Research priorities for expanding access to methadone treatment for opioid use disorder in the United States: A National Institute on Drug Abuse Center for Clinical Trials Network Task Force report.

In the US, methadone treatment can only be provided to patients with opioid use disorder (OUD) through federal and state-regulated opioid treatment programs (OTPs). There is a shortage of OTPs, and racial and geographic inequities exist in access to methadone treatment. The National Institute on Drug Abuse Center for Clinical Trials Network convened the Methadone Access Research Task Force to develop a research agenda to expand and create more equitable access to methadone treatment for OUD. This research agenda included mechanisms that are available within and outside the current regulations. The task force identified 6 areas where research is needed: (1) access to methadone in general medical and other outpatient settings; (2) the impact of methadone treatment setting on patient outcomes; (3) impact of treatment structure on outcomes in patients receiving methadone; (4) comparative effectiveness of different medications to treat OUD; (5) optimal educational and support structure for provision of methadone by medical providers; and (6) benefits and harms of expanded methadone access. In addition to outlining these research priorities, the task force identified important cross-cutting issues, including the impact of patient characteristics, treatment, and treatment system characteristics such as methadone formulation and dose, concurrent behavioral treatment, frequency of dispensing, urine or oral fluid testing, and methods of measuring clinical outcomes. Together, the research priorities and cross-cutting issues represent a compelling research agenda to expand access to methadone in the US.

Per Oral Endoscopic Myotomy in pregnancy.

OBJECTIVE: To report the first successful full-term delivery following Per Oral Endoscopic Myotomy (POEM) performed during pregnancy. METHODS/BACKGROUND: Achalasia is an esophageal motility disorder characterized by dysphagia, regurgitation, reflux, recurrent vomiting, and weight loss. Achalasia in pregnancy can affect nutritional status of the mother, and subsequently, the child, increasing morbidity and creating potential pregnancy complications. POEM is a novel endoscopic procedure which involves cutting the lower esophageal sphincter to allow food to pass, and is considered a safe and effective management option for achalasia in non-pregnant individuals. RESULTS: We discuss the case of a patient with achalasia and a prior Heller myotomy who presented with recrudescence of severe symptoms prompting evaluation and treatment with POEM. CONCLUSION: This is the first report of successful full-term delivery following POEM performed during pregnancy, demonstrating its feasibility and safety in this patient population when approached with a multidisciplinary team.

Mirror syndrome: a systematic literature review.

OBJECTIVE: This study aimed to review the diagnostic criteria for mirror syndrome and describe its clinical presentation. DATA SOURCES: Databases from PubMed, Scopus, Cochrane Library, ClinicalTrials.gov, and CINAHL were inquired for case series containing ≥2 cases of mirror syndrome from inception to February 2022. STUDY ELIGIBILITY CRITERIA: Studies were included if they reported ≥2 cases of mirror syndrome and included case reports, case series, cohort studies, and case-control studies. STUDY APPRAISAL AND SYNTHESIS METHODS: The studies' quality and risk of bias were independently assessed. Data were tabulated using Microsoft Excel and summarized using narrative review and descriptive statistics. This systematic review was conducted according to the Preferred Reporting Item for Systematic Reviews and Meta-Analyses statement. All eligible references were assessed. Screening of records and data extraction were independently performed, and a third author resolved disagreements. RESULTS: Of 13 citations, 12 studies (n=82) reported diagnostic criteria for mirror syndrome: maternal edema (11/12), fetal hydrops (9/12), placental edema (6/12), placentomegaly (5/12), and preeclampsia (2/12); 12 studies (n=82) described the clinical presentation of mirror syndrome as maternal edema (62.2%), hypoalbuminemia (54.9%), anemia (39.0%), and new-onset hypertension (39.0%); 4 studies (n=36) reported that hemodilution was present in all patients; 8 studies (n=36) reported the etiology of fetal hydrops, with the most common being structural cardiac malformations (19.4%), alpha thalassemia (19.4%), Rh isoimmunization (13.9%), and nonimmune hydrops fetalis (13.9%); and 6 studies (n=47) reported maternal complications, 89.4% of which were major: postpartum hemorrhage (44.7%), hemorrhage requiring blood transfusion (19.1%), intensive care unit admission (12.8%), heart failure (10.6%), pulmonary edema (8.5%), and renal dysfunction (8.5%). In 39 cases, the reported fetal outcomes were stillbirth (66.6%) and neonatal or infant death (25.6%). The overall survival rate among continued pregnancies was 7.7%. CONCLUSION: The diagnostic criteria of mirror syndrome differed considerably among studies. Mirror syndrome clinical presentation overlapped with preeclampsia. Only 4 studies discussed hemodilution. Significant maternal morbidity and fetal mortality were associated with mirror syndrome. Further research is warranted to elucidate the pathogenesis of mirror syndrome to better guide clinicians in identifying and managing the condition.

Stepwise implementation of vaginal cleansing and azithromycin at cesarean: a quality improvement study.

OBJECTIVE: We aimed to decrease our surgical site infection (SSI) rate by 30% by sequential implementation of vaginal cleansing and azithromycin for women who underwent a cesarean delivery (CD) after having labored or experienced rupture of membranes. METHODS: This is a quality improvement project that assessed the stepwise implementation of two interventions within three time periods: (1) 12 months prior to implementation of either intervention; (2) 14 months of vaginal cleansing as infection prophylaxis; (3) 16 months of vaginal cleansing and azithromycin as infection prophylaxis. The primary outcome measure was the SSI as defined by the Center for Disease Control and Prevention and analyzed by control charts. The process measures were compliance rates of vaginal cleansing and azithromycin. Significance was detected by rules for determining a special cause variation. This study followed the SQUIRE 2.0 guidelines for reporting on quality improvement. RESULTS: There were 1033 patients included from the three study periods. The total rate of SSI decreased from 22.8% to 15.2% after implementing vaginal cleansing. Special cause variation was detected with an 8-point shift starting 4 months after implementation of vaginal cleansing. This decrease was sustained during the following 26 months. Adding azithromycin did not significantly lower the SSI rate further. When examined separately, deep SSI (p = .009) and endometritis (p = .001) significantly decreased in the post-intervention periods. Pre-operative vaginal cleansing compliance rose to 74%, and then further increased to 85% 1 year after implementation. Azithromycin compliance rose to 75%. Total length of postpartum stay decreased over the study periods from 3.5 ± 1.4 days to 3.2 ± 0.8 days (p = .001). CONCLUSION: In this quality improvement study, implementation of vaginal cleansing decreased the SSI rate by 33%, from 22.8% to 15.2%. The addition of azithromycin did not result in any additional change in SSI rate.

Prophylactic rotation for malposition in the second stage of labor: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: This study aimed to evaluate if manual rotation, undertaken during labor, of fetuses in occiput posterior or occiput transverse position led to an increased rate of spontaneous vaginal delivery. DATA SOURCES: Searches were performed in MEDLINE, Ovid, Scopus, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials with the use of a combination of keywords and text words related to "occiput posterior," "occiput transverse," and "manual rotation" from inception of the databases to July 2021. STUDY ELIGIBILITY CRITERIA: We included all randomized controlled trials evaluating manual rotation of fetuses in the occiput posterior or occiput transverse position during labor. METHODS: The primary outcome was the rate of spontaneous vaginal delivery. Meta-analyses were performed using the random effects model of DerSimonian and Laird to determine the relative risks or mean differences with 95% confidence intervals. RESULTS: A total of 643 records were screened with inclusion of 6 articles and 1002 randomized patients. All included studies compared manual rotation of fetuses in occiput posterior or occiput transverse position, all confirmed using ultrasound examinations, after complete cervical dilation with either no rotation or a sham rotation procedure. There was no difference in the rate of spontaneous vaginal delivery with manual rotation (relative risk, 1.07; 95% confidence interval, 0.95-1.20) nor was there any difference in any other maternal or fetal outcomes. In a subgroup analysis of occiput posterior fetuses, there was a 12.80-minute decrease in the length of the second stage of labor in the manual rotation group (mean difference, -12.80; 95% confidence interval, -22.61 to -2.99). There were no significant differences in any other maternal or fetal outcomes in the occiput posterior subgroup and no differences in the occiput transverse subgroup. CONCLUSION: Prophylactic manual rotation of fetuses in occiput posterior or occiput transverse position, confirmed using ultrasound examination, did not increase the rate of spontaneous vaginal delivery compared with no manual rotation. Manual rotation of the occiput posterior fetal head early during the second stage of labor was associated with a significant 12.8-minute decrease in the length of the second stage of labor with no changes in any other maternal or fetal outcomes. There were no differences demonstrated for fetuses rotated from occiput transverse position or for the combination of occiput posterior and occiput transverse fetuses. Because there is some evidence of benefit, prophylactic manual rotation can be offered to patients during the second stage of labor presenting with occiput posterior position of the fetal head documented during ultrasound examination.

Pregnancy management in a patient with stickler syndrome.

BACKGROUND: Stickler syndrome is a collagen disorder that can affect multiple organ systems. It is characterized by ocular abnormalities, hearing loss, midfacial hypoplasia, hypermobility, and joint abnormalities. The phenotypic expression of Stickler syndrome can vary among those affected. Since Stickler syndrome is a collagen disorder, it is possible to expect pregnancy complications similar to those reported in other collagen disorders. To our knowledge, there is only one case report in the literature on the management of pregnancy and delivery of a patient with Stickler syndrome. METHODS/CASE REPORT: A 37-year-old primigravid woman with a diagnosis of Stickler syndrome presented at 9 weeks gestation for prenatal genetic consultation. At 26, the patient had prophylactic laser therapy for lattice degeneration of the retina. At 32, she was found to be heterozygous for the c.1527 G>T variant in the COL2A1 gene, which is associated with ocular abnormalities and autosomal dominant form of Stickler syndrome. Subsequently, she desired to pursue prenatal diagnostic testing for the familial variant. The patient voiced that the results would impact pregnancy management. Amniocentesis was performed at 16 weeks gestation. Results were negative for the maternal COL2A1 variant. Karyotype was normal (46, XX). RESULTS: A multidisciplinary team using a patient-centered approach including obstetrics, ophthalmology, maternal-fetal medicine, and genetics determined that there were no contraindications for vaginal delivery. At 39 weeks, the patient underwent spontaneous vaginal delivery with no complications. CONCLUSION: There is a paucity of data available regarding the maternal outcomes of women affected with collagen disorders, especially Stickler Syndrome. This case highlights the importance of accurate genetic diagnosis in the prenatal period and provides information to physicians caring for patients with Stickler syndrome.

An IL-6 receptor antagonist attenuates postpartum anhedonia, but has no effect on anhedonia precipitated by subchronic stress in female rats.

RATIONALE: Nearly 60-80% of women experience some form of sadness, anxiety, or anhedonia in the weeks following the birth of a child (Patel et al. 23(2):534-42, 2012; Degner 10: 359;j4692, 2017); however, the exact mechanisms that precipitate these changes in mood postpartum are still unknown. It is well-known that the function of the peripheral immune system is significantly altered during pregnancy in order to protect the developing fetus from being rejected by the maternal immune system (Fallon et al. 17(1):7-17, 2002), and we have recently found a dramatic change in the central immune system during and just after pregnancy in female rats (Sherer et al. 66:201-209, 2017). We observed anhedonia in Sprague-Dawley rat dams on the day of birth that is associated with an increase in interleukin (IL)-6 expression in the brain on the day of birth (Posillico and Schwarz 298(Pt B):218-28, 2016). OBJECTIVES: The goal of the current experiments was to determine whether inhibiting the IL-6 receptor could prevent onset of this postpartum anhedonia, or anhedonia precipitated by subchronic stress in non-pregnant females. RESULTS: Treatment with an IL-6 receptor antibody attenuated postpartum anhedonia as characterized by a decrease in sucrose preference. In contrast, this antibody had no effect on the decrease in sucrose preference induced following a week of forced swim stress in non-pregnant female rats. CONCLUSIONS: The results of these studies suggest that the molecular mechanisms that underlie the onset of anhedonia following birth or mild stress in female rats may be distinct.

An examination of sex differences in the effects of early-life opiate and alcohol exposure.

Early-life exposure to drugs and alcohol is one of the most preventable causes of developmental, behavioural and learning disorders in children. Thus a significant amount of basic, animal and human research has focused on understanding the behavioural consequences and the associated neural effects of exposure to drugs and alcohol during early brain development. Despite this, much of the previous research that has been done on this topic has used predominantly male subjects or rodents. While many of the findings from these male-specific studies may ultimately apply to females, the purpose of this review is to highlight the research that has also examined sex as a factor and found striking differences between the sexes in their response to early-life opiate and alcohol exposure. Finally, we will also provide a framework for scientists interested in examining sex as a factor in future experiments that specifically examine the consequences of early-life drug and alcohol exposure.

Revisión sistemática de evaluaciones económicas en salud para el tratamiento de la obesidad en adultos, 2009-2019

[RESUMEN]. Objetivo. Analizar las evaluaciones económicas en salud para el tratamiento de la obesidad en adultos publicadas en la literatura mundial entre 2009-2019. Métodos. Revisión sistemática aplicando las guías Cochrane, PRISMA y CHEERS para estudios de economía de la salud. Se garantizó la exhaustividad, reproducibilidad y calidad metodológica del protocolo de selección y extracción de la información. Se realizó síntesis cualitativa mediante frecuencia por tipo de evaluación económica. Resultados. Se tamizaron 4 493 artículos y sólo 95 cumplieron con los criterios del protocolo, la mayoría de Estados Unidos (n=38), principalmente con estudios de costo-utilidad (n=39) y descripción de costos (n=18). Se incluyeron personas con múltiples comorbilidades, la más frecuente de las cuales fue la diabetes. Las intervenciones más evaluadas fueron las quirúrgicas (n=53), y los desenlaces más frecuentes fueron la reducción de peso y los años de vida ajustados por calidad. La perspectiva de evaluación más frecuente fue la del tercer pagador (n=46) y el horizonte temporal más empleado fue el corto plazo para las intervenciones dirigidas a los estilos de vida y de largo plazo para las quirúrgicas. Conclusión. Los estudios microeconómicos para el tratamiento de la obesidad se han incrementado en los últimos años; sin embargo, persisten vacíos como la baja aplicación de intervenciones no quirúrgicas, evaluaciones parciales o de costo-efectividad y análisis desde la perspectiva social. Estos constituyen ejes importantes para las prácticas en salud basadas en evidencia y la toma de decisiones relacionando los beneficios en salud con los costos implicados.

[ABSTRACT]. Objective. To analyze health economic evaluations for the treatment of obesity in adults published globally between 2009-2019. Methods. Systematic review applying Cochrane, PRISMA and CHEERS guidelines for health economics studies. The selection and information extraction protocol assured the completeness, reproducibility and methodological quality. Qualitative synthesis was carried out by means of frequency of type of economic evaluation. Results. We screened 4 493 articles and only 95 met the protocol criteria, most of them from the United States (n=38), mainly with cost-utility studies (n=39) and cost descriptions (n=18). People with multiple comorbidities were included, the most common of which was diabetes. The most evaluated interventions were surgical (n=53), and the most frequent outcomes were weight reduction and quality adjusted life years. The most frequent evaluation perspective was that of the third payer (n=46); most common timeline was the short term for lifestyle interventions and the long term for surgical ones. Conclusion. Microeconomic studies for the treatment of obesity have increased in recent years; however, gaps remain such as the low application of non-surgical interventions, partial or cost-effectiveness evaluations, and analyses from the social perspective. These represent important aspects for evidence-based health practices and decision making relating health benefits to the costs involved.