Study design, Setting, Participants
This study was approved by the Regional Ethics Committee (TuKEB 250/2013) and registered on ClinicalTrials.gov (NCT02224222). The inclusion criteria were as follows: age over 18 years, Hungarian citizenship and elective vascular surgery. Exclusion criteria were pregnancy, legal incapacity or considered to have limited capability to understand the study procedures and ethical consent. All clients were capable of making decisions regarding their participation in this study and accordingly their written consent was obtained. A study nurse, a medical student or a doctoral school fellow invited patients to participate in the study during their outpatient anesthesiology visit. Baseline questionnaires were fulfilled 5–30 days before surgery. After signing the informed consent 199 adult patients were enrolled prospectively at the Department of Vascular Surgery of the Heart and Vascular Center of Semmelweis University, in Budapest between September 2014 and August 2017. Thirty-two patients were excluded because of cancellation surgery. Three patients withdrew their consent. Finally, data of 164 patients were used for statistical analysis.
Definitions and measurements (variables and data sources and grouping)
A wide range of clinical and psychosocial factors was assessed as potential determinants of outcome. Clinical factors included perioperative laboratory parameters (blood counts, renal function, ion levels, etc.), intraoperative parameters (operation time, cross-clamp time, blood loss, need for transfusions and fluid balance medications), postoperative parameters (blood loss, medications, etc.), outcomes, incidence and quality of postoperative complications (major cerebrovascular or neurological event; acute or chronic heart failure defined as pulmonary edema, atrial fibrillation, arrhythmias, cyanosis, metabolic disorders, need for inotropes, respiratory failure; infection; acute renal failure /need for renal replacement therapy/; length of mechanical ventilation; length of ICU and in-hospital stay and in-hospital mortality). The American Society of Anesthesiologist risk score (ASA score) [9], and the Vascular Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity (Vascular POSSUM) [10–13] were calculated, too. The vascular-POSSUM consists of two parts, a physiological and an operative score. The physiological part includes age and major vital parameters (cardiac, renal, hematological and neurological function) and the operative part focuses on intraoperative blood loss, peritoneal contamination, possible malignancy and the length and urgency of the procedure.
Psychosocial factors
Psychosocial and demographic anamnestic data were collected as e.g. age, gender, living conditions, smoking, alcohol consumption and education. Then participants were asked to fulfill out many questionnaires measuring psychosocial factors: the Beck Depression Inventory (BDI), the Spielberger State-, and Trait Anxiety Inventory (STAI-S, STAI-T), the Mini Mental State Examination (MMSE), the Geriatric Depression Scale, the Somatic Symptom Severity Scale, the Devins Illness Intrusiveness Rating Scale, the Caldwell Social Support Dimension Scale, and specific parts of the Hungarostudy Query (a representative national study of 2013, used as control group, measuring health status, illnesses, bio-psycho-social background and health-related quality of life /HRQ/).
For mapping, the cognitive function Mini-Mental State Examination (MMSE) was applied. MMSE is a well-established inventory to screen cognitive deficits and signs of dementia. It contains simple questions and problems in many areas including auto- and allopsychic orientation, short term memory, arithmetic computation such as the decreasing serial sevens, language use, and comprehension, as well as basic visual-motor skills. The questionnaire scored 0 to 30. Cut-off values are 23, 18 and 9 signs for mild, moderate and severe cognitive impairment, respectively. [14, 15] To detect the mildest cognitive impairment modified cut-off values were used according to a paper published earlier. [16] In this study, the cut-off value 27 and below was used to detect mild and 23 and below for severe cognitive impairment.
Patients were asked to estimate self-reported happiness and satisfaction using a 1 to 10 scale. These self-reported parameters were reported earlier as an important aspect of determining long-term mortality of healthy adult volunteers. [17]
The State-Trait Anxiety Inventory (STAI) was used for the characterization of the anxiety of patients. The inventory consists of two parts, the STAI-S and the STAI-T axis. The first 20 questions refer to the transitional emotional status evoked by a stressful situation (STAI-S), as e.g. a hospital admission or a surgical intervention. The STAI-T score reflects personal differences in chronic anxiety susceptibility. Each group is scored 20 to 80 calculated from answers which are four-level Likert items. [18, 19] The STAI as a high reliability and validity test is well documented in the Hungarian population.[20] (STAI T and S Cronbach’s α = 0.638 and 0.763, respectively)
The Beck Depression Inventory (BDI) was used for affective disorders,. The BDI, a 21-item questionnaire, is an established tool for depression screening with each item evaluating a symptom of depression, such as bad mood, pessimistic outlook, feelings of guilt and loss of appetite. Each item contains four sentences indicating the degree of severity for that particular symptom. Answers are four-level Likert items; the whole inventory is scored 0 to 60.[21–23] Validity and reliability of the BDI are also well-documented in the Hungarian population. [24] (Cronbach’s α = 0.787)
The Geriatric Depression Scale is a yes-or-no question-based, 30-item inventory for the assessment of depression occurring in the older population. In our set, the short form of the GDS was used which includes 15 questions. Every question is scored either 0 or 1, the sum is normal between 0 and 9. [25] (Cronbach’s α = 0.704)
The Somatic Symptom Severity Scale (Patient Health Questionnaire – PHQ15) refers to different symptoms as e.g. gastrointestinal dysfunction, dizziness, chest pain and dyspnea. It is calculated by assigning scores of 0, 1 and 2 to the response categories of “not at all”, “bothered a little”, and “bothered a lot” for all 13 somatic symptoms. Also, 2 items from the mood module (fatigue and sleep) are scored 0 (“not at all”), 1 (“several days”) or 2 (“more than half the days” or “nearly every day”). We did not use questions regarding pain caused by menstruation or dysmenorrhea for better comparability. Thus the inventory is scored from 0 to 28. Scores of 5, 10, and 15 represent cut-points for low, medium, and high somatic symptom severity, respectively. [26–28] (Cronbach’s α = 0.730)
The Devin’s Illness Intrusiveness Rating Scale measures the effect of illness on different social issues. The 13-item questionnaire was introduced to screen for illness-induced disruptions of lifestyle, activities and interests that can compromise with psychosocial well-being and can contribute to emotional distress in chronic diseases. Answers are seven-level Likert items; the inventory is scored from 13 to 91. [29, 30] (Cronbach’s α = 0.854)
For analysis of the patient’s social web structure, the Caldwell Social Support Dimension Scale was used. This is a novel version of, the Social Support Questionnaire published originally in 1987. [31] The intensity of different interpersonal relationships and supports, such as direct relatives, neighbors, workmates and friends are represented in the query. After the first summary of scores, a distinct familial (parents, spouse, grandparents, children and other relatives) and non-familial (neighbor, schoolmate, workmate, other social or sacral company) support score was created. Answers are a four-level Likert item. [32–34] (Cronbach’s α = 0.570)
Finally, the shortened form of the Athens Insomnia Scale Inventory (AIS-5) was also recorded to detect mild or severe insomnia. The cut-off score of the AIS-5 is ≥ 4, which is related to potential insomnia. [35] (Cronbach’s α = 0.630)
The data were compared to the Hungarostudy (HS) population. Free-access, nationally representative, face-to-face household surveys are conducted in Hungary every 10 years, for the last time in 2013 (n = 2,000). [36, 37] The Hungarostudy is built up from the inventories listed above, it contains the BDI, STAI, CSSDS, Devin’s Illness Intrusiveness Rating Scale, PHQ15 and AIS over basic questions about age, sex, education, marital status, religion, physical status. In HS further questions was about smoking, drinking alcoholic beverages and some about the income of the participant. In our inventory, a shorter form from HS 2013 was used, in this manner, the two populations became comparable. Identical questions were compared by using the propensity score matching method.
Outcomes
The primary outcome of the study was overall mortality. As a secondary outcome, one year and two-year mortality were examined.
Statistical analysis
Descriptive statistics (mean, standard deviation, median and interquartile range) were calculated for all continuous variables. Means and SDs were used in the case of normal distribution, the Kolmogorov-Smirnov test and the Shapiro-Wilk test were used to ascertain the type of distribution. For categorical variable χ2-test was used, for continuous variable non-parametric tests were used, with the Mann Whitney U test as default. Categorical variables were calculated from continuous scales, with well-proved cut-off values. Univariate and multivariable logistic regression (Cox regression) models were also performed. The Kaplan-Meier analysis with log-rank and the Breslow tests were used to investigate differences in short and mid-term survival analyses. P < 0.05 was considered statistically significant. For statistical analysis the IBM SPSS Statistics 24.0 (SPSS Inc., Chicago, Illinois) with R plugin (version 3.2.1) for PS matching was used.
A propensity-matched analysis was performed for comparative analysis of the vascular population and the Hungarian patient cohort. During the propensity score matching pairs were generated from the HS representative group and the vascular surgical group according to age, gender and place of living. Balance on baseline covariates between the treated and control groups were evaluated using absolute standardized differences. A value less than 0.1 was considered as an acceptable standardized bias. As the pairs were created identical questions were compared to analyze the difference in psychological attitude and social state between a general and surgical population.