bluuebunny/crossref_metadata_2025 huggingface dataset:
1963 `Three sides to every story'- Living the patient, carer and staff experience of COVID
Authors: Ramsey S , Hurst H , Briggs M , Wentworth L
Published: January 2024

Introduction

When COVID-19 first entered our world in March 2020 and the country went into lock down, the NHS braced itself for one of its biggest challenges of this century. Older, frail patients were in the highest risk group, with those in care homes not only at higher risk of death, but higher risk of contracting COVID-19, often suffering more psychological disturbances (Hewitt et al., 2020; Numbers & Brodaty, 2021). This study was conceived by two nurse researchers working throughout the pandemic on a COVID ward for predominantly older people, aiming to capture the experiences of patients, families/carers and staff members.

Methods

Phenomenology was the most appropriate methodology to provide an in-depth lived experience perspective. Full ethical approval was obtained and participants were sampled purposively. In-depth unstructured interviews were conducted and transcribed in full before being analysed hermeneutically using the four steps outlined by Fleming et al. (2003).

Results

30 participants were recruited (10 patients, 10 relatives, including several bereaved and 10 staff members). Whilst experience varied between and within groups, core themes emerged:

1. Communication difficulties were poignantly expressed, with staff acting as intermediaries between patients and their family members who were kept apart through visiting restrictions, whilst managing clinical care and their own emotional responses.

2. Challenges of care were experienced by all groups, with anxiety around contagion conflicting with feelings of guilt and long-term psychological impact described by staff. 3. Collective experiences of grief and loss were described as participants grappled with coming to terms with encountering death and dying on an unprecedented scale and under such extraordinary conditions.

Conclusion

This study adds to the growing evidence base around experience of the COVID pandemic, adding insight into the triangulated experience of those affected and highlighting the profound effect on patients, relatives and staff.
2014 The experience of frailty in the Tanzanian hospital system: A qualitative exploration service user and provider perspectives
Authors: Davidson S L , Hardy J , Randall T , Murray A , Lyimo G , Msangi W , Kilasara J , Mariki L , Urasa S , Breckons M , Dotchin C L , Walker R W
Published: January 2024

Background

Frailty is becoming increasingly prevalent in Low- and Middle-Income Countries (LMICs). However, little is known about the lived experience of older people with frailty in their interactions with the healthcare systems in LMICs. This study aimed to explore the experiences, attitudes and needs of hospitalised older people with frailty in a low-income setting, from the perspective of service users and providers.

Methods

A purposive sample of older people with frailty recently admitted to hospital, their carers and healthcare providers, were recruited from four hospitals in the Kilimanjaro Region of Tanzania. One-to-one and dyad interviews were conducted in Swahili, based around a structured topic guide. Recordings were transcribed and translated into English in an iterative process aimed at preserving the original meaning through “transliteration”. Transcripts were analysed using a reflexive thematic paradigm.

Results

Interviews with 43 service users and 15 service providers highlighted the cultural norm of respect and value placed on older people; as such it is considered the role of everyone in society to provide care. However, many working age adults struggle with the competing responsibilities of supporting their parents and their children. Maintaining strong relationships with family and financial preparation were therefore considered critical to healthy ageing. The complex health problems and significant care needs of older people with frailty pose a considerable challenge during hospital admission. On the ward, family often take responsibility for personal care and feeding to reduce the work of healthcare providers. Economic worries and resource scarcity impact every part of the patient journey from struggles in accessing hospital services, to quality of care during admission and after discharge.

Conclusion

Frailty is understood as a communitywide issue in Tanzania, and family are expected to take a much larger role in care during acute hospital admission, partly mitigating the impact of resource scarcity.
1897 Older stroke survivors and rehabilitation therapists’ views on home-based resistance exercise for upper limbs
Authors: Ali K , Shafizadeh M , Nasr N , Balchin T , Hart J , Kelley J
Published: January 2024

Introduction

Upper limb recovery after stroke depends on participating in personalised task-specific exercise programmes. However, older adults with stroke find it challenging to maintain an optimal level of engagement with such exercise programmes due to personal and environmental factors. The aim of this study was to explore the views of stroke survivors and rehabilitation therapists on home-based resistance exercises for upper limbs.

Method

A qualitative study of semi-structured virtual and in-person interviews was conducted between January and March 2023 in England. Participants were 11 older adults >65 years (6 females (55%), with chronic stroke (>1 year after a stroke) and moderate to severe disabilities. Twenty rehabilitation therapists were also interviewed (3 physiotherapists, and 17 Action for Rehabilitation from Neurological Injury (ARNI) instructors). The group was asked about perceived personal and environmental barriers and facilitators as well as expectations of resistance exercises in relation to upper limb neurorehabilitation programmes. Interview sessions were audio recorded for transcription and thematic data analysis. The study was approved by Sheffield Hallam University ethics committee (reference number: AA43961583).

Results

Both groups mentioned that the main barrier to performing upper-limb exercises is weakness in the paretic arm affecting grip strength with consequent adverse impact on adherence to a home-based programme and poor patient motivation. Patients also reported safety concerns such as dropping equipment and being dependent on a carer to undertake regular exercises. Stroke survivors preferred a program that activates the paretic arm and is relevant to their daily functional activities. They preferred simple exercise instructions and demonstrations through visual aids and video materials. Patients also valued regular feedback on adjusting their exercise dose, monitoring progress over time, and ongoing encouragement.

Conclusions

Our study showed that designing home-based resistance exercises for upper limb in older stroke survivors should be individualised, functionally orientated, and motivational.
1898 Feasibility study of a hospital deprescribing intervention: CompreHensive geriAtRician-led MEdication Review (CHARMER)
Authors: Scott S , Martin-Kerry J , Pritchard M , Alldred D A , Clark A B , Hammond A , Murphy K , Colles A , Keevil V , Kellar I , Patel M , Sims E , Taylor J , Turner D , Witham M , Wright D , Bhattacharya D
Published: January 2024

Introduction

CompreHensive geriAtRician-led MEdication Review (CHARMER) is a behaviour change intervention to support geriatricians and pharmacists to proactively deprescribe inappropriate medicines with older adults in hospital. The intervention comprises: formulating a deprescribing action plan, workshops, benchmarking reports and weekly briefings between geriatricians and pharmacists. We assessed feasibility and acceptability of the CHARMER intervention and study processes.

Method

A two-arm purposive allocation feasibility study was undertaken in four hospitals (three intervention, one control) in England in 2022. Data were collected to check completeness and quality, and assess intervention fidelity. Rapid qualitative analysis of staff and patient interviews, intervention implementation observations (action plan launch, pharmacist workshop and geriatrician videos), and study meeting minutes was undertaken.

Results

Study data were feasible to collect, of sufficient completeness and quality. Geriatrician and pharmacist principal investigators managed intervention implementation. They were able to implement most intervention components with ease and fidelity. Principal investigators felt that dedicated support for intervention implementation would better equip them with the resource and expertise to fidelitously implement all intervention components. Detailed instructions for preparing the action plan and how it might be delivered were desired. Geriatricians and pharmacists who received the intervention found it acceptable. Pharmacists felt that the weekly briefings encouraged them to dedicate time to review medicines and raise with geriatricians, opportunities to deprescribe. Geriatricians indicated that participating in CHARMER allowed them to focus on deprescribing conversations with patients and they involved junior doctors more in the deprescribing process.

Conclusion(s)

The CHARMER intervention and trial processes were feasible and acceptable. Revisions to support intervention implementation include providing a template action plan for hospitals to adapt; funds for a project manager one day a week to work with CHARMER principal investigators for three-months to oversee implementation, and support from Eastern Academic Health Science Network in the definitive trial (winter 2023).
1937 The future of research: Participant perspectives on remote trial delivery
Authors: Milczanowska W , Bowyer R C E , García M P , Wadge S , Baleanu A F , Nessa A , Sheedy A , Akdag G , Hart D , Whelan K , Steves C J , Lochlainn M Ni
Published: January 2024

Introduction

The PROMOTe trial was conducted entirely remotely, which aimed to enable a wider recruitment of participants, minimised risk of Covid-19 exposure and adhere to former travel restrictions. Participant experiences with remote clinical trials are not well understood. This work aimed to characterise participant perspectives on the remote delivery of the PROMOTe trial.

Methods

The trial involved remote measurement of short physical performance battery and grip strength, and remote collection of stool, urine, saliva, and capillary blood. Equipment including a dynamometer was posted to participants. Participants returned biological samples by post. A mixed methods approach was used, whereby participants were invited to complete an online questionnaire consisting of Likert, multiple-choice and open-ended questions upon trial completion.

Results

Of 72 trial participants, mean age 73.1, 80.6% (n = 58) completed the questionnaire. 53.5% (n = 31) had no preference between remote or in-person participation. Of those who preferred to take part remotely, 57.1% (n = 4) stated this was because there was no need to travel. 57.1% (n = 12) of those who preferred to take part in-person stated this was because they preferred to talk to the staff and ask questions face-to-face. Participants found that taking 5 out of the 8 physical measures were of similar difficulty over video teleconferencing compared to in-person. 100.0% (n = 58) of participants found it “easy” or “average” to collect stool, urine, and saliva, while 63.2% (n = 36) of participants thought it was “easy” or “average” to collect capillary blood. All participants found packaging and returning all four sample types of “easy” or “average” difficulty.

Conclusion

These findings suggest that the majority of participants found remote trial delivery, including handling equipment and collecting biological samples, both acceptable and manageable. Remote trial delivery has potential for increasing access of older people to trial participation.
Optimizer’s dilemma: optimization strongly influences model selection in transcriptomic prediction
Authors: Crawford Jake , Chikina Maria , Greene Casey S
Published: January 2024

Motivation

Most models can be fit to data using various optimization approaches. While model choice is frequently reported in machine-learning-based research, optimizers are not often noted. We applied two different implementations of LASSO logistic regression implemented in Python’s scikit-learn package, using two different optimization approaches (coordinate descent, implemented in the liblinear library, and stochastic gradient descent, or SGD), to predict mutation status and gene essentiality from gene expression across a variety of pan-cancer driver genes. For varying levels of regularization, we compared performance and model sparsity between optimizers.

Results

After model selection and tuning, we found that liblinear and SGD tended to perform comparably. liblinear models required more extensive tuning of regularization strength, performing best for high model sparsities (more nonzero coefficients), but did not require selection of a learning rate parameter. SGD models required tuning of the learning rate to perform well, but generally performed more robustly across different model sparsities as regularization strength decreased. Given these tradeoffs, we believe that the choice of optimizers should be clearly reported as a part of the model selection and validation process, to allow readers and reviewers to better understand the context in which results have been generated.

Availability and implementation

The code used to carry out the analyses in this study is available at https://github.com/greenelab/pancancer-evaluation/tree/master/01_stratified_classification. Performance/regularization strength curves for all genes in the Vogelstein et al. (2013) dataset are available at https://doi.org/10.6084/m9.figshare.22728644.
HiPhase: jointly phasing small, structural, and tandem repeat variants from HiFi sequencing
Authors: Holt James M , Saunders Christopher T , Rowell William J , Kronenberg Zev , Wenger Aaron M , Eberle Michael
Published: January 2024

Motivation

In diploid organisms, phasing is the problem of assigning the alleles at heterozygous variants to one of two haplotypes. Reads from PacBio HiFi sequencing provide long, accurate observations that can be used as the basis for both calling and phasing variants. HiFi reads also excel at calling larger classes of variation, such as structural or tandem repeat variants. However, current phasing tools typically only phase small variants, leaving larger variants unphased.

Results

We developed HiPhase, a tool that jointly phases SNVs, indels, structural, and tandem repeat variants. The main benefits of HiPhase are (i) dual mode allele assignment for detecting large variants, (ii) a novel application of the A*-algorithm to phasing, and (iii) logic allowing phase blocks to span breaks caused by alignment issues around reference gaps and homozygous deletions. In our assessment, HiPhase produced an average phase block NG50 of 480 kb with 929 switchflip errors and fully phased 93.8% of genes, improving over the current state of the art. Additionally, HiPhase jointly phases SNVs, indels, structural, and tandem repeat variants and includes innate multi-threading, statistics gathering, and concurrent phased alignment output generation.

Availability and implementation

HiPhase is available as source code and a pre-compiled Linux binary with a user guide at https://github.com/PacificBiosciences/HiPhase.
Statistical framework to determine indel-length distribution
Authors: Wygoda Elya , Loewenthal Gil , Moshe Asher , Alburquerque Michael , Mayrose Itay , Pupko Tal
Published: January 2024

Motivation

Insertions and deletions (indels) of short DNA segments, along with substitutions, are the most frequent molecular evolutionary events. Indels were shown to affect numerous macro-evolutionary processes. Because indels may span multiple positions, their impact is a product of both their rate and their length distribution. An accurate inference of indel-length distribution is important for multiple evolutionary and bioinformatics applications, most notably for alignment software. Previous studies counted the number of continuous gap characters in alignments to determine the best-fitting length distribution. However, gap-counting methods are not statistically rigorous, as gap blocks are not synonymous with indels. Furthermore, such methods rely on alignments that regularly contain errors and are biased due to the assumption of alignment methods that indels lengths follow a geometric distribution.

Results

We aimed to determine which indel-length distribution best characterizes alignments using statistical rigorous methodologies. To this end, we reduced the alignment bias using a machine-learning algorithm and applied an Approximate Bayesian Computation methodology for model selection. Moreover, we developed a novel method to test if current indel models provide an adequate representation of the evolutionary process. We found that the best-fitting model varies among alignments, with a Zipf length distribution fitting the vast majority of them.

Availability and implementation

The data underlying this article are available in Github, at https://github.com/elyawy/SpartaSim and https://github.com/elyawy/SpartaPipeline.
Job Polarisation, Labour Market Fluidity and the Flattening of the Phillips Curve
Authors: Siena Daniele , Zago Riccardo
Published: January 2024

This paper shows that job polarisation—i.e., the disappearance of routine jobs—is changing the characteristics of the labour market. This has structural implications for the relationship between inflation and unemployment, the price Phillips curve. Using data from the European Monetary Union and exploiting the fact that job polarisation accelerates during recessions, we obtain two empirical results. First, countries experiencing a bigger shift in the occupational structure during a downturn exhibit a flatter Phillips curve afterwards. Second, the occupational shifts experienced during the Great Recession and the Sovereign Debt Crisis explain more than a fourth of the flattening of the curve in the 2002–18 period. Then, using a New Keynesian model with unemployment and search and matching frictions, we highlight a channel through which labour market characteristics operate on the slope of the Phillips curve. Increasing labour market fluidity—i.e., a higher separation and hiring rate—decreases the slope of the Phillips curve. Using micro-data, we find that in the European Monetary Union non-routine jobs are more fluid. We conclude that job polarisation flattened the Phillips curve.
Impact of congenital heart disease on personality disorders in adulthood
Authors: Stapel Britta , Winter Lotta , Heitland Ivo , Löffler Friederike , Bauersachs Johann , Westhoff-Bleck Mechthild , Kahl Kai G
Published: January 2024

Aims

Adults with congenital heart disease (ACHD) constitute an ever-growing patient population characterized by high risks for cardiovascular- and mental disorders. Personality disorders (PDs) are associated with adverse physical and mental health. Studies assessing PD prevalence in ACHD are lacking.

Methods and results

Personality disorder point prevalence was assessed in 210 ACHD by Structured Clinical Interview for Axis-II Personality Disorders (SCID-II) and compared to meta-analytical data from the general population (GP). Depression and anxiety were measured by self-report (Hospital Anxiety and Depression Scale, HADS) and clinician rating (Montgomery–Åsberg depression rating scale, MADRS). Childhood maltreatment was assessed with the Childhood Trauma Questionnaire and quality-of-life (QOL) with the World Health Organization QOL Scale. PD prevalence was markedly higher in ACHD compared to GP (28.1 vs. 7.7%). Particularly borderline (4.8 vs. 0.9%) and cluster C (i.e. anxious or fearful; 17.1 vs. 3.0%) PDs were overrepresented. PD diagnosis was associated with a surgery age ≤12 years (χ²(1) = 7.861, ϕ = 0.195, P = 0.005) and higher childhood trauma levels (U = 2583.5, Z = −3.585, P < 0.001). ACHD with PD reported higher anxiety (HADS-A: U = 2116.0, Z = −5.723, P < 0.001) and depression (HADS-D: U = 2254.5, Z = −5.392, P < 0.001; MADRS: U = 2645.0, Z = −4.554, P < 0.001) levels and lower QOL (U = 2538.5, Z = −4.723, P < 0.001).

Conclusion

Personality disorders, particularly borderline- and cluster C, are significantly more frequent in ACHD compared to GP and associated with depression, anxiety, and decreased QOL. Data from the GP suggest an association with adverse cardiometabolic and mental health. To ensure guideline-based treatment, clinicians should be aware of the increased PD risk in ACHD.
Exploring Social Determinants of Mental Health of Older Unforced Migrants: A Systematic Review
Authors: Bhatia Pankhuri , McLaren Helen , Huang Yunong
Published: January 2024

Background and Objectives

Although the vulnerabilities stemming from the intersection of aging and migration are widely recognized, the migration contexts and the factors influencing the mental health of older unforced migrants have received scant attention. This review explores the drivers of unforced migrations in later life and the individual, relational, and structural factors influencing their mental health and well-being.

Research Design and Methods

Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic search of 7 databases for English peer-reviewed journal articles was conducted. A total of 21 studies were identified and analyzed inductively.

Results

The review classified motivations for migration as push factors and pull factors: push factors such as escaping structural inequities in the homeland and pull factors included seeking better lifestyle opportunities and reuniting with family. The positive determinants of mental health included cordial family relationships, paid employment, the presence of a partner, and strong support networks. Advanced age, absence of a partner, lifestyle changes, lack of intergenerational support, poor language proficiency, unfavorable policies, lack of access to resources, and systemic biases negatively affected the mental health of older unforced migrants.

Discussion and Implications

The review highlights the need to recognize the diversity among older migrants to develop policies and programs that address their specific circumstances. Recognizing their strengths, rather than focusing solely on their vulnerabilities will help create a more positive and supportive environment, enabling them to thrive in their new communities.
Nurturing Attentiveness: A Naturalistic Observation Study of Personal Care Interactions Between People With Advanced Dementia and Their Caregivers
Authors: Backhouse Tamara , Jeon Yun-Hee , Killett Anne , Green Jessica , Khondoker Mizanur , Mioshi Eneida
Published: January 2024

Background and Objectives

Personal care interactions can provide vital opportunities for caregivers to engage with a person living with advanced dementia. However, interactions may also be a contentious experience, what makes this so is not fully understood. We aimed to examine features of personal care interactions between caregivers and people with advanced dementia to understand how care may be improved.

Research Design and Methods

This was a naturalistic observation study using one-off video-recorded observations of personal care interactions between 14 people with advanced dementia and 12 caregivers (n = 7 care-home staff, n = 5 family carers) in the United Kingdom (total observation time 03:01:52). Observations were analyzed with observational video coding to determine the frequency of actions of people with dementia and qualitative content analysis for in-depth examination.

Results

Refusals of care were present in 32% of video sections. Active engagement of people with dementia was observed in 66% of sections. Rare contentious interactional components were characterized by the person with dementia appearing to show uneasiness and caregivers being flustered and uncertain. However, caregivers typically emanated a nurturing attentiveness, were attuned to the person, and skilled in seamlessly supporting them through care activities.

Discussion and Implications

Findings draw on real-world empirical evidence to reinvigorate the notion of person-centeredness in dementia care. The findings provide much needed insight into practical ways to improve care interactions for people with advanced dementia and enhance their personhood. Appropriate training/guidance for caregivers could support positive personal care experiences for both the person with dementia and caregiver.
IMPACT OF TREATMENT RESPONSE WITH ADALIMUMAB ON RISK OF SERIOUS INFECTIONS IN PATIENTS WITH CROHN’S DISEASE: SECONDARY ANALYSIS OF THE PYRAMID REGISTRY
Authors: Ahuja Dhruv , Luo Jiyu , Qi Yuchen , Syal Gaurav , Boland Brigid , Chang John , Ma Christopher , Jairath Vipul , Xu Ronghui , Singh Siddharth
Published: January 2024

BACKGROUND AND AIMS

Treatment efficacy and safety are primary factors in choosing therapies in patients with Crohn’s disease (CD). However, they can be perceived to be at odds with each other with more potent therapies associated with increased risk of infections. We evaluated the impact of treatment response on the risk of serious infections in adalimumab-treated patients with CD through secondary analysis of the PYRAMID registry.

METHODS

We included patients with CD who newly started adalimumab in the prospective PYRAMID registry (NCT00524537) and classified them as treatment responders (achieved steroid-free clinical remission based on patient-reported outcomes) vs. non-responders (not in steroid-free clinical remission) at 6m after treatment initiation (landmark). We compared the risk of serious infections between responders vs. non-responders between 6-36m after treatment initiation, through stabilized inverse probability of treatment weighted (IPW) Cox proportional hazards model.

RESULTS

Of 1515 adalimumab-treated patients with complete data at 6m, 763 (50.4%) were classified as responders (37±13y, 56% female, disease duration, 9.5y). At time of starting adalimumab (baseline), as compared with non-responders, responders were less likely to have moderate to severe symptoms (55.6% vs. 33%), require steroids (45.5% vs. 17.3%) or opiates (6.6% vs. 1.3%), have had prior CD-related surgery (46.5% vs. 35.1%), without any differences in disease location, perianal disease, and prior CD complications. On follow-up, between 6-36m (observation period after 6m landmark), 123 patients experienced a total of 162 serious infections. Of these, 52 responders (6.8%) experienced a serious infection vs. 71 non-responders (9.4%). Approximately, 58% infections were classified as gastrointestinal in origin. On stabilized IPTW through generalized boosting model, responders were 34% less likely to experience serious infections on follow-up compared with non-responders (HR, 0.66; 95% CI, 0.46-0.96). There was no significant difference in risk of serious infections between responders vs. non-responders based on organ site (gastrointestinal infections: HR, 0.61; 95% CI, 0.38-0.99; extra-intestinal infections: HR, 0.61; 95% CI, 0.46-1.30) (p-value for difference in groups = 1.00). Responders were significantly less likely to require corticosteroids on follow-up (1y: 4.4%, 2y: 8.9%, 3y: 9.6%), compared with non-responders (1y: 50.7%, 2y: 51.6% vs. 3y: 51%).

CONCLUSIONS

Patients with CD who respond to adalimumab have lower risk of developing serious infections, compared with non-responders, after accounting for disease severity. These findings underscore that initiation of advanced therapy for CD may lower the risk of serious infections through effective disease control and avoidance of corticosteroids.
ARGINASE 2 AMELIORATES EXPERIMENTAL COLITIS THROUGH ANTIOXIDANT EFFECTS VIA SPERMIDINE PRODUCTION
Authors: Imazu Noriyuki , Torisu Takehiro , Yokote Akihito , Umeno Junji , Kawasaki Keisuke , Fujioka Shin , Matsuno Yuichi , Nagasue Tomohiro , Kawatoko Shinichiro , Moriyama Tomohiko , Nitahata Tomoki , Uchida Yushi , Aihara Seishi , Kitazono Takanari
Published: January 2024

BACKGROUND

Spermidine which is a type of polyamine, shows elevated levels in patients with ulcerative colitis and is implicated in the pathogenesis of ulcerative colitis (UC). Arginase 2 (ARG2) plays a critical role in spermidine production. This study aimed to determine the role and mechanism of endogenous spermidine by using ARG2-deficient mice.

METHODS

The protective role of spermidine against oxidative stress was examined by intracellular reactive oxygen species levels and cell viability. The physiological role of spermidine was investigated using Arg2 knockdown cells with reduced spermidine. The importance of ARG2 in inflammation was examined in the dextran sulfate sodium-induced colitis model. Protein expression levels of ARG2 and accumulation of spermidine in patients with UC were evaluated by immunohistochemistry of the rectum.

RESULTS

ARG2 protein expression and the accumulation of spermidine were upregulated in the rectum of mice with dextran sulfate sodium colitis. Spermidine upregulated antioxidant genes in the cells. Arg2 knockdown cells showed reduced antioxidant activity. Dextran sulfate sodium colitis was more severe in Arg2-deficient mice, and organoids derived from Arg2-deficient mice showed diminished tolerance to oxidative stress. Furthermore, in the rectum of patients with UC, ARG2 and spermidine expression levels were higher in the active phase than in the remission phase.

CONCLUSIONS

Endogenous spermidine in the intestinal epithelium induced by ARG2 has a protective role in colitis. Spermidine may be a promising new therapeutic target for inflammatory bowel disease.
MULTIPLE BIOSIMILAR INFLIXIMAB SWITCHING IS NOT ASSOCIATED WITH DISEASE FLARE IN INFLAMMATORY BOWEL DISEASE: A REAL-WORLD EFFECTIVENESS ANALYSES IN A NATIONAL U.S. COHORT
Authors: Hou Jason , Pham Codey , Xu Anthony , Sansgiry Shubhada , Modi Varsha , Waljee Akbar
Published: January 2024

BACKGROUND

Infliximab (IFX) biosimilars are available for inflammatory bowel disease (IBD). Many options of IFX biosimilars exist, however there is a paucity of data on the safety and efficacy of switching between multiple IFX biosimilars. The goal of this study is to evaluate the safety and outcomes in patients who received multiple IFX biosimilars in a National U.S. Cohort of patients with IBD.

METHODS

We conducted a retrospective cohort study of IBD patients who received maintenance IFX originator from 2017- 2019 in the national Veterans Affairs (VA) healthcare system. Crohn’s disease (CD) and ulcerative colitis (UC) patients were identified using a previously validated algorithm. All cases, exposures and outcomes were confirmed by chart review. Patents on IFX originator were identified by dispensed medication from the VA Corporate Data Warehouse. Patients were classified as no-switch (NS)- receiving originator but no biosimilar during study period, Single Switch (SS)- switch from IFX originator to one biosimilar, or Double Switch (DS)- switch from IFX originator to two different biosimilars. Primary outcome was IBD flare, defined as escalation of steroid, IBD-related Emergency department visit or hospitalization within 12 months. Secondary outcomes were immunogenicity, serious infection, and infusion reaction. Event rates of the DS group were compared to NS and SS groups using univariate and multivariate logistic regression models adjusting for patient and non-patient factors.

RESULTS

A total of 789 patients (487 CD, 298 UC, 4 IBDU) on maintenance IFX originator were identified during the study period. Of these, 410 patients were categorized as NS, 249 as SS, and 130 as DS. Overall, the rate of flare within 12 months was 19.9% (22.2% NS, 15.3% SS, 21.5% DS, p= 0.08), rate of infection was 11.2% (11.5% NS, 8% SS, 16.2% DS, p= 0.056). No statistically significant differences in rates of immunogenicity or infusion reaction were identified between the DS and NS or SS groups. In multivariate (MV) logistic regression including age, race, gender, concomitant medication, comorbidity, and VA priority status, no significant differences in flares at 12 months was observed between the DS (ref) and NS (aOR 1.12, 95% CI 0.68-1.84), or SS groups (aOR 0.64, 95% CI 0.36-1.12). In MV analyses, SS was associated with lower rate of infection compared to DS (aOR 0.41, 95% CI 0.21-0.82).

CONCLUSION

In a national U.S. cohort of patients with IBD, multiple IFX biosimilar switching was not associated with flare at 12 months compared to patients continued on IFX originator or with a single IFX biosimilar switch. However, double switch was associated with increased odds of infection compared to single switch. These findings provide reassurance that multiple IFX biosimilar switching for IBD is effective but further study on infection risks may be warranted.
NETWORK META-ANALYSIS TO EVALUATE THE COMPARATIVE EFFICACY OF BIOLOGICS FOR MAINTENANCE TREATMENT OF ADULT PATIENTS WITH CROHN’S DISEASE
Authors: Schreiber Stefan , Danese Silvio , Colombel Jean-Frederic , Hisamatsu Tadakazu , Irving Peter , Park Hyunsoo , Kim Dong-Hyeon , Lee Young Nam , Hanauer Stephen
Published: January 2024

INTRODUCTION

While the therapeutic armamentarium for Crohn’s disease (CD) is rapidly expanding, direct evidence on comparative efficacy of various treatments is lacking. CT-P13 subcutaneous (SC) provides patients with a new opportunity for maintenance treatment of their disease.

METHODS

A network meta-analysis (NMA) was conducted to evaluate comparative efficacy of licensed biologics. Phase 3 randomized controlled-trials (RCTs) evaluating biologics approved by the European Medicines Agency or United States Food and Drug Administration as of 31 March 2023 for maintenance treatment of adult patients with moderate-to-severe CD were included, i.e. infliximab (IFX) intravenous (IV) and SC, adalimumab (ADL) SC, vedolizumab (VDZ) IV and SC, ustekinumab (UST) SC, and risankizumab (RZB) SC. Eligible studies evaluated the efficacy of maintenance therapy with follow-up periods of 52–64 weeks in patients who responded to induction treatment. Each study was controlled with placebo (PBO) or an active comparator. Head-to-head studies directly comparing efficacy of licensed biologics in CD (including those with treat-through designs) were also considered for inclusion. Clinical remission rates following the maintenance treatment were compared in a Bayesian NMA fixed-effect model.

RESULTS

Overall, 8 RCTs were identified and included in the analysis (ACCENT I, LIBERTY-CD, CHARM, SEAVUE, GEMINI 2, VISIBLE 2, IM-UNITI, FORTIFY). Most studies enrolled both naïve and biologic- and/or Janus kinase inhibitor-exposed patients, apart from ACCENT-1 and SEAVUE which enrolled only anti-tumor necrosis factor- and biologic-naïve patients, respectively. Among 8 comparator arms, IFX SC 120 mg every 2 weeks (Q2W) showed the highest odds ratio (95% credible interval) vs. PBO for clinical remission during the maintenance phase (3.52 [2.18–5.65]), followed by ADL SC 40 mg Q2W (2.92 [1.90–4.47]), UST SC 90 mg every 8 weeks (Q8W) (2.79 [1.85–4.21]), IFX IV 5 mg/kg Q8W (2.55 [1.29–5.27]), VDZ IV 300 mg Q8W (2.33 [1.43–3.86]), RZB SC 180 mg Q8W (1.80 [1.15–2.84]), VDZ SC 108 mg Q2W (1.76 [1.14–2.70]), and RZB SC 360 mg Q8W (1.60 [1.00–2.52]). In addition, IFX SC 120 mg Q2W showed the highest surface under the cumulative ranking curve (SUCRA) values (0.887), followed by ADL SC 40 mg Q2W (0.763), UST SC 90 mg Q8W (0.718), IFX IV 5 mg/kg Q8W (0.630), VDZ IV 300 mg Q8W (0.566), RZB SC 180 mg Q8W (0.353), VDZ SC 108 mg Q2W (0.327), RZB SC 360 mg Q8W (0.252), and PBO (0.005).

CONCLUSION

In this updated NMA on the comparative efficacy of licensed biologics, IFX SC 120 mg Q2W showed favorable efficacy in terms of clinical remission during maintenance treatment of 52–64 weeks’ duration in patients with moderate-to-severe CD.
MAINTENANCE EFFICACY OF ORAL INDIGO NATURALIS FOR ULCERATIVE COLITIS: A SINGLE-CENTER, OPEN-LABEL, RANDOMIZED, CONTROLLED STUDY
Authors: Matsuno Yuichi , Umeno Junji , Hirano Atsushi , Fuyuno Yuta , Nagasue Tomohiro , Fujioka Shin , Kawasaki Keisuke , Moriyama Tomohiko , Torisu Takehiro
Published: January 2024

BACKGROUND

Indigo naturalis (IN) is one of the herbal medicines in Chinese medicine. Recent reports have demonstrated a strong remission induction efficacy of oral IN in induction therapy for ulcerative colitis (UC), but the efficacy of IN in maintenance therapy for UC is unknown.

OBJECTIVES

We aimed to clarify the maintenance effect of IN.

METHODS

A single-center, open-label, randomized, controlled trial was conducted from August 2017 to August 2020. Patients with UC who received induction therapy with IN and maintenance therapy with IN for at least 1 year were enrolled. Patients with endoscopically confirmed mucosal healing (Mayo endoscopic subscore 0 or 1) were randomized. Patients were randomized to continue or discontinue IN. The primary endpoint was the remission rate at 52 weeks after discontinuation. Patients who relapsed during the observation period were given additional therapy, and remission rates were examined for patients who received an increased dose of IN or resumed oral therapy. The study was registered in the University Hospital Medical Information Network Center Trials registry, UMIN000028574.

RESULTS

A total of 20 patients participated in this study, 10 in the IN-continued group and 10 in the IN-discontinued group. The median age was 32.5 years and 33.5 years in the IN-continued group and IN-discontinued group, respectively, and 6 and 5 patients were male. Two patients in the IN-continued group and three patients in the IN-discontinued group were treated with azathioprine. One patient in the IN-continued group and three patients in the IN-discontinued group were treated with anti-tumor necrosis factor therapy. The remission rates at 52 weeks were 90% (9/10) of patients in the IN-continued group and 20% (2/10) in the IN-discontinued group. The remission rate was significantly higher in the IN-continued group (p = 0.0055). Of the 9 patients who relapsed, 7 were treated with increased or resumed oral IN, and all patients were induced remission again. No serious adverse events were observed during the observation period.

CONCLUSIONS

IN appears to be very effective in maintaining remission; the high efficacy of reintroduction in patients who relapsed after discontinuation of IN suggests that discontinuation of IN in cases of remission may be an option.
THE BURDEN OF INFLAMMATORY BOWEL DISEASE ON COVID-19 HOSPITALIZATIONS: A NATIONWIDE ANALYSIS
Authors: Iqbal Humzah , Haddadin Rakahn , Haidary Hasib , Zhang Patrick , Prajapati Devang
Published: January 2024

BACKGROUND

Inflammatory bowel disease (IBD) is a chronic systemic inflammatory process with primarily gastrointestinal (GI) manifestations, and is comprised of Crohn’s disease (CD) and ulcerative colitis (UC). The COVID-19 pandemic was unprecedented global health crisis that had a profound impact on healthcare burden. Both IBD and COVID-19 are associated with a pro-inflammatory state, however, the relationship between the two disease states remains unclear. Some studies suggest that IBD patients may develop more severe COVID-19 infection. We aim to assess whether patients with a history of IBD have worse outcomes when hospitalized with COVID-19.

METHODS

Patients with a diagnosis of COVID-19 were identified using the 2020 Nationwide Inpatient Sample (NIS). Patients were stratified based on the presence of IBD. Data were collected regarding incidence of shock, sepsis, acute kidney injury (AKI), blood transfusion, mechanical ventilation, and death. Other variables included age, gender, race, primary insurance, median income, hospital region, hospital bed size, and comorbidities. The relationship between outcomes in patients hospitalized with COVID-19 and IBD was analyzed using multivariate regression analysis.

RESULTS

A total of 1,526,805 patients with a diagnosis of COVID-19 were included in the study. Of these, 91,608 (6.0%) had a concurrent diagnosis of either CD or UC. The majority of patients in the IBD group were female (52.2%), White (73.4%), and had Medicare insurance (54.6%). History of IBD was associated with an increased risk of sepsis (aOR 1.15, P = 0.01), shock (aOR 1.26, P = 0.007), and AKI (aOR 1.25, P < 0.001). There was no difference in mechanical ventilation or in-hospital mortality between patients with IBD and those without.

CONCLUSION

Among patients hospitalized with COVID-19 infection, those with a history of IBD had an increased risk of sepsis, shock, and AKI. However, IBD did not confer an increased risk of mechanical ventilation or in-hospital mortality. IBD patients who develop COVID-19 infection should be evaluated diligently as their disease state may predispose them to shock and organ injury. Further studies are needed to elucidate why these patients do not have an increased rate of ventilator-dependent respiratory failure or death.

Inclusion process for the study.
UTILITY OF PR3-ANCA IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Andalucia Carmen , Bentow Chelsea , Aure Mary Ann , Martínez-Prat Laura , Horn Michael P , Mahler Michael
Published: January 2024

BACKGROUND/PURPOSE

Anti-neutrophil cytoplasmic antibodies (ANCA) directed to proteinase 3 (PR3) represent a highly established marker for patients with ANCA-associated vasculitis (AAV). PR3-ANCA have also demonstrated utility in the management of inflammatory bowel disease (IBD) with certain immunoassays. More specifically, PR3-ANCA discriminated patients with ulcerative colitis (UC) from Crohn`s disease (CrD) patients and were associated with disease severity and activity. Lastly, evidence is mounting that PR3-ANCA helps to stratify patients according to treatment response. Here, we aimed to summarize the current data on the diagnostic utility of PR3-ANCA in IBD.

METHODS

A structured systematic literature review including three electronic databases (Pubmed, Scopes, and Web Of Science) was conducted on June 6th 2023 to identify studies assessing the diagnostic accuracy of the QUANTA Flash PR3 assay (RUO for IBD) in UC vs. CrD patients. Electronic searches were supplemented by hand searching. A hierarchical, bivariate, mixed-effect meta-analysis was conducted using metandi function in STATA MP v17.0, as per the Cochrane collaboration recommendations for a review of diagnostic test accuracy studies. Study quality was assessed using QUADAS-2 tool which considers the risk of bias and applicability.

RESULTS

Out of 111 citations retrieved for titles and abstracts screen, a total of 6 studies met the inclusion criteria and reported QUANTA Flash PR3 diagnostic accuracy in UC vs. CrD. Diagnostic test accuracy of individual studies is available in Table 1. The six studies included 667 UC patients and 682 individuals with CrD. Of these, 2 articles (Horn et al. and Laass et al) were case-control studies in children. Sensitivity point estimate for UC was 34.9% [95% confidence interval (CI): 26.2-44.6%]. Specificity point estimate for CrD was 95.9% (95% CI: 92.0-98.0%). This results in a Diagnostic Odds Ratio (DOR) of 12.6 (95% CI: 5.7-27.9%), a positive likelihood ratio of 8.5 (95% CI: 4.2-17.5), and a negative likelihood ratio of 0.68 (95% CI: 0.59-0.78) (Table 2).

The risk of bias was low in the index test and reference standard domains. Four studies (67%) showed an unclear risk of bias in the patient selection and flow and timing domains. All studies had low concerns of applicability in all the domains.

CONCLUSION

In this meta-analysis QUANTA Flash PR3 assay has demonstrated to be able to discriminate between UC from CrD with a sensitivity of 34.9% and a specificity of 95.9%. Due to the limited number of studies published, clinical trials should consider the inclusion of PR3-ANCA as an exploratory biomarker for patient stratification.

Table 1 Summary of diagnostic test accuracy of individual studies.

Table 2 Meta-analysis of diagnostic test accuracy of QUANTA Flash PR3.
EFFECTS OF NUTRITION STATUS AND PERIOPERATIVE NUTRITION SUPPLEMENT COMPLETION ON POSTOPERATIVE OUTCOMES IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE UNDERGOING SURGERY
Authors: Collins Stacey , Castelan Viankail Cedillo , Wernick Rebecca , Banty Andrea , Gwarnicki Colleen , Solomon Theodore , Martirosyan Lilly , Roberts Pamela , Wise Andrea , Hampton Melissa , Nasseri Yosef , Zaghiyan Karen , Fleshner Phil , Melmed Gil , Issokson Kelly
Published: January 2024

BACKGROUND

Malnutrition is common in inflammatory bowel disease, (IBD) and is associated with poor disease activity, greater hospital length of stay (LOS), higher 30-day readmission rates, and increased risk of postoperative complications. Structured, multimodal prehabilitation including nutrition counseling improves various outcomes after elective cancer and orthopedic surgeries. We examined the effects of malnutrition and perioperative nutrition supplementation on surgical outcomes in IBD patients participating in a multimodal prehabilitation program.

METHODS

This was a retrospective study of patients aged 18-80 enrolled in a 10-week prehabilitation program undergoing surgery for IBD. Beginning 4 weeks prior to surgery, patients met with a multidisciplinary team including a nurse practitioner, physical therapist and registered dietitian. Patients were provided 3 preoperative carbohydrate loading oral nutrition supplements (ONS) 48 hours prior to surgery, and 20 perioperative immunonutrition ONS. Malnutrition was defined using the Global Leadership in Malnutrition criteria as moderate or severe. We used Fisher’s exact test to determine associations between malnutrition, ONS use, and postoperative complications (defined by the comprehensive complication index (CCI, with CCI scores >20 classified as severe)), and 30-day readmission. Logistic and linear regression were used to analyze length of stay (LOS), opioid use (defined as morphine milligram equivalents, MME), nutrition status, and ONS completion.

RESULTS

25 patients (48% female, mean age 44, 18 (72%) with Crohn’s disease) completed the prehabilitation program between 05/2022 and 10/2023. 10 patients (40%) met criteria for malnutrition (of these, 50% were moderate and 50% severe). Malnutrition was not significantly associated with CCI severity (p=0.07), LOS (p =0.07), opioid use (p=0.07) or 30 day readmission rates (0.06). Higher ONS use for carbohydrate loading and immunonutrition were more likely to have a LOS<5 days (p=0.05 and p=0.03 respectively).

CONCLUSION

ONS for preoperative carbohydrate loading and perioperative immunonutrition may shorten LOS after surgery among patients with IBD. In our study, higher amounts of ONS consumption led to a shorter LOS. Larger, controlled studies will help to further clarify the effects of malnutrition, carbohydrate loading, and immunonutrition among patients with IBD preparing for surgery.