Multicenter Comparison of Molecular Tumor Boards in The Netherlands:Definition, Composition, Methods, and Targeted Therapy Recommendations

Background Molecular tumor boards (MTBs) provide rational, genomics-driven, patient-tailored treatment recommendations. Worldwide, MTBs differ in terms of scope, composition, methods, and recommendations. This study aimed to assess differences in methods and agreement in treatment recommendations among MTBs from tertiary cancer referral centers in The Netherlands. Materials and Methods MTBs from all tertiary cancer referral centers in The Netherlands were invited to participate. A survey assessing scope, value, logistics, composition, decision-making method, reporting, and registration of the MTBs was completed through on-site interviews with members from each MTB. Targeted therapy recommendations were compared using 10 anonymized cases. Participating MTBs were asked to provide a treatment recommendation in accordance with their own methods. Agreement was based on which molecular alteration(s) was considered actionable with the next line of targeted therapy. Results Interviews with 24 members of eight MTBs revealed that all participating MTBs focused on rare or complex mutational cancer profiles, operated independently of cancer type-specific multidisciplinary teams, and consisted of at least (thoracic and/or medical) oncologists, pathologists, and clinical scientists in molecular pathology. Differences were the types of cancer discussed and the methods used to achieve a recommendation. Nevertheless, agreement among MTB recommendations, based on identified actionable molecular alteration(s), was high for the 10 evaluated cases (86%). Conclusion MTBs associated with tertiary cancer referral centers in The Netherlands are similar in setup and reach a high agreement in recommendations for rare or complex mutational cancer profiles. We propose a "Dutch MTB model" for an optimal, collaborative, and nationally aligned MTB workflow. Implications for Practice Interpretation of genomic analyses for optimal choice of target therapy for patients with cancer is becoming increasingly complex. A molecular tumor board (MTB) supports oncologists in rationalizing therapy options. However, there is no consensus on the most optimal setup for an MTB, which can affect the quality of recommendations. This study reveals that the eight MTBs associated with tertiary cancer referral centers in The Netherlands are similar in setup and reach a high agreement in recommendations for rare or complex mutational profiles. The Dutch MTB model is based on a collaborative and nationally aligned workflow with interinstitutional collaboration and data sharing

Brain ultrasonography findings in neonates with exposure to cocaine during pregnancy

Background: Cocaine exposure during pregnancy has been reported to have detrimental effects on the fetus. Objective: To describe the findings on cranial ultrasonography (CUS) as part of a neonatal screening programme for exposed neonates. Materials and methods: The study was a semiprospective analysis of a 12-year cohort of neonates born to mothers who had used cocaine during their pregnancy and who had follow-up according to a strict clinical protocol. Results: In total, 154 neonates (78 boys, 76 girls) were included, of whom 29 (19%) were born preterm, and 125 (81%) were born full-term. Abnormalities on CUS were seen in 37 neonates (24%; 95% CI 18-31%). The abnormalities were classified as minor in 20 (13%; 95% CI 9-19%) and mildly abnormal in 17 (11%; 95% CI 7-17%). None of the infants showed severe abnormalities. The abnormalities were not associated with the duration or maximum amount of cocaine use during pregnancy. Conclusion: None of the infants had severe abnormalities. Detected abnormalities were not correlated with the duration or maximum amount of cocaine use. Given these findings, we feel that routine cranial ultrasonography in this population is not warranted

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Parents’ needs and perceived gaps in communication with healthcare professionals in the neonatal (intensive) care unit: A qualitative interview study

Objective: To explore parents’ needs and perceived gaps concerning communication with healthcare professionals during their preterm infants’ admission to the neonatal (intensive) care unit (NICU) after birth. Methods: Semi-structured, retrospective interviews with 20 parents of preterm infants (March 2020), admitted to a Dutch NICU (level 2–4) minimally one week, one to five years prior. The interview guide was developed using Epstein and Street's Framework for Patient-Centered Communication. Online interviews were audio-taped and transcribed verbatim. Deductive and inductive thematic analysis was performed by two independent coders. Results: Communication needs and gaps emerged across four main functions of NICU communication: Building/maintaining relationships, exchanging information, (sharing) decision-making, and enabling parent self-management. Communication gaps included: lack of supportive physician communication, disregard of parents’ views and agreements, missing communication about decisions, and the absence of written (discharge) information. Conclusion: This study improves our understanding and conceptualization of adequate NICU communication by revealing persisting gaps in parent-provider interaction. Also, this study provides a steppingstone for further integration of parents as equal partners in neonatal care and communication. Practice implications: The results are relevant to practitioners in the field of neonatal and pediatric care, providing suggestions for tangible improvements in NICU care in the Netherlands and beyond

Adaptation of glucose metabolism to fasting in young children with infectious diseases: a perspective

Hypoglycemia is a frequently encountered complication in young children with infectious diseases and may result in permanent neurological damage or even death. Mortality rate in young children under 5 years of age is increased four- to six-fold when severe infectious disease is complicated by hypoglycemia. Young age, prolonged fasting and severity of disease are considered important risk factors. This perspective describes the combined results of recently conducted studies on the effect of these risk factors on glucose metabolism in children with different infectious diseases. The results of these studies have nutritional implications for the approach in clinical practice towards young children with infectious diseases and specific recommendations are made. A unique finding is the existence of infectious disease-related differences in the adaptation of glucose metabolism during fasting in young childre

Glucose production in response to glucagon is comparable in preterm AGA and SGA infants

Background & Aims: Low plasma glucose concentrations are more often detected in small-for-gestational-age (SGA) than in appropriate-for-gestational-age (AGA) infants. This is ascribed to impaired glucose production due to presumed tower liver glycogen stores in SGA infants. The change in glucose production induced by glucagon is considered to be an indicator of Liver glycogen content. We compared the effect of glucagon on glucose kinetics in preterm AGA and SGA infants. Methods: In 5 AGA and 5 SGA preterm infants (postnatal age: 3-6 days) glucose production and gluconeogenesis were measured using stable isotopes immediately before and for 1 h after a bolus of glucagon. Results: After glucagon the plasma glucose concentration and glucose production increased significantly over time (P <0.05 and P <0.0001, respectively). The changes were comparable between AGA and SGA infants. Glycogenolysis contributed 75-80% to the increase in glucose production. Conclusion: The increase in glucose production after glucagon was similar in preterm AGA and SGA infants, and mainly due to an increase in glycogenolysis. Based on the assumption that glycogenolysis is an indicator of liver glycogen content, our data do not support the hypothesis that liver glycogen content is tower in preterm SGA compared to AGA infants after the first postnatal day. (c) 2005 Elsevier Ltd. ALL rights reserve

Effect of single family rooms for preterm infants on neurodevelopment: study protocol for a systematic review

Introduction Preterm infants are at an increased risk for neurodevelopmental delay. They have to endure many stressors in early life, including parent-infant separation, noise and painful procedures during hospitalisation in the highly technological environment of the modern neonatal ward. Currently, a shift is being noticed in the architectural design of neonatal wards towards single family rooms instead of the common open bay units. The influence of the hospital environment on health and specifically neurodevelopment in this vulnerable patient population remains under discussion. Objectives To assess the effect of single family rooms during hospitalisation primarily on neurodevelopment in preterm infants. Secondary outcome measures will be neonatal (ie, breastfeeding rates, sepsis, growth during hospital stay, length of hospital stay) and parental (ie, parental stress, satisfaction, participation, presence and self-efficacy). Methods and analysis The PRISMA-P 2015 (Preferred Reporting Items for Systematic reviews and Meta-Analyses for Protocols 2015) 17 items checklist was used for the generation of the protocol for this review. The following PICO was formulated: Population: preterm infants with need of hospitalisation in the neonatal ward; Intervention: single family rooms; Comparison: standard neonatal care in open bay units; Outcome: neurodevelopmental outcome of infants from 9 months onwards. If at least two studies, with low or moderate risk of bias, suitable for inclusion are found a meta-analysis will be performed. If quantitative synthesis is not appropriate the data will be presented descriptively. Dissemination plans This will be the first review, systematically assessing the effect of single family rooms on neurodevelopmental outcome in preterm infants. Clinical practice could possibly be optimised to ameliorate neurodevelopment in this vulnerable patient population based on these insights. This systematic review will be published in an international peer-reviewed journal. Registration We registered this systematic review protocol with the PROSPERO (International Prospective Register of Systematic Reviews) on 2 November 2016 (registration number: CRD42016050643). Ethics We will use data from patients enrolled in studies and/or trials already approved by the relevant ethical committees and therefore this systematic review requires no further permission

The functions of adequate communication in the neonatal care unit: A systematic review and meta-synthesis of qualitative research

Objective: To assess the main functions of parent-provider communication in the neonatal (intensive) care unit (NICU) and determine what adequate communication entails according to both parents and health professionals. Methods: A systematic review and meta-synthesis of qualitative research. PubMed, Ebsco/PsycINFO, Wiley/Cochrane Library, Ebsco/CINAHL, Clarivate Analytics/Web of Science Core Collection, and Elsevier/Scopus were searched in October-November 2019 for records on interpersonal communication between parents and providers in neonatal care. Title/abstract screening and full-text analysis were conducted by multiple, independent coders. Data from included articles were analyzed using deductive and inductive thematic analysis. Results: 43 records were included. Thematic analysis of data resulted in the development of the NICU Communication Framework, including four functions of communication (1. building/maintaining relationships, 2. exchanging information, 3. (sharing) decision-making, 4. enabling parent self-management) and five factors that contribute to adequate communication across these functions (topic, aims, location, route, design) and, thereby, to tailored parent-provider communication. Conclusion: The NICU Communication Framework fits with the goals of Family Integrated Care to encourage parent participation in infants’ care. This framework forms a first step towards the conceptualization of (adequate) communication in NICU settings. Practice implications: Findings can be used to improve NICU communication in practice, in particular through the mnemonic TAILORED

The functions of adequate communication in the neonatal care unit: A systematic review and meta-synthesis of qualitative research

Objective: To assess the main functions of parent-provider communication in the neonatal (intensive) care unit (NICU) and determine what adequate communication entails according to both parents and health professionals. Methods: A systematic review and meta-synthesis of qualitative research. PubMed, Ebsco/PsycINFO, Wiley/Cochrane Library, Ebsco/CINAHL, Clarivate Analytics/Web of Science Core Collection, and Elsevier/Scopus were searched in October-November 2019 for records on interpersonal communication between parents and providers in neonatal care. Title/abstract screening and full-text analysis were conducted by multiple, independent coders. Data from included articles were analyzed using deductive and inductive thematic analysis. Results: 43 records were included. Thematic analysis of data resulted in the development of the NICU Communication Framework, including four functions of communication (1. building/maintaining relationships, 2. exchanging information, 3. (sharing) decision-making, 4. enabling parent self-management) and five factors that contribute to adequate communication across these functions (topic, aims, location, route, design) and, thereby, to tailored parent-provider communication. Conclusion: The NICU Communication Framework fits with the goals of Family Integrated Care to encourage parent participation in infants’ care. This framework forms a first step towards the conceptualization of (adequate) communication in NICU settings. Practice implications: Findings can be used to improve NICU communication in practice, in particular through the mnemonic TAILORED