Recent Position Paper Research Articles

Provocations on iSchools and Librarianship: New Priorities for LIS Forward

ABSTRACTFor the last twenty years, the field of library and information science (LIS) has been evolving within the context of iSchools. Now, organizationally melded with other information fields, LIS is better positioned than ever to synergize expertise across disciplines to benefit librarianship. However, the recent LIS Forward position paper asserts that dynamics are changing within iSchools in ways that can strengthen or diminish LIS, surfacing critical tensions and issuing recommendations for the iSchool community. This panel assembles thought leaders to share new perspectives on the provocations of the position paper and to further advance the conversation with the ASIS&T community. The group will consider themes of diversification, competition, and identity and explore two urgent professional concerns—Black librarianship and AI. A moderated discussion will be documented to inform future engagement on charting directions, investments, and grand challenges for the field of LIS and the profession.

Impact of Tafamidis on Delaying Clinical, Functional, and Structural Cardiac Changes in Patients with Wild-Type Transthyretin Amyloid Cardiomyopathy.

Background: This study aimed to evaluate the effect of treatment with tafamidis on clinical, laboratory, functional, and structural cardiovascular imaging parameters at the 12-month follow-up timepoint in patients with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) and to assess the response to treatment in terms of disease progression. Methods: Patients with ATTRwt-CM undergoing treatment with tafamidis for >12 months were included. The patients underwent a comprehensive evaluation (including echocardiography, cardiac magnetic resonance imaging, six-minute walking test, assessment of quality of life, and laboratory tests) at baseline and the 12-month follow-up timepoint. Disease progression was assessed using a set of tools proposed by an international panel of experts, evaluating three main domains (clinical, biochemical, and structural). Results: The study cohort consisted of 25 patients (mean age of 75.9 ± 6.1 years, with 92% males). At the 12-month follow-up timepoint, an improvement in quality of life calculated with the KCCQ overall score (64 ± 20 vs. 75 ± 20, p = 0.002) and a reduction in pulmonary artery pressure (34 ± 10 mmHg vs. 30 ± 5 mmHg, p-value = 0.008) and in native T1 time were observed (1162 ± 66 ms vs. 1116 ± 52 ms, p-value = 0.001). Clinical, biochemical, and structural disease progression was observed in 6 (24%), 13 (52%), and 7 (28%) patients, respectively. Overall disease progression was observed in two patients (8%). Conclusions: This study described the impact of tafamidis treatment on clinical, laboratory, and functional parameters. Disease progression, assessed using a multiparametric tool recommended by a recent position paper of experts, was observed in a minority of patients.

Symptoms and management of cow's milk allergy: perception and evidence.

The diagnosis and management of cow's milk allergy (CMA) is a topic of debate and controversy. Our aim was to compare the opinions of expert groups from the Middle East (n = 14) and the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) (n = 13). These Expert groups voted on statements that were developed by the ESPGHAN group and published in a recent position paper. The voting outcome was compared. Overall, there was consensus amongst both groups of experts. Experts agreed that symptoms of crying, irritability and colic, as single manifestation, are not suggestive of CMA. They agreed that amino-acid based formula (AAF) should be reserved for severe cases (e.g., malnutrition and anaphylaxis) and that there is insufficient evidence to recommend a step-down approach. There was no unanimous consensus on the statement that a cow's milk based extensively hydrolysed formula (eHF) should be the first choice as a diagnostic elimination diet in mild/moderate cases. Although the statements regarding the role for hydrolysed rice formula as a diagnostic and therapeutic elimination diet were accepted, 3/27 disagreed. The votes regarding soy formula highlight the differences in opinion in the role of soy protein in CMA dietary treatment. Generally, soy-based formula is seldom available in the Middle-East region. All ESPGHAN experts agreed that there is insufficient evidence that the addition of probiotics, prebiotics and synbiotics increase the efficacy of elimination diets regarding CMA symptoms (despite other benefits such as decrease of infections and antibiotic intake), whereas 3/14 of the Middle East group thought there was sufficient evidence. Differences in voting are related to geographical, cultural and other conditions, such as cost and availability. This emphasizes the need to develop region-specific guidelines considering social and cultural conditions, and to perform further research in this area.

Exercise addiction in team sports: A systematic literature review.

While regular exercise should be part of the contemporary lifestyle, many people overindulge in it to the point of losing control over their behavior. This condition is known as exercise addiction (EA). Although addiction is an individual phenomenon, and most of the over 1,000 published studies on EA look at individual exercisers, there are studies on team sports athletes, too. Theoretically, these athletes should not manifest exercise addiction, but some studies are projecting the contrary. Therefore, in this literature review, we analyze EA in team athletes. Based on four databases (PsycINFO, SPORTDiscus, Web of Science, and Google Scholar), we located 22 articles conforming to inclusion criteria. These studies suggest a high risk of exercise addiction among team sports participants. While the figures are lower than for individual exercisers, they are in discord with the concept of addiction as a dysfunction, and the lack of a single case of exercise addiction reported (to date) in team sports athletes in the academic literature. In agreement with a recent position paper, we conclude that there are substantial conceptual and measurement errors in exercise addiction research.

Almost 1 in 2 patients with acute coronary syndrome are extremely high-risk and potential candidates for in-hospital triple lipid-lowering therapy: data from the CALLINICUS-Hellas Registry

Abstract Introduction The great heterogeneity of acute coronary syndrome (ACS) patients in the risk for cardiovascular events recurrence, prompted a recent position paper endorsed by the International Lipid Expert Panel to propose criteria, i.e. coexistence of multivessel coronary artery disease (CAD), polyvascular disease, heterozygous familial hypercholesterolemia (heFH), diabetes mellitus (DM) with estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 and/or lipoprotein (a) [Lp(a)] >50 mg/dL etc., which define the extremely high-risk ACS patients for whom an low-density lipoprotein cholesterol (LDL-C) <40 mg/dL was proposed. Purpose To estimate the proportion of patients with ACS that fulfill the criteria of the extremely high-risk group and are potential candidates for "extremely" intensive early lipid-lowering therapy (LLT) aiming at an LDL-C <40 mg/dL. Methods We recruited 780 consecutive patients with ACS who were participants of the CALLINICUS-Hellas Registry which is a prospective multicenter observational study that explores the adherence to LLT, the achievement of LDL-C targets and the cardiovascular events at 6- and 24-months after hospital discharge of patients with ACS. Results The prevalence of high risk components was: heFH 13.5%, multivessel CAD 44%, polyvascular disease 3.2%,and DM with eGFR <60 ml/min/1.73 m2 and/or Lp(a) >50 mg/dL 8.1%. By excluding the overlapping between these conditions, 430 ACS patients (55.1%) had at least one of the characteristics which define the extremely high-risk patients (Figure). Presuming a 65% LDL-C reduction of the levels (the pretreatment if on LLT prior admission or the admission if not on prior LLT) of the extremely high-risk ACS patients by taking a maximum dual LLT (intense statin plus ezetimibe), 312 patients, i.e., 40% of all initially recruited patients would fail to achieve an LDL-C <40 mg/dL suggesting that they require additional LLT, namely, a proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i). Conclusions Almost 1 in 2 patients with ACS have extremely high-risk characteristics and are candidates for in-hospital triple LLT (statin plus ezetimibe plus PCSK9i) aiming at an LDL-C <40 mg/dL, a strategy shown to improve plaque stability and possibly to reduce the recurrence rate of early coronary events.Figure

Advancing LIS in iSchools: Building a Coalition To Ensure a Vibrant Future

ABSTRACTThe LIS Forward initiative is addressing the urgent question: As LIS evolves within the context of iSchools, how do we best position our research and education programs to lead the field and the future of libraries? The initiative stems from the recognition that the evolution of iSchools presents opportunities and challenges for LIS and that there is great value in iSchools working together on charting directions forward. The growing coalition of iSchools is working to support LIS in taking full advantage of the multidisciplinary knowledge and expertise within iSchools, foster future leaders who will champion LIS within iSchools, and confront the dynamic tensions in research intensive iSchools. This session aims to engage international, professional, and academic stakeholders to guide activities and coalition building that can continue to strengthen LIS in iSchools. A panel will present highlights from a recent position paper to catalyze interactive, facilitated dialogue within the ASIS&T community on critical issues in LIS research and education. Breakout sessions will generate responses and recommendations to advance collaborative planning and strategy of value to LIS academic programs and the profession.

Incidence of clinical atrial fibrillation and related complications using a screening algorithm at a nationwide level.

In a recent position paper, the European Heart Rhythm Association (EHRA) proposed an algorithm for the screening and management of arrhythmias using digital devices. In patients with prior stroke, a systematic screening approach for atrial fibrillation (AF) should always be implemented, preferably immediately after the event. Patients with increasing age and with specific cardiovascular or non-cardiovascular comorbidities are also deemed to be at higher risk. From a large nationwide database, the aim was to analyse AF incidence rates derived from this new EHRA algorithm. Using the French administrative hospital discharge database, all patients hospitalized in 2012 without a history of AF, and with at least a 5-year follow-up (FU) (or if they died earlier), were included. The yearly incidence of AF was calculated in each subgroup defined by the algorithm proposed by EHRA based on a history of previous stroke, increasing age, and eight comorbidities identified via International Classification of Diseases 10th Revision codes. Out of the 4526 104 patients included (mean age 58.9 ± 18.9 years, 64.5% women), 1% had a history of stroke. Among those with no history of stroke, 18% were aged 65-74 years and 21% were ≥75 years. During FU, 327 012 patients had an incidence of AF (yearly incidence 1.86% in the overall population). Implementation of the EHRA algorithm divided the population into six risk groups: patients with a history of stroke (group 1); patients > 75 years (group 2); patients aged 65-74 years with or without comorbidity (groups 3a and 3b); and patients < 65 years with or without comorbidity (groups 4a and 4b). The yearly incidences of AF were 4.58% per year (group 2), 6.21% per year (group 2), 3.50% per year (group 3a), 2.01% per year (group 3b), 1.23% per year (group 4a), and 0.35% per year (group 4b). In patients aged < 65 years, the annual incidence of AF increased progressively according to the number of comorbidities from 0.35% (no comorbidities) to 9.08% (eight comorbidities). For those aged 65-75 years, the same trend was observed, i.e. increasing from 2.01% (no comorbidities) to 11.47% (eight comorbidities). These findings at a nationwide scale confirm the relevance of the subgroups in the EHRA algorithm for identifying a higher risk of AF incidence, showing that older patients (>75 years, regardless of comorbidities) have a higher incidence of AF than those with prior ischaemic stroke. Further studies are needed to evaluate the usefulness of algorithm-based risk stratification strategies for AF screening and the impact of screening on major cardiovascular event rates.

Epilepsy with myoclonic absences: A case series

Epilepsy with myoclonic absences (EMA) is a very rare childhood generalized epilepsy syndrome (<1% of all generalized epilepsies) associated with frequent myoclonic absence seizures that was described in 1969 by Tassinari et al. [ [1] Tassinari C.A. Lyagoubi S. Santos V. et al. Study on spike and wave discharges in man. II. Clinical and electroencephalographic aspects of myoclonic absences. Rev Neurol. 1969; 121: 379-383 PubMed Google Scholar ]. Seizures are characterized by bilateral rhythmic jerks of the upper limbs, superimposed on tonic abduction of the arms [ [2] Bureau M. Tassinari C.A. Epilepsy with myoclonic absences. Brain Dev. 2005; 27: 178-184 Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar ]. Ictal EEG consists of 3-Hz generalized spike-and-wave complexes that are time-locked with the upper limb myoclonus, while the EMG generally shows myoclonic jerks followed by tonic contraction of both deltoids. These seizures differ from typical absences of childhood absence epilepsy, since myoclonic jerks are generally not seen in typical absences and, if present, are subtle and spare the arms. The lack of an atonic component also distinguishes these seizures from myoclonic-atonic seizures [ [3] Specchio N. Wirrell E.C. Scheffer I.E. et al. International league against epilepsy classification and definition of epilepsy syndromes with onset in childhood: position paper by the ILAE Task Force on Nosology and Definitions. Epilepsia. 2022; 63: 1398-1442 Crossref PubMed Scopus (46) Google Scholar ]. A recent position paper by the International League Against Epilepsy for the classification of epilepsy syndromes with onset in childhood retained EMA as an independent epilepsy syndrome and defined its diagnostic criteria [ [3] Specchio N. Wirrell E.C. Scheffer I.E. et al. International league against epilepsy classification and definition of epilepsy syndromes with onset in childhood: position paper by the ILAE Task Force on Nosology and Definitions. Epilepsia. 2022; 63: 1398-1442 Crossref PubMed Scopus (46) Google Scholar ]. The mandatory requirements are myoclonic absences as the predominant type of seizures, and regular 3 Hz generalized spike-and-wave complexes synchronous with myoclonus.

Modeling the impact of the new European Heart Rhythm Association algorithm for atrial fibrillation screening using new digital tools

In a recent position paper, the European Heart Rhythm Association (EHRA) of the ESC clarifies the use of digital devises to detect and manage arrhythmias. For patients with a prior stroke, a systematic screening approach for atrial fibrillation (AF) should always be implemented, preferably immediately after the event. As age is the most important risk factor for stroke, suggestions are based on age, with individuals at or above 75 deemed to be at highest risk. For younger individuals, screening might still be warranted based on their risk factors as per the CHA2DS2-VASc score, and in addition for individuals at higher risk such as patients with CKD (chronic kidney disease), COPD (chronic obstructive pulmonary disease), obesity and sleep apnoea. From the French administrative hospital discharge database (PMSI), the objective of our study was the modeling of the results in terms of incident AF according to this new algorithm. Yearly incidence of AF was calculated in subgroup of interest listed in the EHRA algorithm for adult patients seen in French hospitals in 2013 with at least 5-year FU (or dying earlier). AF and comorbidities were identified using ICD-10 codes. In 2013, 2,921,407 patients with no history of AF were seen in French hospitals and then had at least 5 years of follow-up. Among them, 1.4% had a history of stroke, 19.9% were aged 65–74 and 23.6% were ≥ 75 yo. There were 327,012 patients with incident AF during follow-up (yearly incidence 2.4% in the overall population). The yearly incidence of AF in each subgroup is presented on the Fig. 1 below. These results in a contemporary analysis at a nationwide level show the relevance of the suggested workflow by EHRA. Of note, patients aged > 75 (regardless of comorbidities) had a higher incidence of AF than those with prior ischemic stroke, a population for which implantable loop recorder is widely indicated for AF screening. Other studies are still needed to optimize the place of new digital tools for AF screening in patients seen in daily practice and above all to confirm their interest in reducing major cardiovascular events.

Reverse Takotsubo Stress Cardiomyopathy During Liver Transplantation

Reverse Takotsubo Stress Cardiomyopathy During Liver Transplantation

Applying Essential Public Health Functions in building health systems’ resilience globally

Abstract Background The COVID-19 pandemic has exposed Public Health system weaknesses due to chronic underinvestment in Public Health. In this context, Essential Public Health Functions (EPHFs) have been revitalized as an integrated, cost effective and sustainable approach to operationalising Public Health. The World Health Organization's recent position paper on building health systems resilience towards universal health coverage and health security recommended investing in EPHFs as a key mean for countries’ health systems recovery and transformation during COVID-19 and beyond. There is a need for conceptual and operational clarity of EPHFs to support countries to build back better, fairer and more resilient health systems. Methods A rapid review of peer-reviewed and grey literature regarding the EPHFs was conducted to identify different actors’ understandings of EPHFs and key lessons of applying the EPHFs at the global, regional and national levels, in order to identify the added value and key enablers to operationalising EPHFs. A crosswalk analysis of different authoritative lists of EPHFs was conducted to develop a common list of EPHFs as a reference for countries in response to Public Health challenges. Results A consolidated list of 12 EPHFs derived from the crosswalk analysis of different authoritative lists is presented, underpinning the consideration of health systems components and pressing health challenges. Six key enablers are identified from evidence and experience. These enablers are fundamental for countries to build holistic and strong Public Health capacities. Conclusions The EPHFs provide a clear and integrated framing to operationalise Public Health in countries that can be adapted to country contexts to build resilience. Health authorities and other Public Health stakeholders must seize the opportunity brought by COVID-19 recovery to continue advocating for and strengthening Public Health as a priority in health systems’ reconstruction and reform.

Hemimegalencephaly and Epileptic Encephalopathy Associated with a Variant of Uncertain Significance of the TRIO Gene

Objectives: Electrical status epilepticus during sleep (ESES) is a type of EEG pattern seen in children with childhood-onset epileptic seizures and cognitive, language and motor regression. ESES has been associated with different etiologies, with or without structural abnormalities of the brain. To replace the term “ESES”, the recent Position Paper of the ILAE Taskforce on Nosology and Definitions introduced the term Epileptic Encephalopathy with Spike-Wave Activity during Sleep (EE-SWAS), which represents an activation of epileptiform activity, typically 1.5-2.5 Hz during NREM sleep, in a previously normal child and leads to cognitive and motor regression. Pathogenic variants in the TRIO gene are associated with autosomal dominant mental retardation type 44 (MRD44), which is characterized by mildly delayed global development resulting in variable intellectual deficits, learning difficulties, and variable dysmorphic features mostly represented by facial asymmetry, microcephaly, abnormalities of the fingers, and dental anomalies. Materials and methods: We present the case of a 13-year-old girl with onset of atonic seizures at the age of 3 who had undergone different types of antiepileptic drug (AED) therapies and was seizure-free 4 years later. She had an acquired impaired cognitive status as well as hemimegalencephaly, multiple hypopigmented patches on her legs and a large patch of hypopigmentation on the left side of her face extending towards the scalp (Becker’s nevus), dental anomalies (gingival hyperplasia, ogival palate), periventricular gliosis and electroencephalographic and (EEG) findings consistent with SWAS. Outcomes: Genetic testing confirmed a heterozygous variant of uncertain significance (VUS) of the TRIO gene, possibly associated with autosomal dominant MRD44. Although our patient presented with some phenotypic similarities to MRD44, her cognitive impairment improved with control of the SWAS pattern and AED adjustments. Conclusion: Association of structural anomalies of white matter, hemimegalencephaly, and encephalopathy with SWAS and a VUS mutation of the TRIO gene might suggest a different genetic neurocutaneous syndrome altogether.

Boring Problems Are Sometimes the Most Interesting

Abstract In a recent position paper, Turing Award Winners Yoshua Bengio, Geoffrey Hinton, and Yann LeCun make the case that symbolic methods are not needed in AI and that, while there are still many issues to be resolved, AI will be solved using purely neural methods. In this piece I issue a challenge: Demonstrate that a purely neural approach to the problem of text normalization is possible. Various groups have tried, but so far nobody has eliminated the problem of unrecoverable errors, errors where, due to insufficient training data or faulty generalization, the system substitutes some other reading for the correct one. Solutions have been proposed that involve a marriage of traditional finite-state methods with neural models, but thus far nobody has shown that the problem can be solved using neural methods alone. Though text normalization is hardly an “exciting” problem, I argue that until one can solve “boring” problems like that using purely AI methods, one cannot claim that AI is a success.

The Pitfalls of the Ethical Continuum and its Application to Medical Aid in Dying

The Pitfalls of the Ethical Continuum and its Application to Medical Aid in Dying

Cortical Atrophy, White Matter Lesions, and Bulb Configuration in Patients with Idiopathic Olfactory Loss and Other Causes of Olfactory Loss

Introduction: While magnetic resonance imaging (MRI) is not included in the current guidelines for diagnosing olfactory disorders in the most recent position paper on olfactory dysfunction, both 1.5T and 3T MRI are commonly used in the diagnostic workup of many patients with olfactory loss. Often, MRI is used to rule out intracranial tumours, but other useful information may be obtained from MRI scans in these patients. The potential of MRI in olfactory loss depends on sufficient knowledge of structural changes in different aetiologies of olfactory loss. We present common clinical MRI findings in olfactory loss and evaluate the usefulness of structural integrity scores in differentiating between aetiologies. Methods: In this study, we investigated if white matter hyperintensities (WMHs, measured by Fazekas score), global cortical atrophy (GCA), and medial temporal lobe atrophy (MTA) are more common in patients with idiopathic olfactory loss than in patients with acquired olfactory loss due to other aetiologies. Furthermore, we compared olfactory bulb (OB) configurations in different olfactory loss aetiologies. Results: In 88 patients with olfactory loss, WMHs, GCA, and MTA were not more significant findings on MRI in idiopathic olfactory loss (n = 51) compared with other causes of acquired olfactory loss (Fazekas score p = 0.2977; GCA score p = 0.6748; MTA score p = 0.7851). Bulb configurations differed in patients suffering from post-traumatic olfactory loss and may aid in identifying the underlying aetiology in patients where trauma is among the suspected causes of olfactory loss. Conclusion: We recommend that structural MRI with an OB sequence is included in the diagnostic evaluation of olfactory loss with suspected congenital and post-traumatic aetiology and should be considered in idiopathic olfactory loss with suspected central aetiology (e.g., tumour).

Rationale and Design of the Efficacy of a Standardized Diuretic Protocol in Acute Heart Failure Study.

AimsAlthough acute heart failure (AHF) with volume overload is treated with loop diuretics, their dosing and type of administration are mainly based upon expert opinion. A recent position paper from the Heart Failure Association (HFA) proposed a step‐wise pharmacologic diuretic strategy to increase the diuretic response and to achieve rapid decongestion. However, no study has evaluated this protocol prospectively.Methods and resultsThe Efficacy of a Standardized Diuretic Protocol in Acute Heart Failure (ENACT‐HF) study is an international, multicentre, non‐randomized, open‐label, pragmatic study in AHF patients on chronic loop diuretic therapy, admitted to the hospital for intravenous loop diuretic therapy, aiming to enrol 500 patients. Inclusion criteria are as follows: at least one sign of volume overload (oedema, ascites, or pleural effusion), use ≥ 40 mg of furosemide or equivalent for >1 month, and a BNP > 250 ng/L or an N‐terminal pro‐B‐type natriuretic peptide > 1000 pg/L. The study is designed in two sequential phases. During Phase 1, all centres will treat consecutive patients according to the local standard of care. In the Phase 2 of the study, all centres will implement a standardized diuretic protocol in the next cohort of consecutive patients. The protocol is based upon the recently published HFA algorithm on diuretic use and starts with intravenous administration of two times the oral home dose. It includes early assessment of diuretic response with a spot urinary sodium measurement after 2 h and urine output after 6 h. Diuretics will be tailored further based upon these measurements. The study is powered for its primary endpoint of natriuresis after 1 day and will be able to detect a 15% difference with 80% power. Secondary endpoints are natriuresis and diuresis after 2 days, change in congestion score, change in weight, in‐hospital mortality, and length of hospitalization.ConclusionsThe ENACT‐HF study will investigate whether a step‐wise diuretic approach, based upon early assessment of urinary sodium and urine output as proposed by the HFA, is feasible and able to improve decongestion in AHF with volume overload.

O-140 Uterine septum: clinical implications on fertility and obstterics outcomes. A systematic review and meta-analysis

Abstract Study question How does the septate uterus and his metroplasty influence pregnancy rate (PR), live birth rate (LBR), spontaneous abortion rates (SA) and preterm labour rates (PL)? Summary answer Uterine septum is associated with a poor reproductive outcome. Metroplasty reduce the rate of SA but non-conclusive evidence can be extrapolated about PR and PL. What is known already Different studies evaluated the correlation between uterine septum and reproductive outcomes. On one hand, studies reported its association with poor obstetrics outcomes. On the other hand, recent studies raised doubts about the effectiveness of septum metroplasty to improve reproductive outcomes, although recent position papers continue to propose metroplasty in patients with a septate uterus and a history of infertility or miscarriages. Debate is still ongoing on reproductive outcomes of uterine septum on infertile patients and especially on patients with recurrent miscarriage, leading to an unanswered question whether or not these women should be treated. Study design, size, duration Systematic review and meta-analysis of published studies that evaluated the clinical impact of uterine septum and its metroplasty on reproductive and obstetrics outcomes. The meta-analysis included study with infertile patients or patients with a history of recurrent miscarriage. Searches were conducted using the following search terms: uterine septum, septate uterus, metroplasty, pregnancy rate, live birth rate, spontaneous miscarriage, infertility, preterm delivery. Primary outcomes were PR and LBR. Secondary outcomes were SA and PL. Participants/materials, setting, methods The meta-analysis was written following the PRISMA guidelines. Fifty-nine full-text articles were preselected based on title and abstract. Endpoints were evaluated in three subgroups: 1) infertile/recurrent miscarriage patients with septum versus no septum 2) infertile/recurrent miscarriage patients with treated versus untreated septum 3) infertile/recurrent miscarriage patients before-after septum removal. Odds-ratios (OR) with 95% confidence intervals (CI) were calculated for outcome measures. Random-effect meta-analysis was performed and a p-value less than 0.05 was considered statistically significant. Main results and the role of chance Data from 37 articles were extracted. In the first subgroup (10 studies), a lower PR and LBR were associated with septate uterus vs. controls, respectively (OR 0.39, 95% CI 0.26 to 0.58; p &amp;lt; 0.000; low-heterogeneity and OR 0.21, 95% CI 0.12 to 0.39; p &amp;lt; 0.0001; small-heterogeneity) and a higher proportion of SA and PL was associated with septate uterus vs. controls, respectively (OR 4.17, 95% CI 2.83 to 6.15; p &amp;lt; 0.000; moderate-heterogeneity and OR 2.18, 95% CI 1.27 to 3.76; p = 0.005; low-heterogeneity). In the second subgroup (8 studies), PR and PL were not different in removed vs. unremoved septum, respectively (OR 1.10, 95% CI 0.49 to 2.49; p = 0.82; moderate heterogeneity and OR 0.44, 95% CI 0.18 to 1.08; p = 0.08;low-heterogeneity) and a lower proportion of SA was associated with removed vs. unremoved septum (OR 0.40, 95% CI 0.17 to 0.95; p = 0.001; substantial-heterogeneity). In the third subgroup (19 studies), the proportion of LBR was higher after the removal of septum (OR 49.58, 95% CI 29.93 to 82.13; p &amp;lt; 0.0001; moderate-heterogeneity) and the proportion of SA and PL was lower after the removal of septum, respectively (OR 0.02, 95% CI 0.02 to 0.04; p &amp;lt; 0.000; moderate-heterogeneity and OR 0.05, 95% CI 0.03 to 0.08; p = &amp;lt;0.000; low-heterogeneity). Limitations, reasons for caution The present meta-analysis is limited by the observational design of included studies because, in literature, there are no prospective randomized controlled trials (RCTs). In the second and third subgroup of analysis clinical heterogeneity within and between studies represents another limitation. Wider implications of the findings The results of this meta-analysis confirm the detrimental effect of uterine septum on PR, LBR, SA and PL. Its treatment seems to reduce the rate of SA. Metroplasty should still be considered as good clinical practice in patients with a history of infertility and recurrent abortion. Trial registration number Not applicable © The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.

Provision of palliative care to adults with congenital heart disease at the end of life

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by Research Foundation Flanders [grant numbers G097516N to PM, 12E9816N to EG and 1154719N to LVB]; the King Baudouin Foundation (Fund Joseph Oscar Waldmann-Berteau &amp; Fund Walckiers Van Dessel); the National Foundation on Research in Pediatric Cardiology; and the Swedish Research Council for Health, Working Life and Welfare -FORTE (grant number STYA-2018/0004). OnBehalf BELCODAC consortium Background Although recent position papers have discussed and advocated for the integration of palliative care in the treatment course of adults with congenital heart defects (CHD), empirical studies reporting to what extent palliative care is currently provided, are still lacking. Purpose (1) To explore the current provision of palliative care to adults with CHD in the last 6 months of their life; and (2) to describe the profile of patients who received palliative care. Methods In this retrospective study, data of deceased adult patients included in the BELgian COngenital heart disease Database combining Administrative and Clinical data (BELCODAC) were analysed. Palliative care provision (i.e., admission to palliative care ward, or palliative care at home) was identified using nomenclature codes. The level of anatomical complexity was based on the Bethesda classification. Descriptive analyses were performed. Results During the period 2006-2016, 480 adults with CHD died (mean age: 54.4y; 45% simple CHD, 43% moderate CHD, 12% complex CHD). We identified that 75 patients (16%) had at least one nomenclature code linked to palliative care in the last 6 months of their life. More specifically, 16 patients were admitted to an inpatient palliative care service and 67 patients received palliative care at home. Of the patients who received palliative care at home, 40 patients were cared for by a multidisciplinary team specialized in palliative care provision and 59 patients received care from nurses and/or general practitioners while being recognized as a palliative patient. A total of 8 patients received palliative care both at the inpatient palliative care service and at home. Of the 75 patients receiving palliative care, 44 (59%) had a neoplasm as the primary cause of death and a cardiac cause of death was reported for 10 patients (13%) (see Figure 1). The mean age of patients receiving palliative care was 57.9 years. Most patients receiving palliative care had a simple CHD (n = 40; 53%), 29 patients (39%) had a moderate lesion, and 6 patients (8%) had a complex lesion. That means that, respectively, 19%, 14%, and 11% of all deceased patients with a simple, moderate, and complex heart lesion received palliative care. Conclusions This is the first exploratory study on palliative care in adults with CHD. About one in six patients who died received palliative care. Of those who received palliative care, the cause of death was in most cases of a non-cardiac nature. Further research is needed to investigate the care trajectories and care needs of adults with CHD in the last months of life. Figure 1. Causes of death of adults with CHD who received palliative care in the last 6 months of life (n = 75).

Managing uncertainty in antifungal dosing: antibiograms, therapeutic drug monitoring and drug-drug interactions.

A number of pharmacokinetic and pharmacodynamic factors in critically ill or severely immunosuppressed patients influence the effectiveness of antifungal therapy making dosing less certain. Recent position papers from infectious diseases societies and working groups have proposed methods for dosage individualization of antibiotics in critically ill patients using a combination of population pharmacokinetic models, Monte-Carlo simulation and therapeutic drug monitoring (TDM) to guide dosing. In this review, we examine the current limitations and practical issues of adapting a pharmacometrics-guided dosing approaches to dosing of antifungals in critically ill or severely immunosuppressed populations. We review the current status of antifungal susceptibility testing and challenges in incorporating TDM into Bayesian dose prediction models. We also discuss issues facing pharmacometrics dosage adjustment of newer targeted chemotherapies that exhibit severe pharmacokinetic drug-drug interactions with triazole antifungals. Although knowledge of antifungal pharmacokinetic/pharmacodynamic is maturing, the practical application of these concepts towards point-of-care dosage individualization is still limited. User-friendly pharmacometric models are needed to improve the utility of TDM and management of a growing number of severe pharmacokinetic antifungal drug-drug interactions with targeted chemotherapies.

The Smoothed Complexity of Computing Kemeny and Slater Rankings

The computational complexity of winner determination under common voting rules is a classical and fundamental topic in the field of computational social choice. Previous work has established the NP-hardness of winner determination under some commonly-studied voting rules, such as the Kemeny rule and the Slater rule. In a recent position paper, Baumeister, Hogrebe, and Rothe (2020) questioned the relevance of the worst-case nature of NP-hardness in social choice and proposed to conduct smoothed complexity analysis (Spielman and Teng 2009) under Blaser and Manthey’s (2015) framework. In this paper, we develop the first smoothed complexity results for winner determination in voting. We prove the smoothed hardness of Kemeny and Slater using the classical smoothed runtime analysis, and prove a parameterized typical-case smoothed easiness result for Kemeny. We also make an attempt of applying Blaser and Manthey’s (2015) smoothed complexity framework in social choice contexts by proving that the framework categorizes an always-exponential-time brute force search algorithm as being smoothed poly-time, under a natural noise model based on the well-studied Mallows model in social choice and statistics. Overall, our results show that smoothed complexity analysis in computational social choice is a challenging and fruitful topic.