Where there is no genetic counselor: An online decision-aid supports the majority of parents' diagnostic genomic testing choices for their children.

PURPOSE: We evaluated DECIDE, an online pre-test decision-support tool for diagnostic genomic testing, in non-genetics specialty clinics where there are no genetic counselors (GCs). METHODS: Families of children offered genomic testing were eligible to participate. Fifty-six parents/guardians completed DECIDE at home, at their convenience. DECIDE includes an integrated knowledge quiz and decisional conflict screen. Six months later, parents were offered follow-up questionnaires and interviews about their experiences. RESULTS: Forty parents (71%) had sufficient knowledge and no decisional conflict surrounding their testing decision but six of this group had residual questions. These six, plus 16 with decisional conflict or insufficient knowledge, saw a genetic counselor. At follow-up, little-to-no decisional regret and few negative emotions were identified in any parents. Most chose testing and described their decision as easy, yet stressful, and described many motivations for sequencing. Parents appreciated the simple comprehensive information DECIDE provided and the ability to view it in a low stress environment. CONCLUSION: DECIDE provides adequate decision-support to enable most parents to make value-consistent choices about genetic testing for their child. Parents reported that DECIDE helped to clarify motivations for pursuing (or declining) testing. DECIDE is a timely, well tested, and accessible tool in clinical settings without GCs.

Real-world diagnostic outcomes and cost-effectiveness of genome-wide sequencing for developmental and seizure disorders: Evidence from Canada.

PURPOSE: To determine real-world diagnostic rates, cost trajectories, and cost-effectiveness of exome sequencing (ES) and genome sequencing (GS) for children with developmental and/or seizure disorders in British Columbia, Canada. METHODS: Based on medical records review, we estimated real-world costs and outcomes for 491 patients who underwent standard of care (SOC) diagnostic testing at British Columbia Children's Hospital. Results informed a state-transition Markov model examining cost-effectiveness of 3 competing diagnostic strategies: (1) SOC with last-tier access to ES, (2) streamlined ES access, and (3) first-tier GS. RESULTS: Through SOC, 49.4% (95% CI: 40.6, 58.2) of patients were diagnosed at an average cost of C$11,683 per patient (95% CI: 9200, 14,166). Compared with SOC, earlier ES or GS access yielded similar or improved diagnostic rates and shorter times to genetic diagnosis, with 94% of simulations demonstrating cost savings for streamlined ES and 60% for first-tier GS. Net benefit from the perspective of the health care system was C$2956 (95% CI: -608, 6519) for streamlined ES compared with SOC. CONCLUSION: Using real-world data, we found earlier access to ES may yield more rapid genetic diagnosis of childhood developmental and seizure disorders and cost savings compared with current practice in a Canadian health care system.

Genetic counselling considerations with genetic/genomic testing in Neonatal and Pediatric Intensive Care Units: A scoping review.

Genetic and genomic technologies can effectively diagnose numerous genetic disorders. Patients benefit when genetic counselling accompanies genetic testing and international guidelines recommend pre- and post-test genetic counselling with genome-wide sequencing. However, there is a gap in knowledge regarding the unique genetic counselling considerations with different types of genetic testing in the Neonatal Intensive Care Unit (NICU) and the Pediatric Intensive Care Unit (PICU). This scoping review was conducted to identify the gaps in care with respect to genetic counselling for infants/pediatric patients undergoing genetic and genomic testing in NICUs and PICUs and understand areas in need of improvement in order to optimize clinical care for patients, caregivers, and healthcare providers. Five databases (MEDLINE [Ovid], Embase [Ovid], PsycINFO [Ebsco], CENTRAL [Ovid], and CINHAL [Ebsco]) and grey literature were searched. A total of 170 studies were included and used for data extraction and analysis. This scoping review includes descriptive analysis, followed by a narrative account of the extracted data. Results were divided into three groups: pre-test, post-test, and comprehensive (both pre- and post-test) genetic counselling considerations based on indication for testing. More studies were conducted in the NICU than the PICU. Comprehensive genetic counselling was discussed in only 31% of all the included studies demonstrating the need for both pre-test and post-test genetic counselling for different clinical indications in addition to the need to account for different cultural aspects based on ethnicity and geographic factors.

Severe morbidity and hospital-based mortality from Rift Valley fever disease between November 2017 and March 2020 among humans in Uganda.

BACKGROUND: Rift Valley fever (RVF) is a zoonotic viral disease of increasing intensity among humans in Africa and the Arabian Peninsula. In Uganda, cases reported prior to 2016 were mild or not fully documented. We report in this paper on the severe morbidity and hospital-based mortality of human cases in Uganda. METHODS: Between November 2017 and March 2020 human cases reported to the Uganda Virus Research Institute (UVRI) were confirmed by polymerase chain reaction (PCR). Ethical and regulatory approvals were obtained to enrol survivors into a one-year follow-up study. Data were collected on socio-demographics, medical history, laboratory tests, potential risk factors, and analysed using Stata software. RESULTS: Overall, 40 cases were confirmed with acute RVF during this period. Cases were not geographically clustered and nearly all were male (39/40; 98%), median age 32 (range 11-63). The median definitive diagnosis time was 7 days and a delay of three days between presumptive and definitive diagnosis. Most patients (31/40; 78%) presented with fever and bleeding at case detection. Twenty-eight (70%) cases were hospitalised, out of whom 18 (64%) died. Mortality was highest among admissions in regional referral (11/16; 69%) and district (4/5; 80%) hospitals, hospitalized patients with bleeding at case detection (17/27; 63%), and patients older than 44 years (9/9; 100%). Survivors mostly manifested a mild gastro-intestinal syndrome with nausea (83%), anorexia (75%), vomiting (75%), abdominal pain (50%), and diarrhoea (42%), and prolonged symptoms of severe disease including jaundice (67%), visual difficulties (67%), epistaxis (50%), haemoptysis (42%), and dysentery (25%). Symptom duration varied between two to 120 days. CONCLUSION: RVF is associated with high hospital-based mortality, severe and prolonged morbidity among humans that present to the health care system and are confirmed by PCR. One-health composite interventions should be developed to improve environmental and livestock surveillance, prevent infections, promptly detect outbreaks, and improve patient outcomes.

Comparison of Tobacco Product Prices at Fort Liberty Army Installation and Surrounding Community Areas, 2021.

INTRODUCTION: High rates of tobacco use persist in the U.S. military, with 18.4% of service members smoking cigarettes in 2018. The Department of Defense's (DoD) 2017 policy required that tobacco retailers on military installations set tobacco product prices equal to the most common community price, including tax, but there is limited evidence confirming whether local retailers are adhering to this policy. We examined tobacco product pricing in tobacco retailers on- and off-post at the largest U.S. Army installation, Fort Liberty, and Cumberland County, North Carolina. METHODS: Between June-August 2021, we collected data on tobacco product availability, price, and promotions from retailers on Fort Liberty (n=14) and a random sample of off-post retailers within 10-miles of installation gates (n=52). We calculated the mode, mean, and median price of each product, plus the difference in these prices at on- and off-post retailers. We used Welch's t-test to test differences in mean prices between on- vs. off-post retailers. RESULTS: The mode, mean, and median prices of cigarette packs and cartons were lower on-post than off-post (e.g., $0.51-$0.55 cheaper for Marlboro cigarette packs on-post). However, the mode, mean, and median prices of smokeless tobacco products and little cigars were higher on-post than off-post (e.g., $0.82-$0.89 more costly for Swisher Sweets 2-packs on-post). CONCLUSION: Results highlight the need for continued enforcement to ensure compliance with the 2017 DoD policy. Comprehensive policy action to reduce tobacco price disparities on- and off-post is critical to reducing high rates of tobacco use among service members. IMPLICATIONS: Despite the implementation of the 2017 DoD pricing policy, some tobacco products remain cheaper at tobacco retailers on-post compared to off-post retailers. Our results highlight the need for greater routine surveillance to increase implementation of the policy-particularly for cigarettes-to reduce high rates of tobacco use among service members.

Genetic counselors outside of the genetics clinic: Roles, practices, and ethico-legal implications in light of lagging legal recognition across Canada.

Advances in medical genetics have led to a significant increase in demand for genetic services and expertise across almost all medical specialties. Genetic counselors (GCs) in Canada play key roles in genetic services both within and outside of the Genetics Clinic, while not being regulated or legally recognized as healthcare professionals (HCPs) in most provinces. Understanding whether GCs outside of the "traditional" Genetics Clinic influence patient care, their level of professional autonomy and supervisory structure is, therefore, important. In this study, we explore the current landscape of GC practice outside of the Genetics Clinic by describing positions, determining the professional scope of practice, as defined by the Canadian Association of Genetic Counselors (CAGC) and Canadian Board of Genetic Counseling (CBGC) core competencies, and by elucidating associated ethico-legal implications. An online survey was developed and distributed to GCs working with patient-related data in Canada in positions outside of the Genetics Clinic through the CAGC ListServ and accessed between March 5 and April 9, 2021. Thirty GCs were included in the study, with 16/30 in public healthcare system positions. Most respondents held roles with direct (11/30) and indirect (14/30) impact on patient care and management, and the majority reported performing their primary roles with minimal supervision (56%) or complete independence (36%). Most roles (22/25) elicited by respondents were considered to be within the GC scope of practice, except for administrative tasks and special projects. GCs were the only genetics-trained professional(s) in 8/30 of respondents' workplaces. The results of the current study support the value of GCs translatable skillset in positions beyond the Genetics Clinic, and outline ethico-legal implications for GCs, regulated HCPs, patients, and health institutions in the absence of legal recognition, including medical-legal liability and title protection. This study provides evidence in support of regulation of GCs as HCPs.

Exploring Canadian genetic counselors' perspectives and experiences with discussing medical assistance in dying (MAiD).

Medical assistance in dying (MAiD) is the Canadian equivalent of Physician aid-in-dying (PAD) in the United States. Through changes to the eligibility criteria for MAiD in 2021, Canada now has one of the most permissive assisted dying regimens in the world. This study describes Canadian genetic counselors' experiences, knowledge, and preparedness to discuss MAiD with their patients. Survey responses were collected from Canadian genetic counselors (n = 44) and were followed by semi-structured interviews with 14 survey participants. Survey data were analyzed using descriptive statistics, and interview transcripts were analyzed using phronetic iterative analysis and an interpretive description approach. Survey data revealed that genetic counselors have discussed MAiD with patients referred for cancer, neurologic, metabolic, connective tissue, and cardiac indications (n = 18, 40.9%). While most thought that it was important for genetic counselors to be knowledgeable of (n = 41, 93.2%) and prepared to discuss MAiD (n = 43, 97.7%), many were not familiar with the eligibility criteria (n = 27, 61.4%) and the process for accessing MAiD in Canada (n = 29, 65.9%). Interview participants described discussions about MAiD that were initiated by themselves or their patients. Most participants felt prepared to explore a patient's thoughts about MAiD when the patient initiated the discussion but did not feel well-prepared to share detailed information about MAiD. Participants were interested in education and professional guidance to assist them in preparing to discuss MAiD. Learning objectives were developed based on participants' suggestions to assist genetic counselors in their clinical work and self-directed research and to aid in the development of professional guidelines and educational materials for practicing genetic counselors and genetic counseling trainees. As genetic counselors continue engaging in discussions about MAiD, it is critical that these sensitive conversations are approached with increased knowledge and awareness of MAiD legislation, the ethical issues surrounding MAiD in Canada, and relevant patient resources.

Adolescents' implicit and explicit attitudes toward their peers with genetic conditions.

INTRODUCTION: Previous research has demonstrated that children lacking knowledge about genetic disorders may have harmful attitudes toward people with disabilities, but disability awareness can successfully modify these attitudes. We explored adolescents' implicit and explicit attitudes toward peers with genetic conditions to determine whether improved genetics/genomics literacy can mitigate the impact of ableism in this population. METHODS: English-speaking adolescents (10-18 years) from British Columbia were invited to complete a Disability Attitudes Implicit Association Test (DA-IAT) and participate in a semi-structured focus group centering on a fictionalized vignette about an adolescent with Down syndrome. We used pragmatism as an analytical paradigm. Descriptive and inferential statistics were used to analyze DA-IAT and sociodemographic data; phronetic iterative analysis with constant comparison as a coding strategy for transcripts; and interpretive description to develop a conceptual model. RESULTS: Twenty-two adolescents completed the DA-IAT and participated in one of four focus groups. Participants had a statistically significant implicit preference for non-disabled people (D-score = 0.72, SD = 0.44; t = 7.18, p < .00001). They demonstrated greater diversity in their explicit attitudes during the focus groups. Although participants articulated a positive attitude toward improved genetics education, results demonstrate their belief that social and personal interactions with disabled peers would be essential to address negative perceptions. CONCLUSIONS: This study lays important groundwork to understand, explain, and influence the negative attitudes of adolescents toward individuals with disabilities. Findings will be used to inform the design of interventions that address biased perceptions of people with genetic disorders, with the goal of reducing prejudices and improving social interactions.

Evaluation of out-of-pocket pay genetic testing in a publicly funded healthcare system.

When genetic tests are not funded publicly, out-of-pocket (OOP) pay options may be discussed with patients. We evaluated trends in genetic testing and OOP pay for two publicly funded British Columbia clinical programs serving >12 000 patients/year (The Hereditary Cancer Program [HCP] and Provincial Medical Genetics Program [PMGP]) between 2015-2019. Linear and regression models were used to explore the association of OOP pay with patient demographic variables at HCP. An interrupted time series and linear and logistic regression models were used on PMGP data to examine the effect of a change in the funding body. The total number of tests completed through PMGP, and HCP increased by 260% and 320%, respectively. OOP pay increased at HCP by 730%. The mean annual income of patients who paid OOP at HCP was ≥$3500 higher than in the group with funded testing (p < 0.0001). The likelihood of OOP pay increased at PMGP before the funding body change (OR per month: 1.07; 95% CI: 1.04, 1.10); while this likelihood had an immediate 87% drop when the change occurred (OR: 0.13; 95% CI: 0.06, 0.32). Patients with higher incomes are more likely to pay OOP. Financial barriers can create disparities in clinical outcomes. Funding decisions have a significant impact on rate of OOP pay.

A Rapid Review on the Value of Biobanks Containing Genetic Information.

OBJECTIVES: Increasing access to health data through biobanks containing genetic information has the potential to expand the knowledge base and thereby improve screening, diagnosis, and treatment options for many diseases. Nevertheless, although privacy concerns and risks surrounding genetic data sharing are well documented, direct evidence in favor of the hypothesized benefits of data integration is scarce, which complicates decision making in this area. Therefore, the objective of this study is to summarize the available evidence on the research and clinical impacts of biobanks containing genetic information, so as to better understand how to quantify the value of expanding genomic data access. METHODS: Using a rapid review methodology, we performed a search of MEDLINE/PubMed and Embase databases; and websites of biobanks and genomic initiatives published from 2010 to 2022. We classified findings into 11 indicators including outputs (a direct product of the biobank activities) and outcomes (changes in scientific and clinical capacity). RESULTS: Of 8479 abstracts and 101 gray literature sources were reviewed, 96 records were included. Although most records did not report key indicators systematically, the available evidence concentrated on research indicators such as publications and gene-disorder association discoveries (63% of studies), followed by research infrastructure (26%), and clinical indicators (11%) such as supporting the diagnosis of individual patients. CONCLUSIONS: Existing evidence on the benefits of biobanks is skewed toward easily quantifiable research outputs. Measuring a comprehensive set of outputs and outcomes inspired by value frameworks is necessary to generate better evidence on the benefits of genomic data sharing.

Unravelling patient pathways in the context of antibacterial resistance in East Africa.

BACKGROUND: A key factor driving the development and maintenance of antibacterial resistance (ABR) is individuals' use of antibiotics (ABs) to treat illness. To better understand motivations and context for antibiotic use we use the concept of a patient treatment-seeking pathway: a treatment journey encompassing where patients go when they are unwell, what motivates their choices, and how they obtain antibiotics. This paper investigates patterns and determinants of patient treatment-seeking pathways, and how they intersect with AB use in East Africa, a region where ABR-attributable deaths are exceptionally high. METHODS: The Holistic Approach to Unravelling Antibacterial Resistance (HATUA) Consortium collected quantitative data from 6,827 adult outpatients presenting with urinary tract infection (UTI) symptoms in Kenya, Tanzania, and Uganda between February 2019- September 2020, and conducted qualitative in-depth patient interviews with a subset (n = 116). We described patterns of treatment-seeking visually using Sankey plots and explored explanations and motivations using mixed-methods. Using Bayesian hierarchical regression modelling, we investigated the associations between socio-demographic, economic, healthcare, and attitudinal factors and three factors related to ABR: self-treatment as a first step, having a multi-step treatment pathway, and consuming ABs. RESULTS: Although most patients (86%) sought help from medical facilities in the first instance, many (56%) described multi-step, repetitive treatment-seeking pathways, which further increased the likelihood of consuming ABs. Higher socio-economic status patients were more likely to consume ABs and have multi-step pathways. Reasons for choosing providers (e.g., cost, location, time) were conditioned by wider structural factors such as hybrid healthcare systems and AB availability. CONCLUSION: There is likely to be a reinforcing cycle between complex, repetitive treatment pathways, AB consumption and ABR. A focus on individual antibiotic use as the key intervention point in this cycle ignores the contextual challenges patients face when treatment seeking, which include inadequate access to diagnostics, perceived inefficient public healthcare and ease of purchasing antibiotics without prescription. Pluralistic healthcare landscapes may promote more complex treatment seeking and therefore inappropriate AB use. We recommend further attention to healthcare system factors, focussing on medical facilities (e.g., accessible diagnostics, patient-doctor interactions, information flows), and community AB access points (e.g., drug sellers).

Considerations for the use of qualitative methodologies in genetic counseling research.

An abundance of qualitative research is being conducted within the genetic counseling field. As this area of research expands, many within our community are "learning through doing", an approach which is practical, but may lack theoretical grounding. This can result in study outputs that do not have the sort of utility for informing clinical practice that is the hallmark of excellent clinical qualitative research. Furthermore, our alignment as a discipline within the health sciences, which still tends to favor quantitative approaches, means that we may often be obliged to justify the use of qualitative methodologies, especially when we intend to use the findings for informing clinical practice. We aim to address these issues by providing guidance about how we, individually and collectively, might think about what excellent qualitative research can look like in our field. In addition to providing information and resources about current best-practices, we discuss how quality can be ensured and evaluated. We seek to legitimize the idea of developing a philosophy of research in pursuit of establishing genetic counseling as an academic discipline. We argue that the principles, ethics, values, and practices of genetic counseling are sufficiently unique that establishing a discipline-specific qualitative research framework is not only warranted, but essential. Ultimately, we hope that this paper can serve as a launching point from which additional discussion about qualitative research can emanate as we strive towards the elevation of this form of inquiry in our field.

Genetic counselors' research dissemination practices and attitudes.

Benefits have been demonstrated to disseminating aggregate research results to all relevant audiences, including study participants. Despite this, many health researchers face barriers in dissemination to broad audiences and returning aggregate results to participants is not commonly practiced. Due to their research presence and training in communication, genetic counselors can lead in implementing best practices in this area. We explored genetic counselors' current practices and opinions regarding educating study participants and wider audiences of research findings. We distributed a survey of 32 multiple-choice and open-ended questions to National Society of Genetics Counselors (NSGC) and Canadian Association of Genetic Counsellors (CAGC) members. Most respondents (90.1%, n = 128/142) identified with a responsibility to disseminate their research findings to a broad audience and identified several associated benefits. All respondents saw value in communicating aggregate results to study participants, although over half (53.2%, n = 66/124) had never done so. Genetic counselors reported resource and knowledge barriers to research dissemination. Despite expertise in education and communication, genetic counselors face similar barriers as other researchers toward broad dissemination of research. Formal training and professional guidelines specific to research dissemination practices will equip genetic counselors to reach broader audiences and maximize the impact of research findings.

The experiences of adolescent siblings of children with rare genetic conditions: "It's made me who I am".

Childhood genetic conditions impact not only the child who is diagnosed but also the day-to-day lives of all members of a family. However, our understanding of the perspectives and needs of unaffected adolescents in families affected by rare genetic conditions is limited. To address this gap, we conducted semi-structured interviews with 10 participants aged 14-20 years, all of whom had a sibling with a rare genetic condition. An interpretive description approach was used to develop a framework that described how participants' experiences of having a sibling with a rare genetic condition shaped the formation of their identity. This experience influenced identity formation both directly, and indirectly through four other phenomena: (1) normalization, of both their own experiences and their siblings' differences; (2) knowledge seeking, regarding their sibling's condition and what uncertainties remained; (3) caretaking, which limited some opportunities and was associated with uncertainty around the future; and (4) social experience, including their relationship with their affected sibling, with their peers, and with the rest of their family participants felt that they were isolated and lacked appropriate supports. The results of this study can help to inform a family-centered approach to genetic counseling and highlight the importance of tailored supports for this population.

A novel online genomic counseling and variant interpretation certificate: Learning design, learning analytics, and evaluation.

In this paper we describe the analysis, planning, design, development, implementation and evaluation of a new online Graduate Certificate in Genomic Counselling and Variant Interpretation (GCGCVI) at The University of British Columbia (UBC). Genetic counselling is now a prerequisite for diagnostic genomic testing in many countries, demanding that genetic counselling practitioners have up-to-the-moment genomic counselling skills and knowledge. Current practitioners reported a desire for more training in this rapidly developing field: our international survey revealed substantial interest in online continuing education addressing themes such as testing and clinical bioinformatics, applied variant interpretation, evidence-based genomic counselling, and other emerging genomic topics. However, our market analysis found no post-graduate program globally that offered such training. To fill this gap, our oversight team of genetic counsellors and geneticists therefore guided development of curriculum and materials, and online learning specialists developed rigorous interactive asynchronous online graduate courses through collaboration with subject matter experts, following best practices in online learning design. Since launch in September 2020, we have gathered learner feedback using surveys and focus groups, and we have used learning analytics to understand how learners engaged with each other and with course materials. Together, these have helped us understand learner behaviour and guide the continuous process of design improvement to support the learning goals of this audience of professional learners. Our courses have been reviewed and approved by the UBC Faculty of Medicine, UBC Senate, and the Province of British Columbia Ministries of Advanced Education and Health, and assessed by the National Society of Genetic Counselors (NSGC, USA) and the Canadian Association of Genetic Counsellors (CAGC) to enable learners to receive North American continuing education credits. To date, 151 individuals from 18 countries have succeeded in one or more course and 43 have completed the entire certificate.

How to improve research capacity strengthening efforts: learning from the monitoring and evaluation of four research consortia in Africa.

Recent efforts to shift the control and leadership of health research on African issues to Africa have led to increased investments for scientific research capacity strengthening (RCS) on the continent and a greater demand for accountability, value for money and demonstration of return on investment. There is limited literature on monitoring and evaluation (M&E) of RCS systems and there is a clear need to further explore whether the M&E frameworks and approaches that are currently used are fit for purpose. The M&E approaches taken by four African RCS consortia funded under the Developing Excellence in Leadership, Training and Science in Africa (DELTAS) I initiative were assessed using several methods, including a framework comparison of the M&E approaches, semi-structured interviews and facilitated discussion sessions. The findings revealed a wide range in the number of indicators used in the M&E plans of individual consortium, which were uniformly quantitative and at the output and outcome levels. Consortia revealed that additional information could have been captured to better evaluate the success of activities and measure the ripple effects of their efforts. While it is beneficial for RCS consortia to develop and implement their own M&E plans, this could be strengthened by routine engagement with funders/programme managers to further align efforts. It is also important for M&E plans to consider qualitative data capture for assessment of RCS efforts. Efforts could be further enhanced by supporting platforms for cross-consortia sharing, particularly when trying to assess more complex effects. Consortia should make sure that processes for developmental evaluation, and capturing and using the associated learning, are in place. Sharing the learning associated with M&E of RCS efforts is vital to improve future efforts. Investing and improving this aspect of RCS will help ensure tracking of progress and impact of future efforts, and ensure accountability and the return on investment. The findings are also likely applicable well beyond health research.

The effect of rapid exome sequencing on downstream health care utilization for infants with suspected genetic disorders in an intensive care unit.

PURPOSE: This study aimed to compare downstream utilization of medical services among critically ill infants admitted to intensive care units who received rapid exome sequencing (ES) and those who followed alternative diagnostic testing pathways. METHODS: Using propensity score-weighted regression models including sex, age at admission, and severity indicators, we compared a group of 47 infants who underwent rapid ES with a group of 211 infants who did not receive rapid ES. Utilization and cost indicators were compared between cohorts using negative binomial models for utilization and two-part models for costs. RESULTS: After controlling for patients' sociodemographic and clinical characteristics, we found no statistically significant difference in outpatient visits, hospitalizations, intensive care unit or total length of stay, or length of stay-associated costs between the cohorts at 12- or 26-month follow-up. Similarly, there was no evidence of higher utilization or costs by the ES group when infants who died were removed from the analysis. CONCLUSION: When examining utilization during and beyond the diagnostic trajectory, there is no evidence that ES changes frequency of outpatient visits or use of in-hospital resources in critically ill infants with suspected genetic disorders.

Genetic counseling considerations in cerebral palsy.

Genome-wide sequencing (exome and whole genome) has transformed our ability to diagnose patients with suspected genetic disorders. Cerebral palsy (CP), although historically thought to be due to birth injury (perinatal hypoxia), represents a clinical spectrum of disorders, many of which have been attributed to a genetic cause. GWS has elucidated the underlying single gene cause for many patients with CP and has important implications for the customization of treatment, management, and genetic counseling. International guidelines recommend genetic counseling for all families considering genome-wide sequencing. Genetic counselors educate and support families and help them to make testing decisions based on their values. They can help families adapt to, and understand the implications of a genomic diagnosis. Here, we review advances in sequencing for CP, clinical features suggestive of a genetic etiology of CP, practice guidelines for GWS, and a practical approach to the genetic counseling of these families. This includes: the content to be addressed in pre-test and post-test genetic counseling sessions, the benefits of a establishing a genetic cause and importantly, the need for ongoing support.

Elevated serum IL-10 is associated with severity of neonatal encephalopathy and adverse early childhood outcomes.

BACKGROUND: Neonatal encephalopathy (NE) contributes substantially to child mortality and disability globally. We compared cytokine profiles in term Ugandan neonates with and without NE, with and without perinatal infection or inflammation and identified biomarkers predicting neonatal and early childhood outcomes. METHODS: In this exploratory biomarker study, serum IL-1α, IL-6, IL-8, IL-10, TNFα, and VEGF (<12 h) were compared between NE and non-NE infants with and without perinatal infection/inflammation. Neonatal (severity of NE, mortality) and early childhood (death or neurodevelopmental impairment to 2.5 years) outcomes were assessed. Predictors of outcomes were explored with multivariable linear and logistic regression and receiver-operating characteristic analyses. RESULTS: Cytokine assays on 159 NE and 157 non-NE infants were performed; data on early childhood outcomes were available for 150 and 129, respectively. NE infants had higher IL-10 (p < 0.001), higher IL-6 (p < 0.017), and lower VEGF (p < 0.001) levels. Moderate and severe NE was associated with higher IL-10 levels compared to non-NE infants (p < 0.001). Elevated IL-1α was associated with perinatal infection/inflammation (p = 0.013). Among NE infants, IL-10 predicted neonatal mortality (p = 0.01) and adverse early childhood outcome (adjusted OR 2.28, 95% CI 1.35-3.86, p = 0.002). CONCLUSIONS: Our findings support a potential role for IL-10 as a biomarker for adverse outcomes after neonatal encephalopathy. IMPACT: Neonatal encephalopathy is a common cause of child death and disability globally. Inflammatory cytokines are potential biomarkers of encephalopathy severity and outcome. In this Ugandan health facility-based cohort, neonatal encephalopathy was associated with elevated serum IL-10 and IL-6, and reduced VEGF at birth. Elevated serum IL-10 within 12 h after birth predicted severity of neonatal encephalopathy, neonatal mortality, and adverse early childhood developmental outcomes, independent of perinatal infection or inflammation, and provides evidence to the contribution of the inflammatory processes. Our findings support a role for IL-10 as a biomarker for adverse outcomes after neonatal encephalopathy in a sub-Saharan African cohort.

The effect of helminth infection on vaccine responses in humans and animal models: A systematic review and meta-analysis.

Vaccination has potential to eliminate infectious diseases. However, parasitic infections such as helminths may hinder vaccines from providing optimal protection. We reviewed existing literature on the effects of helminth infections and their treatment on vaccine responses in humans and animals. We searched literature until 31 January 2022 in Medline, EMBASE, Global health, Scopus, and Web of science; search terms included WHO licensed vaccines and human helminth types. Standardized mean differences (SMD) in vaccine responses between helminth infected and uninfected or anthelminthic treated and untreated individuals were obtained from each study with suitable data for meta-analysis, and combined using a random effects model. Analysis was stratified by whether helminth exposure was direct or prenatal and by vaccine type. This study is registered with PROSPERO (CRD42019123074). Of the 4402 articles identified, 37 were included in the review of human studies and 24 for animal experiments. For human studies, regardless of vaccine type, overall SMD for helminth uninfected/treated, compared to infected/untreated, was 0.56 (95% CI 0.04-1.07 and I2  = 93.5%) for direct helminth exposure and 0.01 (95% CI -0.04 to 0.07 and I2  = 85.9%) for prenatal helminth exposure. Effects of anthelminthic treatment were inconsistent, with no overall benefit shown. Results differed by vaccine type, with responses to live vaccines most affected by helminth exposure. For animal studies, the most affected vaccine was BCG. This result indicates that helminth-associated impairment of vaccine responses is more severe for direct, than for prenatal, helminth exposure. Further research is needed to ascertain whether deworming of individuals before vaccination may help improve responses.