scholarly journals Thrombolytic treatment in the oldest-old patient with acute ischemic stroke: an update on current evidence

2013 ◽  
pp. 160-165
Author(s):  
Fabiola Maioli ◽  
Gaetano Procaccianti ◽  
Valeria Nativio ◽  
Giorgia Arnone ◽  
Roberto Nardi ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Thrombolytic Therapy ◽  
Acute Ischemic Stroke ◽  
Oldest Old ◽  
Intravenous Thrombolysis ◽  
Cognitive Status ◽  
Screening Tools ◽  
Current Evidence ◽  
Thrombolytic Treatment ◽  
Old Patients

The incidence of ischemic stroke rises exponentially with age, with a steep increase in the age interval between 75 and 85 years. Thrombolytic therapy restores cerebral blood flow in patients with acute ischemic stroke of any etiology by using drugs that dissolve blood clots. Infusion for 1 h of alteplase at the dose of 0.9 mg/kg within 3 h of the start of the symptoms is associated to a 30% increase in the likelihood of gaining a favorable outcome with respect to placebo. There is strong evidence that selected patients with ischemic stroke may benefit from intravenous thrombolysis when treated within 3 h. The aim of the study was to evaluate available evidence for the efficacy and safety of thrombolytic therapy in patients with ischemic stroke aged 80 years and over. Compared to younger stroke patients treated with thrombolytic therapy, those aged 80 years and over have higher acute mortality due to symptomatic intracranial hemorrhage. However, functional outcome at six months is significantly better for over-80-year-olds than younger patients. There is a need for screening tools that take into account pre-stroke functional and cognitive status that are able to identify those over-80-year-old patients with ischemic stroke who can most benefit from thrombolytic treatment. Available evidence supports further recruitment of oldest-old patients into ongoing trials of thrombolysis.

scholarly journals Target: Stroke Was Associated With Faster Intravenous Thrombolysis and Improved One-Year Outcomes for Acute Ischemic Stroke in Medicare Beneficiaries

2020 ◽  
Vol 13 (12) ◽  
Author(s):  
Shumei Man ◽  
Ying Xian ◽  
DaJuanicia N. Holmes ◽  
Roland A. Matsouaka ◽  
Jeffrey L. Saver ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Thrombolytic Therapy ◽  
Acute Ischemic Stroke ◽  
Intravenous Thrombolysis ◽  
Cox Proportional Hazards ◽  
Hazard Ratio ◽  
Medicare Beneficiaries ◽  
Thrombolytic Treatment ◽  
Rate Of Increase ◽  
All Cause Mortality

Background: The benefit of intravenous thrombolytic therapy for acute ischemic stroke is time dependent. To assist hospitals in providing faster thrombolytic treatment, the American Heart Association launched target: stroke quality initiative in January 2010 which disseminated feasible strategies to shorten door-to-needle times for thrombolytic therapy. This study aimed to examine whether target: stroke was associated with improved door-to-needle times and 1-year outcomes. Methods: We analyzed Medicare beneficiaries aged ≥65 years receiving intravenous thrombolytic treatment for acute ischemic stroke at 1490 Get With The Guidelines-Stroke hospitals during January 2006 and December 2009 (preintervention, n=10 804) and January 2010 and December 2014 (postintervention, n=31 249). The median age was 80 years and 42.7% were male. Results: The median door-to-needle times decreased from 80 minutes for the preintervention to 68 minutes for the postintervention ( P <0.001). The proportion of patients receiving intravenous thrombolysis with door-to-needle times 45 minutes and 60 minutes increased from 9.6% and 24.8% for preintervention to 17.1% and 40.6% for postintervention, respectively ( P <0.001). The annual rate of increase in the door-to-needle times of 60 minutes or less accelerated from 0.20% (95% CI, −0.43% to 0.83%) per each 4 quarters for preintervention to 5.68% (95% CI, 5.23%–6.13%) for postintervention ( P <0.001) which was further confirmed in piecewise multivariable generalized estimating analysis (adjusted odds ratio, 1.27 [95% CI, 1.19–1.35]). Cox proportional hazards analysis, after adjusting for patient and hospital characteristics and within-hospital clustering, showed that target: stroke was associated with lower all-cause readmission (40.4% versus 44.1%; hazard ratio, 0.91 [95% CI, 0.88–0.95]), cardiovascular readmission (19.7% versus 22.9%; hazard ratio, 0.85 [95% CI, 0.80–0.89]), and composite of all-cause mortality or readmission (56.0% versus 58.4%; hazard ratio, 0.96 [95% CI, 0.93–1.00]). The risk decline in all-cause mortality dissipated after risk adjustment (adjusted hazard ratio, 0.98 [95% CI, 0.94–1.02]). Conclusions: Target: stroke quality initiative was associated with faster thrombolytic treatment times for acute ischemic stroke and modestly lower 1-year all-cause and cardiovascular readmissions.

Admission Hemoglobin Is Prognostic for In-Hospital Mortality in Oldest-Old Patients with Acute Ischemic Stroke

Gerontology ◽  
2021 ◽  
pp. 1-8
Author(s):  
Mingquan Li ◽  
Xiaoyun Liu ◽  
Liumin Wang ◽  
Lei Shu ◽  
Liqin Luan ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Hospital Mortality ◽  
Hospital Stay ◽  
Acute Ischemic Stroke ◽  
Oldest Old ◽  
Final Analysis ◽  
Short Term ◽  
Old Patients ◽  
Short Term Mortality ◽  
Tertiary Hospitals

<b><i>Introduction:</i></b> Anemia is a common condition encountered in acute ischemic stroke, and only a few pieces of evidence has been produced suggesting its possible association with short-term mortality have been produced. The study sought to assess whether admission anemia status had any impact on short-term clinical outcome among oldest-old patients with acute ischemic stroke. <b><i>Materials and Methods:</i></b> A retrospective review of Electronic Medical Recording System was performed in 2 tertiary hospitals. Data, from the oldest-old patients aged &#x3e; = 80 years consecutively admitted with a diagnosis of acute ischemic stroke between January 1, 2015, and December 31, 2019, were analyzed. Admission hemoglobin was used as indicator for anemia and severity. Univariate and multivariate regression analyses were used to compare in-hospital mortality and length of in-hospital stay in different anemia statuses and normal hemoglobin patients. <b><i>Results:</i></b> A total of 705 acute ischemic stroke patients were admitted, and 572 were included in the final analysis. Of included patients, 240 of them were anemic and 332 nonanemic patients. A statistical difference between the 2 groups was found in in-hospital mortality (<i>p</i> &#x3c; 0.001). After adjustment for baseline characteristics, the odds ratio value of anemia for mortality were 3.91 (95% confidence intervals (CI) 1.60–9.61, <i>p</i> = 0.003) and 7.15 (95% CI: 1.46–34.90, <i>p</i> = 0.015) in moderate and severely anemic patients, respectively. Similarly, length of in-hospital stay was longer in anemic patients (21.64 ± 6.17 days) than in nonanemic patients (19.08 ± 5.48 days, <i>p</i> &#x3c; 0.001). <b><i>Conclusions:</i></b> Increased severity of anemia may be an independent risk factor for increased in-hospital mortality and longer length of stay in oldest-old patients with acute ischemic stroke.

scholarly journals The Role of Personality Associated with In-Hospital Delay in Intravenous Thrombolysis for Acute Ischemic Stroke

2020 ◽  
Author(s):  
Zhenchan Lu ◽  
Caixia Qiu ◽  
Xiangyan Yang ◽  
Honggang Ma ◽  
Shuang Shen ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Thrombolytic Therapy ◽  
Personality Traits ◽  
Acute Ischemic Stroke ◽  
Big Five ◽  
Multivariable Analysis ◽  
Intravenous Thrombolysis ◽  
Big Five Personality ◽  
Effective Strategies

Abstract Background: Decreasing the in-hospital delay is one of the critical effective strategies for thrombolytic therapy for acute ischemic stroke. we examined whether physician personality traits are associated with in-hospital delay in conducting treatment of intravenous thrombolysis for acute ischemic stroke among neurologists.Methods: Overall 354 consecutive patients who received intravenous thrombolysis during a 2.5 year-period in emergency department were included. Self-reported questionnaires of the Big Five Inventory and demographic characteristics were distributed among 13 neurologists. Multivariable analysis was performed to explore the effects of the Big Five Personality Traits on in-hospital delay for acute ischemic stroke. Results: The traits of agreeableness in all physicians decreased the likelihood of in-hospital delay (OR: 0.831, 95% CI: 0.766-0.901, p<0.001). The traits of openness in female physicians (OR:0.646; 95% CI:0.469-0.890; p=0.008) and the traits of extraversion in male physicians (OR:0.613; 95% CI: 0.475-0.791; p<0.001) decreased the likelihood of in-hospital delay. The traits of conscientiousness in female (OR: 1.713, 95% CI: 1.209–2.427; p=0.002) and the traits of openness in male (OR: 1.431; 95% CI: 1.802-1.892; p=0.012) increased the likelihood of in-hospital delay. Conclusions: The study demonstrate that the personality traits of physician are associated with in-hospital delay for thrombolytic therapy in acute ischemic stroke.

scholarly journals Intravenous Thrombolytic Treatment in the Oldest Old

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Juan García-Caldentey ◽  
María Alonso de Leciñana ◽  
Patricia Simal ◽  
Blanca Fuentes ◽  
Gemma Reig ◽  
...  
Keyword(s):  
Intracranial Haemorrhage ◽  
Primary Outcome ◽  
Oldest Old ◽  
Demographic Data ◽  
Intravenous Thrombolysis ◽  
Modified Rankin Scale ◽  
Thrombolytic Treatment ◽  
Old Patients ◽  
Nihss Score ◽  
Tissue Plasminogen

Background and Purpose.Intravenous thrombolysis using tissue plasminogen activator is safe and probably effective in patients >80 years old. Nevertheless, its safety has not been specifically addressed for the oldest old patients (≥85 years old, OO). We assessed the safety and effectiveness of thrombolysis in this group of age.Methods.A prospective registry of patients treated with intravenous thrombolysis. Patients were divided in two groups (<85 years and the OO). Demographic data, stroke aetiology and baseline National Institute Health Stroke Scale (NIHSS) score were recorded. The primary outcome measures were the percentage of symptomatic intracranial haemorrhage (SICH) and functional outcome at 3 months (modified Rankin Scale, mRS).Results.A total of 1,505 patients were registered. 106 patients were OO [median 88, range 85–101]. Female sex, hypertension, elevated blood pressure at admission, cardioembolic strokes and higher basal NIHSS score were more frequent in the OO. SICH transformation rates were similar (3.1% versus 3.7%,P=1.00). The probability of independence at 3 months (mRS 0–2) was lower in the OO (40.2% versus 58.7%,P=0.001) but not after adjustment for confounding factors (adjusted OR, 0.82; 95% CI, 0.50 to 1.37;P=0.455). Three-month mortality was higher in the OO (28.0% versus 11.5%,P<0.001).Conclusion.Intravenous thrombolysis for stroke in OO patients did not increase the risk of SICH although mortality was higher in this group.

Abstract 58: The Iscore Predicts Efficacy Of Thrombolytic Therapy For Acute Ischemic Stroke

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Gustavo Saposnik ◽  
Jiming Fang ◽  
Moira Kapral ◽  
Jack Tu ◽  
Muhammad Mamdani ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Thrombolytic Therapy ◽  
Acute Ischemic Stroke ◽  
Clinical Response ◽  
Intravenous Thrombolysis ◽  
Hemorrhagic Transformation ◽  
Neurological Deterioration ◽  
Stroke Severity ◽  
Risk Of Death ◽  
Poor Outcome

Background: The iScore is a validated tool developed to estimate the risk of death and functional outcomes early after an acute ischemic stroke. It includes demographics, stroke severity and subtype, vascular risk factors, cancer, renal failure, and pre-admission functional status. Limited information is available to predict the clinical response after intravenous thrombolytic therapy (tPA). Objective: To determine the ability of the iScore to predict the clinical response and risk of hemorrhagic transformation after tPA. Methods: We applied the iScore ( www.sorcan.ca/iscore ) to patients presenting with an acute ischemic stroke at 11 stroke centres in Ontario, Canada, between 2003 and 2008, identified from the Registry of the Canadian Stroke Network (RCSN). We compared outcomes between patients receiving and not receiving tPA adjusting for differences in baseline characteristics through matching by propensity scores. Three groups were defined a priori as per the iScore (low risk 180). Outcome Measures: Poor outcome, the primary outcome measure, was defined as disability at discharge or death at 30 days. Secondary outcomes included disability at discharge, neurological deterioration and intracranial hemorrhage (any type and symptomatic). Results: Among 12,686 patients with an acute ischemic stroke, 1696 (13.4%) received intravenous thrombolysis. Overall, 589 tPA patients were matched with 589 non-tPA patients (low iScore risk), 682 tPA were matched with 682 non-tPA patients (medium iScore risk) and 419 tPA patients were matched with 419 non-tPA patients (high iScore risk). There was good matching in all three groups. Higher iScore was associated with poor functional outcome in both the tPA and non-tPA groups (p<0.001). Among those with low and medium iScore risk, tPA use was associated with lower risk of poor outcome (Low iScore RR 0.74; 95%CI 0.67-0.84; medium iScore RR 0.88; 95%CI 0.84-0.93). There was no difference in clinical outcomes between matched patients receiving and not receiving tPA in the highest iScore group (RR 0.97; 95%CI 0.94-1.01). Similar results were observed for disability at discharge and length of stay. The incident risk of neurological deterioration and hemorrhagic transformation (any or symptomatic) increased with the iScore risk ( Figure ). Conclusion: The iScore appears to predict clinical response and risk of hemorrhagic complications after tPA for an acute ischemic stroke. Patients with high iScores may not benefit from tPA and have higher risk of hemorrhagic transformation, though this finding should be validated independently (underway) before clinical use.

Recombinant Tissue-Type Plasminogen Activator Study of Wake-Up Ischemic Strokes Guided by Rapid MRI

2019 ◽  
Vol 48 (1-2) ◽  
pp. 85-90 ◽  
Author(s):  
CuiPing Guo ◽  
QingKe Bai ◽  
ZhenGuo Zhao ◽  
JianYing Zhang
Keyword(s):  
Ischemic Stroke ◽  
Thrombolytic Therapy ◽  
Acute Ischemic Stroke ◽  
Scale Score ◽  
Time Window ◽  
Onset Time ◽  
Intravenous Thrombolysis ◽  
Baseline Data ◽  
Tissue Type ◽  
Rapid Mri

Background: rt-PA intravenous thrombolytic therapy and its efficacy have been widely recognized and proved for strokes. However, for patients with wake-up ischemic stroke (WUIS), they lose the opportunity to receive rt-PA intravenous thrombolytic therapy because of the difficulty of determining the onset time window. Aim: This study is aimed at investigating the intravenous thrombolytic therapy of WUIS guided by rapid MRI. Methods: Data were collected from patients with acute ischemic stroke within 4.5 h and from WUIS patients with uncertain onset time window, who received the treatment of rt-PA intravenous thrombolytic therapy in our hospital from November 2006 to April 2018. The improved Rankin scale was used to evaluate neurological function recovery. According to the Rankin scale score, patients were divided into two groups: those with good prognosis (modified Rankin scale [mRS] score 0–1) and those with poor prognosis (mRS score 2–6). Results: A total of 253 patients received rt-PA intravenous thrombolysis after head MRI evaluation; this included 177 cases of acute ischemic stroke and 76 cases of WUIS (which contains 2 death cases, 0.8% mortality; 3 cases of symptomatic bleeding, 1.2% bleeding rate; and 5 cases of aggravation, 2.0% aggravation rate). There was no statistical difference between the baseline data from the acute ischemic stroke patients with 4.5 h onset time window and the baseline data from the WUIS patients with undetermined onset time window, when the treatment was guided by rapid MRI. There were also no significant statistical differences in National Institutes of Health Stroke Scale score, Rankin scale score, symptomatic bleeding, death and aggravation of the disease between the 2 groups at 24 h, 3 days, and 7 days after admission (p < 0.05). Conclusion: According to the characteristic of undetermined onset time window of WUIS, more WUIS patients would be benefited from the rt-PA intravenous thrombolytic treatment when it is conducted under the guidance of rapid MRI.

The Impact of Body Mass Index on the Thrombolytic Treatment of Acute Ischemic Stroke

2016 ◽  
Vol 42 (3-4) ◽  
pp. 240-246 ◽  
Author(s):  
Anastasios Chatzikonstantinou ◽  
Anne D. Ebert ◽  
Marc E. Wolf
Keyword(s):  
Body Mass Index ◽  
Body Weight ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Blood Volume ◽  
Body Mass ◽  
Intravenous Thrombolysis ◽  
Normal Weight ◽  
Thrombolytic Treatment ◽  
Stroke Patients

Background: Body weight and body mass index (BMI) are regularly assessed factors in stroke patients for manifold reasons. However, their potential role specifically in intravenous thrombolysis has not been thoroughly examined. Methods: Data from 865 consecutive acute ischemic stroke patients treated with intravenous thrombolysis were analyzed. Patients were divided into different BMI categories (underweight, normal weight, overweight, obese) and compared based on the following factors: time window of treatment, clinical scores National Institute of Health Stroke Scale Score (NIHSS), modified Rankin scale (mRS) on admission and discharge, risk factors, stroke characteristics and thrombolysis complications. Recombinant tissue plasminogen activator (rtPA) doses relative to body weight and blood volume were also assessed. In a separate analysis, patients weighing up to 100 and >100 kg were compared. Results: Eighteen patients (2.1%) were underweight, 336 (38.8%) overweight, 194 (22.4%) obese and 317 (36.7%) had normal weight. Higher BMI category was associated with younger age, thrombolytic treatment later than 4.5 h, arterial hypertension, diabetes and higher relative rtPA dose relative to blood volume (p < 0.001). There were no significant differences concerning NIHSS and mRS scores or thrombolysis complications. Forty-six patients (5.3%) weighed over 100 kg. They were younger (p = 0.002) and treated later than patients under 100 kg (p < 0.001). Mean rtPA dose relative to body weight and to blood volume was significantly lower (0.7 vs. 0.9 mg/kg, p < 0.001 and 13 vs. 13.9 mg/l, p < 0.001). There was a marginal difference in NIHSS score improvement ≥4 points (26.1 vs. 40.2%, p = 0.038); otherwise, no outcome differences were found. Conclusion: BMI category does not significantly influence clinical outcome after thrombolysis. However, relevant NIHSS improvement was found more often in patients weighing up to 100 kg compared to those over 100 kg. Interestingly, patients with higher BMI or weight >100 kg were thrombolysed later than other patients.

scholarly journals Curitiba acute ischemic stroke protocol: a university hospital and EMS initiative in a large Brazilian city

2011 ◽  
Vol 69 (3) ◽  
pp. 441-445 ◽  
Author(s):  
Marcos Christiano Lange ◽  
Viviane Flumignan Zétola ◽  
Monica F. Parolin ◽  
Laura N. Zamproni ◽  
Artur F. Fernandes ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Thrombolytic Therapy ◽  
Acute Ischemic Stroke ◽  
Hemorrhagic Stroke ◽  
Hospital Staff ◽  
Rapid Identification ◽  
University Hospital ◽  
Correct Identification ◽  
Thrombolytic Treatment ◽  
Health Hospital

Few healthcare centers in Brazil perform thrombolytic therapy for acute ischemic stroke (AIS) patients. OBJECTIVE: The aim of this study was to describe an interinstitutional protocol for the rapid identification and thrombolytic treatment of AIS patients at a public health hospital in a large Brazilian city. METHOD: Emergency medical services (EMS) personnel evaluated 433 patients with possible stroke during a six-month period. After a standard checklist, patients with suspected AIS and symptoms onset of less than two hours were evaluated at our University Hospital (UH). RESULTS: Sixty-five (15%) patients met the checklist criteria and had a symptom onset of less than two hours, but only 50 (11%) patients were evaluated at the UH. Among them, 35 (70%) patients had ischemic stroke, 10 (20%) had hemorrhagic stroke, and 5 (10%) had other diagnoses. Of the 35 ischemic stroke patients, 15 (43%) underwent IV thrombolysis. CONCLUSION: The present study demonstrated that trained EMS workers could help to improve the rate of thrombolytic treatment in large Brazilian cities. Permanent training programs for EMS and hospital staff, with quality control and correct identification of AIS patients, should be implemented to increase appropriate thrombolytic therapy rates in Brazil.

scholarly journals Stroke outcomes in Thai elderly patients treated with and without intravenous thrombolysis

2013 ◽  
Vol 5 (3) ◽  
pp. 15 ◽  
Author(s):  
Pornpatr A. Dharmasaroja ◽  
Sombat Muengtaweepongsa ◽  
Junya Pattaraarchachai ◽  
Permphan Dharmasaroja
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Retrospective Review ◽  
Intravenous Thrombolysis ◽  
Recombinant Tissue Plasminogen Activator ◽  
Controlled Study ◽  
Control Group ◽  
Base Line ◽  
Old Patients ◽  
Stroke Outcomes

Higher mortality was found in very old patients with acute ischemic stroke treated with intravenous recombinant tissue-plasminogen activator (rtPA) as compared to younger patients. The benefit of thrombolytic treatment in this particular subgroup is still a subject of debate. The purpose of this study was to compare stroke outcomes in Thai patients aged over 70 years treated with and without intravenous rtPA. This was a retrospective review of sequential cases and was not a randomized controlled study. One-hundred and five patients with acute ischemic stroke aged over 70 years who were treated with intravenous rtPA and 105 patients without rtPA treatment (control group) were included in the study. Patients’ base-line characteristics and study outcomes of interest were compared. There were significant differences in the base-line characteristics of the two groups. However, for the subgroup of patients aged over 80 years, these characteristics were similar. Those who were treated with intravenous rtPA had a higher rate of favorable outcomes (40% <em>vs</em> 16%; P=0.137) and a lower rate of mortality (22% <em>vs</em> 44%; P=0.128) than patients who did not receive rtPA treatment. In well-matched subgroups of patients aged over 80 years, our retrospective review revealed there was a trend of a higher rate of favorable outcome and lower mortality in patients receiving rtPA treatment. More study is needed to further confirm the suggested benefit of thrombolysis in Asian octogenarian acute stroke patients.

scholarly journals Clinical Outcomes of Thrombolytic Therapy in Patients with Mild Stroke: Single-Center Experience in a Tertiary Care Institution

2021 ◽  
Author(s):  
Hasan Karadeli ◽  
Ruken Simsekoglu
Keyword(s):  
Ischemic Stroke ◽  
Thrombolytic Therapy ◽  
Acute Ischemic Stroke ◽  
Tertiary Care ◽  
Intravenous Thrombolysis ◽  
Recombinant Tissue Plasminogen Activator ◽  
Stroke Patients ◽  
Maximum Delay ◽  
Mild Stroke ◽  
Iv Tpa

Objective: The term ‘mild stroke’ is used to describe stroke patients with a NIHSS score of 0 to 6. There is still no clear decision regarding the application of iv recombinant tissue plasminogen activator (iv-tPA) to patients who is admitted with an acute ischemic stroke and is in the mild stroke category. In our study, we aimed to analyze the data of patients who applied to our stroke center with an acute mild stroke clinic and received iv-tPA treatment and their three-month follow-up. Methods: A total of 47 (age 69.1 ± 14.1, 28 female) mild stroke patients were included out of 350 patients receiving thrombolytic therapy. Intravenous thrombolysis was initiated with a maximum delay of 4.5 hours in all patients. Patients had a NIHS score less than 6. NIHSS scores immediately before starting thrombolytic therapy and scores 24 hours after treatment were recorded. Modified Rankin Scale scores (mRS) at admission, 1 and 3 months were recorded. Results: NIHSS scores of the patients who received tPA decreased significantly after the treatment (p = 0.001). The patients’ 1st and 3rd month mRS scores were statistically significantly decreased according to the mRS scores when they entered the treatment (p = 0.001). Conclusions: This study highlights the efficacy of iv-tPA in acute ischemic stroke patients with mild symptoms and demonstrates the low risk profile of this therapy.

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