bluuebunny/crossref_metadata_2025 huggingface dataset:
Geographic Peer Effects in Management Earnings Forecasts*
Authors: Matsumoto Dawn , Serfling Matthew , Shaikh Sarah
Published: March 2022

Because of clear economic links among industry peers, prior work has focused on documenting industry peer effects in various settings. Yet, while links also exist among firms in the same geographic area, few studies document geographic peer effects. We fill this gap by examining whether there are geographic peer effects in management earnings forecasts. We find that the likelihood that a firm voluntarily provides an earnings forecast is sensitive to the extent to which other firms in the same geographic area provide earnings forecasts. This geographic peer effect in forecasting is stronger for firms with greater exposure to local institutional investors, and when firms do forecast, liquidity improves more when a larger fraction of their geographic peers forecast. Furthermore, we use instrumental variable techniques to help alleviate the concern that these geographic peer effects are driven by omitted local economic factors that can lead firms to make similar disclosure decisions. Overall, our findings suggest that geographic peer effects in disclosure choices arise in part due to firms responding to capital market incentives created by local investors. Our study, therefore, contributes to the literature by documenting a unique dimension of forecasting decisions.
Business Partnering in Risk Management: A Resilience Perspective on Management Accountants' Responses to a Role Change*
Authors: Tillema Sandra , Trapp Rouven , van Veen‐Dirks Paula
Published: March 2022

This study uses a resilience perspective to examine the opportunities and challenges that management accountants may experience when they are given a role as a business partner in risk management. Drawing on insights from an in‐depth case study in a large European bank, our study sheds light on management accountants' responses to a change from a compliance‐oriented role to a business partner role. In the bank studied, part of the management accountants' new role was to balance various performance objectives and thereby to incorporate risk considerations in managerial decision‐making. Our findings suggest that this role challenged the management accountants due to the ambiguity inherent in the role and also due to unfavorable conditions that surrounded the role change. We find that these circumstances culminated in a move backward, with the management accountants falling back on practices that were consistent with the values and beliefs they had developed in their previous role. In doing so, they emphasized what the resilience literature labels “well‐learned responses.” These responses contributed to an emphasis on a narrow risk management approach and had implications for the management accountants' long‐term position within the organization. We discuss these findings against the background of previous research that suggests that management accountants move forward to the business partner role by engaging in job crafting (i.e., adapting their work) or identity work (i.e., redefining their role identity). By utilizing the concepts of lingering identities and identity asymmetries to explain the management accountants' move backward, we also shed light on new facets related to role identity.
Metabolic response to increasing environmental temperature in the invasive mussel Limnoperna fortunei
Authors: Paolucci Esteban Marcelo , Ron Leila , Thuesen Erik V.
Published: March 2022

Plasticity and variability of morphological and physiological traits are common characteristics that allow invasive species to survive, establish and spread to new environments. In order to study the metabolic response of the invasive mussel Limnoperna fortunei (Dunker) (Mytilidae), which has spread through South America and Asia, oxygen consumption was measured under three different acclimation temperatures (18, 22 and 27°C). After an acclimation period of at least 7 days, oxygen consumption was measured and analysed as functions of length and mass. Biochemical composition was also investigated on specimens collected under natural conditions. Environmental scanning electron microscopy determined that the elemental composition and crystalline structure of the shells were normal as described for L. fortunei previously. Average oxygen consumption per mussel was 1.63 ± 0.12 μmol O2 h−1 for an average ash‐free dry weight (AFDW) of 58.7 ± 3.0 mg. The average standard metabolic rate (SMR) per mussel was 14.94 ± 1.30, 30.04 ± 3.38, and 47.10 ± 3.54 μmol O2 gAFDW−1 h−1, at 18, 22 and 27°C, respectively. Significant higher SMR values were recorded at 27°C than at lower temperatures. This metabolic response allows L. fortunei to survive, reproduce and spread across a wide range of habitats, including tropical and subtropical environments in South America.
Responses of floodplain birds to high‐amplitude precipitation fluctuations over two decades
Authors: Reid Tim , Lada Hania , Selwood Katherine E. , Horrocks Gregory F. B. , Thomson James R. , Mac Nally Ralph
Published: March 2022

Globally, high‐amplitude variation in weather (e.g. precipitation) is increasing in frequency and magnitude. This appears to be so for the southernMurray‐DarlingBasin, Australia, where droughts of unprecedented (in the instrumental record, extending back to the mid‐1800s) depth and duration (1997–first half of 2010; second half of 2012–) are being punctuated by extreme wet periods, albeit of shorter duration (‘Big Wet’, second half of 2010–first half of 2012). We have previously reported on the responses of floodplain‐forest birds to the cessation of the longest recorded drought (‘Big Dry’, 1997–first half of 2010), but we found little evidence of a rebound, at least shortly after the Big Wet. However, we reasoned that there may have been insufficient time for the birds to have responded in that short time, so we repeated the survey program 5 years after the end of the Big Wet (2017). Bird occurrences, reproductive activity and success were substantially greater compared with late in the Big Dry (2009) than they had been soon after the Big Wet (2013). However, bird occurrences still fell well below measurements in theearly‐BigDry (1998), so that the avifauna appears to be in decline, most probably because the length of drought periods far exceeds that of wet periods giving the birds too little time to recover fully.
Productive Workfare? Evidence from Ethiopia's Productive Safety Net Program
Authors: Gazeaud Jules , Stephane Victor
Published: March 2022

Public works programs have long been a popular policy tool to reduce poverty and build productive infrastructure. Although an extensive literature has documented the effect of these programs on poverty, there is virtually no evidence on the productive effect of the infrastructure. This paper attempts to start filling this gap in the context of the Productive Safety Net Program—a large‐scale public works program implemented in Ethiopia since 2005. Under the program, millions of beneficiaries received social transfers conditional on their participation in activities such as land improvements and soil and water conservation measures. We examine the value of these activities using a satellite‐based indicator of agricultural productivity and (reweighted) difference‐in‐differences estimates. Results show that the program is associated with limited changes in agricultural productivity. The upper bound of the main estimate is equivalent to a 2.2% increase in agricultural yield. This contrasts with existing narratives and calls for more research on the productive effects of public works.
Cesarean section rate changes after audit and feedback with the Ten Group Classification System in a French perinatal network: A retrospective pre–post study
Authors: Quibel Thibaud , Chesnais Marion , Bouyer Camille , Rozenberg Patrick , Bouyer Jean
Published: March 2022

Introduction

The rise in the number of cesarean sections (CS) is a major health public problem which concerns nearly all countries. It is suggested that the Ten Group Classification System be adapted to a procedure of audit/feedback cycles, which could have an effect on CS practice. Therefore, we aimed to study changes in CS rates between maternity wards in a perinatal network after implementation of the Ten Group Classification System in an audit with feedback.

Material and methods

This was a retrospective pre–post study of all births from 1 January 2012 to 31 December 2018, in a French perinatal network of 10 maternity wards in the Yvelines district of France. All live births occurring at a gestational age ≥24 weeks in the network were included. During the pre‐period (1 January 2012 to 31 December 2014), the audit and feedback provided only overall CS rates. During the post‐period (1 January 2015 to 31 December 2018), CS rates for each Robson Ten Group Classification System group were provided. Regression models, adjusted for maternal characteristics and maternity ward, were used to compare CS rates globally and for each group of the system. Variability of CS rates between maternity wards was analyzed using the coefficients of variation.

Results

There were 51 082 women who delivered during the pre‐period and 63 964 during the post‐period. The overall CS rate did not decrease (24.5% during the pre‐period vs 25.1% during the post‐period). There were no significant differences in CS rates for any group of the Ten Group Classification System after adjustment for maternity, maternal age and sociodemographic characteristics, nor did audit implementation decrease CS rate variability between maternity wards or within groups of the system.

Conclusions

Implementation of an audit‐and‐feedback cycle using the Ten Group Classification System did not decrease either CS rates or variability between maternity wards.
Real‐World outcomes of adalimumab in adults with non‐infectious uveitis
Authors: Leal Inês , Wong Shiao Wei , Giuffre Chiara , Patil Ajay , Sousa David Cordeiro , Barbosa‐Breda João , Chhabra Ramandeep , Jones Nicholas P. , Steeples Laura R.
Published: March 2022

Purpose

To present real‐world adalimumab (ADA) efficacy and safety outcomes in non‐infectious uveitis (NIU) from a single United Kingdom (UK) tertiary centre.

Methods

Retrospective review of adult patients with NIU treated with ADA. Data were collected at baseline, 6 and 12 months. The primary goal was to evaluate the rate of treatment failure, using the VISUAL‐I/II studies criteria, during 12 months of follow‐up. Secondary aims were to quantify corticosteroid‐sparing effect; to identify safety issues; to assess change in visual acuity; to identify reasons for treatment failure and to compare treatment outcomes at 6 and 12 months for patients classified as active or inactive at baseline.

Results

Fifty‐one patients (102 eyes) with mean age of 48.3 years were included. One third had a known underlying systemic disease and 47.6% had panuveitis. The most common indication for ADA was failure to respond to oral immunosuppression. Treatment failure occurred in 9/51 patients (10 eyes) after 6 months and 13/51 (20 eyes) patients after 12 months. The need for rescue treatment in the 12 months prior to ADA was significantly associated with treatment failure at 12 months. The mean prednisolone dosage was <10 mg/day at 6 and 12 months. There were no serious adverse events.

Conclusion

Patients with NIU who received ADA therapy for 12 months were likely to achieve disease control, to stabilize or improve visual acuity, to experience a reduction in immunosuppression and to reduce corticosteroid dosage. No new safety events were observed.
A digital online platform for education and certification of diabetic retinopathy health care professionals in the Region of Southern Denmark
Authors: Andersen Jakob Kristian Holm , Hubel Martin Slusarczyk , Savarimuthu Thiusius Rajeeth , Rasmussen Malin Lundberg , Sørensen Simon Lyck Bjært , Grauslund Jakob
Published: March 2022

Purpose

The incidence of diabetes continues to increase across the world. As the number of patients rises, so does the need for educated health care professionals. Diabetic retinopathy (DR) remains one of the primary complications in diabetes, and screening has proved to be a cost‐effective measure to avoid DR‐related blindness. Denmark has an established screening programme, but no formal training of the people responsible for analysing retinal images.

Methods

We here present an online learning platform that offers a diabetic eye screening course for health care professionals undertaking screening responsibility in the Region of Southern Denmark. The course is divided into lectures, each focussed on identifying different levels of DR or detecting related lesions. The course is free to use on‐demand, contains instructional videos, interactive tests and exercises, and it is concluded with a certification test. The tools on the platform can in addition be used to generate data for research purposes, such as comparing users or experts in detection of lesions or annotating data for the development of machine learning models.

Results

More than 150 participants have so far completed the course, and the platform is being adopted for education in other regions of Denmark.
A United States expert consensus to standardise definitions, follow‐up, and treatment targets for extra‐intestinal manifestations in inflammatory bowel disease
Authors: Falloon Katherine , Cohen Benjamin , Ananthakrishnan Ashwin N. , Barnes Edward L. , Bhattacharya Abhik , Colombel Jean‐Frederic , Cross Raymond K. , Driscoll Marcia S. , Fernandez Anthony P. , Ha Christina , Herfarth Hans , Horst Sara , Hou Jason , Husni M. Elaine , Kroshinsky Daniela , Kuhn Kristine A. , Lowder Careen Y. , Martin George , Parikh Deep , Sayed Christopher J. , Schocket Lisa , Siaton Bernadette C. , Vedak Priyanka , Weisman Michael H. , Rieder Florian
Published: March 2022

Background and aims

Extra‐intestinal manifestations (EIMs) are a common complication of inflammatory bowel diseases (IBD), affecting up to half of the patients. Despite their high prevalence, information on standardised definitions, diagnostic strategies, and treatment targets is limited.

Methods

As a starting point for a national EIM study network, an interdisciplinary expert panel of 12 gastroenterologists, 4 rheumatologists, 3 ophthalmologists, 6 dermatologists, and 4 patient representatives was assembled. Modified Delphi consensus methodology was used. Fifty‐four candidate items were derived from the literature review and expert opinion focusing on five major EIMs (erythema nodosum, pyoderma gangrenosum, uveitis, peripheral arthritis, and axial arthritis) were rated in three voting rounds.

Results

For use in a clinical practice setting and as part of the creation of a prospective registry of patients with EIMs, the panel developed definitions for erythema nodosum, pyoderma gangrenosum, uveitis, peripheral arthritis, and axial arthritis; identified the appropriate and optimal subspecialists to diagnose and manage each; provided methods to monitor disease course; offered guidance regarding monitoring intervals; and defined resolution and recurrence.

Conclusions

Consensus criteria for appropriate and optimal means of diagnosing and monitoring five EIMs have been developed as a starting point to inform clinical practice and future trial design. Key findings include straightforward diagnostic criteria, guidance regarding who can appropriately and optimally diagnose each, and monitoring options that include patient and physician‐reported outcomes. These findings will be used in a national multicenter study network to optimise the management of EIMs.
Risk of maculopathy with pentosan polysulfate sodium use
Authors: Bae Steven S. , Sodhi Mohit , Maberley David , Kezouh Abbas , Etminan Mahyar
Published: March 2022

Aims

Recent epidemiologic studies have examined the risk of maculopathy with pentosan polysulfate sodium (PPS), a drug indicated for the treatment of interstitial cystitis. However, results have been contradictory. Thus, we quantified the risk of maculopathy with PPS with a focus on risk with duration of use.

Methods

We used a new user, retrospective cohort study with an active comparator. We created a cohort of mutually exclusive 6221 PPS users and 89 744 amitriptyline users, a tricyclic antidepressant also used for the treatment of pain secondary to interstitial cystitis. Subjects were selected from the PharMetrics Plus database (IQVIA, Durham, NC) from 2006 to 2020. Cohort members were followed to the first event of the study outcome (maculopathy) or end of enrolment. A Cox regression model was constructed to adjust for potential confounders.

Results

The mean follow‐up was 3.0 years for PPS users and amitriptyline users. The adjusted hazard ratio (HR) for maculopathy in PPS users was 2.64 (95% confidence interval [CI]: 1.90–3.68). The HR for the sensitivity analysis that combined maculopathy and age‐related macular degeneration (AMD) was 1.38 (95% CI: 1.16–1.65). A cumulative duration‐response pattern was observed, with use greater than 3 years having a 9.5‐fold risk of maculopathy (HR = 9.56, 95% CI: 3.60–25.37) compared to a 2.3‐fold risk of maculopathy with use for 1 year or less (HR = 2.27, 95% CI: 1.50–3.43). The number needed to harm for the first 4 years of use was 250.

Conclusions

The results of this study suggest an increased risk of maculopathy with PPS use, particularly with longer duration of use.
Effect of glucagon‐like peptide‐1 receptor agonists on renal function: A meta‐analysis of randomized controlled trials
Authors: Simental‐Mendía Mario , Linden‐Torres Enrique , Sánchez‐García Adriana , Sahebkar Amirhossein , Simental‐Mendía Luis E.
Published: March 2022

Aims

The objective of this meta‐analysis was to examine the impact of the GLP‐1 RA on renal function parameters in randomized controlled trials.

Methods

A systematic search was performed in PubMed‐MEDLINE, Scopus, Web of Science, ClinicalTrials.gov, and Google Scholar databases. Meta‐analysis was performed using a random‐effects model and sensitivity analysis.

Results

Data from 18 randomized controlled trials involving 12 192 subjects, showed that treatment with GLP‐1 RA had no effect on serum creatinine levels (weighted mean difference [WMD]: 0.00 mg/mL, 95% confidence interval [CI]: −0.01, 0.01, P = .83, I2 = 0%) and glomerular filtration rate (WMD: 1.01 mL/min/1.73 m2, 95% CI: −1.61, 3.63, P = .45, I2 = 75%). On the other hand, a significant reduction in urinary albumin excretion (WMD: −18.01 mg/day, 95% CI: −31.20, −4.82, P = .007, I2 = 23%) and albumin‐to‐creatinine ratio (WMD: −6.74 mg/g, 95% CI: −12.64, −0.85, P = .03, I2 = 68%) was detected after GLP‐1 RA therapy.

Conclusion

Results of our meta‐analysis revealed that GLP‐1 RA treatment decreases urinary albumin excretion and albumin‐to‐creatinine ratio but it did not cause significant changes in creatinine levels and glomerular filtration rate.
A phase 1 study to evaluate the safety, tolerability and pharmacokinetics of TAK‐041 in healthy participants and patients with stable schizophrenia
Authors: Yin Wei , Han David , Khudyakov Polyna , Behrje Rhett , Posener Joel , Laurenza Antonio , Arkilo Dimitrios
Published: March 2022

Aims

TAK‐041 (NBI‐1065846), an orally available, investigational, small molecule agonist of GPR139, an orphan G‐protein‐coupled receptor, has shown promise in preclinical studies for the treatment of symptoms associated with schizophrenia. Here, we report the results from a phase 1 study to evaluate the safety, tolerability and pharmacokinetics of TAK‐041 in healthy adults and exploratory efficacy assessment of TAK‐041 as adjunctive therapy to antipsychotics in adults with stable schizophrenia (ClinicalTrials.gov: NCT02748694).

Methods

The study comprised 4 parts: parts 1–3 were undertaken in healthy adults and part 4 in patients with stable schizophrenia. Part 1 was a single‐rising‐dose study, part 2 was a multiple‐rising‐dose study that assessed plasma exposure and accumulation, part 3 evaluated the bioavailability of tablet formulation versus oral suspension, and part 4 was a repeat multiple‐dose study in patients with stable schizophrenia.

Results

No serious adverse events were reported. TAK‐041 had a nearly linear pharmacokinetics profile, with rapid absorption and long half‐life of 170–302 hours across all doses tested. Bioavailability was similar between the tablet formulation and oral suspension, and no meaningful food effect was detected. Systemic exposure was 22–30% lower for patients with schizophrenia than for healthy volunteers. A potential signal of improvement was detected in the anxiety–depression scale of the Positive and Negative Syndrome Scale (P = .0002, not corrected for multiplicity) and the Temporal Experience of Pleasure Scale in patients with schizophrenia.

Conclusion

TAK‐041 was generally well tolerated in healthy volunteers and adults with schizophrenia. Further investigation of TAK‐041 in individuals with schizophrenia is supported.
Dose banding – Weighing up benefits, risks and therapeutic failure
Authors: Duffull Stephen
Published: March 2022

Aims

Dose banding is a method of dose individualisation in which all patients with similar characteristics are allocated to the same dose. Dose banding results in some patients receiving less intensive treatment which risks a reduction in therapeutic benefit (iatrogenic therapeutic failure) because of variability not predicted by dose banding. This study aims to explore the effects of dose banding on therapeutic success and failure.

Methods

This was a simulation study. Virtual patients were simulated under a simple pharmacokinetic model where the response of interest is the steady‐state average concentration. Clearance was correlated with a covariate used for dose banding. Dose individualisation was based on: one‐dose‐fits‐all, covariate‐based dosing, empirical dose banding, dose banding optimised for net therapeutic benefit and optimised for both benefit and minimising iatrogenic therapeutic failure.

Results

The lowest and highest probability of target attainment (PTA) were 44% for one‐dose‐fits‐all and 72% for covariate‐based dosing. Neither dosing approach would result in iatrogenic therapeutic failure as lower dose intensities do not occur. Empirical dose banding performed better than one‐dose‐fits‐all with 59% PTA but not as good as either optimised method (64–69% PTA) while carrying a risk of iatrogenic therapeutic failure in 25% of patients. Optimising for benefit (only) improved PTA but carried a risk of iatrogenic therapeutic failure of up to 10%. Optimising for benefit and minimising iatrogenic therapeutic failure provided the best balance.

Conclusion

Future application of dose banding needs to consider both the probability of benefit as well the risk of causing iatrogenic therapeutic failure.
Optimal dose of meropenem for the treatment of neonatal sepsis: Dosing guideline variations and clinical practice deviations
Authors: Raza Muhammad Ahmer , Yao Bu‐Fan , Shi Hai‐Yan , Xu Hai‐Yan , Hao Guo‐Xiang , Van Den Anker John , Zhao Wei
Published: March 2022

Aims

Meropenem is increasingly used to treat neonatal sepsis. There are several guidelines recommending different dosing regimens of meropenem in neonates. Furthermore, deviations from these guidelines regularly occur in daily clinical practice. Therefore, the current study aimed to evaluate the variations of meropenem dosing guidelines and compare the difference between guideline and clinical practice in terms of the probability of target attainment.

Methods

This study is based on a population pharmacokinetic model. After defining the predictive performance of the model, Monte Carlo simulations were used to calculate the probability of target attainment of the currently existing dosing guidelines of meropenem and their use in daily clinical practice.

Results

Two guidelines and two labels were included in the Monte Carlo simulations. For 70% fT>MIC (fraction of time when the free meropenem concentration exceeded the minimum inhibitory concentration during the dosing interval), the probability of target attainment of four recommended doses ranged from 59% to 88% (MIC = 2 mg·L−1) and from 17% to 47% (MIC = 8 mg·L−1). At the clinical practice evaluation, only 20% of patients attained target exposure for the MIC of 8 mg·L−1 with 70% fT>MIC, which was much less than those found in the Food and Drug Administration labels (40%).

Conclusion

This model‐based population pharmacokinetics simulation showed that improper guidelines and/or clinical practice deviations will result in low probability of target attainment for patients infected with resistant bacteria and critically ill patients. It is important to develop and adhere to evidence‐based and clinically pragmatic guidelines.
Multimethod quantitative benefit‐risk assessment of treatments for moderate‐to‐severe osteoarthritis
Authors: Mauer Jonathan , Bullok Kristin , Watt Stephen , Whalen Ed , Russo Leo , Junor Rod , Markman John , Hauber Brett , Tervonen Tommi
Published: March 2022

Objective

Demonstrate how benefit‐risk profiles of systemic treatments for moderate‐to‐severe osteoarthritis (OA) can be compared using a quantitative approach accounting for patient preference.

Study design and setting

This study used a multimethod benefit‐risk modelling approach to quantifiably compare treatments of moderate‐to‐severe OA. In total four treatments and placebo were compared. Comparisons were based on four attributes identified as most important to patients. Patient Global Assessment of Osteoarthritis was included as a favourable effect. Unfavourable effects, or risks, included opioid dependence, nonfatal myocardial infarction and rapidly progressive OA leading to total joint replacement. Clinical data from randomized clinical trials, a meta‐analysis of opioid dependence and a long‐term study of celecoxib were mapped into value functions and weighted with patient preferences from a discrete choice experiment.

Results

Lower‐dose NGFi had the highest weighted net benefit‐risk score (0.901), followed by higher‐dose NGFi (0.889) and NSAIDs (0.852), and the lowest score was for opioids (0.762). Lower‐dose NGFi was the highest‐ranked treatment option even when assuming a low incidence (0.34% instead of 4.7%) of opioid dependence (ie, opioid benefit‐risk score 808) and accounting for both the uncertainty in clinical effect estimates (first rank probability 46% vs 20% for NSAIDs) and imprecision in patient preference estimates (predicted choice probability 0.26, 95% confidence interval [CI] 0.25‐0.28 vs 0.21, 95% CI 0.19‐0.23 for NSAIDs).

Conclusion

The multimethod approach to quantitative benefit‐risk modelling allowed the interpretation of clinical data from the patient perspective while accounting for uncertainties in the clinical effect estimates and imprecision in patient preferences.
Personal responsibility and transplant revisited: A case for assigning lower priority to American vaccine refusers
Authors: Appel Jacob M.
Published: March 2022

Priority for solid organ transplant generally does not consider the underlying cause of the need for transplantation. This paper argues that a distinctive set of factors justify assigning lower priority to willfully unvaccinated individuals who require transplant as a result of suffering from COVID‐19. These factors include the personal responsibility of the patients for their own condition and the public outrage likely to ensue if willfully unvaccinated patients receive organs at the expense of vaccinated ones. The paper then proposes a three‐prong test for similar deviations from the current allocation standard that incorporates patient responsibility, foreseeability and avoidability, and the frequency of the occurrence.
Three kinds of suffering and their relative moral significance
Authors: Kious Brent M.
Published: March 2022

Suffering is widely assumed to have particular moral significance, and is of special relevance in medicine. There are, however, many theories about the nature of suffering that seem mutually incompatible. I suggest that there are three overall kinds of view about what suffering is: value‐based theories, including the theory famously expounded by Eric Cassell, which as a group suggest that suffering is something like a state of distress related to threats to things that a person cares about; feeling‐based theories, which equate suffering with aversive feelings or sensations like pain; and objective theories, which suggest that suffering is the absence of objective flourishing. Rather than argue that one or another of these kinds of theory most accurately captures the nature of suffering, I allow that the term is ambiguous and thus that it may have at least three different kinds. I further argue, however, that when we think about suffering as potentially justifying end‐of‐life interventions, especially for cognitively typical adults, we are interested mainly in value‐based suffering. This is because the moral significance of value‐based suffering for persons with decision‐making capacity generally outweighs that of the other types; those other types of suffering achieve overriding moral significance only if they also constitute, or contribute to, value‐based suffering.
Changing trends of splenectomy in hereditary spherocytosis: The experience of a reference Centre in the last 40 years
Authors: Vercellati Cristina , Zaninoni Anna , Marcello Anna P. , Fermo Elisa , Fattizzo Bruno , Giannotta Juri A. , Bianchi Paola , Zanella Alberto , Barcellini Wilma
Published: March 2022

We describe the clinical/haematological characteristics of 446 patients with hereditary spherocytosis diagnosed in the last 40 years in a reference centre. The frequency of splenectomy decreased over time (44% before 1990 to 7% in 2011–2020), notwithstanding a confirmed good efficacy. Age at splenectomy progressively increased (63% in children before 1990 to 88% in patients aged ≥20 years in 2011–2020). Our real‐life experience showed that even a fraction of patients in the trait/mild categories (19/92, 21%) were splenectomised, whilst 30/78 (38%) in the moderate/severe groups were not. Overall, these data pinpoint to the increasing awareness about post‐splenectomy thromboses and infections.
Mind and matter: The neurological complications of thrombotic thrombocytopenic purpura
Authors: Shaw Rebecca J. , Dutt Tina
Published: March 2022

Thrombotic thrombocytopenic purpura (TTP) is a rare and potentially fatal condition, with >90% mortality if untreated; deficiency of ADAMTS13 leads to widespread microvascular thromboses and organ injury particularly affecting organs with high shear stress, including the brain. The acute neurological complications have historically been those most feared by clinicians and synonymous with a poor prognosis. TTP, however, is no longer perceived as two extremes of acute presentation and remission, rather once diagnosed a chronic condition with the potential for a long‐term symptom burden. Optimal neuroimaging timing and modality lacks consensus and as we learn more about the changes seen during the acute and chronic stages of TTP, there is scope for neuroimaging to play a greater role in guiding management and the secondary prevention of vascular disease. Reduced ADAMTS13 activity levels have been associated with increased thrombotic risk and novel therapies including caplacizumab and recombinant ADAMTS13 may offer a neuroprotective role. Given the increasing evidence of the neurocognitive and psychological disease in TTP, the importance of screening and timely intervention should not be underestimated. As more patients are surviving their initial TTP presentation, it is crucial for us to develop a greater understanding of the longer‐term morbidity affecting these patients.
Clonal haematopoiesis as a risk factor for therapy‐related myeloid neoplasms in patients with chronic lymphocytic leukaemia treated with chemo‐(immuno)therapy
Authors: Voso Maria‐Teresa , Pandzic Tatjana , Falconi Giulia , Denčić‐Fekete Marija , De Bellis Eleonora , Scarfo Lydia , Ljungström Viktor , Iskas Michail , Del Poeta Giovanni , Ranghetti Pamela , Laidou Stamatia , Cristiano Antonio , Plevova Karla , Imbergamo Silvia , Engvall Marie , Zucchetto Antonella , Salvetti Chiara , Mauro Francesca R. , Stavroyianni Niki , Cavelier Lucia , Ghia Paolo , Stamatopoulos Kostas , Fabiani Emiliano , Baliakas Panagiotis
Published: March 2022

Clonal haematopoiesis of indeterminate potential (CHIP) may predispose for the development of therapy‐related myeloid neoplasms (t‐MN). Using target next‐generation sequencing (t‐NGS) panels and digital droplet polymerase chain reactions (ddPCR), we studied the myeloid gene mutation profiles of patients with chronic lymphocytic leukaemia (CLL) who developed a t‐MN after treatment with chemo‐(immuno)therapy. Using NGS, we detected a total of 30 pathogenic/likely pathogenic (P/LP) variants in 10 of 13 patients with a t‐MN (77%, median number of variants for patient: 2, range 0–6). The prevalence of CHIP was then backtracked in paired samples taken at CLL diagnosis in eight of these patients. Six of them carried at least one CHIP‐variant at the time of t‐MN (median: 2, range: 1–5), and the same variants were present in the CLL sample in five cases. CHIP variants were present in 34 of 285 patients from a population‐based CLL cohort, which translates into a significantly higher prevalence of CHIP in patients with a CLL who developed a t‐MN, compared to the population‐based cohort (5/8, 62.5% vs. 34/285, 12%, p = 0.0001). Our data show that CHIP may be considered as a novel parameter affecting treatment algorithms in patients with CLL, and highlight the potential of using chemo‐free therapies in CHIP‐positive cases.
What happens to our representation of identity as familiar faces age? Evidence from priming and identity aftereffects
Authors: Laurence Sarah , Baker Kristen A. , Proietti Valentina M. , Mondloch Catherine J.
Published: March 2022

Matching identity in images of unfamiliar faces is error prone, but we can easily recognize highly variable images of familiar faces – even images taken decades apart. Recent theoretical development based on computational modelling can account for how we recognize extremely variable instances of the same identity. We provide complementary behavioural data by examining older adults’ representation of older celebrities who were also famous when young. In Experiment 1, participants completed a long‐lag repetition priming task in which primes and test stimuli were the same age or different ages. In Experiment 2, participants completed an identity after effects task in which the adapting stimulus was an older or young photograph of one celebrity and the test stimulus was a morph between the adapting identity and a different celebrity; the adapting stimulus was the same age as the test stimulus on some trials (e.g., both old) or a different age (e.g., adapter young, test stimulus old). The magnitude of priming and identity after effects were not influenced by whether the prime and adapting stimulus were the same age or different age as the test face. Collectively, our findings suggest that humans have one common mental representation for a familiar face (e.g., Paul McCartney) that incorporates visual changes across decades, rather than multiple age‐specific representations. These findings make novel predictions for state‐of‐the‐art algorithms (e.g., Deep Convolutional Neural Networks).
Prosocial advice to close versus non‐close others
Authors: Zhang Hong , Zhuo Beibei , Wei Li , Chen Chen
Published: March 2022

Six studies (two pre‐registered, total N = 1861) examined whether individuals would be more likely to give advice to close rather than non‐close others against engaging in prosocial behaviours. The results consistently showed that participants were less inclined to advise close (vs. non‐close) others to donate blood (Studies 2 and 3), to donate money (Study 5) and to engage in volunteer activities (Studies 1–6). Moreover, Studies 3, 5 and 6 also provided evidence suggesting that prosocial advice given to close others was more contingent on cost judgements than that given to non‐close others. These findings have significant implications for the understanding of social influences on prosocial behaviours.
Lifestyle factors and hand eczema: A systematic review and meta‐analysis of observational studies
Authors: Loman Laura , Brands Marjolein J. , Massella Patsea Anna A. L. , Politiek Klaziena , Arents Bernd W. M. , Schuttelaar Marie L. A.
Published: March 2022

Evidence regarding the association between lifestyle factors and hand eczema is limited.To extensively investigate the association between lifestyle factors (smoking, alcohol consumption, stress, physical activity, body mass index, diet, and sleep) and the prevalence, incidence, subtype, severity, and prognosis of hand eczema, a systematic review and meta‐analysis were conducted in accordance with the Meta‐analysis Of Observational Studies in Epidemiology consensus statement. MEDLINE, Embase, and Web of Science were searched up to October 2021. The (modified) Newcastle‐Ottawa Scale was used to judge risk of bias. Quality of the evidence was rated using the Grades of Recommendation, Assessment, Development and Evaluation approach. Eligibility and quality were blindly assessed by two independent investigators; disagreements were resolved by a third investigator. Data were pooled using a random‐effects model, and when insufficient for a meta‐analysis, evidence was narratively summarized. Fifty‐five studies were included. The meta‐analysis (17 studies) found very low quality evidence that smoking is associated with a higher prevalence of hand eczema (odds ratio 1.18, 95% confidence interval 1.09‐1.26). No convincing evidence of associations for the other lifestyle factors with hand eczema were found, mostly due to heterogeneity, conflicting results, and/or the limited number of studies per outcome.
Strategic, feasibility, economic, and cultural aspects of phase 0 approaches
Authors: Burt Tal , Roffel Ad F. , Langer Oliver , Anderson Kirsten , DiMasi Joseph
Published: March 2022

Research conducted over the past 2 decades has enhanced the validity and expanded the applications of microdosing and other phase 0 approaches in drug development. Phase 0 approaches can accelerate drug development timelines and reduce attrition in clinical development by increasing the quality of candidates entering clinical development and by reducing the time to “go‐no‐go” decisions. This can be done by adding clinical trial data (both healthy volunteers and patients) to preclinical candidate selection, and by applying methodological and operational advantages that phase 0 have over traditional approaches. The main feature of phase 0 approaches is the limited, subtherapeutic exposure to the test article. This means a reduced risk to research volunteers, and reduced regulatory requirements, timelines, and costs of first‐in‐human (FIH) testing. Whereas many operational aspects of phase 0 approaches are similar to those of other early phase clinical development programs, they have some unique strategic, regulatory, ethical, feasibility, economic, and cultural aspects. Here, we provide a guidance to these operational aspects and include case studies to highlight their potential impact in a range of clinical development scenarios.
Sustained right ventricular dysfunction in severe COVID‐19: The role of disseminated intravascular coagulation
Authors: Malagoli Alessandro , Rossi Luca , Zanni Alessia , Muto Federico , Tosetti Alberto , Tondi Stefano
Published: March 2022

Background

Acute right ventricular (RV) failure is common in patients hospitalized with COVID‐19. Compared to the conventional echocardiographic parameters, right ventricular longitudinal strain (RVLS) is more sensitive and accurate for the diagnosis of RV systolic dysfunction.

Objective

Our purpose was to investigate the sustained RV dysfunction echo‐quantified by RVLS in patients recovered from severe COVID‐19. Furthermore, we aimed to assess whether disseminated intravascular coagulation (DIC) has a key role to predict the impaired RV strain.

Methods

Of 198 consecutive COVID‐19 patients hospitalized from March 1, 2020, to April 15, 2020, 45 selected patients who survived from severe COVID‐19 were enrolled in the study and referred to our echo‐lab for transthoracic echocardiography 6‐months after discharge. RVLS was calculated as the mean of the strain values of RV free wall. DIC was defined with a validated scoring system: DIC score equal to or more than 5 is compatible with overt‐DIC. Categories of acute respiratory distress syndrome (ARDS) were defined based on PaO2/FiO2 ratio.

Results

A total 26 of 45 patients showed impaired RVLS at 6‐months’ follow‐up. DIC score was significantly higher in patients with worse RVLS than in those with better RVLS (4.8 ± .5 vs. 3.6 ± .6, p =.03). Stages of ARDS did not modulate this relationship. Finally, overt‐DIC results the only independent predictor of sustained RV dysfunction (OR 1.233, 95% CI 1.041–1.934, p =.043).

Conclusions

Sustained RV impairment frequently occurs in patients recovered from severe COVID‐19. DIC plays a key role, resulting in an independent predictor of sustained RV dysfunction.
Postoperative intermittent dysfunction of mitral valve prosthesis of unclear etiology identified by three‐dimensional echocardiography
Authors: Cano‐Nieto Mariana M. , Santibañez‐Escobar Felipe , Arias‐Godinez Jose A. , Rodriguez‐Zanella Hugo G. , Ortiz‐Leon Xochitl A. , Ruiz‐Esparza Maria E. , Fritche‐Salazar Juan F. , Posada‐Martinez Edith L.
Published: March 2022

A 56‐year‐old patient with rheumatic heart disease and atrial fibrillation underwent mitral valve replacement with a mechanical prosthesis. The 3D perioperative echocardiogram showed an intermittent immobile medial disk without hemodynamic repercussion in the intensive care unit. The patient was taken back to the operating room and surgeons could not identify the cause. An enlarged left atrium and the size of the prosthetic valve was thought to have precipitated this condition. The heart team decided a biological prosthetic valve replacement would be performed. This case emphasizes the important role of the perioperative 3D echocardiogram in the detection of immediate surgical complications.
Echocardiographic characteristics of non‐resectional ring‐only valve repair in mitral valve prolapse
Authors: Levy Franck , Wautot Fabrice , Dommerc Carine , Iacuzio Laura , Civaia Filippo , Marcacci Cecilia , Eker Armand
Published: March 2022

Background

Simple mitral valve repair (MVR) using a ring‐only approach (ROA) was recently proposed for some complex forms of bileaflet myxomatous mitral valve prolapse (MVP). Nevertheless, few data are available concerning the characteristics of MVP patients that may benefit from this simple repair technique.

Methods

Based on 39 consecutive patients (28 men; mean age 57 ± 15) with severe primary Mitral regurgitation (MR) caused by bileaflet MVP referred for MVR, we sought to identify the preoperative echocardiographic parameters associated with successful ROA repair.

Results

Twenty‐three patients (59%) underwent standard resectional MVR (SMVR) while 16 (41%) underwent ROA. Cardiopulmonary bypass and cross clamp times were lower in ROA than in SMVR (74 ± 27 min vs 99 ± 42 min and 49 ± 19 min vs 70 ± 25 min, respectively, p = 0.03 and p = 0.005). ROA patients were more frequently women (50% vs 13%, p = 0.027). Echocardiographic characteristics of successful ROA were mid‐late systolic MR, a paradoxical systolic papillary muscle displacement, and paradoxical systolic annulus expansion (PAE). A prolapsing depth <10 mm, the absence of flail leaflet and ruptured chordae, the presence of multiple jets, more often in the central part of the valve were also associated with ROA. Non hemodynamic systolic anterior motion and residual trivial MR tended to be more frequent in ROA than in SMVR.

Conclusion

Simple and fast MVR using a ROA is feasible in 4/10 patients with complex forms of bileaflet MVP. Successful ROA patients were more frequently women, with mid‐late systolic central multiple jet, low prolapse depth, absence of chordal rupture or flail leaflet and PAE.
Comparative evaluation of fragment reattachment protocols for the management of teeth with crown‐root fractures
Authors: Lokade Amolkumar , Tewari Nitesh , Goel Shubhi , Mathur Vijay Prakash , Srivastav Sukeshana , Rahul Morankar
Published: March 2022

Background/Aim

A crown‐root fracture is a fracture of both the crown and the root of a tooth. The International Association of Dental Traumatology (2020) guidelines recommended fragment reattachment and stabilization of loose fragments as an immediate management protocol for uncomplicated crown‐root fractures. However, the lack of evidence and unpredictability make it a less popular treatment option. The aim of this study was to compare three protocols of fragment reattachment for the management of teeth with crown‐root fractures.

Methodology

Eighty mandibular bovine incisors with similar dimensions and no structural deformities were selected and randomized into four groups: Group I (Control/sound teeth); Group II (no rehydration); Group III (rehydration in distilled water for 15 min) and Group IV (rehydration in a humidification chamber for 15 min). A fracture was simulated to extend from the labial side of the middle‐third of the crown to the palatal side of the cervical‐third of the root. Fragments were exposed to the environment under normal temperature and pressure. Fragments were later reattached as per the standard protocol following the rehydration as specified for each group. Samples were subjected to thermocycling, and the force required to fracture them was evaluated by using a universal testing machine.

Results

The highest mean force required to fracture was seen in Group IV (208.27 ± 75.99 N) followed by Group III (182.01 ± 90.13 N) and Group II (158.85 ± 68.04 N). These differences were statistically significant. Comparison of the mean difference of force required to fracture between pairs of groups revealed statistically significant mean differences only between the controls and each experimental group.

Conclusion

The force required to fracture the reattached fragments in teeth with crown‐root fractures was affected by rehydration of the fragments. The force was higher in fragments reattached after rehydration, and the highest force was required in the teeth that had been rehydrated in a humidification chamber.