Napoli, Italy

Time for a Diagnostic Paradigm Shift From STEMI/NSTEMI to OMI/NOMI

I. BACKGROUND AND SIGNIFICANCE The patients with acute coronary occlusion (ACO) or potentially imminent occlusion, with insufficient collateral circulation, have myocardium that is at risk of infarction unless they undergo immediate reperfusion via thrombolytics or percutaneous coronary intervention (PCI). One of the most important tasks in emergency cardiology is to immediately identify acute coronary occlusion (ACO) myocardial infarction (OMI) among all patients who present with symptoms compatible with acute myocardial infarction (MI), and distinguish them from those without MI, and from those with MI that does not have ongoing myocyte loss (Non-OMI, or NOMI) who can be managed with medical therapy and for whom potentially harmful invasive interventions can be deferred. The electrocardiogram (ECG) plays a central role in this process. The presence or absence of ST-segment elevation (STE) is principally used to define patients who need emergent coronary revascularization, since subgroup analyses of the Fibrinolytic Therapy Trialists' (FTT) meta-analysis indicated that patients with STE on ECG gain a slightly better survival benefit from emergent reperfusion. After fine-tuning of STE cutoffs used in this analysis, universally agreed STEMI criteria became the current guideline-supported ECG paradigm. It is not clear why a disease of a known pathophysiology (ACO) was named with an inaccurate surrogate ECG sign (Q-wave MI/non-Q-wave MI or STEMI/non-STEMI) instead of the pathologic substrate itself (ACO-MI/non-ACO-MI or OMI for short), but this fundamental mistake created important implications for our current practice. As briefly outlined above, ACO can be reliably recognized with the help of many other ECG findings, such as minor STE not fulfilling STEMI criteria, STE disproportionate to preceding QRS, unusual patterns with contiguous leads showing opposite ST deviations and some patterns not showing STE at all. Recently, the DIagnostic accuracy oF electrocardiogram for acute coronary OCClUsion resuLTing in myocardial infarction (DIFOCCULT) study, compared OMI/non-OMI approach with STEMI/non-STEMI paradigm. This is the largest study specifically designed to question the STEMI/non-STEMI paradigm, in which a set of predefined ECG findings in addition to STEMI criteria were used, and the final outcome was a composite ACO endpoint. In accordance with the previous observations, over one-fourth of the patients initially classified as having non-STEMI were re-classified by the ECG reviewers, blinded to all outcome data, as having OMI. This subgroup had a higher frequency of ACO, myocardial damage, and both in-hospital and long-term mortality compared to the non-OMI group. The OMI/non-OMI approach to the ECG had a superior diagnostic accuracy compared to the STE/non-STEMI approach in the prediction of both ACO and long-term mortality. II. THE HYPOTHESIS Our hypothesis is that the new OMI/NOMI approach will be superior to the established STEMI/NSTEMI paradigm in early detection of ACO, limiting infarct size, reducing rehospitalizations and most important of all, reducing mortality. III. METHODS 1. Application for Institutional Review Board (IRB)/Ethics board approval IRB/Ethics board approval is obtained from Marmara University Ethical Board. Later modifications will be reviewed by Başakşehir Pine and Sakura City Hospital Ethical Board. Each principal investigator at each individual study site will be required to obtain IRB/Ethics board approval from his/her own institution. 2. Study population The adult patients (age >18 years) who are admitted to the emergency department with a clinical picture compatible with acute coronary syndrome will be screened for enrollment into the study. patients with an ECG or clinical (see below) diagnosis of acute myocardial infarction will be enrolled into the study. An ECG will be acquired as soon as possible in all screened patients and serial ECGs will be taken if the first one is not diagnostic. The ECGs will be scanned and digitized via an artificial intelligence (AI)-powered mobile phone application. If the patient gets a STEMI or OMI diagnosis by the ECG or clinical gestalt (refractory pain, hemodynamic instability, arrhythmia, cardiac arrest) they will be included in the study even if the later troponin results turn negative. If the ECG is not diagnostic for OMI or STEMI, a myocardial infarction diagnosis with a positive troponin will be necessary for the inclusion in the study. According to 4th universal definition of MI, the term acute MI will be used when there is acute myocardial injury (detection of a rise and/or fall of cTn values with at least one value above the 99th percentile upper range limit) with at least one of the following clinical indicators of acute myocardial ischemia: - Symptoms of myocardial ischemia; - New ischemic ECG changes; - Development of pathological Q waves; - Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality in a pattern consistent with an ischemic etiology; - Identification of a coronary thrombus by angiography or autopsy; - Post-mortem demonstration of acute atherothrombosis in the artery supplying the infarcted myocardium. All non-procedure related (excluding type 4a and 5 MIs), including type 1 (MI caused by atherothrombotic coronary artery disease which is usually precipitated by atherosclerotic plaque disruption (rupture or erosion)), type 2 (evidence of an imbalance between myocardial oxygen supply and demand unrelated to acute atherothrombosis), type 3 (cardiac death in patients with symptoms suggestive of myocardial ischemia and presumed new ischemic ECG changes before cTn values become available or abnormal) and type 4b and c (stent/scaffold thrombosis ore restenosis associated with percutaneous coronary intervention) will be included in the study. Patients with myocardial injury (either acute, as in acute heart failure or myocarditis, or chronic, as in chronic kidney disease or stable increased troponin levels with structural heart disease) without ischemia (abovementioned following clinical indicators of acute myocardial ischemia) will be excluded from the study. Randomization The patients will be randomized to the current STEMI/NSTEMI versus OMI/NOMI approaches using a cluster randomized trial design. Although the STEMI/NSTEMI approach is the current norm (a diagnosis of STEMI requires emergent catheterization, whereas the patients with NSTEMI are stabilized first and then electively undergo catheterization unless there are high-risk features), it would be unethical for a ECG reviewer, who is trained in recognizing the signs of ACO not fulfilling the current STEMI criteria, to suspend emergent reperfusion therapy after an OMI diagnosis has been made. Therefore, the ECG interpreters who are trained in OMI diagnosis cannot be randomized to STEMI/NSTEMI versus OMI/NOMI approaches. Hence, the groups will be randomized in the following fashion: In each center, a STEMI/NSTEMI and an OMI/NOMI intervention group will be formed. After these two groups are formed, the patients will be block-randomized into STEMI/NSTEMI and OMI/NOMI cohorts according to the team on-duty, i.e., the approach that center will follow on a certain day will be defined by the team on duty. The interventional cardiologists in both groups will be ensured to have a similar experience level (in terms of years of training, and angiography and primary PCI counts in the past year). All possible first responders in the network of a study center (who contact the patient first, according to the center this can be either a referring physician, an emergency physician or a cardiologist) will be provided with an AI-powered application for ECG diagnosis. These responders will receive diagnostic prompts from the application according to the center's on-duty team. If an OMI team member is on duty, the ECG interpretation will be OMI or not-OMI. If a STEMI team member is on-duty, the ECG interpretation will be disabled and will read "follow standard care". The first responder will thus elect to go for catheterization based on this approach and, whether that is by OMI or STEMI paradigm, the patient will be enrolled accordingly and the reason for proceeding to the catheterization laboratory will be written on the study form (or electronic sheet on the dedicated website). In the STEMI/NSTEMI arm, the contributors will blindly continue their usual practice, the ECG interpretation and decision to activate the catheterization laboratory will be done as usual. The STEMI/NSTEMI group will use the following criteria for the diagnosis of STEMI: (1) New ST-segment elevation at the J-point in two contiguous leads with the cut-point: ≥ 1 mm in all leads other than leads V2-V3 where the following cut-points apply: ≥2 mm in men ≥40 years; ≥2.5 mm in men <40 years, or ≥1.5 mm in women regardless of age, and (2) a peak troponin level above 99th percentile with a characteristic rapid rise and fall (retrospectively) and (3) a clinical picture compatible with acute coronary syndrome. If the decision to proceed to the cath lab was done only with the first criterion, the participant will remain in the study, even if the second criterion is not met. The patients meeting only criteria (2) and (3) will be classified as NSTEMI. On OMI/NOMI days, physicians are encouraged to actively search for ACO, regardless of whether STEMI criteria are present on the initial ECG. A diagnosis of OMI can be based on clinical gestalt, ECG findings, and adjunct modalities. Clinical gestalt includes hallmark presentations such as almost pathognomonic chest pain, and ischemic arrhythmias, hemodynamic instability, or cardiac arrest following typical symptoms. ECG diagnosis, whether interpreted by physicians or aided by an AI-powered smartphone application, incorporates static or serial changes for ACO using the DIFOCCULT-1 study algorithm. On OMI/NOMI days, the smartphone application is activated and available to all first responders associated with this center. This application assists diagnosis, but the final decision is left to the interventionalist on duty. Adjunct modalities include bedside echocardiography demonstrating new or presumed new wall motion abnormalities in patients with ongoing or recurrent chest pain, and significantly elevated initial troponin levels. For high-sensitive cardiac troponin (hs-cTn) T, it has been shown that a level exceeding 1000 ng.mL-1 is highly specific for major epicardial coronary artery occlusion. Similarly, a hs-cTn I >200 times the upper limit of normal (e.g., Architect, Abbott Diagnostics, Illinois, USA: 5000 ng/L; ADVIA Centaur, Siemens Healthcare, Tarrytown, USA: 5000 ng/L; Access, Beckman Coulter, Brea, USA: 2400 ng/L) is defined as a marker for OMI in patients with ongoing or fluctuating chest pain. In patients diagnosed with OMI, immediate catheterization laboratory activation with the intent to perform PCI is pursued. In NOMI patients, initial medical stabilization is prioritized, followed by elective catheterization per the NSTEMI pathway unless high-risk features are identified. STEMI and OMI patients (will be taken as STEMI equivalents for therapeutic purposes) will be managed according to the current STEMI guidelines, whereas NSTEMI and NOMI patients are managed according to the current NSTEMI guidelines. A separate diagnostic group with 'probable OMI' and 'high-risk STEMI' is also allowed for patients who do not fulfil STEMI/OMI criteria but need urgent catheterization for other high-risk features or high clinical suspicion for having an ACO. These patients will also be managed according to the current guidelines. However, patients will be excluded from analysis if their early catheterization is based solely on social or logistical considerations, and not based on the medical need. For example, a patient would be excluded if he/she is brought to the cath lab early based on the immediate availability of cath lab or because the patient is already scheduled for elective coronary angiography. The patients who have alternative diagnoses (myocarditis, pericarditis, pulmonary embolism etc.) but were not included due to a clinical or ECG diagnosis of STEMI/NSTEMI or OMI/NOMI will be excluded from the study. Similarly, the patients without a characteristic troponin kinetics who were not included due to a clinical or ECG diagnosis of STEMI/NSTEMI or OMI/NOMI will be excluded from the study. Endpoints The primary composite endpoint is all-cause mortality and all-cause re-hospitalization during follow-up. The co-primary endpoint is all-cause mortality and all-cause re-hospitalization in OMI (+) STEMI (-) patient subgroups. The secondary comparisons will be done for the presence of ACO on angiogram, false positive catheterization laboratory activation rate, the infarct size as defined by 24-72 hour peak troponin, wall motion score index (WMSI), left ventricular ejection fraction (LVEF), in-hospital CPR, intubation and mortality. These will be analyzed both with intention to treat and per protocol approaches. To define this subgroup in the OMI/NOMI arm, all ECGs diagnosed as OMI during the study will be randomly assigned to researchers in the STEMI/NSTEMI arm after study completion. The researchers will then assess whether the ECG is compatible with STEMI or NSTEMI. Patients diagnosed as NSTEMI within the OMI group will be classified as the OMI (+) NSTEMI subgroup in the OMI/NOMI arm. In the STEMI/NSTEMI arm, patients diagnosed with NSTEMI will have their ECGs scanned and interpreted by the AI-powered application. If the ECG is interpreted as OMI, these patients will be included in the OMI (+) NSTEMI subgroup within the STEMI/NSTEMI arm. The OMI diagnosis also includes clinical variables, such as clinical gestalt and very high first troponin levels. However, clinical gestalt cannot be acted upon retrospectively (e.g., bedside echocardiography or serial ECGs). Nevertheless, if a patient is recorded with ongoing chest pain and a very high first troponin level (based on center-specific and troponin kit-specific values), this will be included in the OMI (+) NSTEMI subgroup in the STEMI/NSTEMI arm, even if the ECG is not interpreted as OMI by the AI-powered application. The primary source of outcome data will be the Turkish national electronic database (e-nabız), which provides comprehensive, real-time updates on all deaths and hospitalizations nationwide. To ensure the completeness and accuracy of data, direct phone contact with participants or their families will be conducted as a secondary measure. All collected outcomes will be reviewed by an independent outcome adjudication board blinded to the study arms. Estimated number of subjects to be submitted: It was estimated that the enrollment of 3472 participants would provide the study with a statistical power of 95% to detect a 4% absolute decrease in combined primary endpoint in OMI/NOMI approach compared to STEMI/NSTEMI approach (from 25% to 21%) with the use of a two-sided test at the 0.05 level, with a prediction of an additional 30% OMI in NSTEMI cohort. Similarly, 2351 participants would be necessary to detect a 5% difference in area under curve (AUC, from 0.750 to 0.700) for the comparison of the predictive accuracy of two approaches for primary outcomes. For the co-primary outcome, a total of 880 OMI (+) STEMI (-) participants would provide the study with a statistical power of 95% to detect a 50% relative decrease in combined primary endpoint in OMI/NOMI approach compared to STEMI/NSTEMI approach (from 20% to 13%) with the use of a two-sided test at the 0.05 level. This corresponds to an approximate total sample size of 4000 patients, with a prediction of 1:1.5 STEMI/NSTEMI ratio and a frequency of 25% OMI in NSTEMI cohort. However, a one-year enrollment duration is planned, which is expected to enroll 6000 patients (with a 1:1.5-2 STEMI/NSTEMI ratio) into the study. This total number is also expected to provide the study with a statistical power of 95% to detect at least a 10% relative decrease in infarct size, 10% better left ventricular ejection fraction and 10% better wall-motion score index STEMI (-) OMI (+) patients who underwent early revascularization in OMI arm compared to those who underwent revascularization with standard timing in STEMI/NSTEMI approach, with a prediction of an additional 25% OMI in NSTEMI cohort. 3. Participating centers Listed elsewhere. 4. Data Collection From September 1, 2024, AI-powered ECG App will be distributed to the referring hospitals by the participating centers. The study will start at all participating centers on October 1, 2024. A dedicated website (difoccult.org) will be used for data entry and storage. Study data is collected and managed using REDCap (Research Electronic Data Capture) tool hosted at a dedicated server. REDCap is a secure, web-based software platform designed to support data capture for research studies, providing (1) an intuitive interface for validated data capture; (2) audit trails for tracking data manipulation and export procedures; (3) automated export procedures for seamless data downloads to common statistical packages; and (4) procedures for data integration and interoperability with external sources. A data monitoring board ensures the completeness, integrity, and accuracy of the entries, providing feedback to the data entry team and requesting explanations or modifications as needed. Baseline variables Collected baseline variables and their definitions are listed in the REDCap printout in the supplemental file. Electrocardiogram ECGs will be acquired using standard conventions. If the first ECG is non-diagnostic, serial ECGs will be acquired every 15 minutes for an hour and the first diagnostic ECG will be used in the analyses. If all of them are non-diagnostic the physician may still use additional tools such as the clinical picture, bedside echocardiogram, troponin results to diagnose 'high-risk NSTEMI' or 'possible OMI'. All pre-intervention ECGs and at least one pre-discharge ECG will be uploaded to a central cloud database to be retrospectively reviewed by core lab investigators. The absence of a technically adequate pre-cath ECG will be a reason for the exclusion of the participant. If ECG diagnosis is not compatible with the inclusion criteria for the assigned group, this will be noted and the patient will be excluded from the per-protocol analyses. Following coding will be used for ECGs: Type 1 EGGs: New ST-segment elevation at the J-point in two contiguous leads with the cut-point: ≥ 1 mm in all leads other than leads V2-V3 where the following cut-points apply: ≥ 2mm in men ≥ 40 years; ≥ 2.5 mm in men < 40 years, or ≥ 1.5 mm in women regardless of age. Type 1a: The amplitude, morphology, extent of STE and the presence of additional findings (hyperacute T waves, Q-waves, terminal QRS distortion) make ECG highly obvious for MI presumably due to acute, thrombotic occlusion. These ECGs will be included in both STEMI and OMI definitions. Type 1b: There is ST-segment elevation that meets criteria for STEMI, but it is uncertain whether it is due to MI or to another condition, such as benign variant STE, left ventricular hypertrophy, left bundle branch block, prior MI, pericarditis, etc. These ECGs will be included in the STEMI definition but not in the OMI definition, unless there are additional findings suspicious for acute coronary occlusion as follows: Differential diagnosis for benign variant STE: Type 1b, if fulfills STEMI criteria. But re-classified as Type 2b, if the Aslanger/Smith formula is positive. Aslanger's formula: (R-wave amplitude in lead V4 + QRS amplitude in V2) - (QT interval in millimeters + STE60 in V3) <12 (Aslanger E Am J Cardiol, 2018). Differential diagnosis for left ventricular hypertrophy: Type 1b unless ST segment to R-S-wave magnitude is equal or greater than 15% (then indicates OMI, Type 2b) (Armstrong EJ et al. Am J Cardiol, 2012, Aslanger et al. Arch Turk Soc Cardiol, 2021). Differential diagnosis for isolated left bundle branch block: Will be coded as Type 1b, unless one of the modified Sgarbossa criteria is positive (then indicates OMI, Type 2b): ≥ 1 lead with ≥1 mm of concordant ST elevation, ≥ 1 lead of V1-V3 with ≥ 1 mm of concordant ST depression, ≥ 1 lead anywhere with ≥ 1 mm STE and proportionally excessive discordant STE, as defined by ≥ 25% of the depth of the preceding S-wave (Smith SW et al. Ann Emerg Med 2012). Differential diagnosis for prior MI: Type 1b, unless Smith's rule is positive (then indicates OMI, Type 2b): Smith's rule: If any 1 lead between V1-V4 has a T-wave amplitude to QRS amplitude ratio greater than or equal to 0.36 (Klein LR et al. Am J Emerg Med 2015). Differential diagnosis for pericarditis: Type 1b, unless there is ST-depression in aVL (then indicates OMI, Type 2b) (Bischof JE et al. Am J Emerg Med. 2016). Type 1c: There is ST-segment elevation that meets criteria for STEMI, but there is also T-wave inversion and pathologic Q waves indicative of subacute MI. These ECGs will be excluded from per-protocol analyses, since these patients have ACO on angiogram and higher long-term mortality but gain little, if not any, benefit from reperfusion with both approaches. Patients with preserved QRS complexes (Wellens' pattern) will be included in type 2c ECGs. Type 2 EGGs: ECG that meets acute myocardial ischemia criteria recommended by fourth universal definition of MI. Type 2a: The ECG has "primary'', i.e. cannot be completely explained as secondary to a depolarization disorder, ST-segment depression or T-wave inversion that is nondiagnostic of STEMI but is diagnostic of myocardial ischemia. Type 2b: Does not meet recommended criteria for STEMI, but highly suggestive for ACO, despite being subtle and difficult. Possible findings are minor STE with or without minor reciprocal ST-depression not fulfilling STEMI criteria, hyperacute T-waves or DeWinter's pattern, subtle anterior STE hard to differentiate from benign variant STE and nonconsecutive STE. These ECGs will be included in the OMI definition but not in the STEMI definition. The detailed algorithm defined in the DIFOCCULT trial (Aslanger et al. In J Cardiol Heart Vasc, 2020; Aslanger et al. J Electrocardiol, 2021; Aslanger et al. Arch Turk Soc Cardiol, 2021) will be used for recognizing these ECGs. Type 2c: Patients with preserved QRS complexes (Wellens' pattern), with or without some STE, but with significant T wave negativity will be included in type 2c ECGs. These ECGs will be excluded from per-protocol analyses, since these patients may not gain benefit from emergent reperfusion in both approaches. Type 3 ECGs: Nonspecific ECG that is abnormal but nondiagnostic of any kind of acute coronary syndrome. Minor abnormalities including left ventricular hypertrophy without ST-T changes, arrhythmias, impulse generation and conduction diseases etc. Type 4 ECGs: Completely normal ECG. AI-Powered ECG Application In OMI/NOMI arm ECGs can be digitized and interpreted by AI-powered ECG application prospectively. In STEMI/NSTEMI arm, interpretation will be done retrospectively. The application's functionality varied based on the study arm determined by the team on duty. On OMI/NOMI days, the AI application is fully activated and accessible to all first responders associated with that center. When a user captures a photo of an ECG, the application digitalizes the image, interprets the data, and displays one of two messages: "OMI" or "Not-OMI." First responders were instructed to promptly inform the interventionalist on duty for potential catheterization laboratory activation if result shows "OMI". On STEMI/NSTEMI days, the AI-supported application is deactivated for that center. If a first responder attempts to capture a photo of an ECG, a warning message is displayed: "We are now following the standard STEMI/NSTEMI approach. Please continue your usual practice." A commercial version of the same smartphone application by the same company is also available on the market. During the study, if a network address is detected accessing both the commercial and study-specific applications, the commercial version is deactivated by the company, and a notification mail is sent explaining that the commercial smartphone application will not be available to users in Türkiye for the duration of the study. Additionally, all ECGs stored in the study database will be cross-referenced with the commercial smartphone application's ECG history. If any matches are identified, the corresponding patient will be excluded from the study. After the study completion, ECGs in both study arms will be reviewed and coded as defined above for intention-to-treat and per-protocol analyses. This will be done by two separate ECG interpreter. Should there be any discrepancy between these interpreters, a third interpreter (from data monitoring board) will be consulted. Type 1a, 1b and 1c ECGs will be deemed as compatible with STEMI. Type 1a, 2b and 2c ECGs will be deemed compatible with OMI diagnosis. Troponins The troponin levels will be measured at admission, hourly if needed for the diagnosis, every 6 hours until it peaks after an MI diagnosis is made, and then daily. The 24-72 hour peak troponin level (usually 48h) will be used as a surrogate for infarct size. Angiograms Coronary angiography will be undertaken according to the standard conventions. Each angiogram will be reviewed by two interventionalist. Should there be any discrepancy between these interpreters, a third interpreter (from data monitoring board) will be consulted. Following points will be noted for the presence of an ACO: (1) the Thrombolysis in Myocardial Infarction Study (TIMI) flow level in the infarct-related vessel. The presence of well-developed collaterals to the distal vessel, appearance of the total occlusion, easiness of guidewire crossing will also be assessed to determine if the total occlusion is acute in nature. If necessary, the primary operator will also be contacted. (2) The presence of an acute lesion with definitive culprit features, which was defined based on several angiographic properties including critical stenosis, irregular lesion borders, presence of angiographic thrombus or staining. ACO Adjudication Because the infarct-related artery may spontaneously open by the time of the angiogram or total occlusion may be chronic in nature, a composite ACO using following criteria is defined: 1. An acute culprit lesion with TIMI 0-2 flow PLUS a peak troponin level equal to or greater 5 than five times the ULN PLUS at least 20% rise within the first 24 hours 2. A highly elevated peak (for troponin T>1000 ng/mL and for troponin I 200 times of the average of ULN (known to be highly correlated with ACO)) without an obvious alternative diagnosis or with supporting evidence (ECG evolution, culprit-looking lesion on angiogram in a coronary territory compatible with ECG/echocardiographic area at concern) 3. cardiac arrest before any troponin rise has been documented with supporting clinical evidence of possible ACO. Follow-up The last participant in the study will be followed up to one year. The survival status and re-hospitalization will be checked from the national database and a phone call, if required. Statistical Analysis Baseline characteristics will be summarized using standard descriptive statistics. Comparisons of relevant parameters between groups will be performed by chi-square, Fisher's exact test, Mann-Whitney U, and student t-test, as appropriate. Patients with missing values will be excluded pairwise from analyses. A Cohen's κ test will be used for determination of the intra- and inter-observer agreement for ECG classifications and ACO adjudication. Kaplan-Meier analysis will be performed to determine the cumulative long-term mortality rates in different ECG subgroups. The mortality across groups will be compared using a log-rank test. A Cox-regression model will be used to perform a survival analysis according to basal GRACE risk score, intervention timing and treatment status. Baseline characteristics with a P value of 0.05 or less in the univariate analysis will be included and a step-down procedure will be applied for selection of final covariates. To address potential variability in outcomes due to interventionist or center-related factors, we will incorporate a random effects (frailty) term into the Cox model. The calibration cohort (the patients with type 1a ECGs and treat with the same manner in both arms) will be used to estimate variability attributable to interventionist practices. The random effect variance (σ2) calculated from this cohort will inform the frailty term in the full Cox model, ensuring that differences in outcomes due to interventionist-related variability are appropriately adjusted. The final model will include patient-level covariates, random effects for interventionists or centers, and calibration adjustments based on the calibration cohort. The sensitivity, specificity and diagnostic accuracy of STEMI/NSTEMI or OMI/NOMI ECG approaches will be calculated using receiver operating characteristics analysis. As these parameters are highly dependent on the pre-test probability of the disease and pre-test probability of ACO and long-term mortality are closely associated with the presentation type, the investigators will also repeat these analyses after weighing cases for the total number of hospital admissions in the study period. Statistical analyses will be performed with SPSS (version 24.0; SPSS Inc., Chicago, IL) and MedCalc Software (version 18.2.1 [Evaluation version]; MedCalc Software, Ostend, Belgium). 5. Safety monitoring and reporting Study REDCap forms necessitate in-hospital adverse events to be actively collected to monitor and report any in-hospital adverse events. An independent Data Safety Monitoring Board (DSMB) has been established to oversee the safety and progress of the trial. The DSMB convened via teleconference during the pretrial period, upon enrollment of 20% of the participant sample size, and will continue to meet after each subsequent 20% enrollment milestone. The primary objective of the DSMB is to monitor enrollment milestones and the safety of the interventions. A four-point combined safety endpoint will be closely monitored: (1) myocardial infarction size by 48.hour troponin, ejection fraction and wall motion score index; (2) integrity of coronary intervention by in-hospital stent thrombosis; (3) integrity of in-hospital care by in-hospital intubation, in-hospital cardiopulmonary resuscitation and in-hospital mortality and (4) long-term therapy by discharge treatment. If a statistically significant increase in this four-point combined safety endpoint is observed in either of the study arms after the enrollment of any 20% of the participant sample size, the DSMB will make a recommendation regarding the revision, rearrangement or potential exclusion of the study participants or the study center. 6. Study integrity The study is an investigator-initiated trial conducted under the auspices of the Turkish Society of Cardiology. The Turkish Society of Cardiology supports the investigator team in developing the trial design and organizing the participating centers. The steering committee oversees the processes of recruitment, consent and assent, follow-up, and ensures the validity and integrity of data acquisition. The trial has been approved by the Ethical Board of Marmara University (09.2021.523), any change in protocol or centers will be addressed by this board. The study will be conducted in accordance with Good Clinical Practice guidelines.

Recession Coverage Using Modified Coronally Advanced Tunnel(MCAT)

This study is planned to be conducted with 60 individuals, aged between 18 and 45, who have presented to the Department of Periodontology at Necmettin Erbakan University Faculty of Dentistry for various reasons. Routine initial periodontal examinations and Phase 1 periodontal treatments will be performed on individuals exhibiting gingival recession and associated sensitivity. Standard mucogingival surgical procedures are routinely applied in our faculty to these individuals. In our study, the short- and long-term outcomes of the MCAT technique, a mucogingival approach, will be evaluated. The study will consist of the following three groups: Group 1: Modified coronally advanced tunnel (MCAT) + subepithelial connective tissue graft (n:20) Group 2: Modified coronally advanced tunnel (MCAT) + enamel matrix derivative(n:20) Group 3: Modified coronally advanced tunnel (MCAT) + subepithelial connective tissue graft + enamel matrix derivative(n:20) Our study is designed as a randomized, controlled clinical trial. Measurements will include gingival thickness, the amount of root coverage, and keratinized gingiva parameters, recorded using a Williams probe (Hu-Friedy) and rounded to the nearest millimeter. For gingival recession, plaque index, and gingival index will be obtained from three points: mesial, distal, and midpoints. The plaque index will be calculated according to the criteria defined by Silness and Loe, while the gingival index will be assessed based on the criteria defined by Loe and Silness. Gingival thickness will be measured 3 mm below the gingival margin under topical anesthesia using an endodontic reamer with a stopper. Patients will be asked to complete a chart rating their subjective pain, burning sensation, and discomfort in the surgical area on a visual analogue scale (VAS) ranging from 0 (none) to 100 (very severe) on postoperative days 3 and 7. The clinician will remove the sutures two weeks after surgery and will complete the wound healing index for each tooth individually according to Huang's criteria. This study aims to provide comprehensive insights into the effectiveness and benefits of the MCAT technique and its variations in treating gingival recession.

Maxillary Labial Frenectomy: Diode Lasers Versus Surgical Scalpel

The trial will be performed as a prospective, randomized and controlled, single-blind investigation to study clinical parameters and patients' experiences when performing a frenectomy, comparing diode laser treatment with the conventional scalpel technique. Participants: This study will include 43 participants who will be identified with aberrant papillary frenum attachment according to Mirko et al., and will be referred to the periodontology department. The inclusion criteria for the participants will be: All participants will sign a written informed consent form before participating in the study. Study Groups and Randomization: Before any surgical procedure, all subjects will undergo a thorough medical and dental history review, as well as intraoral and radiographic examinations. Participants who match the inclusion criteria will be provided with oral hygiene instructions tailored to their specific needs. Initially, the clinical periodontal parameters of all participants will be measured. Then, a mechanical cleaning procedure will be carried out using an ultrasonic scaler (CavitronÒ; Dentsply International) and hand instruments (Gracey, 5/6, 7/8, 11/12, 13/14; Hu-Friedy Ins. Co.). A total of 43 participants will be enrolled in the study and assigned to one of two groups using a computer-based randomization table (www.graphpad.com/quickcalcs). The participants will be randomly divided into two groups: the experimental group, which will undergo diode laser surgery (L=20), and the control group, which will undergo conventional scalpel surgery (C=23). Post-treatment Procedure: After the frenectomy procedures in all groups, patients will receive oral hygiene instructions and will be advised to consume soft and cold food for the next 12 hours. Additionally, a 0.12% chlorhexidine gluconate mouth rinse will be prescribed to be used once a day for one minute over five days. For pain relief, 500 mg of acetaminophen (1-2 tablets) will be prescribed as needed, with patients instructed to record the dosage and frequency of use. Clinical Evaluation: Z.T.E. will perform all surgical procedures, while a calibrated single examiner (K.Y) will perform all clinical evaluations. Patients in the C group will undergo primary wound healing with sutures, whereas patients in the L group will not get any sutures. Therefore, neither the clinicians (Z.T.E and K.Y) nor the patients will be kept unaware of the study's details over the entire duration. In order to ensure consistency in the measurements of K.Y, a calibration exercise was conducted until the agreement coefficient achieves a level of 90%. This calibration process was consist of evaluating three patients on two separate occasions within a 24-hour period. The calibration was considered effective if the variation between repeated measurements of periodontal keratinized gingival width (KGW) at the beginning and after 24 hours is less than 3%. The clinical periodontal parameters, such as the plaque index (PI), gingival index (GI), and periodontal pocket depth (PD), will be measured using a periodontal probe from the University of North Carolina (PCPUNC15; Hu-Friedy Ins. Co.). At baseline and at postoperative week 6 and month 6, all periodontal measurements will be taken at six sites per tooth as part of a full-mouth evaluation. KGW on teeth 11 and 12, the heights of the interdental papillae between the incisors (from the tip of an interdental papilla to the line joining the lowest points on the gingival margins of adjacent incisors), interdental papilla width, and the amount of diastema will be measured at baseline and at month 6. Before the operations, the labial frenulum attachments will be classified into four types: I - mucosal attachment; II - gingival attachment; III - papillary attachment; and IV - papilla penetrating attachment. Pain will be evaluated using the visual analogue scale (VAS) on postoperative days 1, 3, 7, 14, 21, and 28. The scale will be comprised of a horizontal line with values ranging from '0' to '10', where '0' indicates the absence of pain and '10' indicates the presence of severe discomfort. Statistical Analysis: Each patient will be accepted as one statistical unit and the statistical analysis will be performed by SPSS 20 (SPSS Corporation, Chicago, IL) with a significance level p < 0.05. The Kolmogorov-Smirnov test will be used to check the distribution for normality. Repeated measurements of clinical parameters will be analyzed with Friedman test and Wilcoxon signed-rank test. The Kruskal-Wallis, Chi-square, and Fisher's exact tests will be used to determine differences among the groups. Moreover, in case of significant difference among groups, the Mann-Whitney U test will be used to compare two groups by Bonferroni correction.

The Impact of Probiotic on Survival and Treatment Response in Metastatic Non-small Cell Lung Cancer Patients

Despite modern treatments, lung cancer remains a leading cause of high mortality worldwide. Over the past decade, significant improvements in patient survival have been achieved with immune checkpoint inhibitors, which enhance the T cell-mediated immune response to eradicate cancer cells. However, therapeutic resistance, drug side effects, and heterogeneous treatment responses limit their effectiveness. Recent studies have established a clear relationship between gut microbiota and cancer immunotherapy. The intestinal microbiota has been shown to stimulate the anti-tumor immune response by modulating immune system cells. Evidence from preclinical and clinical studies indicates that gut microbiota plays a crucial role in the efficacy of immunotherapy and the modulation of drug toxicity. Identifying the microbiota as a potential biomarker could facilitate personalized treatment protocols. Genetic, epigenetic, and microbiota modulation factors are essential for optimizing cancer immunotherapy outcomes. Consequently, research is increasingly focusing on personalized treatment protocols for microbiota modulation, including diet regulation, fecal microbiota transfer, prebiotics, and probiotics. There has been a significant rise in studies demonstrating the clinical benefits of microbial therapy products as complementary treatments. The functional role of microbiota in modulating the systemic immune response has prompted investigations into its impact on cancer immunotherapy, particularly with agents targeting immunological checkpoints like PD-1. Recent studies have identified both positive and negative regulatory bacteria that influence immunotherapy effectiveness. However, sociocultural and dietary lifestyle differences affect gut microbiota composition, leading to variations between populations. Therefore, studies are needed to identify the unique microbiome composition of each population to develop microbiota biological indicators for cancer immunotherapy. No research has been conducted in this area in Türkiye. This study aims to identify bacterial species that may serve as biomarkers for the microbiota specific to Turkish cancer patients receiving immunotherapy and use them for prognostic purposes. Understanding the significant role of probiotics in modulating intestinal microbiota has increased the demand for these food supplements. Studies show that anti-tumor efficacy is specific to the bacterial strain. For instance, Bifidobacteriums have been reported to enhance the effectiveness of PD-1 blockers in experimental rat models. In another study, B. lactis BL-04 reduced immunotherapy-induced colitis in animals. This study will investigate the effect of a probiotic supplement containing Bifidobacterium animalis lactis BL-04 on clinical objective response, clinical benefit rates, and intestinal microbiota in patients with metastatic non-small cell lung cancer (mNSCLC) receiving nivolumab. The results may facilitate the development of specific probiotic supplements as a complementary therapy for mNSCLC treatment.

Providing Hygiene Education Using the Teach-back Method to Pregnant Women Diagnosed With Urinary Tract Infections

Urinary tract infection in women is the second most common discomfort after anemia that occurs during certain periods of life during pregnancy and is also one of the most common bacterial infections (Fihn, 2003; Griebling, 2005; Czajkawski, Bras-Konopeielka and Teliga-Czajkowska, 2021). About 50% of women have urinary tract infections at least once in their lifetime (Gilbert, O'bien, Hutgen et al., 2013). In the presence of urinary tract infection, painful urination is usually observed, frequent emergency toilet trips, while other symptoms include lower abdominal or pelvic pain and pressure, blood in the urine, milky, cloudy or pink/red urine color, fever, heavily scented urine, nausea, vomiting and diarrhea (Habak and Griggs Dec, 2023). Pregnancy, number of pregnancies, age, diabetes mellitus, urethrogenital anomalies, genetic and behavioral factors, hygiene deficiency, anemia, history of urinary system infection (Bekzac, Orgul, Tanacan et al., 2019), factors such as low socio-economic level, inadequate perineal hygiene, vaginal douching, long-term use of antibiotics and steroids, smoking, alcohol consumption and immune deficiencies increase the incidence (Özdemir, Ortabağ, Tosun et al., 2012; Ejder Apay, Özdemir, Nazik et al., 2014; Karahan, 2017). The frequency of sexual experience, the number of sexual partners (current or previous years), not urinating after sexual intercourse, the direction of wiping the perineum after the toilet, urine retention, daily insufficient water consumption also play an important role (Seid, Markas, Aklilu et al., 2023). Physiological, anatomical and hormonal changes experienced during pregnancy increase the predisposition to urinary tract infection (Helli, Dolapçıoğlu and Hammer, 2011). Urinary tract infection has a prevalence rate of 20% among pregnant women (Abdel- Deciz Elzayat, Barnett-Vanes, Dabour et al., 2013; Salari, Khoshbakht, Hemmati et al., 2023). Approximately 5-12% of pregnant women are affected by asymptomatic bacteria, while 30% of women with symptoms may develop cystitis or 50% pyelonephritis. Asymptomatic bacteriuria can lead to many undesirable maternal and neonatal problems if left untreated (De Oliveira Neto et al., 2021). Preeclampsia can cause undesirable consequences such as hypertensive diseases, pyelonephritis, permanent kidney damage, anemia, premature rupture of membranes, premature birth threat, low birth weight, fetal deaths and cesarean section (Lawani, Alade and Oyelaran, 2015; Willy, Wanyoike and Mugo, 2015). These are conditions that cause many physiological and anatomical damages and are common, requiring urgent treatment (Sevil, Özdemir, Aleattin et al., 2013; Apay, Özdemir, Nazik et al., 2014; Karahan, 2017). In addition, more than half of the patients complain of clinical depression and 38.5% of them complain of anxiety. It is reported that significant improvement in quality of life has been observed after appropriate treatment and prophylaxis (Renard, Ballarini, Mascarenhas et al., 2015). It is an important public health problem and can negatively affect the life of women and families, causing deterioration of the quality of life (Sevil, Özdemir, Aleattin et al., 2013; Apay, Özdemir, Nazik et al., 2014; Karahan, 2017). It causes a significant financial impact of up to billions of dollars on both the health system and society (Akram, Shahid and Khan, 2007; Martini, Horner, Roehrs et al., 2007; De Oliveira Neto et al., 2021). Therefore, it is important to plan and implement initiatives aimed at improving and preventing urinary tract infections. When the studies were examined, it was found that incorrect, incomplete or faulty hygiene behaviors increased the incidence of urinary tract infections (Özdemir et al., 2012; Sevil et al., 2013; Karahan, 2017). In urinary tract infections, it is necessary to determine the wrong behaviors first about hygiene and to provide permanent and positive behavioral changes by providing trainings for them (Karahan, 2017). Genital hygiene behaviors are an important factor in the formation and prevention of urinary tract infections. Öner and Çeber Turfan (2020) stated that in addition to medical treatment, urinary tract infection symptoms can be prevented with hygiene education and that it also positively affects genital hygiene behaviors (Öner and Çe October Turfan, 2020). Regarding the educational methods, Sinan et al. A study conducted by (2020) concluded that genital infection awareness training based on the knowledge-motivation-behavior skills model increases women's knowledge level and positively reinforces women's hygiene behaviors (Sinan, Kaplan, Sahin et al., 2020). In another study conducted on genital hygiene behavior training given using audiovisual and brochure, it was found that the intervention group developed more positive behaviors than the control group (Hayati et al., 2018). Parlas and Eryilmaz (2023) It is stated that the knowledge, attitudes and behaviors of women who receive education based on the PRECEDE-PROCEED model are positively affected (Parlas & Eryilmaz, 2023). In particular, in another study, it is stated that planned education and home visits on genital hygiene have a positive effect (Abic, Yatmaz, Altınışık et al., 2024). In addition, web-based genital hygiene education has a positive effect on self-care power and genital hygiene behaviors (Gül and Yağmur, 2023), peer education provided under the guidance of the health improvement model is effective and increases the knowledge levels of young October adults about genital hygiene behaviors (Polat, Küçükkelepçe et al., 2022) is stated. Another study conducted to determine the effect of genital hygiene education given by three different methods, oral education after medical curettage, education with written material and just demonstration on genital hygiene behaviors, found that oral education alone is not effective in providing and developing genital hygiene behaviors, and the demonstration method is more effective than oral and written education methods (Uzun and Göktaş, 2022). As a result of the current literature review, although the importance of genital hygiene education is emphasized, it is clear that there is a need for teaching techniques that will provide permanent behavioral changes. Midwives, who are in contact the most during the pregnancy period and conduct face-to-face interviews, undertake the most important task in teaching genital hygiene behaviors effectively and correctly (Ünsal, Özyazıcıoğu, Sezgin et al. 2010). For this reason, midwives should plan training with a permanent teaching technique that fills in gaps in the lack of knowledge, can get feedback, can be evaluated, while advising pregnant women diagnosed with urinary tract infection on genital hygiene behaviors. The teach back method is a method used for the education, learning, evaluation and development of personal care behaviors of individuals. This approach provides an opportunity for individuals to understand educational materials, improve their level of retention in mind, and evaluate themselves. One of the important advantages is that the educational content is presented as simply as possible, free from medical terms, and that the clients repeat the practices at the end of the training (Ahmed Abd El- hamed, 2023). The practice involves asking patients by a health professional to explain in their own sentences what they have just been told. If there is any misunderstanding, it is clarified by the health professional and the understanding status is evaluated by checking again. This condition continues until the patient tells the truth and remembers the information given to him (Farris, 2015; Talevski, Wong Shee, Rasmussen et al., 2020). The patient's learning about issues related to health information can be improved through continuous feedback. It is stated that this method-based communication approach helps patients to better understand their own medical conditions and health information, and provides benefits in improving their skills of remembering and applying medical information (Tamura, 2013; Laws, 2018; Cheng, Chen, 2023).The Tell what you have learned method provides positive effects on information acquisition, remembering, keeping in mind, as well as health behavior management, personal care behavior development, hospitalization, quality of life and patient satisfaction (Yen and Leasure, 2019; Talevski et al., 2020; Cheng et al., 2023). In addition, it is stated that self-care increases strength and comfort, reduces the cost of health care (Badeczewski et al., 2017; Imanipour, Molazem, Rakhshan et al., 2022). For this reason, midwives can use the tell what you've learned method, which is a permanent teaching technique that fills in gaps in the lack of information, can be reversed, evaluated, while advising pregnant women diagnosed with urinary tract infection on genital hygiene behaviors. Pregnant women diagnosed with urinary tract infection have been given trainings on genital hygiene behaviors in many different methods in the literature, but when the trainings given were examined, it was determined that teaching techniques aimed at improving the education, learning level, evaluation and personal care behaviors of individuals are needed. It is thought that using the tell what you have learned method in order to fill these gaps in education will be beneficial. In this context, the fact that there are no studies on the subject in our country, the fact that evidence-based teaching techniques are tried in new areas constitutes the original value of the project and our main motivation. The project has unique value for a sustainable future in terms of its effects on pregnant women in particular and qualified midwifery care at the social level in general. It will also enable data to be obtained for comparing innovative educational methods with traditional educational methods. Thus, it will help to improve, organize or develop capacity for future initiatives. Hypotheses 1. The education given to pregnant women who have been diagnosed with urinary tract infection by the tell me what you have learned method positively affects genital hygiene behavior. 2. Education given to pregnant women who have been diagnosed with urinary tract infection by the tell-what-you-learned method reduces the level of symptoms.

Women's Perception of Respectful Maternity Care, Birth Experiences and Perception of Traumatic Birth

The research is a randomized controlled trial. The research will conducted with 124 primiparous pregnant women (intervention group n=62, control group n=62) who were hospitalized in the delivery unit of Aksaray Training and Research Hospital between September 2023 and January 2024. The pregnant women in the intervention group will given the intrapartum care model in line with WHO recommendations after cervical dilation reached 5 cm. The control group will received only the standard intrapartum care in the hospital. Data will be collected using the personal information form, birth follow-up form, respectful maternal care scale, birth experience scale, and traumatic birth perception scale.

Breastfeeding Evaluation of Puerperal Women Who Had Cesarean Delivery in Our Hospital

İntroduction The World Health Organisation (WHO) and United Nations Children's Fund (UNICEF) recommends that infants are exclusively breastfed for a minimum of 6 months, with continued breastfeeding recommended until child age of 2 years or over to optimize growth, development, and health. Breast milk shows significant benefits for the physical and mental health of mothers and infants, including the promotion of maternal and infant bonding, the reduction of neonatal mortality, the reduction of maternal postoperative complications, and the development of newborns. Breastfeeding has been associated with improved maternal/infant bonding and increased child intelligence. In addition breastfeeding has many benefits for infant, mother and later child health. The World Health Organization (WHO) and the United Nations Children's Fund (UNICEF) recommend initiation of breastfeeding within the first hour of birth, referred to as "early initiation of breastfeeding." Early initiation of breastfeeding is critical to newborn survival and to establish breastfeeding practice over the long term. When breastfeeding is delayed after birth, the consequences can be life-threatening and the longer newborns are left waiting, the greater the risk. It is also clear that medical interventions during labor and birth, including a caesarean section, impact on women's infant feeding decisions and are a cause for concern given increasing global caesarean birth rates, with woman who have a planned caesarean birth reported as less likely to intend to breastfeed than women who did not have a planned caesarean birth or had a vaginal birth. Infrequent feeding and women's limited mobility in the early days following surgery may impede efforts to provide basic infant care. High levels of postoperative pain, particularly in the first 24 hrs, were also found to have a negative impact on women's breastfeeding experiences. Cesarean delivery is linked with lower rates of early breastfeeding initiation. Pain management after casarean delivery remains challenging. The best-accepted traditional analgesic approach is continuous epidural analgesia. However, epidural analgesia is rapidly being replaced by transversus abdominis plane (TAP) blocks. TAP infiltration is an alternative to epidural blocks for providing postoperative analgesia to the anterior abdominal wall. TAP infiltrations are relatively easy to perform, generally safe, and can be performed in patients who are anti-coagulated. TAP infiltration can be performed as a single injection, or a catheter can be inserted for continuous local anesthetic infusion. We therefore proposed to compare impact of TAP block, epidural analgesia and iv multimodal analgesia after spinal analgesia on maternal comfort in patients with elective caesarean section. We will evaluate the following specific aims, all of which will be assessed over 72 hours, or the duration of hospitalization if shorter: Primary Aim: To compare the effect of pain management after cesarean on the rates of initiation of breastfeeding in the first hour after birth and exclusive breast milk in the first 72 hours in elective cesarean deliveries with spinal anesthesia. Secondary Aim 1: To compare the effect of pain management after cesarean on the rates of the confidence and comfort of breastfeeding mothers after elective cesarean deliveries with spinal anesthesia. Hypothesis. Four quadrant TAP blocks performed after elective inert cesarean section increase the rate of breastfeeding in the first 1 hour and the rate of exclusive breastfeeding in the first 72 hours. 3. Method and Study Design A. Study Overview A randomized double-blind trial is designed comparing TAP blocks , epidural analgesia and ıv multimodal analgesia and placebo in patients having elective inert cesarean deviveries with spinal anesthesia. The study will be performed at Konya City Hospital with IRB approval and written consent from patients. B. Setting and Population Inclusion criteria: - Written informed consent; - 18-45 years old; - ASA Physical Status 1-3; - Scheduled for elective cesarien delivery; - Anticipated hospitalization of at least three nights; - Expected requirement for parenteral opioids for at least 72 hours for postoperative pain; - Able to use IV PCA systems. Exclusion criteria: - Hepatic disease, e.g. twice the normal levels of liver enzymes; - Kidney disease, e.g. twice the normal level of serum creatinine; - Bupivacaine sensitivity or known allergy; - Anticoagulants considered to be a contraindication for TAP blocks; - Surgeries with high port sites; C. Withdrawal Criteria Patients will be free to withdraw from study at any time. Patients will also be removed from study at any time for adverse events, or deemed necessary for patient safety.

Effects of Core Stabilization Exercises in Children with Acute Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia (ALL) is a malignancy resulting from the abnormal proliferation of lymphoid cells that can invade the bone marrow, blood, and extramedullary regions, and it is the most common malignancy in childhood. Specific chemotherapy-related problems are frequently observed in children with ALL. These include a reduction in cardiopulmonary fitness, balance, posture, proximal muscle strength, and flexibility, as well as postural control issues and functional mobility impairments, in addition to fatigue. The aim of this study is to investigate the effects of core stabilization exercises, applied in addition to a conventional exercise program, on physical function, functional muscle strength, functional exercise capacity, postural control, and fatigue in children with Acute Lymphoblastic Leukemia undergoing maintenance therapy. Participants will be divided into two groups: the first group will follow a conventional exercise program, while the second group will receive core stabilization exercises in addition to the conventional program. All participants will be randomly assigned to the groups using the software available at http://www.randomizer.org. The exercise sessions will be conducted three times a week for a total of 8 weeks, with 24 sessions in total. Demographic information will be recorded for participants who agree to take part in the study and meet the inclusion criteria. The scales and tests designed to assess the participants' physical function, functional muscle strength, functional exercise capacity, postural control, and fatigue will be administered both before and after the study.

The Effect of Retatrutide Once Weekly on Cardiovascular Outcomes and Kidney Outcomes in Adults Living With Obesity (TRIUMPH-Outcomes)

The Effect of Animated Movies and Storybooks on Fear and Anxiety Levels in Children With Type 1 Diabetes

This study aims to evaluate the effects of animated films and story books on the fear and anxiety levels of children with newly diagnosed type 1 diabetes. In the study, newly diagnosed children in the experimental group will be shown a 10-minute movie and read the educational booklet. Routine care will continue for the control group.