High-sensitive troponinT, interleukin-8, and interleukin-6 link with post-surgery risk in infant heart surgery.

BACKGROUND: This study focuses on biomarkers in infants after open heart surgery, and examines the association of high-sensitive troponin T (hs-cTnT), interleukin-6 (IL-6), and interleukin-8 (IL-8) with postoperative acute kidney injury (AKI), ventilatory support time and need of vasoactive drugs. METHODS: Secondary exploratory study from a double-blinded clinical randomized trial (Mile-1) on 70 infants undergoing open heart surgery with cardiopulmonary bypass (CPB). In this sub-study, the entire study population was examined without considering the study drugs. The biomarkers' peak concentration (highest concentration at 2 or 6 h post-CPB) were used for statistical analyses. RESULTS: Peak IL-8, hs-cTnT, and IL-6 occurred at 2 h post-CPB for 96%, 79%, and 63% of the patients, respectively. The odds ratio of developing AKI2-3 for IL-6 > 293 pg/mL was 23.4 (95% CI 5.3;104.0), for IL-8 > 100 pg/mL it was 11.5 (3.0;44.2), and for hs-cTnT >5597 pg/mL it was 6.1 (1.5; 24.5). In more than two third of the patients with the highest peak concentrations of IL-8, IL-6, and hs-cTnT, there was a need for ventilatory support for >24 h and use of vasoactive drugs at 24 h post-CPB, while in less than one third of the patients with the lowest peak concentrations of IL-8 and hs-cTnT such requirements were observed. CONCLUSIONS: The peak biomarker concentrations and CPB-time strongly predicted AKI2-3, with IL-6 and IL-8 emerging as strongest predictors. Furthermore, our findings suggest that measuring hs-cTnT and IL-8 just 2 h post-CPB-weaning may assist in identifying infants suitable for early extubation and highlight those at risk of prolonged ventilation.

Severity and impact of accidental bowel leakage two decades after no, one, or two sphincter injuries.

BACKGROUND: Information about the long-term severity and subjective impact of anal incontinence in women after 1 or 2 consecutive obstetrical anal sphincter injuries is still scarce and contradictory. OBJECTIVE: This study aimed to describe the severity and impact of anal incontinence among women with 2 previous deliveries 2 decades after birth and to analyze the relative effect of 1 vs 2 obstetrical anal sphincter injuries in comparison with no obstetrical anal sphincter injuries and the possible influence of obstetrical anal sphincter injury on other pelvic floor disorders. STUDY DESIGN: We linked prospectively registered data in the Swedish Medical Birth Register with information from a postal and web-based questionnaire in 2015. Statistics Sweden identified women with 2 vaginal births from 1992 to 1998, and a simple random sample of 11,000 women was drawn from a source cohort of 64,687 women. To achieve equal-sized groups of women with 1 or 2 obstetrical anal sphincter injuries, the latter group was oversampled from 1987 to 2000. The final study cohorts consisted of 6760 women with no obstetrical anal sphincter injury, 357 women with 1 injury, and 324 women with 2 obstetrical anal sphincter injuries. Third- and fourth-degree perineal tears were grouped together for analysis. Anal incontinence was defined as either fecal or isolated gas incontinence, and fecal incontinence was defined as involuntary leakage of solid or liquid stool with or without concomitant gas. Frequencies of leakage of stool and gas were dichotomized into low frequency (less than once a month) and high frequency (several times a month or more often). Pairwise comparisons were analyzed using Fisher exact tests, Mantel-Haenszel statistics, and the Mann-Whitney U test. Trends were analyzed using Mantel-Haenszel statistics and the Spearman rank correlation test. Logistic regression models were used to obtain the age- and body-mass-index -adjusted odds ratios for outcomes. Statistical significance was set at P<.05. RESULTS: The response rate was 65.5% in the randomly selected cohort and 70.1% among women with 2 obstetrical anal sphincter injuries. Bothersome fecal incontinence occurred in 3.3% (212/6458) of women without obstetrical anal sphincter injury, in 10.4% (36/345) (adjusted odds ratio, 3.25; 95% confidence interval, 2.23-4.73) of those with 1 injury, and in 16.5% (52/315) (adjusted odds ratio, 5.16; 95% confidence interval, 3.69-7.22) of those with 2 obstetrical anal sphincter injuries (trend P<.0001). Fecal incontinence was perceived as bothersome in 28.2% (212/753) of women without an obstetrical anal sphincter injury compared with in 43.9% (36/82) and 46.0% (52/113) of those with 1 or 2 obstetrical anal sphincter injuries (trend P<.0001). Leakage of liquid stool occurred in 10.8% (724/6717) of those without injury, in 21.7% (77/355) of women with 1 injury, and 34.9% (113/324) of women with 2 obstetrical anal sphincter injuries (trend P<.0001). Incontinence affecting daily life was reported by 8.6% (577/6672) of women without injury and by 19.7% (69/351) and 29.6% (96/324) of women with 1 and 2 sphincter injuries, respectively (trend P<.0001). The mean Jorge-Wexner score was 2.44, 3.26, and 3.88 for women with no, 1, or 2 sphincter injuries (trend P<.0001). Among women with a Jorge-Wexner score of 6, >50% had bothersome anal incontinence. The adjusted odds ratio for the overall effect of 1 vs 2 obstetrical anal sphincter injuries on measures of anal incontinence was 2.19 (95% confidence interval, 1.68-2.85) and 3.91 (95% confidence interval, 3.06-5.00), respectively, when compared with no obstetrical anal sphincter injury (both P<.0001). Having 1 or 2 obstetrical anal sphincter injuries had no significant effect on other pelvic floor disorders or on lower urinary tract symptoms (P=.73 and P=.69). CONCLUSION: A consistent additive effect of 1 or 2 sphincter injuries on the severity and impact of anal incontinence was observed in women 2 decades after 2 vaginal births. This information is important for healthcare economics, clinical practice, and policy.

The influence of pregnancy, parity, and mode of delivery on urinary incontinence and prolapse surgery-a national register study.

BACKGROUND: The long-term effects of vaginal delivery, parity, and pregnancy on the pelvic floor remain uncertain and controversial issues. In comparison with studies using self-reported symptoms, surgical register data may offer a more valid means for evaluating the relative influence of these risk factors. OBJECTIVE: This study used data from 3 high-quality nationwide registers, namely the Swedish National Quality Register of Gynecological Surgery, the Swedish Medical Birth Register, and the Total Population Register, to evaluate the contribution of vaginal and cesarean delivery, parity, and factors not related to childbirth to the long-term risk for reconstructive urogenital surgery. STUDY DESIGN: This was a register-based linkage study among women aged ≥45 years who underwent urinary incontinence or prolapse surgery from 2010 to 2017. This surgical cohort was divided into nulliparous women, women with ≥1 cesarean deliveries only, those with ≥1 vaginal deliveries, and according to the number of births. A corresponding reference group was constructed based on women born in 1960 from the Total Population Register (n=2,309,765). The Swedish Medical Birth Register was used to determine the rate of women with cesarean and vaginal delivery and their respective parity. Absolute and relative risk were presented per 1000 women with 95% confidence intervals. Pairwise differences were analyzed with Fisher exact tests and the Mann-Whitney U test for dichotomous and continuous variables. The trend between ≥3 ordered categories of dichotomous variables was analyzed with Mantel-Haenszel statistics. RESULTS: A total of 39,617 women underwent prolapse surgery and 20,488 underwent incontinence surgery. Among women with prolapse surgery, 97.8% had ≥1 vaginal delivery, 0.4% had ≥1 cesarean delivery only, and 1.9% were nullipara. Corresponding figures for those with incontinence surgery were 93.1%, 2.6%, and 4.3%, respectively. Women with vaginal deliveries were overrepresented in the prolapse surgery (relative risk, 1.23; 95% confidence interval, 1.22-1.24; P<.001) and incontinence surgery groups (relative risk, 1.17; 95% confidence interval, 1.15-1.19; P<.001). Nulliparous and cesarean delivered women were underrepresented in the prolapse surgery (relative risk, 0.14; 95% confidence interval, 0.13-0.15 and relative risk 0.055; 95% confidence interval, 0.046-0.065; all P<.001) and incontinence surgery groups (relative risk, 0.31; 95% confidence interval, 0.29-0.33 and relative risk, 0.40; 95% confidence interval, 0.36-0.43). The absolute risk for prolapse surgery was lowest after cesarean delivery (0.09 per 1000 women; 95% confidence interval, 0.08-0.11) and differed by a factor of 23 (absolute risk, 2.11 per 1000 women; 95% confidence interval, 2.09-2.13) from that after vaginal birth. The absolute risk for prolapse and incontinence surgery increased consistently with parity after vaginal births. This trend was not observed after cesarean delivery, which is on par with that of nulliparous women. The first vaginal birth contributed the highest increase in the absolute risk for pelvic organ prolapse surgery (6-fold) and stress urinary incontinence surgery (3-fold). The second vaginal birth contributed the lowest increase in the absolute risk for pelvic organ prolapse surgery (∼1/3 of the first vaginal birth) and for stress urinary incontinence surgery (∼1/10 of the first vaginal birth). CONCLUSION: Surgery for urinary incontinence and prolapse was almost exclusively related to vaginal parity. The risk for prolapse surgery increased consistently with parity after vaginal births but not after cesarean delivery, whereas the risk associated with cesarean delivery was on par with that of nulliparous women. Thus, cesarean delivery seems to offer protection from the need for pelvic organ prolapse and stress urinary incontinence surgery later in life.

The influence of age and health status for outcomes after mid-urethral sling surgery-a nationwide register study.

INTRODUCTION AND HYPOTHESIS: The efficacy of mid-urethral sling (MUS) surgery in older women and women with a significant disease burden is limited. We aimed to determine the influence of chronological age and physical status (assessed by the American Society of Anesthesiologists Physical Status, ASA) classification on outcomes. METHODS: Cure rate, change in frequency of lower urinary tract symptoms, satisfaction, impact, and adverse events after MUS surgery were assessed in 5200 women aged 55-94 years with MUS surgery (2010-2017). Data were analysed by multivariate logistic regression and Mantel-Haenszel chi-square statistics. RESULTS: The cure rate was 64.2% (95% CI, 60.0-68.4) in the ≥ 75-year cohort compared to 88.5% (95% CI, 87.1-89.8) in the 55-64-year cohort (trend p < 0.0001). The estimated probability of cure, improvement, and satisfaction with the procedure decreased by aOR10yr = 0.51 for cure to aOR10yr = 0.59 for satisfaction (all p < 0.0001). Women with a significant health burden (ASA class 3-4) had lower cure rates and satisfaction than those without (65.5% vs. 83.7%, p < 0.0001 and 65.7% vs. 80.6%, p < 0.0001). Older age was more likely to be associated with de novo urgency (p = 0.0022) and nocturia ≥ 2 (p < 0.0001). Adverse events, readmission, and 30-day mortality rates were low. Women, irrespective of age, were equally satisfied if they experienced a decrease of at least one step in leakage frequency. CONCLUSIONS: Even if MUS surgery in older women and those with ASA class 3-4 was associated with a lower cure rate and less satisfactory outcome, a majority were satisfied provided they experienced a reduction of incontinence episodes.

Fecal incontinence in nonpregnant nulliparous women aged 25 to 64 years-a randomly selected national cohort prevalence study.

BACKGROUND: The extent to which fecal incontinence is associated with obstetrical history or pelvic floor injuries is still a controversial and unresolved issue. One crucial first step toward answering this question is the need to study fecal incontinence in nonpregnant, nulliparous women. OBJECTIVE: The aim of this study was to present detailed, descriptive measures of the accidental leakage of liquid or solid stool and gas in a randomly selected, large national cohort of nonpregnant, nulliparous women aged 25 to 64 years. STUDY DESIGN: The Swedish Total Population Register identified the source population. Four independent, age-stratified, simple random samples in a total of 20,000 nulliparous women aged 25 to 64 years were drawn from 625,810 eligible women. Information was collected in 2014 using postal and web-based questionnaires. The 40-item questionnaire included questions about the presence and frequency of the leakage of solid and liquid stool and gas, which provided the basis for the generic terms fecal and anal incontinence. Statistical analyses of the differences between the groups were performed using the Fisher's exact test for dichotomous variables and the Mann-Whitney U-test for continuous variables. The trend between >2 ordered categories of dichotomous variables was analyzed with Mantel-Haenszel statistics. When analyzing the trend between multiple ordered vs nonordered categorical variables, the Kruskal-Wallis test was used. The age-related probability and risk increase per 10 years for incontinence parameters was calculated from logistic regression models adjusted for body mass index. RESULTS: The study population was 9197 women, and the response rate was 52.2%, ranging from 44.7% in women aged 25 to 34 years to 62.4% among those from 55 to 64 years. All the types of incontinence, except severe isolated gas incontinence, increased with age up to 64 years. The estimated probability of fecal incontinence was 8.8% at age 25 years and 17.6% at age 64. The leakage of liquid stool was dominant, occurring in 93.1% (95% confidence interval, 91.4-94.5) of the women with fecal incontinence, whereas leakage of solid stool occurred in 33.9% (95% confidence interval, 31.1-36.7), of which approximately 80% also had concomitant leakage of liquid stool. The leakage of liquid stool increased markedly up to age 65, whereas the increase in the isolated leakage of solid stool was negligible across all ages (overall <0.4%). Liquid and solid stool, separate or in combination, co-occurred with gas in approximately 80%. The distribution pattern of the different types of leakage, single or combined, was similar in all the age groups. Both age and body mass index (kg/m2) were risk factors for fecal incontinence (P<.0001), with an interaction effect of P=.16. CONCLUSION: Abnormal stool consistency has been identified as the strongest risk factor for accidental bowel leakage. The same pattern characterized by a dominance of liquid stool and gas leakage, prevalent concomitant leakage of solid and liquid stool, and a negligible rate of isolated leakage of solid feces was observed across all ages. The low rates of isolated leakage of solid stool support the impression that dysfunction of the continence mechanism of the pelvic floor had a negligible role for bowel incontinence, which is essential information for comparison with women with birth-related injuries.

Symptoms of fecal incontinence two decades after no, one, or two obstetrical anal sphincter injuries.

BACKGROUND: The long-term effects of 1 or 2 consecutive obstetrical anal sphincter injuries on bowel continence are still inadequately investigated, and published results remain contradictory. OBJECTIVE: This study aimed to present detailed descriptive measures of the current bowel incontinence 20 years after the first birth in women who had 2 vaginal deliveries with and without sphincter injuries. STUDY DESIGN: Birth register data were used prospectively and linked to information from a questionnaire survey about current symptoms. Women with 2 singleton vaginal births, from 1992 to 1998, and no further births were retrieved and surveyed by the Swedish Medical Birth Register and Statistics Sweden in 2015. A simple random sample of 11,000 women was drawn from a source cohort of 64,687 women. The cumulative effect was studied in all women with a repeat sphincter injury from 1987 to 2000. Postal and web-based questionnaires were used. The study population consisted of 6760 women with no sphincter injury, 357 with 1 sphincter injury, and 324 women with 2 sphincter injuries. Women with 2 deliveries without sphincter injuries aged 40 to 60 years as reference, were compared with those of women that sustained 1 or 2 consecutive sphincter injuries. Here, third- and fourth-degree perineal tears were presented as 1 group. Fecal incontinence was defined as current involuntary leakage of solid or liquid stool, with and without concomitant leakage of gas. The Fisher exact test and the Mann-Whitney U test were used to compare the results of the 2 groups. The trend was analyzed using the Mantel-Haenszel statistics. Logistic regression models obtained the estimated age-related probability of fecal incontinence components. RESULTS: The risk of sphincter injury at first delivery was 3.9%, and the risk of a repeat sphincter injury was 10.0% (odds ratio, 2.70; 95% confidence interval, 1.80-4.07). The overall prevalence of fecal incontinence in women without sphincter injuries was 11.7%, which doubled to 23.8% (odds ratio, 2.27; 95% confidence interval, 1.75-2.94) in those with 1 sphincter injury and more than tripled to 36.1% (odds ratio, 3.97; 95% confidence interval, 3.11-5.07) after 2 sphincter injuries (trend P<.0001). The proportion of women with severe fecal incontinence increased 3-fold and 5-fold from 1.8% after no obstetrical anal sphincter injury to 5.4% (95% confidence interval, 3.3-8.2) and 9.0% (95% confidence interval, 6.1-12.6) after 1 or 2 obstetrical anal sphincter injuries, respectively (trend P<.0001). In women without sphincter injuries, the estimated probability of fecal incontinence increased from 7.0% at the age of 40 years to 19.8% at the age of 60 years. In contrast, in women with 1 or 2 sphincter injuries, the estimated probability of fecal incontinence increased from 26.1% and 33.3%, respectively, at the age of 40 years to 36.8% and 48.8% at the age of 60 years. The prevalence of fecal incontinence increased after 52 years of age in women with 1 or 2 sphincter injuries. The dominant types of leakage in women with fecal incontinence were the combination of liquid stool and gas, and the triple combination consisting of solid and liquid stools and gas. The triple combination increased from 18.9% in those without sphincter injury to 28.2% in women with 2 injuries (trend P=.0204). CONCLUSION: The risk of sustaining a repeat sphincter injury at the second delivery was almost tripled compared with the risk at the first delivery. Furthermore, 1 or 2 sphincter injuries brought severe long-term consequences for bowel continence. Accidental leakage of stool and gas increased with each sphincter injury, and the effect was proportionally cumulative. After the age of 52 years, the prevalence of fecal incontinence seemed to accelerate.

Childhood nocturnal enuresis-a marker for pelvic floor disorders and urinary tract symptoms in women?

INTRODUCTION AND HYPOTHESIS: A systematic survey on the association between childhood nocturnal enuresis (CNE) and adult pelvic floor disorders (PFDs) has not been presented previously. The aim was to describe the prevalence of PFDs and lower urinary tract symptoms in nulliparous women, with or without a history of CNE, at the age of ≥ 5 years. METHODS: This national survey of urinary (UI) and fecal incontinence (FI) and symptoms of pelvic organ prolapse (sPOP) was a random sample of 20,000 nulliparous women aged 25-64 years conducted in 2014. Women ≥ 5 years of age having CNE were compared with those without the condition. Fisher's exact test and logistic regression adjusted for BMI and age were used to analyze differences between groups. RESULTS: The response rate was 52% and 10.2% of adult women reporting CNE. One or more PFDs occurred in 38.3% of women with CNE compared to 23.8% in those without CNE (p < 0.0001). Mixed UI had the strongest association with CNE, odds ratio (OR) 2.63 (95% CI 2.03-3.40). The rate of FI was 11.2% in the non-CNE group and 16.8% in those with CNE (p < 0.0001) and sPOP 2.6% in the non-CNE and 4.8% in the CNE group (p = 0.0004), respectively. The prevalence of lower urinary tract symptoms was consistently higher in women with a history of CNE: overactive bladder 32.6% versus 18.4% (OR 2.34 95% CI 2.03-3.40), daytime micturition ≥ 8/day 29.6% versus 24.0% (p < 0.0001), and nocturia ≥ 2/night 12.4% versus 7.8% (p < 0.0001) in the CNE group. CONCLUSION: PFDs and lower urinary tract symptoms in nulliparous women were approximately doubled in women with a history of CNE and could therefore act as a strong confounding factor.

Levosimendan Versus Milrinone and Release of Myocardial Biomarkers After Pediatric Cardiac Surgery: Post Hoc Analysis of Clinical Trial Data.

OBJECTIVES: We compared the effect of two inodilators, levosimendan and milrinone, on the plasma levels of myocardial injury biomarkers, that is, high-sensitivity troponin T and heart-type fatty acid binding protein, and on N-terminal prohormone of brain natriuretic peptide as a biomarker of ventricular function. We hypothesized that levosimendan could attenuate the degree of myocardial injury when compared with milrinone. DESIGN: A post hoc, nonprespecified exploratory secondary analysis of the Milrinone versus Levosimendan-1 trial (ClinicalTrials.gov Identifier: NCT02232399). SETTING: Two pediatric tertiary university hospitals. PATIENTS: Infants 1-12 months old, diagnosed with ventricular septal defect, complete atrioventricular septal defect, or Tetralogy of Fallot undergoing corrective surgery with cardiopulmonary bypass. INTERVENTIONS: Seventy patients received a loading dose of either levosimendan or milrinone at the start of cardiopulmonary bypass followed by an infusion of the respective drug, which continued for 26 hours. MEASUREMENTS AND MAIN RESULTS: Plasma levels of the three cardiac biomarkers were measured prior to the initiation of cardiopulmonary bypass and 2, 6, and 24 hours after weaning from cardiopulmonary bypass. In both groups, the levels of high-sensitivity troponin T and heart-type fatty acid binding protein were highest at 2 hours post cardiopulmonary bypass, whereas the highest level of N-terminal prohormone of brain natriuretic peptide occurred at 24 hours post cardiopulmonary bypass. There was no significant difference in the biomarkers' plasma levels between the study groups over time. Neither was there a significant difference in the postoperative peak plasma levels of the cardiac biomarkers. CONCLUSIONS: In this post hoc analysis of the MiLe-1 trial, there was no demonstrable difference in the postoperative cardiac biomarker profile of myocardial injury and ventricular function when comparing infants managed in the perioperative period with levosimendan versus milrinone.

Induction of labour at 41 weeks or expectant management until 42 weeks: A systematic review and an individual participant data meta-analysis of randomised trials.

BACKGROUND: The risk of perinatal death and severe neonatal morbidity increases gradually after 41 weeks of pregnancy. Several randomised controlled trials (RCTs) have assessed if induction of labour (IOL) in uncomplicated pregnancies at 41 weeks will improve perinatal outcomes. We performed an individual participant data meta-analysis (IPD-MA) on this subject. METHODS AND FINDINGS: We searched PubMed, Excerpta Medica dataBASE (Embase), The Cochrane Library, Cumulative Index of Nursing and Allied Health Literature (CINAHL), and PsycINFO on February 21, 2020 for RCTs comparing IOL at 41 weeks with expectant management until 42 weeks in women with uncomplicated pregnancies. Individual participant data (IPD) were sought from eligible RCTs. Primary outcome was a composite of severe adverse perinatal outcomes: mortality and severe neonatal morbidity. Additional outcomes included neonatal admission, mode of delivery, perineal lacerations, and postpartum haemorrhage. Prespecified subgroup analyses were conducted for parity (nulliparous/multiparous), maternal age (<35/≥35 years), and body mass index (BMI) (<30/≥30). Aggregate data meta-analysis (MA) was performed to include data from RCTs for which IPD was not available. From 89 full-text articles, we identified three eligible RCTs (n = 5,161), and two contributed with IPD (n = 4,561). Baseline characteristics were similar between the groups regarding age, parity, BMI, and higher level of education. IOL resulted overall in a decrease of severe adverse perinatal outcome (0.4% [10/2,281] versus 1.0% [23/2,280]; relative risk [RR] 0.43 [95% confidence interval [CI] 0.21 to 0.91], p-value 0.027, risk difference [RD] -57/10,000 [95% CI -106/10,000 to -8/10,000], I2 0%). The number needed to treat (NNT) was 175 (95% CI 94 to 1,267). Perinatal deaths occurred in one (<0.1%) versus eight (0.4%) pregnancies (Peto odds ratio [OR] 0.21 [95% CI 0.06 to 0.78], p-value 0.019, RD -31/10,000, [95% CI -56/10,000 to -5/10,000], I2 0%, NNT 326, [95% CI 177 to 2,014]) and admission to a neonatal care unit ≥4 days occurred in 1.1% (24/2,280) versus 1.9% (46/2,273), (RR 0.52 [95% CI 0.32 to 0.85], p-value 0.009, RD -97/10,000 [95% CI -169/10,000 to -26/10,000], I2 0%, NNT 103 [95% CI 59 to 385]). There was no difference in the rate of cesarean delivery (10.5% versus 10.7%; RR 0.98, [95% CI 0.83 to 1.16], p-value 0.81) nor in other important perinatal, delivery, and maternal outcomes. MA on aggregate data showed similar results. Prespecified subgroup analyses for the primary outcome showed a significant difference in the treatment effect (p = 0.01 for interaction) for parity, but not for maternal age or BMI. The risk of severe adverse perinatal outcome was decreased for nulliparous women in the IOL group (0.3% [4/1,219] versus 1.6% [20/1,264]; RR 0.20 [95% CI 0.07 to 0.60], p-value 0.004, RD -127/10,000, [95% CI -204/10,000 to -50/10,000], I2 0%, NNT 79 [95% CI 49 to 201]) but not for multiparous women (0.6% [6/1,219] versus 0.3% [3/1,264]; RR 1.59 [95% CI 0.15 to 17.30], p-value 0.35, RD 27/10,000, [95% CI -29/10,000 to 84/10,000], I2 55%). A limitation of this IPD-MA was the risk of overestimation of the effect on perinatal mortality due to early stopping of the largest included trial for safety reasons after the advice of the Data and Safety Monitoring Board. Furthermore, only two RCTs were eligible for the IPD-MA; thus, the possibility to assess severe adverse neonatal outcomes with few events was limited. CONCLUSIONS: In this study, we found that, overall, IOL at 41 weeks improved perinatal outcome compared with expectant management until 42 weeks without increasing the cesarean delivery rate. This benefit is shown only in nulliparous women, whereas for multiparous women, the incidence of mortality and morbidity was too low to demonstrate any effect. The magnitude of risk reduction of perinatal mortality remains uncertain. Women with pregnancies approaching 41 weeks should be informed on the risk differences according to parity so that they are able to make an informed choice for IOL at 41 weeks or expectant management until 42 weeks. Study Registration: PROSPERO CRD42020163174.

Symptomatic pelvic organ prolapse in middle-aged women: a national matched cohort study on the influence of childbirth.

BACKGROUND: The relative impact of age, pregnancy, and vaginal delivery on symptomatic pelvic organ prolapse is still an unresolved issue that involves the controversial question about the protective effect of cesarean section. OBJECTIVE: The purpose of this study was to compare the age-related prevalence of symptomatic genital prolapse in nulliparous, vaginal- and cesarean-delivered women aged 40-64 years. STUDY DESIGN: This Swedish, nationwide matched cohort study involved 14,335 women. Three restricted, randomly selected source cohorts of women (nulliparous women unexposed to childbirth [n = 9136], 1-para cesarean delivered women, exposed to 1 pregnancy [n = 1412], and 1-para women exposed to 1 pregnancy followed by vaginal delivery [n = 3787]) were retrieved from the Swedish Medical Birth Register and Statistics Sweden and surveyed in 2008 and 2014. The surveys used a postal and Internet-based questionnaire containing validated questions for pelvic floor disorders. Symptomatic prolapse was defined by the question, "Do you have a sensation of tissue protrusion (a vaginal bulge) from your vagina?" In this study the symptom frequencies, sometimes and often, were defined as a positive response. Parous women were all assessed 20 years postnatally. One-to-one matching with an age interval for pairing of 3 years and 3 units of body mass index (kilograms per square meter) was used in women aged 40-64 years. The procedure succeeded in 2635 of 2640 women (99.8%), resulting in an adequate distribution of age and body mass index (kilograms per square meter) between matched groups. For comparison between groups, a Fisher exact test was used for categorical variables and the Mann-Whitney U test for continuous variables. Trend between matched groups was analyzed with Mantel-Haenszel statistics. Estimated, age-related values of symptomatic prolapse were obtained by logistic regression analysis. RESULTS: In nulliparous and cesarean-delivered women, the prevalence of symptomatic prolapse was relatively similar and below 5% across ages 40-64 years. In contrast, in women after vaginal delivery, there was an accelerating increase in the prevalence of symptomatic genital prolapse up to 65 years of age. Estimated probability from the regression model increased 4-fold, from 3.8% at 40 years to 13.4% at 64 years of age. The observed induction period associated with 1 vaginal delivery seemed to be at least 20 years among women giving birth in their early 20s. At age 64 years, the estimated probability of symptomatic prolapse was 12 times higher after vaginal delivery compared with cesarean deliery (13.4% [95% confidence interval, 9.4-18.9] vs 1.1% [95% confidence interval, 0.4-2.5], P < .0001). The calculated reduction of symptomatic prolapse by cesarean delivery at 64 years of age was thus 92%. CONCLUSION: In this national matched cohort study, the interaction between vaginal delivery and aging was the most important factor for the occurrence of symptomatic prolapse. Because the effect of aging can be modified only to a small extent, preventive strategies for genital prolapse should focus on how to avoid the adverse events related to a vaginal delivery.

The effect of childbirth on urinary incontinence: a matched cohort study in women aged 40-64 years.

BACKGROUND: The relative impact of age, pregnancy and vaginal delivery on urinary incontinence is still an unresolved issue that involves the controversial question about the protective effect of cesarean delivery. OBJECTIVE: The purpose of this study was to estimate and compare the effect size of 1 pregnancy, 1 vaginal delivery, and the derived protective effect of cesarean delivery for different aspects of urinary incontinence in women 40-64 years old, all 20 years after birth. STUDY DESIGN: This Swedish nationwide matched cohort study involved 14,335 women. Data from 3 restricted, randomly selected, source cohorts of (1) nulliparous women who were unexposed to childbirth (n=9136), (2) primiparous women who had experienced cesarean delivery and who had been exposed to 1 pregnancy (n=1412), and (3) primiparous women who had been exposed to 1 pregnancy followed by vaginal delivery (n=3787) were retrieved from The Swedish Medical Birth Register and Statistics Sweden and surveyed in 2008 and 2014, respectively. Parous women were all assessed 20 years postnatally. One-to-one matching with an interval for pairing of 3 years and 3 body mass index units was used in women 40-64 years old with information about body mass index (kilograms/square meters) and urinary incontinence. The procedure succeeded in 2630 of 2635 women (99.8%) and resulted in an adequate distribution of age and body mass index between groups. The surveys used a postal- and an internet-based questionnaire with validated questions for various aspects of urinary incontinence. Fisher's exact test and the Mann-Whitney U test were used for comparisons between matched groups; trend was analyzed with Mantel-Haenszel statistics. Predicted, age-related values of different aspects of urinary incontinence were obtained by logistic regression analysis. RESULTS: Pregnancy increased the prevalence of urinary incontinence from 20.1-30.1% (odds ratio, 1.71; 95% confidence interval, 1.43-2.05; P<.0001]. Urinary incontinence increased further after vaginal delivery to 43.0% (odds ratio, 1.75; 95% confidence interval, 1.49-2.05; P<.0001); "moderate" and "severe" urinary incontinence increased from 12.7-19.5% (odds ratio, 1.67; 95% confidence interval, 1.35-2.07; P <.0001). There was a parallel increase in urinary incontinence from 40-65 years of age in nulliparous and vaginally and cesarean delivered women. Cesarean delivery, compared with vaginal delivery, was associated with a 30.0% reduction of urinary incontinence (P<.0001) and a 35-52% reduction of more severe grades of urinary incontinence (P<.0001) and was unaffected by age. CONCLUSION: Both pregnancy and vaginal delivery incurred an increased risk of urinary incontinence in the long term. The age-related gap for urinary incontinence between nulliparous and primiparous women who were delivered by vaginal delivery or cesarean delivery was constant between parallel trajectories that spanned ages from 40-64 years. The calculated protective effect of cesarean delivery was unaltered and significant during the same age interval.

The role of general anesthesia on traits of neurodevelopmental disorders in a Swedish cohort of twins.

BACKGROUND: The role of general anesthetics as a risk factor for possible neurodevelopmental disorders (NDDs) in humans is unresolved. The investigation of the role of anesthetics in the development of postgeneral anesthesia (anesthesia onward) NDDs has proven to be complicated, partly because of the inherent confounding in clinical cohort studies, and partly by the fact that anesthetics are only one part in the complex process of anesthesia-surgery. METHODS: Utilizing the Swedish databases Child and Adolescent Twins Study in Sweden (CATSS) and National Patient Register (NPR), we investigated twins discordant for anesthesia, born between 1997 and 2004 for traits of NDDs. We identified 68 twin pairs discordant for anesthesia and explored traits of Attention-Deficit/Hyperactivity Disorder (ADHD), Learning Disability (LD), and Autism Spectrum Disorder (ASD) in them while simultaneously taking congenital abnormalities and systemic disorders (CSDs) into account. We analyzed the possible effect of anesthesia on neurodevelopmental problems, and we analyzed the within-pair differences using conditional linear regression. RESULTS: Twins with a recorded episode of anesthesia had higher traits of NDDs than twins without; similarly twins with CSDs had higher mean scores on all traits than twins without CSDs. The within-pair analyses suggested that exposure to anesthesia was associated with higher scores of ADHD (regression coefficient 1.02 and 95% confidence intervals: 0.27-1.78) in monozygotic (MZ) twins discordant for anesthesia. This effect remained when adjusting for congenital abnormalities. DISCUSSION: Our finding that traits of ADHD were slightly associated with anesthesia in a genetically sensitive design is in need of replication and warrants further investigation. Future studies should aim to elucidate mechanisms behind this possible association (e.g. anesthetics doses, age at exposure, exposure duration).

High Mortality Rate in Oral Glucocorticoid Users: A Population-Based Matched Cohort Study.

Objective: The aim of the study was to investigate all-cause and disease-specific mortality in a large population-based cohort of oral glucocorticoid (GC) users. Methods: This was a retrospective, matched cohort study. Information on dispensed prescriptions was obtained from the Swedish Prescribed Drug Register. The cause of death was obtained from the Swedish Cause-of-Death Registry. Patients receiving prednisolone ≥5 mg/day (or equivalent dose of other GC) for ≥21 days between 2007-2014 were included. For each patient, one control subject matched for age and sex was included. The study period was divided into 3-month periods and patients were divided into groups according to a defined daily dose (DDD) of GC used per day. The groups were: Non-users (0 DDD per day), low-dose users (>0 but <0.5 DDD per day), medium-dose users (0.5-1.5 DDD per day) and high-dose users (>1.5 DDD per day). Hazard ratios (HRs), unadjusted and adjusted for age, sex and comorbidities, were calculated using a time-dependent Cox proportional hazard model. Results: Cases (n=223 211) had significantly higher all-cause mortality compared to controls (HR adjusted for age, sex and comorbidities 2.08, 95% confidence interval 2.04 to 2.13). After dividing the cases into subgroups, adjusted HR was 1.31 (1.28 to 1.34) in non-users, 3.64 (3.51 to 3.77) in low-dose users, 5.43 (5.27 to 5.60) in medium-dose users and, 5.12 (4.84 to 5.42) in high-dose users. The highest adjusted hazard ratio was observed in high-dose users for deaths from sepsis 6.71 (5.12 to 8.81) and pulmonary embolism 7.83 (5.71 to 10.74). Conclusion: Oral GC users have an increased mortality rate compared to the background population, even after adjustment for comorbidities. High-dose users have an increased risk of dying from sepsis, and pulmonary embolism compared to controls. Whether the relationship between GC exposure and the excess mortality is causal remains to be elucidated.

A Multinational Cost-Consequence Analysis of a Bone Conduction Hearing Implant System-A Randomized Trial of a Conventional vs. a Less Invasive Treatment With New Abutment Technology.

Background: It is hypothesized that, for patients with hearing loss, surgically placing an implant/abutment combination whilst leaving the subcutaneous tissues intact will improve cosmetic and clinical results, increase quality of life (QoL) for the patient, and reduce medical costs. Here, incremental costs and consequences associated with soft tissue preservation surgery with a hydroxyapatite (HA)-coated abutment (test) were compared with the conventional approach, soft tissue reduction surgery with an all-titanium abutment (control). Methods: A cost-consequence analysis was performed based on data gathered over a period of 3 years in an open randomized (1:1) controlled trial (RCT) running in four European countries (The Netherlands, Spain, France, and Sweden). Subjects with conductive or mixed hearing loss or single-sided sensorineural deafness were included. Results: During the first year, in the Netherlands (NL), France (FR), and Spain (ES) a net cost saving was achieved in favor of the test intervention because of a lower cost associated with surgery time and adverse event treatments [NL €86 (CI -50.33; 219.20), FR €134 (CI -3.63; 261.30), ES €178 (CI 34.12; 97.48)]. In Sweden (SE), the HA-coated abutment was more expensive than the conventional abutment, which neutralized the cost savings and led to a negative cost (SE €-29 CI -160.27; 97.48) of the new treatment modality. After 3 years, the mean cost saving reduced to €17 (CI -191.80; 213.30) in the Netherlands, in Spain to €84.50 (CI -117.90; 289.50), and in France to €80 (CI -99.40; 248.50). The mean additional cost in Sweden increased to €-116 (CI -326.90; 68.10). The consequences in terms of the subjective audiological benefit and Health-related quality of life (HRQoL) were comparable between treatments. A trend was identified for favorable results in the test group for some consequences and statistical significance is achieved for the cosmetic outcome as assessed by the clinician. Conclusions: From this multinational cost-consequence analysis it can be discerned that health care systems can achieve a cost saving during the first year that regresses after 3 years, by implementing soft tissue preservation surgery with a HA-coated abutment in comparison to the conventional treatment. The cosmetic results are better. (sponsored by Cochlear Bone Anchored Solutions AB; Clinical and health economic evaluation with a new Baha® abutment design combined with a minimally invasive surgical technique, ClinicalTrials.gov NCT01796236).