Use of mirabegron in treating overactive bladder

The lack of an alternative to antimuscarinics has led to the search for new drug targets for overactive bladder (OAB) symptoms. The presence of β-3 adrenoreceptors in the bladder has been confirmed, and they are known to have a role in bladder relaxation. Targeting these receptors improves bladder compliance on filling and increases bladder capacity. MEDLINE literature search on efficacy and safety of mirabegron was performed. The US Food and Drug Administration Web site, clinicaltrials.gov, and controlled-trials.com online trial registries were searched for English-language articles containing the term "mirabegron". Finally, abstracts from recent International scientific meetings were searched for randomised controlled trials (RCTs). Studies show that mirabegron reduces the number of micturitions and incontinence episodes in a 24-h period compared with placebo. Dry mouth and gastrointestinal disturbances are the most common side effects, but these have been rated as mild to moderate. A small rise in mean heart rate and blood pressure has been shown. Further investigations are ongoing and results are awaited. Although mirabegron is metabolised by CYP2D6, it is also thought to inhibit the activity of this enzyme. Therefore, potential drug interactions with other CYP2D6 substrates need to be further studied. Mirabegron is a promising alternative to antimuscarinics. Further information on its long-term use in terms of efficacy, safety, and tolerability is awaited.     

Inaccuracies in angiographic staging of renal cell carcinoma

In 54 patients with renal cell carcinoma, the angiographic T category of the International Union Against Cancer (UICC) clasification correlated with the histopathologic (P) staging in only 44.4 per cent. Staging of the primary lesion in renal cell carcinoma must be based on the P category and not the angiographic appearances.     

An analysis of review articles published in four anaesthesia journals

Purpose

To see if the authors of review articles in anaesthesia journals are making use of systematic methods in their preparation.

Methods

Twenty-five review articles published in 1995 in four major anaesthesia journals were analysed and compared with standard guidelines for the appraisal of reviews.

Results

Of the 25 articles, only 14 stated a clear purpose. Only two revealed the search strategy used to identify articles for the review. None of the reviews featured any type of quality assessment of the primary studies included, or stated what criteria, if any, were used to determine what material was included or excluded. Useful areas for future research were highlighted in only seven reviews.

Conclusion

There is little evidence that reviews currently accepted for publication m anaesthesia journals have been prepared systematically.     

Inaccuracies in the assessment of femoral anteversion in proximal femoral replacement prostheses

Accurately judging anteversion of proximal femoral replacement prostheses (PFRPs) during insertion can be difficult and may affect performance/stability. We designed a gravity goniometer jig, which attaches directly to the prosthesis, to improve rotational placement. Our hypotheses were that surgeons cannot accurately estimate anteversion in the context of a PFRP and that our jig would improve rotational placement. In our model, a 15-centimeter PFRP was placed in a saw-bones femur set in a lateral position. The prosthesis could rotate into anteversion/retroversion while the femur was fixed. Orthopedic residents and surgeons made 2 attempts to place the prosthesis into 15 degrees of anteversion; first without, then with the jig. Each attempt was recorded by photograph and angle-measuring jig. Nineteen surgeons and 28 residents participated. Without the jig, the mean PFRP anteversion was 18.3 degrees (range, 1 degrees -50.5 degrees ; SD, 9.6) compared to 14.3 degrees (range, 12.5 degrees -15.5 degrees ; SD, 0.7) using the jig (P = .006). Without a jig, the mean anteversion of resident-placed endoprosthesis was 18.4 degrees (range, 3 degrees -36 degrees ; SD, 8.1) compared to 18.1 degrees (range, 1 degrees -50.5 degrees ; SD, 12.1) (P = .91) recorded for attending physicians. The angle measurements from the jig and photographs were statistically equal. The placement of the PFRP into proper anteversion was more accurate with the aid of the jig. Simple jigs, such as the one developed for this study, may improve rotational placement of PFRPs.     

The efficacy and safety of mirabegron in treating OAB: a systematic review and meta-analysis of phase III trials

Purpose

Mirabegron, a potent and selective β3-adrenoceptor agonist, has been developed for the treatment of overactive bladder (OAB). We carried out a systematic review and meta-analysis to assess the efficacy and safety of the drug for treating OAB.

Methods

A literature review was performed to identify all published randomized double-blind, placebo-controlled phase III trials of mirabegron for the treatment of OAB. The search included the following databases: MEDLINE, EMBASE and the Cochrane Controlled Trials Register. The reference lists of the retrieved studies were also investigated. A systematic review and meta-analysis of phase III trials were conducted.

Results

Four publications involving a total of 5,761 patients were used in the analysis, including four phase III RCTs that compared mirabegron with placebo. We found that mirabegron was effective in treating OAB in our meta-analysis. Co-primary efficacy end points: the mean number of incontinence episodes per 24 h (the standardized mean difference (SMD) = ?0.44, 95 % confidence interval (CI) ?0.59 to ?0.29, p < 0.00001); the mean number of micturitions per 24 h (SMD = ?0.62, 95 % CI ?0.80 to ?0.45, p < 0.00001) and key secondary efficacy end points: mean volume voided per micturition; mean number of urgency episodes per 24 h indicated that mirabegron was more effective than the placebo. Safety assessments included common treatment-emergent adverse events (TEAEs) [OR 1.10, 95 % CI 0.93–1.31, p = 0.25), hypertension, cardiac arrhythmia TEAEs, urinary retention and discontinuations due to adverse event indicated that mirabegron was well tolerated.

Conclusions

This meta-analysis indicates that mirabegron to be an effective and safe treatment for OAB symptoms with a low occurrence of side effects. It offers promise as an effective oral agent for the treatment of OAB with a distinct efficacy/tolerability balance.     

Continuous peripheral nerve blocks: a review of the published evidence

A continuous peripheral nerve block, also termed "perineural local anesthetic infusion," involves the percutaneous insertion of a catheter adjacent to a peripheral nerve, followed by local anesthetic administration via the catheter, providing anesthesia/analgesia for multiple days or even months. Continuous peripheral nerve blocks may be provided in the hospital setting, but the use of lightweight, portable pumps permits ambulatory infusion as well. This technique's most common application is providing analgesia after surgical procedures. However, additional indications include treating intractable hiccups; inducing a sympathectomy and vasodilation to increase blood flow after a vascular accident, digit transfer/replantation, or limb salvage; alleviating vasospasm of Raynaud disease; and treating peripheral embolism and chronic pain such as complex regional pain syndrome, phantom limb pain, trigeminal neuralgia, and cancer-induced pain. After trauma, perineural infusion can provide analgesia during transportation to a distant treatment center, or while simply awaiting surgical repair. Catheter insertion may be accomplished using many possible modalities, including nerve stimulation, ultrasound guidance, paresthesia induction, fluoroscopic imaging, and simple tactile perceptions ("facial click"). Either a nonstimulating epidural-type catheter may be used, or a "stimulating catheter" that delivers electrical current to its tip. Administered infusate generally includes exclusively long-acting, dilute, local anesthetic delivered as a bolus only, basal only, or basal-bolus combination. Documented benefits appear to be dependent on successfully improving analgesia, and include decreasing baseline/breakthrough/dynamic pain, supplemental analgesic requirements, opioid-related side effects, and sleep disturbances. In some cases, patient satisfaction and ambulation/functioning may be improved; an accelerated resumption of passive joint range-of-motion realized; and the time until discharge readiness as well as actual discharge from the hospital or rehabilitation center achieved. Lastly, postoperative joint inflammation and inflammatory markers may be decreased. Nearly all benefits occur during the infusion itself, but several randomized controlled trials suggest that in some situations there are prolonged benefits after catheter removal as well. Easily rectified minor complications occur somewhat frequently, but major risks including clinically relevant infection and nerve injury are relatively rare. This article is an evidence-based review of the published literature involving continuous peripheral nerve blocks.     

Effect of mirabegron on tight junction molecules in primary cultured rat Sertoli cells

Mirabegron is a selective beta3‐adrenoceptor (β₃‐AR) agonist, which is commonly used for the treatment of overactive bladder. This medicine is associated with atrophy of reproductive organs in rats. However, no study has examined the detailed action and mechanism of its toxicity in reproductive cells. In this study, we examined the effect of mirabegron on primary cultured rat Sertoli cells. Firstly, RT‐PCR and immunocytochemistry revealed that β₃‐AR was present in rat Sertoli cells. Then, primary cultured rat Sertoli cells were treated with mirabegron. Quantitative real‐time PCR revealed that mirabegron treatment induced a significant increase in claudin‐11 mRNA, which is crucial for spermatogenesis. Western blot analysis also showed that mirabegron treatment significantly activated p44/42 mitogen‐activated protein kinase (MAPK). After additional treatment with U0126, a specific noncompetitive inhibitor of mitogen‐activated protein kinase kinase (MAPKK), the upregulation of claudin‐11 mRNA induced by mirabegron was reduced. At the same time, immunocytochemistry showed mirabegron treatment disturbed claudin‐11 localisation to tight junction, which was recovered when treated with mirabegron in the presence of U0126. These results suggest that mirabegron treatment is associated with assembly of the blood–testis barrier through p44/42 MAPK pathway. These findings could explain one of the underlying mechanisms of reproductive toxicity induced by mirabegron.     

Emergency department visit patterns in the recently discharged,violently injured patient: Retrospective cohort review

BackgroundAnalysis of the costs associated with emergency department (ED) visits after discharge for violent injury could highlight subgroups for the development of cost-effective interventions to support healing and prevent treatment failures in violently injured patients.MethodsA retrospective cohort review was conducted of all patients with return ED visits within 90 days of discharge after treatment for a violent injury occurring between July 1, 2016, and June 30, 2018. Hospital costs were calculated for each incidence and analyzed against demographic and injury type variables to identify trends.Results218 return ED visits were identified. Hospital costs showed a high frequency of low-cost visits. For more complex visits, distinct cost patterns were observed for Black and LatinX males compared to White males as a function of age.ConclusionsAnalysis of hospital cost per visit identified trends among different subgroups. Underlying etiologies presumably vary between groups, but hypothesis-driven further investigation and needs assessment is required. Understanding the driving forces behind these cost trends may aid in developing effective interventions.     

Resident-as-teacher programs in general surgery residency – A review of published curricula

Introduction

The Liaison Committee on Medical Education (LCME) requires that residents are trained to fulfill their educational duties toward medical students. This study reviews the literature on resident-as-teacher programs (RATPs) aimed at surgical residents.

Inaccuracies in estimated glomerular filtration rate in one Australian renal centre

Background: Early identification of true renal disease (glomerular filtration rate (GFR) < 60 mL/min) results in better patient outcomes. There is now routine reporting in Australia of estimated GFR (eGFR) in all patients over age 18 who have serum creatinine measured, calculated by the Modification of Diet in Renal Disease (MDRD) formula, which was validated in an American Caucasian cohort. Significant clinical decisions and prognosis are often made on the basis of this calculation. Aim: To assess the accuracy of three estimates of GFR in an Australian population by comparing eGFR obtained by the abbreviated MDRD (aMDRD), Cockcroft–Gault corrected for body surface area (BSA) (CG) and Chronic Kidney Disease Epidemiology (CKD‐Epi) formulae with a gold standard, isotopic ⁵¹Cr‐ethylenediaminetetra‐acetic acid (⁵¹Cr‐EDTA) GFR. Methods: Patients referred with an eGFR of <60 mL/min reported by the aMDRD formula underwent isotopic measurement of GFR (over 4 h) and had eGFR calculated using CG corrected for BSA, aMDRD and CKD‐Epi formulae. Data were analysed using Bland–Altman plots and regression analysis to compare methods; bias, precision and the proportion of patients correctly stratified by stage of chronic kidney disease (CKD) were also compared according to the three estimates of GFR, using ⁵¹Cr‐EDTA GFR as the gold standard. Results: A total of 139 patients were recruited (female 45%), mean age 64 years and mean serum creatinine 212 µmol/L. The mean GFR (SD) (mL/min per m²) for isotopic, CG, aMDRD and CKD‐Epi were 47 (28), 37 (20), 32 (17) and 33 (18) (P = 0.001). CG (57%) was more likely to correctly stage CKD than aMDRD (37%) or CKD‐Epi (37%), and absolute bias was significantly lower using CG than either other method (P = 0.001). Conclusion: In this small Australian population the CG formula corrected for BSA agreed more closely with isotopic GFR and correctly staged patients with CKD more often than the aMDRD or CKD‐Epi formulae. It is important that each renal Unit considers the accuracy of estimates of GFR according to their population demographics.     

Splenogonadal fusion: Case report and review of published works

Splenogonadal fusion is a rare congenital anomaly. We report herein a case of splenogonadal fusion associated with contra lateral testicular aplasia, and review the etiology, pathogenesis and management of this rare disease. As far as we know, this is the first reported case of splenogonadal fusion associated with testicular aplasia.     

Xanthogranulomatous pyelonephritis: our experience with review of published reports

BACKGROUND: The aim of this study was to analyse the cases of xanthogranulomatous pyelonephritis with review of published reports. METHODS: We retrospectively reviewed all nephrectomy specimens during February 1995 to January 2006. We found 26 cases of xanthogranulomatous pyelonephritis. We prepared a chart of these cases consisting of preoperative symptoms, laboratory findings, radiological imaging results and preoperative diagnosis. Open nephrectomy was carried out in all cases. RESULTS: Age group of the patients was 6-65 years and male : female ratio was 1.6:1. Twenty-two patients presented to us with intermittent high-grade fever, 21 with flank pain, 18 with loin mass, 2 with haematuria and 1 was detected during screening of vague gastrointestinal symptoms. Twenty-five patients had pyuria and only 10 had sterile urine culture. In all patients, only one kidney was affected. All patients had renal calculi 10-42 mm in size with bilaterally enlarged kidneys. Ipsilateral kidney was enlarged because of hydronephrosis or pyonephrosis in all cases and contralateral kidney was enlarged because of compensatory hypertrophy in 13 cases. Ipsilateral kidney had severely compromised renal function in all cases. Associated psoas abscess was present in one and tuberculosis in another. CONCLUSION: Xanthogranulomatous pyelonephritis is a relatively rare entity that is associated with obstruction, stones and infection of the urinary tract. Late presentation leads to loss of renal parenchyma. It cannot be differentiated preoperatively with renal tumours (renal cell carcinoma and Wilms' tumour), pyonephrosis, infected hydronephrosis and renal lymphoma. Nephrectomy and antibiotics are the treatment of choice.     

Arterial-ureteral fistula: Case study with review of published reports

Arterial-ureteral fistula, a rare cause of gross hematuria, may be associated with life-threatening hemorrhage if not rapidly diagnosed and treated. Recently, a patient at the Hunter H. McGuire Veterans Administration Medical Center developed an arterial-ureteral fistula at the site of the confluence of the external iliac artery and a superior mesenteric artery bypass graft. Review of the world's literature revealed 31 additional reported cases of arterial-ureteral fistulas [1—31]. This current case is only the second one reported in which the diagnosis was made with arteriography. Several common features of arterial-ureteral fistulas were present in this case: a history of ureteral obstruction and urinary tract infections, upper urinary tract disease, and previous vascular surgery. The condition is usually associated with either prior upper urinary tract instrumentation or vascular surgery, and an antecedent period of intermittent hematuria, followed by life-threatening hematuria, is common. A high index of suspicion and early surgical intervention are required for successful management. The major surgical challenges are to establish unobstructed urinary drainage and restore vascular continuity. Exclusion of prosthetic material from potentially infected areas is mandatory.