Bladder instillations versus onabotulinumtoxinA injection for interstitial cystitis/bladder pain syndrome: A randomized clinical trial.

BACKGROUND: Interstitial cystitis/bladder pain syndrome is an unpleasant sensation related to the bladder with lower urinary tract symptoms lasting more than six weeks, unrelated to an otherwise identifiable cause. The etiology is likely multifactorial including urothelial abnormalities, neurogenic pain upregulation, and potentially bladder and vaginal microbiome alterations. Despite treatment effectiveness of both bladder instillations and intradetrusor onabotulinumtoxinA injection for this condition, a head-to-head comparison has not been performed. OBJECTIVES: To compare the efficacy of bladder instillations and intradetrusor onabotulinumtoxinA injection for treatment of interstitial cystitis/bladder pain syndrome. STUDY DESIGN: Patients with O'Leary-Sant (OLS) questionnaire scores of ≥ 6, meeting clinical criteria for interstitial cystitis/bladder pain syndrome, and desiring procedural management were randomized to bladder instillations or intradetrusor onabotulinumtoxinA injection. The primary outcome was the difference in OLS scores at 2 months post-treatment between groups. Secondary outcomes included evaluation of sexual function, physical/mental health status, pain, patient satisfaction, treatment perception, retreatment, and adverse event rates. RESULTS: 47 patients were analyzed with 22 randomized to bladder instillations and 25 to onabotulinumtoxinA injection. There were no differences in demographic and clinical characteristics between groups. From baseline to 2 months post-treatment, there was a decrease in OLS subscales in all patients (Interstitial Cystitis Symptom Index (ICSI) -6.3 (CI -8.54, -3.95), p<.0001; Interstitial Cystitis Problem Index (ICPI) -5.9 (CI -8.18, -3.57), p<.0001). At 2 months post-treatment, patients in the onabotulinumtoxinA group had significantly lower OLS scores compared to those in the bladder instillation group (ICSI 6.3 ± 4.5 [onabotulinumtoxinA] versus 9.6 ± 4.2 [instillation], p=.008; ICPI 5.9 ± 5.1 [onabotulinumtoxinA] versus 8.3 ± 4.0 [instillation], p=.048). The difference in OLS scores between groups did not persist at 6-9 months post-treatment. There were no statistically significant differences between baseline and post-treatment time points for the remaining questionnaires. Eight percent of patients who received onabotulinumtoxinA injection experienced urinary retention requiring self-catheterization. Patients who underwent onabotulinumtoxinA injection were significantly less likely to receive retreatment within 6-9 months compared to patients who received bladder instillations (relative risk 13.6; 95% CI, 1.92-96.6; P=.0002). There were no differences between groups regarding patient satisfaction, perception of treatment convenience, or willingness to undergo retreatment. CONCLUSIONS: Both onabotulinumtoxinA injection and bladder instillations are safe, effective treatments for patients with interstitial cystitis/bladder pain syndrome, with significant clinical improvement demonstrated at 2 months post-treatment. Our findings suggest that intradetrusor onabotulinumtoxinA injection is a more effective procedural treatment for this condition than bladder instillation therapy and associated with decreased rates of retreatment.

Risks of congenital malformations and neonatal intensive care unit admissions with gabapentin use in pregnancy: A cohort study and scoping review with meta-analysis.

BACKGROUND: The increasing and prevalent use of gabapentin among pregnant people highlights the necessity to assess its neonatal safety. OBJECTIVES: This study aimed to investigate the foetal safety of gabapentin during pregnancy using a cohort study and scoping review with a meta-analysis of published evidence. METHODS: We conducted a population-based cohort study using the Manitoba health databases between 1995 and 2019. We examined the association between gabapentin use during pregnancy and the prevalence of major congenital malformations, cardiac and orofacial malformations, and neonatal intensive care unit (NICU) admissions using multivariate regression models. We searched the literature in MEDLINE and EMBASE databases from inception to October 2022 to identify relevant observational studies and conducted a meta-analysis using random-effects models, including our cohort study results. RESULTS: Of the 289,227 included pregnancies, 870 pregnant people were exposed to gabapentin. Gabapentin exposure during the First trimester was not associated with an increased risk of any malformations (adjusted relative risk [aRR]) 1.16 (95% confidence interval [CI] 0.92, 1.46), cardiac malformations (aRR 1.29, 95% CI 0.72, 2.29), orofacial malformations (aRR 1.37, 95% CI 0.50, 3.75), and major congenital malformations (aRR 1.00, 95% CI 0.73, 1.36). whereas exposure during any trimester was associated with an increased NICU admission risk (aRR, 1.99 [95% CI 1.70, 2.32]). The meta-analysis of unadjusted results revealed an increased risk of major congenital malformations (RR 1.44, 95% CI 1.28, 1.61, I2 = 0%), cardiac malformations (RR 1.66, 95% CI 1.11, 2.47, I2 = 68%), and NICU admissions (RR 3.15, 95% CI 2.90, 3.41, I2 = 10%), and increased trend of orofacial malformations (RR 1.98, 95% CI 0.79, 5.00, I2 = 0%). CONCLUSIONS: Gabapentin use was associated with an increased risk of NICU admissions in the cohort study and pooled meta-analysis. Clinicians should prescribe gabapentin with caution during pregnancy and further studies are warranted.

Antibiotics for UTI Prevention After Intradetrusor OnabotulinumtoxinA Injections.

IMPORTANCE: Urinary tract infections (UTIs) occur in 8.6% to 48.1% of patients after intradetrusor onabotulinumtoxinA injections. OBJECTIVE: The objective of this study was to evaluate both choice and duration of antibiotic prophylaxis on the incidence of UTI within 30 days after in-office onabotulinumtoxinA injections. STUDY DESIGN: We included a single-site, retrospective cohort of 305 patients with overactive bladder or bladder pain syndrome receiving postprocedure prophylactic antibiotics for in-office, 100-unit intradetrusor onabotulinumtoxinA injections from 2019 to 2023. Categories of antibiotic prophylaxis compared included (1) nitrofurantoin 100 mg twice daily for 3 days, (2) nitrofurantoin 100 mg twice daily for 5 days, (3) trimethoprim-sulfamethoxazole 160 mg/800 mg twice daily for 3 days, and (4) "other regimens." Primary outcome was incidence of UTI within 30 days. Variables were compared via χ2 test. Crude/adjusted odds were estimated using binary logistic regression. RESULTS: Incidence of UTI was 10.4% for 3-day nitrofurantoin, 20.5% for 5-day nitrofurantoin, 7.4% for 3-day trimethoprim-sulfamethoxazole, and 25.7% among "other regimens" (P = 0.023). Differences among primary regimens were substantial but not statistically significant: 3-day trimethoprim-sulfamethoxazole had 31% lower odds of UTI versus 3-day nitrofurantoin (odds ratio [OR], 0.689; P = 0.518). Compared with 3-day nitrofurantoin regimen, the 5-day nitrofurantoin regimen had twice the odds of UTI (OR, 2.22; P = 0.088). Those receiving "other regimens" had nearly 3 times the odds of UTI (OR, 2.98; P = 0.018). Results were similar adjusting for age and race. Overall urinary retention rate was 1.97%. CONCLUSIONS: Prophylactic antibiotic choice and duration of treatment potentially affect UTI incidence after in-office, intradetrusor onabotulinumtoxinA injections. Nitrofurantoin and trimethoprim-sulfamethoxazole for 3 days have the lowest UTI incidence.

Association of Pelvic Floor Disorders, Perceived Psychological Stress, and Military Service in U.S. Navy Servicewomen: A Cross-Sectional Survey.

IMPORTANCE: Pelvic floor disorders (PFDs) are linked to psychological stress and decreased work performance in civilian populations. Higher psychological stress is reported in female active-duty servicewomen (ADSW), which affects military readiness. OBJECTIVE: This study sought to associate PFDs, work-related challenges, and psychological stress in ADSW. STUDY DESIGN: We conducted a single-site, cross-sectional survey of ADSW seeking care in the urogynecology, family medicine, and women's health clinics between December 2018 and February 2020 using validated questionnaires to determine the prevalence of PFDs and the association with psychological stress, performance of military duties, and continued military service. RESULTS: One hundred seventy-eight U.S. Navy ADSW responded; most were seeking care for PFDs. The reported prevalence rates of PFDs were as follows: urinary incontinence, 53.7%; pelvic organ prolapse, 16.3%; fecal incontinence, 73.2%; and interstitial cystitis/bladder pain syndrome, 20.3%. Active-duty servicewomen with PFDs were more likely to have higher psychological stress scores (22.5 ± 3.7 vs 20.5 ± 4.2, P = 0.002) and body composition failures (22.0% vs 7.3%, P = 0.012), yet more strongly consider remaining on active service if they reported urinary incontinence (22.8% vs 1.8%) or interstitial cystitis/bladder pain syndrome (19.5% vs 1.8%; all P ≤ 0.001). No significant differences were noted in physical fitness failures or other military duties. CONCLUSIONS: For these U.S. Navy ADSW with PFDs, there was no significant difference in duty performance but reported psychological stress levels were higher. The presence of PFD was associated with women more strongly considering ongoing military service compared with other factors such as family, job, or career path.

Antiseizure medication use during pregnancy and neonatal growth outcomes: A systematic review and meta-analysis.

AIMS: We aimed to systematically synthesize the current published literature on neonatal growth outcomes associated with antiseizure medication (ASM) use during pregnancy. METHODS: We searched seven databases, from inception to 23 March 2022. We investigated small for gestational age (SGA) and low birth weight (LBW) as primary outcomes and birth weight, birth height, cephalization index and head circumference as secondary outcomes. The primary analysis included pregnant people exposed to any ASM compared with unexposed pregnant people. Subgroup analysis included ASM class analysis, within epilepsy group analysis and polytherapy compared to monotherapy. RESULTS: We screened 15 720 citations and included 65 studies in the review. Exposed pregnant people had a significantly increased risk of SGA relative risk (RR) 1.33 (95% CI 1.18 to 1.50, I2 74%), LBW RR 1.54 (95% CI 1.33 to 1.77, I2 67%), and decreased birth weight with a mean difference (MD) of -118.87 (95% CI -161.03 to -76.71, I2 42%) g. A non-significant risk change in birth height and head circumference was observed. In subgroup analysis, ASM polytherapy, within epilepsy and ASM class analysis were also associated with an increased risk of SGA and LBW. CONCLUSIONS: This meta-analysis demonstrates that pregnant people exposed to ASMs have a significantly increased risk of adverse fetal growth outcomes including SGA and LBW and decreased birth weight compared to unexposed pregnant people. Polytherapy was associated with higher risks compared to monotherapy. Additional studies are warranted on specific ASM risks.

Preterm birth and stillbirth rates associated with socioeconomic disparities during COVID-19 pandemic: a population-based cross-sectional study.

BACKGROUND: Conflicting evidence exists on the impact of the COVID-19 pandemic restrictions on preterm birth (PTB) and stillbirth rates. We aimed to evaluate changes in PTB and stillbirth rates before and during the pandemic period and assess the potential effect modification of socioeconomic status (SES). METHODS: Using the linked administrative health databases from Manitoba, Canada, we conducted a cross-sectional study among all pregnant women, comparing 3.5 years pre-pandemic (1 October 2016 to 29 February 2020) to the first year of the pandemic (1 March 2020 to 31 March 2021). We used generalised linear models to assess the quarterly rates of PTB (<37 weeks) and stillbirths. We calculated the predicted trends based on pre-pandemic period data. Finally, we evaluated the PTB and stillbirth rates among lower and higher SES pregnant women (average annual household income) using subgroup analysis and interaction models. RESULTS: We examined 70 931 pregnancies in Manitoba during the study period. The risk of PTB increased by 7.7% (95%CI 1.01 to 1.13) and stillbirths by 33% (95% CI 1.08 to 1.64) during the pandemic period. Following COVID-19 restrictions implemented in March 2020, there were increases in the quarterly rates of both PTB (immediate increase (ß2)=1.37; p=0.0247) and stillbirths (immediate increase (ß2)=0.12; p=0.4434). Among the lower income groups, the pandemic restrictions resulted in an immediate relative increase in PTB and stillbirth rates by 20.12% (immediate increase (ß2)=3.17; p=0.0057) and 27.19% (immediate increase (ß2)=0.48; p=0.0852). However, over the pandemic, the overall PTB rate significantly decreased as a rebound effect by 0.85% per quarter (p=0.0004), whereas the overall stillbirth rate did not decrease significantly (slope decrease (ß3) =-0.01; p=0.8296) compared with the pre-pandemic period. The quarterly rates during the pandemic among the higher income group decreased by 0.39% (p=0.1296) for PTB and increased by 0.07% (p=0.1565) for stillbirth. We observed an effect modification by SES for PTB rates (p=0.047). CONCLUSION: While the onset of COVID-19 pandemic restrictions was not associated with significant effects on stillbirth rates, we observed an immediate and rebound effect on PTB rates. The impact of COVID-19 on preterm birth was dependent on SES, with higher influence on families with lower SES. Further studies are needed to detect future trend changes during pandemic waves after 2021 and assess potential underlying mechanisms.

Reduced versus standard intradetrusor OnabotulinumtoxinA injections for treatment of overactive bladder.

BACKGROUND: Intradetrusor onabotulinumtoxinA injection is an effective advanced treatment for overactive bladder. While the effective dosages have been well studied, very little data exist on treatment efficacy using differing injection techniques. The objective of this study was to determine whether the efficacy of a reduced injection technique of 5 injection sites was noninferior to the standard technique of 20 injection sites of intradetrusor onabotulinumtoxinA for treatment of overactive bladder. METHODS: In this randomized noninferiority trial, men and women seeking treatment of overactive bladder with intradetrusor onabotulinumtoxinA injections were randomized to receive 100 units administered via either a reduced injection technique of 5 injection sites or a standard injection technique of 20 injection sites. Subjects completed a series of standardized questionnaires at baseline and at 4-12 weeks postprocedure to determine symptom severity and treatment efficacy. The primary outcome was treatment efficacy as determined by Overactive Bladder Questionnaire-Short Form with a noninferiority margin of 15 points. Secondary outcomes were incidence of urinary tract infection and urinary retention requiring catheterization. RESULTS: Data from 77 subjects were available for analysis with 39 in the control arm (20 injections) and 38 in the study arm (5 injections). There was a significant improvement in both arms from baseline to follow-up in Overactive Bladder Questionnaire-Short Form and International Consultation on Incontinence Questionnaire scores (p < 0.001). Overall treatment success was 68% with no statistically significant difference between arms. A significant difference between arms was found on the Overactive Bladder Questionnaire-Short Form quality of life survey favoring the control arm (confidence interval [CI]: 0.36-20.5, p = 0.04). However, there were no significant differences between arms in the remaining validated questionnaires. The study arm did not demonstrate noninferiority to the control arm. Subjects in the study arm were significantly more likely to express a willingness to undergo the procedure again (odds ratio = 3.8, 95% CI: 1.42-10.67, p = 0.004). Adverse events did not differ between arms. CONCLUSIONS: A reduced injection technique for administration of intradetrusor onabotulinumtoxinA demonstrates similar efficacy to the standard injection technique but did not demonstrate noninferiority. Subjects preferred the reduced injection technique over the standard technique. A reduced injection technique is a safe and effective alternative to the standard technique.

Drug utilization patterns before and during COVID-19 pandemic in Manitoba, Canada: A population-based study.

BACKGROUND: The COVID-19 pandemic has led the Canadian provincial governments to take unprecedented measures, including restrictions to healthcare services and pharmacists. Limited evidence exists on changes in prescription trends in Canada during the pandemic period. OBJECTIVES: To examine the trend of prescription medications' utilization before and during COVID-19, among incident and prevalent users in the general population. We examined 18 major classes of medications. METHODS: We used the administrative health databases from the province of Manitoba, Canada, to conduct a province-wide cross-sectional study. Incident and prevalent use was compared between two time periods; pre-COVID-19: July 2016-March 2020 and during COVID-19: April 2020-March 2021. Interrupted time series analysis using autoregressive models was used to quantify the change in level and slope in quarterly medication use among incident and prevalent users. RESULTS: The quarterly study population ranged from 1,353,485 to 1,411,630 Manitobans. The most common comorbidities were asthma (26.67%), hypertension (20.64%), and diabetes (8.31%). On average, the pandemic restrictions resulted in a 45.55% and 12.17% relative decline in the aggregated utilization of all drugs among both incident and prevalent users, respectively. Subclass analysis showed a 46.83%, 23.05%, and 30.98% relative drop among incident users of antibiotics, cardiovascular drugs and opioids use, respectively. We observed a significant slope increase during COVID-19 among the quarterly cardiovascular, antidiabetics, alpha-1 blockers, and statins incident users compared to the pre-COVID-19 period. We noted a significant decrease in level among NSAIDs, opioids, and antibiotic prevalent users, however, no significant changes in slope were observed. CONCLUSION: Our findings show a significant impact of COVID-19 measures on prescription trends in the general population. The observed decline among several medication classes was temporary. Further research is needed to monitor prescription trends and better understand if those changes were associated with increased health services and worsened outcomes.

Prevalence of Pelvic Floor Disorders in United States Active-Duty Service Women Seeking Medical Care.

IMPORTANCE: In the United States, pelvic floor disorders affect 25% of women. Despite facing unique occupational risk factors that may increase the risk of pelvic floor disorders, there is little research on the prevalence of these disorders in active-duty service women. OBJECTIVES: This study sought to identify the prevalence of and risk factors for pelvic floor disorders in active-duty service women in the United States from diagnostic codes through service utilization. STUDY DESIGN: Utilizing the Military Health System Data Repository, a cross-sectional study was conducted of all active-duty service women in the United States Army, Air Force, Navy, and Marine Corps during fiscal years 2010 to 2019. RESULTS: This study identified 497,255 active-duty service women of whom 9.93% had pelvic floor disorders. Adjusted regression model analyses indicated increasing parity and body mass index significantly affect the risk of pelvic floor disorders. Active-duty women with 3 or more births were 3 times more likely to have pelvic floor disorders compared with the nulliparous group. Finally, subset analysis indicates the risk of pelvic floor disorders were increased 250% in obese women and decreased 20% for underweight women. The rate of pelvic floor disorders appears to be increasing among active-duty women. CONCLUSIONS: Active-duty service women have significantly lower rates of pelvic floor disorders compared with the general population, possibly due to the protective effects of improved weight management and physical fitness requirements for their job performance. However, pelvic floor disorders may be uptrending and need continued monitoring.

The impact of COVID-19 first wave national lockdowns on perinatal outcomes: a rapid review and meta-analysis.

BACKGROUND: Since the emergence of COVID-19, preventative public health measures, including lockdown strategies, were declared in most countries to control viral transmission. Recent studies and anecdotes have reported changes in the prevalence of perinatal outcomes during national COVID-19lockdowns.The objective of this rapid review was to evaluate the impact of COVID-19 lockdowns on the incidence of low birth weight (LBW), preterm birth (PTB), and stillbirth. METHODS: Two reviewers searched EMBASE, CORD-19, LitCovid (PubMed), WHO Global research on corona virus disease (COVID-19), and MedRxiv for studies published in English from the first reports on COVID-19 until 17 July 2021. Perinatal outcomes of interest included LBW (< 2500 g), PTB (< 37 weeks), and stillbirth. RESULTS: Of the 1967 screened articles, 17 publications met the inclusion criteria (14 cohort studies, 1 case control and 2 cross-sectional studies). Studies included data from Denmark, UK, Ireland, Nepal, Italy, Israel, Botswana, Australia, China, Netherlands, Saudi Arabia, Austria, Zimbabwe, India, and Spain. The total sample size ranged from 3399 to 1,599,547 pregnant women. Thirteen studies examined PTB with conflicting results, reporting both an increase and a decrease in PTB incidence, with odds ratios [95% CI] ranging from 0.09 [0.01, 0.40] to 1.93 [0.76, 4.79]. Three studies found a decrease in LBW rates during lockdowns, one of which was statistically significant, with a rate ratio of 3.77 [1.21, 11.75]. Ten studies examined stillbirth rates, including four studies reporting a statistically significant increase in stillbirth rates, with adjusted relative risk ranging from 1.46 [1.13, 1.89] to 3.9 [1.83, 12.0]. Fourteen studies contained data that could be combined in a meta-analysis comparing perinatal outcomes before and during lockdown. We found that lockdown measures were associated with a significant risk of stillbirth with RR = 1.33 [95% CI 1.04, 1.69] when compared to before lockdown period. However, lockdown measures were not associated with a significant risk of PTB, LBW and VLBW compared to prepandemic periods. CONCLUSIONS: This review provides clues about the severity of the indirect influence of COVID-19 lockdown implementation; however, the criteria that lead to unexpected changes in LBW, PTB, and stillbirth remains unclear. Large studies showed conflicting results, reporting both increases and decreases in selected perinatal outcomes. Pooled results show a significant association between lockdown measures and stillbirth rates, but not low birth weight rates. Further studies examining the differences in other countries' lockdowns and sociodemographic groups from low to middle-income countries are needed. Exploration of perinatal outcomes during COVID-19 lockdown poses an opportunity to learn from and make changes to promote the reduction of the leading causes of childhood mortality worldwide.

Preoperative pudendal block with liposomal and plain bupivacaine reduces pain associated with posterior colporrhaphy: a double-blinded, randomized controlled trial.

BACKGROUND: Pelvic reconstructive surgery may cause significant postoperative pain, especially with posterior colporrhaphy, contributing to a longer hospital stay and increased pain medication utilization. Regional blocks are being increasingly utilized in gynecologic surgery to improve postoperative pain and decrease opioid usage, yet preoperative pudendal blocks have not been used routinely during posterior colporrhaphy. OBJECTIVE: This study aimed to compare the effect of preoperative regional pudendal nerve block using a combination of 1.3% liposomal and 0.25% plain bupivacaine vs 0.25% plain bupivacaine alone on vaginal pain after posterior colporrhaphy on postoperative days 1, 2, and 3. We hypothesized that there would be a reduction in vaginal pain scores for the study group vs the control group over the first 72 hours. STUDY DESIGN: This was a double-blinded, randomized controlled trial that included patients undergoing a posterior colporrhaphy, either independently or in conjunction with other vaginal or abdominal reconstructive procedures. Patients were block randomized to receive 20 mL of either a combination of 1.3% liposomal and 0.25% plain bupivacaine (study) or 20 mL of 0.25% plain bupivacaine (control) in a regional pudendal block before the start of surgery. Double blinding was achieved by covering four 5-mL syringes containing the randomized local anesthetic. After induction of anesthesia, a pudendal nerve block was performed per standard technique (5 mL superiorly and 5 mL inferiorly each ischial spine) using a pudendal kit. The primary outcome was to evaluate postoperative vaginal pain using a visual analog scale on postoperative days 1, 2, and 3. Secondary outcomes included total analgesic medication usage through postoperative day 3, postoperative voiding and defecatory dysfunction, and impact of vaginal pain on quality of life factors. RESULTS: A total of 120 patients were enrolled (60 in each group). There were no significant differences in demographic data, including baseline vaginal pain (P=.88). Postoperative vaginal pain scores were significantly lower in the combined liposomal and bupivacaine group at all time points vs the plain bupivacaine group. Median pain scores for the study and control groups, respectively, were 0 (0-2) and 2 (0-4) for postoperative day 1 (P=.03), 2 (1-4) and 3 (2-5) for postoperative day 2 (P=.05), and 2 (1-4) and 3 (2-5) for postoperative day 3 (P=.02). Vaginal pain scores increased from postoperative day 1 to postoperative days 2 and 3 in both groups. There was a significant decrease in ibuprofen (P=.01) and acetaminophen (P=.03) usage in the study group; however, there was no difference between groups in total opioid consumption through postoperative day 3 (P=.82). There was no difference in successful voiding trials (study 72%, control 82%, P=.30), return of bowel function (P>.99), or quality of life factors (sleep, stress, mood, and activity). CONCLUSION: Preoperative regional pudendal block with a combination of liposomal and plain bupivacaine provided more effective vaginal pain control than plain bupivacaine alone for reconstructive surgery that included posterior colporrhaphy. Given the statistically significant decrease in vaginal pain in the study group, this block may be considered as a potential adjunct for multimodal pain reduction in this patient population.

Anti-epileptic drug exposure during pregnancy and neonatal birth weight outcomes: protocol for a systematic review and meta-analysis.

BACKGROUND: The prevalence of epilepsy in pregnant women is estimated at 0.3-1%. Anti-epileptic drug (AED) exposure in-utero has been associated with various adverse health outcomes in neonates, including adverse birth weight outcomes. OBJECTIVE: This review aims to summarize the published evidence on the association between AED exposure in pregnancy and adverse birth weight outcomes METHODS: Studies assessing AED exposure in pregnancy and neonatal birth weight outcomes, including small for gestational age (SGA), low birth weight (LBW), birth weight (BW), length, head circumference, and cephalization index will be identified in MEDLINE®, EMBASE, Cochrane Library, Scopus, Cumulative Index of Nursing and Allied Health Literature (CINAHL), International Pharmaceutical Abstracts (IPA), and Global Health. Open grey, Theses Canada, and ProQuest Dissertations will be used to locate gray literature. Eligible study designs will include both intervention and non-interventional studies. We will not impose any time limit in the review. We will use the Newcastle-Ottawa Scale to assess the methodological quality of observational studies and quasi-experimental studies included in the review. The risk of bias of experimental studies will be appraised using the Cochrane risk-of-bias tool for randomized trials (RoB 2). A meta-analysis will be conducted using a random-effects model. DISCUSSION: The results from this review could improve clinicians' prescribing decisions by highlighting the safest AEDs for women who are pregnant or planning to conceive based on the evidence currently available. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020192713.

New-generation antiepileptic drugs during pregnancy and the risk of attention-deficit hyperactivity disorder: A scoping review.

The use of maternal antiepileptic drug (AED) during pregnancy is associated with an increased risk of cognitive adverse effects among the offspring. As new-generation AEDs continue to enter the market, evidence on their safety during pregnancy is limited yet necessary. To date, there are no published reviews summarizing the evidence of new-generation AED exposure in utero and the development of attention deficit-hyperactivity disorder (ADHD) in the offspring. The objective of this scoping review is to summarize the available evidence on the risk of ADHD after maternal exposure to new-generation AEDs during pregnancy. We searched EMBASE and MEDLINE for articles published from January 1988 to April 2020. New-generation AEDs were considered if marketed after 1988. ADHD was defined as attention-deficit hyperactivity disorder, hyperkinetic disorder, hyperkinesis, or conduct disorder. Of the total articles screened (n = 805), eight publications were finally included (seven cohort studies and one systematic review). Across the studies, the sample size of pregnant women exposed to AEDs ranged from 1 to 1383. Monotherapy was examined in six studies (mostly lamotrigine), while only two studies examined polytherapy. The included studies reported a range of adjusted relative risks, from 0.84 [0.59-1.19] to 1.63 [0.41-6.06]. Lamotrigine monotherapy holds the largest body of evidence, concluding that no significant risk of ADHD exists among the offspring. However, the available evidence is considered scarce and has several methodological limitations. Disentangling the effect of AEDs from epilepsy itself and examining polytherapies are challenges that merit additional investigations. Further comparative safety studies with longer follow-up periods and large sample sizes are needed to accurately quantify the true impact of new-generation AED exposure during pregnancy and ADHD in children.

Head-to-Head Comparison of Three Virtual-Reality Robotic Surgery Simulators.

BACKGROUND AND OBJECTIVES: There are several different commercially available virtual-reality robotic simulators, but very little comparative data. We compared the face and content validity of 3 robotic surgery simulators and their pricing and availability. METHODS: Fifteen participants completed one task on each of the following: dV-Trainer (dVT; Mimic Technologies, Inc., Seattle, Washington, USA), da Vinci Skills Simulator (dVSS; Intuitive Surgical Inc., Sunnyvale, California, USA), and RobotiX Mentor (RM; 3D Systems, Rock Hill, South Carolina, USA). Participants completed previously validated face and content validity questionnaires and a demographics questionnaire. Statistical analysis was then performed on the scores. RESULTS: Participants had a mean age of 29.6 (range, 25-41) years. Most were surgical trainees, having performed a mean of 8.6 robotic primary surgeries. For face validity, ANOVA showed a significant difference favoring the dVSS over the dVT (P = .001), and no significant difference between the RM, dVSS, and dVT. Content validity revealed similar results, with a significant difference between the dVSS and dVT (P = .021), a trend toward a difference between the RM and dVT (P = .092), and no difference between the dVSS and RM (P = .99). CONCLUSION: All simulators demonstrated evidence of face and content validity, with significantly higher scores for the dVSS; it is also the least costly ($80,000 for the simulator), although it is frequently unavailable because of intra-operative use. The dVT and RM have similar face and content validity, are slightly more expensive, and are readily available.

The use of magnetic resonance imaging for studying female sexual function: A review.

Many would agree that there are two quintessential sexual organs in the female: the clitoris and the brain. Using non-invasive techniques of magnetic resonance imaging (MRI), investigators have gained insight into the mental and physical factors involved in female sexual function. Since only the external clitoral glans is easily accessible for direct measurement, the complete anatomy of the clitoris (including the internal components-paired corpora, crura, and bulbs) has only recently been described, with MRI providing the most sensitive way of distinguishing among the various soft tissue planes. Average sizes of clitoral structures and average distances between the clitoral complex and other pelvic landmarks have been measured. These measurements have been correlated with female sexual function: a longer distance between the clitoral complex and the vaginal lumen correlates with poorer sexual function, consistent with prior imaging studies. However, whether clitoral size influences function is debatable, so further studies are needed. Physiological investigations have demonstrated that female arousal disorder is unlikely to be due to inadequate genital engorgement. Some consider the brain to be the ultimate sexual organ, and several recent studies have used functional MRI (fMRI) to reveal sexual excitability in the brain. The normal sexual response requires deactivation of the frontal lobe and activation of the instinctual limbic system of the midbrain. As MR technology continues to improve, the mysteries of female sexuality will be further unraveled.

The influence of personality and coping on female sexual function: a population survey.

INTRODUCTION: Female sexual dysfunction (FSD) is a common disorder with limited data investigating relationships with psychological influences, such as personality traits and coping mechanisms. AIM: To investigate the relationship and impact of personality traits and coping strategies on female sexual function. METHODS: A web-based survey was distributed to a sample of women representative of the area's demographic distribution. MAIN OUTCOME MEASURES: Participants completed the Female Sexual Function Index (FSFI), the Ten Item Personality Index (TIPI), and the Brief COPE. RESULTS: Five hundred twenty-six females responded. The mean total FSFI score was 24.56 (SD 6.77) with lowest scores in the desire domain. Personality scores were similar to published normative values. Subjects displaying stronger tendencies for introversion (r = 0.246, P < 0.001), not being open to new experiences (r = 0.159, P = 0.008), and emotional instability (r = 0.244, P < 0.001) were found to have significantly worse sexual function. Conscientiousness was significantly associated with better desire, orgasm, satisfaction, and total FSFI score (P = 0.029, P = 0.002, P = 0.005, P = 0.003). Moreover, the utilization of negative coping strategies such as self-blame, self-distraction, and behavioral disengagement, significantly correlated with poor sexual function (r = -0.298, P < 0.001, r = -0.360, P < 0.001, r = -0.398, P < 0.001, respectively). CONCLUSION: Personality and coping are linked to sexual function with introversion, not being open to new experiences, emotional instability, and the utilization of negative coping strategies being significantly associated with poor sexual function. Women presenting with sexual function complaints may need further evaluation of their personality and coping strategies in order to mitigate any negative impact of these tendencies.

Female sexual function and the clitoral complex using pelvic MRI assessment.

OBJECTIVE: To report basic measurements of clitoral anatomy, and explore potential relationships between the clitoral complex and female sexual function using MRI assessment. STUDY DESIGN: In this retrospective descriptive study, 20 sexually active women (≥18 years) who had a recent pelvic MRI for various gynecologic concerns were invited to participate. Outcome measures included demographic data, medical and sexual history, quality of life questionnaires: Female Sexual Function Index (FSFI), Body Exposure during Sexual Activities Questionnaire (BESAQ), and Short Form Quality of Life Questionnaire (SF-12). These data were then compared to detailed clitoral MRI measurements and analyzed using the Pearson correlation and Chi square test. RESULTS: FSFI domains of desire, arousal, lubrication, and orgasm were inversely correlated with clitoral size (p=0.01-0.04), as were SF-12 physical composite scores (p=0.003), suggesting improved sexual function and physical health in women with smaller clitoral structures (specifically the clitoral body and crus). CONCLUSION: Sexual function was improved in women with a smaller-sized clitoris, specifically the clitoral body and crus.

Clitoral size and location in relation to sexual function using pelvic MRI.

INTRODUCTION: The female sexual response is dynamic; anatomic mechanisms may ease or enhance the intensity of orgasm. AIM: The aim of this study is to evaluate the clitoral size and location with regard to female sexual function. METHODS: This cross-sectional TriHealth Institutional Board Review approved study compared 10 sexually active women with anorgasmia to 20 orgasmic women matched by age and body mass index (BMI). Data included demographics, sexual history, serum hormone levels, Prolapse/Incontinence Sexual Questionnaire-12 (PISQ-12), Female Sexual Function Index (FSFI), Body Exposure during Sexual Activity Questionnaire (BESAQ), and Short Form Health Survey-12. All subjects underwent pelvic magnetic resonance imaging (MRI) without contrast; measurements of the clitoris were calculated. MAIN OUTCOME MEASURES: Our primary outcomes were clitoral size and location as measured by noncontrast MRI imaging in sagittal, coronal, and axial planes. RESULTS: Thirty premenopausal women completed the study. The mean age was 32 years (standard deviation [SD] 7), mean BMI 25 (SD 4). The majority was white (90%) and married (61%). Total PISQ-12 (P < 0.001) and total FSFI (P < 0.001) were higher for orgasmic subjects, indicating better sexual function. On MRI, the area of the clitoral glans in coronal view was significantly smaller for the anorgasmic group (P = 0.005). A larger distance from the clitoral glans (51 vs. 45 mm, P = 0.049) and body (29 vs. 21 mm, P = 0.008) to the vaginal lumen was found in the anorgasmic subjects. For the entire sample, larger distance between the clitoris and the vagina correlated with poorer scores on the PISQ-12 (r = -0.44, P = 0.02), FSFI (r = -0.43, P = 0.02), and BESAQ (r = -0.37, P = 0.04). CONCLUSION: Women with anorgasmia possessed a smaller clitoral glans and clitoral components farther from the vaginal lumen than women with normal orgasmic function.