NAIP-NLRC4 Inflammasomes Coordinate Intestinal Epithelial Cell Expulsion with Eicosanoid and IL-18 Release via Activation of Caspase-1 and -8.

Intestinal epithelial cells (IECs) form a critical barrier against pathogen invasion. By generation of mice in which inflammasome expression is restricted to IECs, we describe a coordinated epithelium-intrinsic inflammasome response in vivo. This response was sufficient to protect against Salmonella tissue invasion and involved a previously reported IEC expulsion that was coordinated with lipid mediator and cytokine production and lytic IEC death. Excessive inflammasome activation in IECs was sufficient to result in diarrhea and pathology. Experiments with IEC organoids demonstrated that IEC expulsion did not require other cell types. IEC expulsion was accompanied by a major actin rearrangement in neighboring cells that maintained epithelium integrity but did not absolutely require Caspase-1 or Gasdermin D. Analysis of Casp1-/-Casp8-/- mice revealed a functional Caspase-8 inflammasome in vivo. Thus, a coordinated IEC-intrinsic, Caspase-1 and -8 inflammasome response plays a key role in intestinal immune defense and pathology.

Placement of an intrauterine device within 48 hours after second-trimester medical abortion: a randomized controlled trial.

BACKGROUND: International guidelines recommend placement of intrauterine devices immediately after second-trimester medical abortion, but evidence concerning the optimal time for intrauterine device placement is lacking from clinical trials. OBJECTIVE: This study aimed to investigate effectiveness, safety, and acceptability of intrauterine device placement within 48 hours, compared with placement at 2 to 4 weeks after second-trimester medical abortion. We hypothesized that intrauterine device placement within 48 hours would be superior compared with placement at 2 to 4 weeks after the abortion, in terms of the proportion of intrauterine device use after 6 months, with maintained safety and acceptability. STUDY DESIGN: In this open-label, randomized, controlled, superiority trial, we recruited participants at 8 abortion clinics in Sweden. Eligible participants were aged ≥18 years, requesting medical abortion with gestation ≥85 days, and opting for use of a postabortion intrauterine device. Participants were randomized (1:1) to intrauterine device placement either within 48 hours of complete abortion (intervention) or after 2 to 4 weeks (control). Our primary outcome was self-reported use of an intrauterine device after 6 months. Secondary outcomes included expulsion rates, pain at placement, adverse events and complications, acceptability, and subsequent pregnancies and abortions. Differences in nonnormal continuous variables were analyzed with the Mann-Whitney U test, and differences in dichotomous variables with the chi-square or Fisher exact tests. A P value <.05 was considered statistically significant. Group differences are presented by modified intention-to-treat and per-protocol analyses. RESULTS: Between January 2019 and June 2022, we enrolled 179 participants, of whom 90 were assigned to the intervention and 89 to the control arm. Enrollment was prematurely stopped after an interim analysis exceeded a predefined intrauterine device expulsion rate of 20%. According to modified intention-to-treat analysis, use of intrauterine device after 6 months was 50.7% (34/67) in the intervention group vs 71.6% (48/67) in the control group (proportion difference, 20.9%; 95% confidence interval, 4.4%-35.9%; P=.02). The intrauterine device expulsion rate was 30.1% (22/73) in the intervention group vs 2.9% (2/70; P<.001) in the control group. Other adverse events were rare and patient acceptability was high in both groups. CONCLUSION: Intrauterine device placement within 48 hours after second-trimester medical abortion was nonsuperior in terms of the proportion of intrauterine device use after 6 months when compared with placement after 2 to 4 weeks. Placement within 48 hours after second-trimester abortion can be used in selected individuals after counseling on expulsion risk.

Association between prepartum vaginal temperature changes and placenta expulsion time in Holstein dairy cattle.

Retained placenta (RP) adversely affects postpartum productivity and reproduction in dairy cattle. Thus, methods to predict the occurrence of RP before calving would be desirable. Herein, we assessed whether vaginal temperature measurements (which have already been applied to detect calving) could be used to predict the occurrence of RP in cattle. A vaginal temperature recording device was inserted into the vagina of 49 pregnant Holstein-Friesian heifers (n = 16) and cows (n = 33); this device recorded the vaginal temperature every 5 min until the device dropped out at calving. Serum was collected 10 days before the expected calving date. The time points of calving and placental expulsion were identified via video recordings. We further calculated calving duration (temperature decrease to calving) and placenta expulsion time (PE time = calving to placenta expulsion). The PE times were divided into four categories (0-4 h, 4-8 h, 8-12 h, and RP at >12 h), while subsequent analysis revealed that an extension of the PE time dependent on the shortening of the calving duration (P < 0.05). The vaginal temperature patterns also differed in a PE time-dependent manner, and cows with RP did not show any re-elevation of vaginal temperature. Serum analyses indicated an energy deficiency in RP cattle. These results suggest that RP may be detected early as a specific change in the vaginal temperature associated with reproductive hormone secretion.

Self-reported removal and expulsion of the dapivirine vaginal ring: qualitative reports from female ring users and their male partners in the Ring Study (IPM 027).

BACKGROUND/AIMS: The dapivirine vaginal ring is a self-administered, women-initiated, discreet, long-acting HIV-1 prevention option for women. It was found to be safe and effective in healthy HIV-negative women who adhered to product use instructions, and has been approved for use in women aged 18 and older in some African countries. A qualitative study was conducted to explore participants' and their male partners' discussions on accidental/purposeful vaginal ring removals during The Ring Study (IPM 027 clinical trial). METHODS: Data were collected via in-depth interviews and focus group discussions with female trial participants and their male partners, from seven research centres in South Africa and Uganda. Data were thematically analysed using NVivo. RESULTS: More participants reported purposeful ring removals than accidental expulsions. Various factors influenced purposeful ring removal - including individual (discomfort during use/sex and to clean it), partner (to show them, because of discomfort during sex, to test if partners could feel it, and concerns of harm), organisational (doctor's request), and socio-cultural (rumours about sickness and infertility). Some described their own ring use removal, others discussed why other participants removed their rings. CONCLUSIONS: Vaginal ring adherence is critical to improve and support product efficacy. Counselling on vaginal anatomy, vaginal ring insertion and importance of adherence is important to minimise vaginal ring removal. Couples counselling is also important to facilitate support and long-term vaginal ring adherence behaviour. Understanding factors influencing vaginal ring adherence is important for tailoring and targeting messages to support correct and consistent vaginal ring use as it is made available to the public.

Feasibility and Effectiveness of Hysteroscopic Suture Fixation of the Levonorgestrel-Releasing Intrauterine System in the Treatment of Adenomyosis.

STUDY OBJECTIVE: To evaluate the feasibility and effectiveness of hysteroscopic suture fixation of the levonorgestrel-releasing intrauterine system (LNG-IUS) for the treatment of adenomyosis. DESIGN: A retrospective case series. SETTING: Two teaching hospitals with the technology of hysteroscopic suture fixation of the LNG-IUS. PATIENTS: The study reviewed 79 adenomyosis patients who received the hysteroscopic suture fixation of the LNG-IUS from January 2021 to May 2022. INTERVENTION: Hysteroscopic suture fixation of the LNG-IUS to the posterior uterine wall with nondissolvable suture. MEASUREMENTS AND MAIN RESULTS: All patients underwent one-year postoperative follow-up to evaluate the LNG-IUS expulsion rate, postoperative efficacy, and side effects. Two patients (2.6%) experienced expulsion of the LNG-IUS at 8 months and 12 months postoperatively, respectively. The visual analog pain scale, pictorial blood loss assessment chart score and carbohydrate antigen 125 markedly decreased after the suture fixation of the LNG-IUS compared with baseline in all patients (p <.001). Hemoglobin increased significantly (p <.001). The most common side effect was irregular bleeding, which accounted for 44.3%. The second common side effect was weight gain, which accounted for 29.2%. The composite effectiveness based on pain and bleeding showed that the effective treatment rates at 1, 3, 6, and 12 months after surgery were 92.4%, 97.4%, 96.2%, and 97.4% respectively. CONCLUSIONS: Hysteroscopic suture fixation of the LNG-IUS to the uterine fundus was associated with low expulsion rates and significantly improved dysmenorrhea and bleeding.

Molecular mechanisms activating the NAIP-NLRC4 inflammasome: Implications in infectious disease, autoinflammation, and cancer.

Cytosolic innate immune sensing is a cornerstone of innate immunity in mammalian cells and provides a surveillance system for invading pathogens and endogenous danger signals. The NAIP-NLRC4 inflammasome responds to cytosolic flagellin, and the inner rod and needle proteins of the type 3 secretion system of bacteria. This complex induces caspase-1-dependent proteolytic cleavage of the proinflammatory cytokines IL-1ß and IL-18, and the pore-forming protein gasdermin D, leading to inflammation and pyroptosis, respectively. Localized responses triggered by the NAIP-NLRC4 inflammasome are largely protective against bacterial pathogens, owing to several mechanisms, including the release of inflammatory mediators, liberation of concealed intracellular pathogens for killing by other immune mechanisms, activation of apoptotic caspases, caspase-7, and caspase-8, and expulsion of an entire infected cell from the mammalian host. In contrast, aberrant activation of the NAIP-NLRC4 inflammasome caused by de novo gain-of-function mutations in the gene encoding NLRC4 can lead to macrophage activation syndrome, neonatal enterocolitis, fetal thrombotic vasculopathy, familial cold autoinflammatory syndrome, and even death. Some of these clinical manifestations could be treated by therapeutics targeting inflammasome-associated cytokines. In addition, the NAIP-NLRC4 inflammasome has been implicated in the pathogenesis of colorectal cancer, melanoma, glioma, and breast cancer. However, no consensus has been reached on its function in the development of any cancer types. In this review, we highlight the latest advances in the activation mechanisms and structural assembly of the NAIP-NLRC4 inflammasome, and the functions of this inflammasome in different cell types. We also describe progress toward understanding the role of the NAIP-NLRC4 inflammasome in infectious diseases, autoinflammatory diseases, and cancer.

Child-focused infant and early childhood mental health consultation: Shifting adult attributions to reduce the risk for preschool expulsion.

Infant and early childhood mental health consultation (IECMHC) in early care and education (ECE) settings is a promising approach to support young children. Although research on the effects of IECMHC is encouraging, it is limited by the complexities of the systems in which IECMHC is implemented and the variability in IECMHC models. The current study aims to clearly articulate a statewide, child-focused, short-term IECMHC model, assess consultee satisfaction, examine the effects of consultation on children's functioning in the school and home settings, and evaluate changes in teacher perceptions associated with expulsion risk following consultation. In total, 268 children ages 1-5 (69% White, 75% male) and their family and school caregivers participated in consultation in a New England state, and 95 children and caregivers were included in an evaluation subsample. Of this subsample, teachers and ECE administrators, but not families, indicated significant improvement in children's functioning from referral to end of consultation. There was also a significant decrease in children's risk of expulsion, as measured by teachers' perceptions associated with expulsion decisions. This study contributes to the IECMHC literature by providing results specific to a child-focused model of consultation and highlighting the possible role of adult attributions for children in ECE.

La consulta de salud mental infantil y la temprana niñez (IECMHC) en los entornos de cuidados y educación tempranos (ECE) es un acercamiento prometedor para apoyar a los niños pequeños. A pesar de que la investigación sobre los efectos de IECMHC es alentadora, está limitada por las complejidades de los sistemas dentro de los cuales se implementa IECMHC y la variabilidad en los modelos de IECMHC. El presente estudio se propone articular claramente un modelo de IECMHC para todo el estado, con enfoque en el niño y a corto plazo, evaluar la satisfacción que quienes participan de la consulta, examinar los efectos de la consulta sobre el funcionamiento de los niños en la escuela y en el entorno del hogar, así como evaluar los cambios en las percepciones de los maestros asociadas con los riesgos de expulsión después de la consulta. En total, 268 niños de edad 1­5 (69% blancos, 75% varones) y sus familias y quienes les cuidaba en la escuela participaron en la consulta en un estado de Nueva Inglaterra, y se incluyó a 95 niños y sus cuidadores en una evaluación de un subgrupo muestra. De este subgrupo muestra, los maestros y los administradores de ECE, pero no las familias, indicaron significativas mejorías en el funcionamiento de los niños desde la referencia hasta el final de la consulta. Se dio también una significativa disminución en el riesgo de expulsión de los niños, tal como se midió por medio de las percepciones de los maestros asociadas con las decisiones de expulsión. Este estudio contribuye a la literatura informativa sobre IECMHC por medio de ofrecer resultados específicos al modelo de consulta enfocado en el niño y subrayar el posible papel de las atribuciones del adulto para los niños en ECE.

La consultation de santé mentale du nourrisson et de la petite enfance (Infant and early childhood mental health consultation abrégé en anglais IECMHC) dans des contextes éducatifs et de crèches (abrégé ici CEC selon le français) est une approche prometteuse pour le soutien aux jeunes enfants. Bien que les recherches sur les effets de l'IECMHC sont encourageantes, elles sont limitées par les complexités des systèmes dans lesquels l'IECMHC est mise en oeuvre et la variabilité des modèles de l'IECMHC. Cette étude s'est donné pour but de clairement articuler un modèle IECMHC au niveau de l'état, focalisé sur l'enfant et à court terme, d'évaluer la satisfaction de la personne consultée, d'examiner les effets de la consultation sur le fonctionnement des enfants à l'école et à la maison, et d'évaluer les changements dans les perceptions de l'enseignant liée au risque d'expulsion après la consultation. En tout 268 enfants âgés de 1­5 ans (69% blancs, 75% garçons) et leur famille et les personnes prenant soin d'eux à l'école ont participé à une consultation dans un état de nous Nouvelle Angleterre (aux Etats­Unis), et 95 enfants et personnes prenant soin d'eux ont été inclus dans un sous­échantillon d'évaluation. Dans ce sous­échantillon les enseignants et administrateurs CEC, mais pas les familles, ont fait état d'une amélioration important dans le fonctionnement des enfants du moment de la référence à la fin de la consultation. Il n'a pas de baisse importante du risque d'expulsion des enfants, mesurée par les perceptions des enseignants liées aux décisions d'expulsion. Cette étude contribue aux recherches sur l'IECMHC en offrant des résultats spécifiques à un modèle de consultation focalisé sur l'enfant et en mettant en lumière le rôle possible des attributions adultes pour les enfants dans les CEC.

To what extent are anorectal function tests comparable? A study comparing digital rectal examination, anal electromyography, 3-dimensional high-resolution anal manometry, and transperineal ultrasound.

BACKGROUND: Anorectal function tests are helpful for objective investigation of anorectal (dys)function. A variety of tests are available, but there is no recommendation when to perform which test. Furthermore, which test is the most accurate is controversial and the correlation between these tests is not very clear. The aim of our study was to examine the correlation of anal pressures and the possibility to diagnose pelvic floor dyssynergia between digital rectal examination (DRE) and several anorectal function tests. METHODS: Between January 2020 and April 2022, all men and women aged 18 to 80 years, treated at the Proctos Clinic, who were referred for pelvic floor physical therapy (PFPT) by the surgeon and underwent anorectal function tests, were included. DRE was performed to establish the anal pressure at rest and during squeeze and straining. Anorectal function tests included 3D high-resolution anal manometry (3D-HRAM), balloon expulsion test (BET), transperineal ultrasound (TPUS), and surface electromyography (s-EMG). RESULTS: A total of 50 patients, 37 (74%) females, were included. Median age was 51 years. Twenty-three (62%) females had a history of two or more vaginal deliveries. The most frequent reason for referral for PFPT was fecal incontinence in 27 (54%) patients. The assessed pressures and pelvic floor function measured with DRE by the surgeon and the pelvic floor physical therapist during rest, squeeze, and straining correlated in 78%, 78%, and 84%, respectively. Correlation between DRE and 3D-HRAM or s-EMG was better for squeeze pressures than resting pressures. The correlation between s-EMG and 3D-HRAM was better during squeeze than at rest with an agreement of 59% and 37%, respectively. CONCLUSION: DRE by an experienced investigator is of sufficient value for daily clinical practice to detect dyssynergia and to measure sphincter tone. Commonly performed anorectal function tests correlate poorly with DRE and with other anorectal function tests. When conservative treatment fails, further investigation is warranted; however, these results should be interpreted with caution. WHAT DOES THIS PAPER ADD TO THE LITERATURE?: Anorectal function tests such as the 3D high-resolution anorectal manometry, balloon expulsion test, surface electromyography, and transperineal ultrasound are all frequently performed in the diagnostic workup in patients with defecation disorders. No previous study has compared these tests regarding their outcomes, nor has the interrater agreement been measured regarding the digital rectal examination by two experienced observers. Furthermore, transperineal ultrasound is in all probability not frequently used and therefore underexposed in the diagnostic workup of patients with dyssynergic defecation.

Conservative management of complete fetal expulsion into the abdominal cavity after silent uterine rupture - case report.

BACKGROUND: Clinically silent uterine rupture with complete fetal expulsion into the abdominal cavity is an extremely rare complication. Diagnosis can be difficult and the risk to the mother and fetus is high. Conservative management has been described only in a few cases of partial expulsion of the fetus so far. CASE PRESENTATION: We present a case of 43-year-old tercigravida with a history of previous laparotomic myomectomy and subsequent cesarean section. The subsequent pregnancy was complicated by uterine wall loosening and rupture at the site of the previous uterine scar after myomectomy and complete fetal expulsion into the abdominal cavity. The diagnosis was made at 24 + 6 weeks of gestation. Considering the absence of clinical symptomatology and the good condition of the fetus, a conservative approach was chosen with intensive monitoring of the maternal and fetal conditions. The pregnancy ended by elective cesarean section and hysterectomy at 28 + 0 weeks of gestation. The postpartum course was uneventful and the newborn was discharged to home care 63 days after delivery. CONCLUSIONS: Fetal expulsion into the abdominal cavity after silent uterine rupture of the scarred uterus may be accompanied by minimal symptomatology making early diagnosis difficult. This rare complication must be considered in the differential diagnosis in women after major uterine surgery. In selected cases and under conditions of intensive maternal and fetal monitoring, conservative management may be chosen to reduce the risks associated with prematurity.

Effect of the timing of insertion of postpartum intrauterine contraceptive device (PPIUCD) copper T380A on expulsion rates.

Background & objectives: Postpartum intrauterine contraceptive device (PPIUCD) is well accepted and recommended for contraception. However, anxiety at the time of delivery may restrict the acceptance of a PPIUCD for its immediate insertion. So far there is limited evidence to conclude anything concrete on the association between the expulsion rates and the timing of insertion following a vaginal delivery. Thus, this study was undertaken to compare the expulsion rates in immediate and early insertions and their safety and complications. Methods: This prospective comparative study was carried out over 17 months on women delivering vaginally in a tertiary care teaching hospital in South India. A copper device (CuT380A) was inserted using Kelly's placental forceps either within 10 min of placental delivery (immediate group, n=160) or between 10 min upto 48 h postpartum (early group, n=160). Ultrasound was done before discharge from the hospital. The expulsion rates and any other complications at six-week and three-month follow up were studied. Chi-square test was used to compare the difference in expulsion rates. Results: The expulsion rate was five per cent in the immediate compared to 3.7 per cent in the early group (no significant difference). In ten cases, the device was found to be in the lower uterus upon ultrasound before discharge. These were repositioned. There was no case with perforation, irregular bleeding or infection up to the three-month follow up. Higher age, higher parity, lack of satisfaction and motivation to continue were predictors of expulsion. Interpretation & conclusions: In the present study PPIUCD was found to be safe with overall expulsion in 4.3 per cent. It was marginally, though not significantly, higher in the immediate group.

Does change in the shape of intrauterine contraceptive device Cu 375 and Cu T 380A affect the expulsion after post-partum insertion - a prospective randomized control trial.

PURPOSE: The objective of the study was to see the difference in expulsion rates of two types of Copper containing intrauterine contraceptive devices (IUCDs): Cu 375 & CuT 380 A, within or at 6 weeks after insertion. METHODS: It was a randomised control trial. A total of 396 pregnant women were recruited. Ultrasonography was done to look for the position of the IUCD at the time of discharge and at six weeks follow-up and the expulsion rate was calculated. RESULTS: Amongst 396 participants, 22 PPIUCDs were expelled completely at 6 weeks (modified intention to treat analysis [ITA]), 10 (5.3%) and 12 (6.7%) in the Cu 375 and CuT 380 A groups respectively. The expulsion rate was 6.02%. However, this difference was not statistically significant. When ultrasonologically assessed partial expulsions were also considered, the total expulsion rate in both groups (14.3% and 14.1% respectively) was also not significantly different. The expulsion rate was higher in the vaginal delivery group (10.7%) than in the caesarean section (3.6%) group (p = 0.007) and early postpartum insertion 12.3% than in the immediate post-placental insertion group, 3.7% (p = 0.002). CONCLUSIONS: The study concluded that the altered shape of Cu 375 has effectively no role in decreasing the expulsion rate. Placement of IUCD at or near the uterine fundus immediately after delivering the placenta (post-placental) decreases the expulsion rate, thereby increasing the contraceptive efficacy.SHORT CONDENSATIONThe altered shape of Cu 375 has effectively no role in decreasing the expulsion rate. Placement of IUCD at or near the uterine fundus immediately after delivering the placenta (post-placental) decreases the expulsion rate, thereby increasing the contraceptive efficacy.

Expulsion and continuation rates of the 52 mg levonorgestrel intrauterine system in adolescents and adult women.

OBJECTIVE: To compare the continuation rates, expulsion, and other reasons for discontinuation of the hormonal intrauterine device with 52 mg of levonorgestrel (52 mg LNG-IUD) in adolescents and adult women. METHODS: We conducted a retrospective cohort study that included 393 women in whom we placed a 52 mg LNG-IUD and followed up to 5 years. We created two retrospective cohorts, one with 131 adolescents (aged between 12 and 19 years) and the other with 262 women aged ≥20 years. Each adolescent was paired with two adult women who had the same parity and who had a 52 mg LNG-IUD inserted on the same day. We used the Mann-Whitney test to compare numerical variables in both groups, the Kaplan-Meier method, and the log-rank test to compare the continuation, expulsion and other reasons for IUD discontinuation of the two groups. RESULTS: Age of the adolescents and adult women were mean ± SD 18.1 (±1.1) and 31 (±6.8) years, respectively (p = 0.015). Continuation rates by the fifth year of use were 55.6/100 women-years (W-Y) and 70.3/100 W-Y among adolescents and adult women (p = 0.106); and expulsion rates were 8.4/100 and 6.0/100 W-Y, respectively (p = 0.463). Adolescents had a lower continuation rate during 3 to 5 years of follow-up (p = 0.011) and a high rate of removals due to bleeding/pain (18.5 ± 5.7/100 W-Y vs 6.4/100 ± 2.1 W-Y, p = 0.039). CONCLUSION: Adolescents who used the 52 mg LNG-IUD showed a lower continuation rate 3-5 years after device placement than adult women. The expulsion rates were similar in both groups.

Adolescents who used the 52 mg LNG-IUD showed expulsion rates similar than adult women. Despite the good continuation rate, adolescents had a lower continuation rate within 3­5 years of follow-up and high rate of removals due to bleeding/pain than adult users.

An Examination of Suspension & Expulsion in Community Childcare Centers Two Years into the COVID-19 Pandemic.

Suspension and expulsion have been documented concerns in childcare centers throughout the United States for nearly 20 years. This study examined suspension and expulsion practices in community childcare centers two years into the COVID-19 pandemic (May 2022). Survey data from 131 administrators of community childcare programs were analyzed. It was found that at least 67 individual children were reported expelled across 131 programs, a rate similar to pre-pandemic rates and higher than rates at the height of the pandemic. For suspension, 136 individual children were suspended from early learning programs during this time; a rate almost double pre-pandemic levels. Factors (availability of support, prior suspensions, suggesting the program is not a match, reported turnover, waiting lists, enrollment capacity, administrator reported stress, and teacher perceived stress) were examined to determine if they predicted expulsion. None of these factors significantly predicted expulsion. These results and their limitations and implications are discussed.

Expulsion from Community Childcare Centers During the COVID-19 Pandemic: A Review of One State's Practices.

Expulsion has been a well-documented practice in early learning centers throughout the United States. The present study attempted to describe expulsion practices in one state's community childcare centers during the COVID-19 pandemic. Surveys from 161 childcare program administrators were analyzed and, overall, expulsion rates appeared to be lower than they were pre-pandemic. No association was found between whether a program closed and reopened or remained open; the presence of a waiting list; if a program readmitted all or some children; factors that influenced which teachers were rehired; training provided to teaching staff; perceived frequency and intensity of challenging behavior; and availability of support for children with challenging behaviors and expulsion decisions. Results of the current study are analyzed and discussed in this article along with the results and how they fit into the literature.

Complications after interval postpartum intrauterine device insertion.

BACKGROUND: In the United States, up to 57% of women report resumption of sexual activity by the 6 week postpartum visit. Effective contraception should be addressed and provided at that time, to avoid unintended pregnancies and optimize interpregnancy intervals. Long-acting reversible contraceptives are the most effective forms of reversible contraception and are increasingly popular during the postpartum period. However, timing of postpartum intrauterine device (IUD) placement varies among providers and many delay insertion due to concerns for uterine perforation or expulsion of the IUD. OBJECTIVE: This study aimed to evaluate uterine perforation and expulsion rates with IUD insertion at 4-8 weeks postpartum vs 9-36 weeks postpartum. STUDY DESIGN: We performed a retrospective cohort study using the Kaiser Permanente Southern California electronic medical record from 2010 to 2016. We calculated the proportion of perforations and expulsions with IUD insertion at 4-8 weeks vs 9-36 weeks postpartum. Our primary outcome was the perforation rate. Secondarily, we evaluated the expulsion rate. For our minimum sample size calculation, to detect a difference of 0.5% in the perforation rate, with a baseline perforation rate of 0.5% for the 9-36 week postpartum IUD placement group, 80% power, and 5% alpha error rate, we would need at least 4221 participants per group, 8442 in total. RESULTS: A total of 24,959 patients met inclusion criteria (n=13,180 in the 4-8 week group, n=11,777 in the 9-36 week group). Of 430 patients with a confirmed complication, 157 uterine perforations and 273 IUD expulsions were identified. Perforation rates were significantly higher with placement at 4-8 weeks than at 9-36 weeks (0.78% vs 0.46%; P=.001). After adjusting for race and ethnicity, breastfeeding, IUD type, provider type, parity, most recent delivery, and body mass index, the odds of perforation remained higher with placement at 4-8 weeks than at 9-36 weeks (adjusted odds ratio, 1.92; 95% confidence interval, 1.28-2.89). Our Kaplan-Meier survival curve showed that the risk of uterine perforation remained elevated until approximately 22-23 weeks postpartum. Expulsion rates were similar between the 2 groups (1.02 vs 1.17; P=.52). CONCLUSION: Uterine perforation after interval postpartum IUD insertion is greater at 4-8 weeks than at 9-36 weeks, although perforation rates remain low at <1%. Expulsion rates did not differ between the groups. Because overall rates of uterine perforation are low, women can safely be offered IUDs at any interval beyond 4 weeks with minimal concern for perforation.

Making the financial case for immediate postpartum intrauterine device: a budget impact analysis.

BACKGROUND: Clinical guidelines support inpatient postpartum intrauterine device insertion. However, inpatient placement remains infrequent, in part because of inconsistent private insurance reimbursement. OBJECTIVE: The purpose of this study was to explore how the payer's costs and number of unintended pregnancies associated with a postpartum intrauterine device differed on the basis of placement timing. STUDY DESIGN: Using a decision tree model and following a hypothetical cohort of people who intend to use an intrauterine device after their delivery, we conducted a cost analysis comparing the planned approach of inpatient vs outpatient postpartum insertion. Using a 2-year time horizon, the probability and cost estimates were derived from literature review. Our primary outcome was the total accrued costs to the payer. Secondarily, we examined the rates of early repeat pregnancy and sensitivity to estimates of key inputs, including the expulsion rates and the intrauterine device cost. RESULTS: Although an inpatient intrauterine device placement's upfront costs were higher, the total cost of this approach was lower. Including the costs of managing expulsions and complications, our model suggests that for every 1000 people desiring a postpartum intrauterine device, the intended inpatient intrauterine device placement resulted in total cost savings of $211,100 and the prevention of 37 additional pregnancies compared with outpatient placement. The inpatient cost savings were superior to the outpatient savings, largely because of a known high proportion not returning for outpatient placement and the resulting higher number of unintended pregnancies among the patients desiring outpatient placement. In sensitivity analyses, we found that the total cost to the payer was sensitive to the probability of expulsion after immediate postpartum intrauterine device placement. CONCLUSION: For beneficiaries desiring postpartum intrauterine device, payers are likely to save money by fully reimbursing inpatient intrauterine device placement rather than incentivizing placement at the frequently missed postpartum visit. These results support the financial case for private insurers to fully and separately reimburse (ie, "unbundle" from the single payment for delivery) inpatient postpartum intrauterine device placement.

Association between intrauterine device type and risk of perforation and device expulsion: results from the Association of Perforation and Expulsion of Intrauterine Device study.

BACKGROUND: Intrauterine devices, including levonorgestrel-releasing and copper devices, are highly effective long-acting reversible contraceptives. The potential risks associated with intrauterine devices are low and include uterine perforation and device expulsion. OBJECTIVE: This study aimed to evaluate the risk of perforation and expulsion associated with levonorgestrel-releasing devices vs copper devices in clinical practice in the United States. STUDY DESIGN: The Association of Perforation and Expulsion of Intrauterine Device study was a retrospective cohort study of women aged ≤50 years with an intrauterine device insertion during 2001 to 2018 and information on intrauterine device type and patient and medical characteristics. Of note, 4 research sites with access to electronic health records contributed data for the study: 3 Kaiser Permanente-integrated healthcare systems (Northern California, Southern California, and Washington) and 1 healthcare system using data from a healthcare information exchange in Indiana (Regenstrief Institute). Perforation was classified as any extension of the device into or through the myometrium. Expulsion was classified as complete (not visible in the uterus or abdomen or patient reported) or partial (any portion in the cervix or malpositioned). We estimated the crude incidence rates and crude cumulative incidence by intrauterine device type. The risks of perforation and expulsion associated with levonorgestrel-releasing intrauterine devices vs copper intrauterine devices were estimated using Cox proportional-hazards regression with propensity score overlap weighting to adjust for confounders. RESULTS: Among 322,898 women included in this analysis, the incidence rates of perforation per 1000 person-years were 1.64 (95% confidence interval, 1.53-1.76) for levonorgestrel-releasing intrauterine devices and 1.27 (95% confidence interval, 1.08-1.48) for copper intrauterine devices; 1-year and 5-year crude cumulative incidence was 0.22% (95% confidence interval, 0.20-0.24) and 0.63% (95% confidence interval, 0.57-0.68) for levonorgestrel-releasing intrauterine devices and 0.16% (95% confidence interval, 0.13-0.20) and 0.55% (95% confidence interval, 0.44-0.68) for copper intrauterine devices, respectively. The incidence rates of expulsion per 1000 person-years were 13.95 (95% confidence interval, 13.63-14.28) for levonorgestrel-releasing intrauterine devices and 14.08 (95% confidence interval, 13.44-14.75) for copper intrauterine devices; 1-year and 5-year crude cumulative incidence was 2.30% (95% confidence interval, 2.24-2.36) and 4.52% (95% confidence interval, 4.40-4.65) for levonorgestrel-releasing intrauterine devices and 2.30% (95% confidence interval, 2.18-2.44) and 4.82 (95% confidence interval, 4.56-5.10) for copper intrauterine devices, respectively. Comparing levonorgestrel-releasing intrauterine devices with copper intrauterine devices, the adjusted hazard ratios were 1.49 (95% confidence intervals, 1.25-1.78) for perforation and 0.69 (95% confidence intervals, 0.65-0.73) for expulsion. CONCLUSION: After adjusting for potential confounders, levonorgestrel-releasing intrauterine devices were associated with an increased risk of uterine perforation and a decreased risk of expulsion relative to copper intrauterine devices. Given that the absolute numbers of these events are low in both groups, these differences may not be clinically meaningful.

Association between menorrhagia and risk of intrauterine device-related uterine perforation and device expulsion: results from the Association of Uterine Perforation and Expulsion of Intrauterine Device study.

BACKGROUND: Intrauterine devices are effective instruments for contraception, and 1 levonorgestrel-releasing device is also indicated for the treatment of heavy menstrual bleeding (menorrhagia). OBJECTIVE: To compare the incidence of intrauterine device expulsion and uterine perforation in women with and without a diagnosis of menorrhagia within the first 12 months before device insertion STUDY DESIGN: This was a retrospective cohort study conducted in 3 integrated healthcare systems (Kaiser Permanente Northern California, Southern California, and Washington) and a healthcare information exchange (Regenstrief Institute) in the United States using electronic health records. Nonpostpartum women aged ≤50 years with intrauterine device (eg, levonorgestrel or copper) insertions from 2001 to 2018 and without a delivery in the previous 12 months were studied in this analysis. Recent menorrhagia diagnosis (ie, recorded ≤12 months before insertion) was ascertained from the International Classification of Diseases, Ninth and Tenth Revision, Clinical Modification codes. The study outcomes, viz, device expulsion and device-related uterine perforation (complete or partial), were ascertained from electronic medical records and validated in the data sources. The cumulative incidence and crude incidence rates with 95% confidence intervals were estimated. Cox proportional hazards models estimated the crude and adjusted hazard ratios using propensity score overlap weighting (13-16 variables) and 95% confidence intervals. RESULTS: Among 228,834 nonpostpartum women, the mean age was 33.1 years, 44.4% of them were White, and 31,600 (13.8%) had a recent menorrhagia diagnosis. Most women had a levonorgestrel-releasing device (96.4% of those with and 78.2% of those without a menorrhagia diagnosis). Women with a menorrhagia diagnosis were likely to be older, obese, and have dysmenorrhea or fibroids. Women with a menorrhagia diagnosis had a higher intrauterine device-expulsion rate (40.01 vs 10.92 per 1000 person-years) than those without, especially evident in the first few months after insertion. Women with a menorrhagia diagnosis had a higher cumulative incidence (95% confidence interval) of expulsion (7.00% [6.70-7.32] at 1 year and 12.03% [11.52-12.55] at 5 years) vs those without (1.77% [1.70-1.84] at 1 year and 3.69% [3.56-3.83] at 5 years). The risk of expulsion was increased for women with a menorrhagia diagnosis vs for those without (adjusted hazard ratio, 2.84 [95% confidence interval, 2.66-3.03]). The perforation rate was low overall (<1/1000 person-years) but higher in women with a diagnosis of menorrhagia vs in those without (0.98 vs 0.63 per 1000 person-years). The cumulative incidence (95% confidence interval) of uterine perforation was slightly higher for women with a menorrhagia diagnosis (0.09% [0.06-0.14] at 1 year and 0.39% [0.29-0.53] at 5 years) than those without it (0.07% [0.06-0.08] at 1 year and 0.28% [0.24-0.33] at 5 years). The risk of perforation was slightly increased in women with a menorrhagia diagnosis vs in those without (adjusted hazard ratio, 1.53; 95% confidence interval, 1.10-2.13). CONCLUSION: The risk of expulsion is significantly higher in women with a recent diagnosis of menorrhagia. Patient education and counseling regarding the potential expulsion risk is recommended at insertion. The absolute risk of perforation for women with a recent diagnosis of menorrhagia is very low. The increased expulsion and perforation rates observed are likely because of causal factors of menorrhagia.

Clinical value of positive BET and pelvic floor dyssynergia in Chinese patients with functional defecation disorder.

BACKGROUND: Functional defecation disorder (FDD) is a common subtype of functional constipation (FC). Balloon expulsion test (BET) and high resolution anorectal manometry (HR-ARM) are significant tools but their results are not always consistent. AIMS: To investigate the characteristics of patients with positive BET and pelvic floor dyssynergia (PFD) and explore the value of both positive results in FDD diagnosis. METHODS: We retrospectively diagnosed FC subtypes and enrolled FDD patients based on Rome-IV criteria. They underwent HR-ARM, BET and CTT tests. Then they were classified to two groups and further stratified by FDD subtypes. Validated questionnaires were applied to investigate patients' constipation, anxiety/depression and quality of life. RESULTS: 335 FDD patients were finally enrolled. They were classified into two groups according to whether BET and PFD were both positive (consistent or not). 84.48% showed consistent results. These patients had significantly higher anal residual pressure, lower anal relaxation rate, manometric defecation index (MDI) and a more negative rectoanal pressure gradient (RAPG) (Ps < .05). The specific distribution of FDD phenotypes in two groups showed significant difference (p = .021). Males suffered a more negative RAPG (p < .001) and age was correlated with anal relaxation rate (p < .001). A subset (177 individuals) was investigated with validated questionnaires. Scores for Defecation Symptoms, Physical Discomfort and GAD-7 score were significantly high in Consistent Group (Ps < .05). GAD-7 score was associated with Defecation Symptoms (p < .001) while anal residual pressure, GAD-7 and Defecation Symptoms score were linked to Physical Discomfort (Ps < .05). The diagnostic specificity and PPV for FDD rose significantly with positive BET and PFD. CONCLUSION: FDD patients with positive BET and PFD suffered from severe defecation symptoms, anxiety and impaired QOL. Positive BET and PFD could be an ideal tool for screening FDD.

Efficacy of Mirabegron as Medical Expulsive Therapy for Distal Ureteral Stones: A Prospective, Randomized, Double-Blinded, Controlled Study.

BACKGROUND: Today, medical expulsive therapy (MET) is more effective and commonly used in distal ureteral stones when compared with conservative treatments. Many treatments, namely, alpha-adrenergic blockers and calcium channel blockers, prostaglandin synthesis inhibitors, glyceryl trinitrate, and steroids, have been, therefore, utilized to mitigate such complications and accelerate stone expulsion. Several animal and human studies revealed the presence of ß3-receptors in the ureter and bladder, where stimulating these receptors could relax the distal ureteral segment. OBJECTIVES: The aim of the study was to evaluate the efficacy of use of mirabegron as MET for distal ureteral stones (intramural and extramural). METHODS: This is a prospective randomized controlled study including 90 patients who had distal ureteral stones less than 10 mm and were evaluated between January and June 2020. The patients were classified into 3 groups: group (A) 30 patients: mirabegron 50 mg d-1 + diclofenac Na 100 mg tab (to be taken only during colic episodes), group (B) 30 patients: tamsulosin HCL 0.4 mg cap + diclofenac Na 100 mg tab (to be taken only during colic episodes), and group (C) 30 patients: diclofenac Na 100 mg tab only (to be taken only during colic episodes). Age, sex, stone size, laterality, and grade of ureterohydronephrosis were recorded. Patients were observed for 30 days, and ureteroscopy was completed for those with nonexpulsed stones. Follow-up parameters included number of renal colic episodes, duration of medical therapy, stone expulsion time, and stone expulsion rate (SER). RESULTS: In the group (A), 2 (6.6%) patients were excluded due to nasal congestion, and 1 (3.3%) patient was excluded due to a 20-mm Hg systolic blood pressure increase. Four (13.3%) patients in group (B) were noncompliant on medical treatment. In addition, 2 (6.6%) patients in group (A), 1 (3.3%) patient in group (B), and 5 (16.6%) patients in group (C) who did not attend follow-up examinations were excluded from the study. The SER increased significantly in group (A) and (B) when compared with group (C). The mean time of stone expulsion was about 15, 25, and 12 days for groups A, B, and C, respectively, and there was a significant statistical difference (p value = 0.006) among the 3 groups. The mean number of renal colic episodes of group (A) of patients was 1.8 times, while that of group (B) was 2.6 times and that of group (C) was 2.16 times with no significant statistical difference after comparing the 3 groups (p value = 0.660). CONCLUSIONS: Treatment with mirabegron appears to be a safe and effective medical expulsion therapy for distal ureteric stones and is better than tamsulosin.