Efficacy of a pharmacist care protocol to manage uncomplicated female cystitis in community pharmacies: an open-label, multicenter, randomized, controlled, cluster study: the PharmaCyst' protocol.

BACKGROUND: Urinary tract infections are common affections, especially for women. Difficult access to a general practitioner to obtain a prescription has led France to offer dispensing under protocol by community pharmacists. The primary objective of this study is to evaluate the effectiveness of a pharmacist care protocol provided to manage women with urinary tract infection symptoms. This objective will be assessed using the Acute Cystitis Symptom Score. METHODS: PharmaCyst' is an open-label, multicenter, controlled, cluster-randomized study conducted in the Loire region, France. Women aged between 18 and 65 years presenting to a pharmacy complaining of at least one symptom of an uncomplicated urinary tract infection present over the last 3 days (including burning pain during micturition, dysuria, pollakiuria, urgent urination) will be considered for inclusion. All patients will be contacted on day 3, 10, and month 3. A total of 480 patients need to be recruited for the 24 clusters participating in the research. The quantitative data will be described using means and standard deviations and compared using Student's t-test. The qualitative data will be described using numbers and percentages and compared using chi2 test (or Fisher's exact test if necessary). The primary and secondary outcomes analyses will consider the intention-to-treat population. DISCUSSION: PharmaCyst' is the first clinical trial conducted in France only by community pharmacists. Its results could lead to an extension of the protocol. TRIAL REGISTRATION: The protocol has been approved by the French ethics committee on 2022/12/02 and is registered under the number 49RC22_0240 on ClinicalTrials.gov.

Case reports of immune-related cystitis and the antibody combination hypothesis.

Immune-related cystitis is a rare condition, and its diagnostic criteria and pathogenesis are not yet fully understood. Here, we report two cases of immune-related cystitis. Both patients were previously diagnosed with lung squamous cell carcinoma and received combined treatment with immune checkpoint inhibitors and chemotherapy, leading to hemorrhagic cystitis. We reviewed the cystoscopic images and pathological features of previous cases and found that autoantibodies against hemidesmosomes may be the cause of immune-related cystitis, proposing the "antibody combination" hypothesis to explain the tissue specificity of the condition.

Lung squamous cell carcinoma can produce certain proteins called autoantigens. Some patients treated with immune checkpoint inhibitors might develop antibodies against these autoantigens. A specific combination of these antibodies may cause the bladder lining to slough, leading to immune-related cystitis. Symptoms of this condition include frequent urination, urgent need to urinate, painful urination and blood in the urine. These patients typically require treatment with steroids.

Urinary tract infections in chronic kidney disease in Nephrology unit, University Hospital Center of Befelatanana, Antananarivo.

INTRODUCTION: Urinary tract infection is the leading cause of nosocomial infection worldwide. It is a factor in the progression of chronic kidney disease. AIM: To determine the epidemiological, clinical, microbiological, therapeutic and evolving profile of patients with chronic kidney disease and urinary tract infection. METHODS: This was a retrospective, descriptive study lasting 5 years, from January 2014 to december 2018 in chronic kidney disease with urinary tract infection. RESULTS: Fifty-one patients (7.15%) were retained with a mean age of 53.03 years and a sex ratio of 0.55. Chronic kidney disease was in end-stage in 45.1% (n=23). Cystitis was found in 49.02% (n=25) and gram-negative bacilli were found in 74.50% (n=38), predominantly Escherichia coli (54.90%). Third generation of cephalosporins and fluoroquinolones were frequently prescribed as probabilistic antibiotics. Resistance to beta-lactam antibiotics was 50% for Escherichia coli. Factors influencing severe infection were: advanced age, male gender, urinary lithiasis, multiple antibiotic resistance and non-enterobacterial germs. CONCLUSION: Urinary tract infection in chronic kidney disease were frequent and particularly severe.

Renal and Urinary Conditions: Urinary Tract Infections.

Urinary tract infections (UTIs), including cystitis and pyelonephritis, are common. Each year, they account for more than 10 million outpatient visits and more than 3 million emergency department visits. Recurrent UTIs (defined as three in 1 year or two in 6 months) also are common, occurring in 20% to 30% of women. The annual incidence of UTIs is 12.1% among women and 3% among men. Cystitis symptoms include lower abdominal pain, dysuria, and urinary urgency or frequency. Escherichia coli is the most common pathogen. Cystitis often is diagnosed inappropriately when patients have asymptomatic bacteriuria (ie, positive urine culture result without symptoms). This can result in unnecessary antibiotic therapy. For uncomplicated acute cystitis in women, guidelines recommend nitrofurantoin for 5 days, trimethoprim-sulfamethoxazole for 3 days (if local drug-resistance rates are less than 20%), fosfomycin in a single dose, or pivmecillinam for 5 days. Effective prophylactic options for UTI include antibiotics and vaginal estrogen for postmenopausal women. Antibiotics are most effective but are associated with a risk of increased drug resistance. Patients with pyelonephritis present with costovertebral tenderness, fever, and urinary symptoms. Third-generation cephalosporins are preferred for management. Significant complications of pyelonephritis include sepsis or septic shock, obstructive pyelonephritis, emphysematous pyelonephritis, perinephric abscess, and kidney transplant rejection. For pregnant patients with pyelonephritis, hospitalization and intravenous antibiotics are indicated.

An expert consensus on prevention, diagnosis, and management of hemorrhagic cystitis in pediatric hematopoietic cell transplantation, on behalf of the Infectious Disease and Hematopoietic Cell Transplant Working groups of Italian Pediatric Hematology Oncology Association (AIEOP).

The optimal management of hemorrhagic cystitis (HC) in hematopoietic stem cell transplantation (HCT) is debated, both for early onset HC (EOHC) secondary to chemotherapy toxicity and BK Polyomavirus (BKPyV)-related HC, due to the lack of controlled trials, particularly referred to pediatric setting. Actually, clinical practice is mainly based on guidelines of the European Conference on Infections in Leukemia, 6th edition, which considers both adult and pediatric populations but concludes that, despite much progress in understanding the pathogenesis, epidemiology, and risk factors, this complication still represents a disabling unmet clinical need with limited prophylactic and therapeutic options. Additionally, the Guidelines of the American Society of Clinical Oncology define the management of chemotherapeutic toxicity independently from the patients' population. A panel of experts belonging to the Hematopoietic Cell Transplant and Infectious Disease Working Group (WG) of Associazione Italiana di Emato-Oncologia Pediatrica (AIEOP) developed a consensus to define the best practices in prevention, diagnosis, and management of HC in pediatric HCT setting.

'Male cystitis does not exist': A qualitative study of general practitioners' experiences and management of male urinary tract infections in France.

BACKGROUND: Male urinary tract infections (mUTIs) are rare in primary care. The definition of mUTIs varies across countries. The therapeutic management of mUTIs in France is based on a 14-day course of fluoroquinolones despite a high risk of antimicrobial resistance. OBJECTIVES: The objective of this qualitative study was to explore general practitioners' (GPs) experiences and behaviours regarding the diagnostic and therapeutic management of mUTIs. METHODS: GPs were recruited by convenience sampling in Haute Normandie (France) and interviewed individually with semi-structured guides. GPs' experiences and behaviours were recorded and analysed using an interpretive phenomenological approach. RESULTS: From March 2021 to May 2022, 20 GPs were included in the study. Defining a mUTI was perceived as a diagnostic challenge. A diagnosis based on clinical evidence alone was insufficient and complementary tests were required. For GPs: 'male cystitis does not exist'. A mUTI was considered an unusual disease that could reveal an underlying condition. GPs considered fluoroquinolones to be 'potent' antibiotics and treated all patients with the same 14-day course. GPs implemented improvement strategies for antibiotic stewardship and followed the guidelines using a computerised decision support system. CONCLUSIONS: GPs' experiences of mUTIs are limited due to low exposure and variable clinical presentations in primary care, representing a diagnostic and therapeutic challenge. In order to modify GPs' antibiotic prescribing behaviours, a paradigm shift in the guidelines will need to be proposed.KEY MESSAGESDefining a male urinary tract infection represents a diagnostic challenge for GPs.A diagnosis based on clinical evidence alone is insufficient and complementary tests are required.A male urinary tract infection is an unusual disease in primary care and suggests a more serious underlying condition.

A novel nomogram based on inflammation biomarkers for predicting radiation cystitis in patients with local advanced cervical cancer.

BACKGROUNDS: Platelet-to-albumin ratio (PAR) is a new systemic inflammatory prognostic indicator associated with many inflammatory diseases. However, its role in radiation cystitis (RC) is obscure. This study aimed to explore whether PAR could be used as an effective parameter for predicting the RC risk in local advanced cervical cancer (CC) treated with radiotherapy. METHODS: A total of 319 local advanced CC patients who received radical radiotherapy at Fujian Cancer Hospital were enrolled between December 2018 and January 2021. Demographics and clinical parameters were retrospectively analyzed. Univariate and multivariate analyses were used to identify the risk factors for RC. Backward and stepwise regression was applied to construct two monograms-one with primary significant factors and the other with extra inflammatory biomarkers. A DeLong test was applied to compare the prediction abilities of two nomograms. Calibration curves and decision curve analysis (DCA) evaluated its prediction consistency, discrimination ability, and clinical net benefit. RESULTS: Univariate analysis showed that age, tumor size, stage, total radiation dose, pelvic radiation dose, Systemic Immune-Inflammation Index (SII), platelet-to-lymphocyte ratio (PLR), and PAR were significantly associated with RC occurrence (all p < 0.05). Multivariate analyses indicated that age, tumor size, stage, total radiation dose, and PAR were independent factors (all p < 0.05). Then, the area under curve (AUC) value of the nomogramSII+PAR was higher (AUC = 0.774) compared to that of the baseline nomogram (AUC = 0.726) (pDelong = 0.02). Also, the five-cross validation confirmed the stability of the nomogramSII+PAR. Moreover, the calibration curve and DCA exhibited the nomograms' good prediction consistency and clinical practicability. CONCLUSIONS: PAR and SII could be valued for CC patients who are treated with radiation therapy. The nomogram based on PAR and SII could stratify patients who need extra intervention and nursing care to prevent bladder radiation damage and improve patients' quality of life.

[The management and treatment of cystitis: same challenges, new strategies]. / Prise en charge et traitement des cystites : mêmes défis, nouvelles stratégies.

Cystitis is an inflammation of the bladder that is most often caused by bacterial infection and is the most common urinary tract infection. This lower urinary tract infection (UTI) is one of the most frequently encountered infections in women in outpatient practice. The concept of the urobiome, the microbiome of the urinary tract, has recently emerged and has improved our comprehension of the physiopathology of UTI. Recent studies have highlighted the potential limits of additional examinations used in our clinical practice. The emergence of delayed therapy is a novelty in the treatment of lower UTI; it likely allows for an overall reduction in antibiotic consumption while remaining an effective treatment. Alternatives to antibiotic treatment exist but most have yet to be tested in sufficiently powered randomized trials.

La cystite est une inflammation de la vessie, le plus souvent provoquée par une infection bactérienne, et est l'infection urinaire (IU) la plus fréquente. Par ailleurs, l'infection urinaire basse (IUB) est l'infection la plus souvent rencontrée chez la femme dans la pratique ambulatoire. L'étude de l'urobiome, le microbiome du tractus urinaire, a permis des avancées dans la compréhension de la physiopathologie des IU. Des études ont mis en avant les possibles limites des examens complémentaires utilisés dans notre pratique clinique. L'émergence du traitement différé (Delayed Therapy) est une nouveauté dans le traitement des IUB, dans le sens où il permettrait de diminuer la consommation d'antibiotiques tout en restant un traitement efficace. Les alternatives au traitement antibiotique existent, mais la majorité doit encore être validée dans des essais randomisés de meilleure qualité.

[Immunological parameters of urine in differential diagnosis of chronic recurrent cystitis in women].

INTRODUCTION: Chronic recurrent cystitis (CRC) is a complex multifaceted problem of modern uroinfectology. OBJECTIVE: To study the immunological parameters of urine in patients with chronic recurrent cystitis depending on the etiological factor. MATERIALS AND METHODS: The prospective study included 71 patients aged 20-45 years who had previously been diagnosed with recurrent lower urinary tract infection: chronic recurrent cystitis (CRC) during an exacerbation period. Based on the results of bacteriological and PCR studies of urine, scraping of the urethra and vagina, depending on the dominant etiological factor, the patients were divided into three groups: group 1 (n=30) - with papillomavirus CRC (PVI-CRC), group 2 (n=30) - with bacterial CRC (B - CRC), group 3 (n=11) - with candida CRC (C - CRC). Analysis of the assessment of immunological parameters of urine was carried out using an enzyme-linked immunosorbent assay (ELISA-BEST). RESULTS: Based on the results of an immunological study of urine in the study groups, characteristic specific changes in the level of interleukins and interferons were identified, which made it possible to determine a protocol for the differential diagnosis of CRC. CONCLUSIONS: Our study shows the advisability of testing interleukins in urine (IL-1 beta, IL-6, IL-8); these indicators can serve as scoring criteria in the differential diagnosis of CRC of various origins. CONCLUSIONS: , it is reasonable to study the level of IFN-2b and IFN; when identifying the functional inferiority of the IFN system in women with CRC, correction of the IFN system is necessary.

Evaluating ChatGPT ability to answer urinary tract Infection-Related questions.

INTRODUCTION: For the first time, the accuracy and proficiency of ChatGPT answers on urogenital tract infection (UTIs) were evaluated. METHODS: The study aimed to create two lists of questions: frequently asked questions (FAQs, public-based inquiries) on relevant topics, and questions based on guideline information (guideline-based inquiries). ChatGPT responses to FAQs and scientific questions were scored by two urologists and an infectious disease specialist. Quality and reliability of all ChatGPT answers were checked using the Global Quality Score (GQS). The reproducibility of ChatGPT answers was analyzed by asking each question twice. RESULTS: All in all, 96.2 % of FAQs (75/78 inquiries) related to UTIs were correctly and adequately answered by ChatGPT, and scored GQS 5. None of the ChatGPT answers were classified as GQS 2 and GQS 1. Moreover, FAQs about cystitis, urethritis, and epididymo-orchitis were answered by ChatGPT with 100 % accuracy (GQS 5). ChatGPT answers for EAU urological infections guidelines showed that 61 (89.7 %), 5 (7.4 %), and 2 (2.9 %) ChatGPT responses were scored GQS 5, GQS 4, and GQS 3, respectively. None of the ChatGPT responses for EAU urological infections guidelines were categorized as GQS 2 and GQS 1. Comparison of mean GQS values of ChatGPT answers for FAQs and EAU urological guideline questions showed that ChatGPT was similarly able to respond to both question groups (p = 0.168). The ChatGPT response reproducibility rate was highest for the FAQ subgroups of cystitis, urethritis, and epididymo-orchitis (100 % for each subgroup). CONCLUSION: The present study showed that ChatGPT gave accurate and satisfactory answers for both public-based inquiries, and EAU urological infection guideline-based questions. Reproducibility of ChatGPT answers exceeded 90% for both FAQs and scientific questions.

Misdiagnosis of eosinophilic cystitis: A case report and literature review.

RATIONALE: Eosinophilic cystitis (EC) is a rare and specific transmural inflammatory disease in clinic. At present, its etiology is unknown, its clinical manifestations are diverse, and its auxiliary examination lacks specificity, so it is easy to be missed or misdiagnosed in clinical practice. PATIENT CONCERNS: A 72-year-old male patient with symptoms of lower urinary tract obstruction accompanied by hematuria was diagnosed with benign prostatic hyperplasia with bleeding by B-ultrasound and urinary CT examination. After being treated with catheterization, anti-infection and hemostasis, he was selectively treated with transurethral resection of prostate, but he saw a pattern mass on the right back wall of the bladder during the operation. Considering bladder tumor, he removed the lesion and gave pirarubicin for bladder perfusion. However, the postoperative pathological result was EC. DIAGNOSIS: The diagnosis of EC can only rely on pathological examination, and the accurate and positive rate of biopsy can be improved by obtaining muscle tissue as much as possible at the same time of multi-point biopsy. INTERVENTION: Prednisone and cetirizine were given orally after transurethral resection of lesions, and tamsulosin and finasteride were given regularly to treat benign prostatic hyperplasia. OUTCOMES: No recurrence and abnormal urination were found during the follow-up for half a year, and the upper urinary tract function was normal. LESSONS: The clinical manifestations of EC are atypical, the laboratory examination and imaging examination are not specific, and it is difficult to make a definite diagnosis before operation. The diagnosis depends on pathological examination. Transurethral resection of the lesion can obviously improve the positive rate of biopsy while completely removing the lesion, and the combined drug treatment can achieve satisfactory results in a short period of time. Active follow-up after operation is very important to identify the recurrence of the disease and prevent the upper urinary tract function from being damaged.

Risk factors for mortality in children with hemorrhagic cystitis after hematopoietic transplant.

INTRODUCTION: Hemorrhagic cystitis (HC) is a devastating complication of bone marrow (BMT) and stem cell transplant (SCT). Much of the literature has focused on exclusively adult patient populations, with limited evidence regarding risk factors for mortality and morbidity among pediatric HC patients. OBJECTIVE: To examine factors associated with all-cause mortality in children with HC after BMT/SCT. METHODS: The Pediatric Health Information System database was queried for patients with ICD-9/10 codes for hematopoietic transplant and gross hematuria, hematuria unspecified, or cystitis with hematuria. Multivariable logistic regression examined association of medical and surgical interventions frequently employed for hemorrhagic cystitis with mortality and genitourinary morbidity, defined as having received instillation of any bladder medication or having undergone any genitourinary procedure. RESULTS: A total of 811 patients, mean age of 12.4 years and 62% male, were included. Primary diagnosis included 388 (49%) leukemia/lymphoma, 182 (22%) blood dyscrasia, 99 (12%) solid organ tumor, 27 (3%) metabolic disease, 115 (14%) unknown. Transplant type included 377 (46%) bone marrow, 329 (41%) stem cell, 105, and (13%) unknown. Performing any bladder instillation (p < 0.0001) or any type of GU procedure (p < 0.0001) was significantly associated with mortality. On multivariate analysis, dialysis (OR = 10.7, 95% CI = 5.7-20.2), genitourinary morbidity (OR = 4, 95% CI = 2.2-6.8) and intravenous cidofovir (OR = 2.0, 95% CI = 1.2-3.3) were significantly associated with all cause mortality. Having an underlying diagnosis of blood dyscrasia was protective against mortality (OR = 0.425, CI = 0.205-0.88). DISCUSSION: In this large retrospective study evaluating factors associated with mortality in children with HC, all cause mortality was found to be 11%. This is probably an underrepresentation of true mortality in this population, as many patients discharged from the hospital likely die outside the hospital at home or hospice care. This study supports the current literature that invasive GU procedures are not associated with increased survival in patients with severe HC. This study is limited by retrospective use of a billing database that has the potential for errors in data entry and missing data. Patients who were discharged from the hospital were not captured by the PHIS which only collects data from inpatient stays. CONCLUSIONS: Patients with HC who received dialysis, intravenous cidofovir, or underwent GU intervention had significantly higher all-cause mortality. High grade HC is a marker of disease severity and efforts should be made by urologists and oncologists to maximize quality of life and limit futile treatments in this patient population.

Risk factors for hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation in a letermovir-exposed CMV-free population receiving PTCy.

Hemorrhagic cystitis (HC) is a highly impacting complication in allogeneic hematopoietic stem cell transplantation (HSCT), occurring in 12%-37% of patients. The impact of transplant- and patient-specific variables has been described, with a possible role for JCV and BKV, which may be cooperating with cytomegalovirus (CMV). Here, we analyze 134 letermovir-exposed, CMV-free patients, treated with the same cyclophosphamide-based graft-versus-host disease (GVHD) prophylaxis, describing risk factors for HC. The overall incidence of HC was 23%. Patients with HLA mismatched transplant, higher comorbidity score, and receiving three alkylating agents with TBF (thiotepa, busulfan, and fludarabine) conditioning regimen had a higher risk of HC in multivariate analysis (OR: 4.48, 6.32, and 1.32, respectively). A HC-score including male gender, TBF conditioning, and HLA-mismatch stratifies the risk of HC in the first 100 days after HSCT. The role of BKV and JCV was not highly impacting in those patients, suggesting a possible synergistic effect between CMV and JCV in causing HC. HC can be interpreted as the combination of patient-related factors, chemotherapy-related toxicities-especially due to alkylating agents-and immunological elements.

No viable bacterial communities reside in the urinary bladder of cats with feline idiopathic cystitis.

Urinary microbial diversities have been reported in humans according to sex, age and clinical status, including painful bladder syndrome/interstitial cystitis (PBS/IC). To date, the role of the urinary microbiome in the pathogenesis of PBS/IC is debated. Feline idiopathic cystitis (FIC) is a chronic lower urinary tract disorder affecting cats with similarities to PBS/IC in women and represents an important problem in veterinary medicine as its aetiology is currently unknown. In this study, the presence of a bacterial community residing in the urinary bladder of cats with a diagnosis of FIC was investigated. Nineteen cats with clinical signs and history of FIC and without growing bacteria in standard urine culture were included and urine collected with ultrasound-guided cystocentesis. Bacterial community was investigated using a culture-dependent approach consisted of expanded quantitative urine culture techniques and a culture-independent approach consisted of 16S rRNA NGS. Several methodological practices were adopted to both avoid and detect any contamination or bias introduced by means of urine collection and processing which could be relevant due to the low microbial biomass environment of the bladder and urinary tract, including negative controls analysis. All the cats included showed no growing bacteria in the urine analysed. Although few reads were originated using 16S rRNA NGS, a comparable pattern was observed between urine samples and negative controls, and no taxa were confidently classified as non-contaminant. The results obtained suggest the absence of viable bacteria and of bacterial DNA of urinary origin in the urinary bladder of cats with FIC.

Analysis of early clinical signs and risk factors for severe hemorrhagic cystitis after stem cell transplantation in children.

INTRODUCTION: To analyze the characteristics of early clinical symptoms of hemorrhagic cystitis (HC) after hematopoietic stem cell transplantation (HSCT) and the risk factors of severe HC. METHODS: We retrospectively analyzed 77 children with post-HSCT HC treated at our hospital between June 2013 and June 2021. Clinical characteristics were collected and catalogued. RESULTS: Among the children with urinary tract irritation symptoms (UTIS) as the first symptom, symptoms appeared earlier than hematuria symptoms (28 day vs. 31 day, p = 0.027), and the time progressing to severe HC was significantly longer in these children (12 day vs. 7 day, p = 0.038), but there was no significant difference in the number of participants (57.8% vs. 59.4%, p = 0.889). BK polyomavirus (BKV) infection was an independent risk factor (hazard ratio [HR] = 2.782, p = 0.035) for severe HC, which was also positively associated with multi-viral infection (HR = 2.215, p = 0.020). CONCLUSIONS: In HC children, when the first urinary tract symptom was UTIS, it appeared earlier than hematuria, and the time of progression to severe HC was significantly longer, suggesting that we still need more aggressive treatment for these children to prevent the worsening of symptoms. The severity of HC was positively correlated with BKV infection and multiple infections.