Protocol for a longitudinal, prospective cohort study investigating the biology of uterine fibroids and endometriosis, and patients' quality of life: the FENOX study.

INTRODUCTION: Millions of women suffer from the consequences of endometriosis and uterine fibroids, with fibroids the cause for over 50% of hysterectomies in the USA, and direct costs for their treatment estimated at between US$4 and US$9 billion. Endometriosis commonly affects millions of women worldwide predominantly during reproductive age, with severe menstrual and non-menstrual pain and subfertility the main symptoms. Due to the 'unhappy triad' of endometriosis-lack of awareness, lack of clinically relevant biomarkers and the unspecific nature of symptoms-women wait on average for 8-12 years before the definitive endometriosis diagnosis is made. Treatment options for both conditions are not satisfactory at the moment, especially with a view to preserving fertility for the women and families affected. In the Fibroids and Endometriosis Oxford (FENOX) study, we combine the investigation of fibroids and endometriosis, and plan to collect high-quality tissue samples and medical data of participants over a time frame of 5 years after surgical intervention. METHODS AND ANALYSIS: Biological samples such as blood, saliva, urine, fat, peritoneal fluid and-if found-endometrial tissue or fibroids as well as detailed clinical and intraoperative data will be collected from women undergoing surgery and participating in the study after informed consent. We plan to recruit up to 1200 participants per disease arm (ie, endometriosis and uterine fibroids) over 5 years. Participants will fill in detailed and validated questionnaires on their medical history and quality of life, with follow-ups for 5 years. Enrolment started on 2 April 2018, and FENOX will close on 31 March 2028. We will analyse the biological samples using state-of-the-art molecular biology methods and correlate the findings with the medical records and questionnaire data. ETHICS AND DISSEMINATION: The findings will be published in high-ranking journals in the field and presented at national and international conferences. TRIAL REGISTRATION NUMBER: ISRCTN13560263.

Mass cytometry analysis reveals a distinct immune environment in peritoneal fluid in endometriosis: a characterisation study.

BACKGROUND: Endometriosis is a gynaecological condition characterised by immune cell infiltration and distinct inflammatory signatures found in the peritoneal cavity. In this study, we aim to characterise the immune microenvironment in samples isolated from the peritoneal cavity in patients with endometriosis. METHODS: We applied mass cytometry (CyTOF), a recently developed multiparameter single-cell technique, in order to characterise and quantify the immune cells found in peritoneal fluid and peripheral blood from endometriosis and control patients. RESULTS: Our results demonstrate the presence of more than 40 different distinct immune cell types within the peritoneal cavity. This suggests that there is a complex and highly heterogeneous inflammatory microenvironment underpinning the pathology of endometriosis. Stratification by clinical disease stages reveals a dynamic spectrum of cell signatures suggesting that adaptations in the inflammatory system occur due to the severity of the disease. Notably, among the inflammatory microenvironment in peritoneal fluid (PF), the presence of CD69+ T cell subsets is increased in endometriosis when compared to control patient samples. On these CD69+ cells, the expression of markers associated with T cell function are reduced in PF samples compared to blood. Comparisons between CD69+ and CD69- populations reveal distinct phenotypes across peritoneal T cell lineages. Taken together, our results suggest that both the innate and the adaptive immune system play roles in endometriosis. CONCLUSIONS: This study provides a systematic characterisation of the specific immune environment in the peritoneal cavity and identifies cell immune signatures associated with endometriosis. Overall, our results provide novel insights into the specific cell phenotypes governing inflammation in patients with endometriosis. This prospective study offers a useful resource for understanding disease pathology and opportunities for identifying therapeutic targets.

Infants With Technology Dependence: Facilitating the Road to Home.

BACKGROUND: The incidence of premature infants with complex medical needs, dependent upon medical technology at discharge, is on the rise in the United States. PURPOSE: Preparing the family for the hospital-to-home transition can be challenging due to the complex medical and emotional needs of the vulnerable infant and the volume of subspecialty services and equipment required. METHODS/SEARCH STRATEGY: Relevant articles from PubMed, Google Scholar, CINAHLFINDINGS/RESULTS:: There is an increasing incidence of technology dependent infants discharged from neonatal intensive care units in the United States. Transition from hospital to home requires lengthy preparation, multidisciplinary-open communication, and family centered care. IMPLICATIONS FOR PRACTICE: Early assimilation of the parents into the ongoing care of their infant, the provision of comprehendible parental education by neonatal nurses and other members of the healthcare team, the provision of adequate rooming-in experiences prior to discharge, and the collaborative coordination of outpatient community services are crucial elements of the discharge process. Neonatal nurses possess population-specific education, training, commitment, and expertise that make them the ideal experts to implement and evaluate a discharge planning framework, in collaboration with the medical team and the family. IMPLICATIONS FOR RESEARCH: Methods to prevent readmission and ensure successful discharge from hospital to home is indicated. Standardization of a discharge process of infants of technology dependence combining medical team, family, outpatient coordinators, and primary care providers.

Implementing Co-Regulated Feeding with Mothers of Preterm Infants.

PURPOSE: The purpose of this study is to describe implementation of the Co-Regulated Feeding Intervention (CoReg), when provided by mothers and guided by intervention nurses trained in methods of guided participation (GP). Co-regulated feeding intervention aims to prevent stress during feeding and ease the challenge very preterm (VP) infants experience coordinating breathing and swallowing during the early months. Guided participation is a participatory learning method to guide the complex learning required for mothers. STUDY DESIGN AND METHODS: Sixteen mothers of 17 VP infants participated. Each mother received a median of five intervention sessions during the infant's transition to oral feeding. Intervention field notes, audio recordings of the sessions, and video recordings of the nurse-guided feedings were reviewed, organized, and content analyzed to evaluate implementation. RESULTS: The co-regulated feeding intervention was well received by mothers; enrollment, participation, and retention rates were high. Most mothers chose to spread out the intervention sessions across the transition period. Scheduling sessions was the greatest barrier. Mothers had competing demands and infant readiness to eat could not be predicted. The top five issues identified as needing attention by the mother or nurse included reading cues, coregulating breathing, providing motoric stability, regulating milk flow, and providing rest periods. Main GP strategies included joint attention with the mother to the dyad's feeding challenges, auditory assessment of breathing and swallowing, and reflection with planning for future feedings using video playback. CLINICAL IMPLICATIONS: Nurse presence while mothers feed affords rich opportunities to guide coregulated, cue-based feeding. Co-regulated feeding intervention would be enhanced if mothers are guided by the bedside nurse.

Historic condition in a modern child with autism.

CASE: Haven is an 11-year-old primary care patient who you have followed since her birth. She was the 9 lb 6 oz product of a 38-week gestation complicated by maternal hypertension and seizure disorder treated with tegretol. Her delivery and neonatal course were uneventful. She was diagnosed with austistic disorder at age 2 years, at which time she used no functional language or gestures, had repetitive motor mannerisms, and limited eye contact. She had strong tactile sensory aversions. Her diet was very restricted including only banana yogurt and drinking milk and apple juice for the first several years of life. She was followed by a developmental-behavioral pediatrician approximately annually through age 8 years and then more frequently. She was healthy other than lead exposure (maximum serum level 18 at age 3 years) and multiple febrile seizures with other possible absence episodes. Her development remained very delayed with use of single words and short phrases. She developed multiple repetitive, anxious, obsessive behaviors (picking up lint, organizing, cleaning, and freezing in certain postures) that were treated with a selective serotonin reuptake inhibitors fluvoxamine. Sensory issues were ongoing, with restrictive eating (primarily peanut butter and jelly sandwiches, cereal bars, milk, and a kiwi-strawberry drink). She took a liquid multivitamin until age 8.At age 11 years, 3 weeks prior to admission, Haven developed acute loss of ambulation over the course of 1 day, initially dragging her right leg, and then refusing to walk and her parents brought her in to see you. She had fever, vomiting, and general weakness. She developed extensive bruising over her legs, especially in the popliteal fossae. She was also noted to have friability and dark discoloration of her gums. Initially, you suspected a post-viral syndrome and close monitoring. She was seen twice in the next 2 weeks in a local emergency room where her erythrocyte sedimentation rate was reported to be elevated and juvenile rheumatoid arthritis or a reaction to fluvoxamine were suspected. Antibiotics were also prescribed for gingivitis. She was seen by an orthopedist who felt it was not an orthopedic issue and leg films were unremarkable. With her second emergency room visit, she was transferred to a tertiary medical center and admitted for further evaluation. Where would you go from here?

Developing a Co-Regulated, Cue-Based Feeding Practice: The Critical Role of Assessment and Reflection.

Assessment of early feeding skills of vulnerable infants is common practice in neonatal care centers. However, assessment is often merely an identification of feeding outcomes, rather than a description of the infant's capacities and methods of adapting to the feeding challenge. Descriptive assessment of the feeding process takes into account the dynamic nature of feeding and notes changes that occur as the infant matures and gains feeding experience. Assessment of the variability that occurs during the feeding as the challenge changes, due to fatigue or physiologic instability, are critical to understanding the infant's feeding skills. As individual components of the feeding are assessed, such as sucking, swallowing and breathing, a reflective process builds understanding of the patterns of coordination of system components in relation to one another. Taking the whole into account and considering the dynamics of the process is necessary if we are going to select appropriate interventions targeted to the individual infant's feeding skills. Using a very preterm infant case, this paper will illustrate assessment of early feeding skills and demonstrate how reflection on and integration of the components of the assessment identifies potential targets for co-regulated, cue-based feeding.

Practice parameters and financial factors impacting developmental-behavioral pediatrics.

OBJECTIVE: Little has been published about the professional activities of developmental-behavioral (DB) pediatricians. To better understand the settings in which DB pediatricians work, allocation of their professional time, and how financial considerations impact their practice, the Society for Developmental and Behavioral Pediatrics surveyed its membership. METHOD: An extensive on-line three-part survey was conducted in 2006-2007 assessing sociodemographic characteristics, practice descriptors, coding and billing practices, productivity goals and perceived pressures among Society for Developmental and Behavioral Pediatric's 438 physician members. RESULTS: Of the pediatricians responding, representing all regions of the United States, 93% were DB pediatrics subspecialty board certified or eligible. The majority was practicing DB pediatrics full-time (73%); and 67% were exclusively in academic settings. All reported seeing patients, 84% reported teaching, 76% reported having administrative responsibilities, and 46% reported conducting research. Despite having non-clinical responsibilities, full-time equivalent positions included an average of 25 hours per week in direct patient care and 14.5 hours per week (37% of clinical time) in indirect patient care. Only 42% reported working with multidisciplinary teams. Salaries varied widely within and across regions. Deficits in billing/coding practices, awareness of personal clinical productivity, and familiarity with national productivity benchmarks were identified. CONCLUSIONS: DB pediatricians work in diverse settings nationwide. They provide considerable time in indirect patient care, which is poorly reimbursed in general and relative to direct patient care. The results of this survey offer opportunities for provider, institutional and payer education.

Video and CD-ROM as a training tool for performing neurologic examinations of 1-year-old children in a multicenter epidemiologic study.

In lieu of traditional training of examiners to identify cerebral palsy on a neurologic examination at age 1 year, we proposed an alternative approach using a multimedia training video and CD-ROM we developed after a two-step validation process. We hypothesized that use of CD-ROM interactive training will lead to reliable and valid performance of the neurologic examination by both pediatric neurologists and nonpediatric neurologists. All examiners were asked to take one of six interobserver variability tests found on the CD-ROM on two occasions. In the first interobserver variability evaluation, 89% (531 of 594) of the responses agreed with the gold standard responses. Following annotated feedback to the examiners about the two items that had a 60% correct rate, the correct response rate rose to 93% (114 of 123). In the second interobserver variability evaluation, 88% (493 of 560) of the responses agreed with the gold standard responses. Following annotated feedback to the examiners about the four items that had a 70% correct rate, the correct response rate rose to 96% (104 of 108). Interactive CD-ROM examination training is an efficient and cost-effective means of training both neurologists and non-neurologists to perform structured neurologic examinations in 1-year-old children. It provides an effective means to evaluate interobserver variability, offers a route for feedback, and creates an opportunity to reevaluate variability, both immediately and at periodic intervals.

Faculty and resident attitudes about spirituality and religion in the provision of pediatric health care.

OBJECTIVE: To characterize pediatricians' attitudes toward spirituality/religion (S/R) in relationship to the practice of pediatrics. METHODS: Pediatric faculty (n = 100) and residents (n = 65) in an urban academic medical center completed a questionnaire about their attitudes toward and clinical practices related to S/R. Study variables included the strength of personal S/R orientation, attitudes toward S/R, clinicians' discussion of S/R with patients and families, self-reported S/R behaviors, the medical conditions that warrant discussion of S/R, and attitudes toward praying with patients if asked to do so. RESULTS: Sixty-five percent of pediatricians felt that faith plays a role in healing, and 76% reported feeling comfortable praying with a patient if asked to do so. Ninety-three percent would ask about S/R when discussing a life-threatening illness, and 96% when discussing death and dying. A strong personal S/R orientation was associated with beliefs that the pediatrician should discuss S/R with the patient (P <.01); beliefs that faith plays a role in healing (P <.01); and feelings that patients would like to discuss S/R with their pediatrician (P <.01), that the doctor-patient relationship would be strengthened by discussion of S/R (P <.01), and that physicians should call on an S/R leader for an illness or death (P <.01). Personal S/R orientation was not related to whether physicians reported that they discuss S/R issues with their patients (P =.08). Residents were more likely than faculty to state that it is appropriate to pray with patients if asked to do so (P <.05), and compared with pediatricians who were science majors in college, pediatricians who were nonscience majors in college felt more comfortable praying with patients if asked to do so (P <.01). CONCLUSIONS: In an urban, inner-city, academic medical center, pediatric residents and faculty have an overall positive attitude toward the integration of S/R into the practice of pediatrics.