Preventive Task Force Guidelines Research Articles

Abstract A20: AHRR hypomethylation in heavy smokers: Associations with lung cancer risk and mortality

Abstract Hypomethylation of cg05575921 in the aryl-hydrocarbon receptor repressor (AHRR) gene is consistently and strongly associated with higher exposure to smoking (e.g., current smoking, greater number of pack years, and less time since quitting). Although cg05575921 hypomethylation has been reported to be associated with lung cancer risk and mortality, this has not been explored within heavy smokers or by histotype. We assessed cg05575921 methylation for associations with smoking behavior, prospective lung cancer risk, and mortality in 313 cases and controls from the Beta Carotene and Retinol Efficacy Trial (CARET) with ≥20 pack years of smoking and matched on age (±5 years), sex, race/ethnicity, enrollment year, smoking status, occupational asbestos exposure, and follow-up time. Methylation of cg05575921 in blood collected on average 4.3 years prior to diagnosis in cases was assayed using the 850K Illumina EPIC array. Quintiles of cg05575921 methylation were defined based on the control distribution, with the lowest quintile (Q1, referent) representing hypermethylation and the highest (Q5), hypomethylation. Among controls, increasing quintiles of cg05575921 hypomethylation were associated with current smoking status (Cochran-Armitage trend p=3.0 × 10-21), and with decreasing years since last smoked, increasing cigarettes per day, and decreasing body mass index (BMI) (ordinal ANOVA p=3.1 × 10-21, 1.3 × 10-17, and 0.002, respectively). We observed similar patterns in cases. We evaluated associations between cg05575921 methylation and lung cancer risk using logistic regression models conditioned on matching factors and adjusted for age, years since quit, and BMI. We evaluated cg05575921 methylation and lung cancer-specific mortality using Cox proportional hazards models adjusted for stage, age, sex, race, smoking status, intervention arm, asbestos exposure, and pack years smoked. We did not observe clear patterns of associations between cg05575921 methylation and lung cancer risk overall or by histotype. However, we found a linear relationship (p=0.03) between increasing cg05575921 hypomethylation and overall lung cancer mortality, with Q5 vs Q1 Hazard Ratio (HR)=1.60 (95% Confidence Interval (95% CI): 1.00-2.57) for mortality from lung cancer overall, and HR=2.09, 95% CI: 0.96-4.54 for adenocarcinoma (N=121). Our findings provide preliminary support that even among heavy smokers, cg05575921 hypomethylation is associated with more recent and extensive exposure to cigarette smoking, and that prediagnosis cg05575921 hypomethylation in lung cancer cases is associated with an increased hazard of death. However, since the CARET population represents a group who would largely qualify for lung cancer screening with annual low-dose computed tomography per the United States Preventive Task Force guidelines, our results do not provide support for the use of cg05575921 hypomethylation as an indicator for screening-based lung cancer risk stratification. Citation Format: Stefan Graw, Matt J. Barnett, Mark D. Thornquist, Gary E. Goodman, Chu Chen, Devin C. Koestler, Carmen J. Marsit, Jennifer A. Doherty, Laurie Grieshober. AHRR hypomethylation in heavy smokers: Associations with lung cancer risk and mortality [abstract]. In: Proceedings of the AACR Special Conference on Modernizing Population Sciences in the Digital Age; 2019 Feb 19-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(9 Suppl):Abstract nr A20.

Use of Colorectal Cancer Screening Among People With Mobility Disability.

We aimed to assess use of colorectal cancer screening (CRCS) as per United States Preventive Task Force guidelines among people with mobility disability using a nationally representative data set. Individuals with mobility disability have decreased access to health care services, but the impact of mobility disability on CRCS has not been investigated. Data from the 2013 National Health Interview Survey were used to estimate sociodemographic characteristics of adults with mobility disability, prevalence of CRCS, and odds of CRCS given mobility disability among Americans aged 50 to 75. In total, 56.8% of the entire sample (n=81,953,585) were up-to-date with CRCS. Mobility disability was not associated with CRCS status on univariable analysis but was significantly associated after adjustment for covariates including age and comorbidities, with an inverse relationship between the degree of mobility disability and odds of CRCS. Odds ratio for CRCS given progressively severe disability were 0.78 (0.66 to 0.93), 0.71 (0.53 to 0.94), 0.65 (0.31 to 1.19). The present study indicates reduced CRCS among people with mobility disability and highlights the need for CRCS to be especially targeted toward this group. Future research should identify the specific systemic, social, and/or physical barriers to CRCS for this subgroup so that they can be addressed.

Amniotic fluid embolism: diagnosis and management

We sought to provide evidence-based guidelines regarding the diagnosis and management of amniotic fluid embolism. A systematic literature review was performed using MEDLINE, PubMed, EMBASE, and the Cochrane Library. The search was restricted to English-language articles published from 1966 through March 2015. Priority was given to articles reporting original research, in particular randomized controlled trials, although review articles and commentaries were consulted. Abstracts of research presented at symposia and scientific conferences were not considered adequate for inclusion. Evidence reports and published guidelines were also reviewed, and additional studies were located by reviewing bibliographies of identified articles. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used for defining the strength of recommendations and rating quality of the evidence. Consistent with US Preventive Task Force guidelines, references were evaluated for quality based on the highest level of evidence. We recommend the following: (1) we recommend consideration of amniotic fluid embolism in the differential diagnosis of sudden cardiorespiratory collapse in the laboring or recently delivered woman (GRADE 1C); (2) we do not recommend the use of any specific diagnostic laboratory test to either confirm or refute the diagnosis of amniotic fluid embolism; at the present time, amniotic fluid embolism remains a clinical diagnosis (GRADE 1C); (3) we recommend the provision of immediate high-quality cardiopulmonary resuscitation with standard basic cardiac life support and advanced cardiac life support protocols in patients who develop cardiac arrest associated with amniotic fluid embolism (GRADE 1C); (4) we recommend that a multidisciplinary team including anesthesia, respiratory therapy, critical care, and maternal-fetal medicine should be involved in the ongoing care of women with AFE (Best Practice); (5) following cardiac arrest with amniotic fluid embolism, we recommend immediate delivery in the presence of a fetus ≥23 weeks of gestation (GRADE 2C); (6) we recommend the provision of adequate oxygenation and ventilation and, when indicated by hemodynamic status, the use of vasopressors and inotropic agents in the initial management of amniotic fluid embolism. Excessive fluid administration should be avoided (GRADE 1C); and (7) because coagulopathy may follow cardiovascular collapse with amniotic fluid embolism, we recommend the early assessment of clotting status and early aggressive management of clinical bleeding with standard massive transfusion protocols (GRADE 1C).

Reach of the Montana Cancer Control Program to Women with Disabilities.

Women with disabilities have lower screening rates for breast and cervical cancer with some evidence suggesting that people with disabilities experience higher cancer mortality and may receive a different course of treatment. This study examined whether women with and without disabilities using Montana Cancer Control Program (MCCP) differ in use of breast (BCS) and cervical (CCS) screening services, receipt of and follow up for inconclusive or abnormal results, and compliance with BCS and CCS US Preventive Services Task Force recommendations. Study participants were women eligible for MCCP screening services between November 2012 and October 2014, with eligibility based on insurance status (underinsured/no insurance), income requirements (<200% poverty based on income/household size), and age. The data derive from participant self-report (demographic, disability, and health history including previous mammogram or Papanicolaou test) and MCCP records of screening tests (clinical breast exam, mammogram, or Pap test), results, and follow up visits. About 11.5% of MCCP participants reported having a disability. MCCP recipients with a disability were significantly older, more likely to be non-Hispanic White, and more likely to have poor health profiles. Disability status did not affect use of MCCP screening services, screening outcome, or follow up for inconclusive or abnormal results. However, women with disability had significantly lower BCS and CCS compliance (based on US Preventive Task Force guidelines) than women without disability, which persisted in adjusted analyses controlling for other significant factors. The MCCP is reaching un/underinsured Montana women with disabilities. While disability status in this sample was not related to use of MCCP services or screening outcome, MCCP recipients with disabilities have significantly lower BCS and CCS compliance. Efforts to increase compliance for un/underinsured Montana women with a disability are warranted.

Society for Maternal-Fetal Medicine (SMFM) Clinical Guideline #8: The fetus at risk for anemia–diagnosis and management

We sought to provide evidence-based guidelines for the diagnosis and management of fetal anemia. A systematic literature review was performed using MEDLINE, PubMed, EMBASE, and the Cochrane Library. The search was restricted to English-language articles published from 1966 through May 2014. Priority was given to articles reporting original research, in particular randomized controlled trials, although review articles and commentaries were consulted. Abstracts of research presented at symposia and scientific conferences were not considered adequate for inclusion. Evidence reports and published guidelines were also reviewed, and additional studies were located by reviewing bibliographies of identified articles. GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology was used for defining the strength of recommendations and rating the quality of evidence. Consistent with US Preventive Task Force guidelines, references were evaluated for quality based on the highest level of evidence. We recommend the following: (1) middle cerebralartery peak systolic velocity (MCA-PSV) measured by ultrasound Doppler interrogation be used as the primary technique to detect fetal anemia; (2) amniotic fluiddelta OD450not be used to diagnosis fetal anemia; (3) MCA-PSV assessment bereserved for those patients who are at risk of having an anemic fetus (proper techniquefor MCA-PSV evaluation includes assessment of the middle cerebral artery close to its origin, ideally at a zero degree angle without angle correction); (4) if a fetus isdeemed at significant risk for severe fetal anemia (MCA greater than 1.5 multiples of the median or hydropic), fetal blood sampling be performed with preparation for an intrauterine transfusion, unless the pregnancy is at a gestational age when the risks associated with delivery are considered to be less than those associated with the procedure; (5) if a fetus is deemed at significant risk for severe fetal anemia, the patient be referred to a center with expertise in invasive fetal therapy; (6) MCA-PSV be considered to determine the timing of a second transfusion in fetuses with anemia, and, alternatively, a predicted decline in fetal hemoglobin may be used for timing thesecond procedure; and (7) pregnancies with a fetus at significant risk for fetal anemia be delivered at 37-38 weeks of gestation unless indications develop prior to this time.

Society for Maternal-Fetal Medicine (SMFM) Clinical Guideline #7: nonimmune hydrops fetalis

Nonimmune hydrops is the presence of ≥2 abnormal fetal fluid collections in the absence of red cell alloimmunization. The most common etiologies include cardiovascular, chromosomal, and hematologic abnormalities, followed by structural fetal anomalies, complications of monochorionic twinning, infection, and placental abnormalities. We sought to provide evidence-based guidelines for the evaluation and management of nonimmune hydrops fetalis. A systematic literature review was performed using MEDLINE, PubMed, EMBASE, and Cochrane Library. The search was restricted to English-language articles published from 1966 through June 2014. Priority was given to articles reporting original research, although review articles and commentaries also were consulted. Abstracts of research presented at symposia and scientific conferences were not considered adequate for inclusion in this document. Evidence reports and guidelines published by organizations or institutions such as the National Institutes of Health, Agency for Health Research and Quality, American Congress of Obstetricians and Gynecologists, and Society for Maternal-Fetal Medicine were also reviewed, and additional studies were located by reviewing bibliographies of identified articles. Grading of Recommendations Assessment, Development, and Evaluation methodology was employed for defining strength of recommendations and rating quality of evidence. Consistent with US Preventive Task Force guidelines, references were evaluated for quality based on the highest level of evidence. Evaluation of hydrops begins with an antibody screen (indirect Coombs test) to determine if it is nonimmune, detailed sonography of the fetus(es) and placenta, including echocardiography and assessment for fetal arrhythmia, and middle cerebral artery Doppler evaluation for anemia, as well as fetal karyotype and/or chromosomal microarray analysis, regardless of whether a structural fetal anomaly is identified. Recommended treatment depends on the underlying etiology and gestational age; preterm delivery is recommended only for obstetric indications including development of mirror syndrome. Candidates for corticosteroids and antepartum surveillance include those with an idiopathic etiology, an etiology amenable to prenatal or postnatal treatment, and those in whom intervention is planned if fetal deterioration occurs. Such pregnancies should be delivered at a facility with the capability to stabilize and treat critically ill newborns. The prognosis depends on etiology, response to therapy if treatable, and the gestational age at detection and delivery. Aneuploidy confers a poor prognosis, and even in the absence of aneuploidy, neonatal survival is often <50%. Mirror syndrome is a form of severe preeclampsia that may develop in association with fetal hydrops and in most cases necessitates delivery.

Fetal blood sampling

We sought to review indications, technical aspects, risks, and recommendations for fetal blood sampling (FBS). A systematic review was performed using MEDLINE, PubMed, EMBASE, and Cochrane Library using the terms "fetal blood sampling," "percutaneous umbilical blood sampling," and "cordocentesis." The search was restricted to English-language articles published from 1966 through July 2012. Priority was given to articles reporting original research, in particular randomized controlled trials, although review articles and commentaries also were consulted. Abstracts of research presented at symposia and scientific conferences were not considered adequate for inclusion in this document. Evidence reports and guidelines published by organizations or institutions such as the National Institutes of Health, Agency for Health Research and Quality, American Congress of Obstetricians and Gynecologists, and Society for Maternal-Fetal Medicine were also reviewed, and additional studies were located by reviewing bibliographies of identified articles. Grade (Grading of Recommendations Assessment, Development, and Evaluation) methodology was employed for defining strength of recommendations and rating quality of evidence. Consistent with US Preventive Task Force guidelines, references were evaluated for quality based on the highest level of evidence. Ultrasound-guided FBS is the only procedure that provides direct access to the fetal circulation. When invasive testing is planned for suspected severe fetal anemia or thrombocytopenia, we recommend FBS as the procedure of choice, with availability of immediate transfusion if confirmed. We recommend against the use of FBS for indications in which other less invasive, and therefore lower risk, alternatives are available. The overall success rate of FBS is high, and blood samples can be obtained in >98% of patients. We suggest that counseling for FBS include discussion about the potential risk of FBS that may include, but may not be limited to: bleeding from puncture site (20-30%); fetal bradycardia (5-10%); pregnancy loss (≥1.3%, depending on indication, gestational age, and placental penetration); and vertical transmission of hepatitis or human immunodeficiency virus. We recommend that FBS be performed by experienced operators at centers with expertise in invasive fetal procedures when feasible.

Twin-twin transfusion syndrome

We sought to review the natural history, pathophysiology, diagnosis, and treatment options for twin-twin transfusion syndrome (TTTS). A systematic review was performed using MEDLINE database, PubMed, EMBASE, and Cochrane Library. The search was restricted to English-language articles published from 1966 through July 2012. Priority was given to articles reporting original research, in particular randomized controlled trials, although review articles and commentaries also were consulted. Abstracts of research presented at symposia and scientific conferences were not considered adequate for inclusion in this document. Evidence reports and guidelines published by organizations or institutions such as the National Institutes of Health, Agency for Health Research and Quality, American College of Obstetricians and Gynecologists, and Society for Maternal-Fetal Medicine were also reviewed, and additional studies were located by reviewing bibliographies of identified articles. Consistent with US Preventive Task Force guidelines, references were evaluated for quality based on the highest level of evidence, and recommendations were graded accordingly. TTTS is a serious condition that can complicate 8-10% of twin pregnancies with monochorionic diamniotic (MCDA) placentation. The diagnosis of TTTS requires 2 criteria: (1) the presence of a MCDA pregnancy; and (2) the presence of oligohydramnios (defined as a maximal vertical pocket of <2 cm) in one sac, and of polyhydramnios (a maximal vertical pocket of >8 cm) in the other sac. The Quintero staging system appears to be a useful tool for describing the severity of TTTS in a standardized fashion. Serial sonographic evaluation should be considered for all twins with MCDA placentation, usually beginning at around 16 weeks and continuing about every 2 weeks until delivery. Screening for congenital heart disease is warranted in all monochorionic twins, in particular those complicated by TTTS. Extensive counseling should be provided to patients with pregnancies complicated by TTTS including natural history of the disease, as well as management options and their risks and benefits. The natural history of stage I TTTS is that more than three-fourths of cases remain stable or regress without invasive intervention, with perinatal survival of about 86%. Therefore, many patients with stage I TTTS may often be managed expectantly. The natural history of advanced (eg, stage ≥III) TTTS is bleak, with a reported perinatal loss rate of 70-100%, particularly when it presents <26 weeks. Fetoscopic laser photocoagulation of placental anastomoses is considered by most experts to be the best available approach for stages II, III, and IV TTTS in continuing pregnancies at <26 weeks, but the metaanalysis data show no significant survival benefit, and the long-term neurologic outcomes in the Eurofetus trial were not different than in nonlaser-treated controls. Even laser-treated TTTS is associated with a perinatal mortality rate of 30-50%, and a 5-20% chance of long-term neurologic handicap. Steroids for fetal maturation should be considered at 24 0/7 to 33 6/7 weeks, particularly in pregnancies complicated by stage ≥III TTTS, and those undergoing invasive interventions.