Study Design and Population
This international, prospective, observational, multi-center, epidemiological pilot study was conducted during 2005–2006, in accordance with the ethical standards of the responsible committees on human experimentation (institutional and national) and with the 1975 Declaration of Helsinki, as revised in 2000 and 2008. Due to limited evidence of the impact of rUTIs on QoL, this study was designed to evaluate whether rUTIs have a negative impact on patient QoL. The study did not interfere with usual patient management, no special treatment or examination was stipulated, and the physician’s prescribing freedom was maintained. The study population consisted of patients affected by lower rUTIs (defined as ≥3 infectious episodes over the previous 12 months) who were treated by urologists, gynecologists, hospital doctors, or general practitioners. Patients were male or female, >18 years of age, suffering from lower rUTIs, and with a planned preventative treatment. Patients unable to understand or complete the QoL questionnaires, unwilling to participate, who had a deformity of the urinary tract, neurogenic bladder, or presenting with symptoms of vaginitis were excluded from the study.
Data were collected from 151 centers in seven countries: Egypt, Germany, Lebanon, Peru, Poland, Portugal, and Switzerland. To ensure even geographical distribution and fair representation of patients from different geographical areas, physicians were asked to recruit a maximum of five patients meeting the eligibility criteria and willing to participate in the study. Each patient was examined at inclusion (Day 0) and 6 months later (Day 180).
This observational pilot study aimed to substantiate the notion that recurrent cystitis has a negative impact on QoL. The primary endpoint of the study was the relationship between the number of infectious episodes and the Hospital Anxiety and Depression (HAD) scale . The secondary endpoint was the relationship between the Leicester impact scale  and the number of infectious episodes.
Assessments on Day 0 and Day 180
On Day 0 and Day 180, physicians recorded the patient UTI history (date of first infection, date of start of recurrent signs, frequency of infectious episodes, triggering factors, and treatments received), description of urinary symptoms concerning the last infection, description of pain (intensity, duration, and moments of appearance), previous microbiological data (date of last examination and microbiological diagnosis), and number of UTI episodes over the previous 6 months. To assess the presence and level of emotional problems, as well as the social and functional handicap in relation to rUTIs, the physician asked the patient to complete the HAD scale and Leicester impact scale questionnaires.
QoL is an outcome that can only be assessed by the subjects themselves, without reference to any norm. This is a specific approach in which the patients express their perception of the situation and the satisfaction (or dissatisfaction) they experience compared with their expectations . Therefore, QoL assessment was made using two specific questionnaires: a generic form on anxiety and depression disorders (i.e., the HAD scale)  and a UTI-specific questionnaire on the functional and social handicaps associated with UTIs (i.e., the Leicester impact scale) .
Assessment of Emotional Problems
Emotional problems experienced by patients during the previous week were assessed using the HAD scale, which provides a reliable method of detecting the most common signs of anxiety and depressive disorders . The questionnaire comprises 14 questions (7 evaluate anxiety and 7 evaluate depression). Each reply has a value of 0–3, and the assessment was made in a semi-quantitative manner using an adverb or qualifying short sentence to evaluate symptom intensity. Therefore, the possible total score ranged from 0 to 42, with both anxiety and depression subscales ranging from 0 to 21.
The HAD scores were divided into three ranges to assess the presence of anxiety or depression: 0–7 = normal, 8–10 = possibly indicative of anxiety or depression, and ≥11 = probable presence of anxiety or depression. A score of at least 8 on either anxiety or depression subscales indicated an emotional disorder.
Assessment of Social or Functional Handicap
Social or functional handicap was assessed using the Leicester impact scale. This is a valid and reliable, interviewer-administered QoL tool for patients with urinary storage symptoms . It was used to determine the impact of urinary problems on daily activities (part 1) and on mood and behavior (part 2). Part 1 of the scale assessed nine situations in which urinary infections are likely to interfere with daily activities (activity score), categorized as often, rarely, never, activity stopped because of urinary problems, and activity stopped for other reasons. Part 2 of the scale was used to determine the impact of symptoms on mood and behavior (feeling score), categorized as often, rarely, or never. The Leicester impact scale was divided into four ranges: 0–14, 15–20, 21–30, and 31–42. A score of >14 indicated that the patient had some degree of functional or social handicap, a score of >20 was suggestive of a major social or functional handicap, and scores >31 indicated major social and functional handicaps.
Statistical analyses were performed using SAS® Version 8.2 software (SAS Institute Inc., Cary, NC, USA). The significance level was set at 5%. Spearman correlation was used, as appropriate, to assess the degree of correlation between infectious episodes and the HAD and Leicester scores. For each parameter, the comparison between Day 0 and Day 180 was performed using Wilcoxon signed-rank test for quantitative data.