Predictive Models for Assessing Patients' Response to Treatment in Metastatic Prostate Cancer: A Systematic Review.

Background and objective: The treatment landscape of metastatic prostate cancer (mPCa) has evolved significantly over the past two decades. Despite this, the optimal therapy for patients with mPCa has not been determined. This systematic review identifies available predictive models that assess mPCa patients' response to treatment. Methods: We critically reviewed MEDLINE and CENTRAL in December 2022 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Only quantitative studies in English were included with no time restrictions. The quality of the included studies was assessed using the PROBAST tool. Data were extracted following the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews criteria. Key findings and limitations: The search identified 616 citations, of which 15 studies were included in our review. Nine of the included studies were validated internally or externally. Only one study had a low risk of bias and a low risk concerning applicability. Many studies failed to detail model performance adequately, resulting in a high risk of bias. Where reported, the models indicated good or excellent performance. Conclusions and clinical implications: Most of the identified predictive models require additional evaluation and validation in properly designed studies before these can be implemented in clinical practice to assist with treatment decision-making for men with mPCa. Patient summary: In this review, we evaluate studies that predict which treatments will work best for which metastatic prostate cancer patients. We found that existing studies need further improvement before these can be used by health care professionals.

Clinical Characterization of Patients Diagnosed with Prostate Cancer and Undergoing Conservative Management: A PIONEER Analysis Based on Big Data.

BACKGROUND: Conservative management is an option for prostate cancer (PCa) patients either with the objective of delaying or even avoiding curative therapy, or to wait until palliative treatment is needed. PIONEER, funded by the European Commission Innovative Medicines Initiative, aims at improving PCa care across Europe through the application of big data analytics. OBJECTIVE: To describe the clinical characteristics and long-term outcomes of PCa patients on conservative management by using an international large network of real-world data. DESIGN, SETTING, AND PARTICIPANTS: From an initial cohort of >100 000 000 adult individuals included in eight databases evaluated during a virtual study-a-thon hosted by PIONEER, we identified newly diagnosed PCa cases (n = 527 311). Among those, we selected patients who did not receive curative or palliative treatment within 6 mo from diagnosis (n = 123 146). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patient and disease characteristics were reported. The number of patients who experienced the main study outcomes was quantified for each stratum and the overall cohort. Kaplan-Meier analyses were used to estimate the distribution of time to event data. RESULTS AND LIMITATIONS: The most common comorbidities were hypertension (35-73%), obesity (9.2-54%), and type 2 diabetes (11-28%). The rate of PCa-related symptomatic progression ranged between 2.6% and 6.2%. Hospitalization (12-25%) and emergency department visits (10-14%) were common events during the 1st year of follow-up. The probability of being free from both palliative and curative treatments decreased during follow-up. Limitations include a lack of information on patients and disease characteristics and on treatment intent. CONCLUSIONS: Our results allow us to better understand the current landscape of patients with PCa managed with conservative treatment. PIONEER offers a unique opportunity to characterize the baseline features and outcomes of PCa patients managed conservatively using real-world data. PATIENT SUMMARY: Up to 25% of men with prostate cancer (PCa) managed conservatively experienced hospitalization and emergency department visits within the 1st year after diagnosis; 6% experienced PCa-related symptoms. The probability of receiving therapies for PCa decreased according to time elapsed after the diagnosis.

Teaching Adolescents With Type 1 Diabetes Self-Compassion (TADS) to Reduce Diabetes Distress: Protocol for a Randomized Controlled Trial.

BACKGROUND: Adolescents living with type 1 diabetes (T1D) often experience diabetes distress (DD), a construct distinct from depression or anxiety that refers to the negative emotions that arise from living with and managing diabetes. Self-compassion, which involves being open to one's own suffering and treating oneself with the same care one would show to loved ones, is associated with better psychological and clinical outcomes among individuals with T1D. Self-compassion is a skill that can be taught and therefore represents an opportunity for intervention. OBJECTIVE: The overall aim of this study is to assess the effectiveness of a web-based mindful self-compassion for teens (MSC-T) intervention on improving DD, anxiety, depression, diabetes-related disordered eating, and suicidal ideation experienced by youth with T1D (aged between 12 and 17 years) compared with a waitlist control group (standard of care). We will also explore (1) if the effect of the MSC-T intervention changes over time, (2) if the MSC-T intervention has a positive impact on measures of glycemic control, and (3) if the effect of the MSC-T intervention differs based on self-reported gender. METHODS: We will conduct a single-center, parallel-group randomized controlled trial of 140 adolescents with T1D followed for 12 months. Participants will be randomly allocated (using hidden allocation) in a 1:1 ratio to either the MSC-T intervention or the waitlist control group. Our primary outcome is DD, as measured by the Problem Areas in Diabetes-Teen (PAID-T) version at 3 months. Secondary outcomes, assessed at 3 and 12 months, include anxiety (Generalized Anxiety Disorder 7-item [GAD-7] scale), depression (Patient Health Questionnaire-9 [PHQ-9]), diabetes-related disordered eating (Diabetes Eating Problem Survey-Revised [DEPS-R] version), and suicidal ideation (using 1 question from the PHQ-9). RESULTS: Study recruitment began in October 2022 and was completed in March 2023, with a total of 141 participants enrolling. Data collection will be ongoing until March 2024. The first results are expected in June 2024. CONCLUSIONS: This study will be the first randomized trial to assess the effectiveness of the web-based MSC-T intervention on adolescents with T1D. Given that adolescence is a period where individuals are typically required to assume more responsibility for their diabetes care, providing adolescents with the tools they need to better manage the stress that often accompanies T1D management is paramount. TRIAL REGISTRATION: ClinicalTrials.gov NCT05463874; https://clinicaltrials.gov/study/NCT05463874. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53935.

What Are the Short-term Benefits and Potential Harms of Therapeutic Modalities for the Management of Overactive Bladder Syndrome in Women? A Review of Evidence Under the Auspices of the European Association of Urology, Female Non-neurogenic Lower Urinary Tract Symptoms Guidelines Panel.

CONTEXT: Overactive bladder syndrome (OAB) is highly prevalent among women and has a negative impact on their quality of life. The current available treatments for OAB symptoms include conservative, pharmacological, or surgical modalities. OBJECTIVE: To provide an updated contemporary evidence document regarding OAB treatment options and determine the short-term effectiveness, safety, and potential harms of the available treatment modalities for women with OAB syndrome. EVIDENCE ACQUISITION: The Medline, Embase, and Cochrane controlled trial databases and clinicaltrial.gov were searched for all relevant publications up to May 2022. The risk of bias assessment followed the recommended tool in the Cochrane Handbook for Systematic Reviews of Interventions, and quality of evidence was assessed using the modified Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. A meta-analysis was performed where appropriate. EVIDENCE SYNTHESIS: Antimuscarinics and beta-3 agonists were significantly more effective than placebo across most outcomes, with beta-3 agonists being more effective at reducing nocturia episodes and antimuscarinics causing significantly higher adverse events. Onabotulinumtoxin-A (Onabot-A) was more effective than placebo across most outcomes, but with significantly higher rates of acute urinary retention/clean intermittent self-catheterisation (six to eight times) and urinary tract infections (UTIs; two to three times). Onabot-A was also significantly better than antimuscarinics in the cure of urgency urinary incontinence (UUI) but not in the reduction of mean UUI episodes. Success rates of sacral nerve stimulation (SNS) were significantly higher than those of antimuscarinics (61% vs 42%, p = 0.02), with similar rates of adverse events. SNS and Onabot-A were not significantly different in efficacy outcomes. Satisfaction rates were higher with Onabot-A, but with a higher rate of recurrent UTIs (24% vs 10%). SNS was associated with 9% removal rate and 3% revision rate. CONCLUSIONS: Overactive bladder is a manageable condition, with first-line treatment options including antimuscarinics, beta-3 agonists, and posterior tibial nerve stimulation. Second-line options include Onabot-A bladder injections or SNS. The choice of therapies should be guided by individual patient factors. PATIENT SUMMARY: Overactive bladder is a manageable condition. All patients should be informed and advised on conservative treatment measures in the first instance. The first-line treatment options for its management include antimuscarinics or beta-3 agonists medication, and posterior tibial nerve stimulation procedures. The second-line options include onabotulinumtoxin-A bladder injections or sacral nerve stimulation procedure. The therapy should be chosen based on individual patient factors.

Systematic Review of the Incidence of and Risk Factors for Urothelial Cancers and Renal Cell Carcinoma Among Patients with Haematuria.

CONTEXT: The current impact of haematuria investigations on health care organisations is significant. There is currently no consensus on how to investigate patients with haematuria. OBJECTIVE: To evaluate the incidence of bladder cancer, upper tract urothelial carcinoma (UTUC), and renal cell carcinoma (RCC) among patients undergoing investigation for haematuria and identify any risk factors for bladder cancer, UTUC, and RCC (BUR). EVIDENCE ACQUISITION: Medline, Embase, and Cochrane controlled trials databases and ClinicalTrials.gov were searched for all relevant publications from January 1, 2000 to June 2021 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Prospective, retrospective, and cross-sectional studies with a minimum population of 50 patients with haematuria were considered for the review. EVIDENCE SYNTHESIS: A total of 44 studies were included. The total number of participants was 229701. The pooled incidence rate for urothelial bladder cancer was 17% (95% confidence interval [CI] 14-20%) for visible haematuria (VH) and 3.3% (95% CI 2.45-4.3%) for nonvisible haematuria (NVH). The pooled incidence rate for RCC was 2% (95% CI 1-2%) for VH and 0.58% (95% CI 0.42-0.77%) for NVH. The pooled incidence rate for UTUC was 0.75% (95% CI 0.4-1.2%) for VH and 0.17% (95% CI 0.081-0.299%) for NVH. On sensitivity analysis, the proportions of males (risk ratio [RR] 1.14, 95% CI 1.10-1.17 for VH; 1.54, 95% CI 1.34-1.78 for NVH; p < 0.00001; moderate certainty evidence) and individuals with a smoking history (RR 1.41, 95% CI 1.24-1.61 for VH; 1.53, 95% CI 1.36-1.72 for NVH; p < 0.00001; moderate certainty evidence) appeared to be higher in BUR than in non-BUR groups. CONCLUSIONS: Male gender and smoking history are risk factors for BUR cancer in haematuria, with bladder cancer being the commonest cancer. The incidence of RCC and UTUC in NVH is low. The review serves as a reference standard for future policy-making on investigation of haematuria by global organisations. PATIENT SUMMARY: Our review shows that male gender and smoking history are risk factors for cancers of the bladder, kidney, and ureter. The review also provides information on the proportion of patients who have cancer when they have blood in their urine (haematuria) and will allow policy-makers to decide on the most appropriate method for investigating haematuria in patients.

Benefits and Harms of Conservative, Pharmacological, and Surgical Management Options for Women with Bladder Outlet Obstruction: A Systematic Review from the European Association of Urology Non-neurogenic Female LUTS Guidelines Panel.

CONTEXT: While the management of bladder outlet obstruction (BOO) in men has been a topic of several systematic reviews and meta-analyses, no such evidence base exists for female BOO. OBJECTIVE: The aim of this systematic review was to evaluate the benefits and harms of therapeutic interventions for the management of BOO in women. EVIDENCE ACQUISITION: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. The study protocol was registered with PROSPERO (CRD42020183839). A systematic literature search was performed and updated by a research librarian in May 2021. The study population consisted of adult female patients diagnosed with BOO, who underwent treatment. EVIDENCE SYNTHESIS: Out of 6344 records, we identified 33 studies enrolling 1222 participants, of which only six randomized controlled trials (RCTs) were found. One placebo-controlled crossover randomized trial assessed the role of baclofen in 60 female patients with dysfunctional voiding. The trial met its primary endpoint with a significantly greater decrease in the number of voids per day in the baclofen group (-5.53 vs -2.70; p = 0.001). The adverse events were mild and comparable in both groups (25% vs 20%). One placebo-controlled crossover randomized trial assessed the role of sildenafil in 20 women with Fowler's syndrome. There were significant improvements from baseline in maximum urinary flow rate (Qmax), International Prostate Symptom Score (IPSS), and postvoid residual (PVR), but with no statistically significant difference when compared with placebo. In a large RCT including 197 female patients with functional BOO, the alpha-blocker alfuzosin significantly improved IPSS, Qmax, and PVR compared with baseline, but the differences were not statistically significant compared with the placebo group. Several small single-arm prospective series reported improvement of BOO-related symptoms and voiding parameters with urethroplasty, sling revision, urethral dilation, vaginal pessary, and pelvic organ prolapse repair. CONCLUSIONS: Evidence to support the use of conservative, pharmacological, and surgical treatments for BOO is scarce. PATIENT SUMMARY: According to the present systematic review of the literature, evidence to support the use of conservative, pharmacological, and surgical treatments for either anatomical or functional bladder outlet obstruction is scarce.

Stable cross-linked lyotropic gyroid mesophases from single-head/single-tail cross-linkable monomers.

A single-head/single-tail surfactant with a polymerizable group at each end is presented as a new simplified motif for intrinsically cross-linkable, gyroid-phase lyotropic mesogens. The resulting nanoporous polymer networks exhibit excellent structural stability in various solvents and are capable of molecular size discrimination.

Effects of structural modification of (alkyldiene-imidazolium bromide)-based gemini monomers on the formation of the lyotropic bicontinuous cubic phase.

Seven homologues of an amphiphilic gemini monomer were synthesized and screened for the ability to form a bicontinuous cubic (Q) lyotropic liquid crystal phase. Four of these homologues form a Q phase with glycerol or water that can be cross-linked with retention of the nanoporous structure, with one exhibiting a well-ordered Q phase with a wider phase window than the parent monomer.

Rapid Fabrication by Lyotropic Self-Assembly of Thin Nanofiltration Membranes with Uniform 1 Nanometer Pores.

Nanostructured materials with precisely defined and water-bicontinuous 1-nm-scale pores are highly sought after as advanced materials for next-generation nanofiltration membranes. While several self-assembled systems appear to satisfy this need, straightforward fabrication of such materials as submicron films with high-fidelity retention of their ordered nanostructure represents a nontrivial challenge. We report the development of a lyotropic liquid crystal mesophase that addresses the aforementioned issue. Films as thin as ∼200 nm are prepared on conventional support membranes using solution-based methods. Within these films, the system is composed of a hexagonally ordered array of ∼3 nm diameter cylinders of cross-linked polymer, embedded in an aqueous medium. The cylinders are uniformly oriented in the plane of the film, providing a transport-limiting dimension of ∼1 nm, associated with the space between the outer surfaces of nearest-neighbor cylinders. These membranes exhibit molecular weight cutoffs of ∼300 Da for organic solutes and are effective in rejecting dissolved salts, and in particular, divalent species, while exhibiting water permeabilities that rival or exceed current state-of-the-art commercial nanofiltration membranes. These materials have the ability to address a broad range of nanofiltration applications, while structure-property considerations suggest several avenues for potential performance improvements.