Recent Publications by CFE Educators

STUDY QUESTIONS

The primary objective of this study is to determine what parental factors or specific ART may influence the risk for adverse cardiometabolic outcomes among children so conceived and their parents. The secondary objective of this study is to prospectively examine the effects of infertility or ART on the intrauterine environment, obstetric and neonatal outcomes.

WHAT IS KNOWN ALREADY

Pregnancies conceived with ART are at an increased risk of being affected by adverse obstetric and neonatal outcomes when compared to spontaneously conceived (SC) pregnancies among fertile women. Small cohort studies have suggested ART-conceived children may have a higher risk of long-term cardiometabolic disturbances as well. Currently, few studies have compared long-term cardiometabolic outcomes among ART-conceived children and non-IVF treated (NIFT) children, to children conceived spontaneously to parents with infertility (subfertile parents).

STUDY DESIGN SIZE DURATION

The Developmental Epidemiological Study of Children born through Reproductive Technologies (DESCRT) is a prospective cohort study that aims to: establish a biobank and epidemiological cohort of children born to subfertile or infertile parents who either conceived spontaneously (without assistance) or used reproductive technologies to conceive (all offspring were from couples assessed and/or treated in the same institute); prospectively examine the effects of infertility or ART on the intrauterine environment, obstetric and neonatal outcomes; and determine what parental factors or ART may influence the cardiometabolic risk of children so conceived. Pregnancies and resultant children will be compared by mode of conception, namely offspring that were conceived without medical assistance or SC or following NIFT, IVF with fresh embryo transfer or frozen embryo transfer (FET), and by fertilization method (conventional versus ICSI). DESCRT has a Child group evaluating long-term outcomes of children as well as a Pregnancy group that will compare obstetric and neonatal outcomes of children conceived since the commencement of the study. Recruitment started in May of 2017 and is ongoing. When the study began, we estimated that ∼4000 children would be eligible for enrollment.

PARTICIPANTS/MATERIALS SETTING METHODS

Eligible participants are first-trimester pregnancies (Pregnancy group) or children (Child group) born to parents who were evaluated at an infertility center in the University of California, San Francisco, CA, USA who were SC or conceived after reproductive treatments (NIFT, IVF ± ICSI, FET). Children in the Child group were conceived at UCSF and born from 2001 onwards. In the Pregnancy group, enrollment began in November of 2017.The primary outcome is the cardiometabolic health of offspring in the Child group, as measured by blood pressure and laboratory data (homeostatic model assessment for insulin resistance (HOMA-IR), oral glucose disposition). There are several secondary outcome measures, including: outcomes from parental survey response (assessing parent/child medical history since delivery-incidence of cardiometabolic adverse events), anthropomorphic measurements (BMI, waist circumference, skinfold thickness), and laboratory data (liver enzymes, lipid panel, metabolomic profiles). In the Pregnancy group, outcomes include laboratory assessments (bhCG, maternal serum analytes, soluble fms-like tyrosine kinase-1 (sFLT-1), and placental growth factor (PlGF)) and placental assessments (placental volume in the second and third trimester and placental weight at delivery). Importantly, aliquots of blood and urine are stored from parents and offspring as part of a biobank. The DESCRT cohort is unique in two ways. First, there is an extensive amount of clinical and laboratory treatment data: parental medical history and physical examination at the time of treatment, along with ovarian reserve and infertility diagnosis; and treatment specifics: for example, fertilization method, culture O status, embryo quality linked to each participant. These reproductive data will aid in identifying explanatory variables that may influence the primary cardiometabolic outcomes of the offspring-and their parents. Second, the DESCRT control group includes pregnancies and children SC from parents with subfertility, which may help to assess when infertility, as opposed to reproductive treatments, may be affecting offspring cardiometabolic health.

STUDY FUNDING/COMPETING INTERESTS

This study is funded by the National Institutes of Health NICHD (1R01HD084380-01A1). A.J.A. is a shareholder in Carrot and consultant for Flo Health. The other authors have no conflicts of interest.

TRIAL REGISTRATION NUMBER

NCT03799107.

TRIAL REGISTRATION DATE

10 January 2019.

DATE OF FIRST PATIENT’S ENROLLMENT

10 May 2017.

BACKGROUND

Coccidioidal meningitis (CM) is the most severe form of disseminated coccidioidomycosis. Despite years of clinical experience, it remains a difficult condition to treat, often requiring surgical procedures, such as placement of a ventriculoperitoneal shunt, in addition to lifelong antifungal therapy.

METHODS

We performed a retrospective analysis of patients with CM seen in a large referral center in Central Valley, California, from 2010 to 2020. Data pertinent to CM were collected and analyzed.

RESULTS

Among 133 patients with CM identified in the 10-year period, nonadherence to antifungal therapy was noted in 43% of patients. Of the 80 patients who underwent ventriculoperitoneal shunt placement for management of intracranial pressure, shunt failure requiring revision surgery occurred in 42 (52.5%). Rehospitalizations due to CM-related reasons occurred in 78 of 133 patients (59%). Twenty-three percent of patients (n = 29) died due to complications from CM, on an average 22 months after the diagnosis of CM. Encephalopathy at presentation was associated with a significantly higher risk of death.

CONCLUSIONS

Patients with CM in central California are predominantly rural agricultural workers with elevated levels of poverty and low health literacy and many barriers to care, leading to high rates of medication nonadherence and loss to follow-up outpatient care. Management challenges are frequent, such as failure of antifungal therapy, high rates of rehospitalization, and the need for repeated shunt revision surgeries. In addition to the development of curative new antifungal agents, understanding the barriers to patient adherence to care and antifungal therapy and identifying means to overcome such barriers are of paramount importance.

IMPORTANCE

Involvement of palliative care specialists in the care of medical oncology patients has been repeatedly observed to improve patient-reported outcomes, but there is no analogous research in surgical oncology populations.

OBJECTIVE

To determine whether surgeon-palliative care team comanagement, compared with surgeon team alone management, improves patient-reported perioperative outcomes among patients pursuing curative-intent surgery for high morbidity and mortality upper gastrointestinal (GI) cancers.

DESIGN, SETTING, AND PARTICIPANTS

From October 20, 2018, to March 31, 2022, a patient-randomized clinical trial was conducted with patients and clinicians nonblinded but the analysis team blinded to allocation. The trial was conducted in 5 geographically diverse academic medical centers in the US. Individuals pursuing curative-intent surgery for an upper GI cancer who had received no previous specialist palliative care were eligible. Surgeons were encouraged to offer participation to all eligible patients.

INTERVENTION

Surgeon-palliative care comanagement patients met with palliative care either in person or via telephone before surgery, 1 week after surgery, and 1, 2, and 3 months after surgery. For patients in the surgeon-alone group, surgeons were encouraged to follow National Comprehensive Cancer Network-recommended triggers for palliative care consultation.

MAIN OUTCOMES AND MEASURES

The primary outcome of the trial was patient-reported health-related quality of life at 3 months following the operation. Secondary outcomes were patient-reported mental and physical distress. Intention-to-treat analysis was performed.

RESULTS

In total, 359 patients (175 [48.7%] men; mean [SD] age, 64.6 [10.7] years) were randomized to surgeon-alone (n = 177) or surgeon-palliative care comanagement (n = 182), with most patients (206 [57.4%]) undergoing pancreatic cancer surgery. No adverse events were associated with the intervention, and 11% of patients in the surgeon-alone and 90% in the surgeon-palliative care comanagement groups received palliative care consultation. There was no significant difference between study arms in outcomes at 3 months following the operation in patient-reported health-related quality of life (mean [SD], 138.54 [28.28] vs 136.90 [28.96]; P = .62), mental health (mean [SD], -0.07 [0.87] vs -0.07 [0.84]; P = .98), or overall number of deaths (6 [3.7%] vs 7 [4.1%]; P > .99).

CONCLUSIONS AND RELEVANCE

To date, this is the first multisite randomized clinical trial to evaluate perioperative palliative care and the earliest integration of palliative care into cancer care. Unlike in medical oncology practice, the data from this trial do not suggest palliative care-associated improvements in patient-reported outcomes among patients pursuing curative-intent surgeries for upper GI cancers.

TRIAL REGISTRATION

ClinicalTrials.gov Identifier: NCT03611309.