Patient Perception of Bladder Condition after Treatment with Solifenacin and Tolterodine in Overactive Bladder Patients.

BACKGROUND: Solefinacin and Tolterodine are new generation antimuscarinics claimed to have bladder specific action and less adverse effect like dry mouth. The objective of the study was to compare the improvement in urinary symptoms among patients using solefinacin and tolterodine with overactive bladder symptoms. METHODS: A hospital based cross-sectional comparative study was done for one year duration. All patients with overactive bladder symptoms were included and in every alternate patient's solefinacin and tolterodine were given after taking note of baseline OAB symptoms, PPBC score and UPS score. Participants were followed up after one month and noted improvement in endpoint OAB symptoms. Comparison of baseline to end-point symptoms changes among each group of participants were analyzed for statistical significance. RESULTS: Among 101 participants included in the study, 49 participants were in solefinacin group and 52 participants were in tolterodine group. The end-point comparison of urgency symptoms were improved by 20.1±6.76 (mean ± SD) units in solefinacin group and by 17.0 ± 9.18 units in tolterodine group. Urgency perception score improved to 2.1±0.66 for patients under solefinacin and 2±0.73 for tolterodine. Patient perception of bladder condition (PPBC) showed improvement in solefinacin group by 3.2±1.26 units and in tolteradine by 2.8±1.54 units (p = 0.165). Comparing the patient's perception of treatment outcome, massive improvement was reported by 81.6% of those receiving Solefinacinand 65.4% receiving tolterodine, though not statistically significant ( p = 0.131). CONCLUSIONS: Solefinacin and Tolterodine showed improvement in urinary symptoms, UPS and PPBC. Both showed comparable efficacy without significant superiority over one another.

[Recent updates on the antibacterial clofoctol.] / Recenti aggiornamenti sull'antibatterico clofoctolo.

Due to the worry growing increase in bacterial antibiotic resistance and the scanty availability of new antibiotics, it is highly recommended to use not recently synthesized, but still active molecules. Clofoctol is a synthetic chemotherapeutic agent with a different mechanism of action, as compared with the other antibacterial molecules currently available. By reducing intracellular ATP, clofoctol inhibits the synthesis of bacterial cytoplasmic membrane peptidoglycans, inducing the arrest of cell wall synthesis, thus characterizing the molecule as a "membrane-acting agent". More recently, however, it has been shown that clofoctol is also able to induce apoptosis by inhibiting the translation of intracellular proteins. An important property of clofoctol is the rapidity of the antimicrobial effect, which allows the complete eradication of the pathogen and makes the development of resistance unlikely. Administered rectally, the drug rapidly accumulates in the tissues. Most of the clinical studies conducted on clofoctol concern the treatment of respiratory diseases in children. The drug appears to be more active in upper rather than in lower respiratory tract infections. Tolerability was reported to be good, with a low incidence of side effects.

Rapid and sustainable HPLC method for the determination of uremic toxins in human plasma samples.

Protein-bound uremic toxins, mainly indoxyl sulfate (3-INDS), p-cresol sulfate (pCS), and indole-3-acetic acid (3-IAA) but also phenol (Pol) and p-cresol (pC), are progressively accumulated during chronic kidney disease (CKD). Their accurate measurement in biomatrices is demanded for timely diagnosis and adoption of appropriate therapeutic measures. Multianalyte methods allowing the establishment of a uremic metabolite profile are still missing. Hence, the aim of this work was to develop a rapid and sensitive method based on high-performance liquid chromatography with fluorescence detection for the simultaneous quantification of Pol, 3-IAA, pC, 3-INDS, and pCS in human plasma. Separation was attained in 12 min, using a monolithic C18 column and isocratic elution with acetonitrile and phosphate buffer containing an ion-pairing reagent, at a flow rate of 2 mL min-1. Standards were prepared in plasma and quantification was performed using the background subtraction approach. LOQ values were ≤ 0.2 µg mL-1 for all analytes except for pCS (LOQ of 2 µg mL-1). The method proved to be accurate (93.5-112%) and precise (CV ≤ 14.3%). The multianalyte application of the method, associated to a reduced sample volume (50 µL), a less toxic internal standard (eugenol) in comparison to the previously applied 2,6-dimethylphenol and 4-ethylphenol, and a green extraction solvent (ethanol), resulted in the AGREE score of 0.62 which is in line with the recent trend of green and sustainable analytical chemistry. The validated method was successfully applied to the analysis of plasma samples from control subjects exhibiting normal levels of uremic toxins and CKD patients presenting significantly higher levels of 3-IAA, pC, 3-INDS, and pCS that can be further investigated as biomarkers of disease progression.

A new horizon for the old antibacterial drug clofoctol.

The synthetic antibacterial drug clofoctol (CFT) has long been used to treat respiratory tract infections in Europe. In recent years, the drug was found to target two biologically important proteins, the Cdc7/Dbf4 protein kinase complex and the mRNA-binding protein cold shock domain containing E1 (CSDE1), also known as upstream-of-N-Ras protein (UNR). These interactions are at the origin of the antitumor activity of CFT, recently evidenced in prostate cancer and neuroglioma. Drug-protein binding models provide a structural basis to guide the design of more potent anticancer compounds. A renewed interest in CFT can be anticipated for the treatment of cancers, and possibly Coronavirus 2019 (COVID-19).

2,6-Diisobornyl-4-Methylphenol Reduces Postishemic Myocardium Remodeling in Delayed Period after Ischemia/Reperfusion in Rats.

2,6-Diisobornyl-4-methylphenol (Dibornol, 10 mg/kg intragastrically daily for 5 days after myocardial ischemia/reperfusion) 1.5-fold increased rat survival during the acute post-infarction period in comparison with the control group. In survivors, Dibornol reliably prevented post-ischemic progression of heart failure in the delayed post-infarction period (30 days after ischemia/reperfusion), which was seen from an increase in the left-ventricular developed pressure by 22%, left-ventricular contractility index by 19%, and +dP/dt by 34%. Left-ventricular end-diastolic pressure was by 39% lower than in control animals. Morphological study of heart sections from control group animals showed that Dibornol reduced the area of post-ischemic myocardial damage in the delayed period after ischemia/reperfusion to 3±1% (vs 18±2% in the control group).

The Natural Metabolite 4-Cresol Improves Glucose Homeostasis and Enhances ß-Cell Function.

Exposure to natural metabolites contributes to the risk of cardiometabolic diseases (CMDs). Through metabolome profiling, we identify the inverse correlation between serum concentrations of 4-cresol and type 2 diabetes. The chronic administration of non-toxic doses of 4-cresol in complementary preclinical models of CMD reduces adiposity, glucose intolerance, and liver triglycerides, enhances insulin secretion in vivo, stimulates islet density and size, and pancreatic ß-cell proliferation, and increases vascularization, suggesting activated islet enlargement. In vivo insulin sensitivity is not affected by 4-cresol. The incubation of mouse isolated islets with 4-cresol results in enhanced insulin secretion, insulin content, and ß-cell proliferation of a magnitude similar to that induced by GLP-1. In both CMD models and isolated islets, 4-cresol is associated with the downregulated expression of the kinase DYRK1A, which may mediate its biological effects. Our findings identify 4-cresol as an effective regulator of ß-cell function, which opens up perspectives for therapeutic applications in syndromes of insulin deficiency.

Potassium channel activity controls breast cancer metastasis by affecting ß-catenin signaling.

Potassium ion channels are critical in the regulation of cell motility. The acquisition of cell motility is an essential parameter of cancer metastasis. However, the role of K+ channels in cancer metastasis has been poorly studied. High expression of the hG1 gene, which encodes for Kv11.1 channel associates with good prognosis in estrogen receptor-negative breast cancer (BC). We evaluated the efficacy of the Kv11.1 activator NS1643 in arresting metastasis in a triple negative breast cancer (TNBC) mouse model. NS1643 significantly reduces the metastatic spread of breast tumors in vivo by inhibiting cell motility, reprogramming epithelial-mesenchymal transition via attenuation of Wnt/ß-catenin signaling and suppressing cancer cell stemness. Our findings provide important information regarding the clinical relevance of potassium ion channel expression in breast tumors and the mechanisms by which potassium channel activity can modulate tumor biology. Findings suggest that Kv11.1 activators may represent a novel therapeutic approach for the treatment of metastatic estrogen receptor-negative BC. Ion channels are critical factor for cell motility but little is known about their role in metastasis. Stimulation of the Kv11.1 channel suppress the metastatic phenotype in TNBC. This work could represent a paradigm-shifting approach to reducing mortality by targeting a pathway that is central to the development of metastases.

Neuroprotective Effects of Dibornol in Focal Cerebral Ischemia/Reperfusion in Rats.

Neuroprotective activity of 2,6-diisobornyl-4-methylphenol (Dibornol) was studied under conditions of experimental focal cerebral ischemia/reperfusion modeled by intraluminal occlusion of the left middle cerebral artery for 1 h followed by recirculation. Dibornol administered in a dose of 10 mg/kg intragastrically 24 h and 30 min before and 24 h after focal ischemia/reperfusion modeling reduced the size of the brain infarction zone by 52% (48 h after recirculation) and neurological deficit by 1.7-2.4 times in comparison with that in control animals.

Comparative Emergence of Resistance to Clofoctol, Erythromycin, and Amoxicillin against Community-Acquired Bacterial Respiratory Tract Pathogens in Italy.

Due to increasing bacterial resistance and poor availability of new antibiotics, physicians need to use old, still active antibiotics more frequently. In this study, we focused on clo-foctol and aimed to verify the emergence of clofoctol resistance over time. Additionally, the ability of clofoctol to induce resistance under static and dynamic conditions was evaluated. The minimum inhibitory concentration (MIC) values measured in pathogens isolated from 1990 to 1995 were compared to those isolated from 2017 to 2018. The behaviour of clofoctol is similar to that of amoxicillin, while erythromycin shows a different behaviour with an increase in MIC. A rapid decline in CFUs with complete eradication at 96 and 120 h in the case of clofoctol and amoxicillin, respectively, was observed in a dynamic in vitro model of a pharmacokinetic simulation. Erythromycin provides a reduction in CFUs of approximately one order of magnitude for up to 72 h, and then re-growth is observed. The MIC trend was observed during 5 days of kinetic simulation. The clofoctol MICs remain almost stable up to 96 h, after which the colonies are no longer detectable. The MICs of amoxicillin show a 2-fold increase starting from 36 h; however, at 120 h the colonies are no longer detectable. The MICs of erythromycin show a progressive increase starting from 72 h and reaching 32-fold. Clofoctol maintains its activity towards the common pathogens of respiratory tract infections and, similarly to amoxicillin, does not induce resistance in a strain of Streptococcus pneumoniae, resulting in complete eradication, while erythromycin was able to select resistant mutants.

[Comparative study of pain releasing effect of two approaches to acute pulpitis in the night emergency].

PURPOSE: To compare the clinical effect of 2 methods for acute pulpitis in the night emergency. METHODS: Two hundred and twenty-three patients with acute pulpitis were randomly divided into experimental group (107 cases) and control group (109 cases). Patients in the experimental group was enclosed formaldehyde cresol (FC) with CAVITON-GC after removal of crown pulp, while patients in the control group was treated with open drainage. Pain releasing effect was evaluated and analyzed 2 days after treatment．The data were analysed by t test and χ2 test with SPSS19.0 software package. RESULTS: The average pain index of the experimental group was 1.23, which was lower than that of the control group (3.58), the difference was significant (P<0.05). The treatment efficiency was 93.46% in the experimental group, significantly higher than that in the control group (77.98%, P<0.05). CONCLUSIONS: Treatment in the experimental group is more effective to relieve pain than simple drainage in the control group.

Indoxyl sulfate, not p-cresyl sulfate, is associated with cognitive impairment in early-stage chronic kidney disease.

BACKGROUNDS: Patients with chronic kidney disease (CKD) more commonly experience cognitive impairment, but the etiologies are not clear. Uremic toxins such as p-cresyl sulfate (PCS) and indoxyl sulfate (IS) have been shown to increase the risks of cardiovascular diseases and mortality; however, no study has investigated the associations of PCS and IS with cognitive function in patients with CKD. METHODS: Patients with CKD aged ≥50 years and age- and sex-matched non-CKD comparison subjects were recruited. CKD stage was defined according to the National Kidney Foundation guidelines. Cognitive function was evaluated using comprehensive neuropsychological tests. The associations between uremic toxins and cognitive function domains were examined using multiple linear regression analysis. The interaction between uremic toxins and CKD stages on cognitive functions were also examined. RESULTS: In total, 199 patients with CKD and 84 comparison subjects completed the study. The patients with CKD had poorer cognitive function and higher serum PCS and IS levels. A higher serum IS level was associated with poor executive function (ß=-0.31, P=0.003) only in stage 3 CKD patients after adjustment for age, sex and educational level. Serum PCS level was not associated with cognitive function in patients with CKD. CONCLUSIONS: Our study showed that a higher serum IS level was associated with poor executive function in the early stage of CKD. It would be worthwhile to investigate the effect of IS removal in early-stage CKD on the prevention of cognitive impairment in future studies.

Prominent complaint: a guide to medical therapy of overactive bladder syndrome in older women.

To evaluate Overactive bladder (OAB) with detrusor overactivity (DOA) following oxybutynin or tolterodine treatment in recommended doses at a four-week course. A total of 100 Iranian women 45 years or older with urgency that also showed idiopathic detrusor overactivity (IDO) in the filling phase of their cystometry were included in the current study. In this double-blinded trial two parallel groups were randomized by using two kinds of the antimuscarinic drugs for a four- week course [oxybutinin 5mg, t.d.s. or Tolterodin 2mg, b.i.d.] in the same  packages. Data were collected from three-day frequency volume chart (FVC) one month before and after the treatment course. The effectiveness of each drug was compared using the paired, samples t-test. Patients' improvement regarding urinary urgency, frequency and urge incontinence after treatment in both groups was seen, but mean improvements in the terms of urgency and urge incontinence were larger in patients who were treated by oxybutynin. Night-time frequency was shown to be improved by a significantly larger score by tolterodine. Discontinuation of treatment due to adverse events had no significant difference in two groups. Four-week treatment with oxybutynin was better than tolterodine IR in improving urgency and urge incontinence, but there were not statistically significant difference between them. In planning a course of treatment especially in the elderly, the difference in the group of symptoms that reduce patients' quality of life should be considered. Physicians should consider the patient's prominent symptom in selection of anti-muscarinic drugs for the treatment of overactive bladder syndrome especially in elderly patients.

Cost effectiveness of mirabegron compared with tolterodine extended release for the treatment of adults with overactive bladder in the United Kingdom.

BACKGROUND: Overactive bladder (OAB) is highly prevalent and is associated with considerable morbidity and reduced health-related quality of life. ß3-adrenergic receptor (ß3-AR) stimulation is a novel alternative to antimuscarinic therapy for OAB. OBJECTIVE: The objective of this analysis was to assess the cost effectiveness of the ß3-AR agonist mirabegron relative to tolterodine extended release (ER) in patients with OAB from a UK National Health Service (NHS) perspective. METHODS: A Markov model was developed to simulate the management, course of disease, and effect of complications in OAB patients over a period of 5 years. Transition probabilities for symptom severity levels and probabilities of adverse events were estimated from the results of the randomised, double-blind SCORPIO trial in 1,987 patients with OAB. Other model inputs were derived from the literature and on assumptions based on clinical experience. RESULTS: Total 5-year costs per patient were £1,645.62 for mirabegron 50 mg/day and £1,607.75 for tolterodine ER 4 mg/day. Mirabegron was associated with a gain of 0.009 quality-adjusted life-years (QALYs) with an additional cost of £37.88. The resulting incremental cost-effectiveness ratio (ICER) was £4,386/QALY gained. In deterministic sensitivity analyses in the general OAB population and several subgroups, ICERs remained below the generally accepted willingness-to-pay (WTP) threshold of £20,000/QALY gained. The probability of mirabegron 50 mg being cost effective relative to tolterodine ER 4 mg was 89.4 % at the same WTP threshold. CONCLUSIONS: Mirabegron 50 mg/day is likely to be cost effective compared with tolterodine ER 4 mg/day for adult patients with OAB from a UK NHS perspective.

Drug treatment patterns for the management of men with lower urinary tract symptoms associated with benign prostatic hyperplasia who have both storage and voiding symptoms: a study using the health improvement network UK primary care data.

BACKGROUND: Real-world data on the pharmacological management of men who have lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) are limited. OBJECTIVE: To characterize men with LUTS/BPH who had both storage and voiding symptoms and to evaluate treatment patterns in UK primary care. DESIGN, SETTING AND PARTICIPANTS: This was an observational study of men aged ≥45 years with a diagnosis, symptoms or therapies indicative of LUTS/BPH with both storage and voiding components. These men were identified from the large Health Improvement Network (THIN) database between 1 January 2004 and 30 September 2011. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Drug prescriptions and switching/discontinuation patterns for α1-blockers and antimuscarinics. RESULTS AND LIMITATIONS: We identified 8694 men with a median age of 66.0 (interquartile range [IQR], 59.0-74.0) years. Most (7850; 90.3%) received an α1-blocker, and 2167 (24.9%) received antimuscarinic therapy over a median of 2.1 years. The most commonly prescribed α1-blocker was tamsulosin (81.8%); most frequent antimuscarinics were tolterodine (41.0%), oxybutynin (37.2%) and solifenacin (35.7%). Concomitant prescription of α1-blocker and antimuscarinic therapy (within 30 days of each other) was received by 1160 men (14.8% of α1-blocker-treated men). Of α1-blocker recipients, 3024 (38.5%) discontinued during follow-up, while 1149 (53.0%) discontinued antimuscarinic therapy. Of 2167 men who received an antimuscarinic, 476 (22.0%) switched to another antimuscarinic. Of the three most commonly prescribed antimuscarinics, solifenacin had the lowest proportions of discontinuations (43.0%) and switches (15.3%), and the longest median duration of therapy (90 days, IQR 30-300). General practice consultations accounted for most resource use (5307.9 per 1000 patient-years). CONCLUSIONS: This study presents real-world management of men with LUTS/BPH who have both storage and voiding symptoms. The low proportion of men who received concomitant α1-blocker and antimuscarinic therapy suggests that some patients are sub-optimally treated in routine clinical practice.

Tolterodine extended release in the treatment of male OAB/storage LUTS: a systematic review.

BACKGROUND: Overactive bladder (OAB)/ storage lower urinary tract symptoms (LUTS) have a high prevalence affecting up to 90% of men over 80 years. The role of sufficient therapies appears crucial. In the present review, we analyzed the mechanism of action of tolterodine extended-release (ER) with the aim to clarify its efficacy and safety profile, as compared to other active treatments of OAB/storage LUTS. METHODS: A wide Medline search was performed including the combination of following words: "LUTS", "BPH", "OAB", "antimuscarinic", "tolterodine", "tolterodine ER". IPSS, IPSS storage sub-score and IPSS QoL (International Prostate Symptom Score) were the validated efficacy outcomes. In addition, the numbers of urgency episodes/24 h, urgency incontinence episodes/24 h, incontinence episodes/24 h and pad use were considered. We also evaluated the most common adverse events (AEs) reported for tolterodine ER. RESULTS: Of 128 retrieved articles, 109 were excluded. The efficacy and tolerability of tolterodine ER Vs. tolterodine IR have been evaluated in a multicenter, double-blind, randomized placebo controlled study in 1529 patients with OAB. A 71% mean reduction in urgency incontinence episodes was found in the tolterodine ER group compared to a 60% reduction in the tolterodine IR (p < 0.05). Few studies evaluated the clinical efficacy of α-blocker/tolterodine combination therapy. In patients with large prostates (prostate volume >29 cc) only the combination therapy significantly reduced 24-h voiding frequency (2.8 vs. 1.7 with tamsulosin, 1.4 with tolterodine, or 1.6 with placebo). A recent meta-analysis evaluating tolterodine in comparison with other antimuscarinic drugs demonstrated that tolterodine ER was significantly more effective than placebo in reducing micturition/24 h, urinary leakage episodes/24 h, urgency episodes/24 h, and urgency incontinence episodes/24 h. With regard to adverse events, tolterodine ER was associated with a good adverse event profile resulting in the third most favorable antimuscarinic. Antimuscarinic drugs are the mainstay of pharmacological therapy for OAB / storage LUTS; several studies have demonstrated that tolterodine ER is an effective and well tolerated formulation of this class of treatment. CONCLUSION: Tolterodine ER resulted effective in reducing frequency urgency and nocturia and urinary leakage in male patients with OAB/storage LUTS. Dry mouth and constipation are the most frequently reported adverse events.

Are we shortchanging frail older people when it comes to the pharmacological treatment of urgency urinary incontinence?

Overactive bladder and urgency incontinence are common and distressing conditions in older people, for which the first-line pharmacological treatment is a bladder antimuscarinic agent. Of these, oxybutynin is often recommended in guidelines, but is associated with a higher incidence of adverse drug effects, and in particular has been suggested to have deleterious cognitive effects. Despite this, guidelines often suggest oxybutynin as first-line treatment, and insurance based healthcare systems often require oxybutynin to be used as a first-line therapy and fail before reimbursement for the cost of newer anticholinergics is authorised. We reviewed the literature of bladder antimuscarinics in older adults, using the headings overactive bladder, urinary frequency, urgency, urge, oxybutynin, antimuscarinic, older, older people, and frail. In general, oxybutynin had a similar efficacy to other anticholinergic drugs, but a higher incidence of adverse drug events, in particular significant yet unnoticed cognitive impairment. We conclude that oxybutynin should not be used in frail older people.

Combination of sacral neuromodulation and tolterodine for treatment of idiopathic overactive bladder in women: a clinical trial.

PURPOSE: To evaluate the efficacy of intermittent percutaneous needle sacral nerve stimulation (IPN-SNS) in women with idiopathic overactive bladder (IOAB) treated with tolterodine. MATERIALS AND METHODS: A total of 240 female patients diagnosed with IOAB were randomized to receive tolterodine only treatment (group 1, n = 120) or tolterodine combined with IPN-SNS (group 2, n = 120). Each group included 120 participants, who were divided into subgroups depending on whether they had dry OAB (urinary frequency and urgency) or wet OAB (urinary frequency and urgency with urgency incontinence). In the treatment group, patients received percutaneous IPN-SNS plus tolterodine (2 mg once daily), while in the control group, only tolterodine (2 mg once daily) was administered for 3 months. The voiding diary and urodynamic parameters were monitored, and patients' psychological depression and anxiety scores were recorded before and after treatment. RESULTS: There were significantly greater improvements in the conditions of first desire to void (FDV), max­imum cystometric capacity (MCC), and daily average volumes, as well as the daily single maximum voided volumes in group 2 (P = .001) than in group 1. In addition, there were significantly greater decreases in self-rating depression scale (SDS) and self-rating anxiety scale (SAS) scores in group 2 compared with group 1 (P < .001). CONCLUSION: Combined treatment with tolterodine plus IPN-SNS can not only improve the symptoms of voiding dysfunction but can also reduce the concomitant depression and anxiety in women with IOAB, there­by improving patients' quality of life.

Mirabegron 50 mg once-daily for the treatment of symptoms of overactive bladder: an overview of efficacy and tolerability over 12 weeks and 1 year.

The aim of the present review article was to summarize the efficacy and tolerability for mirabegron 50 mg over 12 weeks and 1 year versus placebo (SCORPIO) or tolterodine ER 4 mg (SCORPIO and TAURUS). After a 2-week placebo run-in, adults with overactive bladder symptoms for ≥3 months were randomized if, during a 3-day micturition diary period before baseline, they had an average of ≥8 micturitions/24 h and ≥3 urgency episodes. Efficacy end-points were change from baseline to each study visit and final visit in incontinence, micturitions, volume voided/micturition, urgency incontinence, urgency (grades 3 or 4), level of urgency and nocturia. Additional secondary efficacy variables included patient-reported outcomes. Safety variables included changes in treatment-emergent adverse events and vital signs. For SCORPIO, statistically significant improvements from baseline in efficacy variables and patient-reported outcomes were seen with mirabegron versus placebo from week 4, and were maintained over time. For TAURUS, numerical improvements in efficacy were evident from month 1, and were maintained throughout 12 months. Treatment-emergent adverse events incidence was similar between groups, except for dry mouth, which was reported by fourfold (SCORPIO) and threefold (TAURUS) more patients taking tolterodine than mirabegron. Mirabegron 50 mg for 12 weeks was associated with statistically significant improvements in objective measures of efficacy and patient-reported outcomes. At final visit, improvements with mirabegron 50 mg were statistically greater versus placebo. The efficacy profile of mirabegron 50 mg appears to be maintained over 12 months.

The role of mirabegron in overactive bladder: a systematic review and meta-analysis.

OBJECTIVE: To present a systematic review assessing the efficacy and safety of mirabegron for overactive bladder (OAB). MATERIALS AND METHODS: A literature search was performed using the Cochrane Library, MEDLINE, EMBASE and Science Citation Index Expanded. The literature reviewed included meta-analyses, randomized and nonrandomized prospective studies. We utilized mean difference (MD) to measure the mean number of incontinence episodes and the mean number of micturitions, and OAB questionnaire (OAB-q) and odds ratio (OR) to measure adverse events rates. We used the Cochrane Collaboration's Review Manager 5.1 software for statistical analysis. RESULTS: We identified six publications that strictly met our eligibility criteria. Meta-analysis of extractable data showed that mirabegron was more effective than placebo in treating OAB despite different drug dosages in the efficacy end points: mean number of incontinence episodes per 24 h (MD -0.54; 95% CI -0.63, -0.45; p = 0.001), mean number of micturitions per 24 h (MD -0.55; 95% CI -0.63, -0.47; p = 0.001), OAB-q (MD -4.49; 95% CI -6.27, -2.71; p = 0.001) and adverse events (OR 0.99; 95% CI 0.83, 1.19; p = 0.92). When compared to tolterodine, mirabegron was more effective in terms of mean number of incontinence episodes per 24 h (MD -0.25; 95% CI -0.43, -0.06; p = 0.009). However, there were no differences between mirabegron and tolterodine in mean number of micturitions per 24 h (MD -0.17; 95% CI -0.35, 0.01; p = 0.07) and OAB-q (MD -1.09; 95% CI -2.51, 0.33; p = 0.13). Mirabegron also had a lower adverse reaction rate (OR 0.9; 95% CI 0.8, 1.0; p = 0.04). CONCLUSIONS: In this diverse population, mirabegron was an effective and safe pharmacologic therapy for OAB.

Novel preoperative pharmacologic methods of preventing postoperative sore throat due to tracheal intubation.

Postoperative sore throat (POST) is usually self-limiting but was rated by patients as one of the top 10 most undesirable anesthetic outcomes. Pharmacologic interventions that have been suggested to decrease the incidence of POST include application of local anesthetics and corticosteroids to the cuff of the endotracheal tube. These interventions often require extra steps during induction of general anesthesia. We sought evidence for using nonsteroidal, nonlocal anesthetic, topical pharmacologic interventions conveniently implemented preoperatively to decrease the incidence of POST. One hundred seventeen potential evidence sources were located, with 11 randomized controlled trials meeting inclusion criteria. The evidence examined ketamine, aspirin, and azulene gargle; benzydamine gargle or oral spray; dexpanthenol pastilles; and lozenges containing amyl-m-cresol or magnesium. Although there were methodologic concerns with the studies, the evidence suggested that all the treatment medications decreased the incidence of POST at early and late intervals. The severity of POST was also typically reduced. Preoperative ketamine and aspirin gargle are probably the most promising for providers practicing in the United States. However, before these agents are recommended for general use, large multicenter trials should be done exploring not only efficacy but also dose-response relationships and side effects.