Lower-limb venous symptoms and assessment of quality of life: existing tools






Fabrizio MARIANI, MD
Department of Vascular Surgery
Valdisieve Hospital
Pontassieve, Florence
ITALY

Lower-limb venous symptoms and assessment of quality of life: existing tools


by F. Mariani, Italy



Chronic venous disease (CVD) may affect several aspects of quality of life (QoL). These functional effects are usually operationalized as (limitations in) physical, psychological, and social functioning. CVD can negatively affect patients’ QoL, as it is a painful and disabling disease that can restrict physical functioning and mobility, and that is associated with depression and social isolation. Instruments used to measure QoL can be classified into generic instruments and disease-specific instruments. A number of good evaluative instruments exist that can monitor changes in patients’ status over time and are responsive to disease progression or therapeutic intervention. Each instrument should be carefully studied to ensure that it is valid (capable of quantifying what it is intended to measure), reliable (produces consistent results when used repeatedly on stable subjects), and responsive (capable of detecting clinically important changes). Objective outcome measures and guidelines for the management of patients with venous disease are more important now than ever and will assume even greater importance in the future. Management of patients with CVD is rapidly evolving, and to assess whether a particular treatment is appropriate, reliable, standardized, and objective, evaluation instruments are required. It would be helpful to promote and validate new specific assessment tools about the medical procedures and QoL in venous leg ulcers, in postthrombotic syndrome and in CVD. Specific tools capable of assessing the full spectrum of CVD, its signs and symptoms, impact on QoL, and treatment effects are key to the efficient management of the disease. Secondly, there should be a focus on longitudinal research about the long-term effect of CVD on QoL and on the effect of CVD on the well-being of the partners of the affected individual. In future, it will be necessary to promote an international consensus to approve the same instruments for all clinical studies on CVD/QoL.

Medicographia. 2015;37:37-44 (see French abstract on page 44)



Quality of life (QoL) can be defined as “the functional effect of an illness and its consequent therapy upon a patient, as perceived by the patient.”1 Chronic venous disease (CVD) may affect several aspects of QoL.

These functional effects are usually operationalized as (limitations in) physical, psychological, and social functioning. CVD can negatively affect patients’ QoL, as it is a painful and disabling disease that can restrict physical functioning and mobility, and that is associated with depression and social isolation.2

In consequence, CVD can result in limitation to daily activities, decreased productivity at work, and patients needing to take sick leave, as well as having a negative effect on their self-esteem. The higher the clinical, etiological, anatomical, pathophysiological (CEAP) clinical class, the poorer the diseasespecific QoL, as demonstrated by low scores for physical and social functioning in QoL questionnaires.2 QoL is increasingly seen as an important outcome measure because of the publication of several clinical trials showing that it is responsive to important clinical changes.3

In addition to relieving clinical symptoms and prolonging survival, the primary objective of any health care intervention should be the enhancement of the QoL of the patient.4 Instruments used to measure QoL can be classified into generic instruments and disease-specific instruments.5 Generic instruments allow comparison across populations of patients with different diseases, whereas disease-specific instruments are sensitive to key dimensions of QoL that are impaired by specific diseases. A number of good evaluative instruments exist that can monitor changes in patients’ status over time and are responsive to disease progression or therapeutic intervention. Each instrument should be carefully studied to ensure that it is valid (capable of quantifying what it is intended to measure), reliable (produces consistent results when used repeatedly on stable subjects), and responsive (capable of detecting clinically important changes).6

Objective outcome measures and guidelines for the management of patients with venous disease are more important now than ever and will assume even greater importance in the future. Management of patients with CVD is rapidly evolving and to assess whether a particular treatment is appropriate, reliable, standardized, and objective, evaluation instruments are required. Patients should be objectively classified according to the CEAP classification and a validated QoL instrument combining generic and disease-specific instruments.2 Following treatment at appropriate time intervals, evaluative and QoL measures should be repeated.





Table I
Table I. Main features of an assessment tool instrument.

Review of available instruments

An instrument is reliable when it consistently produces the same results when applied to the same subjects with no evidence of change (Table I).7 One way to assess reliability is to determine the internal consistency reliability coefficient, which reflects the degree of relatedness between the individual items that make up a scale.78 Validity of a QoL measure is usually determined by examining correlations between conceptually-related measures and by studying associations between the measure and various clinical characteristics.7 The tools can be summarized as9:
– clinical, CVD-related signs—assessed by the physicians (CEAP and VSS [Venous Severity Scoring]);
– functional (measuring QoL) or CVD-related symptoms— the symptoms are self-assessed, using patient-related outcome or patient-reported outcome tools.

The VEIN-TERM10 consensus document has clarified venous terminology; venous symptoms may include tingling, aching, burning, pain, muscle cramps, swelling, sensations of throbbing or heaviness, itching skin, restless legs, and leg tiredness, and/or fatigue. Although not pathognomonic, these may be suggestive of CVD, particularly if they are exacerbated by heat or worsen during the course of the day, and are relieved by leg rest and/or elevation.

♦ Clinical investigations
There are three main clinical investigation methods: CEAP, VSS, and Villalta Scale, specific for postthrombotic syndrome (PTS). The CEAP classification was first developed in 1995.11 The original classification was modified in 2004,12 since at the time it was not adequately dynamic nor did it adequately correlate with symptoms. The modified version continued to be physician-centered and hence did not always correlate with patient symptoms. Furthermore, the symptoms related to lymphatic failure in CVD are not considered in the classification. This is a pitfall in all the cases in which the patients have edema of the lower limb. The CEAP classification is descriptive, but many of its components are static and do not change in response to treatment. A disease severity scoring scheme needs to be quantifiable, with gradable elements that can change in response to treatment. The American Venous Forum developed the VSS,13 which was designed to supplement CEAP scoring and to provide a method for serial assessment. VSS is mainly used for longitudinal follow-up of a patient’s condition during and following treatment, it has recently undergone a revision to increase its sensitivity and value.14

The VSS scoring system has three components:
– Venous DisabilityScore (VDS)—this component evaluates the level of work-based disability, disability is scored from 0 to 3;
– Venous Segmental Disease Score (VSDS)—this is based on anatomical and pathophysiological components of CEAP, obstruction, and reflux;
– Venous Clinical Severity Score (VCSS)—this is a dynamic form of CEAP evaluation that has been designed to include ten hallmarks of the most severe complications of CVD, each hallmark is scored on a severity scale ranging from 0 to 3; VCSS is an easy-to-apply, stand-alone scoring system.

A number of clinical tools or scales have been used in clinical investigations to measure the PTS. The International Society on Thrombosis and Haemostasis recommended that the Villalta Scale be adopted in clinical studies to diagnose and grade the severity of PTS.15 The Villalta Scale is a reliable and valid clinical scoring system that is based on severity ratings of PTS symptoms and signs.

♦ Functional investigation
These are generic and disease-specific assessments of QoL. The generic assessments are Short Form 36 (SF-36; 36-item health survey),16 SF-12 (12-item health survey), and EuroQol 5 Dimension (EQ-5D; mobility, self-care, usual activities, pain/ discomfort, anxiety/depression health survey).17 The diseasespecific assessments include the Aberdeen Varicose Vein Questionnaire (AVVQ),18 Specific Quality of life and Outcomes Response-Venous (SQOR-V), ChronIc Venous Insufficiency quality of life Questionnaire (CIVIQ),19 and VEnous INsufficiency Epidemiological and economic Study (VEINES).20 Since the latter ones are more specific in their scope, they have become more popular in evaluating CVD management.

Generic instruments
◊ SF-36
The SF-36 is a valid assessment of QoL. The scoring system is based on two types of health aspects: physical health and mental health. The former is assessed via the patient’s level of functioning, whilst the latter is assessed via an indicator of well-being. These two types include eight domains: assessment of physical and social functioning, role limitations due to physical and emotional problems, mental health, pain, vitality, and health perception. The survey generates a score ranging from 0 to 100, with higher scores indicating better general health perception. The SF-36 is a good way of assessing changes in QoL in CVD.

◊ Nottingham Health Profile
The Nottingham Health Profile (NHP)21 is intended for primary health care to provide a brief indication of a patient’s perceived emotional, social, and physical health problems. It consists of two parts. Part I contains 38 yes/no items in six domains: pain, physical mobility, emotional reaction, energy, social isolation, and sleep. Part II contains seven general yes/no questions concerning problems of daily living.

Disease-specific instruments
◊ CIVIQ
The CIVIQ was developed and validated (relevance, acceptability, reliability, construct validity, and sensitivity) by a French group in 1996.19 The CIVIQ is a 20-item self-reported instrument that includes four categories of questions: physical (4 items), psychological (9 items), social (4 items), and pain (3 items). Its score ranges from 0, the worst score, to 100, the best. There are five possible answers (from 1 to 5) to describe each symptom and the sensation of discomfort.

In a great number of patients the CIVIQ showed good internal consistency, reliability (above 0.80), and discriminating power of items. Factor analysis identified physical, psychological, and pain factors as important, but revealed instability of the social factor. The CIVIQ was highly sensitive to changes in the QoL of patients clinically improved after drug treatment.22

The first version of the CIVIQ questionnaire, CIVIQ 1 (where 1 denotes the first draft) included different numbers of questions in each category. The second version, the CIVIQ 2 (where 2 denotes the second draft of the same questionnaire), provides a global score covering all aspects of the questionnaire and weighs the categories equally. Recently, a new short form of the CIVIQ with a stable factorial structure was validated; the CIVIQ-14 (14-item QoL questionnaire).23,24

The RELIEF (Reflux assEssment and quaLity of lIfe improvEment with micronized Flavonoids) study,25 which was conducted in 23 countries worldwide and included the participation of more than 10 000 patients suffering from CVD, validated the CIVIQ, the first QoL scale specific to CVD, and assessed changes in the QoL of patients suffering from CVD, with or without venous reflux, treated with micronized flavonoids (MF).

The DECIDE study26 evaluated the predictive value of a symptom checklist for CVD in patients seen by general practitioners. The secondary objectives were to assess the relationship between the checklist data and the patient’s QoL evaluated using the CIVIQ, and to monitor the medium-term evolution of this relationship amongst patients prescribed a venoactive drug. A total of 13 131 patients were included, whose acceptance of the symptom checklist was good, since the completion rate was high. The correlation between a positive diagnosis of CVD and positive answer to the symptom checklist was 98.9% (95% confidence interval [CI], 98.3% to 99.3%), indicating that the symptom checklist is of predictive value for CVD. The CIVIQ-20 was of discriminatory value since there was a 12-point difference between patients with and without CVD (64.4±17.9 vs 76.2±16.4, respectively; P<0.001). Of 9953 patients followed up for an average of 63 days, 88.7% received MF 500 mg, 5.1% received another venoactive drug, and 3.5% were left untreated. After the 63-day follow-up, a significant decrease in CVD symptoms was observed in all patients treated with MF 500 mg. Amongst the 7103 patients to whom the CIVIQ-20 was readministered, a significantly greater improvement in QoL was seen in the group treated with MF compared with the other treatment groups. The Vein Consult Program,27 which started in 2009, is an international observational, multicenter, descriptive survey of CVD. In step two of the program, the patients were asked to complete the CIVIQ-14. A total of 69 866 subjects were screened for the first 13 countries participating in the program. It is demonstrated that there is good correlation between two veinspecific QoL tools (AVVQ and CIVIQ-14) across the whole spectrum of disease severity.28

The CIVIQ and CIVIQ-14 have been used extensively as reported in numerous studies, some of which included large samples of patients, and have been validated in seventeen linguistic versions.29

◊ VEINES-QoL/Sym
The VEINES,20 an international prospective cohort study conducted in Belgium, France, Italy, and Canada, has developed the VEINES-QoL/Sym to evaluate QoL and symptoms across the range of conditions (eg, telangiectasias, varicose veins, edema, skin changes, leg ulcers) in CVD. It consists of 35 items distributed in two categories to generate two summary scores: the questionnaire comprises 25 items that estimate the effectof disease on QoL, and 10 items that measure symptoms. The focus of this instrument is on physical discomfort as opposed to psychological and social aspects. This measure of QoL and symptoms is available in four languages (English, French, Italian, and Canadian French). Compared with the CIVIQ, this method focuses more on symptoms than the psychological and social aspects of the disease; furthermore, it was validated for DVT symptoms.30

◊ Phleboscore®
The Phleboscore® is an 11-item self-administered questionnaire that helps predict the risk of developing CVD.31 It includes questions about risk factors as well as questions about the frequency of symptoms and the circumstances in which symptoms worsen (heat, contraceptive pill, long-distance travel). The scores range from 0 to 31. A score >12 identifies patients at risk of CVD, while a score >23 pinpoints a need for venous investigation.

◊ AVVQ
The AVVQ18 addresses multiple aspects of varicose disease, including physical symptoms, social issues, and the cosmetic manifestations of treatment outcomes. The overall evaluation consists of a score with a range of 0 to 100. The AVVQ is a 13-question survey addressing multiple elements of varicose vein disease. Physical symptoms and social issues, including pain, ankle edema, ulcers, compression therapy use, and limitations on daily activities are examined, as well as the cosmetic effect of varicose veins. The questionnaire is scored from 0 (no effect) to 100 (severe effect). A high correlation was found between the AVVQ and the SF-36 for CVD patients, with health perception lower in patients with varicose veins than in the general population. Two recent studies32,33 show that the AVVQ may be the preferred method of rationalizing patients for varicose vein surgery. It could be used to help inform a patient pathway for referral and treatment of varicose veins.

◊ Charing Cross Venous Ulcer Questionnaire (CXVUQ)
The CXVUQ was developed to provide a valid QoL measurement of venous ulcers. This method may be combined with the SF-36 to generate valuable information on the progression of ulcers and their treatment. This questionnaire has been mainly designed for patients with venous ulcers.34 Although it can be intuitively assessed that venous stasis ulcers negatively affect patient QoL, there was no reliable instrument to evaluate the effects of venous ulcer therapies.

◊ Venkatraman Ulcer-specific QoL Questionnaire (VUQ)
In 2005, a cross-sectional survey35 conducted on a representative sample of patients suffering from venous leg ulcers was published. A self-administered six-page questionnaire, Freiburger Lebensqualitäts Questionnaire Assessment (FLQA), was used to collect data. The pilot survey showed the reliability and the reproducibility of the questionnaire and indicated that the VUQ is suitable and has the potential to reflect the perspective on compression therapy and overall QoL of patients suffering from venous leg ulcers. The VUQ was tested in some randomized studies to evaluate compression therapy for venous ulcers or venous surgery, and QoL.36,37

Discussion

A number of findings stand out when reviewing the topic of QoL in patients with CVD:
– patients with varicose veins report a real impairment of QoL;
– patients with venous leg ulceration report impairment of their physical functioning and mobility similar to patients suffering from congestive heart failure,38 and suffer from negative emotions and social isolation;
– patients with venous thrombosis and PTS report pain and impairment of their physical functioning, they also report low health perceptions and high health distress;
– improvement of QoL in CVD after treatment with MF is well demonstrated.

The majority of studies about PTS applied generic QoL measures, in particular the SF-36, which provide the possibility to characterize patients with deep venous thrombosis (DVT) in comparison with other clinical samples and the healthy population. However, the SF-36 could not detect any differences between patients with and without PTS,39 whereas the VEINESQoL/ Sym did detect some differences. The generic measure, SF-36, is also not sensitive to any specific effects of compression therapies. Some studies about the effects of compression and QoL used disease-specific measures, but only a few have been adequately validated in large groups of patients. In most of these instruments, the social dimension has been neglected or only partially captured. Because we feel that this is an important issue, we recommend the use of an instrument that also assesses this domain and that is well validated, such as the CIVIQ, VEINES-QoL/Sym, and VUQ, in association with CEAP classification and the VSS system. There are recognized limitations in questionnaire studies including patients with low literacy skills or poor eyesight who might not be able to complete them, and that long and demanding questionnaires might reduce compliance. In addition, the responses on questionnaires that were administered retrospectively could suffer from a response bias, and most of the used questionnaires have not been formally evaluated for reliability and validity. Furthermore, no symptoms seemed to vary according to the severity of varicose veins and the complaints related to CVD. They can be very complex to detect at the first stages of the CEAP classification and they can have many pathological causes (eg, edema or pain). Early stages of CVD are difficult to assess objectively, particularly in C0s to C1 patients, as symptoms are by definition subjective.


Table II
Table II. A proposal for a modified Venkatraman Ulcer-specific Questionnaire (VUQ) for compression therapy.


The QoL of CVD patients is greatly affected by pain, the complaint that most often leads to the diagnosis of venous disease. The intensity of pain can also fluctuate, from patient to patient or in the same patient with progression of the disease over a period of time. A causal relationship between CVD and pain of venous origin remains difficult to clarify. In the Edinburgh Vein Study,40 the correlation observed between pathologic superficial venous reflux and sensation of swelling, heaviness, or tension was low. In addition, this correlation was limited either solely to men (sensation of swelling) or solely to women (sensation of heaviness or tension). No significant correlation was observed between superficial or deep venous reflux and venous symptoms or pain. Furthermore, no statistical relation is found between the pain score or heaviness score of a patient, evaluated on a 10-point visual analogue scale (VAS), and the clinical severity of venous disease.41,42 There are multiple measures available to assess pain in adult populations.43 Each measure has its own strengths and weaknesses. The VAS and the Numeric Rating Scale for Pain (NRS) are unidimensional single-item scales that provide an estimate of patients’ pain intensity. The VAS is usually a horizontal or vertical line, 10 cm in length, anchored by word descriptors at each end. On this line, the patient marks the point that they feel represents their perception of their current state. To evaluate the multiple dimensions of acute and chronic pain, a number of valid and reliable questionnaires are available. The McGill Pain Questionnaire (MPQ) is a generic pain measure useful largely for research purposes to describe not only the quantity (intensity), but also the quality of the patients’ pain. The Chronic Pain Grade Scale (CPGS) is similarly a generic pain measure useful for research purposes to describe, evaluate, and compare chronic pain severity across groups and in response to treatment effects. The third generic multidimensional pain measure, the SF-36 Bodily Pain Scale (SF-36 BPS) is useful in evaluating pain in the context of overall health status, and therefore most suitable for use in making comparisons across populations and between subgroups within populations. The VAS and SF-36 BPS are the preferred generic assessment instruments for pain. Regarding CVD, since pain is mostly below the half scale, the adequacy of the VAS may be questioned because the amplitude of pain may not be large enough in CVD to assess the therapeutic effects using such means. The CIVIQ questionnaire evaluates pain in CVD with a specific approach, but for everyone involved in CVD, pain is difficult to measure.


Table III
Table III. Norton Scale. All rights reserved.


Another important question is to distinguish the psychic from somatic components in CVD symptoms. Recently the psychic vs somatic venous disease questionnaire (PsySoVDQ) was applied to 1800 participants of the Bonn Vein Study II.44 Factor analysis of the PsySoVDQ distinguishes a psychic component separate from a somatic component. The PsySoVDQ identified somatic and psychic components of the widespread and frequently reported leg symptoms in the general population.

Conclusion

It would be helpful to promote and validate new specific assessment tools for the medical procedures and QoL in venous leg ulcers, PTS, and CVD. We propose to assess a modified VUQ for compression therapy (Table II, page 41). The section of the questionnaire regarding compression therapy is modified and could be validated for the general assessment of QoL with compression bandages and stockings. This questionnaire could be used in association with the Norton Scale (for mental state and joint mobility; Table III),45 the CIVIQ (or VEINES) and CEAP/VSS classification to assess, at the same time, CVD and the effects of compression therapy on QoL. Specific tools capable of assessing the full spectrum of CVD, its signs and symptoms, impact on QOL, and treatment effects are key to the efficient management of the disease.

The European Organization for Research and Treatment of Cancer (EORTC) took the initiative to develop a QoL instrument for patients with cancer, the QLQ-C30, which is validated in 81 languages and used in more than 3000 studies worldwide. It would be an idea for the future if a similar instrument was developed for patients with CVD and applied as a standard measurement in all clinical studies. Until that day, a combination of wellvalidated clinical investigations and disease-specific measures would be the preferred approach. Secondly, there should be a focus on longitudinal research on the long-term effect of CVD on QoL and on the effect of CVD on the well-being of the partners of the affected individual. In future, it will be necessary to promote an international consensus to approve the same instruments for all clinical studies on CVD/QoL.


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Keywords: CEAP classification; primary venous disorder; varices; Venous Clinical Severity Score; venous symptom