Emerging molecular mechanisms and genetic targets for developing novel therapeutic strategies for treating bladder diseases

Bladder diseases affect millions of patients worldwide and compromise their quality of life with a substantial economic impact. The not fully understood aetiologies of bladder diseases limit the current diagnosis and therapeutic options to primarily symptomatic treatment. In addition, bladder targeted drug delivery is challenging due to its unique anatomical features and its natural physiological function of urine storage and frequent voiding. Therefore, current treatment options often fail to provide a highly effective, precisely targeted and long-lasting treatment. With the growing maturity of gene therapy, comprehensive studies are needed to provide a better understanding of the molecular mechanisms underpinning bladder diseases and help to identify novel gene therapeutic targets and biomarkers for treating bladder diseases. In this review, molecular mechanisms involved in pathology of bladder cancer, interstitial cystitis and overactive bladder syndrome are reviewed, with focus on establishing potential novel treatment options. Proposed novel therapies, including gene therapy combined with nanotechnology, localised drug delivery by nanoparticles, and probiotics, are discussed in regard to their safety profiles, efficacy, treatment lenght, precise targeting, and in comparison to conventional treatment methods

The Prevalence and Indications of Intravenous Rehydration Therapy in Hospital Settings: A Systematic Review

(1) Objective: We performed a systematic review to explore the prevalence of intravenous (IV) rehydration therapy in hospital settings, and we assessed it by patient groups and populations. (2) Methods: A systematic review of major databases and grey literature was undertaken from inception to 28 March 2022. Studies reporting prevalence of IV rehydration therapy in a hospital setting were identified. The data were synthesised in a narrative approach. (3) Results: Overall, 29 papers met the inclusion criteria. The prevalence of IV rehydration therapy in paediatric patients ranged from 4.5% (hospitalised with diarrhoea and dehydration) to 100% (admitted to the emergency department with mild to moderate dehydration caused by viral gastroenteritis), and in adults this ranged from 1.5% (had single substance ingestion of modafinil) to 100% (hospitalised with hypercalcemia). The most common indication for IV rehydration therapy in paediatric patients was dehydration due to fluid loss from the gastrointestinal tract. Other causes included malnutrition, neuromuscular disease, bronchiolitis, and influenza. In adults, indications for IV rehydration therapy were much more diverse: fever, diarrhoea, drug intoxication, hypercalcemia, cancer, and postural tachycardia syndrome; (4) Conclusions: This systematic review showed that IV rehydration therapy in paediatric patients is often used to treat dehydration and diarrhoea, while in adults it has a broader spectrum of use. While IV rehydration therapy is important in correcting fluid problems and electrolyte status, the maintenance fluid prescribing practices vary considerably, and guidelines are scarce

Comparative safety of mRNA COVID-19 vaccines to influenza vaccines: A pharmacovigilance analysis using WHO international database.

Funder: New faculty research seed money grant of Yonsei University College of Medicine for 2021 (2021-32-0049).Two messenger RNA (mRNA) vaccines developed by Pfizer-BioNTech and Moderna are being rolled out. Despite the high volume of emerging evidence regarding adverse events (AEs) associated with the COVID-19 mRNA vaccines, previous studies have thus far been largely based on the comparison between vaccinated and unvaccinated control, possibly highlighting the AE risks with COVID-19 mRNA vaccination. Comparing the safety profile of mRNA vaccinated individuals with otherwise vaccinated individuals would enable a more relevant assessment for the safety of mRNA vaccination. We designed a comparative safety study between 18 755 and 27 895 individuals who reported to VigiBase for adverse events following immunization (AEFI) with mRNA COVID-19 and influenza vaccines, respectively, from January 1, 2020, to January 17, 2021. We employed disproportionality analysis to rapidly detect relevant safety signals and compared comparative risks of a diverse span of AEFIs for the vaccines. The safety profile of novel mRNA vaccines was divergent from that of influenza vaccines. The overall pattern suggested that systematic reactions like chill, myalgia, fatigue were more noticeable with the mRNA COVID-19 vaccine, while injection site reactogenicity events were more prevalent with the influenza vaccine. Compared to the influenza vaccine, mRNA COVID-19 vaccines demonstrated a significantly higher risk for a few manageable cardiovascular complications, such as hypertensive crisis (adjusted reporting odds ratio [ROR], 12.72; 95% confidence interval [CI], 2.47-65.54), and supraventricular tachycardia (adjusted ROR, 7.94; 95% CI, 2.62-24.00), but lower risk of neurological complications such as syncope, neuralgia, loss of consciousness, Guillain-Barre syndrome, gait disturbance, visual impairment, and dyskinesia. This study has not identified significant safety concerns regarding mRNA vaccination in real-world settings. The overall safety profile patterned a lower risk of serious AEFI following mRNA vaccines compared to influenza vaccines

The role of Vitamin D in the prevention of Coronavirus Disease 2019 infection and mortality

WHO declared SARS-CoV-2 a global pandemic. The present aim was to propose an hypothesis that there is a potential association between mean levels of vitamin D in various countries with cases and mortality caused by COVID-19. The mean levels of vitamin D for 20 European countries and morbidity and mortality caused by COVID-19 were acquired. Negative correlations between mean levels of vitamin D (average 56 mmol/L, STDEV 10.61) in each country and the number of COVID-19 cases/1 M (mean 295.95, STDEV 298.7, and mortality/1 M (mean 5.96, STDEV 15.13) were observed. Vitamin D levels are severely low in the aging population especially in Spain, Italy and Switzerland. This is also the most vulnerable group of the population in relation to COVID-19. It should be advisable to perform dedicated studies about vitamin D levels in COVID-19 patients with different degrees of disease severity

A paradigm shift in the role of NSAIDs in COVID-19: new pathological mechanisms and potential treatment targets

Objectives: The pathogeny of SARS-COV2 infection is currently not well defined. In this paper, we present a new perspective of how the SARS-CoV2 infection can lead to severe cases and potential pathways of preventing such cases. Methods: In the first part, we describe the role of cyclooxigenase 2 and in the second part, we describe the role of hypoxia inducible factor (HIF). Findings: We hypothesize that cyclooxigenase 2 and hypoxia inducible factor with subsequent inflammation and hypoxia can up-regulate each other in a vicious circle of feed-forward that can ultimately lead to “cytokine storm”. Conclusions: Breaking this cycle early potentially will have beneficial effects either by improving oxygenation (oxygen being given earlier in the course of the treatment) or by inhibiting COX-2. We also believe, that the use of COX-2 inhibitors early in the course of the disease can improve the outcome and clinical trial are urgently needed.

Sexual intercourse and sleep in older age: findings from the English Longitudinal Study of Ageing

Objectives: To investigate associations between sexual intercourse and sleep quality and duration, controlling for a range of confounders, in a large, representative sample of older English adults. Methods: Data were from 2,743 men and 2,990 women aged ? 50 years, participating in the English Longitudinal Study of Ageing. Participants reported whether or not they had engaged in sexual activity in the last year, and those who were sexually active reported frequency of intercourse in the past month. Information on sleep disturbance and duration and socio-demographic and health-related covariates was also collected. Findings: Being sexually active was not associated with sleep disturbance or sleep duration. Men who had less frequent intercourse reported greater sleep disturbance than those who reported no sexual intercourse (OR=1.29, 95% CI 1.02-1.65), but had lower odds of reporting longer than optimal sleep duration (OR=0.45, 95% CI 0.24-0.86). Men who engaged in sexual intercourse once a week or more (OR=0.43, 95% CI 0.23-0.80) also had lower odds of long sleep relative to those who reported no sexual intercourse. Women who engaged in more frequent (? once a week) intercourse reported less sleep disturbance than those who reported no sexual intercourse in the last month (OR=0.68, 95% CI 0.53-0.86), and women who reported sexual intercourse once in the past month had lower odds of long sleep (OR=0.51, 95% CI 0.26-0.996). Conclusions: In a population-based sample of older men and women in England, there was inconsistent evidence of an association between sexual activity and sleep disturbance and sleep duration

Urinary incontinence and quality of life: a longitudinal analysis from the English Longitudinal Study of Ageing

Objectives- To explore the longitudinal association between urinary incontinence (UI) and quality of life (QoL) in the English Longitudinal Study on Ageing, a large study of older UK adults with ten years of follow-up. Study design- Cohort study. Main outcomes interest- To determine the presence of UI, participants reported whether they had lost urine beyond their control in the last 12 months. Participants also reported whether UI lasted more than one month, indicating a more chronic problem. QoL was measured using the CASP (control, autonomy, self-realisation and pleasure)-19, with higher values indicating a higher QoL. Results- Of the 8028 participants (mean age: 65.2 years; 56.7% females) included, 1172 reported UI at baseline. No significant differences in CASP-19 score were found at baseline (p = 0.24). In people with UI, a significant decline in CASP-19 score (from 34.3 ± 14.0 at baseline to 30.9 ± 16.1 in wave 7) (p = 0.016) was observed. The results were stronger in men than in women and with a longer duration of UI. Conclusion- UI was associated with poor QoL over ten years of follow-up in a large cohort of UK participants. Our findings further suggest the importance of UI as a potential risk factor for poor QoL

Association of multimorbidity with higher levels of urinary incontinence: a cross-sectional study of 23 089 individuals aged ≥15 years residing in Spain

International audienceBACKGROUND: One can assume a relatively high prevalence of urinary incontinence (UI) in people with multimorbidity. However, literature in this area is scarce. There is a need for further robust research to aid GPs to identify patients at a particular risk for UI, and to initiate the early treatment and multidisciplinary management of this condition. AIM: To examine the association between multimorbidity and UI in 23 089 individuals aged ≥15 years and residing in Spain. DESIGN AND SETTING: This study used data from the Spanish National Health Survey 2017, a cross-sectional sample of 23 089 participants aged ≥15 years residing in Spain (54.1% female; mean [standard deviation] age = 53.4 [18.9] years). METHOD: UI and 30 other physical and mental chronic conditions were self-reported. Multimorbidity was defined as the presence of ≥2 physical and/or mental chronic conditions (excluding UI). Control variables included sex, age, marital status, education, smoking, and alcohol consumption. Multivariable logistic regression analyses were conducted to assess the association between multimorbidity and UI. RESULTS: The prevalence of UI was 5.9% in this sample. UI was more frequent in the presence than in the absence of each one of the 30 chronic conditions (P<0.001). The proportion of people with UI was also higher in the multimorbidity than in the no-multimorbidity group (9.8% versus 0.7%, P<0.001). After adjusting for several potential confounders (that is, sex, age, marital status, education, smoking, and alcohol), there was a significant and positive relationship between multimorbidity and UI (odds ratio = 5.02, 95% confidence interval [CI] = 3.89 to 6.59, P<0.001). CONCLUSION: In this large sample of Spanish individuals aged ≥15 years, suffering from multimorbidity was associated with a significantly higher level of UI

Empagliflozin Use and Fournier’s Gangrene: Case Report and Systematic Literature Review

Background: Fournier’s gangrene (FG) is a rare necrotising soft tissue infection localised in the genital areas with possible dramatic outcomes. Recently, sodium glucose co-transporter-2 (SGLT2) inhibitors were identified as a risk factor. Methods: We present a case report of a 57-year-old female patient with type 2 diabetes mellitus (T2DM) in treatment with empagliflozin which led to the development of FG. Moreover, we performed a systematic review assessing the association between empagliflozin use and FG. Results: The female patient with 15-years treated diabetes presented a massive FG after 6 months from starting empagliflozin. Over the period of two months, she was successfully treated in a low-income setting. The systematic review included two studies with a total of 9915 participants. Although no participant had FG, there was an increased rate of urinary and genital infection in patients treated with empagliflozin compared to those treated with other antidiabetics or placebo. Conclusions: FG should be considered as a possible complication in patients using SGLT2. Patients should be educated to report early signs of genital infection and healthy behaviours as well as a balanced diet should be promoted to aid in the prevention of FG

Clinical Impact of the Predict Prostate Risk Communication Tool in Men Newly Diagnosed with Nonmetastatic Prostate Cancer: A Multicentre Randomised Controlled Trial.

BACKGROUND: Predict Prostate is a freely available online personalised risk communication tool for men with nonmetastatic prostate cancer. Its accuracy has been assessed in multiple validation studies, but its clinical impact among patients has not hitherto been assessed. OBJECTIVE: To assess the impact of the tool on patient decision-making and disease perception. DESIGN, SETTING, AND PARTICIPANTS: A multicentre randomised controlled trial was performed across eight UK centres among newly diagnosed men considering either active surveillance or radical treatment. A total of 145 patients were included between 2018 and 2020, with median age 67 yr (interquartile range [IQR] 61-72) and prostate-specific antigen 6.8 ng/ml (IQR 5.1-8.8). INTERVENTION: Participants were randomised to either standard of care (SOC) information or SOC and a structured presentation of the Predict Prostate tool. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Validated questionnaires were completed by assessing the impact of the tool on decisional conflict, uncertainty, anxiety, and perception of survival. RESULTS AND LIMITATIONS: Mean Decisional Conflict Scale scores were 26% lower in the Predict Prostate group (mean = 16.1) than in the SOC group (mean = 21.7; p = 0.027). Scores on the "support", "uncertainty", and "value clarity" subscales all favoured Predict Prostate (all p < 0.05). There was no significant difference in anxiety scores or final treatment selection between the two groups. Patient perception of 15-yr prostate cancer-specific mortality (PCSM) and overall survival benefit from radical treatment were considerably lower and more accurate among men in the Predict Prostate group (p < 0.001). In total, 57% of men reported that the Predict Prostate estimates for PCSM were lower than expected, and 36% reported being less likely to select radical treatment. Over 90% of patients in the intervention group found it useful and 94% would recommend it to others. CONCLUSIONS: Predict Prostate reduces decisional conflict and uncertainty, and shifts patient perception around prognosis to be more realistic. This randomised trial demonstrates that Predict Prostate can directly inform the complex decision-making process in prostate cancer and is felt to be useful by patients. Future larger trials are warranted to test its impact upon final treatment decisions. PATIENT SUMMARY: In this national study, we assessed the impact of an individualised risk communication tool, called Predict Prostate, on patient decision-making after a diagnosis of localised prostate cancer. Men were randomly assigned to two groups, which received either standard counselling and information, or this in addition to a structured presentation of the Predict Prostate tool. Men who saw the tool were less conflicted and uncertain in their decision-making, and recommended the tool highly. Those who saw the tool had more realistic perception about their long-term survival and the potential impact of treatment upon this. TAKE HOME MESSAGE: The use of an individualised risk communication tool, such as Predict Prostate, reduces patient decisional conflict and uncertainty when deciding about treatment for nonmetastatic prostate cancer. The tool leads to more realistic perceptions about survival outcomes and prognosis.The Urology Foundatio