Clinical competency is the ability to integrate knowledge, skills, attitudes and values into a clinical situation and it is very important in nursing education, clinical settings, nursing management, and crises. This study aimed to investigate nurses’ professional competence and its correlates before and during the COVID-19 pandemic.We conducted this cross-sectional study before and during the COVID-19 outbreak and recruited all nurses working in hospitals affiliated to Rafsanjan University of Medical Sciences, southern Iran, so we included 260 and 246 nurses in the study before and during the COVID-19 epidemic, respectively. Competency Inventory for Registered Nurses (CIRN) was used to collect data. After inputting the data into SPSS24, we analysed them using descriptive statistics, chi-square and multivariate logistic tests. A significant level of 0.05 was considered.p = 0.03) and desire for research/critical thinking (p = 0.01) were significantly lower before the COVID-19 outbreak than during the COVID-19 outbreak. Only shift type had an association with clinical competency before the COVID-19 outbreak, while work experience had an association with clinical competency during the COVID-19 epidemic.The mean clinical competency scores of nurses were 156.97 ± 31.40 and 161.97 ± 31.36 before and during the COVID-19 epidemic, respectively. The total clinical competency score before the COVID-19 epidemic was not significantly different from that during the COVID-19 epidemic. Interpersonal relationships (The clinical competency among nurses was moderate before and during the COVID-19 epidemic. Paying attention to the clinical competence of nurses can improve the care conditions of patients, and nursing managers should improve the clinical competence of nurses in different situations and crises. Therefore, we suggest further studies identifying factors improving the professional competency among nurses. The COVID-19 disease appeared in Wuhan, China in December 2019 and spread rapidly to other Chinese regions and countries . Iran isThe high prevalence of SARS-Cov-2 indicates the importance of clinical competency among health professionals . StudiesClinical competence is to use technical and communication skills, knowledge, clinical reasoning, emotions and values in clinical settings. It also refers to the ability to carry out professional functions effectively in the area of practice –20. The The COVID-19 outbreak led to a public health emergency of international concern and mainly affected healthcare workers, particularly nurses. Studies reported many mental disorders in healthcare workers and nurses working in high-risk settings, such as anxiety, social problems , posttraThis cross-sectional study investigated nurses’ clinical competences before and during the COVID-19 outbreak in public hospitals  in Rafsanjani, southern Iran.Sampling was performed before (from February to May 2019) and during the COVID-19 outbreak (from February to May 2021) by census method. The study population consisted of 435 nurses before the COVID-19 outbreak and 510 frontline nurses during the outbreak in Ali-Ibn Abi-Talib hospitals in Rafsanjan. Nurses in charge of direct care of patients, nurses with one year of experience, and nurses who had clinical experience for at least three months met the inclusion criteria. The exclusion criteria were a history of mental disorders in nurses and an incomplete questionnaire.n = 246); the data of 506 nurses were used in the final analysis. After obtaining the necessary permits, one of the researchers interviewed nurses at their workplaces to complete clinical competency questionnaire.Three hundred seven nurses completed the questionnaires before the COVID-19 outbreak, but 260 questionnaires were included in the study after removal of the high missing value (47 questionnaires). Therefore, the effective response rate of frontline nurses before the COVID-19 outbreak was 59.77%. Two hundred and eighty-four nurses completed questionnaires during the COVID-19 outbreak, of which thirty-eight questionnaires were removed due to high missing value. The effective response rate of frontline nurses during the COVID-19 outbreak was 48.23%  to assess the nurses’ clinical competence in different clinical settings. The inventory includes 7 dimensions: a) clinical care , b) leadership , c) interpersonal relationships , d) ethical/legal performance , e) professional development , f) coaching/training , and g) desire for research / critical thinking . The CIRN was scored on a five-point Likert scale ranging from 0 to 4 , with a higher score indicating a higher competency . The total score of this questionnaire varies from 0 to 220.Liu et al. reported Cronbach's alpha coefficient of 0.908 (ranging from 0.718 to 0.903) for the internal consistency of CIRN questionnaire . GhasemiAfter obtaining the necessary permits, the researcher went to the Ali-Ibn Abi-Talib Hospital in Rafsanjan city and started sampling. All eligible people were invited to participate in the study and they were asked to complete the questionnaire when they were ready. The data collection process was done during office hours and when the nurses had enough time to complete the questionnaire. The participant could answer the questions with the interviewer. Ali-Ibn Abi-Talib Hospital was the only hospital in Rafsanjan city dedicated to the care of COVID-19 patients.We input the data into SPSS 24 to analyze them. Frequency, percentage, mean and standard deviation were used to define the dimensions of clinical competence and demographic characteristics. Independent t test was used to comparison of the clinical competency ant its dimensions before and during the COVID-19 among nurses. Multivariate logistic regression was used to investigate the relationship between the variables of analysis and clinical competence of nurses. Significance level was considered to be 0.05.n = 214, 82.3%), married , employed , had a bachelor's degree in nursing , rotating shifts , and 5–10 years of work experience . The samples during the COVID-19 outbreak included 246 nurses with a mean age of 35.85 ± 7.68 years. Most of them were female , married , employed , had a bachelor's degree in nursing , rotating shifts , and 31–60 h of overtime per month   and desire for research/critical thinking (p = 0.01) scores were significantly lower before the COVID-19 outbreak than during the COVID-19 outbreak. The nurses' total clinical competency scores did not change significantly before and during the COVID-19 outbreak (p > 0.05)   Table . Before p = 0.009)  supported our results and reported nurses’ moderate clinical competence in the COVID-19 wards , but AlaFaraji et al. (2019)  and JalaLow clinical competence among nurses working in the COVID-19 wards can be due to stressful working conditions, high patient mortality rates, and the need to have high skills. Labrague et al. (2021) reported an association between fears of COVID-19, decreased job satisfaction, and increased psychological distress. They mentioned a high level of fear of COVID-19 among nurses, who were not full-time and did not attend COVID-19 training courses. Labrague argued that nurses working in COVID-19 wards were at a higher risk of infection than the general population, so they were more afraid of transmitting the disease to their family members and friends. An increase in the number of admitted patients, social distancing, and quarantine might exacerbate this condition and affected clinical skills .An important point in our study was that we found no difference in nurses’ clinical competences before and after the COVID-19 epidemic and their clinical competences did not decrease during the COVID-19 outbreak. This result suggests that nurses do their best to take care of patients even in critical conditions. Jang and Cho (2022) reported disaster nursing competencies correlated with age, nursing career, compassion satisfaction, and secondary traumatic stress . ArshadiOur results indicated that the subscales of clinical care and professional development received the highest and lowest scores, respectively. The scores of interpersonal relationships and desire for research/critical thinking before the COVID-19 outbreak were significantly lower than that during the COVID-19 outbreak. Ahmadi et al. (2022) and Saadati et al. (2018) supported our results , 48. TheHowever, Fotohi et al. (2019) did not confirm our results because personal management and practical competence, and desire for research received the highest and lowest scores in their study . KalantaThe study results showed an association between shift type and clinical competence before the COVID-19 outbreak, as well as between work experience and clinical competence during the COVID-19 outbreak. Keshavarzi et al. (2021) demonstrated that the type of shift work had a significant relationship with nurses’ overall clinical skills in neonatal intensive care units  (36). ArHowever, Bahreini et al. (2011) reported no significant relationship between work experience and clinical competence . As studThis study had some limitations: we studied nurses living in a city in southeastern Iran, so the generalization of the results to other societies should be done with caution due to the cultural and social differences. Another limitation was the economic, social and cultural conditions of the participants, which were beyond our control. In the review of the literature, it was found that no study was found to examine the clinical qualifications of nurses during and before the COVID-19 outbreak, so caution should be taken in interpreting the results.According to the study results, work experience can be one of the factors influencing the clinical competence among nurses. Nursing as a clinical discipline is developing and nurses are key members in various settings. Nurses must maintain their professional competences and evaluate and prioritize their clinical competence indicators to improve the healthcare system. Evaluation of clinical competence is particularly important in critical situations, which can improve patients’ condition. Therefore, we suggest policymakers and nurse managers recognizing and increasing nurses’ clinical competences, particularly in critical situations so that they can provide more correct and effective care to the patients. Future studies should focus on the recognition of factors and critical conditions affecting the clinical competence of nurses.


The Republic of Guatemala’s reported COVID-19 vaccination coverage is among the lowest in the Americas and there are limited studies describing the disparities in vaccine uptake within the country. We performed a cross-sectional ecological analysis using multi-level modeling to identify sociodemographic characteristics that were associated with low COVID-19 vaccination coverage among Guatemalan municipalities as of 30 November 2022. Municipalities with a higher proportion of people experiencing poverty  had lower vaccination coverage. Municipalities with a higher proportion of people who had received at least a primary education , children , people aged 60 years and older , and testing for SARS-CoV-2 infection  had higher vaccination coverage. In the simplified multivariable model, these factors explained 59.4% of the variation in COVID-19 vaccination coverage. Poverty remained significantly associated with low COVID-19 vaccination coverage in two subanalyses restricting the data to the time period of the highest national COVID-19-related death rate and to COVID-19 vaccination coverage only among those aged 60 years or older. Poverty is a key factor associated with low COVID-19 vaccination and focusing public health interventions in municipalities most affected by poverty may help address COVID-19 vaccination and health disparities in Guatemala. Guatemala has the largest population among Central American countries over 17 million) and is bordered by Mexico, Belize, Honduras, and El Salvador 7 million,3.Guatemala has the lowest COVID-19 vaccination coverage in Central America and is among the lowest compared with its regional neighbors in South America ,5. As ofThe inequity in the global distribution of COVID-19 vaccines with preferential access for countries with higher per capita incomes and gross domestic products has been well-documented ,14,15. HStrategy to Strengthen the COVID-19 Vaccination Plan in Rural Areas, vaccination activities have more recently incorporated community leader guidance and local media campaigns . Mu. Mu22]. n uptake ,31,32. Wn uptake . Figueron uptake  to estimn uptake . Accordin uptake . COVID-1n uptake ,12. SARSn uptake . A compln uptake . The datHaemophilus influenzae type b), and the Gini coefficient indicating income inequality. The dependent variable was the percent coverage of each municipality population with a complete primary COVID-19 vaccination course. Proportions of municipalities with completed COVID-19 vaccination and SARS-CoV-2 tests exceeding 100.0%  were capped at 99.0%. Given that the proportion of the population that died from COVID-19 by municipality was relatively small, the variable was scaled by 100 in the model to achieve a similar order of magnitude to the other variables.Municipal-level independent variables included in the model were the percentage of each municipality population reported to be of Mayan ethnicity, living in a rural residence, of the female sex, having attained primary school or higher educational level, experiencing poverty, aged 0–17 years or ≥60 years, and having died due to COVID-19 . The repTwo subanalyses were also performed to assess whether the demographic associations with vaccination in the overall model were consistent among the subgroups. In the first, the dependent variable was limited to the population aged 60 years or older who had completed COVID-19 vaccination. We chose this subgroup given the initial national focus on vaccinating older adults. In the second subanalysis, the SARS-CoV-2 cases and COVID-19 vaccination data were confined to the period of the highest national COVID-19-related death rate, from 13 February 2020 to 1 October 2021 [p < 0.05 were included in the simplified multivariable model. We used a normal approximation of a 1000 replicate parametric bootstrap to generate our 95% confidence intervals and present both the marginal R2 (representing the proportion of the variance explained by the model-fixed effects) and conditional R2 (representing the proportion of the variance explained by both the fixed and random effects) for each model. All analyses were performed using R Statistical Software  [We calculated descriptive statistics for sociodemographic characteristics among municipalities and departments. We used Pearson correlation coefficients and variance inflation factors to assess potential collinearity within our model. The poverty indicator used in our analysis was developed using some of the variables included in our model, however, these common variables were not heavily weighted in the poverty index ,35. As tAustria) . We hypop < 0.001) (p < 0.001) with COVID-19 vaccination coverage (p < 0.001)  . The med< 0.001) A. Guatemcoverage B. The me< 0.001) C. Overal< 0.001) . AdditioIn the bivariate analysis of all COVID-19 vaccination data as of 30 November 2022, significant factors (α = 0.05) negatively associated with primary COVID-19 vaccination course coverage by municipality, adjusting for departmental level differences, included the proportion of the municipality identifying as Mayan , the proportion of the municipality living in a rural residence , the proportion of the municipality experiencing poverty , the proportion of the municipality in the 0–17 years age group , departmental-level under-five childhood mortality rate , the proportion of those in the department reporting difficulty accessing healthcare due to distance from a health facility , and the department’s Gini coefficient  . Factors positively associated with primary COVID-19 vaccination series coverage by municipality, adjusting for departmental level differences, included the proportion of the municipality with at least a primary school education , the proportion of female sex in the municipality , proportion of the municipality in the 60 years and older age group , proportion of the municipality tested for SARS-CoV-2 infection , reported deaths due to COVID-19 in the municipality , and proportion of 12–23 months old children in the department who had received the third Pentavalent vaccine . 2 value was 0.496, and the conditional R2 value accounting for the covariates and departmental-level differences was 0.594.After adjusting for all covariates and departmental effects in the full model, the proportions of the municipal population who (1) had received at least a primary school education, (2) were experiencing poverty, (3) were below the age of 18 years, (4) were aged 60 years and above, and (5) tested for SARS-CoV-2 remained significantly associated with complete vaccination coverage  living in a rural residence, (2) having received at least a primary school education, (3) experiencing poverty, (4) of female sex and (5) tested for SARS-CoV-2 remained significantly associated with complete vaccination coverage  had completed a primary COVID-19 vaccine course . In the 2 = 0.615).After adjusting for all covariates and departmental effects in the full model, the proportion of the municipal population (1) having received at least a primary school education, (2) experiencing poverty, (3) aged 60 and above, and (4) tested for SARS-CoV-2 remained significantly associated with complete vaccination coverage (In this cross-sectional analysis of COVID-19 vaccination coverage among Guatemalan municipalities, we provide population-level information on sociodemographic and health system variables associated with vaccination. In the adjusted multi-level model evaluating vaccination data as of 30 November 2022, municipalities with higher proportions of people experiencing poverty had lower COVID-19 vaccination coverage. Municipalities with higher proportions of people who had received at least a primary school education, children, people aged 60 years or older, and testing for SARS-CoV-2 infection had higher COVID-19 vaccination coverage. In our subanalyses, the timing of the country’s response to the pandemic did not appear to notably affect the results, as factors associated with vaccination coverage in the overall model were similar to the point at which Guatemala had just passed its highest daily death rate. Additionally, poverty, educational level, and prevalence of testing for SARS-CoV-2 infection remained significant factors associated with COVID-19 vaccination coverage among Guatemalans aged ≥60 years.Our findings are generally consistent with those from previous studies. Prior studies have largely focused on factors related to the intent to vaccinate rather than the completion of COVID-19 vaccination. A 2022 global, population-based analysis noted that participants identifying as female, in older age groups, with a higher level of education, and with health insurance reported being more willing to get vaccinated . In a stIt is also expected that municipalities with more SARS-CoV-2 testing had a higher proportion of the population that was vaccinated for COVID-19 as these municipalities may have more access to health facilities or services. The MSPAS provided free testing to people with symptoms or to those who were COVID-19 contacts, however, these services were generally offered at health facilities that were not always accessible to rural populations ,39. It iIn unadjusted models, we observed significant associations between lower COVID-19 vaccination coverage and Indigenous identity, rural residence, poverty, and self-reported difficulty accessing healthcare. In the adjusted model, of these sociodemographic variables, only the proportion of the municipality experiencing poverty remained negatively associated with vaccination coverage. It is possible that poverty partially explains the observed associations between COVID-19 vaccination and other sociodemographic variables, such as Indigenous identity, rurality, and healthcare access. We found a few municipalities with high rurality and Indigenous populations that reached at least 70% vaccination coverage. There were only three municipalities with 50% or more of their population experiencing poverty that reached 70% vaccination coverage. Poverty remained significantly associated with low vaccination coverage when the analysis was restricted to the time that COVID-19 deaths peaked, or to coverage among those aged 60 years or older. Even as the risk of mortality due to COVID-19 has been shown to be higher among those in the lowest socioeconomic strata , there iThere are limitations to this study which should be considered. Our analysis was conducted at the municipal level as we did not have access to community estimates or individual-level data that could possibly provide more complex explanations of low vaccination coverage among certain sociodemographic groups. Our conclusions at the population level may not be applicable to specific sociodemographic groups within municipalities. Secondly, factors such as poverty, Indigenous identity, and rurality are complex and interrelated, and it is difficult to assess their relationship to vaccination and healthcare access in isolation. The proxies we used for healthcare access, such as testing for SARS-CoV-2 infections and vaccination program reach, such as childhood Pentavalent vaccination coverage, may not capture the intricacies of the political, economic, and historical reasons for low COVID-19 vaccination coverage. Additionally, our analysis may differ depending on alternative definitions of vaccination coverage, such as partial vaccination with one dose or coverage with booster doses. Lastly, as we relied on data from the most recent national census, some of our findings may not reflect the population during the COVID-19 pandemic.Through our multi-level modeling approach, we were able to identify sociodemographic factors associated with COVID-19 vaccination at the municipality level. Our findings show more granularly where COVID-19 vaccination is lagging in Guatemala and which municipalities could benefit from more focused vaccination activities. Municipalities with populations experiencing higher poverty had lower vaccination coverage, and municipalities with higher proportions of primary education completion, children, people aged 60 years and older, and more testing for SARS-CoV-2 infection had higher vaccination coverage. COVID-19 vaccine delivery and public health outreach may be focused on communities experiencing more poverty. While there has historically been a difficulty with healthcare delivery to communities experiencing poverty, interventions based on poverty indices may help mitigate the effects of the COVID-19 pandemic on such communities and ultimately improve health equity.


Metal-organic frameworks (MOFs) have proven to be very effective carriers for drug delivery in various biological applications. In recent years, the development of hybrid nanostructures has made significant progress, including developing an innovative MOF-loaded nanocomposite with a highly porous structure and low toxicity that can be used to fabricate core-shell nanocomposites by combining complementary materials. This review study discusses using MOF materials in cancer treatment, imaging, and antibacterial effects, focusing on oral cancer cells. For patients with oral cancer, we offer a regular program for accurately designing and producing various anticancer and antibacterial agents to achieve maximum effectiveness and the lowest side effects. Also, we want to ensure that the anticancer agent works optimally and has as few side effects as possible before it is tested in vitro and in vivo. It is also essential that new anticancer drugs for cancer treatment are tested for efficacy and safety before they go into further research. Cancer threatens human health and causes millions of deaths annually ,2. In 20Oral squamous cell carcinomas (OSCC) make up over 90% of all cases of oral cancer, commonly occurring in middle-aged and older populations. Public statistics indicate there will be 377,000 new oral cavity cancer cases and 177,000 new deaths from this disease worldwide in 2020. Over the past three decades, mortality and morbidity rates for OSCC have not changed significantly, although treatment methods have improved dramatically in recent years. The probability that a patient with OSCC will survive five years or longer is usually 40% to 50% ,7,8,9,10In recent decades, various nanomaterials, including organic polymers and inorganic porous materials, have been successfully developed for cancer therapies and bioapplications ,17. HoweMetal-organic frameworks (MOFs), a hybrid inorganic-organic material, comprise metal ions or clusters coordinated with organic ligands to create structures. The organic ligands are referred to as “linkers,” and the inorganic metal clusters are referred to as “secondary-building units” ,18. The Fusobacterium nucleatum and Porphyromonas gingivalis ..115].Zhou et al. performed in vitro and in vivo tests in their investigation after the MOF-DOX@DPSCM nanocarrier was developed to cure OSCC cancer. Fluorescence microscopy assays on the cells were used to determine how well the manufactured nanocarrier was internalized. The dental pulp mesenchymal stem cells (DPSCs) showed an intriguing innate ability to settle in the tumor, and their cell membranes could produce MOF@DPSCM to target OSCC both in vitro and in vivo. Considering what the internalization experiments showed, only a limited amount of FITC-labeled MOF@DPSCM adhered to or penetrated CAL27 cells. The flow cytometry and fluorescence results show that the surface of MOFs with DPSC membrane shells improves the internalization of the cells into CAL27 cells and promotes selective binding specifically. The results of the in vivo assays also proved that the MOF@DPSCM had a unique OSCC targeting capacity, as they were still present in the OSCC and CAL27 tumors 24 h compared to the control groups following injection. Escherichia coli, including MOF-199 and CuBTC (copper(II)-benzene-1,3,5-tricarboxylate) as antibacterial agents  based on 4,4-dicarboxy-2,2-bipyridic acid (H2dcbp) was prepared under different reaction conditions with identical structures exhibiting four different morphologies  2[Zn(TATAT)2/3]-3DMF-H2O. A hexadentate ligand  of 1,3,5-triazine-2,4,6-triyl)triisophthalate (TATAT) and Zn2+ was developed to use Zn2+ as a hexadentate ligand and Zn2+ as a method for the delivery of 5-fluorouracil as an anticancer drug . T. T115]. A study on GO/rGO doped with carboxylic acid doped with AlFu as a natural anticancer agent containing well-ordered saponin. GO carboxylic acid-containing/rGO was delivered to periodontal ligament fibroblasts (PDL) and OSCC with excellent PDL and OSCC GO results. To develop an innovative hybrid nanostructure with high porous properties and nontoxic to saponin loading, it was necessary to use aluminum fumarate (AlFu) as the core-shell nanocomposite of MOF. This study investigated nanocomposites containing aluminum fumarate as an integral component. AlFu modifies graphene oxides (GOs) and reduced graphene oxides (rGOs) in the core-shell nanocomposites. These compounds were determined to be anticancer agents against these cancer cells using two in vitro assays, including flow cytometry and MTT analyses. According to the MTT results, cells from PDL, exposed to AlFu-GO-saponin 250 mg/mL, survived between 74.46 and 16.02%, while cells from OSCC cells exposed to similar concentrations viability between 38.35 and 19.9%, proving that the nanostructure exhibited anticancer activity . The AlFAfter applying various nanostructures to PDL and OSCC cell lines, flow cytometry was performed to determine whether the nanostructures had any adverse effects after being applied to the cells. In addition, Mousavi and colleagues observed whether the nanostructures induced apoptosis in the cells after the nanostructures were used. The results of the experiments show no statistically significant variation between the control group and the treated group in terms of the degree of cell apoptosis in the treated group, which is consistent with the results of the control group. According to the study results, OSCC cells show a significant difference compared to PDL cells regarding the effects of the control group (2.52/0.78%). It was found that both AlFu-GO-saponin groups and AlFu-rGO-saponin groups show an increase in apoptotic cells compared to the control groups. Both groups show an increase in apoptotic cells of 10.98 × 2.36–26.90 × 3.24% and 15.9 × 4.08–29.88 × 0.41%, respectively. In addition to the differences between the Saponin, AlFu-GO, and AlFu-rGO groups in terms of apoptotic cells, there were also some significant differences in the percentages of apoptotic cells between the Saponin, AlFu-GO, and AlFu-rGO groups, with a rate of 13.94% being the highest, 22.75% is the lowest, and 16% being the lowest in the Saponin, AlFu-GO, and AlFu-rGO groups, respectively. In addition to a closer look at these graphs, it is clear that the AlFu-rGO-saponin combination therapy was associated with a significant increase in apoptosis compared with the nanostructures alone; thus, nanoparticles alone did not achieve the same results as the combination  125]..125].3O4@C nanocomposites based on metal-organic frameworks (MOFs). By using this platform in mice with CAL27 tumors, it was found that the combination therapy of chemotherapy and magnetic hyperthermia significantly slowed down the growth of the tumor. The underlying process showed that the high cell death rate of the tumor, together with necrosis and a low microvessel density, inhibited tumor growth. There is much potential for the clinical treatment of cancer with this innovative nano-platform because it is easy to fabricate, releases drugs on demand, and enables magnetically triggered, highly efficient combination therapy of chemotherapy and magnetic hyperthermia [Multifunctional nanomedical MOF platforms offer broad perspectives for imaging-assisted combination therapy in precision medicine for cancer. As an innovative nanomedicine cancer platform for combined cancer therapy with MRI-guided magnetically triggered chemotherapy and hyperthermia, Zhu et al. developed novel porous Ferthermia .Another MOF that has been used as a targeted nanocarrier with hyaluronic acid (HA) is the PCN-224 MOF. DOX-PCN NPs with a HA coating have been developed for dual chemo-photodynamic treatment. The preparation of spherical PCN-224 NPs with a diameter of 100 nm was shown to result in tremendous cellular uptake. The carboxylic acid functional groups of Zr metal nodes and HA established coordination bonds, which resulted in the formation of a HA layer on the surface of the nanoparticles. The hyaluronidase of the cancer cell cleaved the polymeric shell that served as a gatekeeper, releasing Dox. It also possesses hydrophilic properties that contribute to colloidal stability. In this regard, compared with Hek 293T , for CD44-positive cells, such as MDA-MB-231 (human mammary gland or breast cancer cells) and SCC-7 (mouse squamous cell carcinoma), the developed system HA-DOX-PCN demonstrated toxicity and selective cellular uptake under light irradiation . Other MMOFs have developed to the point where they can now be used in various biomedical technologies thanks to recent developments in material science and advanced materials. MOFs have attracted the attention of researchers working in the fields of cancer diagnostics, drug delivery, imaging, and biosensing, to mention a few, due to their adaptability in structure and function. With continued development and study, MOFs will soon be a viable option for usage as a single platform for numerous applications in biology and cancer therapy. One of the main problems of conventional cancer therapies is off-target effects on healthy tissue. Recently, thanks to the development of novel nanomaterials, targeted therapies for tumors have been developed that allow for more targeted cancer treatment with less harmful effects of chemotherapeutic agents on human cells. However, using nanomedicines in clinical practice has several drawbacks, including their reduced ability to overcome biological barriers and unfavorable off-target effects. Since MOF nanomaterials have advantages in imaging, drug delivery, and antibacterial properties, we focus on their use in cancer treatment in this review. There have been many experimental studies on these nanomaterials. Still, there are few clinical trials, so further clinical research is needed to prove the benefits and efficacy of these materials in the clinic. In addition, effective drug release and high drug concentration in target cells are required for clinical treatment; therefore, combination therapies must be used to improve the efficacy of MOFs. To achieve optimal results, it is also crucial that MOFs are carefully synthesized to allow most normal cells to survive during the in vitro and in vivo treatment process. Studies have shown that MOF nanomaterials, such as ZIF, AlFu, and MIL-100, perform exceptionally well in drug delivery. These materials have been proven in vivo and in vitro studies to have low toxicity and high surface area.


Coronary physiology-guided PCIs are recommended worldwide. However, invasive coronary physiology methods prolong the procedure, create additional risks for the patients, and prolong the fluoroscopy time for an interventional cardiologist. Otherwise, there is a noninvasive coronary physiology evaluation method, QFR, that can be safely used even in STEMI patients.A total of 198 patients admitted with STEMI and at least one intermediate (35–75%) diameter stenosis other than the culprit artery between July 2020 and June 2021 were prospectively included in this single-center study. All patients were randomized into one of two groups . A 12-month follow-up with echocardiography, exercise stress test, and quality of life evaluation was performed in all included patients. For the QOF evaluation, the Seattle Angina Score Questionnaire was chosen. Statistical analysis was performed using the Kolmogorov–Smirnov test, Student’s t-test, Mann–Whitney U test, Pearson’s chi-squared test and Kaplan–Meier estimator.Ninety-eight (49.5%) patients were randomized to the first group, and 100 (50.5%) patients were included in the second group. Statistically, significantly more patients had a medical history of dyslipidemia  and slightly better left ventricular ejection fraction  in the QFR group. Six fewer patients required non-culprit artery revascularization within the 12-month FU in the QFR group . Survival analysis proved that patients in the Angio group had a more than 6-fold greater risk for death within a 12-month period after MI , with the highest mortality risk within the first two months after initial treatment.Using QFR in non-culprit lesions in patients with ST-elevation myocardial infarction reduces mortality and revascularization at the 12-month follow-up and improves the quality of life of the patient.The study was approved by the Regional Bioethical Committee and conducted under the principles of the Helsinki Declaration and local laws and regulations.The online version contains supplementary material available at 10.1186/s12872-023-03153-7. When treating patients who have suffered an ST-segment elevation myocardial infarction (STEMI), the initial percutaneous coronary intervention (PCI) should be performed as quickly as possible, and it is recommended that only infarct-related artery (IRA) PCI be performed . On the Despite all improvements, fractional flow reserve (FFR), an invasive hyperemic hemodynamic physiology evaluation method, remains the gold standard for physiological evaluation . HoweverFurthermore, compared to angiography-guided PCI, FFR-guided PCI significantly reduces reinfarction and mortality rates . FFR-guiThe instantaneous wave-free ratio (iFR) is an additional adenosine-free physiology evaluation method that has been introduced in clinical practice because adenosine-caused hyperaemia is very uncomfortable and creates an additional risk for patients. When compared to FFR, iFR is responsible for 27.7% fewer adverse procedural reactions .Two extensive clinical studies compared iFR- and FFR-based PCI in patients with stable coronary artery disease or non-STEMI with a 1-year follow-up , 19. TheSince physiology evaluation is underused worldwide, it was believed that the wireless physiology evaluation method may become a game changer. Even though it can be used offline, it is suitable for physiological evaluation in hemodynamically unstable patients with cardiogenic shock, in contrast to wire-based methods, which significantly extend the procedure time , 21, 24.Despite all novelties, physiology-guided PCIs, especially in ACS patients, remain underused worldwide. Therefore, this study was designed to compare the cardiovascular outcomes of visually estimated only-guided PCI versus noninvasive physiology assessment-guided PCI. As a result, the purpose of the study was to investigate the differences between the non-culprit lesion significance evaluation methods in terms of the quality of life (QOL), the rate of rehospitalization, and the rate of revascularization within the first 12 months following the initial treatment.We prospectively enrolled 198 multivessel diseased STEMI patients who were admitted to our center from July 2020 to June 2021 and had a non-culprit stenosis (35–75%).After giving their written consent, all included patients were randomized into one of two groups: (1) QFR-guided PCI (named QFR) and (2) visual estimation-only guided PCI (named Angio). Patient data, medical history, and medical treatment were collected from their medical records.All coronary artery angiographies (CAGs) were performed in compliance with the recommendation for QFR analysis as described in previous publications .Visual estimation was performed by a CAG performing doctor and discussed at the interventional cardiologists’ meeting. If any additional physiological evaluation was needed upon meeting the judgment, the patient was excluded from the study and treated following European Society of Cardiology (ESC) guidance.The quantitative flow ratio is an innovative method to evaluate the hemodynamic significance of coronary stenoses. The evaluation is based on two different angiographic projections. Special software was used to calculate the pressure differences between pre-stenosis and post-stenosis. In this study, stenoses were observed as hemodynamically significant when the QFR was less than 0,8. For those who were randomized to the QFR group, QFR analyses were performed using the same software - Medis Medical Imaging, Medis QFR® 20.0. All of the QFR analyses were performed offline twice by an experienced and internationally certified QFR observer and averaged. If those two measurements were not matching (the difference between the two measurements was > 0.02), the third measurement was performed, and the three were then averaged. None of the patients were unsuitable for QFR analyses; therefore, none of them were excluded from this group.For the QOL evaluation, the Seattle Angina Score Questionnaire (SASQ) was chosen  within the 12-month follow-up.Pearson’s chi-squared test. Survival analysis was performed using the Kaplan–Meier estimator and expressed as a Kaplan-Meier survival curve. The chosen level of significance was p < 0.05.Statistical analysis was performed using SPSS 28.0 software. The Kolmogorov-Smirnov test was used to test quantitative parameters; if they were normally distributed, differences between two groups were evaluated using the Student’s t-test and expressed as the mean with standard deviation (SD); otherwise, they were evaluated using the Mann-Whitney U test and expressed as the median with interquartile range (IQR). Differences between categorical parameters were tested using The study was approved by the Regional Bioethical Committee and was done according to the principles of the Helsinki Declaration and local laws and rules.Of all, 98 (49.5%) patients were randomized to the QFR-guided PCI group, and 100 (50.5%) patients were included in the angiography-guided PCI group.Significantly more patients had a medical history of dyslipidemia and slightly better left ventricular ejection fraction (LVEF) Table ; Fig. 1 During the 12-month follow-up (FU) period, 6 (6%) patients required additional non-culprit MI artery revascularization, which was decided not to treat according to visual estimation in the Angio group  patients died, 2 (2.04%) in the QFR group and the remaining 12 (12%) in the Angio group. Survival analysis proved that patients in the Angio group had a more than 6-fold greater risk for death within the 12-month period after MI   had significantly better outcomes and six times less non-culprit lesion revascularization during the follow-up period. Additionally, in the one-year period, the QFR-guided group had twice as many rehospitalizations, and their physical limitations were better  or physiology-guided coronary lesion revascularizations , 35. HowThe mortality rate is one of the essential facts of the following period. FFR demonstrated this factor’s efficiency and showed us that it is possible to reduce mortality rates using coronary physiology evaluation methods . In thisThe QFR is a noninvasive coronary physiology evaluation method that is accurate for STEMI patients and can be performed by any qualified team member. The use of QFR for patients with ST-elevation myocardial infarction significantly reduced the mortality rate and revascularization at the 12-month follow-up. The patients who underwent PCI guided by the QFR had lower physical activity limitations during their daily activities.Below is the link to the electronic supplementary material.Additional file: The Seattle Angina Questionnaire


Introduction: The incidence of reverse shoulder arthroplasty (RTSA) in the United States has increased. Patients under 60 years old with failed rotator cuff repairs or degenerative joint disease with glenoid deformity may be candidates for RTSA and contribute to this increase. The single assessment numeric evaluation (SANE) score is a reliable post-operative scoring technique when compared with other post-operative measures. This study aimed to compare the effect of age on the likelihood of reaching clinically significant SANE scores following RTSA.Methods: A multicenter retrospective review was performed with a consecutive series of RTSA from December 2015 to September 2021. Patients were stratified into groups based on their age at the time of operation: (1) less than 60 years old, (2) 60-69 years old, (3) 70-79 years old, and (3) greater than 80 years old. The proportions of patients in all cohorts reaching and surpassing clinically significant thresholds at each visit were determined. Likelihood ratios were determined for each age cohort to compare the likelihood of reaching clinically significant SANE scores.Results: A total of 292 of 885 (33%) patients had completed survey data over two years and were included in the study. The 70-79-year-old group was 3.152 (p=.035) times more likely to achieve minimal clinically important difference (MCID) and 2.125 (p=.048) times more likely to achieve patient-acceptable symptomatic state (PASS) compared with patients <60 years old. The cohort who was 80+ years old was also 4.867 (p=.045) times more likely to achieve MCID compared to the <60-year-old cohort. The <60 cohort had the lowest proportion of all patient cohorts achieving MCID.Conclusion: A lower proportion of patients younger than 60 years old undergoing RTSA achieved clinically significant post-operative SANE scores. The 70-79-year-old age group was more likely to reach MCID and PASS, and the patients who were 80+ years old were more likely to reach MCID compared to patients younger than 60 years old. The incidence of reverse total shoulder arthroplasty (RTSA) has been increasing since 2012 . OverallDespite these promising results associated with specific demographics, RTSA is not without its risks. A recently published review pointed out that younger patients may experience less satisfaction in clinical outcomes following RTSA, possibly due to expectations of higher functional levels post-operatively . Guy et Various markers of clinical significance can be used post-operatively. The minimal clinically important difference (MCID) is the minimal amount of change in an outcome score that the patient perceives to be important -15. The The single assessment numeric evaluation (SANE) questionnaire is a patient scoring technique that assesses improvement post-operatively by asking patients to rate the affected body part from 0% to 100%, with 100% being considered normal and the highest score ,20-23. TIn studies analyzing clinically significant improvements following RTSA, the current literature is largely focused on older cohorts. Shah et al. compared total shoulder arthroplasty (TSA) and RTSA and described a larger proportion of patients greater than 75 years old reaching SCB undergoing TSA compared to RTSA . AdditioThis study aimed to compare cohorts of patients younger and older than 60 years old undergoing RTSA that reached MCID, SCB, and PASS for SANE scores post-operatively. We hypothesized that patients younger than 60 years old were going to be more likely to reach MCID, SCB, and PASS compared with older patients.A multicenter retrospective review was performed on a consecutive series of RTSA from December 2015 to September 2019 via the Arthrex Arthroplasty Database . The study was approved by the Arthrex International Grant Committee and the UConn International Review Board (IRB No. 16-042-1). Arthrex played no role in the study design, data collection, or composition of the final manuscript. Inclusion criteria included (1) RTSA performed between 2015 and 2019 for any indication and (2) completion of baseline, nine-week post-operation, 16-week post-operation, one-year post-operation, and two-year follow-up patient-reported outcomes. Patients were excluded from the study for not completing all post-operative surveys. Surveys were completed by either the operating surgeon or clinical partner within the office visit at follow-up visits at each time point. A total of 292 of 885 (33%) RTSAs performed during the study period met inclusion criteria and were, thus, included in the analysis.To better analyze the effect of age on outcomes and the likelihood of reaching clinical significance, the patients were divided into four groups based on their age at the time of operation: (1) less than 60 years old, (2) 60-69 years old, (3) 70-79 years old, and (3) greater than 80 years old.Surgical techniqueRTSAs were performed by 15 different surgeons within the United States of America using a consistent technique . A deltopectoral approach was used to expose the shoulder, and the biceps tendon was routinely tenodesed. The humeral head was cut at approximately 135° and then covered with a protector plate while the glenoid was prepared. Based on patient pathoanatomy and surgeon preference, a neutral, 4 mm lateralized, or 2.5 mm inferior offset baseplate was chosen with the appropriate diameter between 33 and 42 mm in 3 mm increments. The humeral canal was then broached and fitted with a standard or short press-fit humeral stem . Polyethylene humeral liners and spacer were used to achieve soft tissue balance. Post-operative rehabilitation was not standardized.Statistical analysisMetrics of clinical significance included MCID, SCB, and PASS. Clinical significance was established according to the values reported by Gowd et al: MCID is defined as an improvement in the SANE score by 29 points, SCB is defined as an increase in the SANE score by 50 points, and a PASS threshold is for SANE scores of 75 or greater . These vDescriptive statistics, including mean and standard deviation (continuous variables) and the frequency and proportion , were determined for each age group. Differences between the age group cohorts in demographic and surgical data were determined with ANOVA, chi-square, or Fisher exact tests. Mixed effects logistic regression models were used to determine the individual effect that age and time had on achieving MCID, SCB, and PASS for SANE scores. All regression models included a random intercept to account for repeated measures on each patient. Results for the regression models are reported as odds ratios (OR) with corresponding 95% confidence intervals for the likelihood specific age group cohorts would reach clinically significant SANE scores post-operatively.Fischer’s exact test was used in a post-hoc analysis to compare demographic information of the cohorts, including average BMI, smoking status, diabetes status, implant information, worker’s compensation, and whether the operation was a primary or revision case. A p<.05 was considered statistically significant. All statistical analyses were conducted with STATA .A total of 292 out of 862 patients with complete data for all two-year post-operative visits were included to improve the precision of outcome measurements and, thus, decrease selection bias. Thirty-nine patients were <60 years old, 115 patients 60-69 years old, 115 patients 70-79 years old, and 23 patients older than 80 years old. Table Figure Table This study found that a lower percentage of patients <60 years old reached clinically significant SANE scores after undergoing RTSA at the two-year mark post-operatively. The 70-79-year-old cohort was more likely to reach MCID and PASS, and the cohort who were 80+ years old was more likely to reach MCID when compared to patients <60 years old. More specifically, patients younger than 60 years old had the lowest percentage of patients reaching MCID and were less likely than the cohorts who were 70-79 and 80+ years old to reach MCID or PASS. All age cohorts experienced the largest increase in SANE scores prior to the 26-week visit. Surprisingly, the 80+ cohort had the sharpest decline in the post-operative percentage of patients achieving SCB, with a nearly 20% decline from year one to year two.There have been various studies that have attempted to look at clinical outcomes for RTSA based on the patient’s age. Numerous groups have described improvements in ROM, ASES, SST, and satisfaction in patients younger than 65 -8,28. InThe timeline of increasing SANE scores varied slightly between age groups. Patients <60 years old experienced the largest increase in average SANE scores from 43 to 62 points between the nine-week and 26-week visit. The 60-69-year-old cohort experienced an increase from 50 to 68 points between the nine-week and 26-week visit. The 70-79-year-old cohort experienced its largest increase improving from an average SANE score of 31-50 points between the pre-operative and nine-week visits. Lastly, patients older than 80 years old had the largest increase in mean SANE score from 26 to 58 points between the pre-operative and nine-week visits. Despite the largest increase occurring at slightly different times in our study, each cohort is in agreement with Grubhofer et al. and Shields et al., who both argue that a large majority of healing from shoulder arthroplasty occurs within the first six months following the operation and nearly all improvement occurs within 12 months post-operatively ,31.Additionally, the above findings agree with Clark et al., who described how RTSA can be safe in patients older than 80 and how age should not necessarily be a contraindication to the procedure . Lastly,In our post-hoc analysis, patients <60 years old were found to have a higher rate of smokers. As Hartline et al. describe, patients who identify as current smokers exhibit higher pain scores following RTSA . This hiAdditionally, the younger than 60-year-old cohort had a significantly higher rate of revision cases. Tashjian et al. found that patients undergoing revision RTSA have an increase in pain post-operatively, which could translate to lower SANE scores seen in this group of patients within our less than 60 cohort . It shouOur cohorts did not exhibit statistically significant differences in average BMI. Reid et al. found that obese and non-obese patients are able to achieve clinically significant outcomes following both RTSA and TSA, which corresponds with our patient cohorts . FurtherOne limitation of our study is that there were a large number of patients not included in this analysis due to noncompliance with study protocols and missing study data. This included patients who did not complete the required post-operative visits and surveys at all post-operative visits within the two-year mark. The 33% follow-up rate increases the chances of statistical errors, such as selection bias, and limits generalizability. Another limitation of this study is that surveys were only included through the two-year post-operative visit. As seen in our data, the patients who are 80+ years old displayed the sharpest decline in the proportion of patients achieving SCB; however, it is unknown if further declines in other age cohorts will occur beyond two years. Further research is required to determine how clinically significant SANE scores vary in post-operative visits beyond the two-year mark.In conclusion, a lower proportion of patients younger than 60 years old undergoing RTSA achieved markers of clinical significance for post-operative SANE scores. The 70-79-year-old age group was more likely to reach MCID and PASS, while the patients who are 80+ year old were more likely to reach MCID compared to younger patients. Future studies are warranted to determine whether there are differences among age cohorts in achieving clinically significant SANE scores beyond the two-year post-operative time point.


The 2021 World Health Organization study on the impact of COVID-19 on older people (≥60 years) in the African region highlighted the difficulties they faced as the virus spread across borders and dominated the way of life. These difficulties included disruptions to both essential health care services and social support, as well as disconnections from family and friends. Among those who contracted COVID-19, the risks of severe illness, complications, and mortality were highest among near-old and older persons.Recognizing that older persons are a diverse group including younger- and older-aged individuals, a study was conducted to track the epidemic among near-old (50–59 years) and older persons (≥60 years) in South Africa covering the 2 years since the epidemic emerged.Using a quantitative secondary research approach, data for near-old and older persons were extracted for comparative purposes. COVID-19 surveillance outcomes  and vaccination data were compiled up to March 5th, 2022. COVID-19 surveillance outcomes were plotted by epidemiological week and epidemic waves to visualize the overall growth and trajectory of the epidemic. Means for each age-group and by COVID-19 waves, together with age-specific rates, were calculated.Average numbers of new COVID-19 confirmed cases and hospitalizations were highest among people aged 50–59- and 60–69-years. However, average age-specific infection rates showed that people aged 50–59 years and ≥80 years were most vulnerable to contracting COVID-19. Age-specific hospitalization and death rates increased, with people aged ≥ 70 years most affected. The number of people vaccinated was slightly higher among people aged 50–59 years before Wave Three and during Wave Four, but higher among people aged ≥ 60 years during Wave Three. The findings suggest that uptake of vaccinations stagnated prior to and during Wave Four for both age groups.Health promotion messages and COVID-19 epidemiological surveillance and monitoring are still needed, particularly for older persons living in congregate residential and care facilities. Prompt health-seeking should be encouraged, including testing and diagnosis as well as taking up vaccines and boosters, particularly for high-risk older persons. Africa is described as being the youngest of the five world regions, due to having the lowest proportion of people aged ≥ 60 years of the total population . HoweverThe emergence and spread of COVID-19 brought uncertainty, mental and financial hardship, and far-reaching consequences for infected and affected older persons. Globally COVID-19 has disproportionately affected older people, both directly and indirectly. The health and wellbeing of older persons living in Africa lag behind those of other world regions . A 2020 South Africa had the highest incidence of confirmed COVID-19 cases in the African region and experienced five epidemic waves by May 2022 . The FirOlder persons in South Africa, particularly, have several challenges, including a high proportion with no formal education, approximately one fifth lived below the food poverty line in 2015, and a large proportion of households were headed by female older persons . The sevWeekly epidemiological updates commencing March 2020 were released by the National Institute for Communicable Diseases (NICD) in South Africa, showing the national and provincial trends of confirmed COVID-19 cases by age and sex, together with weekly testing summary reports and hospital surveillance reports from the Data for COVID surveillance system (DATCOV) . Thus, tThe study was approved by the Human Sciences Research Council Ethics Committee (REC) Protocol Number: (REC 3/17/03/21).https://sacoronavirus.co.za/), which were established as valuable information resources for a broad audience early in the epidemic trajectory . Hospitalization and death data were first available from May 30th, 2020  and vaccination data from February 17th, 2021 . All data were extracted up to March 5th, 2022 . There were missing data in confirmed cases in the weekly reports from epidemiological weeks 12–26 in 2021. For deaths, seven data points were missing for epidemiological weeks 30–36 in 2020, inclusive. These were estimated using a ratio to estimate the data for people aged 50–59 years. Hospital admissions and death data for epidemiological weeks 40–43 of 2020 for all age groups were not publicly available. No interpolation or imputation were performed on cases, hospitalizations or deaths to fill in the data gaps. The data were retrieved from the online datasets and analyzed as reported and missing information for the target age groups from the NICD reports were not included in this study. Cumulative vaccines administered were provided for people aged 50–59 years and ≥60 years. Hence these data could not be presented in the 10-year age intervals as listed above.This was a retrospective descriptive epidemiological study using routinely collected surveillance data to describe the differential impacts of COVID-19 on four target age-groups over the first four COVID-19 waves as defined for South Africa . AbsolutCumulative COVID-19 testing data were additionally extracted for the period March 1st, 2020  to January 9th, 2022 . Although testing was not one of the main outcomes of this analyses since these data were not publicly available for the target age groups, they have been included to illustrate the general testing pattern and test positivity over the period. No further analyses were done using the testing data. The testing summary reports contained the proportion that tested positive among specific age groups , and hence were not aligned with our target groups of near-old and older persons age categories.The number of confirmed cases was determined from the number of people who took a COVID-19 test, and the results were submitted through the notification system in South Africa. The number of polymerase chain reaction (PCR) tests as well as the test positivity done for all ages are aligned with the timing of the peaks and troughs observed for the COVID-19 waves . HoweverFor confirmed COVID-19 cases, hospitalization, deaths and vaccinations, the trends and population adjusted age-specific rates were examined by each epidemic wave, within each target age group and compared among the age groups.N = 102,958), followed by their counterparts aged 60–69 years   .The age-specific case rates show that people aged ≥ 80 years had the highest burden in all waves followed by their near-old counterparts aged 50–59 years. The exception was for Wave Three, where people aged 50–59 years had a higher case burden compared to all other target age groups . Review N = 20,371), followed by people aged 60–69 years   . The num 19,193) . Observe 19,193) , increasN = 4,999), compared to people aged 50–59 years  and 70–79 years   . People = 4,134) . The exc= 4,134) . The aveN = 83,149) than people ≥ 60 years  in terms of absolute numbers. This is likely due to the phased national rollout strategy which began with healthcare workers and then rolled out to people aged ≥ 60 years from May 17th, 2021 . In terms of age-specific rates, N = 363,000) than uptake among people aged ≥ 60 years . Age-specific rates for people who took a first dose vaccine after Wave Three and up to and during Wave Four was almost double among near-old people aged 50–59 years compared to older persons aged ≥ 60 years. However, inspection of the vaccine naïve numbers for both age groups show they were similar for people aged 50–59 years and ≥60 years after Wave Three, suggesting consistent gaps and stagnation in vaccine uptake for both age groups.Vaccination numbers were subtracted for each wave period from the total cumulative vaccinations administered, for the near-old and older persons age group . When vaStudying heterogeneity of COVID-19 among near-old and older persons is a crucial step toward identifying their risk level and proposing timely interventions, toward safeguarding their health and wellbeing. Thus, the study examined the growth and trajectory of the epidemic within discrete near-old and older persons age categories over 2 years in South Africa using absolute numbers extracted from freely accessible epidemiological data and age-specific rates for each age group. During this time period, South Africa adopted five lockdown alert levels as part of a risk adjusted strategy from March 27th, 2020 until April 5th, 2022 and some advisories were specific to older persons. During lockdown levels four and five, all people aged ≥ 60 years and those with underlying medical conditions were advised to stay at home unless under exceptional circumstances. As the lockdown level restrictions were relaxed, employers were advised to adopt measures to cater for employees aged ≥ 60 years.Our key findings based on age-specific epidemiological data show different profiles for near-old and older persons over the first four epidemic waves covering a 2-year period in South Africa. Age-related differentials emerged when comparing COVID-19 surveillance outcomes in terms of absolute numbers  between the near-old (50–59 years) and older persons (≥60 years). For instance, a higher burden of COVID-19 confirmed cases, deaths and hospital admissions were observed in people aged 50–59 and 60–69 years, representing the younger of our target age groups. The age-specific case rates suggests that people aged 50–59 years and ≥80 years were most susceptible to acquiring COVID-19 over the 2-year study period. However, severity of outcomes relating to hospital admissions and deaths increased with age.N = 215,028) compared to other age groups  and found that most hospitalizations occurred among people aged 50–59 years (22.5%) and 60–69 years (18.9%)  for all ages but the majority of hospitalizations with a known outcome and severe disease were reported among people aged ≥ 60 years during Waves Two (Beta variant dominant) and Three (Delta variant dominant) .Similar to the hospitalizations, the age-specific death rates across all four epidemic waves examined, suggests that older persons aged ≥ 70 years were most likely to succumb to COVID-19 over the 2-year study period. It must be noted that the mortality estimates do not account for excess deaths. Our findings are consistent with surveillance data reported early in the pandemic, which established that the median age of confirmed COVID-19 cases was 51 years and fatality rates for people over 80 years of age were estimated to be five times higher than the global average as at April 2020 , 29. SimAt a population level, several African countries have lower life expectancies and elevated levels of pre-existing conditions, comorbidities and living circumstances. There are also biological mechanisms relating to the aging immune system which impact on their quality of life and wellbeing . A decliWith the spread of COVID-19, there was a need for rapid mobilization of resources to gather and collate surveillance data for monitoring purposes and several African countries used insights from their surveillance systems . In earlN = 4,825) from 19 facilities by August 2020  of respondents over 55 years were hesitant to receive a COVID-19 vaccine once it became available  among near-old and older persons. Near-old persons represent a group transitioning into older persons. Clinical management of confirmed COVID-19 cases evolved rapidly hence prompt health-seeking behavior should be encouraged, including testing and diagnosis, particularly for those high-risk older persons with comorbidities, to mitigate onset of severe illness or complications. This is especially important in congregate settings such as residential facilities for older persons, or in venues where they receive social care and support for health-related issues. Understanding the factors driving vaccination hesitancy in our target age groups who choose not to vaccinate or receive booster doses is needed. Risk tools and e-health for near-old and older persons should also be developed and made accessible given their technological capacities and challenges, as countries move from a national population-level risk approach to an individual-level risk approach, where the individual takes responsibility for their own risk adjusted strategy to preserve their health and wellbeing.Readily accessible disaggregated data were used to look at near-old and older persons age groups from reports and dashboards and were manually extracted. Thus, the data had to be synthesized and processed for the analyses. Gaps in the data by age had to be removed in the analyses. In addition, testing data were not available for the specific target age groups. Health-seeking behavior differs by age and sex for other health issues, which might contribute to observed differences in the cumulative and new case counts between age groups. This study did not analyze potential risk factors for the observed outcomes for the age groups, due to the lack of individual-level data. Nevertheless, the analyses presented show the utility of using publicly available surveillance data to describe the epidemiological trends of COVID-19 among older persons over a 2-year period to supplement efforts highlighting their specific needs.https://www.nicd.ac.za/diseases-a-z-index/disease-index-covid-19/surveillance-reports/weekly-testing-summary/; https://www.nicd.ac.za/diseases-a-z-index/disease-index-covid-19/surveillance-reports/weekly-epidemiological-brief/; https://www.nicd.ac.za/diseases-a-z-index/disease-index-covid-19/surveillance-reports/daily-hospital-surveillance-datcov-report/; https://www.nicd.ac.za/diseases-a-z-index/disease-index-covid-19/surveillance-reports/daily-hospital-surveillance-datcov-report/; https://sacoronavirus.co.za/vaccine-updates/.Publicly available datasets were analyzed in this study. These data can be found here: The study was approved by the Human Sciences Research Council Ethics Committee (REC) Protocol Number: (REC 3/17/03/21). Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.NA and IN conceptualized the paper. NA, IN, MM, and SD extracted and analyzed the data. NA, IN, and SD drafted the paper. All authors critically reviewed and revised the manuscript and approved it for submission.


It is unclear which stewardship metrics are most effective for audit and feedback to outpatient clinicians. In this study, we explored a metric that captures antibiotic-prescribing for all respiratory tract diagnoses to determine if it could serve as an appropriate metric for feedback.We performed a retrospective cohort study of in-person visits to the 7 walk-in clinics, including 3 Urgent Care locations, within University of Iowa Health Care during 2018-2022. Visits were categorized as respiratory visits (RVs) if a respiratory tract diagnosis was coded and the patient lacked complicating factors, such as a concomitant non-respiratory infection or certain comorbidities. We built a hierarchical logistic regression model that adjusted for antibiotic appropriateness tiers (1-3) to identify factors associated with antibiotic-prescribing for RVs. Using Spearman’s correlation, we compared the frequency at which clinicians prescribed antibiotics for RVs and other types of visits.There were 331,496 visits, and 96,546 (29.1%) led to an antibiotic prescription; 44,498 (46.1%) of these were for RVs (Tables 1 and 2). At the clinician-level (n=89), the mean frequency of antibiotic-prescribing for RVs was 36.4% (standard deviation 11.6). Factors at the visit-level associated with an increased odds of antibiotic use for RVs included age ≥ 65  and having at least one comorbidity . The frequency at which a clinician prescribed antibiotics for RVs was strongly correlated with antibiotic use for all visits . Clinicians who more often prescribed antibiotics for RVs also more often prescribed antibiotics for respiratory infections that are always viral , sinusitis , and non-streptococcal pharyngitis . There was no correlation between antibiotic-prescribing for RVs and the frequency of return visits within 30 days .A metric that quantifies the frequency of antibiotic-prescribing for all respiratory tract diagnoses correlated strongly with clinicians who over-use antibiotics for walk-in visits. Future studies should assess whether this type of metric is acceptable to clinicians and an effective tool for feedback.Daniel J. Livorsi, MD, Merck: Grant/Research Support Kelly M. Percival, PharmD, Gilead Sciences Inc: Advisor/Consultant


TM) faces some barriers in the form of frequent side-effects such as dry mouth. As a result, prostate cancer treatment based on radioactive mAbs conjugates hopes to reduce side-effects while still providing effective treatment to patients with prostate cancer.The prostate-specific membrane antigen (PSMA) protein present in most prostate cancer cells has emerged as a promising target for the imaging and treatment of prostate cancer. With the development of monoclonal antibodies (mAbs) against PSMA, cancer cells can be targeted effectively while minimizing side effects to patients. Radioactivity can be attached to mAbs for imaging and treatment. This manuscript provides an overview of the current development and future prospects of radioactive mAbs conjugates targeting PSMA in prostate cancer. The current FDA approved PSMA radioligand therapy (PluvictoProstate cancer (PCa) is one of the most prevalent cancer diagnoses among men in the United States and in several other developed countries. The prostate specific membrane antigen (PSMA) has been recognized as a promising molecular target in PCa, which has led to the development of specific radionuclide-based tracers for imaging and radiopharmaceuticals for PSMA targeted therapy. These compounds range from small molecule ligands to monoclonal antibodies (mAbs). Monoclonal antibodies play a crucial role in targeting cancer cell-specific antigens with a high degree of specificity while minimizing side effects to normal cells. The same mAb can often be labeled in different ways, such as with radionuclides suitable for imaging with Positron Emission Tomography (β+ positrons), Gamma Camera Scintigraphy (γ photons), or radiotherapy . Accordingly, the use of radionuclide-based PSMA-targeting compounds in molecular imaging and therapeutic applications has significantly grown in recent years. In this article, we will highlight the latest developments and prospects of radiolabeled mAbs that target PSMA for the detection and treatment of prostate cancer. Researchers continue to develop new antibody-based diagnostics and therapeutics for cancer based on their demonstrated effectiveness and ability to selectively bind to specific receptors (or antigens) that are overexpressed in tumor cells. While non-antibody ligands, such as transferrin or folate, may be useful targeting agents for their specific receptors on tumor cells, the same ligands are also abundant in certain normal cells, thereby leading to unacceptably low tumor-to-normal tissue ratios and consequent cytotoxicity. When it comes to specificity and selectivity, mAbs serve as much better vectors for the precise delivery of imaging or radiotherapy components to tumor cells while sparing healthy normal cells . FurtherThe tumor uptake of mAbs is affected by several factors, including blood flow, vascular volume, and antibody size. Additionally, the blood clearance of mAbs is slow and liver uptake is pronounced . By usinThe prostate-specific membrane antigen (PSMA) is a zinc containing metalloenzyme having a molecular weight of 100 kDa and is overexpressed in the vast majority of prostate cancer cells and in tumor neovasculature ,8. FigurAs a glutamate-carboxypeptidase, PSMA functions as a folate hydrolase to catalyze the hydrolysis of N-acetyl aspartyl glutamate (NAAG) and as an NAALADase , which is a neuropeptidase that regulates glutamatergic neurotransmission . These eCurrently, prostate cancer is one of the most prevalent cancer diagnoses among men in the United States and in a number of other countries ,20. It i68Ga-PSMA-11, 18F-DCFPyL, and 18F-rhPSMA-7.3 .,52.51,52 imaging . Subsequ (177Lu) ,55. Figue tumors . In subs6–7 days ,57. Corn6–7 days  evaluateguidance . To redu1, which J591 showed excellent targeting and imaging capabilities for PSMA. However, its translation to the clinic has been hampered for a number of reasons including its poor tumor penetrability, extended delays between agent administration and imaging, and its slow clearance from the blood pool . Neverth177Lu) is an ideal isotope for combined radioimmunotherapeutic and radiodiagnostic applications. It has an acceptable physical half-life of 6.7 days and emits short-range (0.2–0.3 mm) β particles and auger electrons for therapy as well as γ emission used for diagnostic SPECT imaging and dosimetry . As. As74]. a et al. . They reder wall . Notablyl cohort . On the patients . A singlea (57%) .227Th, 18.7 days half-life) complexed with a 3,2-HOPO chelator covalently linked to a fully human PSMA-targeting antibody. In preclinical evaluation studies, PSMA-TTC demonstrated strong antitumor activity. Clinical trials were initiated for PSMA-TTC in a Phase I dose-escalation study (NCT03724747) to determine the safety, tolerability profile, and MTD of PSMA-TTC in mCRPC patients. A second objective was to specify the recommended dose of PSMA-TTC for future clinical trials after assessment of the biodistribution and clearance of the drug from the body -DOTA-YS5 for PSMA-positive and PSMA-negative tumors in preclinical PDX and other xenograft models. Biodistribution studies have demonstrated high tumor uptake of [225Ac]-DOTA-YS5 over 17 days. The [225Ac]-DOTA-YS5 was gradually cleared from all healthy organs except the liver and bones. An evaluation of the therapeutic efficacy of [225Ac]-DOTA-YS5 in prostate cancer models is underway. A toxicology evaluation revealed that the 0.5 Ci activity levels were toxic to the kidneys, most likely because 213Bi was redistributed . M. M64Cu hompounds C. With rulations . Clinica68Ga-PSMA-11, 18F-DCFPyL, and 18F-rhPSMA-7.3. They provide high detection rates and diagnostic accuracy compared to conventional imaging techniques [177Lu-PSMA-617 (Pluvicto™) treatment and to evaluate responses to PSMA targeted therapy.There are currently a number of small molecule radioligands that have been approved by the United States Food and Drug Administration (FDA) for use in PET imaging of prostate cancer. Among them are chniques ,25. AddiMonoclonal antibodies targeting PSMA can be radiolabeled with specific radionuclides that are chosen for particular tumor characteristics and clinical indications, whether it be for targeted radiodiagnosis or systemic radiotherapy, and may serve as an alternative or have a complementary role to PSMA small molecule radioligands.The discovery of novel cell surface biomarkers and the development of mAbs with high specificity for these biomarkers could soon lead to an increased role for radiolabeled mAbs in prostate cancer. Accordingly, the accumulated experiences and lessons learned from previous mAb designs (failures and successes) are contributing to the development of the next generation of antibody-based cancer imaging and therapeutic agents.


ObjectiveThis study aimed to explore the potential of prostate-specific antigen density (PSAD) as a supplementary tool for defining high-risk Prostate Imaging Reporting and Data System (PI-RADS) 3 lesions in the peripheral zone on non-contrast-enhanced MRI. This additional stratification tool could supplement the decision-making process for biopsy, potentially helping in identifying higher-risk patients more accurately, minimizing unnecessary procedures in lower-risk patients, and limiting the need for dynamic contrast-enhanced (DCE) scans.Materials and methodsBetween January 2019 and April 2023, 30 patients with PI-RADS 3 lesions underwent MRI-ultrasound fusion biopsies at our institution. Age and PSAD values were investigated using logistic regression and chi-square automatic interaction detection (CHAID) analysis to discern their predictive value for malignancy.Results2. Logistic regression demonstrated PSAD to be a significant predictor of cancer (p=0.012), but not age (p=0.855). CHAID analysis further identified a PSAD cut-off value of 0.12, below which the cancer detection rate was 23.1% and above which the rate increased to 76.5%.The mean patient age was 64.7 years, and the mean PSAD was 0.13 ng/mLConclusionsThis exploratory study suggests that PSAD might be utilized to enhance the stratification of high-risk PI-RADS 3 lesions in the peripheral zone on non-contrast-enhanced MRI, aiding in decision-making for biopsy. While biopsy remains the gold standard for definitive diagnosis, a high PSAD value may suggest a greater need for biopsy in this specific group. Although further validation in larger cohorts is required, our findings contribute to the ongoing discourse on optimizing PI-RADS 3 lesion management. Limitations include a small sample size, the retrospective nature of the study, and the single-center setting, which may impact the generalizability of our results. Prostate cancer remains the second most common cancer in men globally and a significant cause of cancer-related death . The advPI-RADS 3 lesions on mpMRI represent an indeterminate risk of clinically significant prostate cancer, which complicates clinical decision-making concerning biopsy ,5. This One such parameter, prostate-specific antigen density (PSAD), has been identified as a promising adjunct in patients with PI-RADS 3 lesions . This meIn the current exploratory study, we assess the relationship between age, PSAD, and the presence of malignancy in patients with PI-RADS 3 lesions in the peripheral zone on non-contrast-enhanced MRI. Our intent is not to bypass biopsy but to provide a framework for clinicians to decide which patients would benefit most from the procedure, given the indeterminate risk that PI-RADS 3 lesions pose. We chose to focus on prostate cancer broadly, acknowledging that there are often discrepancies between biopsy and prostatectomy Gleason scores, which can impact the differentiation between prostate cancer and clinically significant prostate cancer ,10. Our We conducted a retrospective review of de-identified patient data from our institution between January 2019 and April 2023. Our study was exploratory in nature and did not require ethics committee approval due to the retrospective and de-identified nature of the data.Imaging techniqueWe performed all imaging using a Siemens Magnetom Verio 3.0 Tesla MRI machine with a body coil. The standard bpMRI protocol for each patient included axial and sagittal T2-weighted images, axial and sagittal diffusion-weighted imaging (DWI) with b values of 50, 400, and 1000 s/mm², an apparent diffusion coefficient (ADC) map, coronal T2-weighted images with fat suppression, and axial T1-weighted DIXON images.PatientsThe study involved patients who underwent a prostate MRI and were identified as having only PI-RADS 3 lesions located in the peripheral zone, as detected through non-contrast-enhanced MRI. These lesions were identified based on the PI-RADS v2.1 criteria. Two experienced radiologists evaluated the MRI images, and any discrepancies were resolved through discussion.We excluded patients who had poor-quality MRI images, lesions classified higher than PI-RADS 3 on the same examination, or findings of acute inflammation on pathology, as this could influence PSA levels and falsely affect the estimated PSAD threshold for stratification.Biopsy procedureWe executed all biopsies using a transrectal approach, facilitated by MRI-ultrasound fusion guidance. This method enabled targeted sampling of the area of interest, with core biopsies taken for pathological assessment.Data analysisWe analyzed the data using SPSS Version 21 . The primary goal of our analysis was to investigate the association of age and PSAD with the presence of malignancy. This analysis was intended to support biopsy decision-making by providing additional information on which patients might be at higher risk, rather than suggesting biopsy is unnecessary. We calculated PSAD by dividing the serum PSA level by the prostate volume as reported on MRI. We used univariable and multivariable logistic regression models to identify predictors of malignancy. We selected cut-off values through CHAID (chi-square automatic interaction detection) decision tree analysis.The patients' age and PSAD served as independent variables, while the biopsy-confirmed presence of malignancy served as the dependent variable. We set statistical significance at p<0.05.In addition to determining the cut-off value using CHAID decision tree analysis, we also performed a receiver operating characteristic (ROC) curve analysis.We included 30 patients with PI-RADS 3 lesions in the peripheral zone in our analysis. The participants' ages ranged from 48 to 74 years. PSAD values ranged from 0.04 to 0.23, with a median value of 0.13.Multivariable logistic regression revealed that age did not significantly correlate with malignancy (p=0.855). However, PSAD displayed a significant positive association p=0.012), suggesting that a higher PSAD could correlate with a higher probability of malignancy in the examined PI-RADS 3 lesions, notwithstanding the need for biopsy confirmation  compared to the CHAID analysis (0.12). However, both analyses showed similar trends in predicting higher risk for the presence of prostate cancer, providing a supplementary tool for biopsy decision-making.In summary, our data suggest a strong correlation between PSAD and the risk of malignancy in PI-RADS 3 lesions in the peripheral zone. It reinforces the importance of biopsy in validating these findings and ensuring accurate diagnosis.Our study sought to investigate the potential of PSAD in defining high-risk PI-RADS 3 lesions located in the peripheral zone using non-contrast-enhanced MRI. Given the current constraints of the PI-RADS v2.1 in its capacity to detect clinically significant prostate cancer, refining the risk stratification approach is crucial ,12. In aPI-RADS v2.1 is widely accepted as an efficient tool for risk stratification in prostate cancer, providing vital assistance in clinical decision-making . HoweverAt the same time, the utility of PSAD as a risk stratification tool has been validated in various studies ,6. In paGiven these uncertainties, our study sought to further explore the potential utility of PSAD in stratifying PI-RADS 3 lesions in the peripheral zone on non-contrast-enhanced MRI, while simultaneously addressing the limitations identified in previous studies. The aim was not only to add to the existing evidence base but also to contribute to optimizing patient management strategies in prostate cancer.While the aim of this study was to evaluate the role of PSAD in risk stratification in the presence of PI-RADS 3 lesions, it is essential to note that we did not strictly distinguish between the detection of prostate cancer and clinically significant prostate cancer. This approach was intentional due to the common discrepancy observed in Gleason scores on biopsy and prostatectomy in the same patient, as noted in existing literature ,10 and oOur analysis suggests that an elevated PSAD may be indicative of an increased likelihood of malignancy in PI-RADS 3 lesions located in the peripheral zone. Consistent with previous studies ,19, thesOf note, the relatively high rate of cancer detection in our PI-RADS 3 cohort could be attributable to the decision to biopsy these patients. The biopsy decisions made by the urologists were based on unspecified criteria, potentially leading to an overrepresentation of cancer cases in our sample. This bias underlines the need for standardized and more refined risk stratification parameters, such as the PSAD cut-off proposed in our study.An important aspect of our study design to highlight pertains to our exclusion criteria. We deliberately excluded cases with low-quality MRI images, lesions classified higher than PI-RADS 3 on the same examination, and instances of acute inflammation on pathology. These choices were made to ensure the accuracy and reliability of our results. Specifically, the exclusion of low-quality images reduces the likelihood of misinterpretation or diagnostic errors due to poor visualization. Likewise, the exclusion of higher classified lesions ensures that our study remains focused on PI-RADS 3 lesions only, maintaining the consistency of our sample population. Additionally, the exclusion of cases with acute inflammation on pathology was decided upon due to the potential for inflammation to cause an increase in PSA levels, which could inadvertently skew the threshold for PSAD stratification. These criteria, while potentially limiting the generalizability of our findings, were crucial in ensuring the reliability of our results and conclusions.Despite the study's promising findings, several limitations must be considered. The relatively small sample size from a single institution limits the generalizability of the results. Moreover, as an exploratory study, our results need to be validated in larger, prospective studies to ascertain the true clinical value of PSAD in this context. Furthermore, the retrospective nature of the study may introduce selection bias. However, this was mitigated to an extent by the fact that all eligible patients during the study period were included in the analysis.Our study underscores the potential utility of PSAD in the identification of higher-risk PI-RADS 3 lesions in the peripheral zone using non-contrast-enhanced MRI. The observed association between increased PSAD and the presence of malignancy suggests that PSAD could be a valuable adjunct in risk stratification for prostate cancer. We propose a PSAD cut-off of 0.12, which could augment biopsy decision-making by aiding in the identification of patients at higher risk who may warrant a biopsy, while potentially reducing unnecessary procedures in lower-risk patients, when aligned with their broader clinical profile. This could, in turn, minimize the need for further contrast-enhanced scans. However, these findings stem from a single-institution study with a small patient sample and, therefore, warrant validation through larger, multi-center studies.