TVT or TVT-O? - A systematic review and meta-analysis comparing efficacy, complications and re-operations.

OBJECTIVES: To compare the efficacy, complications and re-operations after bottom-up tension-free vaginal tape (TVT) and inside-out tension-free vaginal tape - obturator (TVT-O) in the treatment of stress urinary incontinence (SUI) in adult women. STUDY DESIGN: A systematic literature search and review was performed limited to randomized controlled trials. We searched Medline, Embase, Cochrane Library, Cinahl, Guideline International network (GIN), Trip Database and NICE (UK). The certainty in the estimates of the included outcomes was rated using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) method. RESULTS AND CONCLUSIONS: We included 22 randomized controlled trials. The overall certainty in the evidence was moderate across all outcomes. TVT and TVT-O significantly improved the incontinence regarding number of incontinence episodes, subjective patient reported effect and incontinence related quality of life, and there was no difference between TVT and TVT-O. Leg or groin pain was significantly less common 6 months after TVT than TVT-O with RR 0.27 (CI 95 % 0.11 - 0.66), 9 studies, n = 1312. In absolute numbers 83 patients more developed chronic leg or groin pain per 1000 operations with TVT-O compared to TVT. We found no statistically significant differences between chronic pelvic or lower abdominal pain 6 months after TVT and TVT-O. Bladder perforations were significantly more common after TVT with RR 4.53 (CI 95 % 2.32-8.86), 21 studies, n = 3308. In absolute numbers this meant 5 more bladder perforations after TVT per 1000 operations. No statistically significant differences were noted in de novo urgency, re-operations, infection, hematoma, pain during sexual intercourse or sexual function. Bottom-up TVT and inside-out TVT-O showed equal efficacy, but leg and groin pain were much more common with TVT-O. The authors would recommend TVT instead of TVT-O as first line operation in patients who need surgery for SUI.

[Complications in pregnant women with polycystic ovary syndrome]. / Komplikationer hos gravide med polycystisk ovariesyndrom

Pregnant women with polycystic ovary syndrome (PCOS) are at increased risk of pregnancy-related disorders such as gestational diabetes (GDM), gestational hypertension and preeclampsia in the 2nd and 3rd trimester. In addition, the risk of preterm birth, children who are small and large for gestational age, caesarean section and poorer neonatal outcome seem to be elevated, however with less clear evidence. Except for the screening for GDM, there is no evidence of a benefit of increased surveillance during pregnancy for women with PCOS.

[Heterotopic pregnancy following in vitro fertilization with excision of ruptured cornual pregnancy and eventually caesarean section close to term].

We describe a rare case of heterotopic pregnancy following in vitro fertilization with transferring of two embryos in a 39-year-old woman with previous bilateral salpingectomy. An ultrasound examination was performed on the day before admission showing a vital intrauterine pregnancy and no ectopic pregnancy. The woman was admitted with a ruptured cornual pregnancy at ten weeks of gestation. Laparotomy was performed on vital indication with excision of the ruptured haemorrhagic cornual pregnancy. The intrauterine pregnancy continued uneventfully with obstetric and fetal medicine specialist monitoring. A healthy boy was delivered by elective caesarean section.

Formoterol concentrations in blood and urine: the World Anti-Doping Agency 2012 regulations.

INTRODUCTION: We examined urinary and serum concentrations of formoterol in asthmatic and healthy individuals after a single dose of 18 µg inhaled formoterol and after repeated inhaled doses in healthy individuals. Results were evaluated using the World Anti-Doping Agency (WADA) 2012 threshold for formoterol. METHODS: On the day of this open-label, crossover study, 10 asthmatic subjects who regularly used beta2-agonists and 10 healthy participants with no previous use of beta2-agonists received a single dose of 18 µg formoterol. Further, 10 nonasthmatic participants inhaled 18 µg formoterol every second hour until obtaining a total of 72 µg, which is twice the maximum daily dose (36 µg formoterol) permitted by the WADA. Blood samples were collected at baseline, 30 min, 1, 2, 3, 4, and 6 h after the first inhalation. Urine samples were collected at baseline, 0-4, 4-8, and 8-12 h after the first inhalation. RESULTS: Median urine concentration, corrected for specific gravity, after the single-dose administration peaked during 0-4 h after inhalation at a maximum of 7.4 ng·mL(-1) in asthmatic subjects and 7.9 ng·mL(-1) in healthy subjects. Median urine concentration after repeated doses peaked during 4-8 h after inhalation of a total of 72 µg formoterol at a maximum of 16.8 ng·mL(-1) in healthy participants. The maximum individual concentration of 25.6 ng·mL(-1) was found after inhalation of a total of 72 µg formoterol. CONCLUSIONS: We found no significant differences in urinary and serum concentrations of formoterol between asthmatic and healthy subjects. We found high interindividual variability in the concentrations in all groups. Our data support the WADA 2012 urinary threshold of 30 ng·mL(-1) formoterol as being an adverse analytical finding.

The pharmacokinetic profile of inhaled and oral salbutamol in elite athletes with asthma and nonasthmatic subjects.

OBJECTIVE: Data on pharmacokinetics of inhaled and oral salbutamol in elite athletes with asthma are needed to differentiate between therapeutic use and doping in doping control. DESIGN: An interventional open-label crossover. SETTING: Respiratory Research Unit, Copenhagen University Hospital, Bispebjerg. PARTICIPANTS: Eight elite athletes with asthma and 10 nonasthmatic subjects aged 18 to 33 years. INTERVENTION: Administration of 0.8 mg of inhaled salbutamol and 8 mg of oral salbutamol separated by 14 days. MAIN OUTCOME MEASURES: Urine concentration of free salbutamol. RESULTS: Maximum urine concentrations peaked in the period of 0 to 4 hours after the administration of inhaled and oral salbutamol in both groups. Median concentrations after inhaled salbutamol and oral salbutamol were 401.6 and 2108.1 ng/mL in healthy subjects and 334.9 and 2975.2 ng/mL in elite athletes with asthma. There were no significant statistical differences between the groups. One sample exceeded the World Anti-Doping Agency threshold value of 1000 ng/mL with a urinary salbutamol concentration of 1057 ng/mL 4 hours after inhalation, when no correction for urine specific gravity was done. When this sample was corrected for urine specific gravity, the result was 661 ng/mL. CONCLUSIONS: We found no significant difference in pharmacokinetic profile of inhaled and oral salbutamol between elite athletes with asthma and nonasthmatic subjects. Our results indicate that urine salbutamol concentrations should be corrected for urine specific gravity when evaluating doping cases.

Determination of salbutamol and salbutamol glucuronide in human urine by means of liquid chromatography-tandem mass spectrometry.

The determination of salbutamol and its glucuronide in human urine following the inhalative and oral administration of therapeutic doses of salbutamol preparations was performed by means of direct urine injection utilizing liquid chromatography-tandem mass spectrometry (LC-MS/MS) and employing d(3)-salbutamol and d(3)-salbutamol glucuronide as internal standards. Unconjugated salbutamol was detected in all administration study urine samples. Salbutamol concentrations following inhalation were commonly (99%) below 1000 ng/ml whereas values after oral administration frequently (48%) exceeded this threshold. While salbutamol glucuronide was not detected in urine samples collected after inhalation of the drug, 26 out of 82 specimens obtained after oral application contained salbutamol glucuronide with a peak value of 63 ng/ml. The percentage of salbutamol glucuronide compared to unconjugated salbutamol was less than 3%. Authentic doping control urine samples indicating screening results for salbutamol less than 1000 ng/ml, showed salbutamol glucuronide concentrations between 2 and 6 ng/ml, whereas adverse analytical findings resulting from salbutamol levels higher than 1000 ng/ml, had salbutamol glucuronide values between 8 and 15 ng/ml. The approach enabled the rapid determination of salbutamol and its glucuronic acid conjugate in human urine and represents an alternative to existing procedures since time-consuming hydrolysis or derivatization steps were omitted. Moreover, the excretion of salbutamol glucuronide in human urine following the administration of salbutamol was proven.

Is pulmonary function affected by bilateral dual transversus abdominis plane block? A randomized, placebo-controlled, double-blind, crossover pilot study in healthy male volunteers.

BACKGROUND AND OBJECTIVES: Transversus abdominis plane (TAP) blocks have been shown to reduce postoperative pain after various abdominal surgical procedures in several studies. The motor nerves of the abdominal wall are located in the same plane as the sensory nerves affected by the TAP block. The aim of this study was to examine whether the application of an ultrasound-guided TAP block would affect the muscles of the anterior abdominal wall with respect to their function as accessory respiratory muscles and hence pulmonary function. METHODS: Twelve healthy male volunteers were included in a randomized, double-blind, crossover study. Primary outcome measure was change in forced expiratory volume in 1 sec (FEV1) after the bilateral dual injection of either 4 × 15 mL of 0.25% bupivacaine or saline. Secondary outcome measures included forced vital capacity, maximum expiratory pressure, and a number of frontal abdominal quadrants anesthetized. RESULTS: Change in FEV1 following the administration of bupivacaine showed a mean increase of 15 (SEM, 45.5) mL compared with the saline block, which showed a mean increase in FEV1 of 34 (SEM, 57.4) mL (P = 0.62). Similar results were obtained for forced vital capacity and maximum expiratory pressure. Abdominal quadrants were inconsistently anesthetized following administration of bupivacaine blocks. CONCLUSIONS: The administration of ultrasound-guided bilateral dual TAP blocks does not result in clinically relevant or statistically significant changes in the pulmonary function in healthy male subjects.

Asthma in elite athletes: pathogenesis, diagnosis, differential diagnoses, and treatment.

Elite athletes have a high prevalence of asthma and exercise-induced bronchoconstriction. Although respiratory symptoms can be suggestive of asthma, the diagnosis of asthma in elite athletes cannot be based solely on the presence or absence of symptoms; diagnosis should be based on objective measurements, such as the eucapnic voluntary hyperpnea test or exercise test. When considering that not all respiratory symptoms are due to asthma, other diagnoses should be considered. Certain regulations apply to elite athletes who require asthma medication for asthma. Knowledge of these regulations is essential when treating elite athletes. This article is aimed at physicians who diagnose and treat athletes with respiratory symptoms. It focuses on the pathogenesis of asthma and exercise-induced bronchoconstriction in elite athletes and how the diagnosis can be made. Furthermore, treatment of elite athletes with asthma, anti-doping regulations, and differential diagnoses such as exercise-induced laryngomalacia are discussed.

Asthma in elite athletes.

Asthma is frequently found among elite athletes performing endurance sports such as swimming, rowing and cross-country skiing. Although these athletes often report symptoms while exercising, they seldom have symptoms at rest. Moreover, compared with nonathletic asthmatic individuals, elite athletes have been shown to have a different distribution of airway inflammation and unequal response to bronchial provocative test. Elite athletes display signs of exercise-induced symptoms, for example, nonasthmatic inspiratory wheeze, vocal cord dysfunction and cardiac arrhythmias, which could limit their physical capacity. Elite athletes should undergo comprehensive assessment to confirm an asthma diagnosis and determine its degree of severity. Treatment should be as for any other asthmatic individual, including the use of ß2-agonist, inhaled steroid as well as leukotriene-antagonist. It should, however, be noted that daily use of ß-agonists could expose elite athletes to the risk of developing tolerance towards these drugs. Use of ß2-agonist should be replaced with daily inhaled corticosteroid treatment, the most important treatment of exercise-induced asthma. All physicians treating asthma should be aware of the doping aspects. Systemic ß2-agonist intake is strictly prohibited, whereas inhaled treatment is allowed in therapeutic doses when asthma is documented and dispensation has been granted when needed.

Daily use of salmeterol causes tolerance to bronchodilation with terbutaline in asthmatic subjects.

BACKGROUND: The purpose was to assess tolerance to terbutaline after daily use of long-acting beta2- agonist (LABA) and further to evaluate two designs of reversibility test widely used in research and clinic in order to demonstrate tolerance. METHODS: Twenty-eight asthmatics were given daily LABA in 12 weeks and were randomized to challenge test and either conventional reversibility test with 2 puffs terbutaline or reversibility test with refracted doses (1 puff) every 5 min, total 4 puffs. FEV(1) was measured pre-challenge, post-challenge, during and after reversibility test. All subjects had 3 visits: baseline, after 4 weeks and after 12 weeks of LABA treatment. All subjects were non-smokers, aged 18-45 years and had a positive methacholine challenge. RESULTS: The analyses showed a significant fall in reversibility after 4 and 12 weeks of LABA treatment (p=0.001) in the group with the conventional reversibility test. The group with reversibility test using refracted doses also showed a significant fall in reversibility after 4 weeks of LABA treatment (p=0.017) followed by a similar trend after 12 weeks (p=0.054), however, we experienced an interfering number of dropouts at the last visit. CONCLUSION: The bronchodilator response to terbutaline was significantly reduced in asthmatic subjects using daily LABA. The tolerance develops rapidly and is present after 4 weeks of treatment. Our study showed that both the conventional reversibility test and the reversibility test with refracted doses, combined with methacholine challenge is able to demonstrate tolerance to bronchodilator after daily use of LABA.

Blood and urinary concentrations of salbutamol in asthmatic subjects.

PURPOSE: Data on blood and urinary concentrations of salbutamol after inhalation and oral administration in healthy subjects are scarce. Accordingly, we examined the pharmacokinetics of inhaled and oral salbutamol in asthmatic subjects. METHODS: We enrolled 10 men aged 18-45 yr in an open-label study in which 0.8 mg of inhaled or 8 mg of systemic salbutamol was administered in a crossover design. All subjects had doctor-diagnosed asthma, used beta2 agonist when needed, and abstained from any medicine, beta2 agonist inclusive, for 14 d before visit. Urine was collected from all subjects (0-4, 4-8, and 8-12 h), and blood samples were taken at 0, 0.5, 1, 2, 3, 4, and 6 h after salbutamol administration. RESULTS: Maximum urine concentration was reached during the first 4 h after administration of both inhaled and oral salbutamol. We found differences in median urinary concentrations (Cmax) of 260.9 and 2422.2 ng x mL(-1), respectively (P < 0.005). Urinary concentrations show high individual variability irrespective of the route of administration. Blood analyses showed a systemic exposure of salbutamol after both inhaled and oral salbutamol with peak concentration after inhalation before the oral intake (P < 0.05). A difference in median Cmax after inhalation and oral treatment was found: 1.75 and 18.77 ng x mL(-1), respectively (P < 0.05). CONCLUSIONS: Median urinary concentrations after oral administration of 8 mg of salbutamol were significantly higher than those after inhalation of 0.8 mg of salbutamol.