A fluctuating intensity of care: A qualitative study on the experiences of informal caregivers of patients with critical limb-threatening ischemia.

Informal caregivers play a significant role in providing care for older, often vulnerable, patients, and supporting them as they live with chronic diseases. Due to the rising prevalence of older vascular patients and their use of healthcare, the role of their informal caregivers will become more important. However, little is known about the experiences of informal caregivers of patients with critical limb-threatening ischemia and the impact of informal care on different aspects of these caregivers' lives. In addition, literature does not describe the burden this role brings with it, or lack thereof. Therefore a qualitative study using a phenomenological approach, specifically interpretive phenomenological analysis, was used to gain insight into the experiences of the primary informal caregivers of patients with chronic limb-threatening ischemia. Data were collected via semi-structured interviews and focus groups discussions. Fifteen primary informal caregivers of patients with critical limb-threatening ischemia under the care of the vascular surgeon at a tertiary teaching hospital in the Netherlands were included. Data analysis yielded three themes: the perceived identity of this group of caregivers; the varying intensity of informal care; and the collaboration between informal carers, their care recipients and the professional care provider within the vascular surgery department. In contrast to carers of other chronic diseases, the shifting intensity of care that informal caregivers of critical limb-threatening ischemia patients experience seems to prevent long-term overload. Adapting to that fluctuating situation requires flexibility from healthcare providers within the vascular surgery department. In addition, professionals need to involve informal caregivers in the patient's decision-making process and recognize their role in that process.

Understanding delays in chronic limb-threatening ischaemia care: Application of the theoretical domains framework to identify factors affecting primary care clinicians' referral behaviours.

INTRODUCTION: Patients in the community with suspected Chronic limb-threatening ischaemia (CLTI) should be urgently referred to vascular services for investigation and management. The Theoretical Domains Framework (TDF) allows identification of influences on health professional behaviour in order to inform future interventions. Here, the TDF is used to explore primary care clinicians' behaviours with regards to recognition and referral of CLTI. METHODS: Semi-structured interviews were conducted with 20 podiatrists, nurses and general practitioners in primary care. Directed content analysis was performed according to the framework method. Utterances were coded to TDF domains, and belief statements were defined by grouping similar utterances. Relevance of domains was confirmed according to belief frequency, presence of conflicting beliefs and the content of the beliefs indicating relevance. RESULTS: Nine TDF domains were identified as relevant to primary care clinicians: Knowledge, Environmental context and resources, Memory, Decision and attention processes, Beliefs about capabilities, Skills, Emotions, Reinforcement and Behavioural regulation. Relationships across domains were identified, including how primary care clinician confidence and working in a highly pressurized environment can affect behaviour. CONCLUSION: We have identified key barriers and enablers to timely recognition and referral behaviour. These beliefs identify targets for theory-driven behaviour change interventions to reduce delays in CLTI pathways.

A Comparison of Quality of Life in Elderly Patients with Intermittent Claudication and Chronic Limb-Threatening Ischemia.

BACKGROUND: Intermittent claudication (IC) and chronic limb-threatening ischemia (CLTI) are both associated with a decreased health status and possibly quality of life (QOL). A better understanding of the differences in QOL between patients with IC and CLTI could be of additional value in shared decision-making. The aim of this study was to compare the QOL at baseline between patients with IC and patients with CLTI. METHODS: The study population was based on 2 study cohorts, 1 cohort consisted of patients with IC (ELECT registry) and the other cohort of patients with CLTI (KOP-study). Patients with an age of ≥70 years were included. QOL at baseline was measured by the WHOQOL-BREF questionnaire. Nonresponders were excluded from data analyses. Student's t-tests and analysis of covariance (ANCOVA) analyses were used to compare QOL between the 2 groups. Outcomes of the ANCOVA analyses were expressed as estimated marginal means. RESULTS: In total, 308 patients were included, 115 patients with IC and 193 patients with CLTI. Patients with CLTI were older (median age 80 years vs. 75 years, P < 0.001) and had more comorbidities. Patients with IC had a statistically significant higher QOL regarding physical health (mean 13.7 [standard deviation (SD) 2.3] vs. 10.8 [SD 2.8], P < 0.001), psychological health (mean 15.3 [SD 2.1] vs. 14.1 [SD 2.4], P < 0.001), environment (mean 16.3 [SD 2.4] vs. 15.5 [SD 2.0], P < 0.002), and the overall domain (mean 3.5 [SD 0.7] vs. 3.1 [SD 0.9], P < 0.001). After correcting for the confounding effect of age and sex, patients with IC still had a statistically significant higher QOL in the physical, psychological, environment, and overall domain. CONCLUSIONS: Patients with IC had a significantly higher QOL in the physical, psychological, environment, and overall domains of the WHOQOL-BREF questionnaire compared with patients with CLTI. This underlines the importance of strategies that reduce disease progression as disease progression is associated with a decrease in QOL.

Descriptive title: The body with chronic limb-threatening ischaemia: A phenomenologically derived understanding.

AIMS AND OBJECTIVES: To explore person and family lifeworld narratives of chronic limb-threatening ischaemia (CLTI) after major amputation has been offered as a treatment option. BACKGROUND: Chronic limb-threatening ischaemia manifests as ischaemic pain, ulceration and/or gangrene and is receiving heightened attention due to the increasing health system burden from associated complex wounds and hospitalisations for repeat procedures. The patient and family impact of these manifestations is not well-reported: current studies largely seek to measure treatment outcomes. Patient-reported outcome measurements need to be developed but should be underpinned by rigorous qualitative research. DESIGN: Prospective, longitudinal, qualitative design using interpretive phenomenology. METHODS: The journeys of 19 people with CLTI were explored via 42 semi-structured interviews with 14 patient and 13 family participants. The initial interview was conducted soon after the advice of the need for major amputation, and where amputation followed, participants were invited for a second interview 6 months postprocedure. Hermeneutic phenomenological analysis was guided by Merleau-Ponty's philosophy of embodiment. RESULTS: People with embodied CTLI faced an existential crisis due to the catastrophic impact of creeping decay of their flesh and vascular system, relentless pain and a sense of spreading poison from gangrene, infection and drugs, which disrupted the interleaving of the physical and existential body. Consequent to the creeping decay and surgery, participants also experienced shifting body boundaries and an unreliable body. CONCLUSIONS: The lifeworld of the patient and family living with CTLI is irrevocably altered through the disruption of a spontaneous and reliable body. This shapes subsequent therapeutic relationships and discourse. RELEVANCE TO CLINICAL PRACTICE: People facing CLTI require early patient- and family-centred discussions about the possibility for major amputation and its potential to arrest the further decline of the body and to support the body's existential expression.

Important differences between quality of life and health status in elderly patients suffering from critical limb ischemia.

INTRODUCTION: Critical limb ischemia (CLI) patients are often of advanced age with reduced health status (HS) and quality of life (QoL) at baseline. Physical health is considered as the most affected domain due to reduced mobility and ischemic pain. QoL and HS are often used interchangeably in the current literature. HS refers to objectively perceived physical, psychological, and social functioning and in assessing QoL, change is measured subjectively and can only be determined by the individual since it concerns patients' evaluation of their functioning. It is important to distinguish between QoL and HS, especially in the concept of shared decision-making when the opinion of the patient is key. Goal of this study was to examine and compare QoL and HS in elderly CLI patients in relation to the used therapy, with a special interest in conservatively treated patients. METHODS: Patients suffering from CLI and ≥70 years old were included in a prospective study with a follow-up period of 1 year. Patients were divided into three groups; endovascular revascularization, surgical revascularization, and conservative therapy. The WHOQoL-Bref was used to determine QoL, and the 12-Item Short Form Health Survey was used to evaluate HS at baseline, 5-7 days, 6 weeks, 6 months, and 1 year. RESULTS: Physical QoL of endovascularly and surgically treated patients showed immediate significant improvement during follow-up in contrast to delayed increased physical HS at 6 weeks and 6 months (P<0.001). Conservatively treated patients showed significantly improved physical QoL at 6 and 12 months (P=0.02) in contrast to no significant improvement in physical HS. CONCLUSION: This study demonstrates that QoL and HS are indeed not identical concepts and that differentiating between these two concepts could influence the choice of treatment in elderly CLI patients. Discriminating between QoL and HS is, therefore, of major importance for clinical practice, especially to achieve shared decision-making.

A Qualitative Study Exploring Patient Concerns and Values in Chronic Limb-Threatening Ischemia.

BACKGROUND: Chronic limb-threatening ischemia (CLTI) is the debilitating end stage of peripheral artery disease, causing patients to experience low quality of life and poor health outcomes. It is unknown which aspects of care patients with CLTI value. This pilot qualitative study aims to explore patients' concerns and values related to CLTI treatment, to better inform patient-centered care. METHODS: A qualitative study design was piloted to explore the experiences of patients with CLTI undergoing elective vascular surgery. In-depth, semistructured interviews were recorded preoperatively and 3 mo after discharge. Transcribed interviews were analyzed using content analysis, to derive patient-centered themes. Findings were mapped to a framework of patient-centered care. RESULTS: Twelve interviews from six participants were analyzed. Five themes related to participant experiences of CLTI were identified: treatment and diagnosis, concerns about symptoms, limitations in physical function, social function, and emotional function. Participants expressed how CLTI intruded on all aspects of their lives. Framework analysis demonstrated CLTI patients valued patient-centered care relating to both relational and functional aspects of care. In particular, participants valued supportive and trustworthy care, in addition to integrated, holistic care that recognized the patient in the context of their overall health and life. CONCLUSIONS: Feasibility was demonstrated for both study design and methodology. Data obtained from interviews were sufficiently "rich and thick" in quality and quantity to allow for common themes related to experience and health care values in patients with CLTI to be identified. If confirmed in future studies, these findings will enhance patient-centered care in CLTI.

Quality of Life and not Health Status Improves After Major Amputation in the Elderly Critical Limb Ischaemia Patient.

OBJECTIVES: A patient-oriented appraisal of treatment has become extremely important, particularly in elderly patients with critical limb ischaemia (CLI). Quality of life (QoL) is an important patient-reported outcome in vascular surgery. Frequently, the physical domain of QoL questionnaires represents an 'objective' evaluation of performing activities, which is expected to be impaired after major limb amputation. However, an objective appraisal of physical function is an assessment of health status (HS) and not of QoL. Little is known about the subjective appraisal of physical health (QoL). The goal of this study was to evaluate, prospectively, QoL in relation to HS in elderly CLI patients undergoing major limb amputation. METHODS: Patients suffering from CLI aged 70 years or older were included in a prospective observational cohort study with a follow-up period of 1 year. Patients were divided according to having had an amputation or not. The World Health Organization Quality Of Life-BREF (WHOQOL-BREF) was used to asses QoL. The 12-Item Short Form Health Survey (SF-12) was used to measure HS. These self-reported questionnaires were completed five times during follow-up. RESULTS: Two-hundred patients were included of whom 46 underwent a major limb amputation within one year. Amputees had a statistically significant improvement of their physical QoL after six months (14.0 vs. 9.0 (95% CI -7.84;-1.45),p = 0.005) and after a one-year follow-up (14.0 vs. 9.0 (95% CI -9.58;-1.46),p = 0.008). They did not however show any statistically significant difference in HS. For non-amputees, both physical QoL and HS improved. An instant statistically significant improvement of the physical QoL appeared 1 week after inclusion (12.0 vs. 10.9 (95% CI -1.57;-0.63),p<0.001). Similarly, statistically significant improvement in the physical HS first occurred at 1 week follow-up (29.0 vs. 28.9 (95% CI -5.78; -2.23),p = 0.003). CONCLUSIONS: There is a clear difference between patients' functioning (HS) and the patients' appraisal of functioning (QoL). In elderly CLI patients, this study clearly suggests a discrepancy between the physical QoL (WHOQOL-BREF) and HS (SF-12) measurements in vascular amputees. This raises the question, which outcome measurement is the most relevant for elderly CLI patients. Individual treatment goals should be kept in mind when assessing the HS or QoL outcome of patients undergoing hospital care. With respect to shared decision making, distinctive and subjective QoL questionnaires, like the WHOQOL-BREF, provide a very important outcome measurement and should be used in future research.

Investigation of the effect of the virtual reality application on experimental pain severity in healthy

SUMMARY OBJECTIVE: This study aimed to investigate the effect of virtual reality application on experimental ischemic pain created with a blood pressure instrument in healthy volunteers. METHODS: The research sample consisted of 172 volunteer adult students who conformed to the inclusion criteria. These individuals were assigned into an experimental (n=86) and a control group (n=86) by a simple randomization method. All individuals in the experimental and control groups wereexperimentally subjected to pain for two minutes by applying 260 mmHg of pressure 3-4 cm above the antecubital region of the left arm with an aneroid adult-type blood pressure instrument. During the procedure, the volunteers in the experimental group watched virtual reality images, while those in the control group received no intervention. Immediately after the procedure, the pain levels of the individuals in both groups were assessed with a Visual Analog Scale (VAS). RESULTS: We found that the mean pain score of the individuals in the experimental group was 2.62±1.82, and that of individuals in the control group was 5.75±1.65. Results of the statistical analysis showed a statistically significant difference between the mean pain scores of the individuals in the experimental and control groups (p<0.001). CONCLUSION: This study found that the use of virtual reality was effective in reducing the level of pain in healthy individuals. This method used a smartphone with widespread availability and ease of transportation, which can be used by health professionals as a non-pharmacological method in the management of pain.

RESUMO OBJETIVO: El objetivo de este estudio fue investigar el efecto de la aplicación de realidad virtual en el dolor isquémico experimental creado con un instrumento de presión arterial en voluntarios sanos. MÉTODO: La muestra de investigación consistió en 172 estudiantes adultos voluntarios que cumplieron con los criterios de inclusión. A estos individuos se les asignó mediante un método de aleatorización simple en un grupo experimental (n = 86) y uno de control (n = 86). Todos los individuos en los grupos experimentales y de control fueron sometidos experimentalmente a dolor durante dos minutos aplicando 260 mmHg de presión 3-4 cm por encima de la región antecubital del brazo izquierdo con un instrumento de presión arterial aneroide tipo adulto. Durante el procedimiento, los voluntarios en el grupo experimental observaron imágenes de realidad virtual, mientras que los del grupo de control no recibieron ninguna intervención. Inmediatamente después del procedimiento, los niveles de dolor de los individuos en ambos grupos se evaluaron con una Escala Analógica Visual (EAV). RESULTADOS: Se encontró que el puntaje promedio de dolor de los individuos en el grupo experimental fue 2.62 ± 1.82, y el de los individuos en el grupo control fue de 5.75 ± 1.65. Los resultados del análisis estadístico mostraron una diferencia estadísticamente significativa entre las puntuaciones medias de dolor de los individuos en los grupos experimental y control (p<0,000). CONCLUSÃO: Se encontró en este estudio que el uso de la realidad virtual fue efectivo para reducir el nivel de dolor en individuos sanos. Este método, que se lleva a cabo mediante el uso del teléfono inteligente y que ofrece una amplia disponibilidad y facilidad de transporte, puede ser utilizado por profesionales de la salud como un método no farmacológico en el tratamiento del dolor.

Is There an Important Role for Anxiety and Depression in the Elderly Patients with Critical Limb Ischemia, Especially After Major Amputation?

BACKGROUND: In patients with critical limb ischemia, an association is assumed between depression and worse outcome for morbidity, such as major limb amputation. After major amputation, anxiety and depression are common. We aimed to determine the association of depressive and anxiety symptoms in the elderly with critical limb ischemia, especially after major limb amputation. METHODS: Patients with critical limb ischemia aged ≥70 years were included in this prospective observational cohort study between January 2012 and February 2016 in 2 Dutch hospitals. After a multidisciplinary vascular conference, patients were divided into 4 treatment groups: endovascular revascularization, surgical revascularization, conservative therapy, and primary major amputation. In a 1-year follow-up period, depression and anxiety were measured 4 times using the Dutch versions of the Center for Epidemiological Studies Depression Scale and the State-Trait Anxiety Inventory. RESULTS: One Hundred eighty-seven patients were included. Within 1 year, 44 patients underwent a major limb amputation. Lower amputation-free survival did not differ significantly for patients with versus without greater anxiety (X2 [1] = 0.689, P = 0.407) and also not for patients with versus without more depressive symptoms (X2 [1] = 0.614, P = 0.433). For both groups, there were no significant changes in anxiety scores over time. After a median follow-up time of 336.5 days and 365 days, depressive symptoms significantly decreased in amputees, respectively, 8.5 vs. 4.5 (95% CI 1.76-7.48, P = 0.002) and 8.5 vs. 4.3 (95% CI 0.61-9.82, P = 0.027) when compared to the baseline measurement. Similarly, nonamputees had significantly lower overall score for depressive symptoms after a median follow-up time of 365 days (10.1 vs. 4.1, 95% CI 4.49 to 6.90, P < 0.001). CONCLUSIONS: In the opinion of the medical health care provider, amputation is a severe and unwanted end phase of critical limb ischemia. However, depressive symptoms seem to decrease over time and anxiety symptoms do not seem to be affected in patients after major limb amputation. In addition, patients with greater trait anxiety or more depressive symptoms at baseline did not have significantly higher amputation rates. These findings are similar to the course of depressive and anxiety symptoms for the elderly patients without major limb amputation.

Quality of Life and Mortality after Endovascular, Surgical, or Conservative Treatment of Elderly Patients Suffering from Critical Limb Ischemia.

BACKGROUND: Revascularization to relieve ischemic pain and prevent limb loss is the cornerstone of critical limb ischemia (CLI) treatment; however, not all elderly patients are deemed fit for revascularization. Patient-related outcome measurements are important in these patients. Quality of life (QoL) results regarding the effect of endovascular, surgical, and conservative treatment on the QoL in the elderly are scarce in the current literature. The goal of this study was to explore the outcomes of the different treatment modalities in elderly patients suffering from CLI, with a specific focus on QoL. METHODS: A total of 195 CLI patients ≥70 years were prospectively included between January 2012 and February 2016 and divided into 6 groups (endovascular revascularization, surgical revascularization, and conservative treatment). Two age groups (70-79 and >80 years) were analyzed. Follow-up was performed at 5-7 days, 6 weeks, and 6 months. World Health Organization Quality of Life-BREF questionnaire was used to determine QoL. The Vascular-Physiological and Operative Severity Score for Enumeration of Mortality and Morbidity score was noted. QoL was used as the primary end point, with mortality and limb salvage as the secondary end points. RESULTS: Six-month mortality was significantly lower in surgically treated patients aged 70-79 years (4%) as compared with endovascular (24%, P = 0.001) or conservative treatment (25%, P = 0.02). There was no significant difference in 6-month mortality in patients >80 years among endovascularly (38%), surgically (15%), and conservatively treated patients (27%). QoL significantly increased at all follow-up moments in surgically treated patients between 70 and 79 years and at 6 months in endovascularly treated patients. Conservatively treated patients did not improve their QoL in this age group. All patients aged >80 years, including conservatively treated patients, showed significantly improved QoL results at 6 months. CONCLUSIONS: Elderly patients judged fit for surgery may benefit the most from surgical revascularization, reporting low mortality rates, low adverse events and significantly gained QoL in multiple domains. However, all 3 treatment modalities have significantly increased physical health at 6 months. Conservative therapy seems to be an acceptable treatment option in patients unfit for revascularization with gained physical health at 6 months.

Assessment of Minimum Important Difference and Substantial Clinical Benefit with the Vascular Quality of Life Questionnaire-6 when Evaluating Revascularisation Procedures in Peripheral Arterial Disease.

OBJECTIVES: Patient reported outcomes are increasingly used to assess outcomes after peripheral arterial disease (PAD) interventions. VascuQoL-6 (VQ-6) is a PAD specific health-related quality of life (HRQoL) instrument for routine clinical practice and clinical research. This study assessed the minimum important difference for the VQ-6 and determined thresholds for the minimum important difference and substantial clinical benefit following PAD revascularisation. MATERIALS AND METHODS: This was a population-based observational cohort study. VQ-6 data from the Swedvasc Registry (January 2014 to September 2016) was analysed for revascularised PAD patients. The minimum important difference was determined using a combination of a distribution based and an anchor-based method, while receiver operating characteristic curve analysis (ROC) was used to determine optimal thresholds for a substantial clinical benefit following revascularisation. RESULTS: A total of 3194 revascularised PAD patients with complete VQ-6 baseline recordings (intermittent claudication (IC) n = 1622 and critical limb ischaemia (CLI) n = 1572) were studied, of which 2996 had complete VQ-6 recordings 30 days and 1092 a year after the vascular intervention. The minimum important difference 1 year after revascularisation for IC patients ranged from 1.7 to 2.2 scale steps, depending on the method of analysis. Among CLI patients, the minimum important difference after 1 year was 1.9 scale steps. ROC analyses demonstrated that the VQ-6 discriminative properties for a substantial clinical benefit was excellent for IC patients (area under curve (AUC) 0.87, sensitivity 0.81, specificity 0.76) and acceptable in CLI (AUC 0.736, sensitivity 0.63, specificity 0.72). An optimal VQ-6 threshold for a substantial clinical benefit was determined at 3.5 scale steps among IC patients and 4.5 in CLI patients. CONCLUSIONS: The suggested thresholds for minimum important difference and substantial clinical benefit could be used when evaluating VQ-6 outcomes following different interventions in PAD and in the design of clinical trials.

Lifelong limb preservation: A patient-centered description of lower extremity arterial reconstruction outcomes.

BACKGROUND: Life expectancy is short for patients with critical limb ischemia (CLI), many of whom may fear amputation more than death. In light of the reduced life expectancy of these patients, the traditional 5-year freedom from amputation (FFA) statistic may not accurately address their concern. We developed a more relevant patient-centered calculation of major amputation risk during a patient's remaining lifetime to better answer the question, Will I ever lose my leg? METHODS: We identified all limbs undergoing first-time intervention for CLI in a large institutional database from 2005 to 2013. We calculated the traditional metrics of amputation-free survival (AFS, for which failure is death or amputation) and FFA (for which failure is amputation but deaths are censored and removed from further analysis). In addition, we propose a new term, lifelong limb preservation (LLP). LLP defines amputation as failure, but deaths are not censored and therefore reflect that LLP has been achieved. All deaths before 30 days were considered a failure in all three metrics, reflecting the risk of surgery. RESULTS: There were 1006 limbs identified as having first-time intervention for CLI (22% rest pain, 45% ulcer, 27% gangrene; 46% treated by angioplasty with or without stenting, 54% bypass). Using life-table analysis, 7-year AFS was 14% (561 events), FFA was 78% (123 events), and LLP was 86% (123 events). LLP was similar between patients undergoing angioplasty with or without stenting and bypass (7-year rates, 86% and 85%, respectively). For patients undergoing intervention for rest pain, 7-year rates were 14% for AFS, 84% for FFA, and 92% for LLP. For those undergoing treatment for ulcer, 7-year rates were 14% for AFS, 77% for FFA, and 86% for LLP. Finally, in those with gangrene, rates were 10% for AFS, 67% for FFA, and 79% for LLP. Using LLP, patients presenting with an ulcer can be told that although we cannot guarantee how long they will live, with revascularization there is approximately an 86% chance they will not lose the leg. CONCLUSIONS: These results show that the durability of our limb preservation efforts often exceeds the life expectancy of our patients. Using LLP as an outcomes assessment provides a more accurate and patient-centered answer to the question, If I have this procedure, will I ever lose my leg?

Cumulative Number of Treatment Interventions Predicts Health-Related Quality of Life in Patients with Critical Limb Ischemia.

BACKGROUND: Health-related quality of life (QOL) is usually assessed after a defined interval following a single intervention, but critical limb ischemia (CLI) is a chronic condition where multiple interventions are often required over a patient's lifetime. We hypothesized that the impact of CLI treatment interventions on QOL is diminished in the setting of multiple previous interventions. To test this hypothesis, we performed a cross-sectional study evaluating associations between cumulative number of previous peripheral artery disease (PAD) treatment interventions and QOL adjusting for both comorbidity and disease severity. METHODS: Participants with CLI (abnormal ankle brachial index [ABI] plus rest pain and/or tissue loss) were enrolled in a cross-sectional study and completed a disease-specific QOL assessment, (the Vascular Quality of Life Questionnaire-6 [VascuQol-6]). Minimum ABI was used to assess disease severity, and comorbidity was evaluated based on Charlson Comorbidity Index. Cumulative number of PAD treatment interventions was defined based on the lifelong total for both legs. QOL associations were evaluated using a multivariable linear regression model adjusted for age and gender. RESULTS: Thirty-two patients with CLI participated. Mean age was 63 ± 10 years, 72% were men, and 63% were white; mean ABI was 0.6 ± 0.2. Mean VQ-6 score was 11.6 ± 4.2, and QOL was lower in patients with more previous interventions. Multivariable models demonstrated that an increasing number of previous treatment interventions negatively impacted QOL (P = 0.047), whereas positive associations were identified for female gender (P = 0.006) and ABI (P = 0.006). No association between comorbidity and QOL was identified. CONCLUSIONS: Vascular-specific factors appear to be key determinants of QOL among patients with CLI, whereas comorbidity appears less important. Strategies focused on definitive and durable revascularization may reduce cumulative interventions and potentially maximize QOL for patients with CLI.

Clinimetric Evaluation of the Vascular Quality of Life Questionnaire in Patients with Lower Limb Ischaemia.

OBJECTIVES: Although commonly used to measure health related quality of life in patients with lower limb ischaemia, the measurement properties of the VascuQol and its assumed underlying health dimensions have not been studied in depth. The objective of this study was therefore to evaluate aspects of reliability and validity of the Dutch version of the VascuQol in patients with intermittent claudication (IC) and critical limb ischaemia (CLI). METHODS: Two datasets containing 195 patients with IC and 150 patients with CLI were used. Face validity of the VascuQol was examined in interviews with patients and a survey among health professionals. Homogeneity and structural validity of the VascuQol were assessed using Cronbach's α coefficients and explanatory factor analysis. Furthermore, convergent validity and known group validity were assessed. RESULTS: During the face validity interviews, three items were indicated as less relevant. Homogeneity analysis showed that the α coefficient of the VascuQol was .93, while the symptoms and social domains had α coefficients below the threshold of .70. The original five domains of the VascuQol could not be reproduced. Instead, factor analysis yielded a three factor solution. Moderate correlations were found for the activities, social and emotional VascuQol domains and matching health domains of other patient reported outcome measures (PROMs). Lower convergent correlations were observed for the pain domain and the sumscore of the VascuQol. The VascuQol was able to distinguish between patients' level of HRQL in relation to their disease severity (IC versus CLI patients). CONCLUSIONS: There is room for improvement of the VascuQol questionnaire. Further clinimetric studies should be performed to strengthen clinically relevant findings based on this instrument.

Cu, Zn-Superoxide Dismutase Increases the Therapeutic Potential of Adipose-derived Mesenchymal Stem Cells by Maintaining Antioxidant Enzyme Levels.

In the present study, we investigated the ability of Cu, Zn-superoxide dismutase (SOD1) to improve the therapeutic potential of adipose tissue-derived mesenchymal stem cells (Ad-MSCs) against ischemic damage in the spinal cord. Animals were divided into four groups: the control group, vehicle (PEP-1 peptide and artificial cerebrospinal fluid)-treated group, Ad-MSC alone group, and Ad-MSC-treated group with PEP-1-SOD1. The abdominal aorta of the rabbit was occluded for 30 min in the subrenal region to induce ischemic damage, and immediately after reperfusion, artificial cerebrospinal fluid or Ad-MSCs (2 × 105) were administered intrathecally. In addition, PEP-1 or 0.5 mg/kg PEP-1-SOD1 was administered intraperitoneally to the Ad-MSC-treated rabbits. Motor behaviors and NeuN-immunoreactive neurons were significantly decreased in the vehicle-treated group after ischemia/reperfusion. Administration of Ad-MSCs significantly ameliorated the changes in motor behavior and NeuN-immunoreactive neuronal survival. In addition, the combination of PEP-1-SOD1 and Ad-MSCs further increased the ameliorative effects of Ad-MSCs in the spinal cord after ischemia. Furthermore, the administration of Ad-MSCs with PEP-1-SOD1 decreased lipid peroxidation and maintained levels of antioxidants such as SOD1 and glutathione peroxidase compared to the Ad-MSC alone group. These results suggest that combination therapy using Ad-MSCs and PEP-1-SOD1 strongly protects neurons from ischemic damage by modulating the balance of lipid peroxidation and antioxidants.

Quality of Life in Patients Suffering from Critical Limb Ischemia.

BACKGROUND: Various treatment options exist for patients suffering from critical limb ischemia (CLI). These options consist of endovascular procedures, surgical revascularization, primary amputation, or conservative therapy. The effect of the treatment is traditionally focused on outcomes, such as primary patency and limb salvage, though quality of life (QoL) is considered an important additional primary end point in a more patient-oriented healthcare system. The aim of this systematic review is to explore the best clinical decision making possible, to increase QoL in CLI patients. METHODS: This review is based on a systematic electronic literature search using the PubMed and EMBASE databases. Articles evaluating QoL in patients with CLI were selected for further analysis. Only prospective studies, written in English, describing QoL and health status (HS) after endovascular or surgical revascularization, amputation or conservative therapy were considered for inclusion. Treatment results were divided into short-term (≤3-month follow-up) and long-term results (≥1-year follow-up) to achieve a clear view of the QoL in patients suffering for CLI patients. RESULTS: Twenty-five articles describing HS in patients suffering from CLI were included. It was found that while most of these articles reported HS of patients, rarely did they report on QoL. As a result, it is difficult to determine the best treatment to increase HS as studies that focus on the comparison of treatment modalities are lacking. All 4 treatment modalities can raise HS in the short and the long terms; however, endovascular and surgical revascularization seem to positively effect HS the most. QoL results are lacking in both the short and long terms. CONCLUSIONS: All treatment methods included in the study resulted in an increase in patients' HS in both short and long terms. More comparative studies with inclusion of all different treatments of CLI are needed to assist in clinical decision making and perform tailored interventions for the individual patient. QoL and HS are confusingly used in current international literature with abundant HS research. To take patients individual opinions more into account, focus on QoL research is needed to designate the superior treatment in patients suffering from CLI.

Quality of Life After Treatment with Autologous Bone Marrow Derived Cells in No Option Severe Limb Ischemia.

OBJECTIVE: Quality of life (QoL) is an important outcome in evaluating treatment effect in severe limb ischemia. The randomized, double blind, placebo controlled JUVENTAS trial, investigating the effect of bone marrow derived mononuclear cell (BMMNC) administration in no option severe limb ischemia, showed an improved QoL at 6 months compared with baseline in both the treatment and placebo groups. The aim of the present study was to evaluate whether the improved QoL persisted beyond 6 months' follow up, whether this differed in both trial arms, and if major amputation influenced QoL. METHODS: Short form 36 (SF-36) and EuroQol 5D (EQ5D), including the EQ Visual Analogue Scale (EQ-VAS), questionnaires were sent to JUVENTAS trial participants. In the JUVENTAS trial, a norm based scoring method was applied to report the results of the SF-36. The results of the long-term follow up were compared with baseline and 6 month follow up and the results of both trial arms were compared, as were the results of patients with and without amputation. RESULTS: One hundred and nine patients (86.5% of surviving patients) responded to the questionnaires. Median follow up after inclusion was 33 months (interquartile range [IQR] 21.2-50.6) for the BMMNC and 36 months (IQR 21.4-50.9) for the placebo group. The improvement in QoL at 6 months persisted in both arms at a median follow up of 35 months. The long-term QoL did not differ between the BMMNC and placebo group in any of the SF-36 or EQ5D domains. Patients with and without a major amputation had similar QoL scores. CONCLUSIONS: The increased QoL in patients with no option severe limb ischemia persisted until 3 years after inclusion, but did not differ between the BMMNC and placebo arms or between patients with and without a major amputation.

Psychological stress impairs ischemia-induced neovascularization: Protective effect of fluoxetine.

BACKGROUND: Psychological stress (PS) has been associated with the development of cardiovascular diseases and adverse long-term outcomes after ischemic events. However, the precise mechanisms involved are not completely understood. Here we investigated the effect of PS on ischemia-induced neovascularization, and the potential therapeutic effect of fluoxetine in this condition. METHODS AND RESULTS: Balb/c mice were subjected or not to chronic restraint stress. After 3 weeks, hindlimb ischemia was surgically induced by femoral artery removal. We found that blood flow recovery was significantly impaired in mice exposed to PS compared to controls (Doppler flow ratio (DFR) 0.61 ± 0.07 vs. 0.80 ± 0.07, p < 0.05). At the microvascular level, capillary density was significantly reduced in ischemic muscles of mice exposed to PS (38 ± 1 vs. 74 ± 3 capillaries per field, p < 0.001). This correlated with increased oxidative stress levels and reduced expression of VEGF and VEGF signalling molecules (p44/p42 MAPK, Akt) in ischemic muscles. We found that the number of pro-angiogenic cells (PACs) was significantly reduced in mice exposed to PS. In addition, oxidative stress levels (DCF-DA, DHE) were increased in PACs isolated from mice exposed to PS, and this was associated with impaired PAC functional activities (migration, adhesion, and integration into tubules). Importantly, treatment of mice exposed to PS with the selective serotonin reuptake inhibitor (SSRI) fluoxetine improved all the angiogenic parameters, and completely rescued PS-induced impairment of neovascularization. CONCLUSION: PS impairs ischemia-induced neovascularization. Potential mechanisms involved include reduced activation of the VEGF pathway in ischemic tissues, increased oxidative stress levels and reduced number and functional activities of PACs. Our results suggest that fluoxetine may represent a novel therapeutic strategy to improve neovascularization and reduce ischemia in patients suffering from cardiovascular diseases and exposed to PS.

Domains that Determine Quality of Life in Vascular Amputees.

BACKGROUND: Although patients with critical limb ischemia (CLI) commonly undergo major limb amputation, the quality of life (QOL) of this group remains poorly described. Therefore, we sought to describe which domains vascular amputees consider important in determining their health-related QOL. METHODS: We performed 4 focus groups in patients who had major lower extremity amputations resulting from CLI. They were conducted at 4 distinct centers across the United States to ensure broad geographic, socioeconomic, and ethnic representation. RESULTS: Of 26 patients (mean age, 64 years), 19 (73%) were Caucasian, 6 (23%) were African American, and 1 (4%) was Native American. Nearly, three-quarter of patients were men (n = 19, 73%) and had a high-school education or more (n = 19, 73%). Overall, 8 (31%) were double amputees and 17 (65%) had diabetes. Time since amputation varied across patients and ranged from 3 months to more than 27 years (mean, 4.3 years). Patients stated that their current QOL was determined by impaired mobility (65%), pain (60%), progression of disease in the remaining limb (55%), and depression/frustration (54%). Across 26 patients, more than half (n = 16, 62%) described multiple prior revascularization procedures. Although most felt that their physician did his/her best to salvage the affected leg (85%), a sizable minority would have preferred an amputation earlier in their CLI treatment course (27%). Furthermore, when asked how their care might have been improved, patients reported that facilitating peer support (88%), more extensive rehabilitation and prosthetist involvement (71%), earlier mention of amputation as a possible outcome (54%), and the early discontinuation of narcotics (54%) were potential areas of improvement. CONCLUSIONS: Although QOL in vascular amputees seems primarily determined by mobility impairment, pain, and emotional perturbation, our focus groups identified that physician-controlled factors such as the timing of amputation, informed decision making, and postamputation support may also play an important role. The assessment of patient preferences regarding maintenance of mobility at the cost of increased pain versus relief of pain with amputation at a cost of diminished mobility is central to shared decision making in CLI treatment.

Effect of suprarenal aortic cross-clamping.

BACKGROUND: Renal insufficiency is the most frequent complication of surgeries that involve suprarenal aortic cross-clamping. Although some studies have assessed the risk of intraoperative renal ischemia by comparing juxtarenal abdominal aortic aneurysms (AAAs) and infrarenal AAAs, a critical limitation is the difference in these patients' clinical backgrounds and aneurysmal features. The present study evaluated the effect of suprarenal aortic clamping by comparing a juxtarenal AAA group with a subgroup of infrarenal AAAs (ie, short and/or large neck). METHODS AND RESULTS: Among patients who underwent open surgery for AAA, the 2 types of AAA were selected and compared: juxtarenal AAA (JR group: n=35) and infrarenal AAA with short (<15 mm) and/or large (>28 mm) aneurysmal neck that only required infrarenal aortic clamping (SL group: n=26). Postoperative renal function was evaluated using the RIFLE classification. There were no significant differences between groups in baseline characteristics, comorbidities, and intraoperative variables. There were no adverse events leading directly to in-hospital mortality in either group. The rate of postoperative renal insufficiency (estimated glomerular filtration rate decrease ≥-25%) was not significantly different between groups. CONCLUSIONS: The outcomes of the 2 groups were similar, indicating that intraoperative renal ischemia with no specific intraoperative protection would not adversely affect postoperative outcomes.