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The Hierarchical Taxonomy of Psychopathology (HiTOP) has emerged out of the quantitative approach to psychiatric nosology. This approach identifies psychopathology constructs based on patterns of co-variation among signs and symptoms. The initial HiTOP model, which was published in 2017, is based on a large literature that spans decades of research. HiTOP is a living model that undergoes revision as new data become available. Here we discuss advantages and practical considerations of using this system in psychiatric practice and research. We especially highlight limitations of HiTOP and ongoing efforts to address them. We describe differences and similarities between HiTOP and existing diagnostic systems. Next, we review the types of evidence that informed development of HiTOP, including populations in which it has been studied and data on its validity. The paper also describes how HiTOP can facilitate research on genetic and environmental causes of psychopathology as well as the search for neurobiologic mechanisms and novel treatments. Furthermore, we consider implications for public health programs and prevention of mental disorders. We also review data on clinical utility and illustrate clinical application of HiTOP. Importantly, the model is based on measures and practices that are already used widely in clinical settings. HiTOP offers a way to organize and formalize these techniques. This model already can contribute to progress in psychiatry and complement traditional nosologies. Moreover, HiTOP seeks to facilitate research on linkages between phenotypes and biological processes, which may enable construction of a system that encompasses both biomarkers and precise clinical description.
The incidence of scarlet fever has increased dramatically in recent years in Chongqing, China, but there has no effective method to forecast it. This study aimed to develop a forecasting model of the incidence of scarlet fever using a seasonal autoregressive integrated moving average (SARIMA) model. Monthly scarlet fever data between 2011 and 2019 in Chongqing, China were retrieved from the Notifiable Infectious Disease Surveillance System. From 2011 to 2019, a total of 5073 scarlet fever cases were reported in Chongqing, the male-to-female ratio was 1.44:1, children aged 3–9 years old accounted for 81.86% of the cases, while 42.70 and 42.58% of the reported cases were students and kindergarten children, respectively. The data from 2011 to 2018 were used to fit a SARIMA model and data in 2019 were used to validate the model. The normalised Bayesian information criterion (BIC), the coefficient of determination (R2) and the root mean squared error (RMSE) were used to evaluate the goodness-of-fit of the fitted model. The optimal SARIMA model was identified as (3, 1, 3) (3, 1, 0)12. The RMSE and mean absolute per cent error (MAPE) were used to assess the accuracy of the model. The RMSE and MAPE of the predicted values were 19.40 and 0.25 respectively, indicating that the predicted values matched the observed values reasonably well. Taken together, the SARIMA model could be employed to forecast scarlet fever incidence trend, providing support for scarlet fever control and prevention.
Patients on dialysis are at high risk for severe COVID-19 and associated morbidity and mortality. We examined the humoral response to SARS-CoV-2 mRNA vaccine BNT162b2 in a maintenance dialysis population.
Design:
Single-center cohort study.
Setting and participants:
Adult maintenance dialysis patients at 3 outpatient dialysis units of a large academic center.
Methods:
Participants were vaccinated with 2 doses of BNT162b2, 3 weeks apart. We assessed anti–SARS-CoV-2 spike antibodies (anti-S) ∼4–7 weeks after the second dose and evaluated risk factors associated with insufficient response. Definitions of antibody response are as follows: nonresponse (anti-S level, <50 AU/mL), low response (anti-S level, 50–839 AU/mL), and sufficient response (anti-S level, ≥840 AU/mL).
Results:
Among the 173 participants who received 2 vaccine doses, the median age was 60 years (range, 28–88), 53.2% were men, 85% were of Black race, 86% were on in-center hemodialysis and 14% were on peritoneal dialysis. Also, 7 participants (4%) had no response, 27 (15.6%) had a low response, and 139 (80.3%) had a sufficient antibody response. In multivariable analysis, factors significantly associated with insufficient antibody response included end-stage renal disease comorbidity index score ≥5 and absence of prior hepatitis B vaccination response.
Conclusions:
Although most of our study participants seroconverted after 2 doses of BNT162b2, 20% of our cohort did not achieve sufficient humoral response. Our findings demonstrate the urgent need for a more effective vaccine strategy in this high-risk patient population and highlight the importance of ongoing preventative measures until protective immunity is achieved.
We explore experimentally whether axisymmetry breaking can be exploited for the open-loop control of a prototypical hydrodynamic oscillator, namely a low-density inertial jet exhibiting global self-excited axisymmetric oscillations. We find that when forced transversely or axially at a low amplitude, the jet always transitions first from a period-1 limit cycle to $\mathbb {T}^2$ quasiperiodicity via a Neimark–Sacker bifurcation. However, we find that the subsequent transition, from $\mathbb {T}^2$ quasiperiodicity to $1:1$ lock-in, depends on the spatial symmetry of the applied perturbations: axial forcing induces a saddle-node bifurcation at small detuning but an inverse Neimark–Sacker bifurcation at large detuning, whereas transverse forcing always induces an inverse Neimark–Sacker bifurcation irrespective of the detuning. Crucially, we find that only transverse forcing can enable both asynchronous and synchronous quenching of the natural mode to occur without resonant or non-resonant amplification of the forced mode, resulting in substantially lower values of the overall response amplitude across all detuning values. From this, we conclude that breaking the jet axisymmetry via transverse forcing is a more effective control strategy than preserving the jet axisymmetry via axial forcing. Finally, we show that the observed synchronization phenomena can be modelled qualitatively with just two forced coupled Van der Pol oscillators. The success of such a simple low-dimensional model in capturing the complex synchronization dynamics of a multi-modal hydrodynamic system opens up new opportunities for axisymmetry breaking to be exploited for the open-loop control of other globally unstable flows.
We perform a theoretical investigation of the instability of a helical vortex filament beneath a free surface in a semi-infinite ideal fluid. The focus is on the leading-order free-surface boundary effect upon the equilibrium form and instability of the vortex. This effect is characterised by the Froude number $F_r = U(gh^*)^{-{1}/{2}}$ where $g$ is gravity, and $U = \varGamma /(2{\rm \pi} b^*)$ with $\varGamma$ being the strength, $2{\rm \pi} b^*$ the pitch and $h^*$ the centre submergence of the helical vortex. In the case of $F_r \rightarrow 0$ corresponding to the presence of a rigid boundary, a new approximate equilibrium form is found if the vortex possesses a non-zero rotational velocity. Compared with the infinite fluid case (Widnall, J. Fluid Mech., vol. 54, no. 4, 1972, pp. 641–663), the vortex is destabilised (or stabilised) to relatively short- (or long-)wavelength sub-harmonic perturbations, but remains stable to super-harmonic perturbations. The wall-boundary effect becomes stronger for smaller helix angle and could dominate over the self-induced flow effect depending on the submergence. In the case of $F_r > 0$, we obtain the surface wave solution induced by the vortex in the context of linearised potential-flow theory. The wave elevation is unbounded when the $m$th wave mode becomes resonant as $F_r$ approaches the critical Froude numbers ${\mathcal {F}} (m) = (C_0^*/U)^{-1} (mh^*/b^*)^{-{1}/{2}}$, $m=1, 2, \ldots,$ where $C_0^*$ is the induced wave speed. We find that the new approximate equilibrium of the vortex exists if and only if $F_r < {\mathcal {F}}(1)$. Compared with the infinite fluid and $F_r \rightarrow 0$ cases, the wave effect causes the vortex to be destabilised to super-harmonic and long-wavelength sub-harmonic perturbations with generally faster growth rate for greater $F_r$ and smaller helix angle.
Chinese morphological awareness is conceptualized as a multidimensional construct but there is a lack of understanding of how its dimensions are related. Latent change score modeling was used to examine the bivariate relationships of two facets of oral morphological awareness, namely morpheme and structure awareness in Chinese children in grades one through three. Two hundred and three children in China completed morpheme (homonym awareness) and structure awareness (lexical compounding) tasks across the three grades (M = 6.66, SD = .30 at the first time point). Results indicated that growth in structure awareness was predicted in part by previous levels of morpheme awareness, suggesting that morpheme awareness leads the growth of structure awareness. Educational implications are discussed.
The spatio-temporal variation of leaf chlorophyll content is an important crop phenotypic trait that is of great significance for evaluating crop productivity. This study used a soil-plant analysis development (SPAD) chlorophyll meter for non-destructive monitoring of leaf chlorophyll dynamics to characterize the patterns of spatio-temporal variation in the nutritional status of maize (Zea mays L.) leaves under three nitrogen treatments in two cultivars. The results showed that nitrogen levels could affect the maximum leaf SPAD reading (SPADmax) and the duration of high SPAD reading. A rational model was used to measure the changes in SPAD readings over time in single leaves. This model was suitable for predicting the dynamics of the nutrient status for each leaf position under different nitrogen treatments, and model parameter values were position dependent. SPADmax at each leaf decreased with the reduction of nitrogen supply. Leaves at different positions in both cultivars responded differently to higher nitrogen rates. Lower leaves (8th–10th positions) were more sensitive than the other leaves in response to nitrogen. Monitoring the SPAD reading dynamic of lower leaves could accurately characterize and assess the nitrogen supply in plants. The lower leaves in nitrogen-deficient plants had a shorter duration of high SPAD readings compared to nitrogen-sufficient plants; this physiological mechanism should be studied further. In summary, the spatio-temporal variation of plant nitrogen status in maize was analysed to determine critical leaf positions for potentially assisting in the identification of appropriate agronomic management practices, such as the adjustment of nitrogen rates in late fertilization.
The epidemic of tuberculosis has posed a serious burden in Qinghai province, it is necessary to clarify the epidemiological characteristics and spatial-temporal distribution of TB for future prevention and control measures. We used descriptive epidemiological methods and spatial statistical analysis including spatial correlation and spatial-temporal analysis in this study. Furthermore, we applied an exponential smoothing model for TB epidemiological trend forecasting. Of 43 859 TB cases, the sex ratio was 1.27:1 (M:F), and the average annual TB registered incidence was 70.00/100 000 of 2009–2019. More cases were reported in March and April, and the worst TB stricken regions were the prefectures of Golog and Yushu. High TB registered incidences were seen in males, farmers and herdsmen, Tibetans, or elderly people. 7132 cases were intractable, which were recurrent, drug resistant, or co-infected with other infections. Three likely cases clusters with significant high risk were found by spatial-temporal scan on data of 2009–2019. The exponential smoothing winters' additive model was selected as the best-fitting model to forecast monthly TB cases in the future. This research indicated that TB in Qinghai is still a serious threaten to the local residents' health. Multi-departmental collaboration and funds special for TB treatments and control are still needed, and the exponential smoothing model is promising which could be applied for forecasting of TB epidemic trend in this high-altitude province.
Early-life stressful circumstances (i.e. childhood maltreatment) coupled with stressful events later in life increase the likelihood of subsequent depression. However, very few studies have been conducted to examine the specific and cumulative effects of these stressors in the development of depression. There is also a paucity of research that simultaneously considers the role of biological factors combined with psychosocial stressors in the aetiology of depression. Guided by the biopsychosocial model proposed by Engel, the present study aims to examine to what extent the experience of stressors across the lifespan is associated with depression while taking into account the role of genetic predispositions.
Methods
Data analysed were from the Social and Psychiatric Epidemiology Catchment Area of the Southwest of Montreal (ZEPSOM), a large-scale, longitudinal community-based cohort study. A total of 1351 participants with complete information on the lifetime diagnoses of depression over a 10-year follow-up period were included in the study. Stressful events across the lifespan were operationalised as specific, cumulative and latent profiles of stressful experiences. Latent profile analysis (LPA) was used to explore the clustering of studied stressors including childhood maltreatment, poor parent–child relationship, and stressful life events. A polygenetic risk score was calculated for each participant to provide information on genetic liability. Multivariate logistic regression was used to examine the association between specific, cumulative and latent profiles of stressors and subsequent depression.
Results
We found that different subtypes of childhood maltreatment, child–parent bonding and stressful life events predicted subsequent depression. Furthermore, a significant association between combined effects of cumulative stressful experiences and depression was found [odds ratio (OR) = 1.20, 95% confidence interval (CI): 1.12–1.28]. Three latent profiles of lifetime stressors were identified in the present study and named as ‘low-level of stress’ (75.1%), ‘moderate-level of stress’ (6.8%) and ‘high-level of stress’ (18.1%). Individuals with a ‘high-level of stress’ had a substantially higher risk of depression (OR = 1.80, 95% CI: 1.08–3.00) than the other two profiles after adjusting for genetic predispositions, socio-demographic characteristics, and health-related factors.
Conclusions
While controlling for genetic predispositions, the present study provides robust evidence to support the independent and cumulative as well as compositional effects of early- and later-on lifetime psychosocial stressors in the subsequent development of depression. Consequently, mental illness prevention and mental health promotion should target the occurrence of stressful events as well as build resilience in people so they can better cope with stress when it inevitably occurs.
Root-lesion nematodes (Pratylenchus spp.) are a group of economically important pathogens that have caused serious economic losses in many crops. In 2019, root-lesion nematodes were recovered from tomato (Solanum lycopersicum) root samples collected from Sichuan Province, People's Republic of China (PRC). Extracted nematodes were disinfected, and one individual female was cultured on a carrot disc for propagation at 25 °C by parthenogenesis and designated the SC isolate. Afterwards, the isolate was identified on the basis of morphometric and molecular markers. Both morphometric characters and molecular analysis of the internal transcribed spacer region gene (ITS) of ribosomal DNA, the D2-D3 expansion region of the 28S rDNA gene and the mitochondrial cytochrome oxidase I (mtDNA-COI) gene revealed that the species of root-lesion nematode was Pratylenchus scribneri. The Bayesian tree inferred from the ITS rDNA, 28S rDNA and mtDNA-COI gene sequences also showed that this isolate formed a highly supported clade with other P. scribneri isolates. The pathogenicity of the root-lesion nematode SC isolate on tomato was assessed, showing that tomato was a suitable host for P. scribneri. To the best of our knowledge, this is the first report of P. scribneri on tomato in Sichuan Province, PRC. These are also the first molecular data obtained from P. scribneri on tomato in the PRC, and the pathogenicity of P. scribneri to tomato was studied for the first time. This study provides scientific data for the detection, identification and control of tomato root-lesion nematode disease.
The groundbreaking, viewpoint theory of Merker et al. explains several properties of the conscious field, including why the observer cannot directly apprehend itself. We propose that viewpoint theory might also provide a progressive, constitutive marker of consciousness and shed light on why most of the contents of consciousness are encapsulated.
Adequate methods are urgently needed to guarantee the good practice of health technology assessment (HTA) for technologies with novel properties. The aim of the study was to construct a conceptual framework to help understand the innovation of HTA methods (IHTAM). The construction of the IHTAM framework was based on two scoping reviews, one on the current practice of innovating methods, that is existing HTA frameworks, and one on theoretical foundations for innovating methods outside the HTA discipline. Both aimed to identify and synthesize concepts of innovation (i.e., innovation processes and roles of stakeholders in innovation). Using these concepts, the framework was developed in iterative brainstorming sessions and subsequent discussions with representatives from various stakeholder groups. The framework was constructed based on twenty documents on innovating HTA frameworks and fourteen guidelines from three scientific disciplines. It includes a generic innovation process consisting of three phases (“Identification,” “Development,” and “Implementation”) and nine subphases. In the framework, three roles that HTA stakeholders can play in innovation (“Developers,” “Practitioners,” and “Beneficiaries”) are defined, and a process on how the stakeholders innovate HTA methods is included. The IHTAM framework visualizes systematically which elements and stakeholders are important to the development and implementation of novel HTA methods. The framework could be used by all stakeholders involved in HTA innovation to learn how to engage dynamically and collaborate effectively throughout the innovation process. HTA stakeholders in practice have welcomed the framework, though additional testing of its applicability and acceptance is essential.
The cosmic evolution of the chemical elements from the Big Bang to the present time is driven by nuclear fusion reactions inside stars and stellar explosions. A cycle of matter recurrently re-processes metal-enriched stellar ejecta into the next generation of stars. The study of cosmic nucleosynthesis and this matter cycle requires the understanding of the physics of nuclear reactions, of the conditions at which the nuclear reactions are activated inside the stars and stellar explosions, of the stellar ejection mechanisms through winds and explosions, and of the transport of the ejecta towards the next cycle, from hot plasma to cold, star-forming gas. Due to the long timescales of stellar evolution, and because of the infrequent occurrence of stellar explosions, observational studies are challenging, as they have biases in time and space as well as different sensitivities related to the various astronomical methods. Here, we describe in detail the astrophysical and nuclear-physical processes involved in creating two radioactive isotopes useful in such studies,
$^{26}\mathrm{Al}$
and
$^{60}\mathrm{Fe}$
. Due to their radioactive lifetime of the order of a million years, these isotopes are suitable to characterise simultaneously the processes of nuclear fusion reactions and of interstellar transport. We describe and discuss the nuclear reactions involved in the production and destruction of
$^{26}\mathrm{Al}$
and
$^{60}\mathrm{Fe}$
, the key characteristics of the stellar sites of their nucleosynthesis and their interstellar journey after ejection from the nucleosynthesis sites. This allows us to connect the theoretical astrophysical aspects to the variety of astronomical messengers presented here, from stardust and cosmic-ray composition measurements, through observation of
$\gamma$
rays produced by radioactivity, to material deposited in deep-sea ocean crusts and to the inferred composition of the first solids that have formed in the Solar System. We show that considering measurements of the isotopic ratio of
$^{26}\mathrm{Al}$
to
$^{60}\mathrm{Fe}$
eliminate some of the unknowns when interpreting astronomical results, and discuss the lessons learned from these two isotopes on cosmic chemical evolution. This review paper has emerged from an ISSI-BJ Team project in 2017–2019, bringing together nuclear physicists, astronomers, and astrophysicists in this inter-disciplinary discussion.
To describe the cumulative seroprevalence of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) antibodies during the coronavirus disease 2019 (COVID-19) pandemic among employees of a large pediatric healthcare system.
Design, setting, and participants:
Prospective observational cohort study open to adult employees at the Children’s Hospital of Philadelphia, conducted April 20–December 17, 2020.
Methods:
Employees were recruited starting with high-risk exposure groups, utilizing e-mails, flyers, and announcements at virtual town hall meetings. At baseline, 1 month, 2 months, and 6 months, participants reported occupational and community exposures and gave a blood sample for SARS-CoV-2 antibody measurement by enzyme-linked immunosorbent assays (ELISAs). A post hoc Cox proportional hazards regression model was performed to identify factors associated with increased risk for seropositivity.
Results:
In total, 1,740 employees were enrolled. At 6 months, the cumulative seroprevalence was 5.3%, which was below estimated community point seroprevalence. Seroprevalence was 5.8% among employees who provided direct care and was 3.4% among employees who did not perform direct patient care. Most participants who were seropositive at baseline remained positive at follow-up assessments. In a post hoc analysis, direct patient care (hazard ratio [HR], 1.95; 95% confidence interval [CI], 1.03–3.68), Black race (HR, 2.70; 95% CI, 1.24–5.87), and exposure to a confirmed case in a nonhealthcare setting (HR, 4.32; 95% CI, 2.71–6.88) were associated with statistically significant increased risk for seropositivity.
Conclusions:
Employee SARS-CoV-2 seroprevalence rates remained below the point-prevalence rates of the surrounding community. Provision of direct patient care, Black race, and exposure to a confirmed case in a nonhealthcare setting conferred increased risk. These data can inform occupational protection measures to maximize protection of employees within the workplace during future COVID-19 waves or other epidemics.
Background: Standardized magnetic resonance imaging (MRI) guidelines published in 2015 by the Europoean MAGNIMS group and in 2016 by the CMSC are important for the diagnosis and monitoring of patients with multiple sclerosis (MS) and for the appropriate use of MRI in routine clinical practice. Methods: Two panels of experts convened to update existing guidelines for a standardized MRI protocol. The MAGNIMS panel convened in Graz, Austria in April 2019. The CMSC NAIMS panel met separately and independently in Newark, USA in October 2019. Subsequently, the MAGNIMS, NAIMS, and CMSC working groups combined their efforts to reach an international consensus Results: The revised guidelines on MRI in MS merges recommendations from MAGNIMS, CMSC, and NAIMS to improve the use of MRI for diagnosis, prognosis and monitoring of individuals with MS. 3D acquisitions are emphasized for optimal comparison over time. Core brain sequences include a 3D-T2wFLAIR for lesion identification and monitoring treatment effectiveness. Gadolinium-based contrast is recommended for diagnostic studies and judicious use for routine monitoring of MS patients. DWI sequences are recommended for PML safety monitoring. Conclusions: The international consensus guidelines strive for global acceptance of a useful and usable standard of care for patients with MS.
Background: The goal of the study was to assess responder rates at various times after initiating atogepant treatment. Methods: A 12-week phase 3 trial evaluated the safety, efficacy, and tolerability of atogepant for preventive treatment of migraine (ADVANCE; NCT03777059) in adult participants with a ≥1-year history of migraine, experiencing 4-14 migraine days/month. Participants were randomized to atogepant 10, 30, or 60mg, or placebo once daily. These analyses evaluated ≥25%, ≥50%, ≥75%, and 100% reductions in mean monthly migraine days (MMDs) across 12 weeks and each 4-week interval. Adverse events (AEs) in ≥5% of participants are reported. Results: The efficacy analysis population included 873 participants: placebo: n=214; atogepant: 10mg: n=214; 30mg: n=223; 60mg: n=222. Atogepant-treated participants were more likely to experience a ≥50% reduction in the 3-month mean MMDs (56-61% vs 29% with placebo; P<0.0001). The proportions of participants experiencing ≥25%, ≥50%, ≥75%, and 100% reductions in mean MMDs significantly increased during each 4-week interval (≥50% reduction: 48-71% vs 27-47% with placebo). The most common AEs for atogepant were constipation (6.9-7.7%) and nausea (4.4-6.1%). Conclusions: Once-daily atogepant 10, 30, and 60mg significantly increased responder rates at all thresholds with approximately 60% achieving a ≥50% reduction in mean MMDs at 12 weeks.
South-east Asia's diverse coastal wetlands, which span natural mudflats and mangroves to man-made salt pans, offer critical habitat for many migratory waterbird species in the East Asian–Australasian Flyway. Species dependent on these wetlands include nearly the entire population of the Critically Endangered spoon-billed sandpiper Calidris pygmaea and the Endangered spotted greenshank Tringa guttifer, and significant populations of several other globally threatened and declining species. Presently, more than 50 coastal Important Bird and Biodiversity Areas (IBAs) in the region (7.4% of all South-east Asian IBAs) support at least one threatened migratory species. However, recent studies continue to reveal major knowledge gaps on the distribution of migratory waterbirds and important wetland sites along South-east Asia's vast coastline, including undiscovered and potential IBAs. Alongside this, there are critical gaps in the representation of coastal wetlands across the protected area networks of many countries in this region (e.g. Viet Nam, Indonesia, Malaysia), hindering effective conservation. Although a better understanding of the value of coastal wetlands to people and their importance to migratory species is necessary, governments and other stakeholders need to do more to strengthen the conservation of these ecosystems by improving protected area coverage, habitat restoration, and coastal governance and management. This must be underpinned by the judicious use of evidence-based approaches, including satellite-tracking of migratory birds, ecological research and ground surveys.
To describe outcomes of acute coronavirus disease 2019 in paediatric and young adult patients with underlying cardiac disease and evaluate the association between cardiac risk factors and hospitalisation.
Study design
We conducted a retrospective single-institution review of patients with known cardiac disease and positive severe acute respiratory syndrome coronavirus 2 RT-PCR from 1 March, 2020 to 30 November, 2020. Extracardiac comorbidities and cardiac risk factors were compared between those admitted for coronavirus disease 2019 illness and the rest of the cohort using univariate analysis.
Results
Forty-two patients with a mean age of 7.7 ± 6.7 years were identified. Six were 18 years of age or more with the oldest being 22 years of age. Seventy-six percent were Hispanic. The most common cardiac diagnoses were repaired cyanotic (n = 7, 16.6%) and palliated single ventricle (n = 7, 16.6%) congenital heart disease. Fourteen patients (33.3%) had underlying syndromes or chromosomal anomalies, nine (21%) had chronic pulmonary disease and eight (19%) were immunosuppressed. Nineteen patients (47.6%) reported no symptoms. Sixteen (38.1%) reported only mild symptoms. Six patients (14.3%) were admitted to the hospital for acute coronavirus disease 2019 illness. Noncardiac comorbidities were associated with an increased risk of hospitalisation (p = 0.02), particularly chronic pulmonary disease (p = 0.01) and baseline supplemental oxygen requirement (p = 0.007). None of the single ventricle patients who tested positive required admission.
Conclusions
Hospitalisations for coronavirus disease 2019 were rare among children and young adults with underlying cardiac disease. Extracardiac comorbidities like pulmonary disease were associated with increased risk of hospitalisation while cardiac risk factors were not.