bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

SummaryBackground and aimsExtra‐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.MethodsAs 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.ResultsFor 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.ConclusionsConsensus 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

AimsRecent 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.MethodsWe 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.ResultsThe 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.ConclusionsThe 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

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

AimsTAK‐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).MethodsThe 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.ResultsNo 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.ConclusionTAK‐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

AimsDose 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.MethodsThis 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.ResultsThe 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.ConclusionFuture 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

AimsMeropenem 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.MethodsThis 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.ResultsTwo 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%).ConclusionThis 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

ObjectiveDemonstrate 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 settingThis 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.ResultsLower‐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).ConclusionThe 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

AbstractPriority 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

AbstractSuffering 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

SummaryWe 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

SummaryThrombotic 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

AbstractClonal 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

AbstractMatching 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

AbstractSix 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.