Complications of Synthetic Midurethral Slings: Is There a Relevant Discrepancy Between Observational Data and Clinical Trials?

CONTEXT: The complications of synthetic midurethral slings (MUSs) in women with stress urinary incontinence (SUI) have become a globally debated issue. OBJECTIVE: To systematically review the short- and long-term complications of mesh slings reported in observational data compared with clinical trial data, to determine whether the complication rates from clinical trials reflects "real-world" observational data. EVIDENCE ACQUISITION: PubMed and Cochrane Library were searched. Methods as detailed in Preferred Reporting Items for Systematic Reviews and Meta-analyses and Cochrane Handbook for Systematic Reviews of Interventions were followed. EVIDENCE SYNTHESIS: Thirty registries/databases including 709 335 MUS procedures (1-22 yr of follow-up) were identified. MUS procedures were associated with intraoperative bladder perforation in 0.86-3.6%, urethral perforation in 0-0.1%, vascular injury in 0.04-0.1%, voiding lower urinary tract symptoms (LUTS) in 1.47-3.5%, vaginal exposure in 0.2-1.9%, and reoperation in up to 9% of cases. Forty-three randomised clinical trials were identified, including 6284 women who underwent MUS procedures and 2177 women who underwent other interventions (1-10 yr of follow-up). MUS procedures were associated with urinary tract perforation in 2.58%, vaginal injury in 1.43%, de novo voiding LUTS in 4.37%, de novo storage LUTS in 5.41%, mesh extrusion/exposure (vaginal/urinary tract) in 2.54%, dyspareunia in 2.26%, pain (pelvic/suprapubic/perineal) in 2.83%, and reoperation for complications required in 1.82% of cases. Meta-analyses of the randomised controlled trials revealed that retropubic MUSs were associated with more events of urinary tract perforation (risk ratio [RR] 9.81, 95% confidence interval [CI] 5.05-19.04, high certainty of evidence [COE]) and voiding LUTS (RR 1.57, 95% CI 1.19-2.07, high COE) than transobturator MUSs. MUSs were associated with more events of pain than mini-slings (RR 1.72, 95% CI 1.04-2.87, moderate COE). CONCLUSIONS: Short- and long-term data on complications of polypropylene mesh used for female SUI are fairly comparable when using outcome data from well-designed clinical trials or from less structured prospective or retrospective registries. Comparisons have to be made with caution since the two systems of data collection are inherently incomparable. This knowledge should be incorporated in the discussion on how to implement polypropylene mesh for female stress incontinence. PATIENT SUMMARY: In order to know whether mesh tapes used for treating stress incontinence work well and are safe, high-quality information is important. It appears that well-designed clinical studies give similar results to large registration databases. These data should be interpreted with caution in view of the different ways the information was collected. These results will help physicians and patients understand the risks of mesh tapes.

Association between intrapartum epidural use and maternal postpartum depression presenting for medical care: a population-based, matched cohort study.

PURPOSE: To evaluate whether intrapartum epidural use is associated with maternal postpartum depression presenting for medical care. METHODS: Population-based, matched cohort study including all adult nulliparous women in Ontario, Canada from 2006 to 2012 without a history of depression, who had a term vaginal delivery. Seventy covariates including maternal demographics, medical and psychiatric conditions, prenatal and perinatal complications, and healthcare utilization were measured. Primary exposure was intrapartum epidural use. Primary outcome was the onset of depression requiring medical care within 12 months postpartum; and the secondary outcome was self-harm. RESULTS: A total of 40303 women who received an intrapartum epidural were matched 1:1 on age, year of cohort entry, and propensity score to an equal number of women who did not receive an intrapartum epidural. Overall rate of new onset depression presenting to the healthcare system was 0.88% within 12 months postpartum. Intrapartum epidural use was not associated with maternal postpartum physician or hospital visits (adjusted HR 1.05 [95% CI 0.87 to 1.28]) or self-harm (unadjusted HR 0.91 [95% CI 0.57 to 1.48]). CONCLUSIONS: Intrapartum epidural use was not associated with maternal postpartum depression presenting to the healthcare system in term nulliparous women who had a vaginal delivery. Further research is needed to determine if intrapartum epidural use is associated with postpartum depression among women who don't seek care from a physician.

An administrative data algorithm to identify traumatic spinal cord injured patients: a validation study.

OBJECTIVE: To assess the validity of different administrative data sources available for the identification of traumatic spinal cord injured (TSCI) patients. STUDY DESIGN: Retrospective validation study. SETTING: Ontario, Canada. PARTICIPANTS: Adult patients seen in tertiary outpatient spinal cord rehabilitation clinics after 1 April 2002. OUTCOME MEASURES: Sensitivity, specificity, positive and negative predicative values of diagnostic ICD10 codes from Canadian Institutes of Health Discharge Abstracts (CIHI-DAD), Rehabilitation Coding Groups (RCG) from that National Rehabilitation System (NRS), and spinal cord injury fee codes from the Ontario Healthcare Insurance Plan (OHIP). Secondary outcome was the agreement between actual lesion level and RCG/ICD10 coded lesion level. RESULTS: The RCG codes in the NRS have high sensitivity (92%, 95% confidence interval (CI): 87-95%) and specificity (97%, 95% CI: 94-99%) for the identification of true TSCI patients, whereas CIHI-DAD ICD10 codes are highly specific (99%, 95% CI: 95-100) and moderately sensitive (76%, 95% CI: 79-87%). OHIP fee codes had poor sensitivity (64%, 95% CI: 57-71%). Agreement between true lesion level and the NRS and CIHI-DAD coding is good (Kappa of 0.65-0.88 and 0.56-0.70, respectively). CONCLUSION: This study demonstrated that the NRS is able to accurately discriminate between patients with and without a TSCI. A large population of incident and prevalent TSCI patients are identifiable using administrative data. SPONSORSHIP: This study was funded by a grant from the Division of Urology, Western University.

Risk of kidney stones with surgical intervention in living kidney donors.

A kidney stone in a person with a solitary kidney requires urgent attention, which may result in surgical and/or hospital attention. We conducted a matched retrospective cohort study to determine if living kidney donors compared to healthy nondonors have a higher risk of: (i) kidney stones with surgical intervention, and (ii) hospital encounters for kidney stones. We reviewed all predonation charts for living kidney donations from 1992 to 2009 at five major transplant centers in Ontario, Canada, and linked this information to healthcare databases. We selected nondonors from the healthiest segment of the general population and matched 10 nondonors to every donor. Of the 2019 donors and 20 190 nondonors, none had evidence of kidney stones prior to cohort entry. Median follow-up time was 8.4 years (maximum 19.7 years; loss to follow-up <7%). There was no difference in the rate of kidney stones with surgical intervention in donors compared to nondonors (8.3 vs. 9.7 events/10 000 person-years; rate ratio 0.85; 95% confidence interval [CI] 0.47-1.53). Similarly there was no difference in the rate of hospital encounters for kidney stones (12.1 vs. 16.1 events/10 000 person-years; rate ratio 0.75; 95% CI 0.45-1.24). These interim results are reassuring for the safety of living kidney donation.

Bladder cancer in individuals with spinal cord injuries.

STUDY DESIGN: Prospective scoping review. OBJECTIVES: To conduct a scoping review of all the literature related to bladder cancer in individuals with spinal cord injuries (SCI). METHODS: Literature search of the databases Pubmed, CINAHL, ProQuest, PsychINFO and Scopus up to and including August 2012. Articles related to bladder cancer among SCI patients were identified, and data pertaining to epidemiology, risk factors, screening, prevention and management was reviewed and summarized. RESULTS: An association between bladder cancer and SCI was first reported in the 1960s, with some case reports suggesting an alarmingly high rate among SCI patients. More recent epidemiological studies have reported this risk to be substantially lower. However, bladder cancer in SCI patients tends to present at an earlier age and at a more advanced pathological stage than bladder cancer in the general population. Presenting symptoms may be atypical, and early recognition is important to improve prognosis with surgical resection. Several risk factors have been identified, including indwelling catheters, urinary tract infections and bladder calculi. Screening of SCI patients for bladder cancer is routinely recommended in many SCI management guidelines and by expert consensus; however, evidence for screening tools and protocols is lacking. CONCLUSION: Bladder cancer is a rare, and potentially lethal occurrence in SCI patients. Physicians need to have a high index of suspicion for bladder cancer, particularly among SCI patients managed with long-term indwelling catheters.

The surgical management of upper tract stone disease among spinal cord-injured patients.

STUDY DESIGN: Retrospective cohort study, using linked, population-based health-care data. OBJECTIVES: To describe the incidence, management and outcomes of surgically treated kidney stones after spinal cord injury (SCI). To evaluate the impact of a past history of kidney stones on the occurrence of kidney stones. SETTING: Ontario, Canada. METHODS: A total of 5121 patients were followed a median of 4 years after an incident SCI (occurring between 2002 and 2011). The primary outcome was surgical intervention for upper tract kidney stones. RESULTS: In follow-up, 66 patients (1.3%) had 89 episodes of surgically treated kidney stones. Treatments included: ureteroscopic lithotripsy (34%), ureteral stent/percutaneous nephrostomy (30%), shockwave lithotripsy (19%) or percutaneous nephrolithotripsy (17%). Following stone treatment, the 30-day mortality rate was low, and the 30-day admission rate to an intensive care unit was 12%. A history of surgically treated kidney stones before SCI (compared with no such history) was associated with a higher risk of kidney stones after SCI (27 vs 3 per 1000 person-years; adjusted hazard ratio 14.74, 95% confidence interval 5.69-38.22). CONCLUSION: During intermediate follow-up after SCI, surgically treated upper tract kidney stones occur in 1.3% of patients. Ureteroscopy with lithotripsy is the most common treatment. A history of surgically managed kidney stones before SCI portends a higher risk of stones after SCI.

Attempts at formulation of syrup with theophylline.

The aim of this study was attempt to formulate syrup with theophylline. This form of drug would enable easy adjustment of individual doses of drug for therapeutic purposes in children. Due to poor solubility of theophylline in water, attempts at increasing of its solubility by adding special adjuvant substances, which could increase solubility and stabilise the obtained solution, were of particular importance.

Surfactant treatment for ventilation-induced lung injury in rats: effects on lung compliance and cytokines.

The objective of this study was to determine if exogenous surfactant therapy could prevent the harmful effects of ventilation at high tidal volumes without positive end-expiratory pressure (PEEP). Rats were randomized to either a nontreated control group (8 mL/kg 4 cm H2O PEEP), a nontreated injuriously ventilated group (20 mL/kg 0 cm H2O PEEP) or a treatment group of either 50 mg/kg, 50 mg/kg + 5% surfactant-associated protein A, 100 mg/kg exogenous surfactant followed by injurious ventilation. Isolated lungs from animals in all 5 groups were ventilated in a humidified box at 37 degrees C for 2 hours. Pressure-volume curves and light microscopy showed that surfactant treatment reduced the ventilation-induced lung injury (VILI). Inflammatory cytokines (tumor necrosis factor-alpha [TNFalpha], interleukin [IL]-1beta, and IL-6) in the lavage were significantly higher in injuriously ventilated lungs compared to the control group. However the 3 treatment groups had cytokine concentrations that were similar to the injuriously ventilated group. We conclude that surfactant treatment is beneficial in preventing VILI; however, it does not prevent the release of inrflammatory cytokines during mechanical ventilation.

Determination of benzodiazepin-1,4 derivatives in biological material. Part I. An attempt to apply high-performance liquid chromatography (HPLC) in the determination of diazepam and nitrazepam in human serum.

The application of the high performance liquid chromatography method for the determination of diazepam and nitrazepam in serum is described. This method is highly sensitive, and specific, and rapid. Calibration curves are linear in the concentration range 1-1000 ng/ml.