The non-prescription antibiotics dispensing (NPAD) from pharmacies is on the rise in low- and middle-income countries, which contributes to the emergence of antimicrobial resistance (AMR). This study was conducted with the objective to determine the community pharmacy personnel’s perspectives on NPAD and its implications for AMR.A questionnaire-based cross-sectional survey was conducted in Pakistan among 336 pharmacies. The data were analyzed using SPSS v21 and MedCalc for Windows v12.3.0. Modified Bloom’s cut-off point was utilized to categorize the participants’ overall knowledge, attitude, and practice. For univariable logistic regression analyses, odds ratio (OR) was calculated at 95% confidence interval (CI). For multivariable logistic regression analyses, adjusted OR was calculated at 95% CI. Spearman’s rank correlation coefficient test was used to assess the relationships among knowledge, attitude, and/or practice scores.ρ: 0.280; P <0.001) and total attitude and practice  scores were significantly correlated.The majority of the respondents were staff pharmacists (45.5%). About four-fifths (78.9%) and half (50.9%) of the participants demonstrated moderate to good knowledge and practice, respectively. However, about only one-third (33.1%) had a moderate to good attitude. Staff pharmacists had higher odds of moderate to good knowledge  and practice . Total knowledge and practice (Spearman’s The qualified pharmacists had satisfactory knowledge, attitude, and practices toward antibiotics. However, non-pharmacist staff lacked knowledge and had probable NPAD practice, which has a negative impact on public health. Regular refresher training, seminars, and strict enforcement of rules and regulations are essential. HighlightsCommunity pharmacy should be practiced under the proper leadership of qualified pharmacists.The educational intervention, regular refresher trainings, and exercises on the rational use of medicines, as well as the practice of professionalism for community pharmacy personnel, help ensure better practice.Already existing laws must be revitalized and strictly practiced to discourage the dispensing of non-prescription antibiotics.2. The World Health Organization (WHO) has recognized the importance of resistance for a long time; therefore, in 2001, Global Strategy for Containment of Antimicrobial Resistance provided a framework of interventions to slow the emergence of resistance and reduce its spread3. Resistance to antimicrobials has been declared a global emergency; therefore, in May 2015, the 68th World Health Assembly endorsed a Global Action Plan (GAP) to combat antimicrobial resistance (AMR) and control further escalation in the trend4. The incidence of resistance to antibiotics is more prevalent in developing countries due to poor enforcement of laws and a lack of substantial surveillance systems5. This can be attributed to irrational use of antibiotics such as unnecessary, suboptimal , and extensive use of broad-spectrum antibiotics7.The appearance of resistance to antibiotics is one of the greatest threats to public health, responsible for increased morbidity and mortality as well as increased healthcare costs8, as it is believed to be a convenient, time-saving, and cheap way of obtaining the drugs without a physician’s consultation9, consequently promoting the irrational practice which has long-term effects on patient’s health10.In low- and middle-income countries (LMICs), dispensing antibiotics without a prescription is a common trend11. The healthcare system of Pakistan is under a constantly increasing burden of both communicable as well as non-communicable diseases, and a majority of healthcare spending is out of pocket13. In this context, the public finds it easy to get their medicines from local retail drug stores or pharmacies without having a legitimate prescription from a medical practitioner. Even antibiotics can be acquired as over-the-counter (OTC) medicines. A large number of broad-spectrum antibiotics dispensed through community pharmacies subsequently leading to antibiotic resistance has been documented in the literature14. The easy availability of antibiotics without prescription is assigned to poor affordability of the public to seek physician’s advice, previous experience with the same antibiotic, and poor enforcement of the prevailing laws such as Drug Sale Rules as well as Drug Regulatory Authority of Pakistan (DRAP) Act 201216.Pakistan is the sixth most populous country and is categorized as LMIC with a Human Development Index (HDI) value of 0.56017. The Drug Sale Rules 200715 are intended to regular the functioning of the pharmacies and ensure the provision of quality medicines to patients. These rules mandate the sale of drugs under the strict supervision of a qualified, registered, and licensed pharmacist15. Pakistan has endorsed the National Action Plan, 2017, for the containment of AMR, which includes seven key strategic priorities, operational plans, interventions, essential indicators of monitoring, and an evaluation framework18.As far as the policy perspective in Pakistan is concerned, the Drug Act 1976/DRAP Act 2012 provides the legislative impetus for the sale of medicines only under the supervision of a registered pharmacistThe present study aims to evaluate the knowledge, attitude, and practices of the community pharmacy staff about the non-prescription dispensing of antibiotics in the city of Lahore, Pakistan.The research has been performed in accordance with the Declaration of Helsinki. The ethics approval was obtained from the Institution. All the participants were made aware of their voluntary participation and confidentiality prior to the data collection. Informed consent to participate in the study was obtained from the participants.A cross-sectional study was carried out in community pharmacies in Lahore, Pakistan, from January 2019 to September 2019, principally targeting antibiotics dispensing practice from the community pharmacy personnel without prescription.19.It was conducted in accordance with the criteria of STROCSS 202123. It comprised four sections: demographics of participants, knowledge, attitude, and practices of antibiotic dispensing. The knowledge section was based on the concept of the participants. The attitude section proclaims the thinking of the participant. The practice section presents what the respondents perform. Both attitude and practice sections contained statements on a five-point Likert scale. The statements that opposed the notion of knowledge, attitude, and practices were graded 5 points for strongly disagree and 1 point for strongly agree responses. Accordingly, the rest of the responses of disagree, unsure, and agree to 4, 3, and 2 points in decreasing order, respectively. Similarly, the statements that supported the notion of knowledge, attitude, and practices were graded 1 point for strongly disagree and 5 points for strongly agree responses. The rest of the responses were graded accordingly: 2, 3, and 4 for disagree, unsure, and agree responses, respectively.A questionnaire was developed based on the in-depth literature review and the current prevalent practices in community pharmaciesα value of 0.80.The face and content validity of the questionnaire was carried out by three experts at the university. The reliability analysis yielded a Cronbach 24. The maximum knowledge score is 6 and ≥60% of 6 (≥3.6) was considered a moderate to good knowledge score. The maximum attitude score is 40 and ≥60% of 40 (≥24) was considered moderate to a good attitude. Similarly, the maximum practice score is 40 and ≥60% of 40 (≥24) was considered moderate to good practice.Participants’ overall knowledge, behavior, and practice were categorized using Bloom’s cut-off point (as the score is moderate to good if ≥60% and poor if <60%)25, the sample size was 347 pharmacies. It was the number of pharmacies selected rather than the staff. Pharmacies were selected by stratified random sampling based on the administrative towns of Lahore, each town representing one stratum. Simple random sampling was employed in each town to identify the individual pharmacies to be visited. Any person first contacted (staff) at the time of visit was considered a respondent of the study; it could be a pharmacist, technician, dispenser, assistant, or pharmacy manager. Due to the incomplete data and the problem in getting consent, the non-response rate was found to be 3%. Therefore, a total of 336 samples were considered for inclusion in the study . For 3500 pharmacies in Lahoredy Table . The oveχ2 test was used to test for group differences. For binary logistic regression analyses, the odds ratio (OR) was calculated at 95% CI. Multivariable logistic regression was used to determine independent factors associated with moderate to good knowledge, attitude, and practice , and the adjusted odds ratio (AOR) was calculated at 95% CI. Box plots were drawn for the distribution of knowledge, attitude, and practice scores based on education level and areas of work. Spearman’s rank correlation coefficient test was used to assess the relationships among the knowledge, attitude, and/or practice scores.Data were analyzed by IBM SPSS v21. MedCalc for Windows v 12.3.0  was also utilized for further analysis. The total and mean scores of knowledge, attitude, and practice were calculated and recorded into different categorical variables: the moderate to good and poor score groups for each knowledge, attitude, and practice. Socio-demographic characteristics of participants were presented as frequency and proportions. The n=284). Most of the respondents were staff pharmacists, 45.5% (n=153), whereas 35.7% (n=120) were managers. Only 18.8% (n=63) were technicians. The majority of the respondents had an experience of fewer than 2 years, 34.8% (n=117), while 24.1% (n=81) were of 6–10 years of experience and 20.8% (n=70) were of 3–5 years of experience. The majority of the respondents had a bachelor’s degree in pharmacy science , followed by intermediates , and then graduate/master  . The median knowledge score was 5 (25th to 75th percentiles: 4–6). About four-fifths of the participants  had moderate to good knowledge. Male participants had lower odds of good knowledge  than females. Similarly, staff pharmacists had higher odds of moderate to good knowledge  than managers. Participants with an educational level of bachelor’s and/or above in pharmacy had 4.1 times higher odds of good to moderate knowledge  than those with intermediate or diploma in pharmacy  than technicians.In multivariable regression model, managers had higher odds of moderate to good knowledge . The median attitude score was 21 (25th to 75th percentiles: 18–25). About one-third of the participants  had a moderate to good attitude. Neither of the socio-demographic factors was the independent predictor of moderate to good attitudes . The median attitude score was 24 (25th to 75th percentiles: 20–27.8). About half of the participants  had moderate to good practice. Age more than 28 years , male participants , married participants , and experience duration more than 6 years  had lower odds of moderate to good practice. However, staff pharmacists  as compared to managers and educational level bachelor and/or above in pharmacy  had higher odds of moderate to good practice  than unmarried participants.Those participants with bachelor’s and above educational levels had higher median knowledge and practice scores as compared to those with lower educational levels (Intermediate/Diploma in Pharmacy). However, the median attitude scores were comparable across the two groups based on educational level Fig. .Those participants with 6 or more years of experience had lower median knowledge and practice scores as compared to those with 5 or fewer years of experience. However, the median attitude scores were comparable across the two groups based on experience duration Fig. .ρ: −0.052; P-value: 0.345). However, there was a significant correlation between total knowledge and practice scores , and total attitude and practice scores .There was no correlation between total knowledge and attitude scores  is also considered a relevant factor to deal with. It contributes substantially to the prevalence of AMR globally, both in the community and hospital settingsOut of 336 pharmacies visited, a majority had pharmacy graduates (56.8%) holding either a doctor of pharmacy (Pharm.D) or a bachelor of pharmacy (B.Pharm) degree working either as a manager or staff pharmacist while 43.2% of pharmacies visited had technicians or other pharmacy staff. The majority of the pharmacy staff, including pharmacists, had less than 2 years of experience. The unavailability of licensed pharmacists in the pharmacy might contribute to the NPAD resulting in the injudicious use of antibiotics that may lead to an increase in antibiotic resistance.35.In Pakistan, the medicine stores are, to some extent, run by non-technical personnel and pharmacy technicians. The government has given a grace period of 10 years to upgrade their medicine stores to pharmacies. In addition to that, these sale rules have categorized the medicines into different schedules namely A, B, C, G, and F. The medicines included in Schedule-G are those which are to be sold under the strict supervision of a qualified pharmacist, and this schedule includes antibiotics, biologics, blood products, and vaccines. A non-technical person or a technician cannot sell these medicines as per the rulesDespite the drug-related rules and regulations like Drug Act 1976, DRAP Act 2012, and Drug Sale Rules 2007 being in place, the sales of antibiotics are poorly regulated because of poor enforcement by the concerned authority. This consequently leads to dispensing antibiotics without the prescription of a registered medical practitioner.36. Our study revealed that 75% of the pharmacy staff were well aware of the PoM status of antibiotics. The majority of the respondents (75.9%) in this study agreed that antibiotic resistance is a serious public health problem. However, dispensers usually dispense antibiotics as OTC even though having known the PoM status. It is, therefore, necessary that the PoM status of antibiotics should be enforced especially concerning the sales from community pharmacies, to create an enabling environment for healthy behavior. A coordinated approach amongst stakeholders, including healthcare workers, patients, and policy-makers, on the issue of antibiotics sales and use is required37. Therefore, a multipronged approach with intra- as well as inter-professional coordination (IPC) can ensure compliance with the National Action Plan on AMR.Knowledge of the participants, and staff pharmacists, on antibiotic use and dispensing was satisfactory. However, a fair portion of managers and technicians depicted poor knowledge, which may add to the unnecessary and over-dispensing of antibiotics from such personnel38. Different studies across the globe evince a good perception of pharmacy staff regarding the use of antibiotics, but still, they do dispense without a physician’s order without any reluctance39. Our findings are found coherent with these facts. Results showed a prominent agreement of proper guidance of patients regarding the disease state of the patient, drug interactions, and emphasis on the complete course of antibiotics treatment, which is contradictory to the findings of Asian countries as retrieved by the public opinion about practices of pharmacy staff, especially the pharmacists40. About one-third of the respondents stated to dispense antibiotics even for self-limiting and viral infections, which is irrational. On average, more than half of the respondents agreed to provide antibiotics for infectious diseases if the patient gives a direct visit to their pharmacy as soon as the symptoms appear, where only pharmaceutical treatment of symptoms can bring relief. The view of respondents in our study coincided with the fact that there is a need for proper laboratory tests for pathogen identification and sensitivity analysis for initiating antibiotics, but their practice of NPAD does not match this. Such practice accounts for the irrational use of antibiotics in the community as indicated by National Institute for Health & Care Excellence (NICE) guidelines41. Moreover, guidelines suggest using diagnostic tools for assessing the severity of the disease, which will eventually reduce the overuse of antibiotics and avoid the emergence of resistance44.The moderate to good attitude demonstrated by only one-third (33.1%) of the respondents indicates the chances of misuse of antibiotics by pharmacy staff. It demands a need for refresher training and workshops on the rational use of drugs and the practice of professionalism among the pharmacy staff. A difference of opinion is detected among respondents on whether to use antibiotics for minor ailments or not. A good portion of participants stated that antibiotics dispensing without prescription renders ease to patients who visit pharmacies and for those who find it difficult to access healthcare facilities either due to lack of time or affordability45. Good pharmacy practice (GPP) is a landmark standard for achieving rational, cost-effective, and responsible use of medicines to counter the abuse of antibiotics and halt AMR. In Pakistan, regarding AMR, the Ministry of National Health Services Regulations & Coordination Government of Pakistan (MNHSRC) devised a National Action Plan in the year 2017, in which weak curricula of professional education and lack of AMR awareness among professionals are pinpointed as weaknesses of the system18. Our findings are in line with the results presented in a study conducted among the physicians of Lahore, which iterates awareness about antibiotics to all the stakeholders of the healthcare profession46. The study demonstrated that low-dose and extensive use of broad-spectrum antimicrobials due to ease of access from pharmacies is responsible for high rates of AMR in Pakistan46. Another study conducted by Saleem et al.14 in Lahore demonstrated that co-amoxiclav, levofloxacin, ciprofloxacin, and third-generation cephalosporins were among the most widely consumed antimicrobials from private healthcare institutions and pharmacies. If the use of such antimicrobials goes unchecked, it results in more resistant strains of microorganisms such as the outbreak of extensively drug-resistant (XDR) Typhoid in Hyderabad, Pakistan, in 201647.Interventions are always a choice for improvement48. In this context, the role of health authorities is very important; the Government of Pakistan should prioritize the issue of escalating AMR and formulate its containment strategies; however, there have not been sufficient resources allocated so far for this49. Efforts should be made to educate healthcare professionals who deal with drugs, such as pharmacists and physicians, regarding the appropriate use of antibiotics to reduce the likelihood of AMR50. Moreover, pharmacists should be present in the pharmacies and should educate the visitors about self-care and AMR as well. The patients or the public also need to be educated about the use of antibiotics upon prescription by a registered medical practitioner51.According to a broad brush estimate of the global economic cost of antimicrobial drug resistance by 2050, the continually escalated resistance by 2050 will contribute to the death of 10 million people per year. There will be a reduction of 2–3.5% in Gross Domestic Product (GDP), which would cost the world up to 100 trillion United States DollarsThis study signifies the importance of pharmacists and other staff involved in dispensing antibiotics at community pharmacies. The study setting is the second-largest city in LMIC Pakistan. The city is the center of culture, business, and education and has a structured and well-defined network of pharmacies with the highest number of pharmacists. Therefore, the generalizability of the study may not be ensured in rural areas and other countries with different health setups. Also, the respondents tend to provide socially desirable responses when they know their practices are being evaluated and may also not mention true practices, which is an inherent bias in the questionnaire-based study.The overall knowledge and practices of pharmacists working in pharmacies regarding dispensing of antibiotics were satisfactory, while staff other than pharmacists were mostly responsible for non-prescription dispensing of antibiotics in various conditions. Therefore, regular refresher training, tabletop exercises, and workshops on the rational use of medicines and the practice of professionalism must be conducted for the pharmacy personnel. Educational interventions are required for the public as well. The presence of a pharmacist should be made mandatory at all pharmacies, and strict enforcement of the DRAP Act 2012 and Drug Sale Rules 2007 is required for the rational use of medicines.The research has been performed in accordance with the Declaration of Helsinki. The ethics approval was granted by the Humans Ethics Committee (HEC) University College of Pharmacy, University of the Punjab, Lahore (No: HEC/UCP/2045-19).All the participants were made aware of their voluntary participation and confidentiality prior to the data collection. Written informed consent was obtained from the participants for publication and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.This article did not receive any kind of grants.F.K.H.: conceptualization, methodology, investigation, supervision, and writing – original draft; S.K.: conceptualization, methodology, formal analysis, and writing – original draft; G.K.Y.: data curation, formal analysis, methodology, and writing – original draft; M.M.K. and S.U.K.: data curation, investigation, and writing – original draft; H.S. and M.S.: investigation, visualization, and writing – review and editing; S.G.: formal analysis, methodology, and writing – review and editing; M.F.R. and H.H.M.: investigation, supervision, and writing – review and editing; Z.R.: methodology, formal analysis, and writing – review and editing.The author declare no conflicts of interest.Name of the registry: Research Registry.Unique identifying number or registration ID: Researchregistry9005.https://www.researchregistry.com/browse-the-registry#home/registrationdetails/645a6e66d054c200294aa708/.Hyperlink to specific registration (must be publicly accessible and will be checked): Sitaram Khadka, E-mail: sitaram.khadka@naihs.edu.np; Tel.: +977-9851077589. Address: Shree Birendra Hospital, Nepalese Army Institute of Health Sciences, Kathmandu, Nepal.The data are available through the corresponding author on reasonable request.All authors agree to the publication of the peer-review file for transparency.


To develop and validate an artificial intelligence diagnostic system based on X-ray imaging data for diagnosing vertebral compression fractures (VCFs)In total, 1904 patients who underwent X-ray at four independent hospitals were retrospectively (n=1847) and prospectively (n=57) enrolled. The participants were separated into a development cohort, a prospective test cohort and three external test cohorts. The proposed model used a transfer learning method based on the ResNet-18 architecture. The diagnostic performance of the model was evaluated using receiver operating characteristic curve (ROC) analysis and validated using a prospective validation set and three external sets. The performance of the model was compared with three degrees of musculoskeletal expertise: expert, competent, and trainee.The diagnostic accuracy for identifying compression fractures was 0.850 in the testing set, 0.829 in the prospective set, and ranged from 0.757 to 0.832 in the three external validation sets. In the human and deep learning (DL) collaboration dataset, the area under the ROC curves(AUCs) in acute, chronic, and pathological compression fractures were as follows: 0.780, 0.809, 0.734 for the DL model; 0.573, 0.618, 0.541 for the trainee radiologist; 0.701, 0.782, 0.665 for the competent radiologist; 0.707,0.732, 0.667 for the expert radiologist; 0.722, 0.744, 0.610 for the DL and trainee; 0.767, 0.779, 0.729 for the DL and competent; 0.801, 0.825, 0.751 for the DL and expert radiologist. Our study offers a high-accuracy multi-class deep learning model which could assist community-based hospitals in improving the diagnostic accuracy of VCFs. Vertebral compression fractures (VCFs) are common diseases that seriously affect human life and pose a very large challenge to the health care system . With thIn recent years, the incidence of back pain due to compression fractures has increased in patients. Many imaging methods are available for early screening and differentiation of compression fractures, such as X-ray (XR) images, Computed tomography (CT) and magnetic resonance imaging (MRI). Among these procedures, CT is the modality of choice for the evaluation of bone structure and fragments. MRI may be the most useful imaging technique based on its excellent soft tissue contrast that shows the change in the signal intensity and morphological characteristics of the collapsed vertebrae. Acute compression fractures show hyperintensity with bone marrow edema, while chronic compression fractures show no bone marrow edema and are isointense on T2WI fat-suppression sequences. The pathologic VCFs shows low signal intensity on T1WI, isointensity or high signal intensity on T2WI, and homogeneous or inhomogeneous enhancement Figure 1Deep learning (DL), a branch of machine learning, has already shown potential for assisting humans in various medical fields –6. A conThus, the aims of this study were to develop an X-ray-based deep learning model using a four-center dataset and determine whether the model could distinguish the type of VCFs and validate these findings in an independent external cohort.This multicohort diagnostic study was performed with data from four hospitals in China. This study was approved by the institutional review board and ethics committee of the hospital (IRB 2022-108-01). Our retrospective study was approved by the institutional review board of the hospitals with a waiver for written informed consent. Patients in the prospective validation set of compression fractures provided written informed consent prior to participation.Site 1 from 1 January 2014 to 31 October 2021 to determine acute, chronic, and pathological compression fractures. The inclusion criteria were as follows: (1) less than 2 weeks between Digital radiography (DR) and MRI examinations; and (2) the height of the vertebral body was reduced by at least 20% or 4 mm from the baseline height on the lateral radiography of the lumbar spine  or histopathological results. When only MR images are available for a patient, at least two senior diagnosing physicians complete the diagnosis.https://pypi.org/project/labelImg/) and annotated (224×224) (Lesion regions of interest (ROIs) were manually represented with bounding boxes on lateral radiographs of the lumbar spine by an experienced radiologist using the LabelImg software (224×224) Figure 3The images from the development dataset were randomly assigned with a ratio of 8:2 for the training datasets (the deep learning model for compression fracture classification) and the testing datasets . The image of the training set was enhanced, using horizontal flips, vertical flips, and rotations at random angles.ResNet is a type of CNN where the input from the previous layer is added to the output of the current layer. This skip connection makes it easier for the network to learn and brings better performance. The ResNet architecture has been successful in many tasks, including image classification, objection detection, and semantic segmentation. In addition, because ResNet is composed of layers, these networks can obtain any level of spatial representation at any depth. Each ResNet block has 2 convolutional layers , and we connect these two residual blocks as a module. We use 4 such modules, so there are a total of 16 convolutional layers Figure 4https://github.com/Xiongyuchao/VCFNet.In this study, we used the ResNet-18 architecture model, and the input image was resized to 224 × 224 pixels and was normalized with mean=  and std= . We then fine-tuned the model using a dataset of lateral lumbar spine radiographs of acute, chronic, and pathological compression fractures. Codes are available at Site 1.We first validated the performance of the model in classifying VCFs using the testing dataset. We then evaluated the robustness of this model using an external validation dataset from three participating hospitals. Finally, the model was evaluated using prospective data including 74 vertebrae of 57 patients from In addition to the classification research of independent observers, the collaborative research of human and deep learning was also carried out to simulate a real clinical setting. We randomly selected 30% of the images from all external validation sets as the “collaboration dataset”. Three radiologists with different levels of expertise  were asked to independently complete the same test images and compare their results with those of the model. Then the three radiologists reevaluated all the same test images independently after knowing the DL-model diagnosis. These radiologists were not involved in the selection and labeling of images, and the images were obfuscated and unidentified prior to evaluation. The expert radiologist was a professor with more than 20 years of experience in musculoskeletal diagnosis. The competent radiologist was a radiologist with 7 years of experience and completed standardized training for practicing physicians. The trainee is a radiologist with 2 years of experience and obtained the qualification certificate of a licensed doctor.https://github.com/Xiongyuchao/VCFNet). We used receiver operating characteristic (ROC) curves to demonstrate the ability of deep learning algorithms to classify VCFs. An ROC curve is generated by plotting the ratio of true positive cases (sensitivity) to false positive cases (1-specificity) by varying the predicted probability threshold. A larger area under the ROC curve (AUC) indicates better diagnostic performance.All computer codes used for data analysis are stored in GitHub, 0.899  and 0.935  in the testing dataset, respectively; 0.803 , 0.906  and 0.769  in the GZFPH dataset, respectively; 0.779 , 0.798  and 0.903  in the WHTH dataset; 0.807 , 0.836  and 0.796  in the HB672H dataset, respectively.vs. 0.667, 0.653 vs. 0.727, and 0.673 vs. 0.776, respectively). For the classification of pathological compression fractures, the sensitivity of expert radiologists was up to 0.385 and the deep learning model was only 0.308. However, when combined with the deep learning model, the expert radiologist, competent radiologist, and trainee radiologist all had increased sensitivity to pathological compression fracture   Figure 6In this multicenter study, we successfully developed a classification model for acute, chronic and pathological compression fractures by using deep learning neural networks. The model demonstrated high accuracy and specificity in classifying compression fractures in retrospectively stored images as well as in a prospective observational setting. Furthermore, the diagnostic efficiency of deep learning model is higher than that of the trainee radiologists, similar to the competent radiologist, and slightly lower than the expert radiologist. The deep learning model combined with all three expertise levels of radiologists significantly improved the accuracy, specificity, and sensitivity of evaluating compression fractures. To the best of our knowledge, this is the first multicenter study to apply deep learning with CNNs to the classification of acute, chronic, and pathological compression fractures.Previous studies have used information from radiographs to classify compression fractures. Usually, plain radiographs are initially performed to diagnose acute compression fractures by observing small changes such as endplate rupture and anterior wall protrusion  and diagThe classification sensitivity of pathological compression fractures was found to be low for all three radiologists and the deep learning model. Even the combination of all three radiologists and the deep learning model was still low. In addition, 6 vertebrae with pathological compression fractures were misdiagnosed by all three radiologists and the deep learning model. We speculate that the main reasons for these false negatives are the low contrast of X-ray images, the fact that there were no obvious signs of bone damage on the vertebral body, intestinal gas interference and bilateral shadows of the vertebral body, which may be an insurmountable limitation caused by the principle of X-ray imaging. However, deep learning model-assisted diagnosis can improve the sensitivity of pathological compression fracture classification, albeit still at a low level. Furthermore, given the high accuracy of classification of acute and chronic compression fractures, deep learning could be considered cost-effective.There are few studies on compression fractures using deep learning methods, especially based on conventional X-ray images. Only one study used deep learning to evaluate acute and chronic compression fractures on radiographs, which included 1099 patients and used image data from anteroposterior and lateral lumbar spine radiographs as input to a neural network. This study achieved a sensitivity, specificity and AUC of 0.80, 0.68, and 0.80, respectively . The cliDespite these remarkable results, our study has some limitations. First, the subjects who received internal fixation or cementation or who presented with severe scoliosis/deformity were excluded in the development dataset, which may lead to bias. Second, from the nature of CNNs, since a neural network only provides a classification of an image and associated compression fractures, there is no explicit feature definition. Third, the ROIs of the compression fracture were delineated by a manual rectangle. The training of the model relies on the accurate identification of compressed vertebral bodies by radiologists, which requires manual delineation by radiologists. Although there are some differences in the ROIs drawn by different doctors, they will be uniformly processed and then classified after the images are imported into the model. Currently ROI delineation could be finished using automatic, semi-automatic and hand-crafted methods. However, automatic and semi-automatic methods may have a certain deviation which need to be further adjusted manually. Fourth, due to the small numbers of pathological compression fractures in this study with low sensitivity, it is likely the features of pathological fracture might be different from the osteoporotic/traumatic compression fracture and will require a large and specific pathological database to clarify the utilization of deep learning model assistance. Therefore, more studies with larger numbers of patients are required to provide stronger evidence for the accuracy of deep learning models in the prediction of pathological compression fractures. Finally, deep learning model alone was not adequate to detect pathological compression fracture due to the absence of clinical information. Thus, the general applicability of our results in clinical practice could be affected. Clinical information is required in future study to validate the performance of deep learning models.In conclusion, a multiclass deep learning model for compression fractures on radiographs was developed and validated. The classification performance of the model surpassed that of trainee radiologists and was comparable to that of experienced radiologists. When the skills of the radiologists were combined with a deep learning model, better diagnostic performance was observed, which could improve the accuracy of diagnostic classification, thereby improving the diagnostic workflow for patients with compression fractures. We expect to establish an artificial intelligence-assisted diagnosis platform for compression fracture based on X-ray images to provide patients and clinicians with free access to telemedicine assistance, aiming to eliminate the diagnosis and treatment gap between national hospitals and grassroots hospitals.https://github.com/Xiongyuchao/VCFNet). The remaining data are included in the article/The excel files containing raw data included in the main figures and tables can be found in supplementary material. The lumbar spine X-ray imaging data and clinical information are not publicly available for patient privacy reasons but are available from the corresponding authors upon reasonable request . The models and the code used to test and evaluate the model is available on GitHub . The patients/participants provided their written informed consent to participate in this study.Conception and design: FX, YCX; acquisition of additional data: FX, YCX, GXY, YYL, QPD, WYJ, DLW, SC; analysis and interpretation of data: FX, YCX, GXY, ZPL, XWZ; statistical analysis: FX, YYL, GXY; drafting of the manuscript: FX, YCX; critical revision of the manuscript: FX, XWZ; study supervision: XWZ. All authors listed have contributed substantially to the design, data collection and analysis, and editing of the manuscript.


Assessing dietary intake is valuable both in clinical practice and in research. In research and in clinical practice, long-term habitual dietary intake is most often of interest. Therefore, a web-based semi-quantitative Food Frequency Questionnaire (FFQ) was developed to measure habitual intake of nutrients and foods.This study aimed to assess content validity, convergent validity, and reliability of a 32-item semi-quantitative FFQ for adults.A total of three different cohorts of Flemish adults were recruited in the past 10 years. The first cross-sectional validation study took place in 2013, consequently in 2019 and 2021. Content validity was assessed in 2019 through a semi-structured cognitive interview. Convergent validity was assessed by examining mean differences, Wilcoxon signed-rank test, Spearman's correlation coefficients (SCC), and Bland–Altman analysis for energy, nutrient, and food group intake compared with a 3-day food record (FR). Additionally, consumers-only analysis was performed together with cross-classification analysis by assessing the ranking capabilities of the FFQ into quartiles and weighted kappa. Reliability was assessed through the evaluation of SCC and intra-class correlation (ICC) of test–retest assessment of the FFQ.p <0.001 in 2013 and 2019).Spearman's correlation coefficient (SCC) for energy and absolute nutrient intake between the FFQ and the FR ranged from 0.02 to 0.54. Compared with absolute macronutrients, higher SCC was found for the majority of the relative macronutrient intake and most food groups. Bland–Altman plots showed improved agreement and decreasing bias between the FFQ and the FR over time. Misclassification of the FFQ for nutrients was acceptable and decreased over time , but weighted kappa remained mostly fair (κ ≤ 0.20). The reliability of the FFQ was good and improved over time (mean SCC of 0.65 and 0.66 The short web-based FFQ is an easy, low-cost, and feasible tool with good reliability, low misclassification, and acceptable validity to compare nutrient densities and food group intake at the population level. The measurement of absolute intake remains debatable. Assessing dietary intake is valuable both in clinical practice and in research. However, measuring an individual's dietary intake accurately is challenging. The dietary intake of an individual is highly variable due to day-to-day variation, seasonal variation, and the context an individual is in at the time of eating , 2. To aFood Frequency Questionnaires (FFQs) are amongst the most used methods to measure dietary intake in large epidemiological studies . While cThe self-administered semi-quantitative web-based FFQ was developed in Dutch and allows to measure dietary habits, dietary quality, and habitual intake of foods and nutrients during the past month in Belgian adults in both the clinical setting and nutritional research. This study describes the validation of this specific FFQ during the past decade in different cohorts and the improvement of the FFQ accordingly.This study applied the STROBE-NUT guidelines .This research is a sequential cross-sectional validation study of a web-based semi-quantitative Food Frequency Questionnaire (FFQ) in which data were collected in 2013, 2019, and 2021 including different cohorts of the Belgian population. Content validity, reliability, and convergent validity compared with a 3-day food record were assessed at the three different time periods. Convergent validity was assessed in all three studies by comparison with a 3-day food record , reliability was assessed by test–retest assessment in the cohorts of 2013 and 2019, and content validity was solely assessed in 2019 in a sample of 15 participants through a semi-cognitive interview.The studies were approved by the Medical Ethical Committee UZ Leuven (2013) or the Social and Societal Ethics Committee (SMEC) review board  and received registration numbers S54908, G-2017 12, and G-2021-2956, respectively. All participants provided their written informed consent prior to the start of the study. The study protocol of the three cohorts in the different time periods during the past decade is shown in To assess the validity and reliability of the FFQ, a sample size of each time of 100 participants was aimed for. The sample size was based on the recommendations by Cade et al. and Willet et al. stating that a sample size of minimum of 50 participants, preferably at least 100, is sufficient to assess the convergent validity of Food Frequency Questionnaires . The cohThe Food Frequency Questionnaire was developed to acquire standardized data on habitual dietary intake in adults during the past month. It is aimed to use a simple, quick, and low-cost method to assess dietary intake in epidemiological and nutritional studies within the general population in Flanders as well as in a clinical setting, hence its concise format. The FFQ was developed in Dutch (Belgium). The first version of the FFQ consisted of questions on the consumption of 27 food items, where frequency and amount consumed are administered in close-ended questions, based on a previous study –14. TablTo assess the content validity of the FFQ, a semi-structured cognitive interview was performed in 2019, as described by Patrick et al. , 18 Fig. During In all three cohorts, participants were asked to keep a food record for 3 non-consecutive days including 1 day during the weekend . In the * SD. Good agreement was interpreted as at least 95% of the data points lying within the limits of agreement in the BA plot. Reliability was examined by test–retest assessment of two administrations of the FFQ. Spearman's correlation coefficients and intra-class correlation coefficients (ICC) were calculated to assess the reliability of the FFQ, next to a Wilcoxon signed-rank test to examine the statistically significant difference between the mean of the two administrations of the FFQ. ICC was assessed in a two-way mixed-effects model considering absolute agreement for a single measurement, as recommended by Koo et al. for test–retest reliability assessment  registered daily were considered complete and included for analysis. Convergent validity was assessed by comparing mean differences and Spearman's correlation coefficients for energy, macronutrients, micronutrients, and food groups obtained from the FFQ with the mean intake obtained from the food records (FRs). Protein, total fatty acids, saturated fatty acids (SFA), monounsaturated fatty acids (MUFAs), polyunsaturated fatty acids (PUFAs), total carbohydrates, monosaccharides/disaccharides, and polysaccharides were expressed as energy densities , next to the absolute values, to adjust for energy intake. Similarly, micronutrients were expressed as relative values , next to the absolute values. Mean and standard error (SE) for intake of each nutrient and food group measured by the FFQ and the food record were calculated , S2. Sinsessment . Next, csessment . Finally.10 weak . ICCs we.10 weak . A P-valn = 11 (2013), n = 8 (2019), and n = 2 (2021)]. As previously described, participants with a self-reported energy intake lower than 500 or 800 kcal per day for women or men, respectively, or higher than 3,500 or 4,000 kcal per day for women and men, respectively, were excluded as well . The final samples for analysis included 100, 100, and 42 participants in the years 2013, 2019, and 2021, respectively. Only 37 out of 42 participants of the cohort of 2021 responded to the sociodemographic questionnaire. Characteristics of the study population are shown in 2 for the study population in 2013 and 23.7 ± 0.46 (SD) kg/m2 for the study population in 2021. Length and weight were not reported in the study population of 2019. All three cohorts included proportionally more participants with higher education of at least college or university level degree .Initially, 111, 114, and 44 participants were recruited in the cohorts of 2013, 2019, and 2021, respectively. Participants with an incomplete or missing FFQ or 3-day food record were excluded from the analysis [Content validity was assessed in 2019 in a subsample of 15 participants with a mean age of 29 ±1.45 (SE) years old including eight women and seven men. According to this evaluation, correctly estimated portion sizes mentioned in the FFQ by participants ranged from 53.3 to 92.3%. The portion sizes of the food groups “vegetables” and “potatoes” were least often estimated correctly by the participants (estimated correctly in 53.3% of participants for both the food groups). The portion sizes of the food groups “sweet spreads” and “sauce” were most often estimated correctly by 92.3 and 86.7% of the participants, respectively. Overestimation of the portion sizes mentioned in the FFQ was lowest for the food group “sweet spreads” (by 0% of participants) and highest for the food groups “meat” and “vegetables” (both by 33.3% of participants). The portion sizes of the food groups “sauce” and “meat spread” were never underestimated by participants, while the portion sizes of “chick peas,” “fish spread,” and “potatoes” were most often underestimated . The content validity study disclosed further that specific words used in the phrasing of questions in the FFQ are open to multiple interpretations. Afterwards, the phrasing of questions and usage of words were changed according to the feedback received during the interviews in the content validity study.r2 = 0.44 p = 0.001, r2 = 0.53 p = 0.000, r2 = 0.53 p = 0.001 in 2013, 2019, and 2021, respectively)  .r2 = 0.81 p < 0.001) in 2013, coffee (r2 = 0.84 p = < 0.001) in 2019, and juices and soda (r2 = 0.67 p = 0.001) in 2021. The FFQ both underestimates and overestimates the intake of certain food groups. The results show that meat intake was underestimated by the FFQ by 19.42 g/day in 2013, by 25.98 g/day in 2019, and by 6.20 g/day in 2021. Full-fat dairy product intake, in contrast, was overestimated by the FFQ by 1.29 g/day in 2013, by 18.20 g/day in 2019, and by 18.46 g/day in 2021. As represented in The results of the validity analysis for food group intake are presented in p = 0.001) and 2019  and for calcium, phosphorus, and iron in 2021  for all three micronutrients  in 2013 and from 0.58 to 0.81 (p < 0.005) in 2019  compared with the cohorts of 2013 and 2019 , and therefore, the regression trend should be interpreted with caution. For assessing food group intake, the FFQ shows acceptable to good convergent validity but differs greatly between the food groups. Consumers-only analysis results in smaller correlation coefficients compared with validity analysis for all consumers. However, FFQs are not developed to assess absolute nutrient or food group intake but are rather used for ranking populations according to their intake, and misclassification is an important aspect to assess. Generally, misclassification of 10% or less is preferred, which has been achieved by the FFQ for most nutrients and food groups. However, Cohen's kappa values were generally low, which could be caused by chance agreement. Finally, the reliability of the FFQ was shown to be good indicating great precision of the FFQ.In general, the FFQ underestimates energy intake and absolute macro- and micronutrient intake but shows good reliability and acceptable agreement compared with the food record. The estimation of macronutrient density by the FFQ resulted in a small overestimation compared with the food record. However, the overestimation is < 5% for most nutrient densities and is therefore considered acceptable. Low-to-moderate correlations were found for convergent validity of the FFQ compared with the food record for both macro- and micronutrients. However, the Bland–Altman plots provide better insight and showed good agreement between the FFQ and the food record, indicating acceptable accuracy of the FFQ taking the systematic bias into account. Interestingly, the Bland–Altman plots show a clear improvement in the FFQ over the years. In the first validation study in 2013, a strong downward regression trend was present revealing that underestimation increases with higher intake. In 2019, the FFQ was validated for its content and adapted accordingly, next to adding more specific food groups based on the new Flemish Food-Based Dietary Guidelines published in 2019. This could have contributed to the decreased downward regression between intake and underestimation seen on the 2019 Bland–Altman plots until the plot of data in 2021 shows a complete disappearance of downward regression trend and smaller limits of agreement. However, the cohort of 2021 had a considerably smaller sample size , update of the FFQ, different registration method food record , and the changing dietary pattern during the past decades could explain different outcomes in validation as well. Although Spearman's correlation coefficients seem not to improve significantly for macronutrient intake, Bland–Altman plots do show less bias with increasing intake and smaller limits of agreement, indicating improved accuracy. On the contrary, convergent validity of the FFQ seemed to be improved for micronutrient intake, except for sodium, vitamin C, and vitamin D. Convergent validity of food group intake has decreased over the years, showing lower correlation coefficients and intake of most food groups being statistically differently measured by the FFQ compared with the food record. However, these results are probably influenced greatly by the changing dietary pattern and the different age groups, having different and more irregular dietary patterns with more inter-person and between-person variability in the young study population of 2019. Moreover, it can be argued that the food groups questioned in the FFQ are better resembling the “traditional” dietary pattern of the older study population in 2013 and less suitable for study populations of 2019 and 2021 having different dietary patterns and habits including more diverse and “new” foods. The ranking capability of the FFQ seemed similar across the years with good misclassification rates but fair- to low-weighed kappa values. Additionally, comparison between the different cohorts is difficult due to differences in sample size as misclassification in smaller sample sizes can cause large differences in kappa values . Reprodun = 42). The food records of the students showed greater irregularities in the dietary pattern including skipping meals , higher intake of alcoholic beverages, fast food, sweet snacks, and ready-to-eat meals. This is also represented as this study population has the largest mean difference for energy intake between the FFQ and the food record, which is mainly contributed to the discrepancies for mono- and disaccharides. Nevertheless, the data of the different cohorts should be compared with caution. The cohort of 2019 and 2021 used an updated version of the FFQ including 32 food items compared with the original FFQ used in 2013 with 27 items.The strength of this research is the ability to assess the validation in different sample populations while both convergent validity, reliability together with consumers-only analysis, and cross-classification have been evaluated extensively in different time periods. As diet is culture-specific, diet changes also over time. In total, 10 years ago, potatoes and bread were food groups consumed at almost every meal in a typical Belgian diet. However, lately, more “new” foods have been introduced into the Belgian dietary pattern and gained popularity. This was reflected in the dietary records, as well, with food records of 2013 including mostly “traditional” meals with potatoes or bread as the major food group while the latest food records showed a shifted dietary pattern including considerably less bread but more “on-trend” foods, such as oatmeal, avocado, quinoa, and chia seeds. This trend can also be reinforced by the difference in age of the cohorts in the three different validation studies of 2013, 2019, and 2021. In 2013, the cohort was older while the sample population of 2019 consisted mainly of young students and the age of the sample population of 2021 was more generally representative but had a small sample size and was overall highly educated  while our study participants are Belgian. Although the MyFitnessPal application is used in Dutch, it is still embedded with US culture-specific features including US foods or recipes  and measuring units . Moreover, study participants used US measuring units such as cups to indicate portion size in MyFitnessPal while participants are most likely unfamiliar with US units as metric units are the standard in Belgium. The main advantage of MyFitnessPal is being feasible and easy-to-use for participants, while the disadvantage includes the appeal to register meals as a whole  instead of registering the amount of the separate foods contained in one meal . This introduces additional measurement errors resulting in a less accurate reference method. Lastly, a paper-based FFQ was used in 2013, while a web-based version was used in the 2019 and 2021 validation studies. However, the research by Lai et al. and Al-Shaar et al. shows that paper-based versus web-based FFQs show comparable results , 37.In conclusion, the current FFQ shows low validity for estimating absolute nutrient intake but acceptable validity for estimating nutrient density intake and food group intake. Moreover, the reproducibility of the FFQ is good and misclassification is low. Therefore, it is recommended to use the FFQ only to compare nutrient density intakes or food group intake of populations and should not be used to measure actual or absolute intake. The length of the FFQ is rather short which comprises its validity. Nevertheless, this does not outweigh its great feasibility for the researcher and low burden for the participant while being a quick and low-cost dietary assessment tool that can be used on a larger scale.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Social and Societal Ethics Committee and Medical Ethical Committee UZ Leuven. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.JV wrote the manuscript, analyzed and interpreted the data of 2013, 2019, and 2021, and set up the study of 2021. TB set up the study of 2019, interpreted the data of 2013, 2019, and 2021, and reviewed the manuscript. CM set up the study of 2013, 2019, and 2021, interpreted the data of 2013, 2019, and 2021, and reviewed the manuscript. All authors contributed to the article and approved the submitted version.


Physical phenotype and the cumulative deficit model are two well-known concepts of frailty. One of the main components of frailty is loss of muscle mass and function, which may also include swallowing muscles, therefore is a risk factor for dysphagia. Since dysphagia is seen starting from the early stages of Alzheimer’s Disease (AD), in this study we aimed to reveal the relationship between frailty and dysphagia and dysphagia-related quality of life through Swallow Quality of Life  tool in patients with AD and compare them with cognitively intact older adults.Comprehensive geriatric assessment, dysphagia evaluation by Eating-Assessment Tool (EAT-10) and SwalQoL questionnaire, and frailty assessment via FRAIL and Clinical Frailty Scale (CFS) were performed on all 101 participants of the study. Thirty-five patients were cognitively intact, 36 patients were diagnosed with mild AD, and 30 patients were diagnosed with moderate AD.Sex distribution was similar between the groups, however, there was a statistically significant age difference. The prevalence of frailty increased according to both frailty indexes as the cognitive status deteriorated. All parameters of SwalQoL except fear and sleep parameters deteriorated as cognitive status impaired. In quantile regression of the total score of the SwalQoL questionnaire and multivariable logistic regression of EAT-10, frailty, as defined by CFS and FRAIL, was associated with dysphagia and poor quality of life regardless of age, presence of dementia, as well as nutritional status.Swallowing difficulties in AD negatively affects the quality of life, and it is closely related to frailty in mild-to-moderate AD. Dysphagia which is the term to define difficulty in swallowing is a frequent problem in older age and becomes more prevalent in patients with dementia , 2. DyspFrailty is another common geriatric syndrome defined as a clinical state of increased vulnerability to intrinsic and extrinsic stressors and is associated with adverse outcomes like disability, hospitalization, and mortality , 12. LowThere is increasing evidence in terms of frailty-related dysphagia in recent years, it was stated that there is a strong association between deteriorated swallowing function and frailty in older adults . This stThe study was conducted between 01 and 2020 and 01 May 2021 as a cross-sectional study. According to the power analysis [margin of error: 0.05 and confidence interval (CI): 0.80], the study group was determined as 65. After excluding patients who had one or more of the exclusion criteria, 66 patients aged 65 years or older with probable AD according to the National Institute of Neurological and Communicative Disease and Stroke/Alzheimer’s Disease and Related Disorders Association (NINCDS-ADRDA) criteria  admittedThe patients with the below conditions were excluded from the study;mild cognitive impairment (MCI),severe dementia defined with a CDR score of 3.other types of dementia including mixed types of dementia, vascular dementia, Lewy body dementia, frontotemporal dementia,other neurodegenerative diseases neuromuscular diseases,delirium and other psychotic diseases.Basic activities of daily living (ADL) (0–6 Points)  and instFatigue, Resistance, Ambulation, Illness, Loss of Weight (FRAIL) scale (0–5 points)  concerning normal distributions. For comparisons of the data, the chi-square test or Fisher exact test was performed for categorical variables, with Bonferroni correction. Kruskal-Wallis test was wielded for continuous variables, where appropriate. Quantile regression analysis was used to assess the relationship between the total score of SwalQoL and age, sex, malnutrition, cognitive status, and frailty in different quantiles of 25th, 50th (median), and 75th percentiles. Two different regression models were formed to evaluate the possible factors that affect the total SwalQoL scores. The total score of the questionnaire was accepted as the dependent variable, coefficient and 95% CI were presented. n model 1 age, sex, presence of dementia, malnutrition, and CFS score were included. Model 2 consisted of age, sex, presence of dementia, malnutrition, and FRAIL Score. Multivariable binary logistic regression analysis (enter method) was wielded to evaluate the relationship between the presence of dysphagia symptoms screened by EAT-10 and age, sex, malnutrition, cognitive status, and frailty. Two different models were formed, in model 1 age, sex, the presence of dementia, nutritional status, and CFS score were included. Model 2 consisted of age, sex, presence of dementia, nutritional status, and FRAIL Score. Odds ratio (OR) and 95% CI were presented. In all analyses, p value < 0.05 was considered statistically significant.One hundred one (101) patients were included in the study, and they were categorized as normal cognitive function (35 patients), mild AD (36 patients), and moderate AD (30 patients), according to their CDR scores. Sex distribution was similar between the groups (p > 0.05). The mean ± SD age of the cognitively intact group was 73.88 ± 6.76 years, and it was 75.58 ± 5.53 years in patients with mild AD. In patients with moderate AD, the mean ± SD age was 80.60 ± 7.99 years, and these age differences were statistically significant (p < 0.001). No difference was observed regarding chronic conditions except hypothyroidism .The prevalence of frailty increased as the cognitive status deteriorated regarding both frailty indexes. Patients living with frailty were 14.3% and 32.4% in the cognitively intact group by CFS and FRAIL scales, respectively. The rate of patients living with frailty in mild AD was 41.7% by CFS and 44.1% by FRAIL; and 93.3% and 86.7% of patients with moderate AD were living with frailty according to CFS and FRAIL, respectively. These differences were statistically significant (p < 0.001 for both CFS and FRAIL). Geriatric syndromes including falls, incontinence, and malnutrition were more common in mild and moderate AD . ADL and IADL were mostly affected in moderate AD (p < 0.001 for both ADL and IADL) . The total score of SwalQoL was also decreased as the cognitive status of patients got worsened . All parameters of SwalQoL except fear and sleep parameters deteriorated as cognitive status impaired. The most prominent differences were observed in symptom frequency (p < 0.001), food selection (p < 0.001), and social parameters (p < 0.001). Detailed results were shown in Table To investigate the factors that could affect dysphagia defined by EAT-10, a multivariable binary logistic regression analysis was performed. Frailty according to CFS increased the risk of dysphagia regardless of the age, sex, presence of dementia, and nutritional status in Model 1 . According to Model 2, frailty defined by FRAIL was associated with dysphagia  . In model 2, there was a statistically negative and significant relationship between FRAIL scores and total scores in the 25th, 50th quantiles and 75th quantiles . In models 3 and 4, the presence of dementia was replaced with the stage of dementia. In models 3 and 4, the presence of dementia was replaced with the stage of dementia, and CFS and FRAIL were independently associated with dysphagia and dysphagia-related quality of life . In Table According to our study, swallowing problems cause lower quality of life in mild-to-moderate AD patients than in cognitively intact patients. We found that dysphagia screened by EAT-10 and SwalQoL was associated with frailty independent of age, sex, presence of dementia, stage of dementia, and nutritional status.People with dementia are susceptible to swallowing problems as a result of various health conditions. As they have a decline in their cognitive functions, they also have a loss in their body control. People affected with AD unrecognize the food, as a result of oral, visual, and tactile agnosia, and could not nourish themselves due to swallowing and feeding apraxia. Delayed oral transit time and pharyngeal response duration are other factors that cause deglutition problems. Therefore, during the disease process, patients may start to have difficulty swallowing leading to a progressive reduction in eating . DecreasIn a systematic review published in 2016 by Madhavan et al., four risk factors for dysphagia  were revealed , howeverIn a study, frailty was defined as low functional status, increased comorbidity, low handgrip strength, living in a nursing home, and cognitive impairment which was related to oropharyngeal dysphagia in hospitalized patients with community-acquired pneumonia. In anotSwalQoL is a valid and reliable tool for screening oropharyngeal dysphagia since 2002 . It’s suOur study has some strengths and limitations. Although the sample size is relatively small, nevertheless, a special patient group, patients with AD, was included, and also power analysis was conducted for the estimation of the study sample. Even though dysphagia and dysphagia-related decreased quality of life were independently associated with frailty, we could not comment on the cause-effect relationship between frailty and dysphagia because of the cross-sectional design of the study. Another limitation is that dysphagia was investigated only by the EAT-10 and SwalQoL. Since no instrumental methods for the certain diagnosis of dysphagia were applied, self-reported results are needed to confirm with the gold standard tests in large population prospective studies. Sarcopenia and other sarcopenia related parameters were also not assessed in this study, since sarcopenic dysphagia is another research area and we would like to emphasize the frailty and dysphagia relationship in patients with AD. However, our study has also some strengths. This is the first study to the authors’ knowledge, evaluating the quality of life related to dysphagia of the patients with AD screened by SwalQoL. All the patients in the study performed CGA and frailty assessment, and both physical and cumulative deficits frailty and dysphagia were found to be closely related regardless of the age, sex, nutritional status, and presence of dementia. Although frailty is a well-known factor in the emergence of dysphagia, our study is the first study to highlight the importance of frailty in the onset of dysphagia in patients with mild-to-moderate AD. Since the aforementioned limitations, our results could not be generalized for all patients with dysphagia.In conclusion, we showed that older adults with mild-to-moderate AD have significantly lower scores of the SwalQoL for all domains than normal controls. Swallowing difficulties in AD negatively affect their quality of life, especially in the domains of burden, eating duration and desire, symptom frequency, food selection, communication, mental health, and fatigue. Furthermore, irrespective of the patient’s age, sex, nutritional and cognitive status, and even the stage of dementia, frailty  were found to be closely related to dysphagia. Therefore, the evaluation of dysphagia in AD patients should contain a frailty assessment. Although difficult to say the causal relationship between frailty and dysphagia as a result and design of this study, patients with AD living with frailty should be screened earlier for dysphagia. Further long-term studies with a larger study population are needed to confirm our results.


Patients who had experienced an increased number of concerns during the last weeks  had a significantly greater risk of presenting an increased rate of supportive care needs. Notably, male patients with bone cancer presented a significantly greater number of supportive care needs  respectively, in comparison to those with other types of cancer. (4) Conclusions: Supportive care needs arise from a greater concern and specific type of cancer, highlighting the need for supportive care, such as psychosocial and psychological support. This may have significant implications for treatment and patient outcomes in home care settings.(1) Background: Cancer patients are experiencing psychological problems after diagnosis, such as emotional distress and social anxiety, which may increase their demands for emotional and supportive care. This study aimed to assess the influence of both emotional distress and concerns on the supportive care needs of cancer patients receiving home-based healthcare. (2) Methods: In this door-to-door screening program, 97 cancer patients were approached, with a mean age of 73 years old . (3) Results: As expected, 42.3% of patients highlighted their treatment as their main psychological priority, with 20.6% identifying concerns about the future of their family in this regard. No significant associations with respect to sex were identified in terms of focus, though females reported the need for more frequent psychological support (58.7% vs. 37.3%, respectively,  Cancer is a leading cause of death worldwide, accounting for 10 million deaths in 2020, and nearly one in six of all fatalities. European cases represent 9.7% of all cancers among the global population; yet, this area accounts for 22.8% of all cancer diagnoses and 19.6% of all cancer deaths. Individuals over 65 years old account for 60% of all newly diagnosed malignancies and 70% of all cancer deaths .It has been demonstrated that the highest unmet supportive care needs experienced by people with advanced cancer are related to psychological, information, interpersonal, social, physical, family, practical, daily living, spiritual needs, and cognitive needs, irrespective of the type of cancer . In addiRegarding post-hospital cancer care (home-based care) in Greece, it is underdeveloped and fragmented, with few healthcare services available due to a lack of required planning and coordination. Also, there are no national standards for the operation of palliative care services and clinical guidelines for the provision of palliative care. For example, palliative care services are often provided via non-governmental organizations (NGOs); however, NGOs do not have the authorization to prescribe home care services to patients . RegardiIn Greece, the negative impact of cancer-related anxiety and depression on the quality of life of both patients and caregivers has been well documented in several studies, highlighting the need for appropriate interventions to address psychological distress and manage mental health issues ,11. HoweWithin a framework, health professionals caring for older cancer survivors would benefit from information regarding emotional distress issues and trajectories in supportive care needs and to further comprehend whether these patients might benefit from professional support.This study was aimed, therefore, to assess the impact of psychological distress and concerns on supportive care needs, taking into consideration patients’ characteristics, existing comorbidities, and the type of cancer of older patients receiving home-based healthcare services.Cancer patients (of any type) who received in-home health services from three “Help at Home” programs in Heraklion City  were consecutively recruited for a cross-sectional survey for 4 months (between April and July 2016). The ‘Help at Home’ program is supported by the Greek Ministry of Health and operated under the local municipality authorities, providing social care, person-centered nursing, and medical care to their registered members (beneficiaries), mainly to those aged 65 years old and over with chronic disease and disabilities .Since cancer treatment, such as chemotherapy and/or radiotherapy, was not administrated in a home environment, particularly in the “Help at Home” program, but in tertiary hospitals, this constrained the amount of data that could have been collected, such as patients’ medical records and the relationship between the patient and the therapist/oncologist. For this reason, a convenience-sampling method was used, only approaching those with a cancer diagnosis (at least one year) and were registered/beneficiaries of these three “Help at Home” programs. Participants were eligible for participation if they orally consented after being fully informed, were registered members of the “Help at Home” program in Heraklion, were 65 years old or older, had been diagnosed at least one year with any type of cancer , and were able to understand the questions. Patients with severe psychiatric symptoms, impaired health status, and those who refused to participate without giving any reasons were thus excluded. The required licenses by the respective services  were obtained prior to conducting this survey. Nurses working at these Help at Home programs contacted the patients, explained the study procedures, and prompted the patients to fill out the screening tools.Of the total of 457 registered members in these (3) homecare programs, a total of 97 out of 109 had a diagnosis of any type of cancer, met the eligibility criteria, and were willing to participate in this door-to-door screening for supportive care needs assessment (response rate: 89%). Accordingly, data of only cancer patients were included in the statistical analysis.In this door-to-door screening program, patients were asked to provide demographic  data and their medical history , as well as other relevant psychosocial characteristics, such as asking for psychological support. For this data collection procedure, validated screening instruments were applied.As far as the assessment of significant emotional distress concerns, the self-assessment questionnaire for patients (SAQ-P) was used. This questionnaire consisted of 14 items rated on a 5-point Likert scale . These were used to determine whether and to what extent a patient is in significant distress during the past two weeks that may have required the help of a psychosocial oncology counsellor. A large percentage of answers at ranks 4 or 5 was indicative of a high degree of significant distress. In the present study, only the percentages of answers in the 1-3 range and the 4 or 5 range were thus extracted for descriptive purposes . The meaThe self-assessment questionnaire for family and caregivers (SAQ-FC) was also used, which corresponds to the first questionnaire (SAQ-P) with the difference that it refers to the worries and/or concerns of the patient about their support network, such as family members and caregivers. Similarly, it consists of 12 items to varying degrees , assessing patients’ difficulty dealing with their diagnosis and whether significant distress may be experienced . The meaThe concern checklist (CCL) was used to assess the different concerns  that patients may have had both during the last few weeks  and during the last seven days (based on yes/no responses). In this study, answers with ratings of 4 or 5 on the concerns checklist were also considered to indicate a high degree of concern, and these were thus used to present the corresponding descriptive features. In the second part of this questionnaire, referring to patients’ concerns in the last week (LW), the percentage of people who answered “yes” was calculated for each concern. The overall score for the concerns experienced in the last few weeks was then calculated, and the final score was converted to a range from 0 to 100. High mean scores indicated high levels of anxiety. All “yes” answers were summed for each patient to assess the final number of concerns .The original version of the needs evaluation questionnaire (NEQ) was used to identify the supportive care needs of the participants . The NEQp-values), respectively. All correlations among instruments demonstrated an adequate internal consistency ‘reliability’ (p = 0.001), allowing us to further proceed towards statistical analysis , while Kuder–Richardson was applied for the Likert (5-point) items and controlled via the Pearson r and Spearman rs values  of Heraklion, Crete, Greece (where the “Help at Home” program is based). Prior to data collection, patients were informed in detail about the purposes and procedures of this study. Furthermore, they were assured of the confidentiality of their data and reminded about the voluntary nature of participation. The participants were then asked to give their oral (not written) consent and to complete the questionnaires. The procedure was anonymous, in full compliance with the European Union General Data Protection  .2) test was used to identify associations between males and females. Statistical methods  were used to explore possible significant differences among qualitative variables  in cases where comorbidities were present. Yet, Spearman’s rho correlation coefficient was also used to analyze the quantitative variables . To explore our main research question, whether psychological distress and concerns (including confounding variables) exhibit negative or positive effects on supportive care needs, the NEQ was placed as a dependent variable. However, since supportive care needs (NEQ items) were estimated as counts, the Poison regression model was considered more appropriate. However, due to over-dispersion, as confirmed via a likelihood ratio test of alpha = 0: G2 = 191.07 , a standard negative binomial regression model was considered as the most appropriate along with adjusted robust standard errors, even after examination for the model of zero-inflated negative binomial regression, exploring the hypothesis of ‘excessive zeros’ using Vuong’s test (p > 0.05). Statistical analysis was performed using IBM SPSS 20.0 and STATA MP 13, with a p-value set to <0.05.Quantitative variables were presented in the form of mean values and standard deviation, while qualitative ones were presented using frequencies and percentages. The Shapiro–Wilk and Shapiro–Francia statistical tests were used on a case-by-case basis to assess the normality of quantitative variables across this study. The existence of normality was also confirmed or rejected by means of visual oversight of the corresponding histograms, the normal Q–Q plot diagrams, and the box-plots. The median and interquartile range  were used as descriptive measures where normality in the data was rejected. Exact tests were applied to identify possible relations among patients’ characteristics and the transformed scores of the tools in cases considered appropriate. Monte Carlo simulations  were also used in cases considered appropriate. The chi-squared (χn = 25). The next most common cancers were respiratory cancer (n = 23) and digestive cancer (n = 20). Finally, only a few patients (21%) received psychological support (Most respondents (52.6%) were men, and their mean age was 73.4 years (SD = 6.60). The mean time from diagnosis was 3.15 years, and the most common type of cancer using grouping based on anatomical systems was lymphatic cancer ( support .p = 0.036), respectively, Mann–Whitney U = 328.00, p = 0.036), suggesting that chronic diseases are associated with higher rates of significant distress (distress .In p = 0.042), suggesting that comorbidities are associated with a higher feeling of concern. In addition, significant differences in concern during the last week (CC-LW) were observed between patients suffering from comorbidities and those free of comorbidities , suggesting that existed comorbidities significantly increased the feeling of concerns in the last week (The major concern identified during the last week (LW) was about their treatment (85.6%), while 64.9% of respondents reported concerns about their current illness. In addition, 60.8% of the respondents reported being very concerned about their finances. Around half (53.6%) were concerned about how they felt physically, and 46.46% of respondents reported a strong feeling of worrying about the future as their most important concern. Similarly, no associations were observed between males and females regarding their strong feelings of psychological concern during the last week. However, significant differences in concern during the last month (CC-LM) were observed between patients suffering from comorbidities and those free of comorbidities . . p = 0.007) independently of other variables. However, this association was not significant for concerns during the last week .p = 0.027) compared to those who did not receive psychological support, although females significantly reported more frequently “to speak to a psychologist” compared to males (58.7% vs. 37.3%), respectively. No other significant associations were found with respect to an increased rate of supportive care needs  among patients with comorbidities (yes vs. no). Demographic characteristics suggested that comorbidities, age, sex, years of diagnosis, and significant distress are not risk factors for an increased number of supportive care needs in our sample. In addition, significant differences in supportive care needs (NEQ) among males were observed with respect to the organ system, suggesting that male patients suffering from bone cancer  presented with higher supportive care needs compared to patients suffering from other types of cancer , especially about their treatment progress. In comparison to our findings, the results of the current study conducted in a Greek sample of 86 patients newly diagnosed exploring the unmet care needs, social support, and distress from the initial diagnosis to post-surgery in gynecological cancer showed that changes in anxiety levels were associated with changes in needs related to family, need for assistance/care and support, and total needs. However, in agreement with our findings, the overall level of distress did not significantly change from the first post-operative follow-up visit, and 4 months after surgery . Yet, ouFurthermore, it has been found that patients suffering from bone cancer are presented with higher supportive care needs compared to those suffering from other types of cancer. Possible explanations for these associations could be attributed to recovering from bone cancer and adjusting to life after treatment is different for each person, depending on long-term side effects and concerns, such as rehabilitation after bone cancer surgery, self-esteem body image, and sexuality .Another important finding was that accepting psychological support reduces the perceived number of supportive needs, although only 21.6% had received psychological support, and less than half of the patients were willing to accept help for psychological or emotional difficulties. Konstantinidis and his colleagues , demonstThe primary need identified by oncology patients was treatment, followed by reassurance about the future and their families, and then finances. The results of other studies have not identified patients having similar needs, and, in contrast to the current results, previous research has shown that the greatest needs among such patients include managing emotions, accepting death based on religious beliefs, and then managing finances . RecoverThe findings of this study demonstrate the need for home care agencies and healthcare organizations to collaborate to improve care by implementing shared evidence-based practice recommendations that guarantee person-centered care for elderly cancer patients in home care settings. Patient-centered home care is the key model of care in terms of improving the quality of life for elderly cancer patients, and this must be delivered by experienced multidisciplinary teams. Practically, psychosocial interventions are effective in reducing distress in cancer patients ,37, and The most important limitation of the present research is the representativeness of the empowered sample used for this study. In addition, validity and psychometric tests were not performed to confirm the theoretical factor structure of the measurements for the Greek population, although all instruments used demonstrated adequate reliability for our sample. Another important limitation is that the data were drawn from a small sample size and regional focus; thus, the generalization of our findings compared to other national-based population cohort surveys should be made with caution. For future research, it is recommended to recruit a representative considerable number of participants across different Greek regions. In addition, the methodological approach used may not have been the most appropriate in this case due to the requirements of qualitative research. Also, homecare settings have no access to the medical records of each patient, as the treatment is only administrated in hospitals. Hence, we were unable to provide information regarding the stage of each type of cancer due to resource constraints . As the The data suggest that cancer patients who experienced higher levels of long-term psychosocial concerns are associated with an increased number of supportive care needs, highlighting the need for professional support to decrease. Therefore, it is crucial to enhance the training and capacities of health professionals, including oncology nurses working in home-based healthcare, by incorporating specific skills and evidence-based practice recommendations related to palliative care into their daily practice.