Effect of Presenting Survival Information as Text or Pictograph During Periviable Birth Counseling: A Randomized, Controlled Trial.

OBJECTIVES: To examine whether presenting a 30% or a 60% chance of survival in different survival information formats would influence hypothetical periviable birth treatment choice and whether treatment choice would be associated with participants' recall or their intuitive beliefs about the chances of survival. STUDY DESIGN: An internet sample of women (n = 1052) were randomized to view a vignette with either a 30% or 60% chance of survival with intensive care during the periviable period. Participants were randomized to survival information presented as text-only, in a static pictograph, or in an iterative pictograph. Participants chose intensive care or palliative care and reported their recall of the chance of survival and their intuitive beliefs about their infant's chance of survival. RESULTS: There was no difference in treatment choice by presentation with a 30% vs 60% chance of survival (P = .48), by survival information format (P = .80), or their interaction (P = .18). However, participants' intuitive beliefs about chance of survival significantly predicted treatment choice (P < .001) and had the most explanatory power of any participant characteristic. Intuitive beliefs were optimistic and did not differ by presentation of a 30% or 60% chance of survival (P = .65), even among those with accurate recall of the chance of survival (P = .09). CONCLUSIONS: Physicians should recognize that parents may use more than outcome data to make treatment choices and in forming their own, often-optimistic, intuitive beliefs about their infant's chance of survival. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04859114.

Information Order for Periviable Counseling: Does It Make a Difference?

OBJECTIVES: To examine whether the order of presenting survival vs disability information, with or without the description of infant neonatal intensive care unit (NICU) experiences would influence treatment choice during hypothetical periviable birth counseling. STUDY DESIGN: An internet sample of childbearing-aged women (n = 839) viewed a pictograph displaying the chances of survival and a pictograph on the chances of disability for a baby resuscitated during the periviable period. The sample was randomized to the order of pictographs and level of description of infant NICU experiences. Participants selected between intensive care or comfort care and reported their personal values. RESULTS: The order of the information influenced treatment choices (P = .02); participants were more likely to choose intensive care if they saw the survival pictograph first (70%) than the disability pictograph first (62%). Level of description of premature infant NICU experiences did not influence treatment choice (P = .92). Participants who valued sanctity of life, autonomy in making decisions, who were more religious, and had adequate health literacy were more likely to choose intensive care. Such participant characteristics had greater explanatory power than the experimental manipulations. CONCLUSIONS: Subtle differences in how information is presented may influence critical decisions. However, even among women with the same values, diversity in treatment choice remains.

Roadmap to recovery: Reporting on a research taskforce supporting Indigenous responses to COVID-19 in Australia.

In April 2020 a Group of Eight Taskforce was convened, consisting of over 100 researchers, to provide independent, research-based recommendations to the Commonwealth Government on a "Roadmap to Recovery" from COVID-19. The report covered issues ranging from pandemic control and relaxation of social distancing measures, to well-being and special considerations for vulnerable populations. Our work focused on the critical needs of Aboriginal and Torres Strait Islander communities; this paper presents an overview of our recommendations to the Roadmap report. In addressing the global challenges posed by pandemics for citizens around the world, Indigenous people are recognised as highly vulnerable. At the time of writing Australia's First Nations Peoples have been largely spared from COVID-19 in comparison to other Indigenous populations globally. Our recommendations emphasise self-determination and equitable needs-based funding to support Indigenous communities to recover from COVID-19, addressing persistent overcrowded housing, and a focus on workforce, especially for regional and remote communities. These latter two issues have been highlighted as major issues of risk for Indigenous communities in Australia It remains to be seen how governments across Australia take up these recommendations to support Indigenous peoples' health and healing journey through yet another, potentially catastrophic, health crisis.

Effect of Fathers in Preemie Prep for Parents (P3) Program on Couple's Preterm Birth Preparedness.

Objective: Evaluate the effect of fathers' participation in the Preemie Prep for Parents (P3) program on maternal learning and fathers' preterm birth knowledge. Methods: Mothers with preterm birth predisposing medical condition(s) enrolled with or without the baby's father and were randomized to the P3 intervention (text-messages linking to animated videos) or control (patient education webpages). Parent Prematurity Knowledge Questionnaire assessed knowledge, including unmarried fathers' legal neonatal decision-making ability. Results: 104 mothers reported living with the baby's father; 50 participated with the father and 54 participated alone. In the P3 group, mothers participating with the father (n=33) had greater knowledge than mothers participating alone (n=21), 85% correct responses vs. 76%, p =0.033. However, there was no difference in knowledge among the control mothers, 67% vs. 60%, p =0.068. P3 fathers (n=33) knowledge scores were not different than control fathers (n=17), 77% vs. 68%, p =0.054. Parents who viewed the video on fathers' rights (n=58) were more likely than those who did not (n=96) to know unmarried fathers' legal inability to decide neonatal treatments, 84% vs. 41%, p <0.001. Conclusions: Among opposite-sex cohabitating couples, fathers' participation in the P3 program enhanced maternal learning. Practice Implications: The P3 program's potential to educate fathers may benefit high-risk pregnancies.

Black Women and the Preemie Prep for Parents (P3) Program: Exploratory Analysis of a Clinical Trial.

Background: The smartphone Preemie Prep for Parents (P3) program was developed to address the gap in prenatal education of preterm birth in high-risk pregnancies. Despite a higher incidence of preterm birth, Black women are less likely to receive prenatal education. Methods: Pregnant women with medical conditions that predisposed them to preterm birth were randomized to receive the P3 program or links to American College of Obstetricians and Gynecologists webpages (control). The P3 group received periodic text messages, starting as early as 18 weeks gestational age, each with a link to a short, animated educational video. Participants completed the Parent Prematurity Knowledge Questionnaire, PROMIS Anxiety scale, and a feedback survey. This is a subgroup analysis of the Black, non-Hispanic participants in the P3 trial. Results: Of the 26 Black non-Hispanic women enrolled, the P3 group (n=14) had higher knowledge scores than the control group (n=12), 67.5% correct vs. 43.6% (difference 24.0; 95% CI, 7.4 to 40.6), without experiencing an increase in anxiety. More P3 participants reported discussing preterm birth with their partner (100%) than control participants (57%; difference 43; 95% CI, 6 to 80). Conclusions: The P3 program appears to be an effective method of providing preterm birth education to Black pregnant women.

Intensive Care Associated Experiences of Extremely Premature Infants Who Die.

Objective: Pain and quality of death are important considerations in treatment choices for children. Our objective is to assess the intensive care-associated experiences of 22-25 weeks gestational age (GA) infants who die despite intensive care treatment. Study Design: In a 1:1 case-control study, medical records were screened for all inborn 22-25 weeks GA infants who received intensive care treatments between 2014 and 2020. Cases were all infants who died. Each case was matched by GA and birth weight to an infant who survived to discharge (control). Data was collected on cases and controls for a matched timeframe based on the case's duration of intensive care treatment. Information collected included intensive care-associated negative experiences (invasive procedures, surgeries, use of pain medication) and positive experiences (enteral feedings, being held by family). Results: The cases (n=20) survived for 0 to 93 days, with median (IQR) survival 8 (5, 24) days. The mean (SD) number of invasive procedures was higher for cases than controls, 34 (30) vs. 24 (22), p=0.004. Cases underwent 8 surgeries compared to 4 in the controls. Additionally, compared to controls, cases spent more time receiving pain medications (64% vs. 27%, p<0.001) and without being fed (54% vs. 39%, p<0.001). Half of cases were never held by parents until the day they died. Conclusion: Extremely premature infants who die despite intensive care face more treatment burdens than the survivors. Larger studies are needed to confirm these findings and gather information necessary for informed decisions about intensive care treatment of these infants.

Smartphone-Based Video Antenatal Preterm Birth Education: The Preemie Prep for Parents Randomized Clinical Trial.

Importance: Preterm birth is a leading cause of infant mortality and child morbidity. Preterm birth is not always unexpected, yet standard prenatal care does not offer anticipatory education to parents at risk of delivering preterm, which leaves parents unprepared to make health care choices during the pregnancy that can improve survival and decrease morbidity in case of preterm birth. Objective: To evaluate the effect of the Preemie Prep for Parents (P3) program on maternal knowledge of preterm birth, preparation for decision-making, and anxiety. Design, Setting, and Participants: Recruitment for this randomized clinical trial conducted at a US academic medical center took place from February 3, 2020, to April 12, 2021. A total of 120 pregnant persons with a risk factor for preterm birth were enrolled between 16 and 21 weeks' gestational age and followed up through pregnancy completion. Intervention: Starting at 18 weeks' gestational age, P3 program participants received links delivered via text message to 51 gestational age-specific short animated videos. Control participants received links to patient education webpages from the American College of Obstetricians and Gynecologists. Main Outcomes and Measures: At 25 weeks' gestation, scores on the Parent Prematurity Knowledge Questionnaire (scored as percent correct), Preparation for Decision Making Scale (scored 0-100), and Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety computerized adaptive test. Analysis was based on an intention to treat. Results: A total of 120 pregnant participants (mean [SD] age, 32.5 [4.9] years) were included in the study; 60 participants were randomized to each group. Participants in the P3 group scored higher than those in the control group on knowledge of long-term outcomes at 25 weeks (88.5% vs 73.2%; estimated difference, 15.3 percentage points; 95% CI, 8.3-22.5 percentage points; P < .001). Participants in the P3 group reported being significantly more prepared than did participants in the control group for neonatal resuscitation decision-making at 25 weeks (Preparation for Decision Making Scale score, 76.0 vs 52.3; difference, 23.7; 95% CI, 14.1-33.2). There was no difference between the P3 group and the control group in anxiety at 25 weeks (mean [SE] PROMIS Anxiety scores, 53.8 [1.1] vs 54.0 [1.1]; difference, -0.1; 95% CI, -3.2 to 2.9). Conclusions and Relevance: In this randomized clinical trial, pregnant persons randomly assigned to the P3 program had more knowledge of core competencies and were more prepared to make decisions that affect maternal and infant health, without experiencing worse anxiety. Mobile antenatal preterm birth education may provide a unique benefit to parents with preterm birth risk factors. Trial Registration: ClinicalTrials.gov Identifier: NCT04093492.

Interpersonal variability of the human gut virome confounds disease signal detection in IBD.

Viruses are increasingly recognised as important components of the human microbiome, fulfilling numerous ecological roles including bacterial predation, immune stimulation, genetic diversification, horizontal gene transfer, microbial interactions, and augmentation of metabolic functions. However, our current view of the human gut virome is tainted by previous sequencing requirements that necessitated the amplification of starting nucleic acids. In this study, we performed an original longitudinal analysis of 40 healthy control, 19 Crohn's disease, and 20 ulcerative colitis viromes over three time points without an amplification bias, which revealed and highlighted the interpersonal individuality of the human gut virome. In contrast to a 16 S rRNA gene analysis of matched samples, we show that α- and ß-diversity metrics of unamplified viromes are not as efficient at discerning controls from patients with inflammatory bowel disease. Additionally, we explored the intrinsic properties of unamplified gut viromes and show there is considerable interpersonal variability in viral taxa, infrequent longitudinal persistence of intrapersonal viruses, and vast fluctuations in the abundance of temporal viruses. Together, these properties of unamplified faecal viromes confound the ability to discern disease associations but significantly advance toward an unbiased and accurate representation of the human gut virome.

Combined modality therapy for rectal cancer: the relative value of posttreatment versus pretreatment CEA as a prognostic marker for disease recurrence.

PURPOSE: To evaluate the prognostic significance of the first postsurgery carcinoembryonic antigen (CEA) level in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiation (nCRT) and total mesorectal excision. METHODS: A total of 100 patients underwent nCRT and had baseline and posttreatment CEA levels recorded within 6 months of surgery. The median radiotherapy dose was 50.4 Gy. Eighty-six patients received adjuvant 5-fluorouracil-based chemotherapy. Prognostic factors were analyzed for possible associations with freedom from failure (FFF) by univariate and multivariate analyses. Median follow-up was 30 months. RESULTS: The median CEA (ng/ml) levels at baseline before nCRT, after nCRT, and after total mesorectal excision were 3.6, 1.7, and 1.3, respectively. Pathologic complete response was observed in 22%. FFF at 36 months was 78%. Local failure and distant failure occurred in 4 and 20% of the patients, respectively. On univariate analysis, pathologic complete response, margin status, and both pretreatment and postsurgery CEA levels were associated with recurrence (all P < 0.05). On multivariate analysis, pathologic complete response (P < 0.007), margin status (P < 0.001), and postsurgery CEA level (P = 0.003), but not baseline CEA level (P = 0.2), were found to be associated with recurrence. CONCLUSIONS: After nCRT for rectal cancer, postsurgery CEA level may have more prognostic value than pretreatment level. Patients with a postsurgery CEA level of >2.5 ng/ml have higher rates of recurrence and may warrant closer surveillance.

Effective questionnaire design: How to use cognitive interviews to refine questionnaire items.

BACKGROUND: Cognitive interviewing is a technique that can be used to improve and refine questionnaire items. We describe the basic methodology of cognitive interviewing and illustrate its utility through our experience using cognitive interviews to refine a questionnaire assessing parental understanding of concepts related to preterm birth. METHODS: Cognitive interviews were conducted using current best practices. Results were analyzed by the multidisciplinary research team and questionnaire items that were revealed to be problematic were revised. RESULTS: Revisions to the questionnaire items were made to improve clarity and to elicit responses that truly reflected the participants understanding of the concept. CONCLUSION: Cognitive interviewing is a useful methodology for improving validity of questionnaire items, we recommend researchers developing new questionnaire items design and complete cognitive interviews to improve their items and increase confidence in study conclusions.

The Human Gut Virome Is Highly Diverse, Stable, and Individual Specific.

The human gut contains a vast array of viruses, mostly bacteriophages. The majority remain uncharacterized, and their roles in shaping the gut microbiome and in impacting on human health remain poorly understood. We performed longitudinal metagenomic analysis of fecal viruses in healthy adults that reveal high temporal stability, individual specificity, and correlation with the bacterial microbiome. Using a database-independent approach that uses most of the sequencing data, we uncovered the existence of a stable, numerically predominant individual-specific persistent personal virome. Clustering of viral genomes and de novo taxonomic annotation identified several groups of crAss-like and Microviridae bacteriophages as the most stable colonizers of the human gut. CRISPR-based host prediction highlighted connections between these stable viral communities and highly predominant gut bacterial taxa such as Bacteroides, Prevotella, and Faecalibacterium. This study provides insights into the structure of the human gut virome and serves as an important baseline for hypothesis-driven research.

Video Education in Early Pregnancy and Parent Knowledge of Neonatal Resuscitation Options: A Secondary Analysis of a Randomized Clinical Trial.

This secondary analysis of a randomized clinical trial investigates the proportion of correct answers on neonatal resuscitation options among parents after seeing a video on these options.

Reproducible protocols for metagenomic analysis of human faecal phageomes.

BACKGROUND: Recent studies have demonstrated that the human gut is populated by complex, highly individual and stable communities of viruses, the majority of which are bacteriophages. While disease-specific alterations in the gut phageome have been observed in IBD, AIDS and acute malnutrition, the human gut phageome remains poorly characterised. One important obstacle in metagenomic studies of the human gut phageome is a high level of discrepancy between results obtained by different research groups. This is often due to the use of different protocols for enriching virus-like particles, nucleic acid purification and sequencing. The goal of the present study is to develop a relatively simple, reproducible and cost-efficient protocol for the extraction of viral nucleic acids from human faecal samples, suitable for high-throughput studies. We also analyse the effect of certain potential confounding factors, such as storage conditions, repeated freeze-thaw cycles, and operator bias on the resultant phageome profile. Additionally, spiking of faecal samples with an exogenous phage standard was employed to quantitatively analyse phageomes following metagenomic sequencing. Comparative analysis of phageome profiles to bacteriome profiles was also performed following 16S rRNA amplicon sequencing. RESULTS: Faecal phageome profiles exhibit an overall greater individual specificity when compared to bacteriome profiles. The phageome and bacteriome both exhibited moderate change when stored at + 4 °C or room temperature. Phageome profiles were less impacted by multiple freeze-thaw cycles than bacteriome profiles, but there was a greater chance for operator effect in phageome processing. The successful spiking of faecal samples with exogenous bacteriophage demonstrated large variations in the total viral load between individual samples. CONCLUSIONS: The faecal phageome sequencing protocol developed in this study provides a valuable additional view of the human gut microbiota that is complementary to 16S amplicon sequencing and/or metagenomic sequencing of total faecal DNA. The protocol was optimised for several confounding factors that are encountered while processing faecal samples, to reduce discrepancies observed within and between research groups studying the human gut phageome. Rapid storage, limited freeze-thaw cycling and spiking of faecal samples with an exogenous phage standard are recommended for optimum results.