS∙+ radical cation decolorization activity of the acetone cranberry extract was calculated from the standard curve  which was prepared using standard Trolox solutions (375–3000 μmol/L).An ABTSe et al.  and desce et al. . A volum2 = 0.995) which was prepared from standard Trolox solutions . The reducing activity of the acetone cranberry extract was calculated from the standard curve  which was prepared from standard Trolox solutions of 375–2000 μmol/L concentration. The FRAP (ferric reducing antioxidant power) assay was performed by Raudone et al. described methodology . A volumv/v) , formic acid , acetonitrile , hydrochloric acid , and 4-(Dimethylamino)cinnamaldehyde . Reference standards for maslinic acid, corosolic acid, oleanolic acid, ursolic acid, β-Amyrin, campesterol, α-Amyrin, β-Sitosterol, chlorogenic acid, myricetin, quercetin-3-rhamnoside, quercetin-3-α-L-arabinofuranoside, and quercetin-3-α-L-arabinopyranoside were obtained from Sigma-Aldrich . Reference standards for delphinidin-3-galactoside, cyaniding-3-galactoside, cyaniding-3-glucoside, cyaniding-3-arabinoside, peonidin-3-galactoside, peonidin-3-arabinoside, peonidin-3-glucoside, malvidin-3-galactoside, malvidin-3-arabinoside, cyanidin chloride, peonidin chloride, malvidin chloride, and myricetin-3-galactoside were purchased from Extrasynthese . Reference standards for quercetin-3-galactoside and quercetin were obtained from Carl Roth . The reference standard for quercetin-3-O-glucoside was obtained from Biochemistry . In addition, the following reagents were used: Trolox , ABTS 2,2’-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), sodium acetate , potassium peroxydisulfate, TPTZ -s-triazine) , and ferric (III) chloride hexahydrate . The purified deionized water used in the experiments was prepared using a Milli-Q®  water purification system.The following reagents were used in the study: acetone, methanol , ethanol 96%  and SPSS Statistics 21 . During the study, means and standard deviations (SD) of the three independent evaluations were calculated. To evaluate the difference in the amounts of anthocyanins, anthocyanidins, flavonols, chlorogenic acid, proanthocyanidins, and triterpenic compounds between fruit samples of different cranberry cultivars, the one-way analysis of variance ANOVA with Tukey’s test for multiple comparisons was used. Differences at relation .The fruit samples of the large cranberry cultivars grown in the collection of Vilnius University Botanical Garden were investigated and the phytochemical composition of anthocyanins, flavonols, chlorogenic acid, proanthocyanidins, triterpenoids, and phytosterols during the ripening period of the fruit was evaluated. The timing of cranberry collection is one of the relevant factors determining the biologically active compounds quantity in the cranberry raw material. Furthermore, the different characteristics of cranberry cultivars also have a significant effect on the cranberries’ bioactive compounds composition. Cranberries of ‘Early Black’ and ‘Howes’ cultivars at different maturity stages contained high amounts of anthocyanins, proanthocyanidins, flavonols and triterpenoids, as well as the fruit extracts of these cultivars demonstrated high levels of antioxidant activity. Cranberry raw material prepared at the beginning of berry ripeness (in August) have higher levels of flavonols and proanthocyanidins, while cranberry raw material harvested at the end of the ripening period (in October) have high levels of anthocyanins and anthocyanidins. The data of the study provide new information on the phytochemical composition of biologically active compounds and patterns of their biosynthesis and accumulation in fruit samples of cranberry cultivars grown in Lithuania and allow for determining the qualitative and quantitative composition of biologically active compounds. These results can be used to provide recommendations for further introduction, selection, and cultivation of cranberries in the Lithuanian climatic conditions. Moreover, studies on the phytochemical composition of cranberry cultivars are relevant because they can lead to encourage further research into the effects of cranberry biologically active compounds for health benefits and the use of cranberry plant material in the development of new drugs.


Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266.Dear Xinhang Dong et al.,Thank you very much for your thoughts on this study . The hem


Improvements of the happiness of the rural population are an essential sign of the effectiveness of relative poverty governance. In the context of today’s digital economy, assessing the relationship between digital literacy and the subjective happiness of rural low-income groups is of great practicality. Based on data from China Family Panel Studies, the effect of digital literacy on the subjective well-being of rural low-income groups was empirically tested. A significant happiness effect of digital literacy on rural low-income groups was found. Digital literacy promotes the subjective happiness of rural low-income groups through income increase and consumption growth effects. The observed happiness effect is heterogeneous among different characteristic groups, and digital literacy significantly positively impacts the subjective happiness of rural low-income groups. Decomposition of subjective happiness into life satisfaction and job satisfaction shows that digital literacy significantly positively affects the job and life satisfaction of rural low-income groups. This paper demonstrates that digital literacy induces a practical happiness effect. To further strengthen the subjective welfare effect of digital literacy in the construction of digital villages, the government should focus on cultivating digital literacy among low-income groups from the demand side. The construction of digital infrastructure should be actively promoted from the supply side. Over recent years, China has achieved unprecedented poverty eradication, and a total of 55.75 million rural poor people have been completely lifted out of poverty. The lessons learned contribute an important solution to poverty alleviation in developing countries. With the completion of the task of eradicating absolute poverty in China according to current standards, the focus of today’s post-poverty alleviation era will shift to alleviating relative poverty with unbalanced and insufficient development . How to With the construction of information infrastructure, service platforms, and resource systems on the supply side, digital technologies are gradually being integrated into different areas of rural production, life, ecology, and governance. Digital technology applications provide rural residents with diversified opportunities and tend to equalize access and benefit. However, in economic activities, rural residents do not benefit equally from digital development outcomes . DiffereFor rural residents, two levels of digital technology adoption exist in digital technology accessibility, reflecting differences in access and usage of digital technology, as well as differences in digital literacy . PreviouOverall, the existing literature has paid little attention to the relationship between the usage of digital technology and happiness, which is hidden within the accessibility of digital technology. With the improvement of digital infrastructure and its wider availability, the gap in digital technology accessibility continues to narrowThis paper focuses on the impact of digital literacy on the subjective happiness of the rural population, especially addressing the subjective happiness of rural low-income groups. Based on this study, scientific suggestions for relative poverty governance are proposed from the perspective of subjective welfare. The marginal contributions of this paper are: first, the innovation of research perspective. Referring to the mindsponge theory, we construct an analytical framework of digital literacy affecting subjective happiness from an information perspective, which enriches the research results on the antecedents of happiness to a certain extent. Second, the innovation of the research object. The research object is aimed at the rural low-income group, a socially marginalized group. Third, the expansion of the connotation of happiness. This paper decomposes happiness into life satisfaction and job satisfaction, and analyzes the influence of digital literacy on the work and life satisfaction of rural low-income groups, which enriches the connotation of subjective happiness.“Happiness” is a subjective cognitive evaluation and emotional experience of an individual’s real-life state that ranges on a continuum from positive to negative and is a subjective reflection at the psychological level . PreviouFrom a consumption perspective, the level and structure of consumption reflect the outcome of the individual’s realization of the implementation of their rights in the real world, e.g., the right to medical services, education, or housing. Compared to income indicators, the consumption structure provides a more comprehensive representation of individual resource endowments as well as the implementation of economic and social rights. Traditional economic theory suggests that utility is directly derived from consumption. Therefore, changes in the consumption structure exert an important impact on the subjective happiness of rural low-income groups. According to individual needs, consumption structures have been classified into consumption of basic goods, conspicuous consumption, material consumption, and experiential consumption . In the With the implementation of a series of policies (such as “broadband China”), the construction and improvement of China’s information infrastructure have accelerated. The application of digital technologies such as big data, the Internet of Things, and artificial intelligence in the production sector has led to the digital development of rural industries, embedding digital technologies in all stages and sectors of production. Currently, digital technology has derived multiple functions for information interaction, such as digital learning and work, participation in business transactions, and social interaction . AccordiThe absolute advantage of digital technology in information dissemination and employment effects provides the basis for increasing the absolute income and alleviating income inequality . In agriThe imperfection of rural road transport facilities limits the range of products and services available in the offline markets of rural areas. Digital technology has overcome the barriers of information dissemination, increased the circulation of urban and rural goods, and expanded the scope of rural markets . DigitalAccordingly, the following two hypotheses are proposed:Hypothesis 1: Digital literacy has a significant happiness effect; the higher the digital literacy, the higher the subjective happiness of the rural low-income group.Hypothesis 2: Digital literacy enhancement contributes to the subjective happiness of rural low-income groups through the income effect and consumption effects.The following econometric model is constructed to assess the relationship between digital literacy and subjective happiness of rural low-income groups.Where Following the basic model setup described above, in the baseline regression section, ordinary least squares (ols) and ordered probit (oprobit) are adopted for parameter estimation.Digital literacy is essentially an individual’s ability to use digital technology, and endogeneity problems may emerge in the process of causal identification, leading to biased estimations. In this paper, there are two types of endogeneity problems: first, the omission of variables, i.e., certain important variables that affect both digital literacy and subjective happiness may have been omitted from the baseline regression model. Second, reverse causality, i.e., individuals’ subjective happiness affects their digital literacy level and vice versa. For example, individuals may be more likely to learn and use digital technology and thus accumulate digital literacy when they feel positive emotions of happiness.To mitigate endogeneity issues as much as possible, hard-to-observe personality traits as well as individual and family characteristics are controlled for in the baseline regression model. At the same time, an instrumental variable approach is used for parameter estimation. Drawing on existing literature , in thisThis paper uses two-stage least squares (2sls) and an extended regression model (ERM) to deal with the endogeneity problem. Happiness can be considered as both continuous and ordered variables. The two-stage least squares method solves the problem of two-way effects of the independent and dependent variables through two linear regressions, which is applicable when the dependent variable is continuous. The extended regression model (ERM) is based on the multivariate normal distribution and great likelihood estimation. It has the advantage of handling endogeneity problems with endogenous variables, endogenous sample selection, random effects, or a combination of scenarios simultaneously . The extThe data used in this paper originate from the China Family Panel Studies (CFPS) conducted by the China Social Science Research Center of Peking University. The CFPS is conducted every 2 years and provides data from 25 provinces  across China. The database contains individual-level and household economic information, which can comprehensively and systematically reflect the characteristics of Chinese micro subjects. These data provide a good database for this study. This paper discusses the relationship between digital literacy and happiness based on the digital economy. In theory, it needs to be studied in a perfect information and communication facilities environment. In 2018, the scale of China’s digital economy accounted for 34.8% of the total GDP, and the Internet penetration rate was 59.6%. The current construction of information and communication facilities in China can be considered as relatively advanced, and the digital environment has gradually formed. Therefore, this paper uses the latest data from CFPS (2018) as the main data source to test the impact of digital literacy on subjective happiness. The variables of digital literacy, happiness, and individual characteristics are derived from the adult pool, and the variables of income and population size are derived from the family pool. The sample screening process is described in the following.per capita net income below 50% of the average income are considered as low-income households. Finally, exclusion of samples with abnormal or missing core variables formed a sample of 3,013.First, respondents aged 15–64 who have an agricultural household and are of working age were selected for this study. All samples outside of this age group and those from non-rural areas were excluded. Second, low-income groups were screen out, relying on the income data of the previous period (CFPS2016) to identify low-income groups. The reason is that the current period income (CFPS2018) may result from the generation of digital literacy, making it difficult to clearly identify the study population. In this paper, the relative poverty criteria set by the World Bank are used. The average income proportion method is used to measure the low-income group, and households with a In this paper, the dependent variable is the subjective happiness of individuals in rural low-income households. Following the previous literature , a “selfIn this paper, the independent variable is digital literacy. Digital literacy is defined as an individual’s ability to use digital tools and devices correctly and rationally to utilize digital resources, learn new knowledge, and communicate socially with others . Therefoper capita income. The influence of unobservable factors at the village level is considered  and village dummy variables are controlled for.This paper also controls for other factors that may affect happiness, including common individual and household characteristics, such as age, gender, marital status, health status, political identity, religious beliefs, and educational attainment. Among these, individual age may have a non-linear effect on happiness. Therefore, both individual age and the squared term of age are introduced; household characteristics mainly control for household size and household The problem of omitted variables because of possible non-observables is also considered, as it can cause bias in the estimation results. Based on the full coverage of economics, sociology, and psychology, refer to the study of The existing literature is more concerned with the impact of ICT on happiness and focuses on the relationship between changes in the digital environment and happiness . This paF-value of the one-stage estimation is 231.37, indicating that there is no weak instrumental variable problem. In the ERM estimation results, the residual term correlation coefficient is significant, indicating that the results of the instrumental variable method are more reliable than the baseline regression. Overall, when the endogeneity issue has been dealt with, digital literacy significantly enhances the subjective happiness of the rural low-income group at the 1% statistical level. This result supports Hypothesis 1.2sls and ERM were used for parameter estimation. The robustness of the baseline regression results is tested by replacing the core independent variable, the dependent variable, and the health variable.p value of 0.000 for Bartlett’s test were obtained, indicating a strong correlation between indicators and the results of reliable factor analysis. The cumulative variance contribution was 73.34%, indicating that this common factor has relatively strong explanatory power for the indicators. The column (1) of First, the core independent variables are replaced. In this paper, principal component analysis is used to calculate digital literacy . The priSecond, the dependent variable was replaced. The dummy variable for happiness was adjusted according to the mean, and values greater than the mean were set to 1 . RegressThird, the individual health measure variable is replaced. Happiness is an emotional experience of real life that is closely related to the psychological state of an individual . If an iOverall, digital literacy positively affects the subjective happiness of rural low-income groups. However, the results may differ for groups with different characteristics. To clarify the effect of digital literacy on the subjective happiness of rural low-income groups with different characteristics, heterogeneity analysis was conducted in terms of both education level and poverty level.First, rural low-income groups were classified into low education (less than six years) and high education (more than six years) according to their number of years of education . The colper capita income of households. As the basis for this classification, the poverty line  set by the Central Poverty Alleviation Work Conference at the end of 2011 was used  of This empirical result is consistent with the theoretical analysis and existing literature findings. Individuals are processors of information, and the improvement of digital literacy can better exploit the information and employment effects of digital technology, thus contributing to an increase in absolute income . The digThe authors argue that digital literacy may help rural low-income groups pursue social and economic rights. The relationship between digital literacy and consumption growth is further tested using the consumption structure to reflect the reality of the implementation of rights. In the consumption-happiness relationship, expenditures on food, housing, health services, and education contribute to subjective happiness. For low-income households, meeting the subsistence needs and alleviating the relative deprivation level in the right to development and enjoyment can greatly enhance their subjective happiness. Refer to the division of consumption structure by First, the relationship between digital literacy and survival-oriented consumption is analyzed. The results in the column (2) show that the model does not pass the DWH test, which is interpreted as resulting from the results of ols. As shown in the column (1), digital literacy statistically positively affects survival-oriented consumption at the 1% level, indicating that digital literacy promotes the growth of survival-oriented consumption among rural low-income groups. Second, the relationship between digital literacy and developmental consumption is observed. The results in the column (4) show that the model passes the DWH test and the original hypothesis that digital literacy is an exogenous variable is rejected. This is interpreted as resulting from the estimation results of the 2sls. The results in the column (4) show that digital literacy statistically positively affects developmental consumption at the 1% level, reflecting that digital literacy promotes the growth of developmental consumption among rural low-income groups. Finally, the relationship between digital literacy and enjoyment-based consumption is assessed. The results in the column (6) show that the model passes the DWH test, which is interpreted as being the result of the estimation results of the 2sls. The results show that digital literacy statistically positively affects enjoyment-based consumption at the 1% level, reflecting that digital literacy raises the enjoyment-based consumption of rural low-income groups.The findings that digital literacy has consumption effects are consistent with the existing literature. In China, the rise and development of ICT and the technologies, products, and services it has spawned have greatly enriched rural households’ production patterns and lifestyles, such as online shopping, digital education, and platform healthcare . DigitalAs an individual’s emotional response to real society, happiness reflects the individual’s overall experience of his or her life circumstances (including the work environment). Refer to First, regarding the relationship between digital literacy and job satisfaction, the results in the column (2) of This empirical result is supported by previous literature. Digital literacy helps low-income groups to search for and find jobs that match their abilities and promote their career mobility to non-agricultural industries , thus inTaking the low-income group in rural China as research object, this study explored the influence and mechanism of how individual digital literacy affects the subjective happiness of rural residents. The factors that would play a moderating role in this process of promoting or inhibiting the subjective happiness of this group were investigated. The empirical results show that first, digital literacy has a significant happiness effect on rural low-income groups. Digital literacy helps low-income groups reduce the cost of information seeking, processing and dissemination, thereby increasing subjective happiness. Second, in terms of the mechanism, digital literacy mainly affects subjective happiness low-income groups by increasing household income and promoting household consumption. Third, digital literacy significantly impacts the subjective happiness of rural low-income groups with low education level and who experience deep poverty. Fourth, the decomposition of happiness into life satisfaction and job satisfaction, shows that digital literacy has a significant positive impact on job satisfaction and life satisfaction of rural low-income groups.This study also has important practical implications. First, the government should focus on cultivating the digital literacy of low-income groups to effectively provide development and endogenous motivation for enhancing subjective happiness. The government should strengthen the digital education of rural residents and establish a digital literacy cultivation system that meets the needs of rural development. The government can organically play the role of different social organizations in improving the digital literacy of the rural population, for example through school education and social organization training.Second, the government must continue to promote the construction of the digital village, including digital infrastructure construction and rural industry digitization. The government’s improvement of digital infrastructure construction enables the popularization of the Internet and the digital transformation of transportation, energy, and logistics. For example, an intelligent distribution system is vital for circulating urban and rural commodities, and enables convenient circulation of urban and rural products and services.The present study has certain limitations. First, this study did not employ a cross-country sample to test the relationship between digital literacy and subjective happiness. Differences exist in the degree of information and communication facilities among different countries, and the digital environment in which rural low-income groups are located may also differ. The role of digital literacy is strongly related to the digital environment; therefore, whether the findings of this paper can also be applied to other countries remains unknown.Second, the Internet is a platform for information interaction, and the cultural values of individuals affect the process of information processing, which ultimately influences the role digital literacy plays for happiness. However, the data is limited, the cultural values variable cannot be controlled, and it is difficult to observe the heterogeneous influence induced by cultural values. Subject to traditional culture, Chinese villages have a unique cultural atmosphere that also affects the cultural values of villagers. Thus, village-level fixed effects are controlled for and the influence of cultural differences is partially absorbed.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.JW and CL designed and conducted the study and wrote the manuscript. JW analyzed the data. ZC reviewed and revised the manuscript. All authors contributed to the article and approved the submitted version.This study was supported by grants from the National Natural Science Foundation of China and the Ministry of Education of China (grant no. 72003091 and 17YJA790004).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


This study aims to select and summarize the best evidence of temperature management for comatose patients after cardiopulmonary resuscitation in intensive care units (ICUs) at home and abroad.  Some well-known databases at home and abroad have been searched to find the guidelines, expert consensus, original documents, evidence summaries, and systematic evaluation about temperature management for comatose patients after cardiopulmonary resuscitation in ICUs. The databases included PubMed, Up to Date, Cochrane Library, the website of Registered Nurses' Association of Ontario, the Guideline Library of National Institute for Health and Clinical Excellence of the UK, China National Knowledge Infrastructure (CNKI), Wanfang Database, and VIP. The period for search is from the establishment of each database to the present. Two researchers who have received evidence-based nursing training and passed the examination evaluated, extracted, and integrated the literature quality with a blind method to summarize the best evidence.  A total of 10 pieces of literature were included in this study, including 4 in Chinese and 6 in English. Specifically, there were 4 guidelines, 1 expert consensus, 2 evidence summaries, 1 systematic evaluation, 1 literature review, and 1 comparative experiment, accounting for 40.0%, 10.0%, 20.0%, 10.0%, 10.0%, and 10.0%, respectively. The literature and materials were all qualified, and there was no heterogeneity and no significant publication bias in the included literature. The best evidence involved mild hypothermia therapy, rewarming, prevention of mild hypothermia-related complications, and nutritional support, with a total of 21 pieces of evidence . In terms of the recommendation grade, 7 pieces of evidence were at Grade A and 14 at Grade B.  Health care providers should implement hypothermia management in comatose patients after cardiopulmonary resuscitation in ICUs, pay attention to the prevention of related complications, and provide enteral nutrition support. An intensive care unit (ICU) is a place for patients with severe illness or coma to receive diagnosis, treatment, and monitoring. It is also an important part of a medical organization. Cardiopulmonary resuscitation is a life-saving technique for patients with heart disease and respiratory arrest. It aims to restore patients' autonomous circulation and breathing and has been widely used in clinical practice . The nurSome well-known databases at home and abroad have been searched to find the guidelines, expert consensus, original documents, evidence summaries, and systematic evaluation about temperature management for comatose patients after cardiopulmonary resuscitation in ICUs. The search keywords included ICU, cardiopulmonary resuscitation, coma, and temperature management. Evidence-based theme: the effective temperature management for comatose patients after cardiopulmonary resuscitation in ICUs.The up-down search was done according to the 6S Pyramid method. The databases included PubMed, Up to Date, Cochrane Library, the website of Registered Nurses' Association of Ontario, the Guideline Library of National Institute for Health and Clinical Excellence of the UK, China National Knowledge Infrastructure (CNKI), Wanfang Database, and VIP. The period for search was from the establishment of each database to the present.Inclusion criteria: ①the subjects were comatose patients admitted to the ICU after cardiac arrest cardiopulmonary resuscitation; ②the subjects were all adult patients aged 18 to 60 years; ③ the literature involved temperature management; ④the types of literature included guidelines, expert consensus, original document, evidence summary, and systematic evaluation; ⑤ the literature is in Chinese or English.Exclusion criteria: ① the type of literature was draft or abstract only; ② the subjects had certain diseases such as thermoregulatory disorder; ③literature information was incomplete; ④literature failed to meet the evaluation criteria of Joanna Briggs Institute (JBI) in terms of quality.Two researchers who have received evidence-based nursing training and passed the examination evaluated, extracted, and integrated the literature quality with a blind method. If they had the same judgment, the decision would be final. If not, arbitration was made by the evidence-based care team in the hospital. The principle of literature quality evaluation was: preference was given to high-quality evidence, the latest evidence published in authoritative journals, and evidence-based evidence. AMSTAR 2.0 was used to evaluate the included literature on expert consensus, evidence summary, and systematic evaluation. The evaluation method includes 16 entries, of which 7 key entries (entries 2/4/7/9/11/13/15): literature with no or only 1 nonkey entry nonconformity is considered high quality; literature with more than 1 nonkey entry nonconformity is considered medium quality; literature with 1 or more key entries nonconformity with or without nonkey entry nonconformity is considered low quality. High-quality and moderate-quality documents are considered to be up to standard.The included guidelines were evaluated by AGREE II, and the included literature review, comparative experiment, and original literature were evaluated by RevMan 5.3.P > 0.1. The percentage of heterogeneity in the overall study was expressed as I2, and the effect size was expressed as 95% confidence interval (CI). P < 0.05 was considered a statistically significant difference.Heterogeneity tests and risk of bias analyses were performed using RevMan 5.3 software. The included literature was considered not significantly heterogeneous if the Q Statistic A total of 77 literatures were retrieved. Eighteen studies with cases and abstracts only were removed, four articles with subjects with thermoregulatory disorders were excluded, and 26 articles with incomplete information and 19 articles that did not meet the JBI evaluation criteria were removed. Finally, 10 studies were included . The floI2 = 0.24, P = 0.77) and no significant publication bias, as shown in In addition, after statistical analysis, there was no heterogeneity in the included literature . In terms of the recommendation grade, 7 pieces of evidence were at Grade A and 14 at Grade B. See As an important nursing operation for comatose patients after cardiopulmonary resuscitation in ICUs, temperature management is of positive significance in promoting the prognosis and improving the prognosis . HypotheA total of 10 pieces of evidence on temperature management of comatose patients after cardiopulmonary resuscitation in ICUs were included in this study. The literature was qualified, ensuring the preciseness and repeatability of the results of the study. Based on the evidence summary of the included literature, it was found that the temperature management of comatose patients after cardiopulmonary resuscitation in ICUs involved mild hypothermia therapy, rewarming, prevention of mild hypothermia-related complications, and nutritional support. Specifically, 11 pieces of evidence were related to mild hypothermia therapy (recommendation grade: 6 pieces at Grade A and 5 pieces at Grade B); 3 pieces of evidence were related to rewarming (recommendation grade: Grade B); 5 pieces of evidence were related to the prevention of mild hypothermia-related complications (recommendation grade: Grade B); and 2 pieces of evidence were related to nutritional support (recommendation grade: 1 piece at Grade A and 1 piece at Grade B). In addition, the results of the best evidence summary of this study included the indications, contraindications, place of implementation, implementation personnel, start time, target temperature, cooling measures, duration of induced hypothermia, body temperature monitoring methods, and interruption of mild hypothermia therapy, helping nursing personnel screen the target population requiring mild hypothermia therapy and defining the implementation standard of this therapy from all aspects as the core content to guide its popularization and application in clinical practice. In terms of rewarming, the requirements for rewarming speed, body temperature after rewarming, and duration of maintenance clarified the precautions for rewarming after mild hypothermia therapy, ensuring that the patients' body temperature returned to normal in a slow and stable manner and guaranteeing the recovery of physiological and metabolic state. The prevention of mild hypothermia-related complications included the evaluation and control of shivering, the monitoring and treatment of arrhythmia, the monitoring and control of infection, and the monitoring of serum potassium level and the prevention of other complications. It could provide guidance to the medical staff in monitoring the vital signs of patients, ensuring that the patients safely receive mild hypothermia therapy and avoiding any secondary injury caused by complications. Nutritional support included guidance on enteral nutrition and energy intake, ensuring the nutritional supply of patients and avoiding various problems caused by insufficient or excess nutrition. In consideration of previous studies and the author's working experience, it is recommended to strictly refer to the above items and evidence to support the implementation of temperature management for comatose patients after cardiopulmonary resuscitation in ICUs. A study  confirmeHowever, there are still some limitations in this study: (i) there is still room for optimization of the temperature management scheme for comatose patients after cardiopulmonary resuscitation in the ICU, and how to further optimize it to speed up recovery remains to be explored; (ii) patients of different age groups may have different needs for temperature management, and the follow-up study still needs to be refined.For comatose patients after cardiopulmonary resuscitation in ICUs, it is recommended that the indications, contraindications, place of implementation, implementation personnel, start time, target temperature, cooling measures, duration of induced hypothermia, body temperature monitoring methods, interruption of mild hypothermia therapy, rewarming speed, requirements for body temperature and duration of maintenance after rewarming, evaluation and control of shivering, monitoring and treatment of arrhythmia, monitoring and control of infection, monitoring of serum potassium level and prevention of other complications, nutritional support, and other relevant evidence should be referred to in order to support the implementation of body temperature management, so as to promote the prognosis of patients.


We aimed to investigate the anatomical relationship of the coronary sinus (CS) and the mitral valve annulus (MVA) in patients with or without functional mitral regurgitation (FMR) using a multislice CT (MSCT) software to determine (a) the distance and angle of both CS and MVA plane and (b) the mitral annulus geometry.A total of 215 patients with MSCT and CS to MVA topography evaluation were enrolled in this retrospective study.This patient cohort included 145 patients without FMR  and 70 patients (32.6%) with clinically relevant FMR (FMR ≥ 2+). Distance and angulation of CS to MVA planes were highly variable. In all groups, no significant correlation was documented between the distance or angle of CS to MVA planes and left ventricular ejection fraction, left ventricular end-diastolic diameter, or left atrial volume. A significant increase in total CS length could be found in patients with FMR ≥ 2+ compared to the FMR ≤ 1+ group. MVA diameter, area, and perimeter were significantly increased in FMR ≥ 2+ compared to FMR ≤ 1+. In the FMR ≥ 2+ cohort 61% showed a distance of CS to MVA plane <7.8 mm and 58% revealed an angle of CS to MVA plane <14.2°.Distance and angulation of CS to MVA topography using an MSCT approach are similar between patients with or without FMR, while CS length, MVA area, MVA perimeter, anterior-posterior diameter, and intercommissural diameter are significantly increased in all FMR subgroups. However, ~60% of FMR ≥ 2+ patients showed favorable CS to MVA topography for indirect mitral annuloplasty. The Carillon Mitral Contour System  showed a reduction of echocardiographic FMR parameters and improved heart failure symptoms in multicenter trials  and 70 patients with clinically relevant FMR ≥ 2+ [VC > 3 mm, regurgitant volume > 30 ml, effective regurgitant orifice area (EROA) > 0.2 cm* 0.6 mm and rotation time 0.27 s. Prior to the scanning protocol, sublingual nitroglycerine spray (800 mcg) was administered to all patients and metoprolol only if necessary , aiming for a heart rate <65 beats/min. The scan was triggered using an automatic bolus tracking technique, with a region of interest placed in the descending thoracic aorta and a threshold of 150 Hounsfield units (HU). Prospective ECG-gating was used at 75% of the R-R interval. Nevertheless, persistently elevated heart rates required a retrospective helical protocol in some patients. Contrast agent  was administered with a volume of 100 ml (5.7 ml·s-1), followed immediately by a 50 ml saline chaser. Data were reconstructed at 75% of the R-R interval, with a slice thickness of 0.5 mm and a reconstruction interval of 0.3 mm.All patients underwent MSCT for evaluation of coronary artery disease. For MSCT, a 256-slice Brilliance iCT scanner  was used in accordance with the Society of Cardiovascular CT (SCCT) guidelines . A tube The 3mensio Structural Heart (prototype version 10.1) software  was used to analyze the MVA using multiplanar reconstructions and volume rendering techniques, as previously described , 6. OmisMitral valve anatomy was assessed by cubic-spline-interpolation of 16 seeding points, which were manually set along with the insertion of the posterior mitral valve leaflet and along the anterior peak, as previously described . The latTransthoracic echocardiography studies were obtained using a Philips iE 33 echocardiography system . Vena contracta, proximal isovelocity surface area (PISA), EROA, and regurgitant volume for quantitative mitral valve assessment were recorded according to current recommendations . The sevPatients in the FMR ≤ 1+ group showed normal LVEF and systolic pulmonary artery pressure (sPAP) compared to the FMR ≥ 2+ group . The FMRpost-hoc testing for continuous variables. Pearson correlation coefficient was used for correlations between two variables. For ordinal data, Kruskal-Wallis-Test was used. A p-value < 0.05 was considered statistically significant.Statistical analysis was performed using PASW statistics 18 software . All variables were tested for normal distribution with the Kolmogorov-Smirnov test. In the case of normal distribution, the results are given as SEM if not otherwise indicated, or as median and 95% CI. Differences between groups and subgroups were evaluated by chi-square-test for discrete variables and one-way ANOVA with Scheffe All demographic variables are shown in We used a prototype software for CS reconstruction in MSCT to determine the distance and angle of the MVA and the CS planes in FMR ≤ 1+ and FMR ≥ 2+. To investigate the effect of reduced LV-function with dilation of the left ventricle (LV) and atrium (LA) on these parameters, a correlation of LVEF, left ventricular end-diastolic diameter (LVEDD), and LA-volume with either distance or angle of CS to MVA planes was performed in FMR ≤ 1+ and FMR ≥ 2+. No significant difference could be obtained in any of these groups indicating no relationship between these parameters and the distance or angle of CS to MVA planes . HoweverAll parameters of MVA geometry were markedly increased in patients with FMR ≥ 2+ compared to the FMR ≤ 1+ group . MVA dimA CS to MVA topography with a distance of <7.8 mm and an angulation of <14.2° predicts a reduction of FMR after indirect mitral annuloplasty with the Carillon device , 6. In tn = 15 vs. 4.8 ± 2.5 mm, n = 90). Also, total CS length was significantly larger in patients with relevant MR  , which allows us to analyze the different FMR classes separately. All FMR subgroups  showed significantly increased MVA dimension parameters compared to FMR ≤ 1+. Notably, for MVA area/BSA and perimeter/BSA an increase in these parameters over the subgroups could be obtained, indicating the marked dilated MVA in higher FMR classes.Besides the CS to MVA topography, we reported D-shaped mitral annulus dimensions for patients with FMR ≤ 1+ or FMR ≥ 2+. As previously reported, we found enlarged MVA dimensions in patients with FMR ≥ 2+. A study on 27 patients with moderate or severe FMR showed MVA area/BSA (FMR ≥ 2+: 6 ± 1.3 vs. FMR ≤ 1+: 4.7 ± 0.6), perimeter / BSA (FMR ≥ 2+: 67 ± 9 vs. FMR ≤ 1+: 59 ± 5), anterior-posterior distance (FMR ≥ 2+: 18.1 ± 3.3 vs. FMR ≤ 1+: 14.8 ± 1.6) and intercommunal distance (FMR ≥ 2+: 21.2 ± 3.1 vs. FMR ≤ 1+: 20.2 ± 1.9) to be markedly increased . We confvia the CS. Our results show the feasibility of a new non-invasive evaluation of CS to MVA topography and confirmed reference values for D-shaped MVA dimensions in FMR subgroups, which coincide with former studies  in patients with or without FMR. We provided reference values for CS to MVA distance and CS to MVA angulation. Furthermore, we investigated D-shaped MVA dimensions in subgroups of FMR  and compared them to controls with FMR ≤ 1+. It is worth noting that we found about 60% of patients with FMR to have favorable CS to MVA topography for mitral valve repair using annuloplasty  studies , 12, 16.via the CS. Using the 3D-MSCT derived distance and angle of CS to MVA planes in FMR ≥ 2+ patients can be helpful for device selection prior to mitral valve interventions. This might improve the results of percutaneous mitral valve repair using the Carillon Mitral Contour System.Distance and angulation of CS to MVA topography can be derived from MSCT using a novel approach. This might be helpful for patient selection prior to mitral valve interventions for FMR treatment. We reported 60% of FMR ≥ 2+ patients to have favorable CS to MVA topography for mitral valve repair using indirect annuloplasty This is a retrospective, single-center study with consequent statistical limitations. Therefore, the results should be regarded as hypothesis-generating.The datasets used and/or analyzed during this study are available from the corresponding author on reasonable request.Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. The patients/participants provided their written informed consent to participate in this study.DR: conceptualization, data collection, analysis and interpretation, drafting, and final approval. MS: data collection, analysis and interpretation, drafting, and final approval. AÖ: data collection and drafting. HD: conceptualization and critical revision. MH: conceptualization, critical revision, and final approval. All authors contributed to the article and approved the submitted version.HD is a consultant for Biotronik and Cardiac Dimensions. MH is a consultant for Biotronik, Orbus Neich, Robocath and Cardiac Dimensions. He received institutional grants and lecture fees from Biotronik, Cardiac Dimensions, Orbus Neich, SMT and Philips. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Patients affected from hearing loss face many problems when visiting oncologists. We conducted a systematic review to survey if cancer education programs can promote health literacy among deaf and hard of hearing (DHH) patients. The authors searched two databases for RCTs, and cohort studies with interventions promoting cancer health literacy for adult DHH patients. Risk of bias was assessed with SIGN Methodology Checklist for RCTs, and cohort studies. Significance of mean changes over time, and mean differences between comparison groups were used to present outcomes of each study. Surveyed interventions addressed three domains: cancer knowledge, coping skills, and cancer screening. Key information was gathered and synthesized providing a juxtaposition of the content and presenting important effects in detail. Nine RCTs and seven cohorts with 1865 participants were included. In total, 13 studies showed that cancer health literacy interventions improved mean scores significantly from pre- to post-test measures. There are hints that captioning and written texts may be sufficient for milder forms of hearing loss. Three studies showed that resiliency skill training promotes various domains of well-being. Three studies indicated that educational interventions encourage cancer screening practices. Educational programs are an effective way to promote cancer health literacy among DHH patients to facilitate communication with oncologists. As extent of hearing loss was not assessed, the authors cannot say the degree to which results are applicable to all degrees of hearing loss. To obtain hard data, further studies with more diverse populations, various cancer entities, different methods, and exact hearing loss assessments are required. While congenital hearing loss has mostly genetic reasons, various factors cause acquired hearing loss. The WHO refers to hearing loss as hearing threshold of less than 25 dB. It is categorized into four grades: slight 26–40 dB, moderate 41–60 dB, severe 61–80 dB, and profound > 81 dB hearing loss [From a functional point of view, the DHH (deaf and hard of hearing) population is heterogeneous with unique communication needs. Deaf individuals are primarily visual processors of information, preferring visual languages and sign language interpreters. Despite their reduced auditory input, hard of hearing individuals are primarily visual-auditory processors and rely on audition and speech. It is expectable that the first group could benefit from a sign language interpreter, while the second could benefit from captions integrated into videos.DHH patients face many problems when interacting with doctors –7. TheseDHH patients struggle for health information access  to make Can cancer education programs promote health literacy among DHH patients?All decisions were unanimously made by the three authors. In case of disagreement, consensus was found by discussion.Supplementary Material 1). We included German and English RCTs and cohort studies with interventions improving cancer health literacy among DHH patients, assessed by audiometry or self-report, age ≥ 18 years. Other DHH or hearing patients were accepted as comparisons. We surveyed effects on cancer health literacy, satisfaction with healthcare, and satisfaction with QoL .We used a PICO framework to define eligibility criteria . The Oxford Centre for Evidence-Based Medicine: Catalogue of Bias  was emplp-value of ≤ 0.05 was declared the threshold for statistical significance.We used mean changes in assessment methods to present outcomes. In case of missing data, we summarized tendencies. A Surveyed interventions address a variety of health literacy programs. The concept of health literacy comprises understanding and using healthcare information . Our strWe assessed certainty of evidence using Oxford Centre for Evidence-Based Medicine: Levels of Evidence and rated studies from levels 1 to 5 .Supplementary Material 3.Sixteen studies were included in the present review. Our search strategy revealed 961 records in both databases. Checking for duplicates removed 6 hits. After scanning the titles and abstracts for relevance to this research, further 931 publications were excluded. The remaining 24 publications were checked for the prior defined PICO criteria, which lead to the rejection of eight further studies. Reasons for exclusion are shown in Table Individual study characteristics are listed in Table Five RCTs had a high quality and four an acceptable quality in general minimization of bias. All studies had randomized assignments, adequate concealment methods, comparable treatments, and control groups at the beginning. The only group difference was treatment under investigation. Every study used standard, valid, and reliable outcome measurements. Cumberland et al.  did not All included cohorts had a high quality in general minimization of bias. All included studies had clearly focused questions, defined outcomes, comparable study groups, and reliable methods of assessment. All studies have low risk of attrition bias with a drop-out of less than 20%. Included cohorts are affected by a volunteer bias as patients were chosen through flyers in deaf clubs and snowballing techniques. Hearing loss was assessed via self-report. Three studies , 34, 36 Supplementary Material 4 provides a table with an Oxford Centre for Evidence-Based Medicine: Levels of Evidence [Evidence  rating aThe most common endpoint was the gain of cancer knowledge after being exposed to a cancer health literacy intervention. Other outcomes were change in cancer screening behavior and benefits of coping skills. Some adverse events could also be observed. Acquired data are given in Table Six RCTs, and seven cohort studies surveyed the efficacy of cancer health literacy interventions adapted to the needs of DHH patients. Included interventions were adapted through an ASL interpreter and captions. Kaskowitz et al.  did not p ≤ 0.05) from pre- to post-test and to later follow-ups. Cumberland et al. [In case of 12 interventions, the participant’s mean scores improved significantly  as well as perceived stress (p ≤ 0.001) and improves quality of life (p ≤ 0.001) as well as some aspects of resiliency (p ≤ 0.01) significantly after intervention. The improvements maintain significant after 6 months. The results are affected by a small sample bias, and a high drop-out, and therefore have an acceptable quality.Three studies , 31, 32 According to its research designs, nine included RCTs were rated level 2 and seven cohort studies level 3 on the Oxford Centre for Evidence-Based Medicine: Levels of Evidence scale. Cumberland et al.  was downInadequate health literacy is one common characteristic of DHH patients. Tailored health literacy programs are one way to meet their individual health needs , 16. ExiOur results match closely with previous studies . EducatiAlthough most interventions used ASL interpreters to convey information, appropriate English captioning could be sufficient . One stuHowever, hearing individuals had higher increases in cancer knowledge in deaf-tailored programs , 38, 41.We also identified publications with a new approach. Interventions addressing coping mechanisms for neurofibromatosis type II associated hearing loss provide hints for their efficacy. They are affected by attrition bias as well as very small sample sizes and target at a specific population , 31, 32.Aside from health literacy, we also paid attention to cancer screening rates, a meaningful parameter for the effectiveness of educational interventions. They depict persistence, actual use, and benefit of cancer health education. Three studies could show an increase in screening rates , 36, 37.All interventions were carried out in the USA and comprise only seven cancer-related topics. Although not all findings obtained in this context might be applicable to different countries, general principles of health education remain the same and can be adapted in other countries and on different topics. Nevertheless, studies including more participants and addressing further topics are desirable. Included interventions concentrated primary on deaf patients. No data were given on the reason and extent of hearing loss as it was measured through self-report. We do not either know, if participants were allowed to use hearing-aids. We cannot say the degree to which results are applicable to milder forms of hearing loss. All included studies are affected by a selection bias due to their sampling techniques and a volunteer bias. They lead to high baseline scores as participants originate from a medically interested population. Apart from Cumberland et al. , includeWe could not find any data on direct communication strategies for oncologists. A reason for this may be that measures of physician–patient communication reveal mainly poor internal consistency and content validity . A relatWe excluded all studies with Levels of Evidence  below leWe can state that accessible education programs are an effective way to promote cancer health literacy among deaf patients and can therefore have a beneficial influence on oncologist-patient communication. Still, we cannot say the degree to which the effect is dependent on communication preferences and grade of hearing loss. Present data do not include audiometric assessments. Surveyed interventions mostly used ASL interpreters to convey information. It is conceivable that especially milder forms of hearing loss would profit from texts or adequate captioning as it meets their preferred communication mode. Hence, it must be surveyed if given approaches are equally effective for all kinds of hearing loss, and if existing methods could be modified. Further studies with more diverse populations, various cancer entities, different methods, and exact hearing loss assessments are required.Plenty of advice for physicians on how to interact with DHH patients contrasts with only rudimentary evaluated measures of physician–patient communication. To verify these recommendations and to explore most beneficial communication strategies for DHH patients, further research is strongly recommended.


A Health Information System (HIS) assessment is an evaluation of the functioning of the main elements that compose a national HIS. Assessors from nine countries performed peer assessments of each other’s national HIS in the Joint Action on Health Information (InfAct). The aim of this study is to evaluate the advantages and disadvantages of the InfAct peer assessment methodology as well as the different steps involved in this assessment process.Each peer assessment included a preparatory desk report, a country visit with semi-structured interviews with local stakeholders, a final report and a follow-up stakeholder meeting. A qualitative content analysis of the peer HIS assessment was performed based on 12 semi-structured interviews.The main advantage of the assessments is its informal atmosphere, high degree of objectiveness and its networking opportunities. Disadvantages are its informal request format and setting for recommendation uptake. The peer assessment helped the assessors to broaden their understanding of the assessed and their own HISs, to gain knowledge on how to carry out an HIS assessment and to practice their organization, communication, reporting and negotiation skills. All steps of the HIS assessment are essential and each contributes to the enriching experience of the participants.The InfAct peer HIS assessment methodology strengthened capacity in national HISs by building up the knowledge and expertise in participating countries and as such addressed health information inequalities. This study confirms the value and relatively easy to implement methodology, and therefore recommends its wide and more systematic application across Europe. A Health Information System (HIS) assessment is an evaluation of the functioning of the main elements that compose a national HIS. HIS elements include data collection, analysis and synthesis, reporting, and knowledge translation, and the total of resources, stakeholders, activities and outputs to do so.Support tool to assess HISs and develop and strengthen health information strategies is one of these.HIS Stages of Continuous Improvement Toolkit developed by MEASURE.Information Systems for Health Standard Assessment Method of Pan-American Health Organization and the WHO SCORE for Health Data Technical Package.,Several international organizations have developed well-established tools for HIS assessments. The World Health Organization (WHO) Regional Office for Europe One of the goals of the EU Joint Action (JA) on Health Information (InfAct) was to reduce health information inequalities between countries.Therefore, the aim of this study is to evaluate the advantages and disadvantages of the InfAct peer assessment methodology as well as the different steps involved in this assessment process.Assessments were held in Austria, Belgium, Estonia, Latvia, Lithuania, Moldova, Norway, Romania and Serbia. The countries were split into three groups of three countries as shown in The assessments were carried out by one or two peer assessors from each assessing country, meaning a maximum of four assessors in total. All assessors were trained in a 2-day course on how to perform the assessment. A contact person in the assessed country acted as the national liaison during the assessment and organized the peer assessment. The contact person is called the host assessor. A single observer provided support during the assessment based on previous experience with the assessment methodology, to ensure that the assessments were performed according to professional standards and procedures.Each assessment included a preparatory desk report, a country visit with semi-structured face-to-face interviews with local stakeholders, a final report and a follow-up stakeholder meeting. An HIS Assessment Manual was developed providing the objectives, process and guidelines, and roles and tasks related to the InfAct peer review assessment approach.The host assessor developed a 2-day programme for the country visits. Typical stakeholders included Ministries of Health, National Public Health Institutes, Statistical Offices, and Health Insurance Funds. The assessors carried out the interviews using an HIS items list, covering the following domains: resources, indicators, data sources, data management , national HISs data quality/information products and dissemination and use. Based on the outcomes of the interviews, the assessors wrote a final report, which was presented to the local stakeholders, including those in leadership positions, through a virtual multi-stakeholder follow-up meeting in the assessed country. The participants jointly validated the final reports. The final reports included a SWOT  analysis, as well as SMART  recommendations for improvement.N = 9). Additionally, three interviews were carried out with the observer after each cycle. The interviews were carried out between May 2019 and January 2020. The semi-structured interviews were based on two questionnaires: one for the assessors and one for the observer  according to the assessors. However, overall, ‘Those who were well placed in the HIS did not experience difficulties to engage the local stakeholders.’ an interviewer explained. Depending on how familiar the assessors were with the activities of the stakeholder, they experienced difficulties during the actual interviews, according to an interviewee. The following was explained: ‘Those with a wider experience could better exchange with a wider range of stakeholders very actively. Based on their background they may feel more or less comfortable asking certain questions. The wider the background the more capable in carrying out the assessment’.Additional challenges according to the interviews were the organization of the country visits in 2 days and the identification of the right local stakeholders. Stakeholders had varying levels of knowledge and communication skills. As one assessor put it: ‘Some stakeholders like to talk and talk. Others that were expected to talk did not talk that much. They were asked a question and just said yes or no’. A balance had to be found between responsiveness, interest and competency according to the assessors.The assessors experienced the final reports to be useful and they appreciated the format of the report as predefined in the HIS Assessment Manual. ‘The structure is excellent. It is very readable. It really responds to what policy makers are willing to read. It is really what they want to know.’ stated an assessor. The assessors said it was not easy to do the SWOT analysis and to prepare the SMART recommendations because you had to be very short and to the point. An assessor witnessed: ‘Every word is weighed against the interest of the different stakeholders. I liked writing the report, it was a very good exercise. I also liked receiving it’. Over time, the assessors explained that they became more practiced at it and recognized it was best to draft the SWOT and recommendation right after the country visit.The stakeholder follow-up meeting was the most difficult aspect to organize according to the evaluation interviews. The assessors stated that they struggled to get all stakeholders to participate and engage. The purpose of the meeting was to discuss the final report with the stakeholders and support the uptake of the recommendations; therefore, it was essential for the stakeholders to be present.The assessors appreciated the fact that they were involved in three assessments. For most of them, three assessments were the right number because it was easier to work in smaller groups. Bigger groups would have increased the workload and made communication more complex. An assessor explains why carrying out three assessments was ideal for her: ‘My fear was that two times was enough, because after the second time we understood everything, the whole process. But at the end, after the third cycle, we were completely clear about the steps and the procedures’. The ability to perfect the use of the assessment methodology increased in the last assessment according to the assessors.Some assessors indicated that the assessments took more time than expected. Most of the assessors had busy schedules and had difficulties postponing daily activities. ‘Also the two-day country visit was very intense, which allowed us to go in depth in one system and really work on it hard’, as an assessor explains.The assessors appreciated the presence of the observer providing a positive impact. The observer gave the assessment an official role by starting the meeting and moderating the discussion according to the assessors. ‘He was asking very relevant questions at the right time’ explained an assessor. ‘The observer allowed to share experience and facilitate the discussion’.The assessors enjoyed the group composition according to the interviews. Some countries in the same group had similar HISs, others had more diverse HISs. Both were perceived as enriching by the assessors. Having similar HIS helped to see how similar issues can be addressed differently and boosted comprehension. An assessor witnessed: ‘The group was well selected because we have the same starting point 20 years ago. It is interesting to see how each country found its own way of development. After that it is very easy and useful to make a comparison’. The disadvantage of having similar HIS was the difficulty to remain objective. As stated during an interview: ‘The secret in choosing the peers, is striking a balance between how close and how far their HIS is from each other’.The main value of peer HIS assessment approach as carried out in InfAct is its contribution to capacity building in participating countries and its likely reduction of health information inequalities between countries. Initially, it was expected that capacity building would take place by the exchange of best practices. The evaluation suggests that the reduction of health information inequalities may rather have been addressed through the experience and knowledge that was built in the countries during the assessment process. Each step in the assessment process is experienced as essential and brought a different learning experience to the assessors. Each step adds to the capacity building of the assessor. Firstly, the training was important to familiarize the assessors with the HIS assessment tool. Secondly, the preparatory desk report pushed the assessors to synthesize the available information, boosting their reporting skills. Thirdly, the country visits with face-to-face interviews developed their organization and communication skills. The assessors had to organize the country visits in their own country lobbying for participation and engagement of local stakeholders. During the country visits, they had to adapt their way of questioning between the interview which developed their confidence, cultural sensitivity and interview versatility. Fourthly, the final reports developed the assessors’ reporting skills. Fifthly, the stakeholder follow-up meeting developed the assessors’ negotiation skills. They had to incorporate comments of the stakeholders in the final reports, whilst staying true to the information provided in the interviews. Overall, having the peer assessment process in cycles helped the assessors to broaden their understanding of the assessed HISs and their own country HIS, to gain in-depth knowledge on how to carry out an HIS assessment and to repeatedly practice their organization, communication, reporting and negotiation skills. The assessments also created a health information community within and across European countries.A possible limitation may be that the timing of the interview of the assessors was different, i.e. after each of the three rounds, three assessors were interviewed. Their experience changed along the process. On the other hand, covering the whole period, although with different subjects, provided a more comprehensive overview of the different experiences throughout time.The advantage regarding the setting, an EU financed project, is that there is an organization coordinating the activity and taking the lead in organizing such an exercise and that these assessments are done among peers from different countries. Moreover, in such a setting the exercise has a bottom-up approach leading to a collaborative effort. On the downside, the exercise is not part of a more permanent strategy, having an impact on sustainability and potentially the uptake of recommendations.This study has shown that the InfAct peer assessment methodology is a low-threshold, relatively easy to implement method that thoroughly contributes to capacity building and therefore is likely to address health information inequalities. It allows for structured build-up of knowledge and strengthening of expertise. It has proven to function in diverse European regions and systems. This evaluation confirms its utility and value. Therefore, this study strongly recommends the wide deployment of this methodology and its anchorage in systematic HIS capacity building across European countries. Moreover, the assessments ideally should be integrated in HIS governance strategies both at national and international level for the improvement of the European HIS. Two European projects are already intending to apply the methodology based on the positive experience of InfAct. They will further investigate its use in different settings. The Population Health Information Research Infrastructure will use the peer methodology to assess COVID-19 HISs.To strengthen the experience of the assessments and the HIS assessment approach in itself, three additional recommendations emerge from the evaluation. Firstly, the length of the country visits should be extended from 2 to 3 days. This would allow to reduce the intensity of interviews and to organize the final stakeholders meeting directly on the third day. Having this meeting face-to-face on the third day would keep the momentum of interest from the stakeholders and probe the potential uptake of recommendations. Involving the Ministry of Health early on in the process and having the Ministry take ownership of the formulated SMART recommendations may also improve the uptake. Finally, the preparatory report should be prepared in closer collaboration with the host assessor to be a more practical instrument.In conclusion, the InfAct peer HIS assessment methodology strengthens capacity in national HISs by building up the knowledge and expertise in participating countries and as such addresses health information inequalities. Its main advantages are its informal atmosphere, high level of engagement, high degree of objectiveness and networking opportunities. All five steps of the HIS assessment are essential and each contributes to the learning experience of the participants. This study confirms the value and relatively easy to implement the methodology and therefore recommends its wide and systematic application across Europe.EURPUB online.ckac014_Supplementary_DataClick here for additional data file.