bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of the Judiciary: Lessons from the End of Empire
Authors: Stevens Robert
Published: November 2023

This paper is an attempt to analyse the relationship between, on the one hand, the role of courts as governmental institutions; and, on the other, the way and the grounds on which judges are selected to hear particular cases, and the views and attitudes of judges concerning the political significance of their decisions. This issue will be approached through a study of the work of the Judicial Committee of the Privy Council over the last one hundred years. Among other things, the study will bear out Patrick Atiyah’s view that there is an ‘English belief that it is largely immaterial which judges hear which appeals’, which leads to a failure to appreciate that the composition of a court can determine in advance the outcome of cases of political significance
Negligence and Economic Loss
Authors: Dwyer John
Published: November 2023

In the April 1967 issue of the Law Quarterly Review Patrick Atiyah, then a Fellow of New College, published a characteristically thoughtful and lucid paper on ‘Negligence and Economic Loss’. In it he considered the effect of the then recent decision in Hedley Byrne & Co. Ltd. v. Heller & Partners Ltd. (‘Hedley Byrne’) on what he described as ‘the general rule that liability in the tort of negligence did not extend to purely economic loss’. Feldthusen in his monograph Economic Negligence suggests that no such general rule then existed and that Atiyah’s paper was influential in the development of the approach in England and the British Commonwealth which subsumed various categories of economic loss under a general rule.
Denmark
Authors: Marstrand-Jorgensen Mads , Posner Bernhard
Published: November 2023

Denmark became an EC Member State as from 1 January 1973. Consequently Regulation (EEC) 3842/86, and subsequently Regulation (EC) 3295/94 as amended by Regulation (EC) 241/1999 have been applicable in Denmark from the day of their entry into force. Though the provisions of Regulation 3295/94 were directly applicable in Denmark, the national Danish Lawon Application of the Regulation set out a few supplementary provisions regarding the exercise of the powers vested in the customs authority.
France
Authors: Biardeaud Juliette
Published: November 2023

France is not only situated in the geographical heart of Europe, sharing land borders with Belgium, Luxembourg, Germany, Italy, Spain, and a short distance across the Channel from the United Kingdom, but it is also at the forefront of industry, notably in the luxury goods sector. It is therefore an ideal target market for counterfeiters, and also an interesting platform for transit purposes.
Hungary
Authors: Bérczes László
Published: November 2023

Hungary introduced the first law on border measures in respect of goods suspected of infringing certain intellectual property rights in 1997 in the form of the Government Decree No 128 of 1997 (‘the 1997 Decree’) which entered into force as of 1 August 1997. This law was inspired by the provisions of EC Regulation 3295/94and the TRIPs Agreement.However it was applied not only to counterfeit or pirated goods but also to parallel imports.
Lithuania
Authors: Lukošiūtė Asta
Published: November 2023

The effective fight against counterfeiting and piracy in Lithuania started in the spring of 2000 and was considerably strengthened with the adoption on 21 December 2001 of the Law on the protection of intellectual property rights upon importation and exportation of goods (‘the Intellectual Property Law’).This Law entered into force on 1 January 2001 and was already in line with Council Regulation (EC) 3295/94,but more importantly, it anticipated the draft document that became Council Regulation (EC) 1383/2003.
Luxembourg
Authors: Cywie Gary
Published: November 2023

Council Regulation (EEC) 3842/86 of 1 December 1986 laying down measures to prohibit the release for free circulation of counterfeit goodsentered into force in Luxembourg on 1 January 1988. Considering that the provisions of this Regulation were directly applicable in Luxembourg as of the day of its publication in the Official Journal of the European Communities,the Luxembourg authorities satisfied themselves with adopting a Decree on 29 June 1988 relating to the application of Regulation 3842/86, which specified the competent authority referred to in Article 3 of this Regulation.
The Netherlands
Authors: Noordzij Christine , Maks Marchien , Mutsaerts Frits , Grondman Maaike
Published: November 2023

Before Council Regulation (EC) No 1383/2003(the ‘Regulation’) came into force on 1 July 2004, the Netherlands, being a founding Member State of the European Community, already actively enforced the previous Council Regulations No 3842/86 and No 3295/94 (the ‘Previous Regulations’).Through the years national law has been amended in the Netherlands to ensure consistency with these Previous Regulations. Since the Regulation is based on its predecessors, no additional amendments were required.
Poland
Authors: Rzążewska Dorota , Senda Zofia
Published: November 2023

Poland’s accession to the European Union—on 1 May 2004—is an important turning point in the transition from national legislation on border measures to the Regulations of European Law. Until 30 April 2004, proceedings conducted by Polish customs authorities in the case of suspected entry into the Polish customs area of infringed goods were based on national law.
Molecular diagnostic yield for Blau syndrome in previously diagnosed juvenile idiopathic arthritis with uveitis or cutaneous lesions
Authors: Zhong Zhenyu , Dai Lingyu , Ding Jiadong , Gao Yu , Su Guannan , Zhu Yunyun , Deng Yang , Li Fuzhen , Gao Yuan , Yang Peizeng
Published: November 2023

Objective

Diagnostic pitfalls often arise in the community because of potentially misleading similarities between juvenile idiopathic arthritis (JIA) and Blau syndrome, an immune-related disorder caused by NOD2 gene mutations. It remains unclear in which population and to what extent next-generation sequencing techniques can aid in diagnosis.

Methods

We evaluated clinical usefulness of targeted next-generation sequencing in previously diagnosed JIA. Participants were required to have symptoms and signs suspected of Blau syndrome, including at least uveitis or cutaneous lesions in addition to arthritis. Targeted sequencing was conducted on NOD2 gene to detect diagnostic variants classified as pathogenic or likely pathogenic for Blau syndrome. We assessed the molecular diagnostic yield and clinical implications for patient care.

Results

Between 1 May 2008 and 1 June 2021, sequencing data were accrued from 123 previously diagnosed JIA (median age: 5 years; female: 62.6%). Targeted NOD2 sequencing yielded a positive molecular diagnosis of Blau syndrome in 21.1% (95% CI: 14.9%, 29.2%), encompassing six heterozygous missense mutations classified as pathogenic variants. Among those receiving a molecular diagnosis, changes in clinical management and treatment were considered as having occurred in 38.5%. Nine predictors were identified as being associated with a higher diagnostic yield, providing clinical clues to suspect the possibility of Blau syndrome.

Conclusion

Among some patients with paediatric-onset arthritis complicated with uveitis or cutaneous lesions, reassessment of the diagnosis of JIA may be warranted. Targeted NOD2 sequencing established the molecular diagnosis of Blau syndrome in nearly one-fifth of these cases and provided clinically relevant information for patient-care decisions.
Patient-reported swelling in arthralgia patients at risk for rheumatoid arthritis: is it of value?
Authors: Boeren Anna M P , Khidir Sarah J H , de Jong Pascal H P , van der Helm-van Mil Annette H M , van Mulligen Elise
Published: November 2023

Objective

Patients with clinically suspect arthralgia (CSA) are at risk for developing rheumatoid arthritis (RA). These patients often report joint swelling while this is not objectified by physical examination. To explore the value of patient-reported swelling in CSA, we aimed to determine its association with subclinical joint inflammation on imaging and RA development.

Methods

In two independent, similarly designed CSA cohorts from the Netherlands, symptomatic patients at risk for RA were studied. At baseline, patients indicated whether they had experienced swelling in hand joints. Subclinical joint inflammation was assessed with MRI or US. Patients were followed for inflammatory arthritis development.

Results

In total, 534 CSA patients from two independent cohorts were studied, and patient-reported swelling was present in 57% in cohort 1 and in 43% in cohort 2. In both cohorts patient-reported swelling was associated with subclinical joint inflammation. Using MRI, it associated specifically with tenosynovitis (odds ratio [OR] 3.7 [95% CI: 2.0, 6.9]) and when using US with synovitis (OR 2.3 [95% CI: 1.04, 5.3]). CSA patients with self-reported swelling at baseline developed arthritis more often, with hazard ratios of 3.7 (95% CI: 2.0, 6.9) and 3.4 (95% CI: 1.4, 8.4) in cohort 1 and 2, respectively. This was independent of clinical predictors (e.g. morning stiffness), autoantibody positivity and US-detected subclinical joint inflammation. However, when corrected for MRI-detected subclinical joint inflammation, self-reported swelling was no longer an independent predictor.

Conclusion

Patient-reported joint swelling in CSA relates to subclinical joint inflammation and is an independent risk factor for RA development, but it is less predictive than the presence of MRI-detected subclinical joint inflammation.
Convergent Adaptation of True Crabs (Decapoda: Brachyura) to a Gradient of Terrestrial Environments
Authors: Wolfe Joanna M , Ballou Lauren , Luque Javier , Watson-Zink Victoria M , Ahyong Shane T , Barido-Sottani Joëlle , Chan Tin-Yam , Chu Ka Hou , Crandall Keith A , Daniels Savel R , Felder Darryl L , Mancke Harrison , Martin Joel W , Ng Peter K L , Ortega-Hernández Javier , Palacios Theil Emma , Pentcheff N Dean , Robles Rafael , Thoma Brent P , Tsang Ling Ming , Wetzer Regina , Windsor Amanda M , Bracken-Grissom Heather D
Published: November 2023

For much of terrestrial biodiversity, the evolutionary pathways of adaptation from marine ancestors are poorly understood and have usually been viewed as a binary trait. True crabs, the decapod crustacean infraorder Brachyura, comprise over 7600 species representing a striking diversity of morphology and ecology, including repeated adaptation to non-marine habitats. Here, we reconstruct the evolutionary history of Brachyura using new and published sequences of 10 genes for 344 tips spanning 88 of 109 brachyuran families. Using 36 newly vetted fossil calibrations, we infer that brachyurans most likely diverged in the Triassic, with family-level splits in the late Cretaceous and early Paleogene. By contrast, the root age is underestimated with automated sampling of 328 fossil occurrences explicitly incorporated into the tree prior, suggesting such models are a poor fit under heterogeneous fossil preservation. We apply recently defined trait-by-environment associations to classify a gradient of transitions from marine to terrestrial lifestyles. We estimate that crabs left the marine environment at least 7 and up to 17 times convergently, and returned to the sea from non-marine environments at least twice. Although the most highly terrestrial- and many freshwater-adapted crabs are concentrated in Thoracotremata, Bayesian threshold models of ancestral state reconstruction fail to identify shifts to higher terrestrial grades due to the degree of underlying change required. Lineages throughout our tree inhabit intertidal and marginal marine environments, corroborating the inference that the early stages of terrestrial adaptation have a lower threshold to evolve. Our framework and extensive new fossil and natural history datasets will enable future comparisons of non-marine adaptation at the morphological and molecular level. Crabs provide an important window into the early processes of adaptation to novel environments, and different degrees of evolutionary constraint that might help predict these pathways. [Brachyura; convergent evolution; crustaceans; divergence times; fossil calibration; molecular phylogeny; terrestrialization; threshold model.]
Metabolic insights and background from naturally affected pigs during Streptococcus suis outbreaks
Authors: Fabà Lluís , Aragon Virginia , Litjens Ralph , Galofré-Milà Núria , Segura Mariela , Gottschalk Marcelo , Doelman John
Published: November 2023

Streptococcus suis (S. suis) is an endemic zoonotic pathogen still lacking adequate prevention in pigs. The present case study looked back to the occurrence and consequences of S. suis outbreaks in our swine research facilities in search of new metabolic and physiological insight. From a series of outbreaks, a dataset was created including 56 pigs sampled during disease detection based on clinical signs. Pigs suspected with S. suis infection were defined as diseased (n = 28) and included pigs defined as neurologically diseased (n = 20) when severe neurological signs (central nervous system dysfunctions, i.e., opisthotonos, ataxia, and generalized tremor) were observed. Another set of 28 pigs included respective pen mates from each case and were defined as control. Representative deaths were confirmed to be caused by S. suis. Tonsillar swabs were collected and analyzed by quantitative polymerase chain reaction (qPCR) for total bacteria, total S. suis, and S. suis serotypes (SS) 2 (and/or 1/2) and 9. Blood and sera were analyzed to quantify blood gases, minerals, and S. suis reactive immunoglobulins against current isolates. Data collected included litter sibling associations, birth and weaning body weight (BW), and average daily gain (ADG) 7 d after the disease detection. In general, the disease increased pH, sO2 and the incidence of alkalosis, but reduced pCO2, glucose, Ca, P, Mg, K, and Na in blood/serum compared to control. The SS2 (and/or SS1/2) prevalence was significantly (P < 0.05) increased in neurologically diseased pigs and its relative abundance tended (P < 0.10) to increase in tonsils. In contrast, the relative abundance of total S. suis was lower (P > 0.05) in diseased pigs than control pigs. Levels of S. suis reactive IgG2 were lower, but IgM were higher (P < 0.03) in neurologically affected pigs compared to control. Furthermore, there was an increased proportion of sibling pigs that were diseased compared to control. In conclusion, our results evidence that naturally affected pigs were associated to average performing pigs without any predisease trait to highlight but a sow/litter effect. Besides, neurologically affected pigs had increased S. suis (SS2 and/or 1/2) prevalence and relative abundance, a respiratory alkalosis profile, and mineral loss.
Neuro‐HIV—New insights into pathogenesis and emerging therapeutic targets
Authors: Sviridov Dmitri , Bukrinsky Michael
Published: November 2023

HIV‐associated neurocognitive disorders (HAND) is a term describing a complex set of cognitive impairments accompanying HIV infection. Successful antiretroviral therapy (ART) reduces the most severe forms of HAND, but milder forms affect over 50% of people living with HIV (PLWH). Pathogenesis of HAND in the ART era remains unknown. A variety of pathogenic factors, such as persistent HIV replication in the brain reservoir, HIV proteins released from infected brain cells, HIV‐induced neuroinflammation, and some components of ART, have been implicated in driving HAND pathogenesis in ART‐treated individuals. Here, we propose another factor—impairment of cholesterol homeostasis and lipid rafts by HIV‐1 protein Nef—as a possible contributor to HAND pathogenesis. These effects of Nef on cholesterol may also underlie the effects of other pathogenic factors that constitute the multifactorial nature of HAND pathogenesis. The proposed Nef‐ and cholesterol‐focused mechanism may provide a long‐sought unified explanation of HAND pathogenesis that takes into account all contributing factors. Evidence for the impairment by Nef of cellular cholesterol balance, potential effects of this impairment on brain cells, and opportunities to therapeutically target this element of HAND pathogenesis are discussed.
PA and NP general practice employment in the Netherlands
Authors: van den Brink Geert TWJ , Kouwen Arjan J. , Hooker Roderick S. , Vermeulen Hester , Laurant Miranda GH
Published: November 2023

General practitioners (GPs) are the cornerstone of primary healthcare in the Netherlands. As a national strategy, physician associates/assistants (PAs) and NPs were introduced to address growing healthcare demand. In this study, four representative practices were analyzed quantitatively and qualitatively—two solo practices with a PA or NP and two group practices with a PA or NP. A reference group of GPs served as experts. The annual encounters per full-time GP averaged 6,839; for the NPs, 2,636; and the PAs, 4,926. Billable services were 70% to 100%, averaging 71% for NPs and 85% for PAs, and in three of the four practices, the employment of the NP or PA was cost-efficient. The qualitative data show that PAs and NPs contribute to general practice, easing the workload so that the GP has more time for complex patients. PA and NP employment was financially beneficial in 75% of cases.
NP and PA transition to practice
Authors: Morgan Perri , Barnes Hilary , Batchelder Heather R. , Tuttle Brandi , Covelli Asefeh Faraz , Everett Christine , Jackson George L. , Anglin Lorraine , Pate Nathalie Ortiz , Dieter Patricia , Bludorn Janelle
Published: November 2023

Objectives:

Newly graduated NPs and physician associates/assistants (PAs) benefit from transition to practice (TTP) support to move successfully into practice. TTP programs (such as onboarding programs, fellowships, and residencies) hold promise for improving workforce outcomes. The purpose of this scoping review was to describe the literature regarding NP/PA TTP programs.

Methods:

Using the Joanna Briggs Institute methodology, a specific approach for systematically conducting reviews, publications from January 1990 to May 2022 were included if they addressed fellowships, residencies, or onboarding programs for NPs or PAs. Final data extraction involved 216 articles.

Results:

The pace of publication increased over time, with a noticeable increase since 2015. Articles were most commonly about fellowships or residencies, NPs, and programs set in nonrural, acute care US settings and in academic health centers.

Conclusions:

A gap exists in our understanding of onboarding programs and programs focusing on PAs, as well as TTP support in rural and primary care settings. In addition, few articles assess TTP program outcomes such as benefits and costs. This review describes the need for more published literature in these areas.
Trends in Location of Death for Individuals With Ovarian Cancer in the United States
Authors: Mathew Angelin T. , Jain Bhav , Patel Tej A. , Hammond Alessandro , Dee Edward Christopher , Chino Fumiko
Published: November 2023

Using the publicly available Centers for Disease Control and Prevention’s WONDER (Wide-ranging Online Data for Epidemiologic Research) database from 2003 to 2019, we evaluated associations between decedent characteristics and location of death for patients with ovarian malignancy. We found that Black, Native American, Asian American, and Hispanic patients were more likely to die in hospitals than White patients, despite an overall reduction in hospital deaths and an overall increase in hospice facility deaths. Additionally, patients with lesser educational attainment were more likely to die in nursing facilities and less likely to die in hospice facilities. Although there may be some contribution from cultural preferences, these findings may represent disparities in access to palliative care affecting people with cancer from racial and ethnic minoritized groups.
Medical Management of Ovarian Endometriomas
Authors: Eberle Alexa , Nguyen Dong Bach , Smith Jessica Papillon , Mansour Fady W. , Krishnamurthy Srinivasan , Zakhari Andrew
Published: November 2023

OBJECTIVE:

To estimate the effect of medical management on the size of ovarian endometriomas.

DATA SOURCE:

Online databases were searched from inception to October 2022, including Ovid MEDLINE, Ovid EMBASE, PubMed, EBM Reviews—Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, and Web of Science.

METHODS OF STUDY SELECTION:

Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we included all English-language, full-text articles that reported on change in endometrioma size (either diameter or volume) after medical interventions. Studies evaluating surgical interventions or postoperative recurrence were excluded. All screening and data extraction were performed independently by two authors. Risk of bias assessment was performed with either the Cochrane Risk of Bias Tool for randomized controlled trials or a modified Newcastle-Ottawa Scale for observational studies.

TABULATION, INTEGRATION, AND RESULTS:

After removal of duplicates, 9,332 studies were screened, with 33 full-text articles deemed eligible for inclusion. In the meta-analysis, dienogest showed significant reduction in cyst diameter (reduction 1.32 cm, 95% CI, 0.91–1.73, eight studies, n=418 cysts) and volume (mean difference of log-transformed volume 1.35, 95% CI, 0.87–1.83, seven studies, n=282 cysts). Similarly, significant reductions were seen with the oral contraceptive pill (OCP) (1.06 cm, 95% CI, 0.59–1.53, nine studies, n=455), gonadotropin-releasing hormone (GnRH) agonists (1.17 cm, 95% CI, 0.42–1.92, four studies, n=128 cysts), norethindrone acetate (0.6 cm, 95% CI, 0.27–0.94, two studies, n=88 cysts), and danazol (1.95 cm, 95% CI, 1.18–2.73, two studies, n=34 cysts). Norethindrone acetate with aromatase inhibitor was also effective in reducing endometrioma volume (mean difference of log-transformed volume 1.47, 95% CI, 0.16–2.78, two studies, n=34 cysts).

CONCLUSION:

Medical management with dienogest, OCPs, GnRH agonists, norethindrone acetate, norethindrone acetate with aromatase inhibitor, or danazol can reduce the size of ovarian endometriomas.

SYSTEMATIC REVIEW REGISTRATION:

PROSPERO, CRD 42022363319.
Evaluation and Management of Endometriosis in the Adolescent
Authors: Shim Jessica Y. , Laufer Marc R. , King Cara R. , Lee Ted T. M. , Einarsson Jon I. , Tyson Nichole
Published: November 2023

Endometriosis is a chronic condition, with debilitating symptoms affecting all ages. Dysmenorrhea and pelvic pain often begin in adolescence, affecting school, daily activities, and relationships. Despite the profound burden of endometriosis, many adolescents experience suboptimal management and significant delay in diagnosis. The symptomatology and laparoscopic findings of endometriosis in adolescents are often different than in adults, and the medical and surgical treatments for adolescents may differ from those for adults as well. This Narrative Review summarizes the diagnosis, evaluation, and management of endometriosis in adolescents. Given the unique challenges and complexities associated with diagnosing endometriosis in this age group, it is crucial to maintain a heightened level of suspicion and to remain vigilant for signs and symptoms. By maintaining this lower threshold for consideration, we can ensure timely and accurate diagnosis, enabling early intervention and improved management in our adolescent patients.
The Biomechanics of the Transpedicular Endoscopic Approach
Authors: Meisterhans Michel , Hagel Vincent , Spirig José M. , Fasser Marie-Rosa , Farshad Mazda , Widmer Jonas
Published: November 2023

Study Design.

Biomechanical cadaveric study.

Objective.

The goal of this study was to analyze the effects of an endoscopic transpedicular approach with different drill diameters (6 and 8 mm) and compare them with the intact native side. In addition, the influence of bone quality on the resistance of the pedicle was investigated.

Summary of Background Data.

Clinical studies have repeatedly highlighted the benefits of endoscopic transpedicular decompression for downmigrated lumbar disc herniations. However, the biomechanical effects on pedicle stability have not been studied up to now.

Materials and Methods.

Twenty-four vertebras originating from four fresh-frozen cadavers were tested under uniaxial compression load in a ramp-to-failure test: (1) the tunneled pedicle on one side, and (2) the native pedicle on the other side. Twelve lumbar vertebrae were assigned to drill diameter of 6 mm and the other 12 to diameter of 8 mm.

Results.

The median ratio of sustained force for the operated side compared with the intact contralateral side is equal to 74% (63–88) for both drill diameters combined. An 8 mm transpedicular approach recorded an axial resistance of 77% (60–88) compared with the intact contralateral side (P=0.002). A 6 mm approach resulted in an axial resistance of 72% (66–84) compared with the intact opposite side (P=0.01). No significant difference between the two different drill diameters was recorded (P=1). For all three subgroups (intact, 8 mm, 6 mm) the Hounsfield units-values and the absolute resistance force showed significant correlations (intact: ρ=0.859; P<0.001; 8 mm: ρ=0.902; P<0.001; 6 mm: ρ=0.835; P<0.001).

Conclusion.

The transpedicular approach significantly reduces the axial resistance force of the pedicle, which may lead to pedicle fracture. Bone quality correlated positively with the absolute resistance force of the pedicle, whereas the influence of the drill hole diameter plays only a limited role.
Institutional Structures and Processes to Support Sepsis Care: A Multihospital Study
Authors: Lóser Meghan K. , Horowitz Jennifer K. , England Peter , Esteitie Rania , Kaatz Scott , McLaughlin Elizabeth , Munroe Elizabeth , Heath Megan , Posa Pat , Flanders Scott A. , Prescott Hallie C.
Published: November 2023

OBJECTIVES:

To identify opportunities for improving hospital-based sepsis care and to inform an ongoing statewide quality improvement initiative in Michigan.

DESIGN:

Surveys on hospital sepsis processes, including a self-assessment of practices using a 3-point Likert scale, were administered to 51 hospitals participating in the Michigan Hospital Medicine Safety Consortium, a Collaborative Quality Initiative sponsored by Blue Cross Blue Shield of Michigan, at two time points (2020, 2022). Forty-eight hospitals also submitted sepsis protocols for structured review.

SETTING:

Multicenter quality improvement consortium.

SUBJECTS:

Fifty-one hospitals in Michigan.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Of the included hospitals, 92.2% (n = 47/51) were nonprofit, 88.2% (n = 45/51) urban, 11.8% (n = 6/51) rural, and 80.4% (n = 41/51) teaching hospitals. One hundred percent (n = 51/51) responded to the survey, and 94.1% (n = 48/51) provided a sepsis policy/protocol. All surveyed hospitals used at least one quality improvement approach, including audit/feedback (98.0%, n = 50/51) and/or clinician education (68.6%, n = 35/51). Protocols included the Sepsis-1 (18.8%, n = 9/48) or Sepsis-2 (31.3%, n = 15/48) definitions; none (n = 0/48) used Sepsis-3. All hospitals (n = 51/51) used at least one process to facilitate rapid sepsis treatment, including order sets (96.1%, n = 49/51) and/or stocking of commonly used antibiotics in at least one clinical setting (92.2%, n = 47/51). Treatment protocols included guidance on antimicrobial therapy (68.8%, n = 33/48), fluid resuscitation (70.8%, n = 34/48), and vasopressor administration (62.5%, n = 30/48). On self-assessment, hospitals reported the lowest scores for peridischarge practices, including screening for cognitive impairment (2.0%, n = 1/51 responded “we are good at this”) and providing anticipatory guidance (3.9%, n = 2/51). There were no meaningful associations of the Centers for Medicare and Medicaid Services’ Severe Sepsis and Septic Shock: Management Bundle performance with differences in hospital characteristics or sepsis policy document characteristics.

CONCLUSIONS:

Most hospitals used audit/feedback, order sets, and clinician education to facilitate sepsis care. Hospitals did not consistently incorporate organ dysfunction criteria into sepsis definitions. Existing processes focused on early recognition and treatment rather than recovery-based practices.
Data Missingness Reporting and Use of Methods to Address It in Critical Care Cohort Studies
Authors: Wu Ting Ting , Smith Louisa H. , Vernooij Lisette M. , Patel Emi , Devlin John W.
Published: November 2023

IMPORTANCE:

Failure to recognize and address data missingness in cohort studies may lead to biased results. Although Strengthening the Reporting of Observational Studies in Epidemiology reporting guidelines advocate data missingness reporting, the degree to which missingness is reported and addressed in the critical care literature remains unclear.

OBJECTIVES:

To review published ICU cohort studies to characterize data missingness reporting and the use of methods to address it.

DESIGN, SETTING, AND PARTICIPANTS:

We searched the 2022 table of contents of 29 critical care/critical care subspecialty journals having a 2021 impact factor greater than or equal to 3 to identify published prospective clinical or retrospective database cohort studies enrolling greater than or equal to 100 patients.

MAIN OUTCOMES AND MEASURES:

In duplicate, two trained researchers conducted a manuscript/supplemental material PDF word search for “missing*” and extracted study type, patient age, ICU type, sample size, missingness reporting, and the use of methods to address it.

RESULTS:

A total of 656 studies were reviewed. Of the 334 of 656 (50.9%) studies mentioning missingness, missingness was reported for greater than or equal to 1 variable in 234 (70.1%) and it exceeded 5% for at least one variable in 160 (47.9%). Among the 334 studies mentioning missingness, 88 (26.3%) used exclusion criteria, 36 (10.8%) used complete-case analysis, and 164 (49.1%) used a formal method to avoid missingness. In these 164 studies, imputation only was used in 100 (61.0%), an analytic strategy only in 24 (14.6%), and both in 40 (24.4%). Only missingness greater than 5% (in ≥ 1 variable) was independently associated with greater use of a missingness method (adjusted odds ratio 2.91; 95% CI, 1.85–4.60). Among 140 studies using imputation, multiple imputation was used in 87 studies (62.1%) and simple imputation in 49 studies (35.0%). For the 64 studies using an analytic method, 12 studies (18.8%) assigned missingness as an unknown category, whereas sensitivity analysis was used in 47 studies (73.4%).

CONCLUSIONS AND RELEVANCE:

Among published critical care cohort studies, only half mentioned result missingness, one-third reported actual missingness and only one-quarter used a method to manage missingness. Educational strategies to promote missingness reporting and resolution methods are required.
Lessons Learned From a Systematic, Hospital-Wide Implementation of the ABCDEF Bundle: A Survey Evaluation
Authors: Brown Joan C. , Ding Li , Querubin Jynette A. , Peden Carol J. , Barr Juliana , Cobb Joseph Perren
Published: November 2023

Objective:

We recently reported the first part of a study testing the impact of data literacy training on “assessing pain, spontaneous awakening and breathing trials, choice of analgesia and sedation, delirium monitoring/management, early exercise/mobility, and family and patient empowerment” [ABCDEF [A-F]) compliance. The purpose of the current study, part 2, was to evaluate the effectiveness of the implementation approach by surveying clinical staff to examine staff knowledge, skill, motivation, and organizational resources.

DESIGN:

The Clark and Estes Gap Analysis framework was used to study knowledge, motivation, and organization (KMO) influences. Assumed influences identified in the literature were used to design the A-F bundle implementation strategies. The influences were validated against a survey distributed to the ICU interprofessional team.

SETTING:

Single-center study was conducted in eight adult ICUs in a quaternary academic medical center.

SUBJECTS:

Interprofessional ICU clinical team.

INTERVENTIONS:

A quantitative survey was sent to 386 participants to evaluate the implementation design postimplementation. An exploratory factor analysis was performed to understand the relationship between the KMO influences and the questions posed to validate the influence. Descriptive statistics were used to identify strengths needed to sustain performance and weaknesses that required improvement to increase A-F bundle adherence.

MEASUREMENT AND RESULTS:

The survey received an 83% response rate. The exploratory factor analysis confirmed that 38 of 42 questions had a strong relationship to the KMO influences, validating the survey’s utility in evaluating the effectiveness of implementation design. A total of 12 KMO influences were identified, 8 were categorized as a strength and 4 as a weakness of the implementation.

CONCLUSIONS:

Our study used an evidence-based gap analysis framework to demonstrate key implementation approaches needed to increase A-F bundle compliance. The following drivers were recommended as essential methods required for successful protocol implementation: data literacy training and performance monitoring, organizational support, value proposition, multidisciplinary collaboration, and interprofessional teamwork activities. We believe the learning generated in this two-part study is applicable to implementation design beyond the A-F bundle.
The role of the purinergic ligand-gated ion channel 7 receptor in common digestive system cancers
Authors: Wang Xin , Yu Qingqing , Bai Xue , Li Xinyu , Sun Yanli , Peng Xiaoxiang , Zhao Ronglan
Published: November 2023

The incidence of digestive malignancies has increased in recent years, including colorectal cancer (CRC), hepatocellular carcinoma (HCC) and pancreatic cancer. Advanced stages of these cancers are prone to metastasis, which seriously reduce the standard of living of patients and lead to decline in the survival rate of patients. So far there are no good specific drugs to stop this phenomenon. It is very important and urgent to find new biomarkers and therapeutic targets. Purinergic ligand-gated ion channel 7 receptor (P2X7R) is ATP-gated and nonselective ion channel receptor involved in many inflammatory processes and cancer progression. P2X7R is present in many cancer cells and promotes or inhibits cancer development through signal transduction. Studies have presented that P2X7R plays a role in the proliferation and migration of digestive system cancers, such as CRC, HCC and pancreatic cancer. Therefore, P2X7R may serve as a biomarker or therapeutic target for digestive system cancers. This paper describes the structure and function of P2X7R, and mainly reviews the research progress on the role of P2X7R in CRC, HCC and pancreatic cancer.
Mediterranean diet and colorectal adenomas: a systematic review and meta-analysis of observational studies
Authors: Jafari Nasab Saeede , Clark Cain C. T. , Entezari Mohammadhasan
Published: November 2023

Colorectal adenomas (CRAs) are epithelial lesions of the large bowel that can develop into colorectal cancer. Some studies have shown an inverse association of the Mediterranean diet (MED) with adenoma, but the extent of the association is equivocal. Owing to the lack of meta-analytical evidence in the literature, we sought to assess the association between MED and CRAs by conducting a systematic review and meta-analysis. A comprehensive systematic literature search of observational studies was conducted via PubMed, Scopus, Google Scholar and Web of Sciences up to May 2023. Studies were included in our review if they evaluated the association between MED and CRA, following an observational study design. Six studies were included in this study. We found that adherence to MED was inversely associated with CRA risk (odds ratio, 0.79; confidence interval, 0.73–0.85); implying that higher adherence to MED could reduce the risk of CRA by ~21%. Stratification by the year of studies, sex, study design, country and exposure showed a significant association between MED and CRA. The results of the current study provide evidence of an inverse association between adherence to MED and CRAs.
Pharmacokinetic Consideration of Venetoclax in Acute Myeloid Leukemia Patients: A Potential Candidate for TDM? A Short Communication
Authors: Philippe Michael , Guitton Jérôme , Goutelle Sylvain , Thoma Yann , Favier Bertrand , Chtiba Nour , Michallet Mauricette , Belhabri Amine
Published: November 2023

Background:

Venetoclax (VNX)-based regimens have demonstrated significantly favorable outcomes in patients with acute myeloid leukemia (AML) and are now becoming the standard treatment. Tyrosine kinase inhibitors are administered at a fixed dose, irrespective of body surface area or weight. For such orally targeted therapies, real-world data have highlighted a larger pharmacokinetic (PK) interindividual variability (IIV) than expected. Even if VNX PKs have been well characterized and described in the literature, only 1 clinical trial–based PK study has been conducted in patients with AML. This study aimed to evaluate the PK of VNX in AML patients.

Material and methods:

We retrospectively analyzed all patients treated with a combination of VNX–azacitidine between January and July 2022 at our center, using at least 1 available VNX blood sample. Based on a previously published population PK model, individual PK parameters were estimated to evaluate the exposure and IIV.

Results:

and Discussion. Twenty patients received VNX in combination with azacitidine, according to the PK data. A total of 93 plasma concentrations were collected. The dose of VNX was 400 mg, except in 7 patients who received concomitant posaconazole (VNX 70 mg). The patients' weight ranged from 49 kg to 108 kg (mean = 78 kg). Mean individual clearance was 13.5 ± 9.4 L/h with mean individual daily area under the concentration–time curves of 35.8 mg.h/L with significant IIV (coefficient of variation = 41.1%). Ten patients were still alive (8 in complete response), but all experienced at least 1 hematological toxicity of grade ≥ 3.

Conclusions:

Based on the observed large PK variability in the data from our real-world AML patients, the risk of drug interactions and the recommended fixed-dosage regimen of VNX therapeutic drug monitoring may be useful.
An online mind-body program improves mental health and quality of life in primary biliary cholangitis: A randomized controlled trial
Authors: Watt Makayla , Hyde Ashley , Johnson Emily , Wright Gail M. , Vander Well Shauna , Sadasivan Chikku , Lee-Baggley Dayna , Spence John C. , Mason Andrew , Ko Hin Hin , Tam Edward , Tandon Puneeta
Published: November 2023

Background and Aims:

People with primary biliary cholangitis (PBC) experience high rates of mental distress and fatigue despite standard of care therapy. We aimed to assess the impact of an online mind-body intervention on these symptoms.

Methods:

This 12-week RCT used sequential mixed-methods evaluation. Alongside standard of care, participants with primary biliary cholangitis were randomized to receive weekly countdown emails, or the intervention consisting of (i) a weekly 20–30 minute-mind-body follow-along video, (ii) weekly 5–10-minute psychology-based “managing chronic disease skills videos,” and (iii) 10-minute telephone check-ins. The primary outcome was a change in the Hospital Anxiety and Depression Scale (HADS). Secondary outcomes evaluated changes in fatigue, perceived stress, resilience, and health-related quality of life. ANCOVA determined between-group differences.

Results:

Of the 87 randomized patients (control group: n = 44, intervention group: n = 43), the between-group HADS total score improved by 20.0% (95% CI 4.7, 35.2,p= 0.011). Significant improvements were seen in depression (25.8%), perceived stress (15.2%), and 2 primary biliary cholangitis-40 domains [emotional symptoms (16.3%) and social symptoms (11.8%)] with a mean satisfaction of 82/100. This corresponded with end-of-study qualitative findings. Although no improvements were observed in fatigue in the main analysis, a significant benefit was observed in the subgroup of intervention participants (20/36;56%) who completed the mind-body video routine at least 3 times per week.

Conclusion:

This intervention improved measures of mental wellness and quality of life with high satisfaction and reasonable adherence. Future studies could explore strategies to optimize adherence and target fatigue.
The Evolution of Employee Assistance Programs to Best Support Healthcare Organizations
Authors: Couser Gregory P. , Nation Jody L. , Apker Dennis P. , Connaughty Susan M. , Hyde Mark A.
Published: November 2023

Goal:

Employee assistance programs (EAPs) have been evolving since they first became prevalent in the 1970s. The important counseling component of EAPs is sometimes lost in discussions about what they do, with many EAPs marketing a broad portfolio of services such as childcare, elder care, legal referral, and other concierge services rather than counseling. The objective of this study was to examine outcomes for the EAP of one organization (Mayo Clinic), compare them to outcomes reported in the literature, and gain insights to help all healthcare organizations best support their employees.

Methods:

Consistent with customary EAP practice, data for this study was collected through an anonymous survey link distributed by e-mail to users of individual counseling as well as users of organizational consulting services such as advising leaders and supervisors and leading educational sessions.

Principal Findings:

All (n= 82) individual counseling respondents indicated they would recommend the EAP, none reported worse symptoms, 90% decreased their stress levels, 92% reduced their feelings of anxiety, 88% enjoyed an overall improvement in mood, and 95% developed new skills. If their concern was work-related, 96% agreed the counselor understood the work culture and was able to provide helpful guidance; of the clients who were feeling burned out, 86% agreed they gained strategies to reduce its symptoms. Thematic analysis of individual counseling services indicated that participants highly valued their counselors. Regarding organizational consulting services, respondents (n= 50) indicated EAP services increased their confidence as leaders, supported their work, and provided tangible guidance. They appreciated having an internal EAP counselor. Thematic analysis of organizational consulting services indicated that EAP supported leaders by listening, coaching, and empowering them to normalize issues.

Practical Applications:

EAPs have evolved into distinct internal, external, and hybrid internal–external models. Internal model counselors are company employees with inside knowledge of company culture, external EAP model counselors are contracted outside of the company, and hybrid models combine a small cadre of internal counselors with the support of outside contractors. Regardless of the model, EAP counselors must collaborate with internal stakeholders, notably the human resources department, to efficiently identify and troubleshoot employee relational issues and allow for customized initiatives to improve mental health. Based upon these findings and the authors' direct experiences with EAP providers, components of an ideal EAP are outlined to show how EAPs can best support employees. Healthcare leaders seeking to add EAP services are advised to focus on offerings that are custom fit to the organization.
Outcomes of Recipients Aged 65 Years and Older Bridged to Lung Transplant With Extracorporeal Membrane Oxygenation
Authors: Zhou Alice L. , Jenkins Reed T. , Ruck Jessica M. , Shou Benjamin L. , Larson Emily L. , Casillan Alfred J. , Ha Jinny S. , Merlo Christian A. , Bush Errol L.
Published: November 2023

Extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplant (BTT) has been used for critically ill candidates with excellent outcomes, but data on this strategy in older recipients remain limited. We compared outcomes of no BTT, mechanical ventilation (MV)-only BTT, and ECMO BTT in recipients of greater than or equal to 65 years. Lung-only recipients of greater than or equal to 65 years in the United Network for Organ Sharing database between 2008 and 2022 were included and stratified by bridging strategy. Of the 9,936 transplants included, 226 (2.3%) were MV-only BTT and 159 (1.6%) were ECMO BTT. Extracorporeal membrane oxygenation BTT recipients were more likely to have restrictive disease pathology, had higher median lung allocation score, and spent fewer days on the waitlist (all p < 0.001). Compared to no-BTT recipients, ECMO BTT recipients were more likely to be intubated or on ECMO at 72 hours posttransplant and had longer hospital lengths of stay (all p < 0.001). Extracorporeal membrane oxygenation BTT recipients had increased risk of 3 years mortality compared to both no-BTT (adjusted hazard ratio [aHR] = 1.48 [95% confidence interval {CI}: 1.14–1.91], p = 0.003) and MV-only recipients (aHR = 1.50 [95% CI: 1.08–2.07], p = 0.02). Overall, we found that ECMO BTT in older recipients is associated with inferior posttransplant outcomes compared to MV-only or no BTT, but over half of recipients remained alive at 3 years posttransplant.
Epidemiological study of hereditary hemorrhagic disorders in Najaf province, Iraq
Authors: Ajeena Ezzate Hasson , Saleem Ali Adil
Published: November 2023

Hemophilia and Von Willbrand disease (VWD) are the most well known types of hereditary hemorrhagic disorders (HHD). Hemophilia affects about 200 000 people worldwide, while VWD affects about 80 000. Because there is a scarcity of epidemiologic studies on hemophilia in Iraq, this study was carried out to evaluate the prevalence and incidence trends, as well as to identify some clinical and epidemiological features of hemophilia patients in Najaf province, Iraq. This study was carried out in the Najaf's hemophilia center. The data were obtained by reviewing all patients’ documents, as well as the center registration book from 2011 to 2021. In addition, the Ministry of Health provided relevant population data for Najaf. Notably, there are currently 214 patients registered in Najaf province. The results revealed that the severe form of hemophilia A was the permanent type of HHDs in the patients compared with the rest of the types that include HHD with no significant differencePat least 0.05. The frequency of this group of disorders appeared to increase in the period between 2011 and 2013, especially in 2012 followed by a decline in the incidence until 2021, which recorded a sudden increase in these disorders. These findings highlight that hemophilia types A and B were the most prevalent disorders of HHD in Najaf province, and the increase in number of newly recorded cases because of consanguineous marriage increased recently in this area.