
Introduction: Placental site trophoblastic tumor (PSTT) is a rare form of gestational trophoblastic disease (GTD) that is usually associated with high mortality compared to the other subtypes because of its unpredictable biological behavior, less responsiveness to chemotherapy, and poor prognosis. Case Presentation: We present a 27year old nulliparous lady referred to our centre for recurrent vaginal bleeding following two evacuations for an incomplete spontaneous miscarriage after eight weeks of amenorrhea. Her assessment revealed low serum beta-human chorionic gonadotropin (βhCG) and high human placental lactogen (hPL) levels. Ultrasound scan and Doppler study showed a highly vascular tumor infiltrating the myometrium. She strongly desired to preserve her fertility and was initially commenced on low dose Methotrexate with marginal reduction in tumor volume and resistance on higher dose. She responded well to combination chemotherapy and the tumor disappeared after the second course. She received three additional courses and was followed up with serial ultrasonography for one year. She subsequently conceived spontaneously, with vaginal delivery of a live, normal female baby at term. Conclusion: Though hysterectomy combined with chemotherapy is the recommended management for PSTT and serum hPL is the usual tumor marker for follow-up, we present a case of successful treatment with combination chemotherapy alone and follow-up with subsequent cure, spontaneous conception, and delivery of a live baby.
According to the literature, COVID-19 vaccines reduce long COVID-19 symptoms such as cognitive dysfunction, kidney diseases, myalgia, and sleeping disorders (5-7). Therefore, the results of the meta-analysis support the clinical safety and efficacy of SARS-CoV-2 vaccines against long COVID-19. However, the available studies have several limitations: 1) there were individuals that exhibited natural improvement of long COVID-19 symptoms which may have been underestimated as vaccination in clinical setting; 2) studies used wide range of COVID-19 vaccines including both inactivated vaccines and mRNA COVID-19 vaccines. Thus, findings should be interpreted with caution. Since booster vaccines show great promise in both prevention of infection and progression, further research on boosters and omicron-specific vaccination is needed to be performed. Consequently, the current comprehensive literature recommends SARS-CoV-2 vaccine to reduce the risk of long COVID-19 in cases of progression. There are no findings of a negative effect of COVID-19 vaccination on worsening symptoms of COVID-19. Therefore, SARS-CoV-2 vaccination should be improved as soon as possible, especially offering a full course of vaccination. More research is needed to discover the mechanism of action of the COVID-19 vaccines on long COVID-19 in the future.
Background: Effective trauma management requires specialized skills, and advanced technologies such as Virtual Reality (VR) can enhance medical education. This study aimed to evaluate the effectiveness of VR-based educational content in training emergency medicine students on managing multiple trauma victims. Materials and Methods: This educational study involved 40 emergency medicine students who were randomly assigned to two groups. The first group underwent VR-based training in pairs (two students per team) over four sessions, focusing on multiple trauma scenarios. The second group practiced scenario simulations using moulages. Both groups received feedback after each session and had the opportunity to repeat the scenarios. Results: In this study, the performance of 40 emergency medicine students was evaluated using pre- and post-tests. The results demonstrated that both educational methods—Virtual Reality and live simulation—significantly enhanced student performance. A comparison between the two approaches revealed no significant difference in effectiveness, as both methods led to comparable improvements. Conclusion: Virtual Reality was recognized as an effective tool for teaching trauma management and could be widely used in clinical education. However, further studies are necessary for a more comprehensive evaluation and to establish the effectiveness of this technology in educational settings.
Introduction: Polycystic ovarian syndrome (PCOS) is one of the most common hormonal disorders affecting women of reproductive age. Numerous studies have suggested the involvement of inflammation in the pathogenesis of PCOS. As a result, drugs with anti-inflammatory effects may offer therapeutic benefits for this condition. The standard medications used in treating PCOS include cyproterone compound (cyproterone acetate + ethinyl estradiol) combined with spironolactone, metformin, and pioglitazone. This study aimed to compare the effects of these drugs on the serum levels of inflammatory markers, including hs-CRP, C3, and C4, in women with PCOS.Materials and methodsNinety women with PCOS were randomly assigned to three treatment groups for 90 days as follows: Group CC-SP received cyproterone compound (cyproterone acetate 2 mg + ethinyl estradiol 35 µg) daily, along with 100 mg/day spironolactone; Group M received metformin (1500 mg/day); and Group P received pioglitazone (30 mg/day). Serum levels of hs-CRP, C3, and C4 were measured before and after treatment.Comparisons of changes in variables between groups were performed using the ANOVA test. Additionally, covariance (ANCOVA) analysis was used to examine differences between groups, adjusting for confounding variables. Probability values of ≤ 0.05 were considered statistically significant.ResultsThe C3, C4, and hs-CRP levels were increased in the CC-SP group while significantly decreased in the pioglitazone group (p<0.05). These changes were not statistically significant in the metformin group.ConclusionsPioglitazone reduces the serum levels of inflammatory markers and may be effectively combined with cyproterone and spironolactone in the treatment of PCOS.
This article systematically reviews the psychological and professional injuries psychotherapists experience during therapy sessions. A comprehensive search was conducted across databases such as PubMed, PsycINFO, Scopus, and Noormags to identify relevant studies. The findings revealed that psychotherapists are exposed to significant risks, including burnout, occupational stress, secondary trauma, and empathy fatigue, all of which can severely impact their mental health, job satisfaction, and professional performance. These risks are influenced by various factors, such as the type of clients they work with, the severity of mental health issues presented by clients, and the duration of therapy sessions. Effective mitigation strategies, such as developing structured self-care programs, promoting psychological exercises, and fostering a supportive organizational culture, were highlighted as essential. Additionally, providing professional counseling, reducing workloads, and enhancing work-life balance are key measures to address these challenges. Further research is crucial to explore innovative and effective strategies for reducing these occupational hazards and improving psychotherapists' well-being.
Introduction: Diabetes mellitus (DM) significantly contributes to morbidity, mortality, and healthcare costs. This study aims to evaluate diabetes control and treatment outcomes in individuals treated at primary healthcare centers and a tertiary care hospital in rural Thailand.Methods: Data from 27,266 type 2 diabetes patients receiving care in Sakon Nakhon province in 2023 were analyzed. Participants’ treatment outcomes, including blood sugar, blood pressure control, and screening rates, were compared across urban community health centers, subdistrict health-promoting hospitals, and a tertiary care hospital.Results: Primary care settings demonstrated better management of central obesity and renal screening compared to tertiary care. However, blood sugar and blood pressure control rates were suboptimal across all settings, and HbA1c testing frequency remained low. Mortality rates did not differ significantly between settings.Conclusion: While diabetes management in primary and tertiary care showed similarities, primary care settings were more effective in managing BMI and renal screening. These findings highlight the importance of reinforcing diabetes management strategies, particularly in primary care, to enhance outcomes.
INTRODUCTION: there is no clear relationship between the threshold cycle of COVID-19 and severity of pulmonary involvement in the CT scan of patients. Methods: 254 patients were included. The number of cycle of threshold virus, was extracted. The severity of pulmonary involvement was categorized based on the percentage of involvement of each lobe Based on CT scan. The relationship between the CT number and the involvement in the CT scan, was measured.Results: 254 patients with COVID-19 such as 158 (62.2%) men and 96 (37.8%) women with a mean age and standard deviation of 17.785 ± 60.99 years. The average threshold cycle (CT Value) is 5.912 ± 19.38 and it’s minimum and maximum are 9 and 36. The percentage of right lung involvement was 29.7±46.7% and the percentage of left lung involvement was 29.8±47.8%. The number of people without conflict is 6 (2.4) %, with mild conflict 39 (15.4) %, moderate 65 (25.6%) and severe 144 (56.7%). The number of people without involvement of the right lobe is 11 (4.3%), score 1, 42 (16.5%), score 2, 75 (29.5%), score 3, 51 (20.1%), involvement Score 4, 75 (29.5%).The number of people without left lobe involvement is 12 (4.7%), score 1, 46 (18.1%), score 2, 71 (28%), score 3, 48 (18.9%), involvement Score 4, 77 (30.3%) .Conclusion: With the increase of lung involvement, the amount of threshold cycle has decreased, which can indicate the inverse relationship of threshold cycle with the severity of disease involvement.
Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly, significantly impacting their quality of life. AMD is classified into two main types: dry (non-neovascular) and wet (neovascular) AMD. While the dry form is more prevalent, the wet form is associated with more severe vision impairment. The variability of AMD, influenced by genetic, environmental, and lifestyle factors, presents a significant challenge in its management. Precision medicine, which tailors healthcare according to individual differences, has emerged as a promising approach for diagnosing, treating, and preventing AMD. This represents a paradigm shift in the management of AMD. By customizing treatments based on individual genetic, environmental, and lifestyle factors, precision medicine can potentially improve outcomes for AMD patients. This review comprehensively evaluates current precision medicine strategies in AMD, addresses existing challenges, and explores the potential for personalized interventions to enhance patient outcomes.
Background: Cystic fibrosis (CF) is associated with numerous nutritional and health challenges that significantly impact the patient's quality of life and clinical outcomes. Nutritional management plays a vital role in addressing issues such as pancreatic insufficiency, fat malabsorption, vitamin and mineral deficiencies, and complications like CF-related diabetes (CFRD) and liver disease (CFLD). This review provides an overview of the essential nutritional assessment, management strategies, and the role of CFTR modulator therapies in improving the nutritional status and health outcomes in CF patients.Methods: A comprehensive review of the current literature regarding the nutritional needs, deficiencies, and therapies in CF patients was conducted, including a focus on pancreatic enzyme replacement therapy (PERT), vitamin and mineral supplementation, and the management of bone disease, CFRD, and CFLD. Additionally, the impact of CFTR modulators on nutritional outcomes and related complications was examined.Results: Nutritional assessment in CF is multifaceted, incorporating clinical, anthropometric, body composition, and biochemical evaluations. Early intervention strategies, including PERT and tailored supplementation, are critical for managing fat-soluble vitamin deficiencies, mineral imbalances, and maintaining adequate body mass. The prevalence of CFRD and CFLD significantly impacts CF management, necessitating regular screening and appropriate treatments. CFTR modulator therapies have led to improvements in lung function and nutritional status, though regular monitoring is essential to prevent complications such as hypervitaminosis, altered lipid metabolism, and insulin sensitivity.Conclusion: A proactive, individualized approach to nutritional management is essential in CF, emphasizing early intervention, regular screening, and personalized therapy to address the diverse challenges faced by these patients.
Background: Uterine fibroids or Leiomyoma (UFs) are one of a common problem that affects the quality of life in women. Recently use of vitamin D for treating Leiomyoma has been considered. Study's PurposeThis Systematic Review was performed with aim to evaluate the current evidence for the efficacy of vitamin D in treating uterine fibroids.Methods: Relevant studies were identified from the following Electronic searching of Medline, PubMed, Scopus, Cochrane, Embase, Web of science, SID and Google Scholar up to Feb 2021. Inclusion criteria consist of Both English and Persian, published, clinical trials using vitamin D as medical for treatment of uterine fibroids. In the long run four RCTs met the inclusion criteria. The quality of these trials was evaluated by two researchers who carried out the data extraction, using Oxford Center for Evidence Based Medicine checklist. Statistical analysis was performed by Comprehensive Meta-analysis (CMA) Version 2. To assess the publication bias and heterogeneity, Egger’s and Begg’s tests and I2 were used, respectively. In addition, the Random effects model was employed to perform the meta-analysis. Findings: The heterogeneity in the studies was determined as 95.17% (p<0.000). There was publication bias among the studies included; the p-values of Egger’s and Begg’s tests were 0.05 and 0.05, respectively. The effects of Vit D on UFs was statistically significant [mean difference (MD) =2.88; 95% confidence interval (CI): (4.72-1.044); p<0.002]. Conclusion: Vitamin D for treating uterine fibroids can be an effective method, but more studies are needed to confirm these findings.
Introduction: Tribulus terrestris is rich in bioactive compounds such as saponins, flavonoids, and alkaloids, which have been researched for their therapeutic properties. Its diuretic effects can help with hypertension and edema, its aphrodisiac properties can aid sexual function, and its antilithic properties can prevent kidney stone formation. The physicochemical and pharmacological characteristics of Tribulus terrestris are currently being studied.Methods and Materials: We utilized the PubChem database to gather data on the studied compounds, including their formulas and structures. Subsequently, we employed SwissADME software to assess the physicochemical and pharmacological properties of these compounds in Tribulus terrestris (TT).Results and Discussion: Steroidal saponins and sterols exhibit varying solubility levels in physiological fluids due to their hydrophobic nature and glycosylation patterns. Flavonoids, on the other hand, demonstrate favorable solubility. Compounds like (25R)-Spirosta-3,5-dien, β-sitosterol, and stigmasterol have low polarity, whereas Terrestrosin K, Terrestrosin F, Terrestroside B, Protodioscin, and Kaempferol-3-O-rutinoside can form more hydrogen bonds. Steroidal saponins are more readily absorbed in the gastrointestinal tract and can penetrate the blood-brain barrier. Kaempferol, chrysin, and quercetin show inhibitory effects on specific cytochrome P450 enzymes. β-sitosterol and stigmasterol have high rates of skin absorption. The bioavailability score ranges from 0.11 to 0.55, and synthetic accessibility scores are generally high.Conclusion: The steroidal saponins and flavonoids found in Tribulus terrestris show therapeutic potential for conditions such as hypertension, edema, and sexual dysfunction. Many of them possess favorable pharmaceutical properties for clinical use.
Introduction: The COVID-19 pandemic has underscored the necessity of investigating the relationship between radiological and laboratory findings with disease outcome in COVID-19 patients. This study aimed to explore the association between CT-scan finding and laboratory results with disease outcome, including recovery without complications, ICU admission, or mortality.Methods: This retrospective cross-sectional study analyzed medical records and laboratory data from COVID-19 patients at our institution from September 2020 onwards. All demographic, laboratory findings, as well as CT-scan data such as ground-glass opacity, consolidation, pleural effusion, cardiomegaly, mediastinal lymphadenopathy, and pulmonary involvement score at admission were collected. Patients were categorized based on outcome status and compared for all study variables. Results: Significance differences were observed for CT-score values between deceased patients and those who recovered (P<0.001), indicating a more severe lung changes in patients who died due to COVID-19. Additionally ICU-admitted patients had higher likelihood of underlying comorbidities and elevated CT-score levels. Laboratory markers such as ESR, Ferritin, LDH, Neutrophil count, and RDW were significantly higher in patients requiring ICU admission (P<0.05). Deceased patients were more likely to have underlying diseases, ground glass opacity, cardiomegaly, and higher CT-scores. Laboratory markers such as ESR, CRP, Ferritin, LDH, and others were also significantly higher in expired patients.Conclusion: There was a strong association between laboratory and CT-scan findings with disease outcomes in COVID-19 patients. The combination of laboratory markers and CT-scan findings can serve as robust predictors of disease outcomes. Further studies are needed to validate these findings in larger cohorts.
Introduction Cystic fibrosis (CF) is a genetic disorder caused by CFTR gene mutations, leading to thick mucus that affects multiple organs, resulting in maldigestion, malabsorption, and poor appetite. These factors increase energy needs, causing undernutrition in CF patients. Body mass index (BMI) is commonly used but doesn't differentiate lean body mass (LBM) and bone mass. Bioelectrical impedance analysis (BIA) provides a more detailed assessment of body composition. This study aims to evaluate the nutritional status of children with CF by analyzing fat mass (FM) and fat-free mass (FFM) using BIA.Methods This study included CF patients aged 7 to 18 years from the Cystic Fibrosis Specialty Clinic at Akbar Children's Hospital in Mashhad, Iran. Excluded were patients with pulmonary exacerbation, severe diarrhea-induced dehydration, or those who did not give informed consent. Anthropometric measurements were assessed using the Tanita BC 418 BIA device.Results 47 patients (48.9% female, 51.1% male) with a mean age of 10.74 ± 2.99 years were evaluated. Significant positive correlations were found between FM and weight Z-score (r=0.512, p<0.001), BMI (r=0.430, p=0.003), and BMI Z-score (r=0.633, p<0.001). FFM was strongly correlated with age (r=0.814, p<0.001), height (r=0.931, p<0.001), and weight (r=0.977, p<0.001). The prevalence of low FM and FFM was 21.3% and 40.4%, respectively. Low FM was significantly associated with increased hospital admission (p=0.021, OR=15.62).Conclusion FM and FFM are strongly linked to growth and nutritional indicators in CF, with low FM correlating to more hospital admissions, highlighting the need for targeted nutritional interventions to improve outcomes.
Aims: Intussusception is the second leading cause of acute abdominal pain in preschool children and infants, which is idiopathic in origin at this stage of life. Management options include hydrostatic reduction and surgery with subsequent procedures. Considering the urgency of intussusception, the existence of multiple interventional methods, and unequal complications of these methods, this research aimed to evaluate the characteristics of intussusception patients and therapeutic interventions performed to manage intussusception in Akbar Children's Hospital in Mashhad, Razavi Khorasan Province, Iran.Methods & Materials: This descriptive cross-sectional research was performed on all children under 18 years of age, who admitted to this hospital from 2017 to 2022 and underwent reduction or surgery with the final diagnosis of intussusception. Patient information was extracted from the hospital's information system (HIS). All data were analyzed using SPSS software Version 26.Results: Totally, 348 patients were included in this research, of whom 68.4% were male. The mean age of the patients was 32.18 ±39.54 (SD) months; 35.1% were less than one year, 45.4% were between 1 and 5 years, and 19.5% were more than 5 years. Out of 348 patients, 318 (91.8%) cases had the first visit, 22 (6.5%) had the second visit, and eight (1.9%) had the third visit. Regarding the treatment type, 304 (87.5%) patients were cured with reduction, and 44 patients underwent surgery.Conclusion: This study findings showed that most of the patients (87.5%) recovered with reduction, and a limited percentage of them needed surgery, indicating the effectiveness of the reduction method.
This case report documents a unique presentation of hepatic encephalopathy induced by the reactivation of chronic hepatitis B due to Cytomegalovirus (CMV) infection in a 76-year-old female patient. The patient was admitted with a diminished level of consciousness subsequent to a week of anorexia, intermittent fever, chills, postprandial nausea, and vomiting. Laboratory tests revealed significant hepatocellular injury, while imaging suggested cirrhosis. The presence of hepatitis B surface antigen and a detectable hepatitis B virus (HBV) DNA qualitative analysis was noted, alongside an elevated CMV viral load, indicating reactivation of chronic hepatitis due to CMV infection. Therapeutic interventions included Ganciclovir for CMV infection, Colistin for an Enterococcus urinary infection, and Tenofovir for hepatitis. Upon stabilization, the patient was discharged for continued medical management. The case highlights the significance of considering reactivation of chronic viral hepatitis in the differential diagnosis of hepatic encephalopathy. It underscores the critical role of comprehensive diagnostic investigation in patients presenting with reduced consciousness, especially those with a history of liver disease. Moreover, it emphasizes the importance of managing concurrent infections in the context of liver disease, and serves as a reminder of the potential for CMV to reactivate chronic hepatitis, leading to serious complications such as hepatic encephalopathy.
Introduction: Small nucleolar RNA host genes (SNHGs) are a class of long non-coding RNAs that have been increasingly associated with various cancers and are emerging as key players in cancer progression.This systematic review aimed to analyze the expression patterns and potential roles of SNHG5, SNHG17, and SNHG26 in various solid tumors.Methods: A comprehensive literature search was conducted across databases including PubMed, Cochrane, and Google Scholar, to identify relevant studies. Initially retrieved papers were screened based on titles and abstracts for relevance, with exclusion criteria applied to eliminate duplicate publications, case reports, conference abstracts, and irrelevant studies.Results: A total of 21 papers met the criteria for this systematic review, focusing on SNHG5 (5 articles), SNHG17 (7 articles), and SNHG26 (9 articles). These studies consistently highlighted the upregulation of SNHG5, SNHG17, and SNHG26 in various cancer types, emphasizing their potential as prognostic and therapeutic targets in solid tumors.Conclusion: The findings suggest a consistent overexpression of SNHG5, SNHG17, and SNHG26 in cancerous tissues, supporting their potential as prognostic markers in solid tumors. Further investigations should consider the regulatory mechanisms of SNHGs and explore their therapeutic implications in cancer management. This review highlights the importance of understanding the roles of SNHGs in cancer progression and calls for continued research efforts.
Objective: Ataxia telangiectasia-like disorder (ATLD) is a rare autosomal recessive disorder caused by mutations in the MRE11 gene. The diagnosis of patients with Ataxia telangiectasia-like disorder and Ataxia telangiectasia may be challenging due to similar clinical manifestations. In the present study, we describe a patient with a homozygous variant of uncertain significance (VUS) in the MRE11 gene that was correlated clinically with ATLD. Methods: We performed a brain MRI scan to find the cause of the patient's ataxia. After ventriculoperitoneal shunting due to obstructive hydrocephalus, there was no clinical change; so, we carried out whole exome sequencing. Additionally, Variants were classified using several databases and predicted according to the ACMG 2015 guidelines. Results: A 2-year-6-month-old boy with ataxia, tonic seizure, and speech delay was found during studies. The WES and in silico analysis identified a homozygous variant of uncertain significance (VUS) in the MRE11 NM_005591.4 (MRE 11): c.173 G>T (p. GIv58Val).Conclusion: This case report highlights that genetic testing can be useful for the precise diagnosis when clinical manifestations are not associated with MRI results. Furthermore, we could categorize a variant in the MRE11 gene from VUS to likely pathogenic based on clinical features.
Background/Objective:Head and neck cancer treatment often leads to stomatitis, influenced by multiple factors. Mouthwashes, with diverse formulations, offer potential therapeutic benefits. This study examines the relationship between stomatitis severity improvement post-radiotherapy and mouthwash use, considering patient characteristics like gender, age, duration, and dosage.Methods:A systematic review (2015–2023) evaluated mouthwash efficacy for radiotherapy-induced stomatitis. Searches in PubMed, Scopus, Web of Science, and Cochrane Library identified clinical trials, cohort, and case-control studies. Inclusion criteria focused on mouthwash effectiveness; quality was assessed using the Jadad scale.Results:Out of 480 screened studies, 16 met inclusion criteria. Traditional antiseptic mouthwashes (e.g., chlorhexidine) reduced infection risk but had mixed effects on pain and inflammation. Specialized formulations (e.g., aloe vera, honey, benzydamine) improved pain relief and mucosal healing. Combination therapies showed the best outcomes, though study variability limited conclusions.Conclusion:Mouthwashes, from antiseptics to specialized formulations, show potential for managing stomatitis. Antiseptics reduce infection, while specialized products aid pain relief and healing. Personalized interventions and further research are needed to optimize formulations for diverse patients.
Background: Approximately 20 million low-birth-weight infants are annually born worldwide. Prematurity and low birth weight are significantly linked to infant mortality rates. Neonates in neonatal intensive care units are often separated from their mothers, leading to a lack of parental involvement in care, which poses numerous risks and threats.Kangaroo mother care has been identified as an alternative method that can mitigate these risks. Methods: This semi-experimental clinical trial examined the effects of independent variables (kangaroo mother care and incubator care) on dependent variables (body temperature, weight gain, exclusive breastfeeding, and physiological measures) in 130 low birth weight infants admitted to the neonatal intensive care unit at Tehran Imam Hussein Hospital during 2019-2020.Results: This study observed an increase in maternal presence at the hospital. There were no significant differences between the two groups of mothers in terms of quantitative variables such as maternal age, number of pregnancies, and length of maternal hospital stay post-delivery. The average duration of kangaroo mother care was 12 ± 8.7 days, No differences were found between the two groups in variables such as gestational age, Apgar score, and weight and height at birth, at stability, and at discharge.Conclusion: This study demonstrated that kangaroo mother care reduces mortality, promotes exclusive breastfeeding, enhances emotional bonding between parents and neonates, reduces sepsis and patent ductus arteriosus, and shortens the duration of antibiotic use. This study supports the development of guidelines for educational programs to incorporate this alternative care method in neonatal intensive care units.
Clostridium difficile infection (CDI) is a significant health-related infection rarely seen in colorectal patients after surgery. However, over the past two decades, there has been an increase in the incidence and severity of CDI. In addition, the healthcare system is impacted significantly by the morbidity, mortality, and costs associated with CDI. While antibiotic use was initially thought to be the only cause, CDI has now been associated with hospitalization and residence in long-term care facilities. The risk of developing CDI is higher for patients who undergo gastrointestinal procedures, including colectomy. Hence, targeting preventive measures and reducing the burden associated with CDI can be achieved by identifying colorectal surgery patients at high risk for this increasingly prevalent disease. In the present article, we aim to review the current evidence of pre- and postoperative CDI in patients with underlying colorectal surgeries due to benign or malignant conditions, pointing to risk factors for infection, clinical impact, and outcomes.