Hospitalization of nursing home (NH) residents impose a significant healthcare burden. However, there is still a lack of information regarding the risk of hospitalization from inappropriate prescribing in NH residents. We aimed to estimate the nationwide prevalence of potentially inappropriate medication (PIM) use among NH residents using the Korean tool and 2019 Beers criteria and to assess their associations with hospitalization or emergency department (ED) visits.We included older adults aged 65 years or above who were admitted to NHs between July 2008 and December 2018 using national senior cohort database. The prevalence of PIM use based on the Korean medication review tool and Beers criteria on the date of admission to NH was estimated. And the adjusted hazard ratios (aHRs) of polypharmacy, numbers of PIM, each PIM category for hospitalization/ED visits within 30 days of admission to NH was calculated using Cox proportional hazard model to show the association.Among 20,306 NH residents, the average number of medications per person was 7.5 ± 4.7. A total of 89.3% and 67.9% of the NH residents had at least one PIM based on the Korean tool and 2019 Beers criteria, respectively. The risk of ED visits or hospitalization significantly increased with the number of PIMs based on the Korean tool . Having four or more PIMs based on the Beers criteria increased the risk significantly  while using 1–3 PIMs was not significantly associated . Residents with any potential medication omission according to the Korean criteria, were at 23% higher risk of hospitalization or ED visits .This study demonstrated that PIMs, based on the Korean tool and Beers criteria, were prevalent among older adults living in NHs and the use of PIMs were associated with hospitalization or ED visits. The number of PIMs based on the Korean tool showed dose-response increase in the risk of hospitalization or ED visits.The online version contains supplementary material available at 10.1186/s12877-023-04165-w. The global population is getting older because of its increased life expectancy. In 2015, the proportion of older adults aged 65 years or above reached 8.5%, and it is expected to be 16.7% by 2050 , 4.Many residents in nursing home (NH) have one or more chronic diseases, which expose them to polypharmacy . PreviouResidents in NHs tend to get hospitalized or visit the emergency department (ED) frequently. According to US data, more than one-fourth of long-stay NH residents get hospitalized each year, and many of these cases could potentially have been avoided , 10. SucTo minimize the potential harm related to medication use in vulnerable older adults, several screening tools for older adults’ prescriptions have been developed, including the Beers criteria of the American Geriatrics Society, STOPP/START criteria from Europe, and other adapted tools for specific countries , 15. MorEven though a pilot study has been conducted in two Korean NHs to test the applicability of the Korean MR tool-LTCF , there iFor this study, we used a senior cohort database from the National Health Insurance Service (NHIS)-Senior Cohort (NHIS-SC). The NHIS provides health insurance to all citizens in South Korea as the single national insurer and also covers LTC insurance . Older aThis senior cohort database consists of 18 years (2002–2019) of cumulative records of 511,953 stratified randomly sampled older adults aged 60 to 80 years, as of 2008, with an annual replacement of 8% of adults who turned 60 from 2009 to 2018; all the data is de-identified. The data contains demographic information, medical resource utilization data, and LTC service utilization data, including the grade for LTC services of the population.In this cross-sectional study, we analyzed the medication use at the time of NH admission. Therefore, we included older adults aged 65 years or above who were admitted to NHs between July 2008 and December 2018, according to the time of enforcement of LTC insurance by NHIS. We excluded residents who did not have any medication on the day of admission to NHs or residents who had less than 30 consecutive days of stay from the admission day. Furthermore, if a resident was readmitted to the NH within seven days of discharge, it was considered a single episode.We estimated the prevalence of PIM use with the medications used on the date of admission to NH for each resident. For each resident, PIMs were identified by the Korean MR tool-LTCF  and Beers criteria, which is the most utilized and recognized screening tool in South Korea. We could not include two items of Dose-PIM , one item of DDI-PIM (when to take bisphosphonate), and three items of Omission-PIM  from the Korean criteria due to the limited information in claims database. Similarly, we did not include the following: items of PIMs related to kidney function, eight items of General-PIMs, and one item from the Ds-PIM of Beers criteria. The included items by the modified PIM definitions in the analysis and the list of Anatomical Therapeutic Chemical codes for each item are listed in Supplementary Tables The outcomes of interest were the first hospitalization or ED visits within 30 days of admission to NH. Due to the limitations of claims data, we were unable to distinguish between unplanned and planned hospitalizations. Therefore, for the purpose of this study, we included any hospitalization regardless of whether it was planned or unplanned. ED visits with a length of stay of one day were classified differently from hospitalizations, which were defined as stays of two or more days, including those through the ED. To assess the association between PIM use, which include both the overall number of PIMs and specific categories of PIMs, and hospitalization/ED visits, we employed a multivariable-adjusted Cox proportional hazard analysis. Furthermore, to gain a more comprehensive understanding of the specific effects of PIMs on ED visits or hospitalization among NH elderly residents, we also examined the associations of individual PIM items.p-value < 0.05 was considered statistically significant.The demographic characteristics and prevalence of PIM use in the study population were described using descriptive statistics. A t-test and a chi-square test were used to compare continuous and categorical variables, respectively, between residents who had experienced ED visit/hospitalization. To assess the risk of hospitalization or ED visits associated with PIM use, including the total number of PIMs, specific categories of PIMs, and individual PIM items, we employed the multivariable-adjusted Cox proportional hazard model. We adjusted several potential confounding variables, including age, sex, insurance type, disability level, LTC grade, Charlson comorbidity index (CCI), and underlying diseases such as dementia, hypertension, diabetes, ischemic heart disease, heart failure, chronic obstructive pulmonary disease, asthma, peptic ulcer disease, history of fractures, history of pneumonia, and cancer  and Omission-PIMs (77.2%) based on the Beers and Korean criteria, respectively .Cox-proportional hazard model analysis showed that the risk of hospitalization or ED visits within a month after admission to NH increased with the use of PIMs after adjusting for confounding factors Table . ResidenResidents with one or more Ds-PIMs  or General-PIMs based on Beers criteria  had a significantly higher risk of ED visits or hospitalization. Residents with any Omission-PIM, the classification type according to the Korean criteria, were at 23% higher risk of hospitalization/ED visits .The most prevalent item among the General-PIM that may affect hospitalization/ED visits in NH residents was the “use of proton pump inhibitor (PPI),” with 8.3%, which increased the risk of hospitalization/ED visits by 22% . The “use of ketorolac” as a General-PIM by Beers criteria has been associated with a four-fold increased risk of hospitalization or ED visits . Regarding Ds-PIM, only one item from the Korean criteria, “diuretics use in patients with urinary incontinence,” showed a significant association with an aHR of 1.38 (95% CI 1.00-1.90). Concurrent use of warfarin + macrolides/quinolones and oral anticoagulants + antiplatelet drugs significantly increased the risk of hospitalization or ED visits, with an aHR of 3.24 (95% CI 1.04–10.12) and 1.75 (95% CI 1.25–2.44), respectively. Regarding Omission-PIM, “omission of vitamin D and calcium supplements in patients with a history of fall or risk of osteoporosis” and “omission of vitamin D in patients with severe renal impairment” increased the risk of hospitalization or ED visits with an aHR of 1.13 (95% CI 1.00-1.27) and 1.27 (95% CI 1.01–1.60), respectively , and those exposed to one to three PIMs had an aHR of 1.24 (95% CI 1.03–1.49) compared to those without PIMs. These results confirmed the previous findings. One study conducted in the US showed that NH residents with PIMs based on the Beers criteria were at a 28% higher risk of hospitalization . Price eAnalysis of the association of categories or individual items of PIMs with adverse outcomes revealed that ketorolac and dronedarone/amiodarone in General-PIM were highly associated with ED visits or hospitalization. Short/rapid-acting insulin and PPI also increased the risk of adverse outcomes and were relatively common in the residents. Similarly, Lohman et al. investigated the hospitalization risk in Medicare home health nursing patients and reported that patients taking hormone and gastrointestinal medications had 17% and 33% greater risk of hospitalization than those not taking PIMs in these respective classes . RegardiIn our study, more than 40% of residents were exposed to one of the Omission-PIMs, the absence of vitamin D and calcium supplements in patients with risk of fall or osteoporosis, which increased the risk of ED visits or hospitalization by 13%. One study conducted in Spain demonstrated similar results, detecting Omission-PIMs using START criteria in 81 older adults living in a NH . The mosTo the best of our knowledge, this is the first study that applies the Korean criteria to investigate the prevalence of PIMs and their association with a negative outcome in NH residents using claims data. Moreover, as we used nationwide claims data from NHIS, which covers the entire Korean population with health insurance and medical aid, we consider our study population representative. Additionally, we analyzed all the individual items of respective criteria to find not only the prevalence in NH residents but also its association with ED visits or hospitalization.However, there are several limitations to this study. First, we analyzed the medications that older adults were taking on the day of admission to NHs. There may be differences between these medications and those taken continuously after admission to NHs. However, older adults tend to maintain their prescriptions without changes after admission to NHs. It is also possible that medication used solely on the day of admission to the NH are included in our analysis. Nevertheless, it is important to consider that most older adults are transferred to NHs when they are in a stable condition. Therefore, we believe that analyzing only the medications taken on the day of admission will not have a significant impact on the results. Second, owing to limited information in the claims data, we could not identify and analyze certain PIMs, such as Dose-PIM, DDI-PIM related to bisphosphonate administration, and PIMs related to renal function. Furthermore, the claims data used in the study did not allow for distinguishing between hospitalizations that were unplanned or planned. Therefore, there is a possibility of overestimation in the association between PIM use and hospitalization. To address these limitations, additional information, such as laboratory data or patient interviews, would be needed.Third, we could not confirm whether residents were taking medications as prescribed in the claims data. Moreover, over-the-counter medications were not considered. Fourth, it is important to note that we did not analyze the specific reasons for hospitalization and ED visits in this study. Therefore, we could not confirm whether the observed hospitalization/ED visits were directly related to medication/PIM use. It is possible that there were other factors unrelated to PIM use that contributed to these outcomes. However, in older adults, polypharmacy and the presence of PIMs are known to be factors that contribute adverse health outcomes such as falls, or adverse drug reactions, which can subsequently lead to ED visits and hospitalization –32.Our study findings demonstrated that the use of PIM is prevalent among older adults in NHs, and such use is associated with an increased risk of ED visits or hospitalization. Unlike other countries such as Canada or Australia , 34, KorOur study findings underscore the widespread occurrence of PIMs among older adults residing in NHs, as assessed by both the Korean tool and Beers criteria. Importantly, the results demonstrate a clear association between the use of PIMs and an elevated risk of hospitalization or ED visits. Notably, the analysis reveals a dose-response relationship, wherein an increasing number of PIMs identified using the Korean tool is linked to a higher likelihood of hospitalization or ED visits.Below is the link to the electronic supplementary material.Supplementary Material 1


Frailty is associated with mortality among older adults. We aimed to determine the appropriate time and frailty index (FI) threshold for frailty intervention in Chinese community-dwelling older adults.In this prospective cohort study, we used data from the 2011 wave of the Chinese Longitudinal Healthy Longevity Study. Follow-up was performed for seven years from baseline. Using the FI to evaluate frailty and define frailty status, we explored the best time point and FI score for frailty intervention, by comparing the relationships of FI and frailty status with mortality.P < 0.001); female sex, living in the city, being married, and living with spouse were found to be protective factors, whereas ageing was a risk factor for frailty. The mortality risk was higher in pre-frail than in frail participants . Piecewise linear regression analysis revealed an FI score threshold of 0.5. When the FI score was > 0.5, the HR of mortality based on the FI was 15.758 ; when the FI score was ≤ 0.5, the HR of mortality based on the FI was 48.944 .From 2011 to 2018, 8642 participants were included and followed-up. A total of 4458 participants died during the study period. After adjusting for variables such as age, sex, marital status, education level, and living conditions, the hazard ratio (HR) of mortality risk based on the FI at baseline was 37.484 (95% confidence interval [CI]: 30.217–46.498; Using FI as a continuous variable to predict death is more accurate than frailty status. The advancement of early interventions for mortality risk reduction is more beneficial in pre-frail than in frail patients, and an FI score of 0.5 was found to be the threshold for mortality prediction using the FI. Rapid ageing of the worldwide population has become a major trend in the global demographic structure owing to reduced fertility and increased mortality rates , 2. FraiThe frailty index (FI) is one of the most commonly used tools to measure frailty. FI is evaluated based on the concept that frailty is a state caused by a life-long accumulation of health deficits; the higher the number of health deficits, the greater the tendency for frailty. These health deficits include symptoms, disease, disability, abnormal laboratory findings, and social characteristics –12. FI iFI has been shown to vary with time; thus, it is evaluated using cross-sectional studies that cannot accurately predict mortality risk , 18. TheWe aimed to collect and evaluate longitudinal data at different time points, and to accurately determine the best time point for frailty intervention using a long follow-up duration. Our findings will potentially enhance decision-making regarding frailty intervention and the effective utilization of medical resources.The Chinese Longitudinal Healthy Longevity Survey (CLHLS) is a nationwide longitudinal survey conducted in a randomly selected half of the counties and cities in 22 of the 31 provinces in China. All the participants provided written informed consent . We usedHealth deficits were evaluated using the FI. We selected 42 items on self-related health, physical function, psychological and cognitive function, comorbidity, and social deficits , 26. CogCox proportional hazards regression and piecewise linear regression  were useA total of 8642 older people participated in the baseline survey in 2011. Table P < 0.001), whereas the AUC of frailty status was 0.537 , thereby showing a weaker prediction with mortality . Female sex , living in the city , being married and living with spouse  were found to be protective factors, whereas ageing  was a risk factor for mortality (Table The hazard ratio (HR) of mortality according to the FI at baseline was 37.484 , P < 0.001) when the frailty status was dichotomized. The female sex, education level, being married, and living with spouse were found to be protective factors, whereas ageing was a risk factor of frailty. The HR for mortality was higher in pre-frail  than in frail  participants, when the frailty status was evaluated as robust, pre-frailty, and frailty. The female sex, being married, and living with spouse were found to be protective factors, whereas ageing was a risk factor of frailty (Table We further classified frailty as non-frailty (FI < 0.25) and frailty (FI ≥ 0.25), and analysed the HR for mortality in different states of frailty. The HR of mortality according to the FI was 2.209 ; however, when the FI score was ≤ 0.5, the HR was 48.944 . The female sex, living in the city, being married, and living with spouse were found to be protective factors, whereas ageing was a risk factor of frailty  and during follow-up (2014 and 2018), to establish suitable frailty interventions . When exFrailty, defined by phenotype or FI, was found to be significantly associated with an increased risk of all-cause mortality in community-dwelling Chinese older adults based on previous studies , 35. PreFrailty is associated with and predictive of all-cause mortality. Although the effect of intervention in the pre-frailty period may be better than that in the frailty period, intervention with FI below 0.5 may be more beneficial. It is recommended to conduct frailty screening and intervention management for the older adults in Chinese communities.


Intracerebral hemorrhage (ICH) is a significant cause of global mortality and morbidity. This study aimed to analyze the burden of ICH and its variation trends across 204 countries and territories from 1990 to 2019.The study population comprised individuals of all ages and genders with ICH in 204 countries and regions between 1990 and 2019. Utilizing data from the Global Burden of Disease (GBD) study 2019, we collected information on age-standardized incidence rate (ASIR), age-standardized death rate (ASDR), and disability-adjusted life-years (DALYs) rate, which were compared by age, gender, and socio-demographic index (SDI).In 2019, there were an estimated 3.4 million (3.0–3.9) incident cases, resulting in 2.8 million (2.6–3.0) deaths and 68.5 million (63.2–73.6) DALYs due to ICH. Between 1990 and 2019, the absolute number of incident cases, deaths, and DALYs increased by 43.0% (41.0–45.0), 37.0% (22.0–51.0), and 25.0% (12.0–36.0), respectively. However, the ASIR, ASDR, and DALYs showed a decreasing trend of-29.0% (−28.0 to −30.0), −36.0% (−29.0 to −43.0), and − 37.0% (−43.0 to −31.0), respectively. Countries with lower SDI tended to have higher ASIR, ASDR, and DALY rates.While the ASDR and DALY rates decreased from 1990 to 2019, the decline in ASIR was less pronounced. The global burden of ICH remains high, exhibiting significant variation across different genders, age groups, and SDI levels. Intracerebral hemorrhage (ICH) is a significant global contributor to both mortality and morbidity, making it a major public health concern . Over thThe Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) is a comprehensive and systematic evaluation that assesses the global burden of 354 diseases and injuries across different age groups, genders, and geographical locations. This study is updated annually, providing valuable insights into the global health landscape . By condThe findings from the GBD study of 2016 and 2017 indicated a decline in the incidence and mortality rates of stroke; however, the overall burden of stroke remained high , 12. In We collected data including ASIR, ASDR, YLLs, YLDs, and DALYs from 1990 to 2019 in 204 countries and regions. The data were obtained from the Institute of Health Metrics and Evaluation (IHME) website.Each estimate was calculated as the mean of 1,000 draws from the posterior distribution, considering factors such as age, sex, location, and year. The 95% uncertainty intervals (UI) were determined as the 25th and 975th values of the ordered draws, with statistical significance defined as a 95% UI excluding zero for all estimates.On the basis of the GBD study, ICH was defined based on the WHO diagnosis criteria as a non-traumatic, primary event identified by brain imaging, rapidly developing clinical signs of focal  disturbance of cerebral function lasting for more than 24 h or leading to death with no apparent cause other than that of vascular origin , 12. Briper capita, average years of schooling among the population aged 15 and over, and the total fertility rate. A higher value on the SDI scale indicates a more favorable development status. The countries were then categorized into five SDI quintiles: low, low-middle, middle, high-middle, and high. This classification allowed for the assessment of the disease burden in relation to the varying levels of development across different regions and countries.In order to examine the relationship between the development status of regions or countries and the burden of disease, a sociodemographic index (SDI) ranging from 0 to 1 was utilized, which provides a comprehensive reflection of a location’s development status. SDI is calculated as the geometric mean of normalized values for three key factors: income The figures were generated through the GBD Results Tool and the GBD Compare Tool.As shown in By the age group, the incidence rate per 100,000 of ICH increased with increasing age in 2019 in both genders . As showAs shown in As shown in By the age group, the mortality rate per 100,000 of ICH increased with increasing age except the neonatal groups in 2019 in both genders . As showAs shown in As shown in As shown in As shown in In the current study, we conducted a systematic analysis of the global burden of ICH from 1990 to 2019. We compared this burden across different genders, age groups, and SDI levels. Our findings reveal that the global burden of ICH remains alarmingly high, with over 3.4 million incident cases, 2.8 million deaths, and 68.5 million DALYs reported in 2019. Notably, the global number of incident cases and deaths due to ICH has increased by approximately 43.0 and 37.0%, respectively, during the studied period. However, when considering ASIR and ASDR, most countries and regions have witnessed a decrease in these rates from 1990 to 2019. Furthermore, while the age-standardized DALYs rate, which quantifies the overall burden of ICH, has decreased, the absolute number of DALYs has actually increased from 54.7 million to 68.5 million. This increase in absolute numbers is mainly attributed to population growth and the aging of populations worldwide. These findings underscore the persistent and significant impact of ICH on global health. It highlights the need for continued efforts in prevention, early detection, and effective management of ICH, particularly in light of the increasing burden associated with population growth and aging.Our study reveals diverse patterns and variations in the global burden of ICH across different age groups and genders. Specifically, when considering age groups, the number of incident cases of ICH peaked at the ages of 60–64 years in both genders in 1990 and at the ages of 55–59 years in men and 60–64 years in women in 2019. Between 1990 and 2019, men consistently had a higher number of new ICH cases than women in the age groups of 20–74 years. Moreover, the age-standardized incidence rate (ASIR) per 100,000 of ICH increased with advancing age, indicating a higher risk of developing ICH as individuals get older. In terms of mortality, the number of deaths due to ICH peaked at the ages of 65–69 years in men and at the ages of 75–79 years in women. Women had a relatively larger number of deaths than men in the age groups of 75 years or older. The ASDR per 100,000 of ICH generally increased with age, except in the neonatal groups. This indicates a higher mortality rate associated with ICH as individuals get older, with neonates being an exception. The age group with the highest DALYs rate, which quantifies the overall burden of ICH, changed from 75 to 79 years in 1990 to 85–89 years in 2019. This suggests that the impact of ICH on disability-adjusted life-years has shifted toward older age groups over time. Similar to our study’s conclusion, a previous systematic review and meta-analysis revealed that the incidence of ICH was observed to increase with age, and older individuals were at a higher risk of experiencing ICH compared to younger age groups . These dThese findings emphasize the importance of considering age and sex as critical factors in understanding the burden of ICH. Considering the age-related variations in ICH burden, tailored interventions for different age groups may be necessary. For instance, public health campaigns promoting hypertension control and healthy lifestyles might be particularly beneficial for the elderly, while interventions targeting younger populations could focus on preventive measures including promoting physical activity and healthy dietary habits.Our study findings highlight significant variations in the burden of ICH across different countries and territories. Specifically, we observed that the countries with lower SDI quintiles had the highest ASIR, ASDR, and DALYs rate associated with ICH. Additionally, the lowest percentage decrease in ASIR, ASDR, and DALYs was observed in the low or low-middle SDI quintiles. Furthermore, specific regions such as Oceania, Southeast Asia, Central Asia, and Sub-Saharan Africa exhibited relatively higher ASIR and ASDR for ICH. These regional differences in the burden of ICH are crucial for informing resource allocation strategies and the implementation of guidelines tailored to local medical conditions. Given the observed disparities, it is imperative to prioritize and allocate greater efforts toward countries in the low SDI quintile as well as developing and low-income countries. These regions often face additional challenges in terms of healthcare infrastructure, resources, and access to quality medical care. Addressing the burden of ICH in these areas will require targeted interventions, increased healthcare investments, and the development of context-specific guidelines and policies. By recognizing the regional variations in the burden of ICH, healthcare systems and policymakers can better allocate resources, implement effective interventions, and improve outcomes for individuals affected by ICH in different parts of the world , 23.While previous studies have reported on the global burden of stroke using data from the Global Burden of Disease (GBD) study in 2016 and 2017, there has been a lack of separate estimates specifically focusing on ICH , 12. ConThis study has certain limitations that should be acknowledged. First, the availability of primary data in some low-middle income areas was limited within the GBD study dataset. This may have influenced the accuracy and completeness of the estimates in those regions. Second, we did not conduct a systematic analysis of the attributable risk factors for ICH, which is an important aspect that should be addressed in future studies. The GBD study of 2019 did not provide a comparison of age-standardized incidence rate (ASIR), age-standardized death rate (ASDR), and disability-adjusted life-years (DALYs) rates by race. However, we did observe significant variation in the burden of ICH across different socio-demographic index (SDI) levels and countries, indicating the complex nature of this condition and the need for further investigation.The global burden of intracerebral hemorrhage (ICH) remains substantial despite a decrease in ASIR, ASDR, and DALY rates from 1990 to 2019. However, it is important to note that the absolute number of incident cases, deaths, and DALYs associated with ICH has actually increased significantly during this period. This suggests that while progress has been made in reducing the rates of ICH, the overall impact of the condition on a global scale continues to grow.The burden of ICH exhibits wide variations across different age groups, geographic locations, and SDI levels. It is crucial to recognize these regional differences in burden and allocate appropriate resources and interventions accordingly. Particularly, greater attention and efforts should be directed toward countries with lower SDI levels as they tend to experience higher rates of ICH and face additional challenges in terms of healthcare resources and infrastructure.Addressing the burden of ICH requires a comprehensive approach that focuses on prevention, early detection, and effective treatment strategies. By targeting high-risk populations, implementing interventions to address modifiable risk factors, and improving access to quality healthcare services, we can work toward reducing the global burden of ICH and improving outcomes for those affected by this condition.http://ghdx.healthdata.org/gbd-results-tool.Publicly available datasets were analyzed in this study. This data can be found here: Institute for Health Metrics and Evaluation (IHME), Global Health Data Exchange (GHDx), 2019 Global Burden of Disease (GBD) study, Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. Written informed consent from the patients/participants or patients/participants’ legal guardian/next of kin was not required to participate in this study in accordance with the national legislation and the institutional requirements.TS contributed to conceptualization, methodology, quality assessment, and writing the original draft. YY and YZ contributed to data curation, software, and formal analysis. YY and KW contributed to investigation. CY contributed to conceptualization, quality assessment, and manuscript revision. JG contributed to conceptualization, quality assessment, supervision, funding acquisition, and manuscript revision. All authors approved the final manuscript.


Data were obtained from medical records and cost databases, assessed for a period of one year before and after PHC implementation. The results were expressed as mean absolute frequencies for number of hospitalizations and as average annual expenses expressed in dollars (US$) in relation to cost data.there was a reduction in hospitalization expenses after implementing supplementary PHC (p=0.01) and a decrease in the frequency of hospitalizations for the entire sample (p=0.006). There was a reduction in the frequency of consultations at the Emergency Room among frail older adults (p=0.011).there was a reduction in hospitalization costs and frequency of visits to the Emergency Room after supplementary PHC. According to the World Health Organization (WHO), between 1950 and 2025, the group of older adults in the country should increase fifteen times, while the population will increase about five times. Population aging, in particular, has been changing the epidemiological profile in Brazil, with an increase in mortality due to chronic noncommunicable diseases (NCDs), to the detriment of infectious and parasitic diseases.The Brazilian population is aging rapidly. In 2016, life expectancy was 76.6 years, which meant an increase of 31.1 years, for both sexes, compared to 1940. Among the main chronic cardiovascular diseases are coronary artery disease (CAD) and heart failure (HF). These diseases, in addition to being highly disabling, lead the demand for medical services, especially in older adults-5. In 2015, specifically, CAD occupied a prominent position and was responsible for 47.7% of global cardiovascular mortality.Among NCDs, cardiovascular diseases have the highest morbidity and mortality rates in Brazil and worldwide. The public system is represented by the Unified Health System (SUS - Sistema Único de Saúde), open for access by all Brazilians to health services. Both the public system and the supplementary health system can offer a specific model of organization of care and health services, called Primary Health Care (PHC). PHC has four essential attributes: first contact access, coordination, longitudinality and comprehensiveness. It is responsible for acting as a gateway to the health system, facilitating the way for patients to find the right professional at the right time and in the right place.Brazil has a health care model in which public and private investments coexist in provision, demanding the use of health services. The private segment is called supplementary health and is made up of health insurance operators, which, through the payment of private insurance, contribute to minimizing the public system overloadUsifamília, in the city of Ipatinga-MG, Brazil, inspired by the Cambridge Health Alliance Primary Care model, Boston, United States of America. This resulted in a mixed model of health care based on PHC assumptions and the paradigm of older adults’ health, called health management centered on older adults. This model aims to better manage the health of beneficiaries and their families, through a technically qualified team and the PHC model, a differentiated physical structure and a patient-centered care flow. The health team that makes up this supplementary PHC is made up of doctors, nurses and nursing technicians, and the multidisciplinary team is made up of a nutritionist, pharmacist, social and administrative worker. Usifamília units have a high standard service structure with individualized service and modern equipment that meet the needs of its users. Professionals use the electronic medical record, the same used by the hospital in the FSFX network, facilitating the referral and counter-referral with the health team in information processing. Patients are actively monitored and systematically followed up. Strategies that strengthen PHC capacity and emphasize health promotion tend to improve health status and reduce costs with hospitalizations and medical procedures. However, in order to have a broad view of the benefits generated by the implementation of supplementary PHC programs, it is still necessary to develop methods for assessing and quantifying the results obtained to justify the investment in this care model.The São Francisco Xavier Foundation (FSFX), in December 2014, started its operations in the first PHC Unit called To identify whether implementing a supplementary PHC system makes it possible to reduce care costs for older adults with heart diseases.Faculdade de Ciências Médicas de Minas Gerais (FCM-MG), in November 2016.The study was conducted in accordance with national and international ethical guidelines, being approved by the Research Ethics Committee of the Usifamília from 01/01/2015 to 12/31/2015. Also considering that the classification of functionality of older adults is relevant, as it can provide support to guide quality care in health services, in this work we used the Clinical-Functional Vulnerability Index-20  to classify older adults according to their functional capabilities. All costs with medical care and procedures were surveyed one year before and one year after the first consultation at PHC. Data collection was obtained in 2017. To prepare the manuscript, the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) recommendations were followed, being carried out based on patients’ electronic medical record and the total care cost , described in the Electronic Data Interchange (EDI).This is a retrospective cohort that included all subjects aged ≥ 60 years previously diagnosed with heart failure (HF), unstable angina or who had already had an acute myocardial infarction (AMI) and who had their first medical consultation at supplementary PHC Electronic medical records of patients who did not have heart disease described at least one year before the first medical consultation at PHC as well as those who did not have at least 12 months of follow-up before and after the first medical consultation at PHC and those with incomplete record. According to the exclusion criteria, 223 medical records of patients were selected.Data were obtained from the electronic medical record, which analyzes the medical evolution of the first consultation at PHC, and from consultations with a cardiologist before that date. Selected variables were sex, age, weight, height, smoking, clinical history , date of first consultation at PHC, vulnerability index according to IVCF-20, total cost of care  and frequency of use of Emergency Room and hospital admissions.. The IVCF-20 is useful to be used for initial screening in PHC and represents a systematic attempt to objectively verify the ability of an individual to perform the activities necessary for self-care, based on the assessment of different skills, allowing the development of an interdisciplinary health care plan especially aimed at optimizing older adults’ performance.In Brazil, PHC professionals tend to consider older adults as fragile based on their general appearance, or when these individuals have multiple illnesses or comorbidities. The IVCF-20 is an index of vulnerability of older adults obtained through a questionnaire that considers multidimensional aspects of the health condition, being considered a screening and classification tool for frailty and loss of functional capacity in older adults. Each domain has a specific score that makes up a maximum value of forty points. The higher the value obtained, the greater the risk of clinical and functional vulnerability of older adults, which can be classified: 0 to 6 points: (robust older adults) they can exercise their autonomy and independence and develop all their activities of daily living independently, without showing functional disability; 7 to 14 points: (older adults at risk of frailty) present a decrease in their functional clinical condition, i.e., physical and mental weakness, but present themselves as independent and autonomous; and ≥ 15 points: (frail older adults) semi-dependent or totally dependent on their activities, i.e., they are unable to manage their lives independently and autonomously. At PHC Usifamília, this questionnaire is routinely applied by duly trained nursing technicians and later checked by the unit’s nurse. Application time is approximately 10 minutes.The questionnaire consists of twenty questions, distributed in different domains: age, self-perceived health, functional impairment, cognition, mood, mobility, communication and multiple comorbidities-13. Individuals were classified as underweight, with a BMI ≤ 22 kg/m2, eutrophic or adequate weight, with a BMI between 22 kg/m2 and 27 kg/m2, and overweight, with a BMI ≥ 27 kg/m2-13.To calculate the BMI, the cut-off points proposed by Lipschitz and the Ministry of Health were used, taking into account the changes in body composition that occur with aging, when compared with adult individuals, according to the cut-off points proposed by the WHOFor cost assessment , the average annual costs in the 12-month periods prior to the date of the first appointment at PHC and 12 months after were considered . Outpatient costs refer to elective medical consultations, Emergency Room consultations and laboratory tests. There was no monetary correction of values, since each patient in the sample had a different admission date at PHC. Only direct costs were taken into account in this study. All costs were originally calculated in the national currency (reais). These amounts were then converted into US dollars, according to data provided by the Central Bank corresponding to 10/04/2020 (1US$ =4.60 BRL).Qualitative variables were presented as absolute and relative frequencies, and quantitative variables as mean ± standard deviation and median. Quantitative variables were submitted to the Shapiro-Wilk normality test. To assess the association between categorical variables, the chi-square test of independence was used. Comparison of three or more means was performed using the Kruskal-Wallis test, and for multiple comparisons, the Dunn test was adopted. Comparison of expenses before and after PHC implementation was performed using the Wilcoxon test for paired samples. Analyzes were developed in the free program R version 3.2.2, adopting a significance level of 5%.2, and 67.5% were overweight. Regarding clinical history, 77.1% had AMI, 18.4%, HF, and 9%, angina. Only 9.6% were smokers , with a higher proportion of women (p<0.001), with HF (p=0.002) and a lower proportion of AMI (p<0.001). Robust older adults had a higher proportion of men (p<0.001), with AMI (p<0.001) and smokers (p <0.001) .The reduction in the cost of total health care after implementing PHC was not significant for the entire sample  nor among the analyzed subgroups. There was no significant difference in total cost reduction by sex, age, medical history, BMI, smoking, and IVCF-20 classification .However, there was a significant reduction in hospitalization costs after implementing a PHC for the entire sample . When stratifying the groups, there was a significant difference in hospitalization costs for men (p=0.041), between 71 and 80 years old (p=0.005), who had AMI (p=0.023), eutrophic according to BMI (p= 0.027), non-smokers (p=0.020) and classified as robust according to IVCF-20 (p=0.013) .There was a reduction in the frequency of hospital admissions with PHC implementation for the entire sample (p=0.006), and among men (p=0.014), between 71 and 80 years old (p=0.001), classified as robust by IVCF-20 (p=0.025) and who had already been diagnosed with AMI (p=0.027). There was a reduction in the frequency of consultations in the Emergency Room among older adults classified as frail in IVCF-20 (p=0.011) .In this study, patients were mostly male, and the mean age was 73.8, of which (40.4%) were between 60 and 70 years old. The majority (67.5%) were overweight. More patients with AMI were observed (77.1%), and most were classified as robust according to the IVCF-20 (50.7%). The frail older adults were older and mostly female (60%), with HF (lesser proportion with AMI). After implementing a PHC for frail older adults, there was a reduction in the number of medical consultations in Emergency Room Units, and for robust older adults, a reduction in the number of hospitalizations. Although the reduction in total cost after implementing the supplementary PHC was not significant, a significant reduction in costs and frequency of hospital admissions was observed for the entire sample. When stratifying the groups, there was a significant difference in hospitalization costs for men, aged between 71 and 80 years, who had AMI, eutrophic according to BMI, non-smokers and classified as robust according to IVCF-20. Regarding the frequency of hospitalization, there was a reduction with the implementation of a PHC for the entire sample and among men, aged between 71 and 80 years, classified as robust by the IVCF-20 and diagnosed with AMI. A reduction in the frequency of Emergency Room consultations was also observed among older adults classified as frail in IVCF-20. The results show the importance of implementing the supplementary PHC, both in terms of health and the system’s financial sustainability, by avoiding hospitalizations and also possible health complications in a population of older adults with heart disease who are more vulnerable.. However, it is noteworthy that, in this case, contrary to the practice of this study, the results were obtained among all individuals, without any type of classification, and which constituted a certain portfolio of clients in relation to all individuals in the portfolio of another client without the implementation of a PHC, not following the same individual, as in the case of this study. However, both in the case of PHC Usifamília and that of the referred operator, we observed the impact of PHC in the reduction of hospital admissions.As for the results of this study, and for comparison purposes, it is interesting to mention that the reduction in hospitalizations was also observed by another supplementary health care provider in the city of Belo Horizonte, Minas Gerais, Brazil, which recorded a 13% reduction in hospitalizations after implementing PHC. A higher proportion of overweight older adults (67.5%) was observed in this study, when compared to data obtained from a survey carried out by the Ministry of Health, published in 2020, in the bulletin Vigitel (Vigilância de fatores de risco e proteção para doenças crônicas por inquérito telefônico), in which 60.9% of older adults aged 65 years or older were overweight. Regarding smoking, the proportion was lower (9.6%), compared to the 2013 data from the Brazilian Institute of Geography and Statistics (IBGE - Instituto Brasileiro de Geografia e Estatística) (13.7%) for the Southeast. It is known that the control of risk factors is responsible for at least 50% of reduction in mortality from cardiovascular diseases.We know that many chronic conditions are linked to aging, but also derive from the lifestyle of citizens, characterized by unhealthy habits, in addition to genetic predisposition-26. AMI had the highest proportion between the groups (77.1%), followed by HF (18.4%) and angina (9%). HF showed a higher proportion in frail older adults, an expected fact, since HF is a predictor of dependence in hospitalized older adults and increases the chance of functional loss fivefold. In our study, the costs of caring for patients with HF were higher than the costs of treating conditions related to AMI or angina. This was already expected, since HF expenses tend to be higher, because they entail a series of consequences, such as pulmonary edema, low perfusion of noble organs with consequent functional alterations.Like AMI, unstable angina and HF are the most prevalent NCDs in older adults and with high morbidity and mortality.There is great concern about maintaining the quality of health care for older adults without losing control of costs or failing to provide the necessary treatments. The high rates of hospitalization of older adults show the impact of the Brazilian population aging on the health sector and represent a major challenge for health systems, due to the risk of not offering the necessary assistance to the demands of this group. In 2009, older adults accounted for 21% of hospitalizations. The main causes of hospitalizations for PHC-sensitive conditions reported for older adults are HF, angina, pulmonary diseases and cerebrovascular diseases.The higher health care costs for older adults in Brazil are mainly due to repeated hospitalizations. In a study carried out with older adults of PHC in the SUS, diseases of the circulatory system were also the main cause of hospitalization (28.4%). Hospitalizations for HF and myocardial revascularization surgeries were responsible for the largest share of SUS costs. From 1998 to 2010, DATASUS (SUS IT department) estimated a historical series of hospitalizations due to AMI, angioplasty and revascularization, bringing an average cost per patient to US$ 1,138.26 in the public system and US$ 3,675.00 in the systems private. It is noteworthy that the average cost of hospitalization due to AMI before implementing PHC Usifamília in our study was US$ 1,769.18 ± 2,124.49 and represents an intermediate value between those mentioned in the analysis, being above for the SUS and below for private systems. On the other hand, the average cost of US$ 1,048.42 ± 1,877.60 (p=0.023), with the same type of hospitalization, after implementing PHC Usifamília, shows a clear reduction in relation to those mentioned in the SUS and in private systems.Analyzing data on hospitalizations of older adults in 2014, in Brazilian private hospitals that serve the supplementary health network, it is observed that the main causes of hospitalization among older adults were diseases of the circulatory systemIn this context, monitoring older adults in PHC services proposes patient-focused care, in order to reduce the frequency of hospitalizations and/or reduce the demand for Emergency Room services. Avoiding hospitalizations in older adults is relevant both for health and quality of life issues and for cost reduction.Usifamília allowed for greater investment in elective consultations, diagnostic tests, prevention, reflecting on better health. These actions, taken together, make it possible to improve the health system efficiency and allow for an improvement in older adults’ quality of life.We observed a significant reduction in hospitalization costs after implementing a PHC for the entire sample and in men, aged between 71 and 80 years, with a previous diagnosis of AMI, eutrophic BMI, non-smokers and classified as robust. Moreover, after implementing PHC, it was observed that there was no increase in total costs, but a significant reduction in the need for hospitalization and, consequently, a reduction in hospitalization costs . Implementing PHC It was also verified, in this study, that frail older adults had a reduction in the number of medical consultations in Emergency Room Units (p=0.001) and lower costs  with PHC implementation. However, no statistically significant differences were observed in these last variables for the group of individuals. It can be inferred, from the results obtained, that frail older adults are more subject to prolonged hospitalizations, successive readmissions and worse prognosis.This study shows the importance of implementing a PHC network to care for older adults with heart disease, since not only do we have a reduction in health costs, but also a decrease in the number of hospitalizations and emergency room visits. These are data that not only help in the strategic economic planning for implementing health programs, but also allow inferring an improvement in the quality of life of this population.st consultation at PHC.Only older adults with a diagnosis registered in the medical records of AMI, HF and angina in the evolution of the first PHC consultation were included in the study. It is possible to observe that some older adults who had these heart diseases were excluded from the study due to lack of records of the evolution at the time of the first consultation. Some subjects probably developed HF secondary to an AMI. However, we did not verify AMI history in these cases, and the starting point for their allocation in the group was the diagnosis declared in this 1The results allow us to broaden our understanding of the care network for older adults, enabling planning strategies to identify older adults with the potential for hospitalization and Emergency Room consultations.A clear reduction in the frequency and costs of hospitalization was observed for older adult patients with heart disease who were previously treated in supplementary PHC. Although the reduction in the total health cost was not statistically significant for the entire sample, we must remember that costs with services provided by supplementary PHC were taken into account, showing that expenses with the service implementation did not burden the health system. Our results as a whole suggest that implementing the PHC improved quality of care for older adults diagnosed with heart disease. It is evident, therefore, the need to act to focus PHC teams on monitoring older adults, especially with regard to monitoring the time of return to care, in addition to intensifying preventive actions in order to identify early risk factors for cardiovascular diseases.0034-7167-reben-76-03-e20220486-sup01Click here for additional data file.


Pseudomonas aeruginosa. However, changes in mortality rates were not statistically significant (p = 0.057). ASP positively reduced costs and antimicrobial consumption, with no statistically significant effect on the overall mortality rate. However, a long-term evaluation of the ASP's impact is needed to conclude its lasting impact on infection-related mortality and antimicrobial susceptibility pattern.Antimicrobial misuse is a worldwide issue, and antimicrobial resistance is considered the most challenging aspect of health care. It has been reported that as much as 30–50% of antimicrobials prescribed in hospitals are deemed unnecessary or inappropriate. Antibiotic stewardship programs (ASPs) include policies that apply continuous management of judicious anti-infectious treatment in the clinical setting. Therefore, the objectives of this study were to evaluate the effect of ASPs on antibiotic consumption, the costs of antibiotic expenditure, and the sensitivity of antimicrobials. A retrospective, quasi-experimental study was performed to assess the effect of ASP at An-Najah National University Hospital, a tertiary care hospital in the West Bank, Palestine, over a period of 20 months before and 17 months after the implementation of the ASP. Data on antibiotic consumption were reported monthly as days of therapy per 1000 patient-days and monthly costs (USD/1000 patient-days). A total of 2367 patients who received one or more of the targeted antibiotics  during their hospital stay were included in the study. They have split into two groups: 1710 patients in the pre-ASP group, and 657 patients in the post ASP group. The most significant reduction in DOT per 1000 patient-days was seen with tigecycline, with a percentage of change of − 62.08%. Furthermore, the mean cost of the three antibiotics decreased significantly by 55.5% in the post-ASP phase compared to the pre-ASP phase. After the implementation of ASP, there was a statistically significant increase in susceptibility to meropenem, piperacillin and piperacillin/tazobactam with respect to  Moreover, that was strongly associated with an increased risk of the emergence and spread of multidrug-resistant organisms (MDRO) to others within the hospital or the community. As a result, the role of antibiotic stewardship programs (ASPs) has arisen, and implementing such programs has led to better outcomes.Misuse and overuse of antimicrobial agents are dangerous phenomena, and increases in antibiotic resistance among hospital-acquired pathogens are driven mainly by increased antibiotic utilization in the hospital setting2. Studies conducted in the 1970s showed that antimicrobials were not used appropriately in acute care settings. Around 14–43% of all prescribed antimicrobial therapy courses were not considered necessary, since there was no apparent source of infection2. This transom persisted over the decade, and in US acute care hospitals, about 30% of prescribed antimicrobials are either not necessary or suboptimal2. Moreover, this inappropriate use increases antibiotic pressure and shortages. Meanwhile, few new antimicrobial agents are available, meaning clinicians are left with scanty effective therapeutic options for their patients3. This is also correlated with an increased risk of toxicities and adverse drug effects.As reported, nearly 30–50% of hospital antibiotics are considered unnecessary or inappropriateIn Palestine, we lack studies investigating the impact of ASPs on antimicrobial utilization and the emergence of antimicrobial resistance (AMR). Therefore, our study was the first to assess the influence of antimicrobial stewardship programs on antibiotic consumption, cost, and antimicrobial resistance. ASP was implemented in September 2019 based on the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) guidelines, in an attempt to reduce the use of restricted antimicrobials. After establishing our ASP, 4 Ds of optimal antimicrobial therapy were implemented and followed: right Drug, right Dose, De-escalation to pathogen-directed therapy and right Duration of therapy. In addition, our implementation took into account the significant variations in medical practice, the repercussions on clinical outcomes and mortality rates among patients, multi-drug resistance of major pathogens, and utilization of antibiotics pre-and post- ASP implementation.Our objectives were to evaluate the effect of ASPs on antibiotic consumption, antibiotic expenditure costs, and antimicrobial sensitivity patterns. In addition, we aimed to enhance patient outcomes and safety by using the most suitable antimicrobials, identifying the economic impact of ASPs, and assessing the effects of ASPs on the in-hospital mortality rate.A retrospective and quasi-experimental study, introduced in September 2019, was performed to determine the effect of our ASP on three restricted antimicrobials’  consumption, costs, and the hospital’s antibiogram. We compared the consumption, cost, and antibiogram pattern over a period that encompassed 20 months before  and 16 months after the implementation of the ASP .In our hospital, antibiotic stewardship was delivered by in-person coaching by an infectious disease (ID) clinical pharmacist and an ID specialist. The ID specialist made two rounds per week with the ID clinical pharmacist. The ID clinical pharmacist with direct contact with ID specialist performed the remaining weekly rounds. The clinical rounds were held six days per week. Consultations were available by calling the ID team on holidays and off hours. The pre-authorization process was implemented as policy in the hospital setting by which the list of restricted antibiotics was stated in addition to the approval process agents. The order approval and sign by the ID team is done within 24 h. Exceptions for giving the initial or STAT doses were clarified in the policy as in septic shock cases for patients with a history of microorganisms that necessitate using any of the targeted three agents.4.The study was conducted at An-Najah National University Hospital, a 120 bedded tertiary care hospital that provides surgical, medical, oncological and hemodialysis services for adults and pediatrics, and is considered one of the Palestinian’s leading institutions in the field of health care, in the West Bank, Palestine. So, an institutionally supported educational ASP was implemented in An-Najah National University Hospital, a non-profit tertiary care center hospital and the only teaching hospital in Palestine with 120 beds that provides several medical services. More than 60% of the services are provided for oncology patients—both pediatrics and adults—in the forms of departments, intensive care units (ICUs) and bone marrow transplant (BMT) units. The remaining services are divided between the surgical ward, surgical ICU, and cardiology unitsAll patients admitted to the hospital who received at least one of the three restricted antibiotics between January 1 2018 and December 31 2020 from all hospital departments were included in this study.Pseudomonas aeruginosa treatment, for example. Same for Vancomycin-resistant Enterococcus (VRE) management, only tigecycline and linezolid . So we aimed to control the prescription of these agents that are considered our last reservoir as the new or approved other agents are not available in Palestine.Information about patients who received antimicrobials was obtained from the hospital’s patient information system and pharmacy computer system. In addition, data regarding antibiotic consumption was collected using an excel sheet and reported as days of therapy per 1000 patient-days, together with monthly costs (USD/1000 patient-days). All patients receiving antibiotics had their history and course of the disease, laboratory and microbiological findings, indications, and drug choices evaluated during the rounds. Daily direct contact with the microbiology team was obtained to detect preliminary and final microbiologic culture results, thus guiding the selection of definitive therapy. Regarding the cause of selecting these three agents to work on is based on available agents in the formulary list, the cost, and the broadness of the spectrum of activity of the agents. Actually, these agents are considered the last option for treating resistant pathogens in our developing country. The other agents approved for MDR pathogens management were unavailable in the setting, and these three agents were considered our major resources. For colistin, it is the only available agent for carbapenem-resistant Enterobacterales (CRE) or MDR p-values < 0.05 were considered significant.The Statistical Package for Social Sciences program (IBM-SPSS), version 21, was used to enter and analyze patient data. Testing for data normality was done via the Kolmogorov–Smirnov test. Student t-test (independent sample t-test) was used for normally distributed data, while the Mann–Whitney U test (two independent sample test) was used for non-normally distributed data. In addition, a Chi-square test was used to determine the relationship between antimicrobial susceptibility and the year the microbe was isolated to determine the trend of susceptibility over time. For all tests, Institutional Review Boards (IRB) of An-Najah National University had authorized all components of the study protocol, including access to and use of patient clinical data. We can confirm that the information gathered was only used for clinical research. The information was kept private and was only utilized for the purposes of this study. The data was acquired with only limited access to the project's working staff. We did not share identifiable patient information; we used numbers as codes for patients instead of their names. All experiments in our study were performed in accordance with relevant guidelines and regulations. Because we used retrospective data, IRB of An-Najah National University waived the requirement for informed consent.The This study included a total of 2367 patients who took at least one of the targeted antibiotics  during their hospital stay. These included patients admitted to the hospital's different departments. They were divided into two groups: 1710 patients in the pre-ASP group and 657 patients in the post-ASP group. In addition, they received at least one of the restricted antibiotics.For the selected antimicrobials, there was a statistically significant difference in days of therapy (DOT) per 1000 patient-days between the two groups. The most significant reduction in DOT per 1000 patient-days was seen with tigecycline, with a percentage of change of − 62.08%, as shown in Table The mean cost of the three antibiotics dropped significantly by 55.5% in the post-ASP phase, as shown in Table p = 0.057).The mortality rate was evaluated in all patients in the hospital during the study period, spanning from January 2018 to December 2020. The total mortality rate fluctuated throughout that period; the mortality mean was 2.34 ± 0.57 in the pre-ASP period, while the mean was 2.88 ± 0.95 in the post-ASP period. However, these changes in mortality rates were not statistically significant . At the same time, there was no significant change in susceptibility to ceftazidime. Meanwhile, there was a statistically significant decrease in imipenem susceptibility (p < 0.001); (Table Trends in antibiotic sensitivity were observed between January 2018 and December 2020. Regarding ); Table .Table 3AKlebsiella pneumoniae (p = 0.034) and Escherichia coli (p = 0.014). However, while K. pneumoniae had a significant decrease in susceptibility to amikacin (p = 0.022), E. coli exhibited an increased susceptibility to amikacin (p < 0.001). As for other gram-negative bacterial isolates, there was a significant increase in the susceptibility of both Proteus spp. and Acinetobacter baumannii to piperacillin/tazobactam . Meanwhile, A. baumannii significantly decreased susceptibility to trimethoprim-sulfamethoxazole (p = 0.022)  while Enterococcus faecalis and Enterococcus faecium did not have a significant change in its susceptibility to antibiotics during the study period  before ASP. After ASP implementation, the median was reduced to 88 (72.63–107), reducing meropenem use by 38%. Similar results were seen in another study, in which meropenem was the second most commonly used antibiotic, and its usage was reduced by 50% after the implementation of the program18. Another study conducted in Spain showed a similar reduction in meropenem consumption19. ASP has many benefits beyond the reduction in antimicrobial utilization. It can indirectly help reduce hospital stays, accelerate the transition from intravenous to oral antimicrobials, reduce the risk of MDR organisms, reduce the incidence of adverse effects, and discontinue unnecessary antimicrobial agents.Regarding antibiotic consumption and the effects of ASP, our results showed that days of therapy per 1000 patient-days were reduced for the selected antimicrobials after program implementation. The most significant reduction was observed with tigecycline, with a percentage of change of − 62.08%. This impact of ASP on the utilization of antimicrobials was found in 24 studies with a rate of 11–38%20.As ASPs are designed to optimize patients’ clinical outcomes, multiple factors should be considered when selecting the antimicrobial agent, such as demographic characteristics, the severity of the patient’s illness, provision for the healthcare provider, and the level of adherence to the ASP guidelines21. The impact of ASP in our hospital throughout the study period was significant in terms of reducing the consumption of the mentioned antibiotics and the related costs. Although there was a slight increase in overall mortality in the post-ASP period, the change in the mortality rate was not statistically significant, in agreement with results found in other studies23. The increase in overall mortality rate after September 2019 could be attributed to the pandemic of Coronavirus disease 2019 (COVID-19) as the hospital provided services for COVID-19 patients through a dedicated department and ICU and as the study that was performed to study the impact of COVID-19 on healthcare care-associated infections in intensive care units in low- and middle- income countries showed mortality rates were 15.2% and 23.2% for 2019 and 2020 (p < 0.0001), respectively24.The program's benefits were observed not only in the clinical aspect but also in the financial aspect, where the mean cost of selected antimicrobials was significantly reduced by 55.5% in the post-ASP phase. Furthermore, the average cost saved during the intervention phase was 5669.21 USD. These results are similar to those seen in another study, in which the cost reduction in cost was 41.3%25. Trends in antibiotic sensitivity were observed during the study period, between January 2018 and December 2020. Regarding P. aeruginosa, there was a significant increase in susceptibility to all antibiotics tested except ceftazidime, which showed no change, and imipenem, where a decrease in susceptibility was observed throughout the study period. A study conducted in Qatar showed that susceptibility to certain antimicrobials improved after the ASP was implemented in August 2015. The prevalence of MDR P. aeruginosa showed a sustained decrease from 2014 (9%) to 2017 (5.46%) (p = 0.019). There was a 23.9% reduction in studied antimicrobial consumption following ASP implementation (p = 0.008)26. In contrast to our findings in terms of P. aeruginosa sensitivity, the resistance of P. aeruginosa to imipenem and meropenem dropped significantly from 76.0 to 38.5% (p = 0.019) and from 74.1 to 30.0% (p = 0.012), respectively in the study done by Abdallah et al., 2017. The susceptibility pattern of P. aeruginosa to other antibacterial was not affected by carbapenem restriction27.Cumulative antibiogram reports are necessary to monitor rising trends in resistance and to influence clinical decisions and infection control interventionsE. coli and K. pneumoniae to carbapenems. This is in contrast to the Greek study in which colistin-resistant K. pneumoniae decreased from 31.9% in 2015 to 22.1% in 2016 (p = 0.10) and colistin-resistant A. baumannii from 13.8% in 2015 to 8.1% in 2016. Additionally, while K. pneumoniae isolates showed decreasing amikacin susceptibility, E. coli isolates showed increasing amikacin susceptibility. The evidence suggests that the decrease of E. coli and K. pneumoniae sensitivity to meropenem is due to the prevalence of carbapenem-resistant Enterobacteriaceae in our hospital. As a referral hospital, we deal with a large number of patients who have been infected or colonized with these resistant bacteria, resulting in secondary infections. This high burden of carbapenem-resistant Enterobacteriaceae is likely to have contributed to the decline in meropenem sensitivity of these two bacterial species29. As a result, we must take this issue seriously and implement appropriate solutions, such as antibiotic stewardship programs and infection control practices. We can reduce the spread of resistant bacteria and improve the efficacy of antibiotic treatments for all patients by doing so. The COVID-19 pandemic has undoubtedly presented unprecedented challenges to the global healthcare system30. One of the most concerning consequences of the pandemic has been an increase in antibiotic consumption32, both in the community and in other hospitals. This rise in antibiotic use could have a significant impact on the prevalence of MDR isolates in our hospital. As a result, it is critical that we remain vigilant and take all necessary steps to reduce the overuse of antibiotics, which could exacerbate the already dire situation of antibiotic resistance. Regarding A. baumannii, our study found an increase in susceptibility to piperacillin/tazobactam and a decrease in susceptibility to trimethoprim-sulfamethoxazole, while in the study performed by Chamieh et al., 2019 the overall extensively drug-resistantA. baumanii isolation decreased by 64.7% from period pre to post ASP periods. In addition, isolates from post-ASP period were more antimicrobial-susceptible: 64.8% sensitive to ceftazidime and cefepime, 17.6% to piperacillin/tazobactam, and 17.6% to carbapenems33.Our study also found a significant decrease in the susceptibility of S. aureus susceptibility to moxifloxacin and a non-significant decrease in the susceptibility of E. faecium to vancomycin. Meanwhile, a Greek tertiary care hospital study showed a reduction of vancomycin-resistant enterococci (VRE) from 22.5% in 2015 to 18.2% in 2016 (p = 0.52)34.Regarding Gram-positive bacteria, our study found a significant increase in Our study has some limitations, including the lack of demographic data of the patients and our study is limited to a quasi-experimental pre-and post-implementation design and is limited to a single center. In addition, there wasn’t a washout period while the ASP was getting up and running in the first months. Another limitation was the non-equality of the months between the pre- and post-intervention periods.This study demonstrated that the ASP positively reduced costs and antimicrobial consumption, with no statistically significant effect on the mortality rate. However, a long-term evaluation of the ASP's impact is needed to ascertain its enduring influence on antimicrobial susceptibility patterns and infection-related mortality. Therefore, we recommend that all healthcare centers adopt ASP and its relevant interventions based on the most common practices in the healthcare setting, closely follow its impacts, and adjust interventions accordingly to combat antimicrobial resistance and preserve last-line therapeutic regimens.


Furthermore, subgroup analysis revealed that the protective effect of nuts on NAFLD was more significant in females . In summary, our findings provide support for a protective relationship between nut intake and risk of NAFLD. Further exploration of the association between other dietary components and NAFLD is an important avenue for future research.Although previous epidemiological studies have been conducted to investigate the relationship between nut consumption and the risk of nonalcoholic fatty liver disease (NAFLD), the evidence remains inconclusive and contentious. The aim of our study was to further conduct a meta-analysis of observational studies to explore the latest evidence of the influence of nut consumption on NAFLD. This meta-analysis included a comprehensive search of all articles published in the PubMed and Web of Science online databases as of April 2023. A total of 11 articles were included, comprising 2 prospective cohort studies, 3 cross-sectional studies, and 7 case–control studies, and a random effects model was used to evaluate the relationship between nuts and NAFLD. Results showed that the odds ratio (OR) of NAFLD was 0.90 (95% CI: 0.81–0.99,  Nonalcoholic fatty liver disease (NAFLD) is a significant public health concern and is the primary cause of chronic liver disease. NAFLD is a liver manifestation of metabolic syndrome and is prevalent in obese and diabetic patients . With thMetabolic-associated fatty liver disease (MAFLD) is a novel concept proposed in 2020. Nut consumption is a crucial part of the Mediterranean diet and an important contributor of plant white matter, unsaturated fat acid (UFA), dietary fibers (DF), antioxidants and polyphenols, protein, vitamin E, and some trace elements (such as zinc and selenium) ,6. Nuts p = 0.0004) [Nut consumption has a protective effect on cognitive function, particularly among individuals at high risk of cognitive decline . Naghshi 0.0004) .Another cross-sectional study revealed that moderate intake of nuts and seeds significantly reduced the incidence of NAFLD in males (9%) and females (15%) compared with nonconsumers . Recent Previous meta-analysis has explored the relationship between nut consumption and the risk of various diseases, such as diabetes, obesity, and cancer ,27,28. HThe design and reporting in our study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) . This woTo identify observational studies on the relationship between nut intake and NAFLD, we conducted a systematic search of the PubMed and Web of Science databases for articles published online prior to April 2023. Metabolic-dysfunction-associated fatty liver disease (MAFLD) is a novel concept proposed in 2020 . We alsoThe criteria for inclusion in this study were as follows: (1) observational epidemiological studies, cohort studies, case–control studies, or cross-sectional studies; (2) the correlation between nut intake and the risk of NAFLD; (3) data such as hazard ratio (HR), risk ratio (RR), or odds ratio (OR), and a reported confidence interval (CI) of 95%; (4) the intake of nuts  as exposure variables and the risk of NAFLD as the outcome variable. If more than 1 dataset was published in different articles, we selected the latest version for analysis. When referring to articles, we excluded the following: (1) letters, reviews, case reports, and comments; (2) studies that did not contain nut intake; (3) studies related to animals and cells; (4) studies that did not contain HR, RR, or OR ,31.L.P. and Y.X., independently screened the title, abstract, and full text of the study, retaining articles that met the criteria. Any differences were resolved through discussion, mediation, and consultation with a third researcher (J.S.). From each study, the year of publication, the name of the first author, the type of study, the duration of the study, the location of the study, the number of participants, their gender, confounding variables, and the OR, HR, or RR between nut intake and NAFLD risk, as well as the corresponding 95% CI, were extracted.Quality was assessed using the Newcastle-Ottawa Scale (NOS) scored on a scale of 0 to 9 . The scoI2. Acceptable heterogeneity of the results was defined as I2 ≤ 50%, whereas high heterogeneity was defined as I2 > 50%. When significant heterogeneity between studies was detected, subgroup analysis was conducted to identify possible sources of heterogeneity based on participant gender, sample size, geographic location, and study design. Publication bias was evaluated using Begg’s funnel plot and the Egger test. All statistical analyses were performed with Stata statistical software version 15.0.This study used OR or RR or HR to represent the magnitude of the effect. The random effects model was used to determine the heterogeneity of the articles by calculating Cochran’s Q and As shown in The characteristics included in the study are shown in p < 0.001) between nut intake and total NAFLD risk, indicating a negative correlation. Heterogeneity was observed in the study . Subgroup analysis explained the heterogeneity between studies by evaluating study design, gender, sample size, and nut intake. The asymmetric Egger linear regression test obtained a value of p = 0.463, and the Begg’s test was also used to obtain a value of p = 0.443. Therefore, there was no publication bias in this study.The study used a random effects model to calculate the relationship between nut intake and total NAFLD risk. The meta-analysis results are shown in p < 0.001). There was significant negative correlation between nut intake and NAFLD risk for women  when compared with the risk for men . In the subgroup analysis by region, we did not observe a correlation between nut intake and NAFLD risk in the Asian , Europe  and North American groups . In terms of study design, we observed a significant negative correlation between nut consumption and NAFLD in the cohort study  and cross-sectional studies . However, no significant correlation was observed in case–control studies . Finally, we also conducted a subgroup analysis based on the number of participants, with 1000 people as the grouping markers. Compared to the group with <1000 participants , the group with ≥1000 participants  had a significantly stronger correlation between the protective effect of consuming nuts on NAFLD.This study also conducted a subgroup analysis based on gender, region, and study design, and the results are shown in Nuts are rich in fiber, monounsaturated fatty acids (MUFA), and polyunsaturated fatty acids (PUFA), which could effectively prevent cardiovascular diseases and chronic diseases such as diabetes ,38. Recen-6: n-3 PUFA diet could upturn the metabolic phenotype of adolescents with fatty liver [n-6 PUFA can reduce liver fat and moderately improve metabolic status without losing weight [We have attempted to propose some mechanisms to explain the relationship between nut intake and NAFLD. The first mechanism involved antioxidant activity and inhibition of oxidative stress reactions. Nuts are rich in antioxidants and unsaturated fats , such asty liver . A case–g weight . Polypheg weight ,50,51. Ag weight . The inhg weight .p < 0.05) [In addition, consuming nuts can affect the risk of NAFLD through its effect on weight control. NAFLD is the most common liver manifestation of metabolic syndrome, closely related to obesity and insulin resistance ,55. Weig < 0.05) . Nuts ar < 0.05) . Tindall < 0.05) . Multipl < 0.05) ,61,62. T < 0.05) .Finally, the anti-inflammatory effect of nuts is also an important mechanism for achieving protective effects on a fatty liver. NAFLD is a general term that encompasses nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) . Inflammp < 0.001). However, a study by Han et al. reported that nuts do not have a protective effect towards NAFLD in both males and females  [Our final study showed that consuming nuts can effectively reduce the risk of NAFLD  . The res50–3.39) ,25. Nuts50–3.39) . The exc50–3.39) ,72. This50–3.39) . Chronic50–3.39) .Our meta-analysis has several strengths. First, it includes a large sample size of 92,621 participants and provides a comprehensive analysis of the effect of edible nuts on NAFLD. Previous meta-analyses on nuts have primarily focused on their relationship with cancer incidence and mortality rates. Second, we conducted a stratified analysis to investigate the impact of various confounding factors on the relationship between nut consumption and NAFLD risk. In addition, we attempted to propose two potential mechanisms to explain the protective effect of nuts on NAFLD. To the best of our knowledge, our study is the first meta-analysis to investigate the relationship between nut consumption and the risk of NAFLD, which is a significant contribution to the field.However, when interpreting our findings, we must also consider its potential limitations. First, the number of studies analyzing the relationship between nuts and NAFLD was limited, with only 12 studies meeting our inclusion criteria. Due to the differences in study design, population characteristics, and other factors, there was a high degree of heterogeneity among the studies. In addition, the limited number of studies included in subgroup analyses may have led to biased results. Finally, as participants’ daily intake of food was not limited to nuts, but also contained other vegetables, fruits, and so on, it is possible that the potential impact of other dietary factors on the risk of NAFLD was not fully controlled for in the included studies, despite attempts to adjust for confounding variables. However, the protective effect of specific nuts on the liver could not be investigated because there were few studies. This will also be the focus of our future studies.Our findings suggested a significant association between nut intake and a reduced risk of NAFLD, indicating a protective effect. Although gender-specific data were limited, our findings suggested that nuts may have a stronger protective effect towards NAFLD in women. Despite the growing evidence of the health benefits of nuts, research on the relationship between nuts and NAFLD remains limited. To our knowledge, our study is the first meta-analysis to investigate the impact of nut consumption on NAFLD risk, and we proposed two potential mechanisms to explain the protective effect. Nuts could be an important dietary component in the prevention of NAFLD, and further research is needed to better understand the protective effects of nuts on NAFLD and the relationship between other food types and NAFLD.