Oral health‐related quality of life (OHRQoL) is an important dental patient‐reported outcome which is commonly based on 4 dimensions, namely Oral Function, Orofacial Pain, Orofacial Appearance and Psychosocial Impact. The Oral Health Impact Profile (OHIP) is the most used OHRQoL instrument designed for adults; nevertheless, it is used off‐label for children as well. Our aim was to describe the OHRQoL impact on children measured by OHIP and map the information to the 4‐dimensions framework of OHRQoL. A systematic literature review following the PRISMA statement was conducted to include studies assessing OHRQoL of children ≤ 18 years using OHIP. The OHIP seven‐domain information was converted to the OHRQoL 4‐dimension scores accompanied by their means and 95% confidence interval. Risk of bias was assessed using a six‐item modified version of quality assessment tool for prevalence studies. We identified 647 articles, after abstracts screening, 111 articles were reviewed in full text. Twelve articles were included, and their information was mapped to the 4‐dimensional OHRQoL. Most included studies had low risk of bias. OHRQoL highest impact was observed for Oral Function, Orofacial Pain, and Orofacial Appearance for children with: Decayed‐Missing‐Filled‐Surface (DMFS) of ≥10, anterior tooth extraction without replacement and untreated fractured anterior teeth, respectively. Across all oral health conditions, Psychosocial Impact was less affected than the other three dimensions. OHIP has been applied to a considerable number of children and adolescents within the literature. One instrument and a standardised set of 4‐OHRQoL dimensions across the entire lifespan seem to be a promising measurement approach in dental and oral medicine. The most often used ones includes the Child Perceptions Questionnaire (CPQ),In adults, the Oral Health Impact Profile (OHIP)Recent studies have demonstrated that OHRQoL has four main components, so called dimensions—Oral Function, Orofacial Pain, Orofacial Appearance and Psychosocial Impact, which could provide a standardised and an efficient approach to measure what matters to patients.Although instruments measuring OHRQoL in adults such as OHIP were also applied to measure oral health problems in children and adolescents, possibly under the assumption that capturing oral problems could be similar for both,Advantages of the novel approach of characterising the oral impact for children and adults using a 4‐dimensional impact would be to allow measuring oral health impact across the entire lifespan. Adults and children could have one measurement system and not two—the current situation.Therefore, the overall aim of this project was to perform a systematic review in order to identify publications with information about OHRQoL dimensions in children measured using OHIP and map the available seven‐domain information to the 4‐dimensional framework of OHRQoL , which was characterised previously in adults. Moreover, we aimed to describe the levels of OHRQoL of different oral conditions including their clinical relevance in paediatric patients and the general population of children/adolescents.22.1A systematic literature review with the subsequent identification of instruments and extraction of data was conducted. The protocol was published in the PROSPERO database (registration number: CRD42017064033), and the PRISMA statement for reporting systematic reviews was followed.2.2Publications reporting about children population or paediatric patients (≤ 18 years)Publications reporting OHRQoL using OHIP instrument .functional limitations, physical pain, psychological discomfort, physical disability, psychological disability, social disability and handicap.OHIP seven domains have to be available, including Measure of central tendency, in addition to measure of dispersion, has to be available for the scores of the seven OHIP domains.In case of mixed population of children and adults, the following criteria were adopted .English language.2.3Not full‐text publications .Responses to the instrument are not in the proper 0 to 4 OHIP item response format.2.4As this review was part of a larger project on the 4 dimension‐model of the OHIP, a pool search was carried out that provided data for all four OHIP domains complemented by a manual search for the specific domains. The electronic literature search was conducted by a trained librarian  using the search terms ‘Oral Health Impact Profile’ OR ‘OHIP’ to identify articles that measure OHRQoL by OHIP for any oral health condition. The search was then limited to children or adolescents using controlled vocabulary and keywords: adolescent[MeSH] OR child[MeSH] OR child[tiab] OR adolescen*[tiab] OR teen*[tiab] OR student*[tiab]. An electronic search was conducted in MEDLINE (PubMed), EMBASE, Cochrane, CINAHL and PsycINFO from the inception of respective databases to 9 January 2019 Table .2.5Two researchers  independently screened all titles and abstracts for inclusion based on the inclusion criteria mentioned above . The two reviewers then discussed points of disagreements in inclusion of articles and agreed to the final decision. All potentially eligible articles underwent a full‐text review to ensure that they fulfilled the inclusion criteria. Again, disagreements within this step of the review were discussed until consensus was achieved between the two reviewers.2.6Two researchers (MO and MTJ) assessed the risk of bias for the eligible articles using a modified version of the quality assessment for prevalence studies tool developed by Munn et al2.7Surname of the first author of the articleYear of publicationCountry of studyStudy designOHIP version used in the articlePopulation characteristicsCondition/s description of the individual samples,Number of the extracted subjects of the individual samplesOHIP domain score central tendency values (eg mean) andOHIP domain score dispersion values (eg standard deviations).Data extraction of the included articles was carried out by one researcher (MO), and 10% of the extracted data was checked by another researcher (MTJ). For studies that included several follow‐up time points, only the first time point was used. A particular publication could contain populations with one or more samples of patients. For each article, the following information was extracted:2.8The study determined the number of publications, the number of clinically relevant patient groups, (referred to as ‘populations’), and the number of patient samples per population with 4‐dimensional OHRQoL information.The study also included mean values derived from any version of the OHIP questionnaire (14‐item and 49‐item). The data from OHIP‐49 were converted to OHIP‐14 means together with 95% confidence interval values restricted to fit on a 0 to 8 scale. Mean and standard deviation values were derived directly from the articles.3The literature search identified 647 articles. After screening of abstracts, 111 articles were reviewed in full text Table  and 12 anot mutually exclusive), 6 articles addressed malocclusion and patients undergoing orthodontic treatment. Two articles investigated skeletal discrepancies and orofacial clefting, and one investigated non‐syndromic hypodontia. Half of all articles (N = 6) assessed OHRQoL in non‐patient populations, mostly school children/adolescents and addressed several oral health conditions, for example anterior tooth extraction without replacement, presence of dental restorations, untreated fractured anterior teeth and DMFS . For our study, a total of 2687 subjects were included, and populations were identified with an overall number of 26 samples, which presented 4‐dimensional OHRQoL information. The included samples were from both the general (non‐patient) population as well as patient populations. In respect of the main conditions of the articles (3.1The risk of bias assessment showed a high risk in the representativeness of the target population (does the source of population adequately represent the target population?), followed by the proper recruitment of the study participants . Another high risk and a large number of unclear risk of bias were shown by the coverage domain, which is a comparison of actual subjects/patients with the intended or planned subjects/patients . Nevertheless, because the included studies used OHIP which is validated in many languages, and well tested for its psychometric properties, the reliability and standard domains presented only low risk of bias. In addition, characterisation (if the study subjects and setting were sufficiently described) showed a low risk of bias as well. In general, a high proportion of studies (n = 8) and individual samples (n = 19) was deemed to have a low risk of bias Figure .3.2Overall results of the 0 to 8 converted OHIP scale showed that the most affected dimensions of the examined population were Oral Function, Orofacial Pain and Orofacial Appearance, while Psychosocial Impact was least affected.When dimensions were investigated within the non–follow‐up studies Figure , the OraThe Psychosocial Impact was less affected when compared to other impact dimensions. Psychosocial impact conditions were ranging from 0 to 2, with the highest values similar to the Orofacial Appearance impact in the anterior tooth extraction without replacement and untreated fractured anterior teeth.Regarding the prospective longitudinal studies or follow‐up studies Figure , the ort4Oral health conditions in children are in principle similar to adults, especially in terms of how they affect their lives and quality of life. Similar to using a pharmaceutical drug off‐label for an unapproved indication or in an unapproved age group, the OHIP was used for different age groups for which it was originally developed in a considerable number of studies (n = 111). Out of those 111 articles, 12 publications met our inclusion criteria including cross‐sectional and longitudinal studies with a total of 2687 subjects suffering from several health conditions. When characterising the suffering from oral diseases of paediatric patients or non‐patient's populations, our results provided information about oral health conditions in children for which adults would suffer as well. Similar to adults, OHRQoL in children could be divided into the 4 dimensions including Oral Function, Orofacial Pain, Orofacial Appearance and Psychosocial Impact.We investigated the non–follow‐up studies and found the highest levels of functional impairment in the general population of adolescents with DMFS of ≥10. This is consistent with adults and even elderly population studies.Regarding Orofacial Pain, interestingly, the highest pain value was found in the sample with the condition of anterior tooth extraction without replacement. The descriptive nature of our study cannot generate a reason for that, however, extraction of anterior teeth in school children could be related to possible traumatic injuries or dental caries.The highest values were observed within the psychosocial impact were in two conditions equally, including anterior tooth extraction without replacement and untreated fractured anterior teeth. Untreated fractured anterior teeth were emphasised by Cortes et al as having a high socio‐dental impact on daily living of children when compared to children with no traumatic dental injury.Furthermore, this review included several conditions and populations, among them also populations of general adolescents from urban and rural areas. Our results showed that urban general adolescents were better in all of the four OHRQoL dimensions than the rural ones. This finding is in line with studies which investigated OHRQoL in urban and rural adults. It was found that individuals in urban area had better OHRQoL.In respect of longitudinal follow‐up studies findings, patient populations were reported, and conditions included were malocclusion, orofacial clefting, severe skeletal discrepancies and orthodontic patients with different types of brackets. Patients with severe dentofacial deformities have major conditions which affect OHRQoL in general and Orofacial Appearance in particular. Our study showed that severe skeletal discrepancies (which need both orthodontic treatment and surgery) as the highest value within the appearance dimension in the follow‐up studies. This result is in concordance with other studies which found that the satisfaction of patients with the surgery outcomes depends mainly on the improvement of aesthetics regardless of other post‐operative problems such as functional ones.In both follow‐up and non–follow‐up studies, the psychosocial impact of the examined populations/conditions showed in general numerically lower values, that is better OHRQoL, of the examined conditions within the 0 to 8 converted OHIP scale when compared to the other three OHRQoL dimension impacts.Our study included patients as well as general population studies, which was important to review the OHRQoL impact in children on both groups representing the community. This emphasises the role of OHRQoL in clinical practice including measures for personalised treatment and monitoring of patient's improvement. Additionally, OHRQoL is important for public health and community dentistry fields and can be used in epidemiological studies to determine several population characteristics and other population‐based preventive and treatment strategies. Therefore, this review demonstrated the use and applicability of the newly proposed 4‐dimension OHRQoL in patients and the general population of children.A widely used instrument which was specifically designed for children is the child perception questionnaire. CPQ was originally developed in Canada by Jokovic et al to measure OHRQoL in children and adolescents aged from 6 to 14 years old.Prevention strategies and proper monitoring of oral health throughout life lead to preservation of good OHRQoL. Consequently, OHRQoL assessment is an integral component in any treatment or intervention strategy and should be performed prior to any preventative or therapeutic intervention. ‘One instrument for all ages’ to measure oral health impact would be an approach which will allow testing and investigating several hypotheses related to live‐long impact of oral diseases. A good example for that is malocclusion. With a proper measurement system in place, the long‐term impact, that is when patients are adults, of malocclusion and the effects of orthodontic treatments could be investigated.Another example for a live‐long impact is caries, starting from early childhood caries (ECC), to caries affecting individuals later in life and impacting all aspects of OHRQOL. Previous caries experience is considered the most dominant caries predictor in all age groups.Therefore, the concept of 4‐dimensions’ impact of OHRQoL when used for adults and children could allow measuring patients´ suffering across all ages, as well as providing more consistent and standardised dimensions of the OHRQoL. Accordingly, a proper and continuous monitoring strategy for preserving oral health of populations and implementing value‐based health care will be achieved. Furthermore, it would facilitate research projects for comparing different age groups using a standardised instrument.Regarding younger children assessment, since the 4 dimensions are the major areas of dental patients' suffering across the entire age span, methods to collect the information, for example self‐ versus proxy assessment or the mode of questionnaire administration, can be flexibly adapted according to the specific settings and the needs of the examined persons. However, more research will be needed to investigate this approach in younger children.In general, standardisation and consistency of the measurements used for a specific construct, for example OHRQoL, are important for comparing different studies, populations and different age groups as well as enabling the follow‐up of persons over the life span.4.1Through OHIP being used ‘off‐label’, that is applying the instrument to an age groups it was not designed for, standardised 4‐dimensional information became available and the represented oral health conditions was low. Interestingly, researchers used OHIP in children and found it suitable for measuring several conditions including such important dental patient populations such as patients with malocclusion. Although many OHIP papers exist in children, we could not use all of them for the current project because we needed domain values (for the dimensions). Therefore, more OHRQoL information is actually available.5A considerable number of international researchers have applied OHIP, an OHRQoL instrument for adults, to children and adolescents. Moreover, using OHIP for paediatric patients and the general population of children and mapping the information to the four OHRQoL dimensions Oral Function, Orofacial Pain, Orofacial Appearance and Psychosocial Impact provide meaningful results about magnitude and variation of OHRQoL impairment. While more research on the psychometric properties of OHIP in children is needed, one instrument and a standardised set of four OHRQoL dimensions across the entire lifespan seems to be a promising measurement approach in dental and oral medicine.The authors declare that no conflicts of interest exist.MO, KB and TS conceived the ideas. MO and KB collected the data. MO, KB and TS analysed the data. MO, KB and TS wrote the manuscript. MO, KB and TS revised and approved the manuscript.https://publons.com/publon/10.1111/joor.13066.The peer review history for this article is available at Supplementary MaterialClick here for additional data file.


Pre‐participation cardiovascular screening (PPCS) is recommended by several scientific and sporting organizations on the premise that early detection of cardiac disease provides a platform for individualized risk assessment and management; which has been proven to lower mortality rates for certain conditions associated with sudden cardiac arrest (SCA) and sudden cardiac death (SCD). What constitutes the most effective strategy for PPCS of young athletes remains a topic of considerable debate. The addition of the electrocardiogram (ECG) to the medical history and physical examination undoubtedly enhances early detection of disease, which meets the primary objective of PPCS. The benefit of enhanced sensitivity must be carefully balanced against the risk of potential harm through increased false‐positive findings, costly downstream investigations, and unnecessary restriction/disqualification from competitive sports. To mitigate this risk, it is essential that ECG‐based PPCS programs are implemented by institutions with a strong infrastructure and by physicians appropriately trained in modern ECG standards with adequate cardiology resources to guide downstream investigations. While PPCS is compulsory for most competitive athletes, the current debate surrounding ECG‐based programs exists in a binary form; whereby ECG screening is mandated for all competitive athletes or none at all. This polarized approach fails to consider individualized patient risk and the available sports cardiology resources. The limitations of a uniform approach are highlighted by evolving data, which suggest that athletes display a differential risk profile for SCA/SCD, which is influenced by age, sex, ethnicity, sporting discipline, and standard of play. Evaluation of the etiology of SCA/SCD within high‐risk populations reveals a disproportionately higher prevalence of ECG‐detectable conditions. Selective ECG screening using a risk‐based approach may, therefore, offer a more cost‐effective and feasible approach to PPCS in the setting of limited sports cardiology resources, although this approach is not without important ethical considerations. As such, these highly emotional events are afforded significant visibility and galvanize discussion between physicians and the lay community with an emphasis on improving our understanding of the conditions predisposing to sudden cardiac arrest (SCA)/sudden cardiac death (SCD) and the development of effective preventative strategies.Exercise is a recognized trigger for ominous ventricular tachyarrhythmias in predisposed athletes that harbor a hereditary or congenital cardiac abnormality associated with SCA/SCD. Naturally, there is a desire to identify these at‐risk conditions on the premise that the majority of these athletes can be detected during life through pre‐participation cardiovascular screening (PPCS). The primary objective of PPCS is to identify underlying cardiac disorders predisposing to SCA/SCD with the intent to reduce morbidity and mortality by mitigating risk through individualized, patient‐centered, and disease‐specific medical management.Determining what constitutes the most effective PPCS strategy for young athletes has created an intense debate regarding the need and feasibility of electrocardiogram (ECG)‐based screening programs. Critics of a widespread ECG‐based screening program highlight concerns related to the lack of robust evidence for its efficacy to reduce athlete fatalities, reliability of outcomes , and overall cost. Proponents of ECG screening recognize the relative failure of the history and physical examination to meet the primary objective of PPCS, specifically to detect athletes with at‐risk cardiac conditions, and the wealth of evidence demonstrating the high false‐positive response rate and very low positive predictive value of symptom and family history questionnaires.The paradigm of ECG screening has been debated in a binary “all or nothing” form, whereby programs are mandated to include ECG for all young athletes, or none at all. These polarized options contradict the fundamental approach to preventative medicine, which ordinarily requires assessment of individualized patient risk and the available medical resources. This article will address the current landscape of PPCS and review the epidemiological data of SCA/SCD in young athletes, which may support a novel risk‐based approach to PPCS.2Understanding the etiology of SCA/SCD is paramount to inform the development of an effective preventative strategy for young athletes. Hypertrophic cardiomyopathy (HCM) is historically recognized as the leading cause of SCA/SCD in the United States while in Italy, arrhythmogenic cardiomyopathy predominates. Genetic variation, ascertainment bias of identified cases, and variable criteria and expertise for pathological diagnosis contribute to these regional discrepancies. More recent data suggest that autopsy negative sudden unexplained death in athletes with presumed SCD may be more prevalent than previously thought. Data from a specialist cardiac pathology center in the United Kingdom in 357 athletes has shown that in up to 42% of cases, the heart is structurally normal, and when the toxicology screen is negative, these deaths are classified as sudden arrhythmic death syndrome (SADS).3SCA/SCD is the leading medical cause of death in young athletes during sports and exercise.Survival rates of SCA in athletes have significantly improved following more widespread implementation of emergency response plans and automated external defibrillators (AEDs).Appreciation of these methodological inconsistencies is particularly important when scrutinizing the validity of estimates drawn from larger systematic reviews. Mohaneney et al recently evaluated the global incidence of sports‐related SCD in young athletes through a meta‐analysis of 21 studies which included 1994 cases of sports‐related SCD over 430 million athlete‐years (AY). The pooled incidence of SCD reported was 0.72 per 100 000 AY. However, the significant variation of reported incidence (0.09‐13.09 per 100 000 AY) across the 21 studies is attributable to considerable heterogeneity in study methodology as described above, and evenly weighting studies with both poor and robust methodology is likely to bias the analysis and underestimate the pooled incidence of SCD.Harmon et al performed a comprehensive review of studies that have examined the incidence of SCA/SCD in young athletes.The underpinning of the screening debate is centered on the perceived incidence of SCD in young athletes. The screening community must interpret the validity of incidence estimates with a keen eye on the rigor of the methodology used to obtain them. Further studies using data from mandatory reporting systems and inclusive of all deaths and survivors are clearly warranted if we are to improve our understanding of the magnitude of SCA/SCD in young athletes.4Evolving data supports a differential risk profile for SCA/SCD in certain populations of athletes Figure .The incidence rate of SCA/SCD in athletes appears to be determined by age, sex, race, sporting discipline, and standard of play Figure . AthleteClear sex differences exist, with males reported to be at 3 to 10‐fold higher risk compared to female counterparts in competitive sport, and up to 20‐fold higher risk in recreational sport.Two prominent studies of young athletes in the United States have mirrored these findings with regard to sex, but also suggest that the risk of SCA/SCD is further determined by the athlete's race, sporting discipline, and standard of competition. Garberich et al recently evaluated the demographics of 842 young athletes with autopsy confirmed SCD within a large forensic registry of competitive US athletes over a 32‐year period. The incidence of SCD in male athletes exceeded that in female athletes by 6.5‐fold (1:122 000 vs 1:787 000 AY), while the risk in black athletes exceeded that in white athletes by almost fivefold (1:13 000 vs 1:61 000 AY).Harmon et al evaluated 79 cardiac‐related deaths taken from a large database of National Collegiate Athletic Association (NCAA) athletes over 10 years which included 4 242 519 total AY of participation. It is worth noting that all athletes had previously undergone PPCS predominantly without an ECG and incidence rates did not include survivors of SCA. The overall incidence of SCD in NCAA athletes was 1:54 000 AY. Again, male athletes were at threefold higher risk than female counterparts (1:38 000 vs 1:12 2000 AY) and black athletes were threefold higher risk than white athletes (1:21 000 vs 1:68 000 AY). Breaking these results down further, male‐black athletes demonstrated a risk of 1:16 000 AY, male basketball players 1:9000 AY, and male NCAA division I basketball players a risk of 1:5200 AY. Men's basketball represents only 4% of male NCAA athletes, but almost 20% of all SCD cases. Male basketball and American‐football players together represent 23% of all male NCAA athletes but 50% of all SCD cases. In combination, these two sports  consistently account for the majority (50%‐61%) of all identified cases of SCA/SCD in the United States.In a Canadian study, Landry et al undertook a retrospective 5‐year analysis of a population‐based registry of out‐of‐hospital SCA occurring in young athletes.5The AHA recommends that all athletes are screened with a 14‐element assessment via a medical history and a physical examination. Secondary evaluation is considered for any athlete with a positive response to any one of the 14 elements. The AHA's pragmatic approach is widely practiced but limited when one considers that up to 80% of young athletes are asymptomatic prior to their SCA/SCD.The weight of scientific evidence has led to widespread agreement that ECG enhances the detection of conditions associated with SCA/SCD to better meet the primary objective of PPCS. Screening with ECG may identify more athletes with at‐risk disease, but does this equate to saving lives? Limited long‐term morality data is available to support the efficacy of an ECG‐based PPCS strategy.Only one other study provides long‐term mortality data in combination with findings from baseline PPCS. Malhotra et al reported findings in 11 168 elite adolescent soccer players screened at a mean age of 16.4 years with a health questionnaire, physical examination, ECG, and echocardiogram, and followed for a mean of 10.6 years. Forty‐two athletes (0.38%) were identified with a cardiac disorder associated with SCA/SCD. Only four of these athletes (9.5%) presented with symptoms and/or findings on physical examination, whereas 36 (86%) had an abnormal ECG. Athletes with pathological cardiac disorders received disease‐specific medical management, procedural interventions, and exercise restrictions as indicated to mitigate their risk. Two athletes with HCM who returned to sport against medical recommendations died, while SCA/SCD was potentially averted in 40 of 42 athletes optimally managed after early detection of a pathological cardiac disorder.This raises the important issue regarding the frequency and timing for PPCS when one considers the variable age at which certain conditions manifest on ECG. The optimal age to introduce PPSC for athletes remains largely uncertain. Most consensus guidelines suggest PPCS start at age 12 when pubertal maturation and the expression of many disorders associated with SCD may begin.While outcome‐based studies remain limited and the natural history of conditions associated with SCA/SCD remains largely unknown, PPCS inclusive of ECG is further supported by disease‐specific data, which demonstrates that early detection in conjunction with individualized risk stratification and management lowers mortality rates for certain cardiac conditions associated with SCA/SCD, including HCM and long QT syndrome.The ESC's uniform approach in favor of ECG screening for all young athletes raises numerous practical limitations, which warrant careful review. The ECG will not detect all conditions, which predispose athletes to SCA/SCD. The ECG may be normal in up to 10% of athletes with HCM, 70% who are genotype positive for long QT syndrome, and 90% with premature coronary artery disease. Furthermore, the resting ECG is normal in almost all individuals with anomalous coronary arteries, catecholaminergic polymorphic ventricular tachycardia, and aortopathies. These false‐negatives may result in false reassurance for a small proportion of athletes that harbor CV conditions associated with SCA/SCD, but the rate of false‐negative screens is substantially lower than if using the less sensitive evaluation of history and physical examination alone.False‐positive ECG findings are another important limitation to consider. Regular exercise leads to a constellation of electrical and structural cardiac alterations which collectively form the phenotype of the “athlete's heart.” These physiological changes manifest as electrical changes on the athlete's ECG and, in some cases, mimic those observed in patients with cardiomyopathy. A notable example of this is the relatively high prevalence of anterior T‐wave inversion in black male athletes and some adult endurance athletes. Misinterpretation of physiological ECG findings leads to unnecessary downstream investigations and, in some cases, inappropriate restriction from competitive sports. The financial implications of false‐positive findings provide the central argument against national legislation for ECG screening in most countries.6Standardized ECG interpretation criteria, first introduced by the ESC in 2010, distinguished physiological adaptations from pathological abnormalities, which led to improvements in interpretation accuracy. Refinement of these criteria over the last decade has been facilitated by a greater understanding of the athlete's heart. Contemporary criteria have increasingly accounted for adolescent athletes, black ethnicity and some nonspecific electrical anomalies, including axis deviation and voltage criteria for atrial enlargement, and sequentially improved the specificity of ECG screening by driving down the false‐positive rate from 25% to less than 5%. In a study of 5258 NCAA athletes, the false‐positive rate was only 1.3% when experienced clinicians applied the latest international criteria , breast, and colon cancer, is primarily judged by their ability to detect disease, assuming perhaps without definitive evidence that early detection will reduce mortality through modern treatment. Furthermore, these programs consider higher risk groups in their target population. Population‐based screening programs for AAA were first established in the United States and United Kingdom over 10 years ago.Guidelines for the primary prevention of CV disease routinely recommend physicians to consider the individual's estimated risk of adverse CV events as a guide to management decisions.The American Medical Society for Sports Medicine (AMSSM) recently proposed a new PPCS framework, which considers the individual risk of the athlete as well as physician expertise and available cardiology resources for accurate ECG interpretation and the secondary evaluation of ECG abnormalities.The AMSSM's risk‐based framework is supported by the outcome of a recent surveillance study of young athletes in the United States. Peterson et al prospectively evaluated the etiology of SCA/SCD cases in the United States through a national surveillance program over a 2‐year period.When ample sports cardiology resources are available, routine use of ECG is possible in the PPSC of all athletes. However, reserving the ECG for smaller populations of higher risk groups may offer a more pragmatic approach for institutions that are not equipped with the infrastructure and expertise to adequately support an ECG‐based model on a larger scale.It is prudent, however, to consider the ethical issues of such an approach. Institutions may argue that equivalent screening services should be available to all athletes under their care and not differentiated based on sex, race, or sport. This notion is supported by data from France, Denmark, and the United States, which has demonstrated that the incidence of SCD in recreational athletes and nonathletic individuals, is higher than previously thought.8The paradigm of PPCS has disputed the merits of an ECG‐based program as a binary “all or nothing” approach. This perspective fails to consider the individual risk of the athlete and the available sports cardiology expertise, which are essential to providing sound preventative care. Evolving data supports that certain populations of athletes  are at higher risk of SCA/SCD than others. The higher prevalence of ECG‐detectable conditions  reported in these high‐risk groups, favors a more intensive approach with ECG screening. In the setting of limited sports cardiology resources, a risk‐based approach may be the most pragmatic method to perform effective PPCS. While targeted screening for higher risk individuals has precedence in other medical prevention programs, the merits, and feasibility of this strategy must be carefully balanced against the ethical concerns associated with screening only a subset of athletes and the need for more definitive outcomes data.


Interventions aimed at improving accessing of health care services, including HIV testing, remain a priority in global HIV eradication efforts. Grassroot Soccer Zimbabwe (GRSZ) is an adolescent health organisation that uses the popularity of soccer to promote healthy behaviours. We assessed HIV knowledge levels, risky behaviours and attitudes in school going adolescents and young adults who attended GRSZ programmes and determined if HIV knowledge levels were associated with increased levels of accessing of health care services by youths.This was a cross-sectional study carried out on 450 participants aged 13–30 years who attended at least one of the three programmes offered by GRSZ. Self-administered and self-reporting questionnaires were used to collect information on participants’ demographics, knowledge on HIV and reproductive health, sources of information, access to HIV and reproductive health services and attitudes and risky behaviours.p = 0.045).A total of 392 (87.1%) responses were received. High HIV and reproductive health knowledge levels were recorded (77.7%) on our scale with females recording higher levels (81.1%) than males (71.1%). The majority of participants (72%) indicated willingness to abstain from risky behaviours such as use of drugs and attending youth sex parties. However about 33.3% of the participants who had sexual intercourse reported having condomless sex. There was marginal association between high HIV and reproductive health knowledge levels and accessing health care services in the past 24 months (HIV and reproductive health knowledge levels were relatively high among adolescents and were associated with accessing health care services in the past 24 months. There however are some gaps associated with engaging in risky sexual behaviours such as condomless sex which could be addressed by using these findings to assist organizations working with adolescents, educators and policy makers in developing programmes that address adolescent sexual behaviours. Efforts aimed at ending HIV infections require that people regularly visit health care institutions for services such as HIV testing. Grassroot Soccer Zimbabwe (GRSZ) is an adolescent health organisation that uses the popularity of soccer to promote healthy behaviours. We assessed HIV knowledge levels, risky behaviours and attitudes in school going adolescents and young adults who attended GRSZ programmes and determined if HIV knowledge levels were associated with increased levels of accessing of health care services by youths. In this study we collected information from 450 individuals aged 13–30 years who had attended at least one of the three programmes offered by GRSZ. We collected information on demographics of the participants, their knowledge on HIV and reproductive health, sources of information, access to HIV and reproductive health services and attitudes and risky behaviours. A total of 392 (87.1%) responses were received. High HIV and reproductive health knowledge levels were recorded (77.7%) on our scale with females recording higher levels (81.1%) than males (71.1%). The majority of participants (72%) indicated willingness to abstain from risky behaviours such as use of drugs and attending youth sex parties. However about 33.3% of the participants who had sexual intercourse reported having condomless sex. Our results indicate that individuals who had sought health-care services in the past 24 months had higher HIV and reproductive health knowledge levels compared to those who had not. Participants indicated willingness to abstain from risky behaviours although some risky sexual practises such as condomless sex were reported indicating a need to address such gaps. The findings of the study may assist organizations working with adolescents, educators and policy makers in developing programmes that address adolescent needs aimed at improving their health and eradicating HIV.Adolescent girls and young women aged 15–24 years, who account for just 11% of the adult population, accounted for 20% of new HIV infections among adults globally in 2015 compared to 14% in young men of the same age group . AdditioGlobal co-operation and strategies are needed to end the HIV epidemic. In 2014, the United Nations programme on HIV/AIDS introduced a goal to end the AIDS epidemic by 2030 and a programme referred to as the 90–90-90 concept is part of the plan towards achieving this goal [Grassroot Soccer Zimbabwe (GRSZ) is an adolescent health organisation that uses the popularity of soccer to promote healthy behaviours and educate youth in areas such as HIV, healthy relationships, multiple partners, intergenerational sex, and gender based violence. Entertainment has been used as an educational tool for HIV intervention in other programmes . In GRSZIn this study we assessed HIV knowledge levels, behaviours and attitudes in school going adolescents and young adults who had attended GRSZ programmes and gauged the impact of such programmes as an HIV intervention method and vehicle for improving accessing of health care services among adolescents.The evaluation was conducted in Bulawayo where the schools that implemented the three SKILLZ programmes are located. Eleven 11) secondary schools that have participated in the GRSZ programmes were purposively selected for the evaluation exercise , education attainment goals and family type  and size (Number of siblings). Section B had 10 questions covering reproductive health and HIV transmission, prevention and treatment to measure HIV Knowledge levels. Participants were asked to indicate if each question was ‘True’, ‘False’ or ‘I don’t know’. Knowledge level score was categorized as ‘high’ for a score greater than 63% and ‘low’ for a score less than 63%. Section C asked questions on sources of information on HIV and puberty and accessing of health care services. Participants were asked the questions ‘Do you find it difficult or easy to talk to your parents about things that you consider important to you?’ and, ‘Have you ever discussed sex-related matters with your parents or guardian?’ They were then asked to indicate from a provided list in each case what had been important sources of information on puberty for them, which health care service providers they had accessed in the past 24 months and the services accessed. Section D measured attitudes and risky behaviours. Participants were asked to indicate the social activities they like attending or taking part in from a list that included the following: Youth sex parties, nightclubs, sporting activities and other activities that they had to specify. The next set of questions required participants to answer, ‘YES’ or ‘NO’ to the questions, ‘Do you ever drink alcohol?’, ‘Do you ever smoke cigarettes or take other drugs such as marijuana (mbanje) and others?’, and ‘Have you ever had sexual intercourse?’. Participants who indicated ‘YES’ to ever had sexual intercourse were to respond to further questions covering age at first sexual intercourse, age of sexual partners, last time they had had sexual intercourse and protection method used against infections and pregnancy. Self-efficacy to abstain from sexual intercourse was assessed by asking the question, ‘What are your reasons for not having intercourse?’ and to choose a statement that best describes their future plans about sexual intercourse. Lastly participants were to indicate if they, ‘strongly agree’, ‘agree’, ‘disagree’ or ‘strongly disagree’ with the following statements: ‘It is OK for people my age to have sex with different partners’, ‘Condoms should be used if a person my age is having sex’, ‘Engaging in sexual intercourse at my age makes me popular’ and ‘There is nothing wrong with unmarried boys and girls having sexual intercourse if they love each other’.The outcome variables were: HIV and reproductive health knowledge levels recorded as high or low, Sources of information on HIV and puberty as a categorical variable, Health care services accessed in the past 24 months measured as categorical variable and Attitudes and risky behaviours measured as a binary variable. These were measured against Sex, age, family type and the level of education participants expected to reach as independent variables. Univariate analysis was conducted to come up with frequencies and proportions for categorical variables. Bivariate analysis was done to test associations between demographic characteristics and knowledge levels and also between access to health care services and knowledge levels.Ethical approval was obtained from the Medical Research Council of Zimbabwe (Ref. A/2226). Additional approvals were obtained from the Ministry of Education and the participating schools. Informed consent was obtained from all the adolescents and their parents. The questionnaire was completed privately and did not contain any personally identifiable information.A total of 392 responses were received from 450 questionnaires distributed, a response rate of 87.1%. The majority of respondents were female (76.3%) and most respondents belonged to the 15–19 years age group (78.3%). Table The school teacher was the most frequently picked source of information on puberty (62.2%) and GRSZ was the third most frequently picked source (55.9%). Health facility was also included in the list and about a quarter of the respondents (24.5%) picked it as an important source of information on puberty. Parents were cited as important sources of information by 66.2% of the respondents with the majority of participants in Generation SKILLZ (57.9%) and SKILLZ street (61.6%) reporting that it was easy for them to talk to parents about issues that are important to them.The clinic was the health service provider that was most frequently visited by respondents from Generation SKILLZ and SKILLZ Street programmes (28.5 and 39.5% respectively) while GRSZ boot camp provided health care services for 48% of participants from SKILLZ holiday Fig. . Voluntaχ2 =3.19, p = 0.07), family type as categorized in Table χ2 =3.0, p = 0.40) and age of the participants . HIV and reproductive health knowledge levels were however associated with accessing health care services in the past 24 months (p = 0.045).HIV and reproductive health knowledge levels were ‘high’ for 77.7% of the participants. More females (81.1%) had higher knowledge of HIV and reproductive behaviour than males (71.1%). Among participants categorized as having ‘low’ HIV and reproductive health knowledge levels, siblings staying alone constituted the highest proportion (41.7%). We wanted to know if there was an association between participants’ knowledge levels and demographic variables measured. The test of association between ‘knowledge level of HIV and reproductive health’ and the variables was as follows: Participants’ sex (χ2 (df = 1) = 13.78, p-value = 0.001) with boys more likely to report condom use than females. Only one participant from the 15–19 age group reported that she had sexual intercourse with a man 10+ years older than her and there were 15 participants, 4 males and 11 females, who had their first sexual encounter before the age of 15 years.The majority of participants 72%) demonstrated willingness to abstain from risky activities such as youth sexual parties (known as Vuzu parties) and also reported abstaining from drugs and alcohol. Figure % demonstMost participants also showed a positive attitude against risky sexual behaviours . They did not support the opinion of having multiple sexual partners and supported condom use if sexually active. However, males and females differed on whether it was appropriate or not for boys and girls to have sexual intercourse if they love each other with the majority of boys (55%) agreeing or strongly agreeing with the statement.We report on HIV and reproductive health knowledge, attitudes and risky behaviours among adolescents and young adults in Bulawayo Zimbabwe. A self-administered questionnaire was used to gather information on participants’ knowledge levels on HIV and reproductive health related issues, their sources of information on puberty and access to HIV and reproductive health services. The questionnaire also covered attitudes and risky behaviours that may lead to acquisition of HIV and STIs including unwanted pregnancies and knowledge on methods of prevention. High HIV and reproductive health knowledge levels were recorded on our scale. It must however be noted that there are various other organizations offering programmes on HIV and reproductive health and targeting the same participants as GRSZ. A number of studies on HIV knowledge, reproductive health, risky behaviours and suggested interventions among adolescents in various parts of Zimbabwe have been reported over the years but challenges still persist –13. StudAlthough a large number of respondents indicated that it was easy for them to talk to their parents/guardians about things that are important to them, e.g. up to 61.6% for SKILLZ Street, our data indicates that there is need for the communication to include sexual and reproduction health issues. We noted that among those who find it easy to talk to their parents, sex related topics were not discussed and the school teacher was the major source of information on puberty. One study in Cameroon also reported that 66.4% of youth aged 13–24 obtained their information on HIV from school programmes . A studyThere was an association between HIV and reproductive health knowledge levels and accessing health care services. The majority of participants visited health care services for HIV testing and medical male circumcision. This may indicate that intensifying HIV and reproductive health education can lead to more adolescents visiting health care institutions to access HIV testing services. Many people are reluctant to access HIV testing services with the UNAIDS reporting that approximately 40% of people living with HIV do not know their status .The majority of participants demonstrated willingness to abstain from risky behaviours and had knowledge of the consequences of such risky behaviours although some risky sexual practises such as condomless sex were reported indicating a need to address such gaps. Intergenerational sexual relationships among our participants were low. This practice can contribute to the spread of HIV and other STIs –25 as yoThere were however some limitations to the study. Firstly, because of the SKILLZ street programme which only recruits girls, the majority of participants were girls which affected analysis and sex-disaggregation of findings. Although the self-administered questionnaire allowed participants to respond anonymously, there may have been reluctance to respond to questions that directly required answers on sexual behaviour resulting in high percentage on non-responders to this issue. As the sampling was non-random, the findings may not be representative of the population being studied.HIV and reproductive health knowledge was associated with accessing health care services in the past 24 months. Intensification of HIV and reproductive health education to adolescents using youth friendly strategies such as soccer may therefore be used as a way of increasing accessing of health care services including HIV testing and voluntary medical male circumcision. There however were some gaps associated with engaging in risky sexual behaviours such as condomless sex which could be addressed by using these findings to assist organizations working with adolescents, educators and policy makers in developing programmes that address adolescent sexual behaviours. Some suggested strategies include integration of HIV and adolescents health care delivery and the use of outreach as an option for HIV testing among adolescents.Additional file 1. Participant questionnaire: Grassrootsoccer Zimbabwe (GRS ZW) SKILLZ programmes evaluation. Description of data: Questionnaire


Callithrix jaccus, is a platyrrhine primate species that has provided much insight into studies of the primate placenta, maternal condition, and metabolic programming, yet the relationships between maternal weight and placental DNAm are unknown. Here, we report genome‐wide DNAm from term marmoset placentas using reduced representation bisulfite sequencing. We identified 74 genes whose DNAm pattern is associated with maternal weight during gestation. These genes are predominantly involved in energy metabolism and homeostasis, including the regulation of glycolytic and lipid metabolic processes pathways.Accumulating evidence suggests that dysregulation of placental DNA methylation (DNAm) is a mechanism linking maternal weight during pregnancy to metabolic programming outcomes. The common marmoset,  Current model demonstrating the potential role of placental DNA methylation (DNAm) in developmental programming of obesity. Maternal weight influences ovulation number and is related to placental DNAm patterns in gene pathways involved in energy metabolism and homeostasis. Downstream effects of altered DNAm in these pathways likely leads to physiological adaptations in the fetus with consequences for long‐term metabolic health. The placental DNA methylation (DNAm) landscape of the marmoset placenta presents unique differences and similarities with human placental methylation patterns.Maternal weight is associated with placental DNAm in genes that are predominantly involved in energy metabolism and homeostasis.The impact of altered placental DNAm on placental function and development may also contribute to the potential role of placental DNAm in developmental programming in the marmoset monkey. As a major regulator of fetal development in utero, the placenta is responsive to both maternal and fetal needs as well as limits. In addition to the immediate purpose that the placenta serves in utero, we now understand that the placenta plays a role in the developmental origins of health and disease. Variation in maternal health  alters placental function and regulation of fetal development in ways that affect offspring health outcomes later in life  is an ideal non‐human primate candidate in which to explore placental DNAm in the context of maternal weight. Our group has demonstrated that the litter size that a mother carries is related to her weight at the time of ovulation  in San Antonio, TX, and the Barshop Institute for Longevity and Aging Studies at the University of Texas Health Science Center at San Antonio. Data and placental tissue were collected from 10 adult female marmoset monkeys that were enrolled in an ongoing project assessing longitudinal and intergenerational effects of maternal development on reproductive outcomes. Between 2012 and 2015, each marmoset female reproduced one to two times per year resulting in data and placental tissue available from a total of 17 pregnancies, produced by a total of 10 dams. Prior, during, and following pregnancy, dams were fed a commercial marmoset diet in ad libitum quantities. All animal procedures, husbandry, and housing comply with the American Society of Primatologists Principles for the Ethical Treatment of Non‐Human Primates and were reviewed and approved by Institutional Animal Care and Use Committees at the University of Illinois at Chicago, Texas Biomedical Research Foundation, and the University of Texas Health Science Center San Antonio.2.2Upon detection of pregnancy via ultrasound, estimated gestational age was determined using previously established growth curves . The tissue samples were immediately placed in RNase‐free tubes with 5 ml of RNAlater  and stored at −80° C until further processing.Delivery was not induced in this sample and gestational age and delivery dates were estimated based on growth curves as done in previous work . All reagents and equipment in the manufacturer's protocol were followed with the addition of RNase A digestion to yield RNA‐free genomic DNA. Genomic DNA was quantified using two dsDNA assay methods: Quant‐iT Picogreen  and Qubit System . The quality of the DNA was further assessed through gel electrophoresis.2.6MspI which is a methylation insensitive restriction enzyme that recognizes CCGG sites. As MspI is insensitive to methylation status, all CCGG sites were cut between the two C's resulting in small fragments with a high frequency of potential CpG methylation sites. Following MspI digestion, the fragments underwent adaptor ligation, final repair, bisulfite conversion, and polymerase chain reaction (PCR) amplification to produce the final libraries for sequencing. The five pools were sequenced on five lanes in the HiSeq 4000  with paired‐end reads 100 nt in length. Trimming was performed using Python scripts provided by NuGen to remove low‐quality bases, adaptor sequences, and the sequence diversity provided by the NuGEN RRBS adaptor. The trimmed bisulfite sequence was then aligned to the marmoset genome  using the bwa‐meth package in R which uses bwa‐mem to perform the alignment  was performed on 100 ng of genomic DNA input at the Roy J. Carver Biotechnology Center at the University of Illinois in Urbana, IL, using Ovation RRBS Methyl‐Seq System 1–16 . The 34 samples were randomly assigned to five lanes and the samples were run in five pools, four lanes with seven samples and one lane with six samples. RRBS uses 2.7All analyses were conducted using R (version 3.3.2) and RStudio (version 1.0.136) with packages available through CRAN and Bioconductor. Each placenta was treated independently given that previous work by our group has demonstrated high within‐subject variability in litter size and placental phenotypic characteristics from pregnancy to pregnancy ; M = β/(1−β) . It is important to note that enrichment does not mean an overall category or its constitutive genes are hypermethylated or hypomethylated; it does not imply directionality relative to maternal weight category. Adjustment for multiple comparisons was done using the Benjamini–Hochberg method with an FDR < 0.05.Although methylation can occur and be detected at non‐CpG sites  through RRBS, only CpG sites were evaluated in this study. For inclusion in analyses, we required CpG sites to have the counts from at least 75% of the samples with at least one sample to have greater than 20 counts. Using the methylation count data, ); M = β/−β (Du et33.1n = 8). Total litter weight increased with respect to litter size, and average infant weight for the sample was 29.64 g. Maternal weight was assessed at three different time points throughout gestation: (a) gestational Day 60 (42% of term); (b) gestational Day 90 (63% of term); and (c) gestational Day 120 (84% of term). The sample demonstrated a wide range in maternal weight at each time point, however, as expected, mean maternal weight increased throughout gestation. Quintuplet pregnancies are a rare occurrence and when the one quintuplet pregnancy that occurred in this sample was removed from analyses, maternal weight was significantly correlated with litter weight at each gestational time point , as well as with litter size at gestational Day 120 .Maternal, placental, and infant characteristics are presented in Table 3.2M‐value of −7 represents completely unmethylated CpG sites, an M‐value of 7 represents completely methylated CpG sites, and an M‐value of zero represents hemimethylated CpG sites . The sequencing read data and distribution of DNAm demonstrate a slight negative skew with a higher proportion demonstrating M‐values greater than zero. Sixty‐five percent of CpG sites had an M‐value greater than zero with 12% of CpG sites demonstrating complete methylation.After applying our inclusion criteria to RRBS data from 17 placental samples, a total of 15,397,706 CpG sites were included. This corresponds to 18,208 marmoset gene IDs and 11,555 unique gene names. Table S1 summarizes the sequencing reads obtained per CpG site and per sample. The distribution of DNAm across all CpG sites is shown in Figure DNAm within gene regions was calculated using the reads that were aligned within the ±3‐kb region of the transcription start site . The general pattern observed was that DNAm decreased in the upstream region as it approached the TSS. DNAm was lowest at the TSS and increased as the downstream distance from the TSS increased. In this study, 0.06% of CpG sites captured were located at a TSS and 32.97% were within the promoter region.Completely methylated and completely unmethylated CpGs were compared within (<3 kb) and outside (≥3 kb) the promoter region to explore any patterns in the occurrence of completely methylated and completely unmethylated CpG sites in the marmoset placenta. Figure 3.3p < .05, FDR 0.05), unique gene identifiers, and unique gene names for each maternal weight predictor are shown in Figure regulation of glycolytic processes , carnitine shuttle , regulation of carbohydrate catabolic processes , and regulation of lipid metabolic processes .The number of significant CpG sites (44.1M‐values greater than zero, suggesting that marmoset placentas may be more globally methylated at CpG sites than human placentas.In humans and other mammals, the placenta is a globally hypomethylated organ (reviewed in Schroeder et al., While the present study captured a higher extent of genome‐wide DNAm than expected, the pattern of methylation in the marmoset placenta may be similar to the human placenta in that hypomethylation is not uniform across the entire placental genome (Robinson & Price, Both marmoset and human demonstrate low levels of methylation within gene promoter regions and higher levels of DNAm outside of promoters. Our data suggest that the greater extent of DNAm outside the promoter in marmosets may be due to differences in CpG site density between the two genomes. It has yet to be explored whether or not the higher levels of DNAm outside the gene promoters contribute to functional changes that are specific to marmoset placentas. Yet, it is likely that the lower levels of methylation that occur within gene promoter regions of the marmoset placenta lead to similar patterns of increased transcription and expression that are characteristic of the mammalian placenta (Novakovic et al., 4.2An important and biologically significant aspect of our results in the marmoset is that heavier marmosets exhibit metabolic alterations such as increased fasting glucose, hemoglobin A1C, triglycerides, and very low‐density lipoproteins (Tardif et al., regulation of glycolytic processes and regulation of carbohydrate catabolic processes pathway will be of particular interest in future studies given that glucose is the primary substrate that the placenta uses to generate energy for growth and development of the fetoplacental unit. Future studies exploring placental DNAm in a multilevel context inclusive of gene and protein expression as well as nutrient consumption and disposition will contribute to a better understanding of how the maternal metabolic milieu influences the metabolic dynamics of the marmoset placenta through placental DNAm of genes within the regulation of glycolytic processes and regulation of carbohydrate catabolic processes pathways.The placenta is a metabolically active tissue that conducts significant nutrient uptake from the maternal circulation. For example, in the human placenta, 50% of the glucose taken up from maternal circulation is metabolized via glycolysis to serve the metabolic needs of the placenta Illsley, . The mat4.3We've previously reported on the developmental programming outcomes and placental phenotypic differences that are observed in the marmoset based on litter size (reviewed in Riesche et al., Our results here demonstrate that one way in which the placenta may negotiate higher fetal demand and lower relative maternal energetic supply in larger marmoset mothers is through placental DNA methylation in genes and gene pathways involved in supplying glucose and lipids to the fetus. The consequences of alterations in these pathways may influence fetal growth and development in ways that impact the health trajectories of offspring born to larger litters and are likely involved in the health disparities observed between offspring from different litter sizes Figure . Recent 4.4We assumed that the marmoset genome acts similarly to the human genome in the orchestration and execution of biological processes and that DNAm has the same impacts on gene transcription and expression as is known in other species. Considering the phylogenetic similarities and shared sequence homology among primates it is likely that these similarities do exist, however, further studies will be necessary to rule out evolutionary differences and variants that may impact the dynamics of the marmoset genome and DNAm. For example, marmosets differ from humans in their type of maternal‐placental pattern of interdigitation with trabecular and villous interdigitations, respectively Mossman, . To thatAs this is the first study to report genome‐wide DNAm in the marmoset monkey, many avenues are now open for further elucidating the epigenetic characteristics and mechanisms of the marmoset placenta. These avenues, which are beyond the scope of this current study, include exploring how directional changes in DNAm relate to gene and protein expression as well as overall functional changes in metabolic and energetic pathways within the placenta. Another exciting avenue which we are situated to begin exploring is what the associations between maternal weight and placental DNAm mean for fetal development and offspring outcomes. As with the current hypothesis that parturition is governed by the balance between maternal and fetal metabolism (Dunsworth, Warrener, Deacon, Ellison, & Pontzer, The authors declare that there are no conflict of interests.https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE143200.This article has earned an Open Data badge for making publicly available the digitally‐shareable data necessary to reproduce the reported results. The data is available at Supporting informationClick here for additional data file.


Self‐reported questionnaire and clinical assessments.N = 417) and older people (N = 74) completed the modified Quality of Care from a Patient Perspective instrument and person‐related items. Older people's oral health status was clinically assessed using the Revised Oral Assessment Guide. Data were analysed using descriptive and analytic statistics. The data were collected from 2013–2016.Nursing staff (Nursing staff's perceptions of humanity aspects of oral care quality were related to gender, work role and care environment. Older people's perceptions of humanity aspects of oral care quality were related to self‐reported physical health. Nursing staff in short‐term care units perceived the subjective importance of humanity aspects of oral care quality higher compared with older people in short‐term care units. An STC unit is a form of intermediate care concerned with a person's transition between hospital and home , county hospitals  and local hospitals .RNs have an overall responsibility for ensuring quality nursing care in STC units and ICUs  all agreed to participate in the study. Table All older people admitted to the selected 23 STC units and another nine STC units in the 19 municipalities were eligible for study participation. The inclusion criteria were ≥65 years of age, having stayed 3 days or more in an STC unit, being dependent on help with oral care, understanding Swedish and having a health status—as estimated by the responsible RN in each STC unit—that allowed for participation and the ability to answer the questionnaire. A total of 74 out of 391 older people fulfilled the inclusion criteria, and they (The study part concerning older people and nursing staff in STC units was based on data from a larger research project (SOFIA) whose aim was to explore different aspects related to oral health in older people staying in STC units  in STC units and nurse managers or RNs appointed by nurse managers in ICUs gave information verbally to the nursing staff. Each nursing staff member was given a questionnaire with an addressed and prepaid envelope. Along with the questionnaire, nursing staff received written information about the study. Completed questionnaires in STC units were returned to the responsible researcher in the SOFIA project, and completed questionnaires in ICUs were returned to the first author (MA).Quality of Care from a Patient Perspective (QPP) questionnaire  and subjective oral care importance (SI). Each item's PR described how nursing staff and older people experienced various oral care aspects and thus reported their perceptions of actual care. Each item's SI described how important nursing staff and older people considered various aspects of oral care to be and thus reported their preferences.The PR items were responded to on a four‐point Likert‐type scale as one , two (partly agree), three (agree) and four (completely agree). The SI items were responded as one (little or no importance), two (quite high importance), three (high importance) and four (very high importance). Each PR and SI item also had a “non‐applicable” response  . Older people's person‐related conditions were assessed by age, gender, education, self‐reported physical health, oral health condition, psychological well‐being and assessment of oral health status using the 4.6Humanity aspects of oral care quality including the QPP dimensions ID and SC, person‐related conditions and care environments were examined with descriptive statistics.t test was used when comparing two groups. One‐way analysis of variance (ANOVA) was used when comparing three groups. Statistically significant interactions in the ANOVA were followed by Tukey's test for post hoc comparisons to analyse differences in mean values between groups  were involved, the alpha level was adjusted to p < .10 . The Regional Ethical Review Board in Uppsala, Sweden, approved the study for STC units (Dnr 2013/100) and for ICUs (Dnr 2015/457).55.15.1.1The mean age of the nursing staff was 47 years. Most participants (96%) were women, 60% were ENs, and 63% of the nursing staff worked in STC units Table .5.1.2The mean age of the older people was 84 years, and 61% were male. In terms of education status, 71% had compulsory school as their highest level of education. The older people's self‐reported physical health conditions varied, with 43% reporting that they had good or very good physical health and 42% reporting that they had poor or very poor physical health. Fifty‐nine per cent of older people reported that their oral health was good to very good, despite the fact that 70% of them were clinically assessed to have moderate oral health problems and 30% to have severe oral health problems. Good‐to‐very good psychological well‐being was reported by 54% and poor‐to‐very poor psychological well‐being by 30%  were interpreted as optimal oral care quality, and PR scores of not agree to partly agree (<3) were interpreted as suboptimal oral care quality. SI scores of high or very high importance (≥3) were interpreted as high subjective importance for oral care quality, and SI scores of little or no importance (<3) were interpreted as low importance for oral care quality.5.2.1Most (91%) of nursing staff scored optimal oral care quality (PR) on the QPP dimension ID and on the PR item related to respect towards older people/patients in connection with oral care. Respect was also the item that 96% perceived as having high SI for oral care quality. The highest proportion (68%) of nursing staff scored suboptimal oral care quality (PR) on the QPP dimension ID and on the PR item concerning best possible oral care information. Providing the patient/older person with the opportunity to participate in oral care was the item most commonly scored (21%) by the nursing staff to have low SI for oral care quality.Fifty‐four per cent of nursing staff perceived optimal oral care quality (PR) on the QPP dimension SC and on the PR item concerning determination of oral care based on older people's needs and requests. Eighty‐six per cent perceived that this was of high SI for oral care quality Table .The range “non‐applicable” responses in PR and SI scales for nursing staff, were mostly between on to four, except items related to information and participation. The item information had 23 “non‐applicable” responses in PR and 17 “non‐applicable responses” in SI. The item participation had 29 “non‐applicable” responses in PR and 23 “non‐applicable” responses in SI.5.2.2On the QPP dimension ID and the PR item concerning respect, 88% of older people reported optimal oral care quality (PR) and 90% perceived respect to have high SI for oral care quality. Sixty‐one per cent of older people perceived suboptimal oral care quality (PR) concerning PR item best possible oral care information, and 46% perceived such information to have low SI for oral care quality.On the QPP dimension SC and the PR item concerning determination of oral care based on their needs and requests, 46% of older persons reported optimal oral care quality (PR) and 68% perceived that this was of high SI for oral care quality Table . No “non5.3The SI on the QPP dimension ID was statistically significantly higher among women, ENs and nursing staff working in STC units compared with men, RNs and those working in ICUs. There were no statistically significant differences for nursing staff's perceptions of PR on the QPP dimension ID in relation to age, gender, work role or care environment.The QPP dimension SC's PR and SI mean values were statistically significantly higher among ENs compared with RNs. The SI mean value in the dimension was also statistically significantly higher among nursing staff working in STC units compared with nursing staff working in ICUs. There were no statistically significant differences in the QPP dimension SC's PR mean value in relation to age, gender or care environment or in the SI mean value in relation to age or gender Table .p = .065) compared with older people with a self‐reported physical health condition of neither good nor poor who scored a SI mean value of 2.40 (1.17) (not shown in table).On the QPP dimension SC, older people with a self‐reported physical health condition  of good to very good scored a SI mean value of 3.10 (0.77), which was statistically significantly higher  and SC (PR and SI) in relation to age, gender and education showed no statistically significant differences. There were also no statistically significant differences between the QPP dimension's PR and SI in relation to self‐reported physical health, oral health condition or psychological well‐being (not shown in table).5.4The mean values for SI in humanity aspects of oral care quality, including QPP dimension ID and SC, were statistically significantly higher among nursing staff compared with older people. For PR, no statistically significant differences were found in humanity aspects of oral care quality between nursing staff and older people in STC units Table .66.1Perceptions of humanity aspects of oral care quality including QPP dimensions ID and SC  showed that women and ENs and those working in STC units scored the humanity aspects of oral care quality, including both PR and SI, higher compared with men, RNs and those working in ICUs.Intensive care is primarily aimed to saving lives, and the application of life‐sustaining technology, advanced treatment and close observations (Marshall et al., Participation in their nursing care has been shown to make the patients feel better and to start to believe in their recovery (Karlsson et al., Identity‐oriented aspects such as participation and information might decrease fear and insecurity and improve the recovery process for patients in ICUs (Wassenaar, Schouten, & Schoonhoven, In the present study, ENs scored humanity aspects of oral care quality as more important compared with RNs. This might be because ENs in STC units, in contrast to the RNs in STC units, are more frequently involved in direct care for older people (Etherton‐Beer et al., 6.2Older people scored the humanity aspects of oral care quality to be suboptimal in terms of both PR and SI. Older people with higher self‐reported physical health considered it more important that oral care was based on their own needs and preferences compared with those with lower self‐reported physical health.Previous studies have shown that older patients' preferences for involvement in decision‐making differ and that some of them prefer a more active role than others (Kiselev, Suija, Oona, Mellenthin, & Steinhagen‐Thiessen, 6.3The comparison between nursing staff and older people's perceptions showed differences in SI of humanity aspects where nursing staff scored the SI of humanity aspects of oral care quality higher compared with older people.The humanity aspect of oral care quality was perceived by nursing staff and older people to be suboptimal. Information is important to be able to participate, and information might help older people to perceive themselves as being involved in their own care (Xie, Wang, Feldman, & Zhou, 6.4It should be noted that the selected person‐related conditions in the present study did not cover all aspects; for example, culture, socioeconomics or nursing staff's education in oral health and the care environment only covered the type of unit. Care environment aspects of interest could have been, for example, number of RNs in the units, how nursing care was organized, how many beds in the units and average length of patients/older people stay in the units.All nursing staff and older people who met the inclusion criteria were invited to participate, and the response rate for nursing staff was 51%. Due to incomplete data about nursing staff's person‐related conditions in STC units, no analysis of dropouts could be performed. There might be several reasons why nursing staff in this study chose not to participate. For example, high workloads might have had a negative impact on participants' ability to answer the questionnaire, or participants might have considered the study subject to not be relevant to them (Morton, Bandara, Robinson, & Atatoa Carr, There were a greater number of STC units where older people participated in the study than the number of STC units where nursing staff participated. The explanation for this is that the nursing staff worked in more than one STC unit, but they indicated the unit where they spent most of their working time.The internal consistency of the modified version of QPP was acceptable. The modification of the questionnaire is based on a selection of items from the short version of QPP (Wilde Larsson & Larsson, More nursing staff in ICUs than nursing staff in STC units gave “non‐applicable” responses about information and participation. An explanation might be that the nursing staff in ICUs might not see active patient participation as possible because of patients' life‐threatening health conditions.Responsible RNs in each STC unit decided which older people to ask to participate based on their health status and their ability to answer the questionnaire. The RNs might have had somewhat different views of an older person's health condition, and according to Polit and Beck , this isThe self‐reported questionnaire might have been challenging for older people with limited functional capacity. If necessary, the research assistants helped older people by filling in the questionnaire based on the person's answers to each item. This could have influenced older people's oral care quality perceptions (Wilde Larsson, Statistically significant differences are mainly dependent on the number of participants and larger samples have smaller samplings errors, but in quantification of differences, it is important to distinguish clinical significance from statistical significance (Angst, Aeschlimann, & Angst, Statistical significance, however, does not guarantee that results will have clinical significance, and for drawing conclusions about clinical significance at group levels, values might be stipulated Polit, . In the In the present study, there were several statistical significances between participants' perceptions of humanity aspects of oral care quality and person‐related conditions. Despite small differences in several mean scores, the results might be considered as clinically relevant. The knowledge of the variation in participants' perceptions according to person‐related conditions might help RNs and ENs to be aware of older people needing special attention, thereby enhancing provision of person‐centred care. The awareness of differences might also increase the commitment for improving oral care because according to Stelson, Hille, Eseonu, and Doolen , the nurThe ICU represented different sizes in four different regions, and the STC units represented municipalities from both densely and sparsely populated regions in Sweden. Perception variations about humanity aspects of oral care quality might be considered representative to nursing staff and make the present results generalizable to similar staffing arrangements. Participating older people in the present study represent a variety of reasons for being admitted to STC units. Common for the older people is that they all share the temporary need for oral care. The distribution of the older people among the different STC units was between 1–8 participants per STC units and might reflect older people who receive STC in Sweden and their perceptions about humanity aspects of oral care quality.7Despite differences between and within organizations of oral care across ICUs and STC units, all healthcare services should deliver oral care according to older people's needs and preferences. Most nursing staff perceived that insufficient attention was given to humanity aspects of oral care that they felt was important. However, they might not be able to convert intentions into practice unless the older person asks for it. It seems that nursing staff provide optimal oral care that to a higher degree acknowledges the needs and preferences of older people with higher self‐reported physical health. They might not always provide optimal quality oral care for older people with declining health conditions.The authors declare no conflict of interest.


Brown carbon (BrC) is an organic aerosol material that preferentially absorbs light of shorter wavelengths. Global‐scale radiative impacts of BrC have been difficult to assess due to the lack of BrC observational data. To address this, aerosol filters were continuously collected with near pole‐to‐pole latitudinal coverage over the Pacific and Atlantic basins in three seasons as part of the Atmospheric Tomography Mission. BrC chromophores in filter extracts were measured. We find that globally, BrC was highly spatially heterogeneous, mostly detected in air masses that had been transported from regions of extensive biomass burning. We calculate the average direct radiative effect due to BrC absorption accounted for approximately 7% to 48% of the top of the atmosphere clear‐sky instantaneous forcing by all absorbing carbonaceous aerosols in the remote atmosphere, indicating that BrC from biomass burning is an important component of the global radiative balance. Globally, biomass burning is a large source of light‐absorbing carbonaceous aerosol that directly affect the planetary radiation balanceTransported over long distances, brown carbon is a significant component of these aerosols, but its contribution was highly variableBrown carbon contributed up to 48% of average clear‐sky instantaneous forcing by light absorption by carbonaceous aerosols Other modeling studies that included both bleaching and the added effect of BrC enhancement relative to BC with increasing altitude  in past studies treated OA as wholly nonabsorbing  DC‐8 aircraft conducted research flights nearly pole to pole along the central Pacific (north to south) and Atlantic (south to north) Oceans at altitudes systematically alternating from near surface 180 m) to ~13 km above sea level over four deployments, one in each season  was determined by three times the standard deviation of field blank filters, combining all blanks from a given deployment Table .  dissolved in solution, not the absorption of suspended particulate. This technique was used since it exclusively measures BrC optical properties (BC is not included), resulting in a highly sensitive approach required for this remote atmosphere study; however, when used for analysis of filters, the main limitation is blank variability, as noted above. Past studies, based on measured BrC aerosol size distributions and Mie theory, indicate that a multiplication factor of 1.8 to 2.1  can be used to estimate the light absorption by aerosol particles based on measurements of chromophores in the bulk liquid extracts  content of individual particles was measured with a single particle soot photometer (SP2). Integrated BC concentrations have been adjusted to account for accumulation‐mode BC outside of the SP2's detection size range . Fires of FRP greater than 100 MW are only included in the analysis. Air mass transport time from fire emissions to the point of aircraft sampling was estimated based on HYSPLIT back trajectories from the sampling location to the nearest FIRMS‐identified wildfire intersected by the trajectory. Type of fuel, or other variables that may affect emissions, were not considered. More details are provided in the Air mass 72‐hr back trajectories were computed using the Hybrid Single‐Particle Lagrangian Integrated Trajectory (HYSPLIT) analysis method   and an AAE value of 5 , was used to compute absorption at all wavelengths  model  for WS BrC to aerosol absorption at a wavelength of 405 nm, consistent with the factor of 4 here, considering uncertainly  DRE due to only scattering, (2) DRE due to scattering and BC absorption, and (3) DRE due to scattering, BC absorption, and BrC absorption. We estimated the DRE of BC by subtracting (1) from (2), and the DRE of BrC by subtracting (2) from (3). More model details are provided in the 33.1BrC measured in ATom‐2, ATom‐3, and ATom‐4 is shown in Figure In the tropical or mid‐Atlantic region, enhanced levels of WS BrC were recorded in all three missions. FIRMS‐identified wildfires and back trajectories suggest that the BrC source for this region was either fires in South America or Africa. In ATom‐2 (January–February), most fires were in equatorial regions in northern South America and Africa, coinciding with the dry period for these regions (January–April). These measurements accounted for a majority of the observed BrC above LOD for the complete ATom‐2 mission. During ATom‐3 (September–October), the fires in South America were found further south, following the movement of dryer regions southward, dictated by the annual movement of the Inter‐Tropical Convergence Zone. Compared to ATom‐2, the wildfires were also more extensive in ATom‐3 in terms of both fire density and radiative power (FRP). In the last mission, ATom‐4 (April–May), the extent of fires in these regions decreased to the lowest levels relative to the ATom‐2 and ATom‐3 missions. Levels of BrC recorded in the mid‐Atlantic tracked these seasonal trends.For the North Pacific Basin in Figure As can be seen in Figure 3.2Correlations provide further evidence that the BrC was associated with mainly biomass burning. Biomass burning emits BC and BrC, although there are differences in emissions rates depending on fuel and burning temperature, and how these species may be altered with atmospheric age. More BrC is emitted per fuel burned in smoldering compared to flaming fires  and between K+BB versus BC (see Table +BB). The trend was also seen in BrC and the PALMS estimate of biomass burning particle mass ; the correlation was weaker in ATom‐3 (0.75) and lowest in ATom‐4 (0.53). A similar, although somewhat stronger correlation trend, was found for BrC versus estimated biomass burning potassium , that measurable amounts of BrC were associated with tracers of smoke such as BC, potassium, and PALMS single particle composition. Such smoke contained variable amounts of BrC, which was often detected great distances from the burning regions , persisting for more than 3 days following emissions. This BrC made a significant contribution to the overall absorption by carbonaceous aerosols and the top of atmospheric DRE; however, the spatial distribution of the BrC forcing was highly heterogeneous.Supporting Information S1Click here for additional data file.


The latency of the swallowing reflex is an important factor causing dysphagia in head and neck cancer patients. Although there are many reports comparing voluntary swallowing function before and after treatment, few studies have focused on the latency of the swallowing reflex, which is a risk factor for pneumonia due to silent aspiration. The aim of this retrospective study was to clarify the changes in the latency of the swallowing reflex before and after treatment.The latency of the swallowing reflex was quantified using the time from the injection of 1 ml of distilled water into the pharynx through a nasal catheter to the onset of swallowing.The latency time of the swallowing reflex was significantly decreased 3 months after treatment compared to before treatment. A significant reduction was also observed in patients with pharyngeal cancer who underwent chemoradiation therapy.This retrospective study showed that a delayed swallowing reflex improved with treatment in advanced head and neck cancer patients.2014–1-274).The Institutional Review Board of Tohoku University Hospital (Number  Advanced head and neck cancer and its treatment cause swallowing disorders that reduce patients’ quality of life and decrease survival , 2. The This retrospective study was performed in accordance with the Helsinki Declaration and approved by The Institutional Review Board of Tohoku University Hospital (Number 2014–1-274). All patients who received treatment, including surgery and radiation therapy with or without chemotherapy, for advanced head and neck cancer and whose latency of the swallowing reflex was assessed both before and 3 months after treatment at the Department of Otolaryngology-Head and Neck Surgery of Tohoku University Hospital between April 2014 and March 2019 were included. Patients who underwent total laryngectomy at the same time or had recurrence within 3 month after treatment were excluded. The assessments were done at 3 month after completion of adjuvant treatment in patients who received post-operative therapy. In this study, 116 patients have received treatment for advanced head and neck cancer with laryngeal preservation, of which 73 patients have assessed the latency of the swallowing reflex before treatment. Finally, 53 patients have received the assessment both before and after treatment. Assessment of the latency of the swallowing reflex was performed before flexible endoscopic evaluation of swallowing, which was performed as standard practice for all patients with advanced head and neck cancer after they provided their written, informed consent.Individual latency time of the swallowing reflex was assessed before and 3 months after treatment. The swallowing reflex was induced by a bolus injection of 1 ml of distilled water into the pharynx through an 8-Fr nasal catheter. Before injection, the catheter was positioned below the soft palate. The subjects were unaware of the actual injection. Swallowing was identified by visual observation of characteristic laryngeal movement. The latency of the swallowing reflex was quantified using the time from the injection to the onset of swallowing, and the average of 3 measurements was used in the analysis . Accordit-test, Wilcoxon rank-sum test, or Fisher’s exact test. Values are presented as means ± SD.Differences were evaluated for significance using the paired A total of 53 patients (37 men and 16 women) were enrolled in this study, with an age range of 18–82 (median 65) years. The characteristics of the patients are shown in Table p = 0.012, paired t-test, Fig. p = 0.0073, Fisher’s exact test, Fig. To evaluate whether the treatment of head and neck cancer changes the swallowing reflex, the latency time of the swallowing reflex was compared before and 3 months after treatment. The latency time of the swallowing reflex was significantly decreased at 3 months after treatment (1.91 ± 0.61 s) compared to before treatment  and the pharynx (n = 25), which was further subdivided into oropharynx (n = 17) and hypopharynx (n = 8). Whereas there was no significant difference between before and 3 months after treatment in patients with the cancers of the oral cavity , a significant reduction of the latency time of the swallowing reflex was observed in patients with cancers of the pharynx , whereas a significant reduction was observed in patients with cancers of the pharynx  and those treated with chemoradiation (n = 22). Patients who underwent both surgery and chemoradiation (n = 6) and those who underwent radiation without chemotherapy (n = 2) were excluded because of their small numbers. Whereas there was no significant difference between before and 3 months after treatment in the patients who underwent surgery , significant reduction of the latency time of the swallowing reflex was observed in the patients who underwent chemoradiation , whereas a significant reduction was observed in the patients who underwent chemoradiation . This is thought to be because oral food intake is affected by many factors other than the latency of the swallowing reflex, such as prophylactic nutrition tube placement, xerostomia, and dysgeusia . Second,This retrospective study showed that a delayed swallowing reflex improved after treatment in advanced head and neck cancer patients.


As the population ages, clinicians will encounter a growing number of nonagenarians suffering from severe aortic stenosis who may be candidates for transcatheter aortic valve replacement (TAVR). By virtue of a healthy survivor effect or a referral bias, these patients may paradoxically have greater resilience and fewer comorbidities than their octogenarian counterparts. They tend to, on average, tolerate the TAVR procedure quite well with low in‐hospital and 1‐year mortality rates of 5.5% and 23%, respectively. Appropriate patient selection should consider individualized estimates of procedural risk, potential for functional recovery and for improved quantity and quality of life. Frailty is much more revealing than chronological age, and it can be measured by brief tools such as the Essential Frailty Toolset. Ultimately, the process of shared decision‐making is paramount to ensure that the course of action is patient‐centered and balances the procedure's expected risks and benefits with the nonagenarian's preferences and values. However, a “healthy survivor” effect has been observed whereby nonagenarians—by virtue of their achieved survival—have paradoxically lower rates of comorbidities. Still, most nonagenarians with severe AS will likely have at least one significant comorbidity. In a Spanish study of nonagenarians with severe AS managed both with TAVR and conservatively, the most common comorbidity was chronic kidney disease, which was present in 70% of the cohort.Frailty, defined as a diminished capability to recover from pathological or iatrogenic stressors due to cumulative age‐related impairments, is a key consideration in nonagenarians. Impairments may be broadly categorized as physical , cognitive, and psychosocial. Numerous scales have been developed to operationalize the assessment of these impairments, with the prevalence and prognostic impact of frailty varying non‐negligibly depending on the scale used. The FRAILTY‐AVR study was conducted to compare the value of seven different frailty scales in >1000 patients 70 to 99 years of age undergoing transcatheter or surgical aortic valve replacement. In this study, the Essential Frailty Toolset (EFT) was found to be most predictive of 1‐year mortality  and worsening disability .Several age‐related cardiac impairments have been described in nonagenarians.3The evidence for TAVR in nonagenarians stems primarily from cohort studies and case series   or those in lower‐volume centers may be less encouraging. Thirdly, objective measures of frailty were not consistently reported or systematically used to guide patient selection. Frailty may be especially useful in this subgroup of patients given the expected dissimilarity in risks‐to‐benefits for frail 90‐year‐olds as compared to robust 90‐year‐olds. Notwithstanding these limitations, we can conclude that TAVR is a safe and effective therapeutic option for many nonagenarians—if carefully selected.4http://riskcalc.sts.org/) was developed for SAVR but is still appropriately used as a benchmark to stratify candidates for TAVR.http://tools.acc.org/TAVRRisk/). Absolute complication rates remain low on average, and comorbidity‐complication dyads may be more telling to guide decisions, that is, chronic kidney disease and risk of acute kidney injury, protruding aortic atheroma and risk of stroke, bulky aortic valve calcification and risk of coronary occlusion, peripheral arterial disease and risk of vascular complications—particularly if femoral access is not feasible. Escalation of procedural complexity  is not trivial in nonagenarians and can materially shift the delicate balance of risks.Selecting the appropriate nonagenarian for TAVR involves forecasting short‐term risks, mid‐term recovery, and long‐term benefits of the procedure. In the short‐term, is the patient at risk for a major procedural complication? The STS Risk calculator . Functional capacity can and should be objectively assessed with the 6‐minute walk test.In the long‐term, is the patient likely to benefit from the implanted TAVR in terms of both quantity and quality of life? Irrespective of the technical success of the TAVR procedure, attributes that may preclude any improvement in functional capacity include: Once the information for forecasting risks and benefits has been acquired and analyzed, the clinician can better present the therapeutic options to the patient and assist them in reaching an informed decision that is in‐line with their preferences and values5Despite appropriate selection and technical execution, 30%‐40% of older patients report persistently poor functional status and quality of life following TAVR—especially frail older patients who were deconditioned before and increasingly‐so after the procedure. Therefore, frailty should not only be viewed as a prognostic marker, but also a therapeutic target than can be improved with exercise and nutrition, ideally in the context of a structured cardiac rehabilitation program.6As the population ages, clinicians will encounter a growing number of nonagenarians suffering from severe AS. By virtue of a healthy survivor effect , these patients can paradoxically have greater resilience and fewer comorbidities. They can, on average, tolerate the TAVR procedure quite well with low in‐hospital and 1‐year adverse event rates; acknowledging that this subgroup of patients is under‐represented or at the very least highly selected in randomized trials, and that the evidence to‐date stems mostly from observational studies. Appropriate patient selection should consider individualized estimates of procedural risk, potential for functional recovery and for improved quantity and quality of life. Age alone is inadequate to stratify patients. Frailty is much more revealing, and it can be measured by brief tools such as the EFT, and in selected cases by deeper evaluations such as that offered by a comprehensive geriatric assessment. Ultimately, the process of shared decision‐making is paramount to ensure that the course of action is patient‐centered and balances the procedure's expected risks and benefits with the nonagenarian's preferences and values.The authors declare no potential conflict of interests.