Subcutaneously administered tirzepatide vs semaglutide for adults with type 2 diabetes: a systematic review and network meta-analysis of randomised controlled trials.

AIMS/HYPOTHESIS: We conducted a systematic review and network meta-analysis to compare the efficacy and safety of s.c. administered tirzepatide vs s.c. administered semaglutide for adults of both sexes with type 2 diabetes mellitus. METHODS: We searched PubMed and Cochrane up to 11 November 2023 for RCTs with an intervention duration of at least 12 weeks assessing s.c. tirzepatide at maintenance doses of 5 mg, 10 mg or 15 mg once weekly, or s.c. semaglutide at maintenance doses of 0.5 mg, 1.0 mg or 2.0 mg once weekly, in adults with type 2 diabetes, regardless of background glucose-lowering treatment. Eligible trials compared any of the specified doses of tirzepatide and semaglutide against each other, placebo or other glucose-lowering drugs. Primary outcomes were changes in HbA1c and body weight from baseline. Secondary outcomes were achievement of HbA1c target of ≤48 mmol/mol (≤6.5%) or <53 mmol/mol (<7.0%), body weight loss of at least 10%, and safety outcomes including gastrointestinal adverse events and severe hypoglycaemia. We used version 2 of the Cochrane risk-of-bias tool (ROB 2) to assess the risk of bias, conducted frequentist random-effects network meta-analyses and evaluated confidence in effect estimates utilising the Confidence In Network Meta-Analysis (CINeMA) framework. RESULTS: A total of 28 trials with 23,622 participants (44.2% female) were included. Compared with placebo, tirzepatide 15 mg was the most efficacious treatment in reducing HbA1c (mean difference -21.61 mmol/mol [-1.96%]) followed by tirzepatide 10 mg (-20.19 mmol/mol [-1.84%]), semaglutide 2.0 mg (-17.74 mmol/mol [-1.59%]), tirzepatide 5 mg (-17.60 mmol/mol [-1.60%]), semaglutide 1.0 mg (-15.25 mmol/mol [-1.39%]) and semaglutide 0.5 mg (-12.00 mmol/mol [-1.09%]). In between-drug comparisons, all tirzepatide doses were comparable with semaglutide 2.0 mg and superior to semaglutide 1.0 mg and 0.5 mg. Compared with placebo, tirzepatide was more efficacious than semaglutide for reducing body weight, with reductions ranging from 9.57 kg (tirzepatide 15 mg) to 5.27 kg (tirzepatide 5 mg). Semaglutide had a less pronounced effect, with reductions ranging from 4.97 kg (semaglutide 2.0 mg) to 2.52 kg (semaglutide 0.5 mg). In between-drug comparisons, tirzepatide 15 mg, 10 mg and 5 mg demonstrated greater efficacy than semaglutide 2.0 mg, 1.0 mg and 0.5 mg, respectively. Both drugs increased incidence of gastrointestinal adverse events compared with placebo, while neither tirzepatide nor semaglutide increased the risk of serious adverse events or severe hypoglycaemia. CONCLUSIONS/INTERPRETATION: Our data show that s.c. tirzepatide had a more pronounced effect on HbA1c and weight reduction compared with s.c. semaglutide in people with type 2 diabetes. Both drugs, particularly higher doses of tirzepatide, increased gastrointestinal adverse events. REGISTRATION: PROSPERO registration no. CRD42022382594.

Quality Indicators and Clinical Outcomes of Acute Stroke: Results from a Prospective Multicenter Registry in Greece (SUN4P).

AIM: The Stroke Units Necessity for Patients (SUN4P) project aims to provide essential data on stroke healthcare in Greece. Herein, we present results on established quality indicators and outcomes after first-ever stroke occurrences. METHODS: This prospective multicenter study included consecutive patients admitted to nine hospitals across Greece in 2019-2021. Descriptive statistics were used to present patients' characteristics, key performance measures and stroke outcomes. RESULTS: Among 892 patients, 755 had ischemic stroke (IS) (mean age 75.6 ± 13.6, 48.7% males) and 137 had hemorrhagic stroke (HS) (mean age 75.8 ± 13.2, 57.7% males). Of those, 15.4% of IS and 8% of HS patients were treated in the acute stroke unit (ASU) and 20.7% and 33.8% were admitted to the intensive care unit (ICU) or high-dependency unit (HDU), respectively. A total of 35 (4.6%) out of 125 eligible patients received intravenous alteplase with a door-to needle time of 60 min (21-90). The time to first scan for IS patients was 60 min (31-105) with 53.2% undergoing a CT scan within 60 min post presentation. Furthermore, 94.4% were discharged on antiplatelets, 69.8% on lipid-lowering therapy and 61.6% on antihypertensives. Oral anticoagulants (OAC) were initiated in 73.2% of the 153 IS patients with atrial fibrillation (AF). Among the 687 IS patients who survived, 85.4% were discharged home, 12% were transferred to rehabilitation centers, 1.2% to nursing homes and 1.3% to another hospital. CONCLUSIONS: The SUN4P Registry is the first study to provide data from a prospectively collected cohort of consecutive patients from nine representative national hospitals. It represents an important step in the evaluation and improvement of the quality of acute stroke care in Greece.

The Cost and the Value of Stroke Care in Greece: Results from the SUN4P Study.

The aim of this study was to measure the one-year total cost of strokes and to investigate the value of stroke care, defined as cost per QALY. The study population included 892 patients with first-ever acute strokes, hemorrhagic strokes, and ischemic strokes, (ICD-10 codes: I61, I63, and I64) admitted within 48 h of symptoms onset to nine public hospitals located in six cities. We conducted a bottom-up cost analysis from the societal point of view. All cost components including direct medical costs, productivity losses due to morbidity and mortality, and informal care costs were considered. We used an annual time horizon, including all costs for 2021, irrespective of the time of disease onset. The average cost (direct and indirect) was extrapolated in order to estimate the national annual burden associated with stroke. We estimated the total cost of stroke in Greece at EUR 343.1 mil. a year in 2021, (EUR 10,722/patient or EUR 23,308 per QALY). Out of EUR 343.1 mil., 53.3% (EUR 182.9 mil.) consisted of direct healthcare costs, representing 1.1% of current health expenditure in 2021. Overall, productivity losses were calculated at EUR 160.2 mil. The mean productivity losses were estimated to be 116 work days with 55.1 days lost due to premature retirement and absenteeism from work, 18.5 days lost due to mortality, and 42.4 days lost due to informal caregiving by family members. This study highlights the burden of stroke and underlines the need for stakeholders and policymakers to re-organize stroke care and promote interventions that have been proven cost-effective.

Midday Dipping and Circadian Blood Pressure Patterns in Acute Ischemic Stroke.

The purpose of this study was to investigate the alterations in blood pressure (BP) during midday and the changes in circadian BP patterns in the acute phase of ischemic stroke (AIS) with the severity of stroke and their predictive role outcomes within 3 months. A total of 228 AIS patients (a prospective multicenter follow-up study) underwent 24 h ambulatory blood pressure monitoring (ABPM). Mean BP parameters during the day (7:00-22:59), the midday (13:00-16:59), and the night (23:00-6:59), and midday and nocturnal dipping were calculated. Midday SBP dippers had less severe stroke, lower incidence of hypertension and SBP/DBP on admission, lower levels of serum glucose and WBCs, and delayed initiation of ABPM compared to risers. There was a reverse relation between midday SBP dipping and both nocturnal dipping and stroke severity. The "double dippers" (midday and nocturnal dipping) had the least severe stroke, the lowest SBP/DBP on admission, the lowest heart rate from ABPM, and a lower risk of an unfavorable outcome, while the "double risers" had the opposite results, by an approximately five-fold risk of death/disability at 3 months. These findings indicate different circadian BP patterns during the acute phase of AIS, which could be considered a marker of stroke severity and prognosis.

Prognostic significance of 24-h blood pressure and variability indices in the outcome of acute ischaemic stroke.

BACKGROUND: The association between blood pressure (BP) levels and BP variability (BPV) following acute ischaemic stroke (AIS) and outcome remains controversial. AIMS: To investigate the predictive value of systolic BP (SBP) and diastolic BP (DBP) and BPV measured using 24-h ambulatory blood pressure monitoring (ABPM) methods during AIS regarding outcome. METHODS: A total of 228 AIS patients (175 without prior disability) underwent ABPM every 20 min within 48 h from onset using an automated oscillometric device (TM 2430, A&D Company Ltd) during day time (7:00-22:59) and night time (23:00-6:59). Risk factors, stroke subtypes, clinical and laboratory findings were recorded. Mean BP parameters and several BPV indices were calculated. End-points were death and unfavourable functional outcome (disability/death) at 3 months. RESULTS: A total of 61 (26.7%) patients eventually died. Multivariate logistic regression analysis revealed that only mean night-time DBP (hazard ratio (HR): 1.04; 95% confidence interval (CI): 1.00-1.07) was an independent prognostic factor of death. Of the 175 patients without prior disability, 79 (45.1%) finally met the end-point of unfavourable functional outcome. Mean 24-h SBP (HR: 1.03; 95% CI: 1.00-1.05), day-time SBP (HR: 1.02; 95% CI: 1.00-1.05) and night-time SBP (HR: 1.03; 95% CI: 1.01-1.05), SBP nocturnal decline (HR: 0.93; 95% CI: 0.88-0.99), mean 24-h DBP (HR: 1.08; 95% CI: 1.03-1.13), day-time DBP (HR: 1.07; 95% CI: 1.03-1.12) and night-time DBP (HR: 1.06; 95% CI: 1.02-1.10) were independent prognostic factors of an unfavourable functional outcome. CONCLUSIONS: In contrast with BPV indices, ABPM-derived BP levels and lower or absence of BP nocturnal decline in the acute phase are prognostic factors of outcome in AIS patients.

Time of blood pressure in target range in acute ischemic stroke.

OBJECTIVE: The purpose of this study was to investigate the association of blood pressure (BP) time-in-target range (TTR) derived from 24-h ambulatory BP monitoring (ABPM) during the acute phase of ischemic stroke (AIS), with the severity of stroke and its predictive value for the 3 months outcome. METHODS: A total of 228 AIS patients (prospective multicenter follow-up study) underwent ABPM every 20 min within 48 h from stroke onset using an automated oscillometric device. Clinical and laboratory findings were recorded. Mean BP parameters, BP variability and TTR for SBP (90-140 mmHg), DBP (60-90 mmHg), and mean arterial pressure (MAP) were calculated. Endpoints were death and disability/death at 3 months. RESULTS: A total of 14 942 BP measurements were recorded (∼66 per AIS patient) within 72 h of stroke onset. Patient's 24-h TTR was 34.7 ±â€Š29.9, 64.3 ±â€Š24.2, and 55.3 ±â€Š29.4% for SBP, DBP and MAP, respectively. In patients without prior hypertension, TTR was lower as stroke severity increased for both DBP (P = 0.031) and MAP (P = 0.016). In 175 patients without prior disability, increase in TTR of DBP and MAP associated significantly with a decreased risk of disability/death (hazard ratio 0.96, 95% CI 0.95-0.99, P = 0.007 and hazard ratio 0.97, 95% CI 0.96-0.99, P = 0.007). TTR of SBP in 130-180 mmHg and 110-160 mmHg ranges seems to be related with mortality and disability outcomes, respectively. CONCLUSION: TTR can be included for a more detailed description of BP course, according to stroke severity, and for the evaluation of BP predictive role, in addition to mean BP values, derived from ABPM during the acute phase of AIS. CLINICAL TRIAL REGISTRATIONURL: http://www.clinicaltrials.gov. Unique identifier: NCT01915862.

Assessment of Atherosclerosis in Ischemic Stroke by means of Ultrasound of Extracranial/Intracranial Circulation and Serum, Urine, and Tissue Biomarkers.

It is a common practice to take into consideration age, diabetes, smoking, treated and untreated systolic blood pressure, total cholesterol, and high-density lipoprotein cholesterol for the prediction of atherosclerosis and stroke. There are, however, ultrasound markers in use for the assessment of atherosclerosis and the evaluation of stroke risk. Two areas of investigation are of interest: the carotid artery and the intracranial arterial circulation. Again, within the domain of the carotid artery, two ultrasonic markers have attracted our attention: intima media thickness of the carotid artery and the presence of carotid plaque with its various focal characteristics. In the domain of intracranial circulation, the presence of arterial stenosis and the recruitment of collaterals are considered significant ultrasonic markers for the above-mentioned purpose. On the other hand, a series of serum, urine, and tissue biomarkers are found to be related to atherosclerotic disease. Future studies might address the issue of whether the addition of proven ultrasonic carotid indices to the aforementioned serum, urine, and tissue biomarkers could provide the vascular specialist with a better assessment of the atherosclerotic load and solidify their position as surrogate markers for the evaluation of atherosclerosis and stroke risk.

Stroke Units Necessity for Patients, Web-Based "SUN4P" Registry: Descriptive Characteristics of the Population.

The aim of this study was to present the descriptive characteristics of the Stroke Units Necessity for Patients (SUN4P) registry. METHODS: The study population derived from the web-based SUN4P registry included 823 patients with first-ever acute stroke. Descriptive statistics were used to present patients' characteristics. RESULTS: The vast majority of patients (80.4%) had an ischemic stroke, whereas 15.4% had a hemorrhagic stroke. Hypertension was the leading risk factor in both patients. The patients with ischemic stroke had higher prevalence of traditional cardiovascular risk factors such as diabetes mellitus, dyslipidemia and smoking and most commonly cryptogenic stroke (39%). National Institutes of Health Stroke Scale (NIHSS) was higher among patients with hemorrhagic in comparison to those with ischemic stroke (10.5 vs 6 respectively). Moreover, all patients had similar rate of disability prior to stroke, as shown by Modified Rankin Scale (mRS=0). CONCLUSIONS: These data are in accordance with current evidence and should be thoroughly assessed in order to ensure optimal therapeutic management of stroke patients.

Inpatient Cost of Stroke Care in Greece: Preliminary Results of the Web-Based "SUN4P" Registry.

The aim of this study was to calculate the average operational cost per sub-type of stroke patient and to investigate cost drivers (e.g. ALoS, NIHSS score, age) correlated to cost. METHODS: Direct medical costs (diagnostic imaging and clinical laboratory exams, overheads/bed cost, pharmaceuticals, ringers and other non-durables and inpatient rehabilitation) per patient were calculated from the providers' (hospitals') perspective. Resource use data derived from the "SUN4P" web-based registry and unit costs were retrieved from publically available sources and were assigned to resource use. RESULTS: The sample comprised 6,282 inpatient days of 750 patients (mean age: 75.5±13.3 years) admitted from July 2019 to July 2021, in nine public hospitals. Mean length of stay was 8.4±7.6 days and mean total operational cost was calculated to €1,239.4 (from which 45% and 35% related to diagnostic exams and overheads/bed cost respectively). Mean cost related to hemorrhagic stroke patients that were discharged alive was calculated significantly higher compared to mean cost related to ischemic stroke patients who didn't undertake thrombolysis and were also discharged alive from the hospital (€2,155.2 vs. €945.2, p<0.001). Linear regression analysis revealed that length of stay was significantly correlated with cost (coefficient beta=232, 95% CI confidence interval = 220-243, p<0.001). CONCLUSIONS: These findings are in accordance with current evidence and should be thoroughly assessed to rationalize inpatient reimbursement rates in order to achieve improved value of care.

Recommendations for lipid modification in patients with ischemic stroke or transient ischemic attack: A clinical guide by the Hellenic Stroke Organization and the Hellenic Atherosclerosis Society.

This document presents the consensus recommendations of the Hellenic Stroke Organization and the Hellenic Atherosclerosis Society for lipid modification in patients with ischemic stroke or transient ischemic attack. This clinical guide summarizes the current literature on lipid management and can be of assistance to the physicians treating stroke patients in clinical practice.

Climate change but not unemployment explains the changing suicidality in Thessaloniki Greece (2000-2012).

INTRODUCTION: Recently there was a debate concerning the etiology behind attempts and completed suicides. The aim of the current study was to search for possible correlations between the rates of attempted and completed suicide and climate variables and regional unemployment per year in the county of Thessaloniki, Macedonia, northern Greece, for the years 2000-12. MATERIAL AND METHODS: The regional rates of suicide and attempted suicide as well as regional unemployment were available from previous publications of the authors. The climate variables were calculated from the daily E-OBS gridded dataset which is based on observational data RESULTS: Only the male suicide rates correlate significantly with high mean annual temperature but not with unemployment. The multiple linear regression analysis results suggest that temperature is the only variable that determines male suicides and explains 51% of their variance. Unemployment fails to contribute significantly to the model. There seems to be a seasonal distribution for attempts with mean rates being higher for the period from May to October and the rates clearly correlate with temperature. The highest mean rates were observed during May and August and the lowest during December and February. Multiple linear regression analysis suggests that temperature also determines the female attempts rate although the explained variable is significant but very low (3-5%) CONCLUSION: Climate variables and specifically high temperature correlate both with suicide and attempted suicide rates but with a different way between males and females. The climate effect was stronger than the effect of unemployment.

Prognostic value of 24-h ABPM in acute ischemic stroke for short-, medium-, and long-term outcome: a systematic review and meta-analysis.

BACKGROUND: The association of blood pressure levels during the acute phase of ischemic stroke with outcome remains controversial. AIMS: The objective of this systematic review is to assess the predictive value for stroke outcome assessed by the modified Rankin scale score of systolic and diastolic blood pressure, measured by ambulatory blood pressure monitoring methods during the acute phase of ischemic stroke, compared with the values of casually derived blood pressure measurement on admission. METHODS: We searched for studies with patients admitted within 24 h of stroke onset, and who had ambulatory blood pressure monitoring during the first 24 h of admission. We identified studies that reported blood pressure in those with good outcome and in those with poor outcome at end of follow-up, and performed a meta-analysis of the effect of mean blood pressure on outcome. RESULTS: High systolic and diastolic blood pressure levels derived with ambulatory blood pressure monitoring were associated with poor short-, medium-, and long-term outcome, but the same was not found for casual blood pressure measurements. An increase in systolic blood pressure of 9·1 mmHg (95% confidence interval: 6·6-11·6, P < 0·001; I(2) = 9%) and an increase in diastolic blood pressure of 2·3 mmHg (95% confidence interval: 0·8-3·7, P = 0·002; I(2) = 0%) were associated with poor outcome. CONCLUSIONS: Higher systolic and diastolic blood pressure levels derived with ambulatory blood pressure monitoring were associated with poor outcome. The same was not found for higher casual blood pressure measurements on admission, and it is possible that ambulatory blood pressure monitoring conveys better prognostic information.

Is anemia a new cardiovascular risk factor?

Anemia is frequent in patients with cardiovascular disease and is often characterized as the fifth cardiovascular risk factor. It is considered to develop due to a complex interaction of iron deficiency, cytokine production and impaired renal function, although other factors, such as blood loss, may also contribute. Unfortunately, treatment of anemia in cardiovascular disease lacks clear targets and specific therapy is not defined. Treatment with erythropoietin-stimulating agents in combination with iron is the basic strategy but clear guidelines are not currently available. This review aims to clarify poorly investigated and defined issues concerning the relation of anemia and cardiovascular risk--in particular in patients with acute coronary syndromes and chronic heart failure--as well as the current therapeutic strategies in these clinical conditions.

Riedel's lobe of the liver: a case report.

Riedel lobe of the liver is a simple anatomical variation, a downward tongue-like projection of the anterior edge of the right lobe of the liver to the right of the gallbladder with its typical case to be rare.We report the case of a 71-year-old woman with typical feature of a nonpalpable Riedel's lobe of the liver, as an incidental finding who was referred for reported hypergammaglobulinemia (22.7% [9%-19%]). Both features were attributed to a chronic inflammation because of an abscess in the right iliopsoas caused by infection due to bilateral hip replacement which underwent revision surgery. This was confirmed by her medical history, the imaging findings combined with elevated C-reactive protein, and by cross-reaction weak positive autoantibodies.Generally, knowledge or suspicion of Riedel's lobe of the liver is important, as it does not always remain clinically latent, as in our case, and it can be complicated by its torsion or hepatic tumors.

Initially lymphocytic Sweet's syndrome in male patients with myelodysplasia: a distinguished clinicopathological entity? Case report and systematic review of the literature.

BACKGROUND: Sweet's syndrome (SS) is an acute febrile neutrophilic dermatosis. It can occur as an idiopathic, drug-induced or malignancy-associated entity. SS is also seen in patients with myelodysplastic syndrome (MDS) where it may present atypically, both clinically and histologically. In a few rare cases of MDS, lymphocytic infiltrates are the presenting feature of SS. METHODS: MEDLINE and Scopus were the data sources for our review. RESULTS: A clinicopathological subsetemerged of 12 male SS patients with MDS and a mean age of 67.3 years in which the initial SS lesions were lymphocytic infiltrates. However, from 0.5 to 8 years later, sequential biopsies revealed neutrophilic dermal infiltration typical of SS. CONCLUSION: Initially lymphocytic infiltrates in this subset could be attributed either to an early timing of the biopsy concerning the age of the lesion or to the dysgranulopoiesis syndrome. A possible relationship between the dysfunction of the receptor of the granulocyte-macrophage colony stimulating factor, the gene of which is located on the pseudoautosomal X-Y region, may exist in MDS patients with initially lymphocytic SS. This could explain the male gender of this subset and might establish initially lymphocytic SS as a distinguished clinicopathological entity for predicting the occurrence and even the prognosis of MDS.

The prognostic efficacy of myocardial perfusion imaging in optimally treated diabetic patients with no manifestations of coronary artery disease.

OBJECTIVE: This study investigates the efficacy of radionuclide myocardial perfusion imaging (MPI) in the evaluation of cardiac outcome in optimally treated diabetic patients without manifestations of coronary artery disease (CAD) in relation to the inherent clinical risk. METHODS: Follow-up data were collected from 86 diabetic patients who had undergone adenosine stressing MPI. These patients either had no symptoms or had noncardiac chest discomfort, had a normal resting electrocardiogram, had no known CAD or prior positive stress test results, and were receiving currently recommended therapy. Endpoints were cardiac death, myocardial infarction, new-onset heart failure, and CAD diagnosed by angiography at least 2 months from the MPI, irrespective of subsequent revascularization. RESULTS: Twenty-six (30%) diabetic patients had abnormal perfusion and the remaining had a normal scan. Over a median follow-up period of 32.5 months 14 cardiac events occurred. In patients with normal MPI, the annual cardiac event rate was 4.0% compared with 12.2% in those with abnormal MPI (P=0.008). In multivariate analysis, myocardial ischemia (hazard ratio 5.3; P=0.006), obesity (hazard ratio 6.8; P=0.005), the ALFEDIAM/SFC risk (hazard ratio 6.8; P=0.002), and type 2 diabetes (hazard ratio 5.3; P=0.035) were found to be independent predictors of cardiac events. The former two variables remained independent determinants of the outcome, together with peripheral arterial disease, when a different clinical risk classification system was applied. MPI provided incremental prognostic information over both clinical models formed. CONCLUSION: Adenosine MPI can effectively risk-stratify optimally treated diabetic patients without manifestations of CAD. In this subset, clinical variables can also determine the outcome independently, but MPI adds incremental predictability over them.