Urinary tract infections (UTIs) are common, with an estimated annual global incidence of at least 250 million, with the vast majority (84%) of visits related to female patients presenting with acute uncomplicated cystitis (AC) [1
]. Although AC is a benign condition, recurrent episodes are associated with a reduction in quality of life, a negative impact on everyday activity and working ability, disturbances in sexual life and psychosexual disorders [4
]. In the recent years, several studies have shown specific risk factors for recurrent AC [7
], and large studies revealed its microbial etiology. Clinical tests for diagnosing AC vary widely, depending on comorbidities and different treatment strategies [9
Several studies and current guidelines do not consider urinalysis or microbiologic investigation necessary but rely on patients’ complaints only, even though telephone conversation [12
]. Various urinary symptoms have been used to assess the diagnosis and severity of AC in women. Diaries, questionnaires, and symptom scores used in these studies were mainly adapted from other tools. Only a few publications devoted to the studies regarding the development of the questionnaires, evaluating the severity of symptoms of the AC and their interference with activities [15
]. However, up to today, no single, unified, valid, and specific questionnaire existed for diagnosis, differential diagnosis, assessment of symptoms’ severity, and quality of life that is also available to monitor treatment efficacy [4
]. We have recently presented a new self-reporting questionnaire—ACSS—for diagnosis, differential diagnosis, and patient-reported outcome in female patients with AUC, assessing typical and differential symptoms, quality of life, and possible changes after therapy [18
Since the first 58 subjects who filled in the precursor version of the ACSS (USQOLAT) [20
], which differed in a few aspects from the current version of the ACSS, were included in the former validation, a reevaluation of the current Uzbek and Russian versions of the ACSS was performed excluding these patients. Now, the present study includes only the results of the final 228 subjects (107 patients with AC and 121 controls without AC) who filled in the current versions of the Uzbek or Russian ACSS (Supplementary Figures S1 and S2
2. Development and Evaluation Process of the Acute Cystitis Symptom Score (ACSS) Questionnaire
Regarding the purpose of the development of the ACSS questionnaire, PubMed’s medical subject headings (MeSH) service was used for the literature search. Different combinations of such MeSH terms as “urinary tract infections”, “cystitis”, and “signs and symptoms” were used for the identification of the key clinical symptoms/signs of AC. The literature search was limited to the publications in the English language. Thereafter, different versions of multiple choice questions regarding the presence and severity of symptoms were developed in Uzbek and Russian languages, and furtherly were revised and commented by Russian-speaking, Uzbek-speaking, and bilingual (speaking both in Uzbek and Russian languages) female staff of the hospital. Although the Uzbek language is the official state language in Uzbekistan, Russian is the second common language and remains in widespread use (https://en.wikipedia.org/wiki/Uzbekistan
), with the majority of the population speaking both languages.
Following the approval of the Institutional Review Board (Clinical ethics committee) of the Republican Specialized Center of Urology/JSC “Republican Specialized Center of Urology” (RSCU) (Akilov FA, Mukhtarov ShT, Khvan AL: No. 429/23) in September 2009, preliminary versions of the questionnaire were tested as described earlier with females from different social areas, with different levels of education, nationalities, and age after informed consent was obtained prior to enrollment of the participants [18
]. Based on their comments and requests, a multidimensional scaling analysis was performed, and the most appropriate versions of questions and answers were chosen by the research team for the development of the preliminary questionnaire titled as “Urinary Symptoms and Quality of Life Assessment Tool (USQOLAT).” The reliability analysis, performed on the first 58 subjects (32 patients with AC and 26 controls without AC), showed a mean Cronbach’s alpha of 0.84, a Split-half reliability of 0.82, and a Spearman-Brown prophecy of 0.9 [20
From the preliminary (precursor) version (USQOLAT), the current ACSS was further updated as follows: (i) the scores for question 1 (frequency of urination) were related to the number of urinations per 24 h, (ii) the symptoms were clearly divided into “typical” and “differential” symptoms, and (iii) five questions on additional conditions were added.
The consulting physicians diagnosed AC according to their clinical practice and based on the results of laboratory investigations. Besides the typical history and symptoms, urinalysis was performed in 99.1% patients (only 1 missing data) with positive pyuria in 94.5% of cases. Although microscopic bacteriuria and positive urine culture was only found in 75/106 (70.8%) and 39/64 (60.9%) of patients, respectively, it should be noted that only cases with a bacteriuria of at least 105
CFU/mL found in microscopy [23
] and at least 104
CFU/mL in urine culture, could be considered as positive in the clinical practice.
In contrast, Stamm et al. had already shown that the traditional diagnostic criterion, ≥105
CFU/mL of midstream urine, has a very high degree of diagnostic specificity (99%) but a very low level of sensitivity (51%) [31
]. That means that this threshold of urine culture may identify only 51% of symptomatic women with lower UTI whose bladder urine (obtained by suprapubic aspiration or by catheter) contains coliforms. The authors found the best diagnostic criterion to be ≥102
CFU/mL (sensitivity, 95%; specificity, 85%) and suggested that clinicians and microbiologists should alter their approach to the diagnosis and treatment of women with acute symptomatic coliform infection of the lower urinary tract.
Hooton et al., however, confirmed in a more recent study that colony counts of E. coli
as low as even 101
CFU/mL in midstream urine were sensitive and specific for the presence of E. coli
in catheter urine in symptomatic women [32
]. Although using such low counts as a threshold, still no uropathogens could be cultured neither from catheter nor midstream urine in 22% of patients with typical symptoms of AC. It follows, that for diagnosing AC the symptomatology has become more decisive than any urinary bacterial count.
The results of our investigation demonstrate that the ACSS is a reliable, valid, and easy-to-use questionnaire, which may help to diagnose AC in women in primary healthcare settings and to assess treatment efficacy. The ACSS is a reliable diagnostic tool for patients and physicians, not only in premenopausal, non-pregnant women but also in pregnant women and in postmenopausal women. It can be self-administered and completed in a short time by respondents or surveyees. Questions and versions of answers are easy to understand and may be used for epidemiological surveys and/or drug studies.
The current version of the ACSS was tested in 228 women visiting urologist’s office for different reasons. The Uzbek, as well as the Russian versions, are clear and understandable for women of any age, educational level, and employment status. Our study demonstrated high reliability and validity of the questionnaire. The items of ACSS have excellent internal consistency and validity.
The results of the present study, including only the 228 women to whom the current ACSS was applied, did not show clinically relevant diagnostic differences to the study published earlier [19
], which included an additional 58 women, to whom the precursor questionnaire, USQOLAT, was administered (Table 1
Health-related quality of life is gaining increasing importance, combining characteristics of physical, psychological, emotional, and social human functioning based on subjective perception [33
]. The assessment of the quality of life is usually performed by patient self-reporting and may be much more useful even if it mismatches the physician’s view. Although standard medical and biological parameters are often basic criteria of treatment efficacy, they cannot reflect the patient’s feeling of well-being and performance of everyday activities. Therefore, indeed the self-assessment may be the most informative index of the patient’s status of health in many cases [36
]. In this context, symptom scores and questionnaires are valuable tools. In urology, international validated questionnaires such as the IPSS (International Prostate Symptom Score) and the NIH-CPSI (National Institutes of Health Chronic Prostatitis Symptom Index) are broadly used for various conditions [37
Until recently, there was no generally accepted questionnaire for AC available for combined assessment of severity of symptoms and impact on quality of life. Our study aimed to develop a highly sensitive and specific as well as simple patient self-reporting questionnaire assessing the symptoms of AC and their impact on quality of life, differentiating AC from other urogynecological disorders with similar symptomatology, and assessing treatment efficacy.
In previous studies on UTIs, numerous different diaries, symptoms questionnaires and scales for separately assessing “bladder symptoms” and health-related quality of life were used separately [4
]. Some researchers assessed general conditions and wellbeing of patients rather than urinary symptoms [17
]. Others have used “self-made” questionnaires or algorithmic schemes for assessing symptoms in patients with pre-diagnosed AC before and after treatment [12
]. The symptom score used in the study of Bleidorn et al. [27
] contained questions regarding only three key symptoms of AC (dysuria, frequency, and lower abdominal pain), while the ACSS contains also questions about other key symptoms of AC (urgency, incomplete bladder emptying and hematuria). However, the ACSS is not the first questionnaire in the area of UTIs. Earlier, two other questionnaires—the UTI Symptoms Assessment (UTISA) and the Activity Impairment Assessment (AIA)—were published [15
]. While the UTISA evaluates the severity of lower UTI, the AIA investigates the impact on impaired activity. Unfortunately, important statistical information like sensitivity, specificity, responsiveness and discriminative abilities have not been reported for both. The ACSS was developed and validated considering these parameters. It also contains questions to differentiate AC from other commonly community-acquired urological and gynecological diseases (“Differential” domain) and items for conditions that may affect therapy (“Additional” domain) and therefore requiring broader and more thorough investigation. These additional items may add more accuracy and be useful for epidemiological surveys.
The discriminative ability of “Typical” domain of the questionnaire may allow easier distinguishment of the patients with AC from those without it. During our analysis, we have found statistically significant correlations between scores of the questionnaire and results of urinalyses. High levels of sensitivity and specificity in combination with excellent discriminative ability and responsiveness make this questionnaire very useful for diagnosing AC in women and assessment of treatment efficacy. The ACSS also evaluates the severity of symptoms and their influence on the quality of life and may assist to differentiate AC from other urological disorders with the help of the “Differential” domain. Complicating and affecting factors may be revealed by the analysis of the “Additional” domain. A special domain assessing dynamics evaluates treatment efficacy. These distinctive features are the main advantages of the ACSS compared to other existing UTI symptom scores [12
Our study has limitations that should be acknowledged. First, the questionnaire was limited to Uzbek- and Russian-speaking women. Second, the study was performed in a single center, and only 48% of all patients with AC returned for a follow-up visit to test responsiveness. Nevertheless, the reevaluation of the questionnaire was performed in a large number of patients and controls. Results of the validation of the ACSS in German and UK English languages were published recently [42
] and is planned or ongoing in other languages.