Tibiotalocalcaneal arthrodesis (TTCA) using the intramedullary nail has been conducted for severe deformity of both ankle and subtalar joints. While good clinical outcomes have been reported for TTCA, its nonunion rate is relatively high. We report a case of a 65-year-old male with nonunion of the tibiotalar joint and destruction of the subtalar joint after TTCA using a retrograde intramedullary nail. For this patient, we conducted a salvage procedure for the subtalar joint along with revision surgery for the tibiotalar joint to achieve bone union. The intramedullary nail was removed and the tibiotalar joint was debrided. Two osteochondral plugs were harvested from the lateral aspect of the talus and transplanted to the subtalar joint. The tibiotalar joint was fixed using screws and staples, with bone grafting. Magnetic resonance imaging (MRI) at six months after surgery showed that the articular surface of the subtalar joint was flushed and the osteochondral plugs were united with the surrounding bone. At one year and three months after surgery, the pain in the tibiotalar and subtalar joints had completely disappeared. Plain radiographs revealed that bone union of the tibiotalar joint and joint space of the subtalar joint was maintained. Japanese Society for Surgery of the Foot (JSSF) hindfoot scale improved from 53 points to 84 points at the final follow-up. Reconstruction of the subtalar joint using osteochondral autologous transplantation is a useful technique for failure cases with nonunion of the tibiotalar and subtalar joints after TTCA.  For severe osteoarthritis (OA) of the ankle, arthrodesis for the ankle joint is frequently performed to relieve pain and obtain stability . DespiteTibiotalocalcaneal arthrodesis (TTCA) with a retrograde intramedullary nail has been used to treat severe deformities in both the ankle and subtalar joint due to OA or rheumatoid arthritis . While gA 65-year-old man had undergone ankle arthrodesis for OA of the ankle using the retrograde intramedullary nail eight months ago. However, he complained of severe pain at the tibiotalar and subtalar joints and plantar sensory disturbance. Therefore, he was referred to our hospital for further treatment. His left ankle exhibited swelling and tenderness in the tibiotalar and subtalar joints. The range of motion of the Chopart joint was 0° in dorsiflexion and 5° in plantar flexion, accompanied by pain. The range of motion in supination and pronation of the hindfoot was 5°, accompanied by pain. On plain radiographs, bone union was not achieved in the ankle joint, with an enlargement of the intramedullary nail canal in the talus and calcaneus, which was more pronounced distally Figure .The lateral malleolus was removed 10 cm from the medial malleolus tip. The intramedullary nail was transfixed with three screws at the tibia. The distal part of the intramedullary nail was not fixed to the calcaneus, because an intramedullary nail with fin-like longitudinal ridges was used. On computed tomography (CT), nonunion was observed in the ankle joint and the intramedullary nail canal was enlarged, particularly in the calcaneus Figure .The joint contour in the subtalar joint was intact, except for the intramedullary nail canal. which led to the idea that preservation of the subtalar joint by the reconstruction of the cartilage surface would provide a better clinical outcome than TTCA because of the mobility of the subtalar joint. For ankle arthrodesis, a combination of screws and compression staples would be planned to use because this combination can provide firm fixation . Because The intramedullary canal of the calcaneus was filled with the β-TCP through a plantar incision Figure , 5. Postoperatively, a short leg cast was applied for six weeks. Full weight bearing was permitted from four weeks using a short leg cast with a rubber walking heel. On radiographs taken two months after surgery, the bone union of the ankle joint was observed. Magnetic resonance imaging (MRI) six months after surgery revealed that the articular surface of the subtalar joint was flushed and osteochondral plugs were united with the surrounding bone Figure .As his plantar sensory disturbance was not alleviated, surgery was performed in an attempt to resolve this issue. The tibial nerve ruptured at the level of the medial malleolus, and a 5 cm gap was observed. Therefore, the deep peroneal nerve was transferred to the medial plantar nerve and the saphenous nerve to the lateral plantar nerve was performed. One year and three months postoperatively, there was no residual complaint of pain. The range of motion of midfoot was 5° in dorsiflexion and 10° in plantar flexion and 10° in supination and pronation of the calcaneus. The plain radiographs showed the bone union of the tibiotalar joint, and joint space of the subtalar joint was maintained Figure .The Japanese Society for Surgery of the Foot (JSSF) hindfoot scale improved from 53 to 84 points ,11. On tOur case showed that salvage surgical reconstruction of the articular surface of the subtalar joint after the failure of tibiotalocalcaneal fusion with a retrograde intramedullary nail yielded good clinical outcomes. This technique is useful for revision cases of TTCA without subtalar joint preparation. A systematic review of the TTCA using a retrograde intramedullary nail revealed a 56% complication rate . Among tA previous report showed good clinical outcomes for osteochondral lesions of the talus by autologous osteochondral transplantation from the talar articular facet . Good clWe described a salvage surgery for nonunion of the tibiotalar and subtalar joints after the failure of tibiotalocalcaneal fusion using intramedullary nail fixation. Good clinical results were obtained by tibiotalar arthrodesis and reconstruction of the subtalar joint using OAT. OAT for the subtalar joint in combination with the tibiotalar arthrodesis could improve the symptoms, particularly pain, in the case of intramedullary nail failure without subtalar joint debridement.


Vaccinium oxycoccos L. are an important source of bioactive compounds with antibacterial, antifungal, and anti-inflammatory effects. Studies on the phytochemical analysis of cranberry fruit samples showed that the qualitative and quantitative composition of biologically active compounds varied in cranberry fruit samples collected from different types of wetland sites: the total anthocyanin content was 698 ± 24–8352 ± 200 µg/g, the total flavonol content—518 ± 16–2811 ± 31 µg/g, the total content of triterpene compounds—4060 ± 122–6542 ± 157 µg/g, the content of chlorogenic acid—17 ± 0.4 µg/g to 1224 ± 41 µg/g, and the total content of proanthocyanidins—919 ± 19 µg EE/g to 3038 ± 137 µg EE/g. The percentage composition of anthocyanins in cranberry fruit varied between the different wetland sites: in some cranberry fruit samples, four anthocyanins  were predominant, while in other samples, six anthocyanins  predominated. The results of these studies showed the differences in the composition of secondary metabolites in the studied cranberry samples and prove that the standardization of the qualitative and quantitative composition of cranberry fruit raw materials and the application of routine tests are necessary for the expansion of the use of botanical raw materials in the production of functional foods and phytopreparations.The fruits of  Vaccinium oxycoccos L. , called small cranberry, bog cranberry, or European cranberry, is a perennial evergreen plant that is widespread in the natural coenopopulations of raised and intermediate wetlands in Europe, North America, and Asia [Vaccinium oxycoccos L. are harvested in European countries from their natural habitats and are used for food  and folk medicine to prevent urinary tract infections [and Asia ,2,3. Thefections ,5.In the second half of the 20th century, land reclamation in Lithuania drained a large number of raised and intermediate wetlands, which reduced the natural habitat of cranberries . The curCranberry fruit samples were found to contain proanthocyanidins , phenoliVaccinium oxycoccos) as an alternative to the increasingly cultivated large cranberries (Vaccinium macrocarpon) due to their similar sensory properties and chemical composition [Since ancient times, people in Lithuania have followed the tradition of picking small cranberries in the high and intermediate wetland areas, using the berries in traditional dishes, drinks, and folk medicine. In order to substantiate the use of cranberries in scientific medicine and the development of pharmaceutical preparations, it is important to carry out detailed qualitative and quantitative studies on the composition of the biologically active compounds in cranberry fruit. The results obtained would enable the use of small cranberries  on the quantitative composition of biologically active compounds in cranberry fruits.The aim of the study was to carry out a phytochemical analysis of cranberry fruits growing in the territories of the Lithuanian state-owned reserves Žuvintas and Kamanai, to determine the variation in the qualitative and quantitative composition of anthocyanins, flavonols, chlorogenic acid, proanthocyanidins, and triterpene compounds, and to evaluate the chemotypes of Cranberry fruit samples were collected at different sites in the wetlands of Žuvintas and Kamanai reserves . Cranberry fruit samples were collected at the beginning of berry ripening (at the end of August 2021) and after the berries had reached ripeness (in October 2021). During the study, we carried out the qualitative and quantitative analysis of proanthocyanidins, anthocyanins, chlorogenic acid, flavonols, and triterpene compounds as well as the analysis of the phytochemical profile of the cranberry fruit samples collected from different sites.p < 0.05). The lowest total anthocyanin content (698 ± 24 µg/g) was found in cranberry fruit samples collected in oligotrophic-type wetland (site L) in Žuvintas reserve at the end of August (p < 0.05). Cranberry fruit samples collected in October showed up to four times higher total anthocyanin content (1649 ± 35–8352 ± 200 µg/g) than cranberry fruit samples collected at the end of August did (698 ± 24–3403 ± 51 µg/g). The increase in anthocyanin content in the cranberry fruit samples collected from the mesotrophic-type wetland in Kamanai reserve (site D) was not statistically significant (p > 0.05).The qualitative and quantitative analysis of anthocyanins and anthocyanidins is presented in After analyzing cranberry fruit samples collected from different types of wetlands, they were divided into two groups according to the phytochemical profile of the predominant anthocyanins. The first group consisted of fruit samples collected in the mesotrophic (sites A and D) and oligotrophic (site E) wetlands of Kamanai reserve and in oligotrophic (sites L) and mesotrophic (site M) wetlands of Žuvintas reserve. Four anthocyanins, cyanidin-3galactoside, cyanidin-3-arabinoside, peonidin-3-galactoside, and peonidin-3-arabinoside, predominated in the fruit samples collected from these wetlands, accounting for 88.84% ± 4.2% of the total anthocyanin content . The secp < 0.05). The lowest total flavonol content (518 ± 16 µg/g) was detected in cranberry fruit samples collected in the mesotrophic-type wetland of Žuvintas reserve (site K) at the end of August. The quantitative composition of flavonols in fruit samples collected from this site was not statistically significantly different from the flavonol content in cranberry fruit samples collected from the eutrophic-type wetland site (site C) at the end of August or in cranberry fruit samples collected from the oligotrophic-type wetland site (site G) in October (p > 0.05).The results of the qualitative and quantitative analysis of flavonol composition are presented in Qualitative and quantitative analyses of cranberry fruit samples collected from the Kamanai and Žuvintas reserves confirmed that the phytochemical profile of flavonols was characteristic of cranberry fruit. The flavonol group compounds myricetin-3-galactoside (31.38% ± 7.68%) and quercetin-3-galactoside (38.33% ± 5.10%) dominated in the investigated cranberry fruit samples. Other compounds in the flavanol group were found in lower amounts. These were quercetin-3-arabinofuranoside (12.37% ± 2.41%), quercetin-3-rhamnoside (4.87% ± 2.03%), quercetin-3-glucoside (4.63% ± 2.84%), quercetin-3-arabinopyranoside (4.57% ± 1.60%), myricetin (1.82% ± 0.71%), and quercetin (2.02% ± 0.66%).p > 0.05). The lowest total amount of triterpene compounds (4060 ± 122 µg/g) was detected in cranberry fruit samples collected from a mesotrophic-type wetland vegetation (site D) in October (p < 0.05).The data of the qualitative and quantitative analysis of the composition of the triterpene compounds is presented in The analysis of triterpene compounds showed that ursolic acid was the most abundant in all the cranberry fruit samples, accounting for 76.24% ± 1.91% of the total triterpene content. The amount of oleanolic acid accounted for 17.44% ± 1.17% of the total amount of triterpene compounds in the studied cranberry fruit samples. The triterpene compounds found at lower total amounts were maslinic acid (0.91% ± 0.48%), corosolic acid (3.32% ± 1.49%), α-amyrin (1.98% ± 1.39%), and β-amyrin (0.10% ± 0.24%). Cranberry fruit samples collected from the oligotrophic-type wetlands of the Kamanai reserve (site E) showed higher levels of maslinic acid and corosolic acid, which accounted for, respectively, 2% and 7% of the total content of the triterpene compounds in the fruit samples of both collections.p < 0.05).The results of the quantitative analyses of chlorogenic acid and proanthocyanidins are presented in p > 0.05).The total amount of proanthocyanidins in cranberry fruit samples varied from 919 ± 19 µg EE/g to 3038 ± 137 µg EE/g. The highest total proanthocyanidin content (3038 ± 137 µg EE/g) was detected in cranberry fruit samples collected from the mesotrophic-type wetland (site K) of Žuvintas reserve in October, which was not statistically significantly different from the proanthocyanidin content found in cranberry fruit samples collected from the oligotrophic-type wetlands  of Kamanai reserve at the end of August (The pattern of compound accumulation in cranberry fruit samples collected during the first (Sample 1) and the second harvesting (Sample 2) is shown in In the phytochemical composition model , the phyV. oxycoccos fruit samples collected from different types of wetlands in Lithuania allows for comparing it with the qualitative and quantitative composition of biologically active compounds in fruit samples of V. macrocarpon cultivated in Lithuania. Anthocyanins found in V. macrocarpon fruit samples have been shown to increase the composition of good gut bacteria [V. oxycoccos berries for health promotion purposes.The analysis of the qualitative and quantitative composition of biologically active individual compounds in bacteria  and inhibacteria , proanthbacteria , and tribacteria  and inhibacteria . ComparaV. oxycoccos) grown under Lithuanian climatic conditions was similar to that of the fruits of the previously studied large cranberry (V. macrocarpon) cultivars grown under Lithuanian climatic conditions [V. oxycoccos fruit samples during the ripening period was 698 ± 24–8352 ± 200 µg/g, while in the previously studied V. macrocarpon fruit samples, it was found to be 309 ± 15–9629 ± 266 µg/g [O-glucosyltransferase (UFGT) are increased, leading to an increase in anthocyanin content of the fruit [The phytochemical profile of the fruits of the small cranberry , cyanidin-3-arabinoside (25.3% ± 2.7%), peonidin-3-galactoside, (24.5% ± 4.2%), and peonidin-3-arabinoside (17.3% ± 7.7%) and smaller amounts of cyanidin-3-glucoside (1.5% ± 1.1%) and peonidin-3-glucoside (4.7% ± 2.1%) [V. oxycoccos chemotype was found to have larger amounts of cyanidin-3-glucoside (19.5% ± 6.5%), peonidin-3-glucoside (54.5% ± 9.6%), cyanidin-3-arabinoside (13.1% ± 4.8%), and peonidin-3-arabinoside (12.0% ± 8.3%) and smaller amounts of cyanidin-3-galactoside (0.5% ± 0.7%) and peonidin-3-galactoside (0.4% ± 0.8%) [V. oxycoccos showed a similar anthocyanin composition profile to that of V. macrocarpon, while the diploid type of the cranberry was characterized by a higher content of cyanidin and peonidin glucosides [The study found that the quantitative composition of anthocyanins varied between different natural habitats. Four anthocyanins  were predominant in the cranberry fruit samples collected from Kamanai reserve wetland  and from Žuvintas reserve wetland (sites L and M), while in the cranberry samples collected from sites B, C, F, G, H, and J of Kamanai reserve wetland and site K of Žuvintas reserve wetland, six anthocyanins  predominated. Vosra et al. investigated small cranberry fruit samples and found that ploidy 2× and 4× resulted in different percentages of anthocyanins arabinosides, galactosides, and glucosides in those samples . They fo ± 2.1%) . The dip ± 0.8%) . Česonieucosides . The genV. macrocarpon and V. oxycoccos fruit samples showed that the total flavonol content (1465.56 ± 31.22 µg/g to 3688.52 ± 22.85 µg/g) in the large cranberry fruit samples varied more widely than the total flavonol content (518 ± 16 µg/g to 2811 ± 31 µg/g) in the small cranberry fruit samples [V. macrocarpon fruit samples  was consistent with the quantitative composition of the flavonols found in fruit samples of V. oxycoccos [V. macrocarpon fruit samples and found that the amount of quercetin-3-galactoside was 31–46%, the amount of myricetin-3-galactoside—19–32%, the amount of quercetin-3-α-L-arabinofuranoside—7–17%, and the amount of quercetin-3-rhamnoside—7–14% [V. oxycoccos evaluated in our study.Another important group of bioactive compounds in cranberry fruits that determines the biological effects of fruit preparations are flavanols. A comparative analysis of the qualitative and quantitative composition of flavonols in de—7–14% . These rThe coefficient of variation for flavanols in the small cranberry fruit samples was 50.50%. In the cranberry fruit samples (sample 1 and sample 2), higher concentrations of flavonols were found in the samples collected from oligotrophic-type wetlands , while lower concentrations were detected in the cranberry fruit samples harvested from eutrophic- and mesotrophic-type wetlands . Cranberry fruit samples collected in October in the oligotrophic-type wetland habitat (site G) showed by 2.7 times lower flavonol levels than those found in cranberry fruit samples from the same site collected at the end of August. A 2.5-fold decrease in flavonols was also found in the cranberry fruit samples collected in the mesotrophic-type wetland habitat (site D). Changes in flavonol composition found in the other fruit samples collected from other habitats were not huge. Šedbarė et al. found that the total amount of flavonols in V. macrocarpon fruits halved during the ripening period (from 12 August to 22 October) .The coefficient of variation of the total proanthocyanidin content in the tested cranberry fruit samples was 25.98%. Cranberry fruit samples collected in October in Kamanai reserve wetland habitats  showed lower proanthocyanidin levels compared to the levels detected in the samples collected in late August. Cranberry fruit samples collected in October from Žuvintas reserve wetland habitats  showed higher levels of proanthocyanidins compared to those detected in cranberry fruit samples collected in the same habitats at the end of August. Data from Wang et al. showed that similar (high/low) levels of proanthocyanidins in the cranberry fruit samples were related to genetic factors influencing flavonoid synthesis . Yu et aV. oxycoccos fruit samples, it was 919 ± 19 µg EE/g to 3038 ± 137 µg EE/g and was lower than the total proanthocyanidin content of the V. macrocarpon fruit samples (2280 ± 220 mg EE/g to 8870 ± 570 mg EE/g) [V. macrocarpon and V. oxycoccos and found that the total proanthocyanidin content of the samples differed little [V. oxycoccos fruit was by up to 15 times lower than that in V. macrocarpon fruit, and that differences in the qualitative and quantitative composition of proanthocyanidins might lead to differences in the efficacy of the species of Vaccinium in the treatment of urinary tract infections [A comparative analysis of the total amount of proanthocyanidins showed that in V. macrocarpon cultivars Baifay, Howes, Pilgrim, Early Black, Red Star, and Stevens, and its levels remain constant during fruit ripening of [V. oxycoccos fruits to accumulate chlorogenic acid, similarly to V. macrocarpon fruits, is determined by the genotype of the cranberry species, and can therefore also be regarded as a chemotype marker for V. oxycoccos fruits.Phenolic (phenolcarboxylic) acids are an important group of biologically active compounds that determine the sensory and biological properties of fruit ,39. In tening of . The abiV. oxycoccos fruits grown under Lithuanian climatic conditions was similar to that in V. macrocarpon fruits [V. oxycoccos fruit samples, it was 4060 ± 122–6542 ± 157 µg/g, whereas in V. macrocarpon fruit samples, it ranged from 1560.43 ± 90.81 µg/g to 4827.19 ± 91.71 µg/g [The content of triterpene compounds in cranberry fruit samples varied the least among the groups of the compounds studied, the coefficient of variation being 10.52%. The triterpenic, oleanolic, and ursolic acids accounted for 93.68% ± 2.32% of the total amount of triterpene compounds in cranberry fruit samples. The composition profile of triterpene compounds in n fruits . A compa.71 µg/g .Changes in the composition of bioactive compounds are determined by genetic factors , environThe analysis of the phytochemical composition of small cranberries showed that the qualitative and quantitative composition of anthocyanins, chlorogenic acid, flavonols, proanthocyanins, and triterpene compounds found in cranberry fruit samples depended on the type of the habitat and the time of fruit collection. The phytochemical profile found in the fruit samples of small cranberry and large cranberry was virtually the same, but due to the quantitative differences in the bioactive compounds, it is expedient to standardize the phytochemical composition of cranberry raw material and the preparations produced in order to ensure the quality and effectiveness of the products. The phytochemical composition of cranberry fruit is influenced by genetic and environmental factors and the interactions between these factors, and the application of appropriate methodologies and routine tests is thus important to justify the use of cranberry fruit raw materials in the production of functional foods and phytopreparations, ensuring the control of the standardized quantitative indicators. In view of the phytochemical composition of small cranberry fruits identified in the study, the following compounds could be used as phytochemical markers: chlorogenic acid, the main anthocyanins , flavonols myricetin-3-galactoside and quercetin-3-galactoside, and triterpenoid ursolic and oleanolic acids.Vaccinium Oxycoccos L.) were collected (300 g) in the habitats of Kamanai and Žuvintas reserves . The cranberry fruits were subsequently freeze-dried in a Zirbus lyophilizer  at a condenser temperature of −85 °C and a pressure of 0.01 mbar. Freeze-dried cranberry fruits were ground using a Retsch GM 200 electric mill . Losses on drying were evaluated using the method proposed in the European Pharmacopoeia .v/v) was bought from AB Stumbras . Solvents , reagents (hydrochloric acid and 4-(dimethylamino) cinnamaldehyde), and reference standards  were bought from Sigma-Aldrich . Trolox  was purchased from Scharlau . Formic acid was purchased from Merck . The standard for quercetin-3-glucoside was purchased from Biochemistry . Standards for quercetin-3-galactoside and quercetin were bought from Carl Roth . Reference standards for peonidin chloride, cyanidin chloride, myricetin-3-galactoside, malvidin-3-galactoside, malvidin chloride, malvidin-3-arabinoside, cyaniding-3-galactoside, peonidin-3-arabinoside, peonidin-3-glucoside, delphinidin-3-galactoside, cyaniding-3-glucoside peonidin-3-galactoside, and cyaniding-3-arabinoside were bought from Extrasynthese .All reagents, standards, and solvents were of analytical reagent grade. Ethanol 96% (v/v) in an ultrasonic bath  . Following that, the prepared cranberry extracts were filtered into a 20 mL volumetric flask. The extraction of freeze-dried cranberry fruit samples was performed three times. The prepared cranberry extracts were kept in dark glass containers at −20 °C.Extraction of proanthocyanidins, flavonols, and anthocyanins from cranberry fruits was carried out by extracting 1 g of freeze-dried cranberry powder (exact weight) with 70% ethanol acidified with 1% hydrochloric acid (v/v) acetone in an ultrasonic bath  . Following that, the prepared cranberry extracts were filtered into a 10 mL volumetric flask. The extraction of freeze-dried cranberry fruit samples was performed three times. The prepared cranberry extracts were kept in dark glass containers at −20 °C.Extraction of triterpenoids from cranberries was carried out by extracting 1 g of freeze-dried cranberry fruit powder (exact weight) with 10 mL of 100% (m/v) in ethanol-hydrochloric acid at 9:1 (v/v)) and measured the absorbance of this solution at 640 nm after 5 min [m/v) in ethanol-hydrochloric acid at 9:1 (v/v)). The data were expressed in terms of (–)-epicatechin equivalent (µg/g (–)-epicatechin equivalent (EE) dry weight). The calibration equation was y = 0.7021x + 0.0138; R2 = 0.9994.Freeze-dried cranberry fruit extracts were analyzed with a spectrophotometer . We mixed 20 μL of cranberry fruit extract with 3 mL of DMCA (4-(dimethylamino)cinnamaldehyde)  aqueous 10% formic acid solution (v/v) (solvent B), and the solvent flow rate was 0.5 mL/min. The column temperature was set at 30 °C. The gradient used was 0.0–2.0 min, 95% B; 2.0–7.0 min, 91% B; 7.0–9.0 min, 88% B; 9.0–10.0 min, 75% B; 10.0–10.5 min, 20% B; 10.5–11.0 min, 20% B; and 11.0–12.0 min, 95% B. The amounts of anthocyanins and anthocyanidins were evaluated at the wavelength of 520 nm. Chromatograms of cranberry fruit samples are provided in the The content of anthocyanins and anthocyanidins in cranberry fruit extracts was evaluated according to the methodology described by Vilkickyte et al. . The mobv/v) (solvent A) and aqueous 0.1% formic acid solution (v/v) (solvent B), and the solvent flow rate was 0.5 mL/min. The column temperature was set at 30 °C. The gradient used was 0 min, 95% B; 1 min, 88% B; 3 min, 88% B; 4 min, 87% B; 9 min, 75% B; 10.5 min, 70% B; 12 min, 70% B; 12.5 min, 10% B; 13 min, 10% B; 13.5 min, 95% B; and 14.5 min, 95% B. The column was allowed to equilibrate for 2 min between the injections. The amounts of flavonols were evaluated at the wavelength of 360 nm. Chromatograms of cranberry fruit samples are provided in the The content of flavonols in cranberry fruit extracts was established according to the methodology described by Urbstaite et al. . The mobv/v) (solvent A) and aqueous 0.1% formic acid (v/v) (solvent B), and the solvent flow rate was 0.2 mL/min. The column temperature was set at 25 °C. The gradient used was 0 min, 8% B; 8 min, 3% B; 9 min, 2% B; 29.5 min, 2% B; and 30 min, 8% B. The column was allowed to equilibrate for 10 min between the injections. The amounts of triterpene compounds were evaluated at the wavelength of 205 nm. Chromatograms of cranberry fruit samples are provided in the The content of triterpenoids in cranberry fruit extracts was established according to the methodology described by Sedbare et al. . The mobp < 0.05 were regarded as statistically significant. The data are reported as mean ± standard deviation (SD).Statistical analysis was carried out using computer software programs SPSS Statistics 21  and Microsoft Excel 2016 . The Kruskal–Wallis one-way ANOVA test was used to evaluate differences in the content of the identified compounds between cranberry samples. Differences at An analysis of the phytochemical composition of small cranberry fruits grown in Lithuanian climatic conditions was conducted. Studies on the qualitative and quantitative composition of cranberry fruit samples provide new insights into the variation in the composition of anthocyanins, proanthocyanidins, chlorogenic acid, triterpene compounds, and flavonols in small cranberry fruit and enable the assessment of the quality of cranberry fruit and the use of high-quality cranberry fruit raw material for food and health promotion purposes.V. oxycoccos and V. macrocarpon fruit samples showed that there was little difference in the phytochemical profile of these plant species, but due to the quantitative differences in the bioactive compounds, it is expedient to standardize the phytochemical composition of cranberry raw material and preparations to ensure their quality and effectiveness.In view of the phytochemical composition of small cranberry fruits found in the study, the following compounds could be used as phytochemical markers: chlorogenic acid, the main anthocyanins , flavonols myricetin-3-galactoside and quercetin-3-galactoside, and triterpenoid acids ursolic and oleanolic acids. A comparative analysis of the chemical composition of


To evaluate benefits and harms of transcutaneous electrical nerve stimulation (TENS) for chronic primary low back pain (CPLBP) in adults to inform a World Health Organization (WHO) standard clinical guideline.We searched for randomized controlled trials (RCTs) from various electronic databases from July 1, 2007 to March 9, 2022. Eligible RCTs targeted TENS compared to placebo/sham, usual care, no intervention, or interventions with isolated TENS effects  in adults with CPLBP. We extracted outcomes requested by the WHO Guideline Development Group, appraised the risk of bias, conducted meta-analyses where appropriate, and graded the certainty of evidence using GRADE.Seventeen RCTs  out of 2010 records and 89 full text RCTs screened were included. The evidence suggested that TENS resulted in a marginal reduction in pain compared to sham (9 RCTs) in the immediate term (2 weeks) (mean difference (MD) = -0.90, 95% confidence interval  -1.54 to -0.26), and a reduction in pain catastrophizing in the short term (3 months) with TENS versus no intervention or interventions with TENS specific effects (1 RCT) . For other outcomes, little or no difference was found between TENS and the comparison interventions. The certainty of the evidence for all outcomes was very low.Based on very low certainty evidence, TENS resulted in brief and marginal reductions in pain  and a short-term reduction in pain catastrophizing in adults with CPLBP, while little to no differences were found for other outcomes.The online version contains supplementary material available at 10.1007/s10926-023-10121-7. Electrical stimulation therapies are therapeutic adjuncts used in the management of chronic pain conditions such as osteoarthritis, fibromyalgia, and chronic primary low back pain (CPLBP) –3. They Both are reported to have similar mechanisms of action, namely acting through segmental inhibition or activation of descending pain-inhibitory systems . TENS unIn 2008, Khadilkar and colleagues published a Cochrane systematic review to assess the effectiveness of TENS versus placebo for the management of CPLBP  [The objectives of this systematic review of RCTs were to determine: (1) the benefits and harms (as reported in RCTs) of TENS compared to placebo/sham, usual care, or no intervention for the management of CPLBP in adults, including older adults (aged ≥ 60 years); and (2) whether the benefits and harms of TENS vary by age, gender/sex, presence of leg pain, race/ethnicity, or national economic development of the countries where the RCTs were conducted.This systematic review was conducted as part of a series of reviews to inform the WHO guideline on the management of CPLBP in adults. The development of this guideline was ongoing at the time of submission of this manuscript. The methods are detailed in the methodology article of this series , 6.Briefly, we updated and expanded the scope of the previously published high-quality Cochrane systematic review by Khadilkar et al. (2008) . We regiWe included RCTs that compared TENS to placebo/sham, usual care, and no intervention  in adults (aged ≥ 20 years) with CPLBP. TENS interventions could be applied using device settings of any of the stimulation parameters including pulse intensity, frequency, duration, and type (burst or continuous). RCTs of electrical stimulation administered percutaneously using needles were excluded. In addition to the main critical outcomes requested by the WHO Guideline Development Group (GDG) and assessed for all reviews in this series , we also assessed additional critical outcomes requested by the WHO GDG for this review – the change in use of medications and falls in older adults (aged ≥ 60 years). We reported outcomes based on post-intervention follow-up intervals including: (1) immediate term (closest to 2 weeks after the intervention period); (2) short term (closest to 3 months after the intervention period); (3) intermediate term (closest to 6 months after the intervention period); (4) long term (closest to 12 months after the intervention period); and (5) extra-long term (more than 12 months after the intervention period).We assessed between-group differences to determine the magnitude of the effect of an intervention and to assess its effectiveness , 8 , we conducted the following pre-specified sub-group and sensitivity analyses: number of treatment sessions  and removal of RCTs rated as high risk of bias.We conducted random-effects meta-analyses and narrative synthesis where meta-analysis was not appropriate , and graWe screened 2010 records and 89 full-text reports  , 34, 35,1 RCTs , The certainty of the evidence for all outcomes was very low, and was downgraded due to risk of bias, inconsistency, indirectness, and imprecision of the effect estimates .pain  in the immediate term  = -0.90, 95% confidence interval (CI) -1.54 to -0.26)  [Due to very low certainty evidence, it is uncertain whether TENS reduces t 1.1.1) , 34, 35.t 1.1.1) , 35.function in the immediate  = -0.96, 95% CI -3.20 to 1.28; benefit indicated by lower values) (plot 1.2.1) [scale 0 to 50, 0 = no disability) (plot 1.2.2) [health-related quality of life  in the immediate term  [depression  in the short term  (plot 1.5.1) [adverse events/harms (1 RCT)  [Due to very low certainty evidence, it is uncertain whether TENS makes little or no difference to t 1.2.1) , 31, 32,t 1.2.2) . It is ut 1.4.1) , 34. It t 1.5.1) . It is unthesis) . None ofpain  in the immediate term  (plot 1.6.1.1) [Due to very low certainty evidence, in older adults, it is uncertain whether TENS makes little or no difference to 1.6.1.1) .pain  in the immediate   [Due to very low certainty evidence, it is uncertain whether TENS makes little or no difference to t 2.1.1) , 30–33, t 2.1.1) , 31.function  in the immediate  (plot 2.2.1) [health-related quality of life  in the immediate term  [depression  in the short term  (plot 2.5.1) [pain catastrophizing  in the short term  (plot 2.6.1) [adverse events/harms in the immediate term (1 RCT)  [Due to very low certainty evidence, it is uncertain whether TENS makes little or no difference to t 2.2.1) , 30, 31,t 2.2.1) , 31. It t 2.4.1) . It is ut 2.5.1) . It is uThe results of the subgroup analyses did not substantially alter our main findings; however, the subgroups require further investigation. For all comparisons, the subgroups were small (consisting of 1–3 RCTs with sample sizes ranging from 11 to 134 adults per group) and yielded small, pooled effects with marked imprecision (wide 95% CIs) and unclear clinical implications. Therefore, subgroup differences could not be explained and/or the differences between subgroups would likely not result in different recommendations for different subgroups (see Online Resource 7). This is due to the very low certainty evidence and little or no differences between TENS and comparisons for all outcomes.The evidence regarding the benefits and harms of TENS for CPLBP in adults is based on 17 RCTs with a total of 1027 adults. Of these, two RCTs  assessed older adults aged ≥ 60 years) [0 years [Our findings are similar to those in the review by Khadilkar et al. (2008)  concludiSince the publication of Khadilkar et al. in 2008, we identified one related systematic review assessing the effectiveness of TENS versus placebo for CLBP, the findings of which aligned with ours. Resende et al. (2018)  found loOur systematic review has strengths. To begin with, our team consisted of clinical and methodological experts from around the world, specializing in LBP, systematic reviews, and evidence syntheses. Secondly, our review process involved conducting thorough and peer-reviewed literature searches without any language restrictions. Third, during the screening and ROB assessments, a core team member  was involved in each screening and ROB pair. Fourth, our ROB assessments did not rely on summary scores or the number of items at risk of bias, as some other systematic reviews have done. Instead, we created supplementary guidance forms based on the ROB1 criteria , 13, whiOur review has potential limitations. One limitation is the possibility that we missed relevant RCTs. However, we attempted to address this by using comprehensive and peer-reviewed literature search strategies developed with the assistance of experienced health sciences librarians. Additionally, we searched the reference lists of included RCTs and related systematic reviews. Another limitation is that we did not search the grey literature, which could introduce publication bias as studies published in peer-reviewed journals tend to report larger intervention effects than those in the grey literature . NonetheOf note, the WHO GDG sought a homogeneous population comprising adults with CPLBP . That isWe identified several gaps in the evidence that applied across all comparisons involving TENS. First, we did not identify any RCTs reporting on the benefits or harms of TENS beyond the short term . Second, we did not identify any RCTs assessing the effects of TENS on fear avoidance, anxiety, self-efficacy, or social participation including work. Finally, we were unable to assess whether benefits or harms of TENS vary by race/ethnicity. For the comparison of TENS to sham in all adults, we found no RCTs assessing the effects of treatment on catastrophizing behaviours. In older adults (aged ≥ 60 years), two small RCTs assessed pain; we found no RCTs assessing function, health-related quality of life, depression, fear avoidance, change in medication use, falls, or harms. We were also unable to assess whether the benefits or harms of TENS in older adults vary by gender, presence of leg pain/symptoms, or in people from higher versus lower income countries. For the comparison of TENS to no intervention or interventions where the effects of TENS could be isolated, we found no RCTs reporting on fear avoidance behaviours, anxiety, self-efficacy, or social participation including work, and no RCTs in older adults. Finally, we found no RCTs comparing TENS to usual care. These identified gaps may be an avenue for further research, as well as comparing the effects of different doses, frequencies, and durations of TENS. Harms, including those that may be associated with persistent long-term use, should also be investigated systematically.Based on very low certainty evidence, adults with CPLBP experienced brief and marginal reductions in pain  and a short-term reduction in pain catastrophizing with the use of TENS. Harms from TENS are unclear, as only one included RCT assessed adverse events. The remaining evidence showed little to no difference in benefits between TENS and the comparison interventions for a range of other outcomes . Care plans for patients should be created through shared decision making, considering the scientific data and other contextual factors, such as patient preferences and values.Below is the link to the electronic supplementary material.Supplementary Material 1


Across the globe, student champions are building the social prescribing student movement. Given the numerous linkages between social prescribing and students, there is a need to understand the extent and type of evidence on social prescribing and students. Doing so will address an important gap in the literature, as there are no evidence reviews on this topic. Thus, this scoping review aims to understand the extent and type of evidence on social prescribing and students. This review will be conducted in accordance with the JBI methodology for scoping reviews and will be reported in line with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). The search strategy will aim to locate both published and unpublished literature. No language or date restrictions will be placed on the search. The databases to be searched include MEDLINE (Ovid), CINAHL (EBSCO), Embase (Ovid), PsycINFO (Ovid), AMED (Ovid), ASSIA (ProQuest), Sociological Abstracts (ProQuest), Global Health (Ovid), Web of Science (Clarivate), Epistemonikos, JBI EBP Database (Ovid), and Cochrane Library. Sources of gray literature to be searched include Google, Google Scholar, Social Care Online , SIREN Evidence and Resource Library , and websites of social prescribing organizations and networks. Additionally, a request for evidence sources will be sent out to members of the Global Social Prescribing Student Council. Two independent reviewers will perform title and abstract screening, retrieval and assessment of full-text evidence sources, and data extraction. Data analysis will consist of basic descriptive analysis. Results will be presented in tabular and/or diagrammatic format alongside a narrative summary. Social  to you’  p. 9. Al to you’ .Across the globe, student champions are supporting this work by building the social prescribing student movement. There are student groups in Australia, Canada, Japan, Portugal, Singapore, the United Kingdom, and the United States , and thiStudents have a critical role to play in shaping the wider social prescribing movement . Indeed,Students also stand to benefit from social prescribing. Even before the COVID-19 pandemic, students were experiencing high rates of mental health challenges , 6. As aIt is also necessary to consider the importance of this topic in relation to the global healthcare crisis. As tomorrow’s leaders, students need to be equipped with the necessary tools to address this seemingly insurmountable challenge . Social Given the numerous linkages between social prescribing and students, there is a need to understand the extent and type of evidence on social prescribing and students. A preliminary search of PROSPERO, MEDLINE (Ovid), JBI EBP Database (Ovid), Cochrane Library, Google, and Google Scholar was conducted on April 12, 2023. Only one underway evidence review on social prescribing and students was found , which iThere are several different types of evidence reviews . ScopingThis scoping review aims to understand the extent and type of evidence on social prescribing and students. Knowledge gaps in the evidence base will be identified. The implications of the findings for the social prescribing student movement and the wider social prescribing movement will be discussed.What is the extent and type of evidence on social prescribing and students?What are the knowledge gaps in the evidence base around social prescribing and students?This review will consider evidence sources with participants who are labelled as students. Evidence sources with participants who are not labelled as students will be excluded. Age will not be considered–eligibility will be determined solely based on the use of the term ‘student’.This review will consider evidence sources that explore a concept that meets the following operational definition of social prescribing, even if it is not labelled as social prescribing:Social prescribing is “a holistic, person-centred, and community-based approach to health and wellbeing that satisfies Condition 1 and either Condition 2 or Conditions 3 and 4:Condition 1: Identifier identifies that person has non-medical, health-related social needs Condition 2: Identifier connects person to non-clinical supports and services within the community by co-producing a non-medical prescriptionCondition 3: Identifier refers person to connectorCondition 4: Connector connects person to non-clinical supports and services within the community by co-producing a non-medical prescription”  p. 9.Evidence sources that explore a concept that does not meet this definition will be excluded.This review will consider evidence sources from any context.This review will consider both published and unpublished literature. Evidence sources with quantitative, qualitative, and mixed methods study designs will be considered. In addition to primary research, this review will consider reviews and meta-analyses, theses and dissertations, and reports. Evidence sources without full text, text and opinion papers, and protocols will be excluded.This protocol has been registered on Open Science Framework (osf.io/m3ura) and published in this journal to promote transparency. This protocol was developed according to best practice guidance for scoping review protocols from the JBI Scoping Review Methodology Group . This reThe search strategy will aim to locate both published and unpublished literature. An initial limited search of MEDLINE (Ovid) and CINAHL (EBSCO) was undertaken to identify evidence sources on the topic. The text words contained in the titles and abstracts of relevant evidence sources, and the index terms used to describe the evidence sources, were used to develop a full search strategy for MEDLINE (Ovid) in The databases to be searched include MEDLINE (Ovid), CINAHL (EBSCO), Embase (Ovid), PsycINFO (Ovid), AMED (Ovid), ASSIA (ProQuest), Sociological Abstracts (ProQuest), Global Health (Ovid), Web of Science (Clarivate), Epistemonikos, JBI EBP Database (Ovid), and Cochrane Library. Sources of gray literature to be searched include Google, Google Scholar, Social Care Online , SIREN Evidence and Resource Library , and websites of social prescribing organizations and networks, including the Social Prescribing Network, the Social Prescribing Youth Network, the Global Social Prescribing Alliance, the National Academy for Social Prescribing, and the Canadian Institute for Social Prescribing. Additionally, a request for evidence sources will be sent out to members of the Global Social Prescribing Student Council.Following the search, all identified evidence sources will be collated and imported into Covidence  and duplicates removed. Following a pilot test, titles and abstracts will then be screened by two independent reviewers for assessment against the inclusion criteria for the review. Potentially relevant evidence sources will be retrieved in full, imported into Covidence, and assessed in detail against the inclusion criteria by two independent reviewers. Reasons for exclusion of evidence sources at full text that do not meet the inclusion criteria will be recorded and reported in the scoping review. Any disagreements that arise between the reviewers at each stage of the selection process will be resolved through discussion or with a third reviewer. The results of the search and the evidence source inclusion process will be reported in full in the final scoping review and presented in a PRISMA-ScR flow diagram .Data will be extracted from evidence sources included in the scoping review by two independent reviewers using a data extraction tool developed by the research team. The data extracted will include specific details about the objective, participants, concept, context, methods, and key findings relevant to the review questions. A draft data extraction tool is provided in Data analysis will consist of basic descriptive analysis. Results will be presented in tabular and/or diagrammatic format in a manner that aligns with the review objective. A narrative summary will accompany the tabulated and/or charted results and will describe how the results relate to the review objective and questions.S1 Appendix(PDF)Click here for additional data file.


Immunoglobulin (Ig) is a costly blood product prescribed as immune replacement or modulation therapy to treat a wide spectrum of medical conditions. While the FDA has approved Ig for a limited number of indications, there are multiple off-label uses that have demonstrated proven clinical benefit or are currently in various phases of clinical study. There are also diagnoses for which Ig is prescribed, but for which no evidence-based efficacy data are available. Many conditions for which Ig has been prescribed are extremely rare, and a controlled clinical trial is not logistically possible. These conditions may be denied insurance authorization because of limited medical evidence that supports the use of Ig in their treatment. This limited evidence consists of uncontrolled studies, case series and reports, and expert opinion. Limiting the use of Ig therapy to cases with the best supporting evidence may control health care expenditure, but it may also limit the potential body of knowledge from publications by physicians with experience in treating these conditions. Specialty pharmacy providers can collect longitudinal outcomes, and data from their publications could provide support for improved managed care criteria or areas of future medical research.To (a) assess levels of supporting evidence by diagnosis for a sample of Ig requests submitted through the managed care prior authorization (PA) process and (b) provide a descriptive review of such requests and resultant benefit coverage determinations by individual diagnosis, overarching diagnostic category, patient age group, and assessed levels of evidence.Through collaboration with 6 health plans, we obtained and analyzed 2,548 managed care PA requests for Ig therapy received between February 2008 and August 2012, as well as resulting benefit coverage determinations. A literature review of 7 established treatment guidelines and expert consensus statements was conducted and used to evaluate all indications for Ig treatment presented among obtained requests and to assign each request to 1 of 5 categorical levels of supporting evidence.Of the 2,548 Ig requests reviewed, 1,467 (57.6%) were found to be “supported” in the relevant literature; 830 (32.6%) were designated “conditional”; 127 (5%) were “lacking consensus”; 74 (2.9%) were “currently not supported”; and 50 (2%) were “undetermined.” Overall, 2,094 (82.2%) of the requests were authorized by the health plans. Of the total requests, 1,633 (64.1%) were for FDA-approved diagnostic indications, of which 1,393 (85.3%) were authorized by the sampled health plans. The majority of requests for Ig were for treatment of neurological and immunological conditions. A total of 181 unique indications were identified, yet 833 (32.7%) of the requests were for just 2 indications—common variable immunodeficiency and chronic inflammatory demyelinating polyneuropathy. Patients aged 45 to 64 years represented 1,318 (51.7%) of all requests.This analysis provides insight into the prescribed medical usage of Ig and the conditions for which it may be authorized through the managed care PA process. We identified 181 unique diagnostic indications for Ig, for which only 97 had established expert consensus. Although many diagnostic indications were identified, most requests were for indications with strong supporting evidence, and most of these were authorized by the health plans. The number of indications identified highlights the ongoing need for publications from physicians and specialty pharmacies with experience in treating these conditions in order to increase the body of knowledge surrounding use of this therapy.


National guidelines for rational opioid prescribing for acute postoperative pain are needed to optimise postoperative pain control and function whilst minimising opioid-related harm.This overview of systematic reviews aims to summarise and critically assess the quality of systematic reviews related to the 20 recommendations from two previously published consensus guideline papers . It also aims to identify gaps in research that require further efforts to fill these in order to augment the evidence behind creating national guidelines for rational opioid prescribing for acute postoperative pain.A systematic database search using PubMed/MEDLINE and Cochrane was conducted in November 2022. Furthermore, reference lists were reviewed. All identified systematic reviews were assessed for eligibility. Data from each study was extracted using a pre-standardised data extraction form. The methodological quality of the included reviews was assessed by two independent reviewers using the AMSTAR 2 checklist. Descriptive synthesis of the results was performed.A total of 12 papers were eligible for analysis. Only eight out of the total 20 prioritised recommendations had systematic reviews that provided evidence related to them. These systematic reviews were most commonly of critically low quality.The consensus papers provide guidance and recommendations based on the consensus of expert opinion that is based on the best available evidence. However, there is a lack of evidence supporting many of these consensus statements. Efforts to further analyse interventions that aim to reduce the rates of opioid prescribing and their adverse effects should therefore continue. Prescri% from 0.% to 1.5%To solve this problem, guidelines have been proposed in different countries, as well as consensus documents to implement their content, but also to consider aspects that have not included. In the United Kingdom (UK), the Faculty of Pain Medicine released recommendations composed by a multi-organisational and multidisciplinary collaboration, setting out guiding principles for preoperative, perioperative, postoperative and post discharge opioid management. The aim of these recommendations is to reduce postoperative opioid use and the adverse effects caused by them. In summary, the Best Practice document gives the following recommendations on aspects of postoperative opioid management: 1) pain relief should be optimised; 2) pain assessment should involve functional assessment; 3) immediate-release opioids are preferred; 4) give advice on medicine self-administration on discharge; 5) local protocols for the prescription of discharge medications after surgery should be developed; 6) hospital discharge letter must explicitly state the recommended opioid dose, amount supplied and planned duration of use; 7) identify patients for de-escalation of opioids; 8) guidance should be given about necessary medicine review post-discharge [., was an international multidisciplinary consensus statement, which aimed to provide guidance in order to “assist healthcare professionals and hospitals across the world to implement effective opioid stewardship practices that achieve a balance between the administration of sufficient opioid analgesia to facilitate recovery and restoration of function, while concurrently minimising the risk of opioid-related harms” [. provides ten priority recommendations based on best evidence and, in the absence of such, expert opinion. The second statement was by Forget et al., which aimed to propose a consensus, not only on the prescribing of opioids, but also on policies for system-level interventions. Their ten recommendations were approved by a panel of experts in the field, along with healthcare representatives from different related medical disciplines and patient representatives from around the world. Therefore, the research reflects the view of a multi-stakeholder panel and represents a breadth of perspectives [But guidelines are necessary but not enough, and local guidance should consider local aspects and include educational programme, as recently considered as the highest priority in the context of multimodal, opioid-sparing, analgesia . Accordid harms” . Levy etpectives .Although both papers provide valuable recommendations for opioid prescribing practices, they are based on expert opinion. Expert opinion is often sought during the development of governance and regulatory policies when there is insufficient empirical evidence to implement a policy or change , but it The primary aim of this overview of SRs is to summarise the evidence and critically assess the quality of SRs that are relevant to the ten priorities of each of the Levy et al.  and ForgThis overview of reviews was conducted in accordance with the Cochrane Handbook for the Systematic Review of Interventions and reported following the Reporting guideline for overviews of healthcare interventions: the Preferred Reporting Items for Overviews of Reviews (PRIOR) statement , 12.Due to the nature of this literature-based project, no ethics approval was required. However, each of the SRs included state the ethics considerations and approval that they required.The inclusion and exclusion criteria are shown in Table . (2020) consensus and the ten priorities of the Forget et al. consensus [The search strategy involved looking at the SRs cited in reference lists of the consensus statements by Levy et al.  and Forg. 020 conseonsensus  and consAll identified citations were collated and uploaded to RefWorks 2 and duplicates were removed. Two independent reviewers  screened the titles and abstracts of identified articles to assess relevancy. Irrelevant articles were removed at this stage. Subsequently, full texts of selected articles were accessed and further screened by the same two reviewers  by applying the inclusion and exclusion criteria to assess eligibility. Articles that did not meet the eligibility criteria were removed. Any queries or uncertainties were discussed and resolved through discussion and consensus between the two reviewers  and a supervisor (PF).A standardised data extraction form was predefined to portray the study characteristics of included articles. The following data was extracted from each article into this data extraction form by a single author (CM): author, title, year of publication, country, search period, number of primary studies included, total number of participants, effect size, intervention, outcome measures, study methods, quality evaluation method, degree of certainty, meta-analysis (yes/no) and main findings.The methodological quality of the included SRs was assessed by two independent reviewers  using the Assessment of Multiple Systematic Reviews 2 (AMSTAR 2) checklist . The AMSA quantitative meta-analytic synthesis of the included SRs was not performed due to great heterogeneity across the reviews arising from differences in sample characteristics, as well as differences between methods and outcome measures. Therefore, the data was grouped to the relevant ten priorities of the Levy consensus and the ten priorities of the Forget consensus and descriptive synthesis of the results was performed , 8.In total, 1,063 studies were identified. 276 duplicate records were removed, leaving 787 studies to be screened. After title and abstract analysis, a further 771 papers were excluded based on inclusion and exclusion criteria. The full texts of 16 studies were sought for retrieval. One study could not be fully retrieved, therefore 15 full texts were retrieved and assessed. 12 studies met the inclusion and exclusion criteria and were used in this overview  [n = 2) [n = 1) [n = 1) [n = 1) [n = 1) [n = 1) [A summary of the detailed characteristics of the included SRs is presented in Table n = 5) –20, UK ( [n = 2) , 22, Aus [n = 1) , Canada  [n = 1) , France  [n = 1) , Poland  [n = 1)  and Swit [n = 1) . Three r [n = 1) , 27; thr [n = 1) , 23, 24; [n = 1) , 20, 21; [n = 1) . The num [n = 1) . Only fo [n = 1) , 27.Tabl.There was heterogeneity with regards to quality evaluation methods used in the included SRs. Three SRs used the Newcastle–Ottawa Quality Assessment Scale , 19, 23;. and Martinez et al. could, therefore, not be fully assessed using the AMSTAR 2 checklist [. had enough information in its full text and therefore was fully assessed; however, we cannot say if their supplementary material contains information that may alter their AMSTAR 2 tool results [The quality of the included SRs was assessed using AMSTAR 2 checklist, which is presented in Table hecklist , 25. The results .Table 4QAccording to the criteria of AMSTAR 2, seven of the ten SRs that could be fully assessed were of critically low quality, two were of low quality and one was of high quality. Items 2, 7 10, 11, 12 and 15 were rated particularly low amongst the included SRs. Only one SR that was able to be fully assessed reported the funding sources of the included SRs . A summaThe aim of this overview was to summarise the evidence and critically assess the quality of SRs that are relevant to the ten priorities of the Levy consensus and the ten priorities of the Forget consensus , 8. ThisThe SRs that were identified were generally of low quality according to the AMSTAR 2 checklist . Hence, further research is required to produce evidence of a higher quality to support the consensuses and pave the way for future safer opioid prescribing. The AMSTAR 2 tool was developed in 2017 as an upgraded version of the original AMSTAR tool. It is a well-used valid and reliable appraisal tool .. Sng et al. graded education as the highest priority that determines the use of opioid-sparing analgesia. Their recommendation is that more leadership and specific guidelines for multimodal analgesia could increase the adoption of these techniques. Our work could inform that kind of efforts and, here, follow specific suggestions that could be considered for implementation, in regard to the level of certainty and quality.The prescribing of opioids for acute postoperative pain remains a highly controversial topic. The two consensus statements provide very promising progress for the development of national protocols for the safe prescribing and stewardship of postoperative opioids. With regards to these two consensus statements, both at patient/prescriber and system/Public Health levels, they are based on variable levels of certainty and on analyses of variable quality. This has implications when integrating these aspects into clinical practice. Indeed, levels of certainty can impact both guidelines and guidance, even if both can be based on other sources, at the condition that generalisable, high quality, evidence, is identifiable. Expert opinion can then be considered when evidence is lacking or impossible to generate. Differentiating these levels of evidence is essential to robustly secure high quality local guidance and educational programmes, which have been described as essential to implement recommendations and to confirm their local validity . Sng et . provided evidence to support this statement. They concluded that strategies, such as proactively screening for at-risk individuals, should be priorities to reduce the substantial burden that persistent opioid use after surgery elicits on public health. Lawal et al. reported that preoperative use of opioids and cocaine and the presence of comorbid pain conditions before surgery were found to have the strongest associations with persistent opioid use after surgery [With regards to priority 1 of the Levy consensus  , the SR  surgery . These m. concluded that addressing the psychological needs of patients through preoperative education can decrease acute postoperative pain, and therefore decrease the need for opioid consumption [. found evidence that suggested preoperative psychological preparation may be beneficial for various outcomes, such as postoperative pain, behavioural recovery, negative affect and length of stay in hospital [. analysed the relations between presurgical psychological factors and acute postoperative pain. They identified numerous psychological variables that could be considered for optimising preoperative psychological risk factors before surgery, as recommended by Levy et al.  [. and Sobol-Kwapinska et al., but was high for the Powell et al. SR [Priority 2 of the Levy consensus   has thresumption . Additiohospital . However et al.  , 26. Thet al. SR , 22, 26.. provided evidence for priority 3 of the Levy consensus  [Baamer et al alone”)  by chall alone”) . The quaPriority 4 of the Levy consensus   was suppth priority of the Levy consensus  [. reported that surgical patients are using substantially less opioid than prescribed, leading to excess opioids that may be used inappropriately by patients or others. The authors agreed that strategies and clinical practice guidelines are needed to better educate prescribers and help standardise postoperative opioid prescriptions [There are two SRs found through the methodology of this overview that provide evidence for the 6a week”) . Arwi ana week”) . Howeverriptions . It shouth priority of the Levy consensus ”) [. provides further evidence for the 10th priority. This paper concluded that postoperative opioid prescriptions often go unused, unlocked and undisposed, leading to a reservoir of opioids that contribute to the non-medical use of these products [th priority of the Levy consensus.The 10amily)”)  was alsoamily)”) . The SR products . Althoug. provides further evidence for priority 10 of the Levy consensus. They found that opioids are overprescribed for acute postoperative pain, and baseline rates of surplus opioid disposal are low. Furthermore, their results showed that drug disposal kits or bags help to significantly increase these rates [The SR by Lamplot et alse rates . Due to st priority  [With regards to the Forget consensus, the 1spital”)  has one spital”) . The qua. found that there is overall low certainty of evidence that high-dose intraoperative opioids in patients under general anaesthesia increases pain scores and contributes to hyperalgesia in the postoperative period when compared to low-dose regimen. However, they proposed that additional robust methodology trials could better define the impact of each opioid regime on hospital and health-system recourses [. SR was low according to the AMSTAR 2 checklist.Finally, Albrecht et alecourses . This agecourses  by suggeThe number of drug-related deaths has vastly risen over the past few decades in the UK. According to the National Drug-Related Deaths Database (NDRDD) for Scotland, there were 1,209 deaths in 2018 that were drug related in Scotland. Opioids were implicated in 77% of these deaths. This is a significant increase from 2017, when there were 867 drug-related deaths in Scotland . In EnglThe Levy and Forget consensuses provide a strong framework for such protocols. They are predominantly expert opinion based , 8. HistThis overview included SRs of varying settings that covered a range of topics regarding rational opioid prescribing, enabling the concise evaluation and summarisation of literature related to the ten priorities of the Levy consensus and the ten priorities of the Forget consensus , 8. It tThere are several limitations of this overview. Firstly, there was one SR that could not be accessed for full-text analysis which may have offered valuable evidence . AdditioThere was significant heterogeneity amongst the SRs regarding interventions, outcome measures, and quality evaluation method, with only four out of the 12 included SRs including meta-analysis. This meant that the SRs were not comparable. However, they provided valuable evidence for the aim of this overview.The search strategy aimed to identify SRs for evidence for the ten priorities of the Levy consensus and the ten priorities of the Forget consensus through various database searches , 8. Howe. and Forget et al. consensus statements on rational opioid prescribing. However, there is a dearth of research that is required to implement valid and reliable nation opioid prescribing protocols. This overview found that there are not enough papers with high quality evidence to support the Levy et al. and Forget et al. consensus statements. The papers that were identified were mainly of low quality. Therefore, more research of a higher quality is required. The liberal prescribing of opioids for acute postoperative pain requires urgent attention. For now, it could be greatly beneficial to implement the recommendations given in the Levy et al. and Forget et al. consensus statements. The consensus papers provide guidance based on the consensus of expert opinion that is based on the best available evidence. However, efforts to further analyse interventions that aim to promote safter opioid prescribing and reduce their adverse effects should continue.In conclusion, this overview of SRs provides valuable insight into the evidence behind the Levy et al((wean opioids) OR (taper opioids)) AND (acute pain) AND ((postsurg*) OR (postop*)).Results = 24((preoperative education) OR (opioid education)) AND (acute pain) AND ((postsurg*) OR postop*)).Results = 20 AND ((postsurg*) OR (postop*)).Results = 2 AND (acute pain) AND ((postsurg*) OR (postop*)).Results = 0((non-opioid) OR (opioid-free) AND (acute pain) AND ((postsurg*) OR (postop*)).Results = 12(long-acting opioids) AND (acute pain) AND ((postsurg*) OR (postop*)).Results = 2(compound opioids) AND (acute pain) AND ((postsurg*) OR (postop*)).Results = 1 AND (acute pain) AND ((postsurg*) OR (postop*)).Results = 30((weaning opioids) OR (tapering opioids)) AND (acute pain) AND ((postsurg*) OR (postop*)).Results = 1(repeat prescription) AND (acute pain) AND ((postsurg*) OR (postop*)).Results = 0((persistent pain) OR (chronic pain) AND (acute pain) AND ((postsurg*) OR (postop*)).Results = 190


Incorporating emerging knowledge into Emergency Medical Service (EMS) competency assessments is critical to reflect current evidence-based out-of-hospital care. However, a standardized approach is needed to incorporate new evidence into EMS competency assessments because of the rapid pace of knowledge generation.The objective was to develop a framework to evaluate and integrate new source material into EMS competency assessments.The National Registry of Emergency Medical Technicians  and the Prehospital Guidelines Consortium (PGC) convened a panel of experts. A Delphi method, consisting of virtual meetings and electronic surveys, was used to develop a Table of Evidence matrix that defines sources of EMS evidence. In Round One, participants listed all potential sources of evidence available to inform EMS education. In Round Two, participants categorized these sources into: (a) levels of evidence quality; and (b) type of source material. In Round Three, the panel revised a proposed Table of Evidence. Finally, in Round Four, participants provided recommendations on how each source should be incorporated into competency assessments depending on type and quality. Descriptive statistics were calculated with qualitative analyses conducted by two independent reviewers and a third arbitrator.In Round One, 24 sources of evidence were identified. In Round Two, these were classified into high- (n = 4), medium- (n = 15), and low-quality (n = 5) of evidence, followed by categorization by purpose into providing recommendations (n = 10), primary research (n = 7), and educational content (n = 7). In Round Three, the Table of Evidence was revised based on participant feedback. In Round Four, the panel developed a tiered system of evidence integration from immediate incorporation of high-quality sources to more stringent requirements for lower-quality sources.The Table of Evidence provides a framework for the rapid and standardized incorporation of new source material into EMS competency assessments. Future goals are to evaluate the application of the Table of Evidence framework in initial and continued competency assessments. Evidence-based national guidance documents have been developed to support literature integration. Still, they are challenged due to the vast amount of scientific literature produced, the need to review the data, and its large variability in quality. To address this, the Prehospital Guidelines Consortium  created a repository of evidence-based guidelines (EBGs) and a mechanism to evaluate the quality of these documents for potential integration into educational frameworks. Yet, significant gaps exist among available prehospital guidelines, which do not address all aspects of EMS medicine. Therefore, knowledge from primary scientific literature and other available educational materials must be integrated into prehospital care while identifying knowledge gaps for future evaluation.Emergency Medical Service (EMS) clinicians require current evidence-based, state-of-the-art education to optimize patient care provided in the prehospital setting, The educational structure is framed by the national EMS education standards, core content, and scope of practice to set the standard and provide guidance for educational curricula. These educational systems, though rigorous, are updated infrequently and are not designed to address changes that require immediate implementation. For example, when rapid, impactful evidence was published in 2015 and 2016 concerning resuscitation and spinal motion guidelines, the National Registry of Emergency Medical Technicians  released statements describing the emergent integration of these concepts into certification testing, driving immediate integration of this content at all levels of education. However, a precise mechanism was unavailable to facilitate integration, and the community leaned on position statements by the certification organization for evidence integration. This delay in evidence integration creates gaps between the recognized evidence-enhancing patient outcomes with education and prehospital services implementation. Another complication for evidence integration is the quality of the evidence being reviewed. Recognizing the vast heterogeneity in the available sources of materials for EMS clinicians , the data quality may only be apparent to some content consumers. In the absence of mechanisms to identify high-quality primary source material, EMS clinicians and EMS educators may need assistance identifying high-priority primary data sources to prioritize in EMS education that aligns with certification.Unfortunately, there are no rapid mechanisms to integrate new, high-quality evidence or guideline recommendations into the EMS educational and credentialing systems, including initial training, continued competency, and high-stakes assessment.Therefore, a standardized method and hierarchy for integrating emerging evidence and knowledge into educational curricula or high-stakes examinations for EMS are necessary to optimize patient care. The objective was to obtain consensus from prehospital care experts to develop a valid, consistent, and transparent process for integrating and implementing new science into educational curricula and high-stakes testing, specifically how the National Registry will identify high- and low-quality emerging source material as a guide for EMS educators and clinicians when incorporating primary source material into educational content. Using a modified Delphi evaluation to gain consensus from prehospital experts on implementing valid medical knowledge into the educational curriculum and the national certification examinations, the National Registry convened a Task Force (TF) in July 2020 that consisted of 11 subject matter experts in clinical practice, prehospital research, educational programming, EMS medical direction, and evidence review experts from the PGC . The purpose of the TF was to provide recommendations to: (1) categorize medical evidence into a level of evidence hierarchy; and (2) implement these data into the national EMS certification examinations and education. The American Institutes of Research  IRB deemed this study exempted (Protocol number IRB00000436).Accredited by the National Commission for Certifying Agencies , the National Registry is a nonprofit organization that provides certifications for EMS clinicians in more than 46 states, territories, and federal agencies. Rounds were done synchronously, and follow-up surveys were sent. When surveys were used, participation reminders were sent out one to two weeks after each round’s invitation, following Dillman’s tailored design methodology to improve survey response and participation. The primary outcome of interest was the development of consensus around the type and quality of prehospital evidence and the impact of integration into the national certification examination. Data were collected through online surveys utilizing the 2020 Alchemer, LLC  survey platform.A four-round modified Delphi method Figure  was usedRound One—The initial round of data collection focused on having the experts identify potential source material available to EMS clinicians, EMS educators, and certification organizations. With many sources available to readers, understanding the specific types of evidence that may describe the standards of prehospital care is critical. Experts in Round One defined the potential sources and were asked to assign a categorical description of each type of evidence, including Primary Research, Recommendations for Care, and Information and Educational Content. In answering this query, participants were asked to consider a broad view of all the domains of EMS care, from cognitive to operational, and the associated literature that may inform decisions in these areas . Data were collected in a real-time interactive virtual meeting where all participants could brainstorm and generate ideas. Responses were collected and tabulated for the panel to evaluate.Round Two—In Round Two, participants were asked to complete two tasks using the information from Round One. First, participants were asked to categorize each type of evidence identified in Round One into specific levels of evidence quality. As a baseline, participants were provided a framework of “high, medium, and low” levels of evidence that would describe the reliability and rigor of the evidence. Second, each participant also identified the evidence as either serving the purpose of “providing recommendations for diagnosis or care in the prehospital setting,” “primary research that does not provide care recommendations but reports data or evidence,” or “informational or educational content.”Round Three—In Round Three, participants were asked to revise their judgments and provide feedback on the newly created Table of Evidence from data generated in the first two rounds. The table used a 3x3 format with rows being “Quality of Evidence” from high to low and columns being “Types of Evidence” as “Recommendations for Care,” “Primary Research,” and “Informational or Educational Content.” The TF then voted to categorize the evidence type with the appropriate quality level. The votes were tallied and shared with the members. This activity occurred in a virtual meeting with opportunities for each participant to provide feedback.Round Four—During the final round, the recommendations from the previous rounds were discussed, and feedback was requested concerning the generated Table of Evidence. The TF was then asked to define the best practices for integrating each evidence level into certification examination frameworks, including time goals. Finally, to support the discussion on the impact of evidence integration on certification examination processes, the examinations team from the National Registry provided additional details on exam development processes and production cadences. For Round Two, quality of evidence data for each evidence type were collected, and high-, medium-, and low-quality responses were coded with scores of six, three, and one. Average scores for evidence quality were then tabulated and provided to the TF. These scores were used as a guide for final categorization into high-, medium-, and low-quality evidence categories.The primary outcome was the development of a unanimous consensus around the type and quality of prehospital evidence and the impact on integration into the national certification examination. Descriptive statistics were calculated for each round using Stata IC 17 .1) generated a list of potential content sources that could be interpreted as informing EMS education or certifying exam content. Appendix 2 (available online only) shows these sources with a definition or example, recognizing that any particular content source may fit multiple types. In addition, the panel also identified potential categories that these sources of content could be subdivided into, including evidence that provided “recommendations for patient care” or sources of “primary research.” But again, these were examples of distinct categories, not a comprehensive list.The TF members gathered virtually in July 2020, where they were introduced to the overall project’s goals and the study plan. In Round One, the TF members (Appendix 3 (available online only). All other sources were categorized as medium or low levels of evidence. Since the medium-quality of evidence category was noted to have significant internal heterogeneity in the quality of evidence, the panel recommended a subdivision and ranking  within this category to allow for more accurate stratification  II tool and a categorization scheme based on whether guidelines meet the NAM criteria for “Clinical Practice Guidelines We Can Trust.”This manuscript describes how prehospital care experts developed a robust and transparent process for integrating and implementing new evidence into educational curricula and high-stakes testing. Leveraging a modified Delphi process, experts developed a Table of Evidence that weighs the quality and type of evidence to assist educators and test designers with new evidence incorporation for initial certification and continuing education requirements. Additionally, this framework provides a process for immediate integration of high-quality content into EMS clinician education, both initial and through continuing education, to facilitate the implementation of high-quality content that can directly improve patient clinical outcomes. To improve safety, quality of care, and patient-centered outcomes, the prehospital educational system leverages certification as an independent validation to confirm provider knowledge, skills, and abilities. Though structures have been described for integrating evidence into continuing professional development, one continued theme is that timely information transfer from the release of new evidence to integration into teaching at the initial certification level is a significant barrier. Educators often depend on textbook manufacturers for content since this is one of the primary training tools used in the classroom setting. Still, with the current pace of new medical knowledge generation , the challenge for timely evidence integration into initial education is great. The structured paradigm for identifying high-quality evidence outlined in this manuscript can improve the process.This work is the first example of a systematic structure to guide new evidence integration into prehospital education and testing. Prior work has demonstrated that inconsistencies in evidence integration into clinical practice can lead to inappropriate or unsafe care.The developed Table of Evidence also addresses another challenge noted by the TF: variability in the quality of evidence available to EMS clinicians. As listed in Table  The PGC has also defined gaps in the content of prehospital guidelines that could improve patient outcomes. Applying structured approaches to primary source material can help identify high-quality evidence and prioritize implementing new knowledge by applying the Table of Evidence.One critical next step the TF noted is to begin categorizing evidence applicable to prehospital care using the Table of Evidence. For prehospital EBGs, the PGC has curated a repository of EBGs and has reviewed the quality of evidence evaluation and development of recommendations for prehospital care within these guidelines.The analysis has several limitations, with many associated with the Delphi method. First, due to COVID-19, much of the TF’s work was done using electronic mail, online meetings, and survey platforms. However, the researchers leveraged serial debriefings in each round to manage possible limitations in electronic communications. Additionally, the consensus decisions reached by this group of subject matter experts result from their backgrounds and experiences in EMS. Therefore, it is possible that a different group of experts may have generated a different outcome for the Table of Evidence. Lastly, validation of the Table of Evidence framework for facilitating evidence integration into educational program curricula and continued competency platforms is an important future initiative.A Task Force of prehospital experts developed a Table of Evidence that will provide national, state, and local agencies with a more transparent mechanism for integrating new evidence into certification examinations and educational guidelines. Additionally, this framework places value on the immediate integration of high-quality content and a process for timely updates to educational curricula.


This is the first study to assess Egyptian dental practitioners’ knowledge about conservative caries management approaches and investigate whether this knowledge transfers into clinical practice and the barriers to translating research into evidence-based practice.A sample of dental practitioners was surveyed using an online questionnaire. Convenience and snowball sampling were used to collect data from February to June 2022. We included graduated dentists from Egyptian universities who practiced in Egypt. Data were analyzed with descriptive statistics, and the associations between variables were checked using Kruskal Wallis and Chi-Square tests.p = 0.002) and between specialization and tools used to detect carious lesions (p < 0.001). Most participants (59.1%) used G.V Black’s classification, and (80.8%) removed caries based on the feature of dentin hardness and color, whereas (67%) removed caries until hard dentine remained. The participants’ primary hurdle to staying up-to-date was their belief that the newly gained information would not be clinically applicable due to a lack of equipment or working in low-economic areas. Patient-related barriers were the major obstacles for participants in implementing evidence-based practice.This study included 396 participants from throughout Egypt. There were significant correlations between specialty and participants’ knowledge and behaviors toward evidence-based caries management (Egyptian dentists did not fully embrace minimal invasive approaches for caries management, and practitioners’ experiences continue to shape decision-making. It emphasizes the imperative to practically educate dentists using effective knowledge translation dissemination to promote evidence adoption in daily practice and advocate value-based dental care to address the economic crisis’s impact on Egypt’s healthcare.The online version contains supplementary material available at 10.1186/s12903-023-03333-z. Dental caries remains a significant health problem worldwide , affectiCaries-management concepts have shifted substantially in recent years towards a deeper understanding of caries’ pathophysiology and tissue healing capabilities, resulting in more conservative approaches , 11. MinIn the last decades, the evidence-based practice concept has emerged in dentistry in responding to the imperative to improve the quality of standard patient care –18, whicStill, there is a big gap between research evidence and dental practice that leads to the loss of the evidence-based practice value in patient dental care , 26, refThis study followed the STROBE guidelines for reporting cross-sectional observational studies . The stuThe questionnaire included several question styles . After reviewing published cariology surveys, we designed these questions to assess three primary areas: knowledge Questions evaluating participants’ knowledge and behavior toward caries management in terms of evidence-based practice.Questions about participants’ behavior toward continuing education and keeping up-to-date on cariology and restorative dentistry, as well as the barriers to doing so.Questions about participants’ attitudes towards evidence-based dentistry and their barriers to establishing an evidence-based practice.Convenience and snowball sampling were performed. We contacted university course directors, inviting them to complete and distribute the questionnaire to their residents, intern, and postgraduate students. Also, we used social media platforms to reach general practitioners and cover dental professionals throughout Egypt. The survey was opened in February and closed in June of 2022. We included graduated dentists with a bachelor’s or higher degree from Egyptian universities who practiced in Egypt. We excluded undergraduate students and dentists who obtained their undergraduate qualification abroad or practiced outside Egypt.While World Health Organization (WHO) estimated the number of dentists in Egypt to be 32,848 in December 2018 , the Egyp < 0.05. All statistical analyses were performed using SPSS 28 .Descriptive statistics were used to present the demographic characteristics of the participants and their questionnaire responses as frequencies and percentages for categorical variables. Kruskal Wallis and Chi-Square tests were performed for group comparisons according to the respective data. Statistically significant differences were assumed if Due to the nature of our recruitment methods (respondent-driven sampling), we could not estimate the total number of dental professionals who received our survey invitation. Among the 410 questionnaires received, 14 were excluded because they did not meet the eligibility criteria; ten obtained their bachelor’s degree abroad, three were duplicated, and one had incomplete responses. After excluding these invalid responses, we included 396 individuals from throughout Egypt (44.9% men and 63.1% women), with 44.9% being practicing dentists, 20.5% intern students, 16.4% academics , 13.6% postgraduate students, and 4.5% residents. The majority (71.5%) graduated from public universities; 28.5% graduated from private universities. 49.2% were general practitioners, 17.7% restorative dentistry specialists, and 12.6% specialized in oral and maxillofacial surgery or prosthodontics. Most participants (82.6%) worked in capitals, with 8.3% in the delta region, 6.1% in upper Egypt, and 1.5% in the east. 53.5% worked in the public sector and 46.5% in the private sector. 65.2% of participants had a BDS degree, 34.8% a postgraduate degree . (Table p = 0.002), with restorative dentists having a higher median score  than oral medicine, pathology, and radiology specialists , oral and maxillofacial surgery and prosthodontics specialists , and general practitioners  (Appendix Table p < 0.001) since oral medicine, pathology, and radiology dentists (88.9%) used visual and tactile examination to detect carious lesions more than other disciplines, while academics (60.0%) used visual-tactile and radiographic examination. Additionally, the percentage of dentists who used caries-detector dyes to detect carious lesions was higher in endodontists (11.1%) than in other specialties; also, those who used recent diagnostic tools to detect carious lesions were higher in endodontists (7.4%) (Appendix Table Table p < 0.001) since the dentists who believed that and pursued postgraduate education were 94.9%. Also, there was a significant correlation between that belief and years since graduation (p < 0.001), as 96.4% of dentists who believed that there had been a significant change in the operative dental practice had 10 to 14 years following graduation (96.4%) , and 26.5% preferred the in-person courses and workshops to stay up-to-date with cariology and restorative dentistry Table . Howeverp < 0.001), as the participants who did not pursue postgraduate education and found it difficult were 43.4%; in contrast, those who disagreed and took a postgraduate education were 47.1%. Furthermore, there was a significant correlation between postgraduate education and the feeling that some evidence-based information is time-consuming and not clinically applicable in daily practice (p = 0.001) since the participants who agreed with that and did not pursue postgraduate education were 45.3%; in contrast, participants who disagreed and took a postgraduate education were 30.4% (and 8.7% strongly disagreed) (Appendix Table Most participants agreed that it is difficult to find a trusted source for evidence-based information 41.9%) and hard to understand the results of scientific articles due to the statistical portion 38.9%). They also agreed that the evidence-based information is time-consuming, not clinically applicable in daily practice (39.6%), and not clinically applicable due to the economic burden (44.7%). The main barrier to establishing an evidence-based practice in cariology and restorative dentistry for 32.1% of participants was the financial barrier, followed by the inability of participants to find trusted information (16.9%)  removed caries based on the feature of dentin hardness and color, and (about 67%) removed caries in small to moderate-sized cavities until hard dentine remained. Such behavior relies on the correlation between bacterial count and dentin hardness , 42; henThe results revealed that most practitioners (more than 52.3%) still relied on the conventional approach of removing all soft dentine and considered step-wise excavation the best treatment for deep lesions (around 63.4%). Such an approach raises the risk of pulp exposure and issues; pulp exposure treatment is costly and may compromise tooth longevity; still, it is either invasive or unsuccessful in the long term –47. HoweWithout a doubt, the main goal of healthcare practitioners is to provide patients with the best possible care. Although several studies assessed dental students’ and practitioners’ understanding of conservative caries management approaches, they were focused mainly on the knowledge and its implication on daily practice –56. HoweThe main barrier for 62.7% of participants to update their knowledge was that the newly gained information would not be clinically applicable due to a lack of equipment or working in a low-economic area. This misconception stems from the common belief that evidence-based practice is synonymous with more scientific and expensive practice, contrary to the purpose of evidence-based practice: patient-centered and empirically grounded care to provide optimal clinical decisions , 60. SucPatient-related barriers  were the major obstacles for participants in implementing evidence-based practice. Such barriers are rational and supposed to increase globally due to the rise in living costs and economic crisis, often affecting the patient’s dental care and preferences , 69. ThiThis study has some limitations; first, this research is based on quantitative evaluations by collecting data using an electronic survey; hence, it could not provide a deeper understanding of the participant’s knowledge and the barriers and enablers of implementing evidence-based dental practice in Egypt. Second, participants were recruited using non-probability sampling methods since this study was the first to be done about the cariology and evidence-based dentistry era in Egypt. Therefore, more population-based surveys and qualitative studies are needed to support these findings, provide a deeper grasp of the participants’ knowledge and barriers and enablers of the evidence-based dental practice, and further explain the reasons behind their behaviors.In Egypt dental practices, some conventional concepts  remain prevalent, and practitioners’ experience and familiarity are still predominant in shaping clinical decision-making. Practitioners could not utilize research evidence in their dental practice due to some patient-related  and evidence-related  barriers. As a result, it emphasizes the imperative of practically teaching dental practitioners in minimal intervention approaches through effective research knowledge translation means rather than written materials and guidelines, as well as the prioritization of dental research and advocating value-based dental care to address the economic crisis’s impact on Egypt’s healthcare.Below is the link to the electronic supplementary material.Supplementary Material 1Supplementary Material 2