bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between long-term statin use and cataract surgery: a nationwide study on 505 105 cataract surgery patients
Authors: Halili Andrim , Haxha Saranda , Zareini Bochra , Lund-Andersen Casper , Kold Sørensen Kathrine , Torp-Pedersen Christian , Eroglu Talip E , Bang Casper Niels 
Published: July 2024

Aims
To assess the association between statin use and cataract surgery according to different statin treatment durations in patients with different cardiovascular risk profiles.

Methods and results
We performed a nested case–control study using Danish registries, covering the period from 1 January 1996 to 31 December 2020. We defined cases as surgically treated cataract patients, matched in a 1:1 ratio by sex and age with controls not undergoing cataract surgery. The exposure of interest was statin use in different durations (1, 5 and 10 years) compared with never use of statins. Conditional logistic regression provided adjusted HRs and corresponding 95% CIs in subgroups defined by established atherosclerotic cardiovascular disease, diabetes, hypertension and individuals without these comorbidities. We identified 505 150 cataract surgery cases and found no increased HR of cataract surgery with statin treatment at any duration in any of the subgroups with established atherosclerotic cardiovascular disease, diabetes or hypertension.

Conclusion
Our findings do not support a possible association between long-term statin use and cataract in patients with established atherosclerotic cardiovascular disease, diabetes or hypertension. Although we found an association between statin use and cataract in individuals without these comorbidities, increasing durations of statin use did not yield higher cataract surgery rates.
Decision-making regarding accessing paediatric unscheduled healthcare during the COVID-19 pandemic: a mixed methods rapid review and thematic synthesis
Authors: Dowling-Cullen Cian , Sakellariou Dikaios 
Published: July 2024

ObjectiveReductions in paediatric unscheduled healthcare utilisation were seen during the COVID-19 pandemic, with concerns around their impact on children’s health. The reasons for these changes are not well described. This review aims to explore the factors reported by parents that influenced their decision-making around accessing paediatric unscheduled healthcare during the COVID-19 pandemic.DesignMixed methods rapid review and thematic synthesis based on the Enhancing Transparency of Reporting the Synthesis of Qualitative research framework.Data sourcesMEDLINE, Embase, Web of Science, PsycEXTRA, PsycINFO, Global Health, Global Index Medicus, Dissertations and Theses Global, Google Scholar and OAISter. Studies published from January 2020 to July 2023 were included.Eligibility criteria for selecting studiesQualitative, quantitative and mixed methods studies that assessed the perspectives of parents on decisions to access or delay or avoid accessing paediatric unscheduled healthcare during the COVID-19 pandemic.Data extraction and synthesisNvivo 14.23.0 was used to code results the of the primary studies and develop themes, following a thematic synthesis approach.ResultsTwelve studies were included, all from high-income settings, mainly in Europe. The studies were conducted across varying times and levels of COVID-19-related restrictions. The principal descriptive themes identified were (i) concerns about COVID-19 infection, (ii) balancing and navigating risks, (iii) perception of healthcare service status and conditions and (iv) perception of information and advice. These were developed into analytic themes to further describe the decision-making process.ConclusionsParents balanced a range of risks, concerns, advice and responsibilities when considering accessing paediatric unscheduled healthcare during the COVID-19 pandemic. External sources of advice and information were important; misconceptions around public health advice may reflect the multitude of information sources and the rapidly changing circumstances of the pandemic. Public health policy and planning should consider parent perspectives when developing measures to ensure equitable access to appropriate paediatric healthcare services.
Do primary care quality improvement frameworks consider equity?
Authors: Barrell Alice Macdonald , Johnson Lucy , Dehn Lunn Amy , Ford John Alexander 
Published: July 2024

BackgroundQuality improvement (QI) is used by healthcare organisations internationally to improve care. Unless QI explicitly addresses equity, projects that aim to improve care may exacerbate health and care inequalities for disadvantaged groups. There are several QI frameworks used in primary care, but we do not know the extent to which they consider equity. This work aimed to investigate whether primary care QI frameworks consider equity.MethodsWe conducted a search of MEDLINE, EMBASE and key websites to compile a list of the QI frameworks used in primary care. This list was refined by an expert panel. Guidance documents for each of the QI frameworks were identified from national websites or QI organisations. We undertook a document analysis of the guidance using NVivo.ResultsWe analysed 15 guidance documents. We identified the following themes: (1) there was a limited discussion of equity or targeted QI for disadvantaged groups in the documents, (2) there were indirect considerations of inequalities via patient involvement or targeting QI to patient demographics and (3) there was a greater focus on efficiency than equity in the documents.ConclusionThere is limited consideration of equity in QI frameworks used in primary care. Where equity is discussed, it is implicit and open to interpretation. This research demonstrates a need for frameworks to be revised with an explicit equity focus to ensure the distribution of benefits from QI is equitable.
Impact of the US Food and Drug Administration warning regarding increased risk of aortic aneurysms or aortic dissections on fluoroquinolone prescribing trends
Authors: Rizk John G , Slejko Julia F , Heil Emily L , Seo Dominique , Qato Danya M 
Published: July 2024

BackgroundThe US Food and Drug Administration (FDA) issued a warning in December 2018 regarding an increased risk of aortic aneurysms and aortic dissections associated with fluoroquinolone (FQ) use. This warning specifically targeted older adults and patients with conditions such as hypertension, Marfan syndrome, Ehlers-Danlos syndrome, atherosclerosis, peripheral vascular disease and history of aneurysms.ObjectiveTo evaluate the impact of the safety warning on prescribing trends of FQs in the targeted population.MethodsThis cross-sectional study with an interrupted time series (ITS) analysis (January 2018–December 2019) used a 25% random sample of IQVIA PharMetrics®Plus for Academics health plan claims database. The impact of the warning on FQ utilisation was quantified among the targeted population and a non-targeted population.ResultsFrom 2018 to 2019, both study populations saw a decrease in the year-over-year percent change of FQ prescriptions per 100 000 beneficiaries (−11%, from 14 227 to 12 662, targeted; −15%, from 5227 to 4446, non-targeted) and proportion of FQ use versus other antibiotics (from 15.6% to 13.8%, targeted; from 9.4% to 8%, non-targeted). In the targeted population, the ITS analysis did not show a significant trend change, a change in level or postwarning trend in the monthly rate of FQ prescriptions per 1000 beneficiaries. A positive trend change was observed in the non-targeted population (0.07, <0.01–0.13), but there were no significant changes in level or post-warning trend.ConclusionWe did not find a change in FQ prescription rates after the warning. The utility of safety advisories as a primary tool for mitigating FQ use in high-risk populations should be revisited.
Impacts of the COVID-19 pandemic on HIV care and treatment services among adolescents attending a tertiary hospital in Dar es Salaam, Tanzania: a qualitative study
Authors: Kidabulo Eva , Nkinda Lilian , Mwakawanga Dorkasi L , Joachim Agricola 
Published: July 2024

BackgroundThe COVID-19 pandemic has caused substantial disruption on HIV care and treatment programmes, especially for adolescents living with HIV (ALHIV) who are known to have poorer health outcomes compared with adults. Efforts made to overcome the pre-existing challenges were hampered by the emergence of the pandemic which interrupted adolescent-friendly healthcare services. Therefore, the aim of this study was to assess the impacts of the pandemic on HIV care and treatment services from healthcare providers and adolescents’ experiences at a tertiary hospital in Dar es Salaam, Tanzania.MethodsA descriptive qualitative study using in-depth interviews was conducted with 17 study participants. Purposive and convenient sampling techniques were used to recruit healthcare providers and adolescents, respectively. Swahili semistructured interview guide was used to conduct interviews. Thematic analysis was conducted to generate themes and subthemes describing the experiences on effects brought by COVID-19 on HIV care and treatment among adolescents.ResultsThe study revealed that alteration of approach in delivery of healthcare and limited human and non-human resources in healthcare facilities during the COVID-19 pandemic decreased effectiveness and quality of care which resulted in adolescent’s poor adherence to medication and loss to follow-up. Loss of family income, food insecurity and limited socialisation posed threat to adolescent’s mental health and overall quality of life.ConclusionOur findings underscore the impacts of COVID-19 and its immediate responses that significantly affected adolescent HIV care and treatment services. Reinforcement of sustainable ALHIV programmes and funding supports to these programmes are essential to promote retention and engagement to care during pandemics.
Circulating tumour DNA in patients with hepatocellular carcinoma across tumour stages and treatments
Authors: Campani Claudia , Imbeaud Sandrine , Couchy Gabrielle , Ziol Marianne , Hirsch Theo Z , Rebouissou Sandra , Noblet Bénédicte , Nahon Pierre , Hormigos Katia , Sidali Sabrina , Seror Olivier , Taly Valerie , Ganne Carrie Nathalie , Laurent-Puig Pierre , Zucman-Rossi Jessica , Nault Jean-Charles 
Published: July 2024

Objective
Circulating tumour DNA (ctDNA) is a promising non-invasive biomarker in cancer. We aim to assess the dynamic of ctDNA in patients with hepatocellular carcinoma (HCC).

Design

We analysed 772 plasmas from 173 patients with HCC collected at the time of diagnosis or treatment (n=502), 24 hours after locoregional treatment (n=154) and during follow-up (n=116). For controls, 56 plasmas from patients with chronic liver disease without HCC were analysed. All samples were analysed for cell free DNA (cfDNA) concentration, and for mutations in
TERT
promoter,
CTNNB1
,
TP53
,
PIK3CA
and
NFE2L2
by sequencing and droplet-based digital PCR. Results were compared with 232 corresponding tumour samples.

Results

In patients with active HCC, 40.2% of the ctDNA was mutated vs 14.6% in patients with inactive HCC and 1.8% in controls (p<0.001). In active HCC, we identified 27.5% of mutations in
TERT
promoter, 21.3% in
TP53
, 13.1% in
CTNNB1
, 0.4% in
PIK3CA
and 0.2% in
NFE2L2,
most of the times similar to those identified in the corresponding tumour. CtDNA mutation rate increased with advanced tumour stages (p<0.001). In 103 patients treated by percutaneous ablation, the presence and number of mutations in the ctDNA before treatment were associated with higher risk of death (p=0.001) and recurrence (p<0.001). Interestingly, cfDNA concentration and detectable mutations increased 24 hours after a locoregional treatment. Among 356 plasmas collected in 53 patients treated by systemic treatments, we detected mutations at baseline in 60.4% of the cases. In patients treated by atezolizumab-bevacizumab, persistence of mutation in ctDNA was associated with radiological progression (63.6% vs 36.4% for disappearance, p=0.019). In two patients progressing under systemic treatments, we detected the occurrence of mutations in
CTNNB1
in the plasma that was subclonal in the tumour for one patient and not detectable in the tumour for the other one.

Conclusion
ctDNA offers dynamic information reflecting tumour biology. It represents a non-invasive tool useful to guide HCC clinical management.
Impact of prenatal and postnatal maternal IBD status on offspring’s risk of IBD: a population-based cohort study
Authors: Bonfils Linéa , Poulsen Gry , Agrawal Manasi , Julsgaard Mette , Torres Joana , Jess Tine , Allin Kristine Højgaard 
Published: July 2024

Objective
In utero exposure to maternal inflammation may impact immune system development and subsequent risk of disease. We investigated whether a maternal diagnosis of IBD before childbirth is linked to a higher risk of IBD in offspring compared with a diagnosis after childbirth. Further, we analysed paternal IBD status for comparison.

Design
Using Danish health registers, we identified all individuals born in Denmark between 1997 and 2022 and their legal parents, as well as their IBD status. Cox proportional hazards regression analyses adjusted for calendar period and mode of delivery were used to estimate offspring IBD risk by maternal and paternal IBD status before and after childbirth.

Results
Of 1 290 358 children, 10 041 (0.8%) had mothers with IBD diagnosis before childbirth and 9985 (0.8%) had mothers with IBD diagnosis after childbirth. Over 18 370 420 person-years, 3537 individuals were diagnosed with IBD. Offspring of mothers with IBD before childbirth had an adjusted HR of IBD of 6.27 (95% CI 5.21, 7.54) compared with those without maternal IBD, while offspring of mothers with IBD after childbirth had an adjusted HR of 3.88 (95% CI 3.27, 4.60). Corresponding adjusted HRs were 5.26 (95% CI 4.22, 6.56) among offspring with paternal IBD before childbirth and 3.73 (95% CI 3.10, 4.50) for paternal IBD after childbirth.

Conclusion
Offspring had a greater risk of IBD when either parent was diagnosed before childbirth rather than later, emphasising genetic predisposition and environmental risk factors rather than maternal inflammation in utero as risk factors for IBD.
Unintentional firearms mortality disparities across states—USA, 2001–2021
Authors: Schwebel David C 
Published: July 2024

BackgroundFirearms kill over 130 Americans daily. Most deaths are the result of intentional acts, but in 2021, 549 deaths (1.5 deaths/day) were unintentional. Strategies to prevent unintentional versus intentional firearms deaths differ. This study describes unintentional firearm-related mortality across the US states and within individual states between 2001 and 2021 and considers factors that might explain disparities across states.MethodsUnintentional firearms mortality from 2001 to 2021, both for the full country and by state, was obtained online along with data for five state-level predictors: rurality, non-white population, poverty, population and gun ownership.ResultsThe highest unintentional firearm-related mortality rates clustered in Southeastern states, followed by states in the Northern Plains and Mountain West. The lowest rates were in the Northeast, followed by scattered states in the West and Midwest. At the state level, unintentional firearms mortality correlated positively with per cent below the poverty level (r=0.54, p<0.01), rural (r=0.59, p<0.01) and owning firearms (r=0.72, p<0.01). In a multivariable regression model predicting unintentional firearms mortality by state, three factors emerged as significant: per cent white (β=−0.22, p<0.05), below the poverty level (β=0.43, p<0.01) and owning firearms (β=0.54, p<0.01).ConclusionsLarge disparities exist across the 50 US states in unintentional firearms mortality. Crude rates in the most afflicted states are ~10 times those in the least afflicted states. Nationwide, over 12 000 lives were lost to unintentional firearms mortality between 2001 and 2021. Factors that create disparities are multifaceted and include rurality, poverty and firearms ownership.
Characteristics of fatal and non-fatal drownings at a Texas level-1 paediatric trauma centre
Authors: Abbe Marisa , Rix Kevin , Aguilar David , Alderete Jesus , Fernandez Alejandra , Messiah Sarah 
Published: July 2024

Background
Drowning is a leading cause of death for young children and knowing what puts a child at risk helps efforts across the spectrum of prevention. The purpose of this study was to identify risk and protective factors associated with hospital admission and mortality following paediatric drowning from a large level-1 paediatric trauma centre.

Methods
Children (ages 0–17) who presented at an emergency department or were admitted for a drowning event between 2017 and 2023 were included in this retrospective cohort study (n=698). This study examined differences between patients who were admitted compared with not admitted, and those who survived compared with those who did not survive.

Results
Participants who had adult supervision at the time of their drowning were significantly less likely to be admitted (OR=0.31, 95% CI 0.22 to 0.43, p<0.001) and significantly more likely to survive (OR=6.9, 95% CI 3.2 to 15.4, p<0.001). The environment also played a significant role in drowning outcomes. Children who drowned in a pool compared with other bodies of water were significantly more likely to survive (OR=3.0, 95% CI 1.6 to 5.5, p<0.001). Children from communities with higher child opportunity compared with those from very low opportunity were both simultaneously more likely to be admitted (IRR=1.7–2.4, 95% CI 1.3 to 3.3, p<0.001) and more often survived (IRR=1.7–3.0, 95% CI 1.3 to 3.5, p<0.001).

Conclusion
Our analysis revealed significant differences in drowning risk related to adult supervision, location of drowning and where a child lives. These findings can help drowning prevention strategies mitigate the severity of drowning by enhancing educational messages, resources and policy.
Enhanced IL-15-mediated NK cell activation and proliferation by an ADAM17 function-blocking antibody involves CD16A, CD137, and accessory cells
Authors: Matson Anders W , Hullsiek Rob , Dixon Kate J , Wang Sam , Lindstedt Anders J , Friess Ryan R , Phung Shee Kwan , Freedman Tanya S , Felices Martin , Truckenbrod Emily N , Wu Jianming , Miller Jeffrey S , Walcheck Bruce 
Published: July 2024

BackgroundNatural killer (NK) cells are being extensively studied as a cell therapy for cancer. These cells are activated by recognition of ligands and antigens on tumor cells. Cytokine therapies, such as IL-15, are also broadly used to stimulate endogenous and adoptively transferred NK cells in patients with cancer. These stimuli activate the membrane protease ADAM17, which cleaves various cell-surface receptors on NK cells as a negative feedback loop to limit their cytolytic function. ADAM17 inhibition can enhance IL-15-mediated NK cell proliferation in vitro and in vivo. In this study, we investigated the underlying mechanism of this process.MethodsPeripheral blood mononuclear cells (PBMCs) or enriched NK cells from human peripheral blood, either unlabeled or labeled with a cell proliferation dye, were cultured for up to 7 days in the presence of rhIL-15±an ADAM17 function-blocking antibody. Different fully human versions of the antibody were generated; Medi-1 (IgG1), Medi-4 (IgG4), Medi-PGLALA, Medi-F(ab′)2, and TAB16 (anti-ADAM17 and anti-CD16 bispecific) to modulate CD16A binding. Flow cytometry was used to assess NK cell proliferation and phenotypic markers, immunoblotting to examine CD16A signaling, and IncuCyte-based live cell imaging to measure NK cell antitumor activity.ResultsThe ADAM17 function-blocking monoclonal antibody (mAb) Medi-1 markedly increased early NK cell activation by IL-15. By using different engineered versions of the antibody, we demonstrate involvement by CD16A, an activating Fcγ receptor and well-described ADAM17 substrate. Hence, Medi-1 when bound to ADAM17 on NK cells is engaged by CD16A and blocks its shedding, inducing and prolonging its signaling. This process did not promote evident NK cell fratricide or dysfunction. Synergistic signaling by Medi-1 and IL-15 enhanced the upregulation of CD137 on CD16A+NK cells and augmented their proliferation in the presence of PBMC accessory cells or an anti-CD137 agonistic mAb.ConclusionsOur data reveal for the first time that CD16A and CD137 underpin Medi-1 enhancement of IL-15-driven NK cell activation and proliferation, respectively, with the latter requiring PBMC accessory cells. The use of Medi-1 represents a novel strategy to enhance IL-15-driven NK cell proliferation, and it may be of therapeutic importance by increasing the antitumor activity of NK cells in patients with cancer.
Effectiveness of secukinumab in radiographic and non-radiographic axial spondyloarthritis: a European routine-care observational study
Authors: Christiansen Sara Nysom , Horskjær Rasmussen Simon , Ostergaard Mikkel , Pons Marion , Michelsen Brigitte , Pavelka Karel , Codreanu Catalin , Ciurea Adrian , Glintborg Bente , Santos Maria Jose , Sari Ismail , Rotar Ziga , Gudbjornsson Bjorn , Macfarlane Gary J , Relas Heikki , Iannone Florenzo , Laas Karin , Wallman Johan K , van de Sande Marleen , Provan Sella Aarrestad , Castrejon Isabel , Zavada Jakub , Mogosan Corina , Nissen Michael J , Loft Anne Gitte , Barcelos Anabela , Erez Yesim , Pirkmajer Katja Perdan , Grondal Gerdur , Jones Gareth T , Hokkanen Anna-Mari , Chimenti Maria Sole , Vorobjov Sigrid , Di Giuseppe Daniela , Kvien Tore K , Otero-Varela Lucia , van der Horst-Bruinsma Irene , Hetland Merete Lund , Ørnbjerg Lykke Midtbøll 
Published: July 2024

Objectives
To compare the treatment effectiveness of secukinumab in radiographic (r) versus non-radiographic (nr) axial spondyloarthritis (axSpA) patients treated in routine care across Europe.

Methods
Prospectively collected data on secukinumab-treated axSpA patients with known radiographic status were pooled from nine countries.
Remission rates based on patient-reported outcomes (PROs; Numeric Rating Scale (0–10), for example, pain ≤2/Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≤2 and Ankylosing Spondylitis Disease Activity Score (ASDAS) inactive disease (ID) <1.3 after 6/12/24 months of secukinumab treatment were calculated.
Remission and drug retention rates in r-axSpA versus nr-axSpA patients were compared by logistic and Cox regression models (unadjusted/adjusted for age+sex/adjusted for multiple confounders).

Results
Overall, 1161 secukinumab-treated patients were included (r-axSpA/nr-axSpA: 922/239). At baseline, r-axSpA patients had longer disease duration and higher C reactive protein, were more often male and HLA-B27 positive and had received fewer prior biological or targeted synthetic disease-modifying antirheumatic drugs compared with nr-axSpA patients, whereas PROs were largely similar.
During follow-up, crude PRO remission rates were significantly higher in r-axSpA compared with nr-axSpA patients (6 months: pain≤2: 40%/28%, OR=1.7; BASDAI≤2: 37%/25%, OR=1.8), as were drug retention rates (24 months: 66%/58%, HR 0.73 (ref: r-axSpA)). Proportions of patients achieving ASDAS ID were low for both groups, particularly nr-axSpA (6 months: 11%/8%).
However, when adjusting for age+sex, these differences diminished, and after adjusting for multiple confounders, no significant between-group differences remained for either remission or drug retention rates.

Conclusion
Crude remission/drug retention rates in European secukinumab-treated patients were higher in r-axSpA compared with nr-axSpA patients. In adjusted analyses, secukinumab effectiveness was similar in both groups, suggesting that observed differences were related to factors other than radiographic status.