Assessment of a clinical pathway for investigation of haematuria that reduces the need for cystoscopy.

AIM: To evaluate prospectively a clinical pathway for investigation of haematuria that involves an initial screening using a urinary biomarker of bladder cancer (Cxbladder Triage™ (CxbT)) in combination with either a renal ultrasound or a computed tomography imaging. Only test-positive patients are referred for specialist assessment and flexible cystoscopy. METHODS: The clinical outcomes of 884 patients with haematuria who presented to their general practitioner were reviewed. Outcome measurements included the findings of laboratory tests, imaging, cystoscopies, specialist assessment and histology. RESULTS: Forty-eight transitional cell carcinomas (TCC) and three small cell carcinomas were diagnosed in the study cohort. The clinical pathway missed a solitary, small, low-risk TCC. When combined, imaging and CxbT had a sensitivity of 98.1% and a negative predictive value of 99.9% to detect a bladder cancer. Follow-up for a median of 21 months showed no further new cases of bladder cancer had occurred in the patient cohort. Review of all new bladder cancers diagnosed in the 15 months following the study showed that none had been missed by haematuria assessment using the clinical pathway. CONCLUSIONS: The combination of CxbT and imaging reliably identifies patients with haematuria who can be managed safely in primary care without the need for a secondary care referral and a flexible cystoscopy.

Additional assessment of Acute Cystitis Symptom Score questionnaire for patient-reported outcome measure in female patients with acute uncomplicated cystitis: part II.

PURPOSE: Since symptomatic, non-antibiotic therapy has become an alternative approach to treat acute cystitis (AC) in women, suitable patient-reported outcome measures (PROM) are urgently needed. The aim of this part II of a larger non-interventional, case-control study was the additional assessment of the ACSS as a suitable PROM. METHODS: Data from 134 female patients with diagnosed acute uncomplicated cystitis were included in the current analysis with (1) a summary score of "Typical" domain of 6 and more; (2) at least one follow-up evaluation after the baseline visit; (3) no missing values in the ACSS questionnaire data. Six different predefined thresholds based on the scoring of the ACSS items were evaluated to define "clinical cure", also considering the draft FDA and EMA guidelines. RESULTS: Of the six different thresholds tested, a summary score of the five typical symptoms of 5 and lower with no symptom more than 1 (mild), without visible blood in urine, with or without including QoL issues was favoured, which partially also could be adapted to the draft FDA and EMA guidelines. The overall patient's clinical assessment ("Dynamic" domain) alone was not sensitive enough for a suitable PROM. CONCLUSIONS: Scoring of the severity of symptoms is needed not only for diagnosis, but also for PROM to define "clinical cure" of any intervention, which could be combined with QoL issues. Results of the study demonstrated that the ACSS questionnaire has the potential to be used as a suitable PROM and should further be tested in prospective clinical studies.

Radiation-induced cystitis treated with hyperbaric oxygen therapy (RICH-ART): a randomised, controlled, phase 2-3 trial.

BACKGROUND: Late radiation cystitis is an adverse effect of cancer treatment with radiotherapy in the pelvic region. Symptoms of late radiation cystitis can be assessed with the Expanded Prostate Index Composite Score (EPIC). Previous reports indicate that hyperbaric oxygen therapy reduces symptoms from late radiation cystitis, but the evidence is predominantly based on non-randomised and retrospective studies. We aimed to assess whether hyperbaric oxygen therapy would mitigate symptoms of late radiation cystitis. METHODS: We did a randomised, controlled, phase 2-3 trial (RICH-ART [Radiation Induced Cystitis treated with Hyperbaric oxygen-A Randomised controlled Trial]) at five Nordic university hospitals. All patients aged 18-80 years, with pelvic radiotherapy completed at least 6 months previously, a score of less than 80 in the urinary domain of the Expanded Prostate Index Composite Score (EPIC), and referred to participating hyperbaric clinics due to symptoms of late radiation cystitis, were eligible for inclusion. Exclusion criteria were ongoing bleeding requiring blood transfusion exceeding 500 mL in the past 4 weeks, permanent urinary catheter, bladder capacity less than 100 mL, fistula in the urinary bladder, previous treatment with hyperbaric oxygen therapy for late radiation injuries, and contraindications to hyperbaric oxygen therapy. After computer-generated 1:1 randomisation with block sizes of four for each stratification group (sex, time from radiotherapy to inclusion, and previous invasive surgery in the pelvic area), patients received hyperbaric oxygen therapy (30-40 sessions, 100% oxygen, breathed at a pressure of 240-250 kPa, for 80-90 min daily) or standard care with no restrictions for other medications or interventions. No masking was applied. The primary outcome was change in patient-perceived urinary symptoms assessed with EPIC from inclusion to follow-up at visit 4 (6-8 months later), measured as absolute change in EPIC urinary total score. RICH-ART closed enrolment on Dec 31, 2017; the last follow-up data will be compiled in 2023. RICH-ART is registered with ClinicalTrials.gov, number NCT01659723, and with the European Medicines Agency, number EudraCT 2012-001381-15. FINDINGS: Of 223 patients screened between May 9, 2012, and Dec 20, 2017, 87 patients were enrolled and randomly assigned to either hyperbaric oxygen therapy (n=42) or standard care (n=45). After excluding eight patients who withdrew consent directly after randomisation (one in the hyperbaric oxygen therapy group and seven in the standard care group), 79 were included in the intention-to-treat analyses (n=41 in the hyperbaric oxygen therapy group, n=38 in the standard care group). Median time from randomisation to visit 4 was 234 days (IQR 210-262) in the hyperbaric oxygen therapy group and 217 days (195-237) in the standard care group. The difference between change in group mean of EPIC urinary total score at visit 4 was 10·1 points (95% CI 2·2-18·1; p=0·013; 17·8 points [SD 18·4] in the hyperbaric oxygen therapy group vs 7·7 points [15·5] in the standard care group). 17 (41%) of 41 patients in the hyperbaric oxygen therapy group experienced transient grade 1-2 adverse events, related to sight and hearing, during the period of hyperbaric oxygen therapy. INTERPRETATION: Our results suggest that hyperbaric oxygen therapy relieves symptoms of late radiation cystitis. We conclude that hyperbaric oxygen therapy is a safe and well tolerated treatment. FUNDING: The regional research fund of Region Västra Götaland, Sweden, the regional Health Technology Assessment Centre at Sahlgrenska University Hospital, Sweden, and Lions Cancer Research Fund of Western Sweden.

The IOU Consensus Recommendations for Empirical Therapy of Cystitis in Nursing Home Residents.

OBJECTIVE: To establish consensus recommendations for empirical treatment of uncomplicated cystitis with anti-infectives in noncatheterized older nursing home residents to be implemented in the Improving Outcomes of UTI Management in Long-Term Care Project (IOU) funded by the Agency for Healthcare Research and Quality. DESIGN: Two-round modified Delphi survey. PARTICIPANTS: Expert panel of 19 clinical pharmacists. MEASUREMENTS: Comprehensive literature search and development/review/edit of draft survey by the investigative group (one geriatric clinical pharmacist, two geriatric medicine physicians, and one infectious disease physician). The expert panel members rated their agreement with each of 31 recommendations for drugs of choice, dosing medications at various levels of renal function, drug-drug interactions to avoid, and duration of therapy by sex on a 5-point Likert scale (1 = strongly disagree to 5 = strongly agree). Consensus agreement was defined as a lower 95% confidence limit of 4.0 or higher for the recommendation-specific mean score. RESULTS: The response rate was 95% for the first round, and three recommendations achieved consensus (dosing for nitrofurantoin and trimethoprim/sulfamethoxazole in those without chronic kidney disease, and drug-drug interaction between trimethoprim/sulfamethoxazole and warfarin). In the second round, 90% responded and reached consensus on an additional eight recommendations (two for nitrofurantoin or trimethoprim/sulfamethoxazole as initial drugs of choice, three for dosing ciprofloxacin, nitrofurantoin, and trimethoprim/sulfamethoxazole at various levels of chronic kidney disease, and three drug-drug interactions to avoid: trimethoprim/sulfamethoxazole with phenytoin and ciprofloxacin with theophylline or with tizanidine). CONCLUSION: An expert panel of clinical pharmacists was able to reach consensus on a set of recommendations for the empirical treatment of cystitis with oral anti-infective medications in older nursing home residents. The recommendations were incorporated into a treatment algorithm for uncomplicated cystitis in noncatheterized nursing home residents and used in educational materials for health professionals in an ongoing controlled intervention study. J Am Geriatr Soc 67:539-545, 2019.

The 2017 Update of the German Clinical Guideline on Epidemiology, Diagnostics, Therapy, Prevention, and Management of Uncomplicated Urinary Tract Infections in Adult Patients. Part II: Therapy and Prevention.

BACKGROUND: We aimed to update the 2010 evidence- and consensus-based national clinical guideline on the diagnosis and management of uncomplicated urinary tract infections (UTIs) in adult patients. Results are published in 2 parts. Part 1 covers methods, the definition of patient groups, and diagnostics. This second publication focuses on treatment of acute episodes of cystitis and pyelonephritis as well as on prophylaxis of recurrent UTIs. MATERIALS AND METHODS: An interdisciplinary group consisting of 17 representatives of 12 medical societies and a patient representative was formed. Systematic literature searches were conducted in MEDLINE, EMBASE, and the Cochrane Library to identify literature published in 2010-2015. RESULTS: For the treatment of acute uncomplicated cystitis (AUC), fosfomycin-trometamol, nitrofurantoin, nitroxoline, pivmecillinam, and trimethoprim (depending on the local rate of resistance) are all equally recommended. Cotrimoxazole, fluoroquinolones, and cephalosporins are not recommended as antibiotics of first choice, for concern of an unfavorable impact on the microbiome. Mild to moderate uncomplicated pyelonephritis should be treated with oral cefpodoxime, ceftibuten, ciprofloxacin, or levofloxacin. For AUC with mild to moderate symptoms, instead of antibiotics symptomatic treatment alone may be considered depending on patient preference after discussing adverse events and outcomes. Primarily non-antibiotic options are recommended for prophylaxis of recurrent urinary tract infection. CONCLUSION: In accordance with the global antibiotic stewardship initiative and considering new insights in scientific research, we updated our German clinical UTI guideline to promote a responsible antibiotic use and to give clear hands-on recommendations for the diagnosis and management of UTIs in adults in Germany for healthcare providers and patients.

The 2017 Update of the German Clinical Guideline on Epidemiology, Diagnostics, Therapy, Prevention, and Management of Uncomplicated Urinary Tract Infections in Adult Patients: Part 1.

OBJECTIVES: We aimed to update the 2010 evidence- and consensus-based national clinical guideline on the diagnosis and management of uncomplicated urinary tract infections (UTIs) in adult patients. MATERIALS AND METHODS: An interdisciplinary group consisting of 17 representatives of 12 medical societies and a patient representative was formed. Systematic literature searches were conducted in MEDLINE, -EMBASE, and the Cochrane Library to identify literature published in 2010-2015. RESULTS: We provide 75 recommendations and 68 statements in the updated evidence- and consensus-based national clinical guideline. The diagnostics part covers practical recommendations on cystitis and pyelonephritis for each defined patient group. Clinical examinations, as well as laboratory testing and microbiological pathogen assessment, are addressed. CONCLUSION: In accordance with the global antibiotic stewardship initiative and considering new insights in scientific research, we updated our German clinical UTI guideline to promote a responsible antibiotic use and to give clear hands-on recommendations for the diagnosis and management of UTIs in adults in Germany for healthcare providers and patients.

Histopathological assessment of inflammation and expression of inflammatory markers in patients with ketamine-induced cystitis.

The aim of the current study was to evaluate the histopathological features of inflammation and the expression levels of inflammatory markers in tissue samples from patients with ketamine­induced cystitis. Bladder biopsy samples for histological analysis were obtained from 23 patients (18 men and 5 women) with a self­reported history of ketamine use and who were treated for cystitis at the Tri­Service General Hospital of Taipei, Taiwan. Immunohistochemical staining for cyclooxygenase­2 (COX­2), inducible nitric oxide synthase (iNOS), matrix metallopeptidase­9 (MMP­9), mammalian target of rapamycin (mTOR), and phosphorylated 40S ribosomal protein S6 (Phos­S6) was performed. The results revealed urothelial atypia in all patients, and intravascular eosinophil accumulation in 22 patients. Histopathological features included denuded urothelial mucosa, ulceration, collagen deposition, smooth muscle degeneration and vessel proliferation. Tissue samples were immunopositive for all of the inflammation markers, including the urothelium, vessel walls, and smooth muscle. COX­2 staining revealed a significant difference between the inflammatory levels in the urothelium and smooth muscle, and iNOS staining differed significantly between inflammatory levels in smooth muscle (p=0.029). A positive correlation was observed between the percentage of Phos­S6­positive cells and the levels of inflammation in the urothelium. These results add to the descriptive literature on the histopathological aspects of ketamine­induced cystitis, emphasizing the inflammatory nature and a possible role for proteins such as COX­2, iNOS and Phos­S6 in the degree of inflammation.

Assessment of voiding function in inhabitants infected with Schistosoma haematobium.

Voiding function of Schistosoma haematobium infected students was evaluated in 45 schoolboys in Kwale district, Coast province, Kenya, using a questionnaire and uroflowmetry. Sixty-eight schoolboys who were S. haematobium negative were also examined. Symptoms related to the lower urinary tract were qualitatively assessed using the International Prostate Symptoms Score (I-PSS) questionnaire. The I-PSS showed that S. haematobium infected boys felt the need to strain to urinate and post voiding some urine still remained. To examine the disturbances revealed by I-PSS quantitatively, voiding was assessed by a portable uroflowmeter and a bladder scanner. Unexpectedly, no significant residual urine post voiding and no decline in urine flow rates were found in S. haematobium infected boys. However, volume-corrected maximum and average flow rates in S. haematobium infected boys were higher than in those not infected. These results suggest that cystitis associated with S. haematobium infection causes irritation and hypercontraction of the bladder.

The tools of an evidence-based culture: implementing clinical-practice guidelines in an Israeli HMO.

PURPOSE: Although clinical-practice guidelines (CPGs) are implemented on the assumption that they will improve the quality, efficiency, and consistency of health care, they generally have limited effect in changing physicians' behavior. The purpose of this study was to design and implement an effective program for formulating, promulgating, and implementing CPGs to foster the development of an evidence-based culture in an Israeli HMO. METHOD: The authors implemented a four-stage program of stepwise collaborative efforts with academic institutions composed of developing quantitative tools to evaluate prescribing patterns, updating CPGs, collecting MDs' input via focus groups and quantitative surveys, and conducting a randomized controlled trial of a two-stage, multipronged intervention. The test case for this study was the development, dissemination, and implementation of CPG for the treatment of acute uncomplicated cystitis in adult women. Interventions in the form of a lecture at a conference and a letter with personalized feedback were implemented, both individually and combined, to improve physicians' rates of prescribing the first-line drug, nitrofurantoin, and, in the absence of nitrofurantoin, adhering to the recommended duration of three days of treatment with ofloxacin. RESULTS: The tools and data-generating capabilities designed and constructed in Stage I of the project were integral components of all subsequent stages of the program. Personalized feedback alone was sufficient to improve the rate of adherence to the guidelines by 19.4% (95% CI = 16.7, 22.1). CONCLUSIONS: This study provides a template for introducing the component of experimentation essential for cultivating an evidence-based culture. This process, composed of collaborative efforts between academic institutions and a managed care organization, may be beneficial to other health care systems.

A 'gap' between physician and patient assessment of symptom severity in acute cystitis?: a multicenter trial of women treated with extended-release ciprofloxacin.

The current trial assessed differences in physician and patient symptom-severity perceptions in ambulatory outpatient females with uncomplicated urinary tract infections (uUTIs). We also investigated the efficacy and safety profile of once-daily ciprofloxacin in a 500-mg PO extended-release formulation for 3 days to treat acute cystitis. This prospective, open-label, multicenter (1,972 sites), phase 4 clinical trial enrolled 7,614 adult women with a clinical diagnosis of an acute uUTI. After assessing the patient's cystitis symptoms, physicians rated each cystitis-related symptom on a 4-point severity scale. Patients independently completed a pretreatment survey including a self-assessment of these same symptoms. Clinical outcomes were assessed at the end-of-study visit (2 to 7 days post-therapy). Exact agreement on symptom severity between physician and patient was between 54% and 57% for symptoms. The discrepancies between assessments were significant in the marginal homogeneity tests (P less than 0.00001). Clinical cure following this regimen was 91.3% of efficacy-valid women. Women who had 2 or more UTI episodes in the previous 12 months tended to have lower rates of clinical cure than those who had 1 or no episodes in that time.

Outcomes from use of an evidence-based practice guideline.

The aim of evidence-based guidelines is primarily to improve patient outcomes without adding to the existing cost of care because both payers and policymakers want to identify health care costs that do not result in benefit to the patient. The purpose of the reported project was to generate a practice guideline for the treatment of uncomplicated acute cystitis in a female population, to determine the extent to which the guideline would be used by providers and to measure the cost and quality of outcomes from its use. A retrospective chart review was used to gather pre-guideline practice and cost data. Measurements included the type, frequency, and duration of antibiotic therapy and the use of urine cultures and both complications and routine followup visits. The implementation of an outpatient practice guideline resulted in a significant change in antibiotic prescribing and a trend toward a change in ordering cultures and clinic followup. There was also a significant decrease in treatment costs.

'Telephone treatment' of uncomplicated acute cystitis.

Acute cystitis in women is typically uncomplicated and amenable to empiric antimicrobial therapy. We advocate a simple approach, in which women with uncomplicated cases are treated over the telephone. Such a program has been in place at the Cleveland Clinic since 1992, and has yielded good results.

Practice guidelines for urinary tract infection in the era of managed care.

Acute uncomplicated cystitis among young women is very common, relatively easy to diagnose, and easy to treat with short-course antimicrobial regimens. However, there is great variability among physicians in the approaches to diagnosis and management. Cystitis, therefore, lends itself well to management by clinical practice guidelines which de-emphasize costly office visits, pre-therapy urine cultures and long courses of therapy. As cystitis guidelines continue to be developed by medical care organizations, however, it is important that they be evidence based, include the participation of practicing physicians and provide a mechanism for evaluation to ensure that quality of care and patient satisfaction are not compromised.

The effectiveness of a clinical practice guideline for the management of presumed uncomplicated urinary tract infection in women.

PURPOSE: Acute uncomplicated urinary tract infection is a common and costly disorder in women. To reduce potentially unnecessary expense and inconvenience, a large staff-model health maintenance organization instituted a telephone-based clinical practice guideline for managing presumed cystitis in which women 18 to 55 years of age who met specific criteria were managed without a clinic visit or laboratory testing. We sought to evaluate the effects of the guideline. SUBJECTS AND METHODS: We performed a population-based, before-and-after study with concurrent control groups at 24 primary care clinics to assess the effect of guideline implementation on resource utilization and on the occurrence of potential adverse outcomes. We measured the proportion of patients with presumed uncomplicated cystitis who had a return office visit for cystitis or sexually transmitted disease or who developed pyelonephritis within 60 days of the initial diagnosis. Relative risks (RR) and 95% confidence intervals (CI) were estimated, adjusting for the effects of clustering within clinics. RESULTS: A total of 3,889 eligible patients with presumed acute uncomplicated cystitis were evaluated. As compared with baseline, guideline implementation significantly decreased the proportion of patients with presumed cystitis who received urinalysis (RR = 0.75; CI, 0.70 to 0.80), urine culture (RR = 0.73; CI, 0.68 to 0.79), and an initial office visit (RR = 0.67; CI, 0.62 to 0.73), while increasing the proportion who received a guideline-recommended antibiotic 2.9-fold (CI, 2.4 to 3.7-fold). In the prospective comparison of the 22 intervention and two control clinics, the guideline decreased the proportion of patients who had urinalyses performed (RR = 0.80; CI, 0.65 to 0.98) and increased the proportion of patients who were prescribed a guideline-recommended antibiotic (RR = 1.53; CI, 1.01 to 2.33). Adverse outcomes did not increase significantly in either comparison. CONCLUSION: Guideline use decreased laboratory utilization and overall costs while maintaining or improving the quality of care for patients who were presumptively treated for acute uncomplicated cystitis.

Mechanism of action and impact of a cystitis clinical practice guideline on outcomes and costs of care in an HMO.

BACKGROUND: A study was conducted in 1995 at five primary care clinics of a staff-model health maintenance organization in the Midwest to assess the impact of a cystitis clinical guideline and to help elucidate the guideline implementation process. METHODOLOGY: Two hundred one eligible women with uncomplicated cystitis were treated in a three-month period before the guideline, and 241 similar cases were treated in a three-month period after the guideline. Nursing supervisors and clinic managers at each clinic were interviewed about how the cystitis guideline was implemented at each clinic. RESULTS: Use of a recommended three-day antibiotic treatment increased from 28% to 52% of cases (chi-square = 25.01, p < 0.001). Use of urine cultures decreased from 70% to 37% of cases (chi-square = 48.19, p < 0.001). The proportion of eligible cystitis cases coordinated primarily by the nurse increased from 21% to 78% (chi-square = 142.93, p < 0.001). However, desired changes in use of antibiotics and urine cultures were limited to nurse-coordinated cases. There was no increase in hospital admissions, emergency room visits, repeat office visits (p > 0.05), or repeat antibiotic courses (p > 0.05) after cystitis guideline implementation. Cost of cystitis care delivered after guideline implementation was 35% lower than before guideline implementation. CONCLUSIONS: Use of the guideline was associated with desirable changes in antibiotic use, nurse coordination of care, costs of care, and comparable clinical outcomes. Clinics that used clinical systems and tools to support nurse-coordinated cystitis care had greater guideline adherence than clinics that did not support nurse-coordinated care.