bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hyperpigmentary abnormalities in age-related macular degeneration: association with progression and impact on visual sensitivity
Authors: Goh Kai Lyn , Kumar Himeesh , Hadoux Xavier , Jannaud Maxime , Abbott Carla , Hodgson Lauren , Robman Luba , Makeyeva Galina , Van Wijngaarden Peter , Guymer Robyn , Wu Zhichao 
Published: December 2022

Background/aimsTo investigate the additional prognostic value of quantifying the extent of colour fundus photography (CFP)-defined hyperpigmentary abnormalities (HPAs) compared with their presence alone for predicting progression to late-stage age-related macular degeneration (AMD) and to understand their association with visual sensitivity in individuals with intermediate AMD.Methods140 participants with bilateral large drusen underwent multimodal imaging and microperimetry at baseline and then every 6 months for up to 3 years. Baseline CFPs were graded for the presence of HPAs and their extent was quantified. Optical coherence tomography (OCT) scans were used to quantify drusen volume. Predictive models for progression to late AMD (including OCT signs of atrophy) were developed using either HPA presence or extent. The association between HPA extent with mean visual sensitivity (both overall and sector based) was also evaluated. All models were adjusted for the confounders of baseline age and drusen volume.ResultsThe predictive performance for late AMD development was not significantly different for HPA presence or extent (p=0.92). Increasing HPA extent in each sector, but not its overall extent in an eye, was associated with reduced sector-based visual sensitivity (p<0.001 and p=0.671, respectively).ConclusionIn a cohort with bilateral large drusen, quantifying HPA extent did not improve the prediction of late AMD development compared with presence alone. HPA extent was associated with more local, rather than generalised, reductions in visual sensitivity. These findings suggest that quantification of HPA extent adds little to the prediction of AMD progression, but that it provides an imaging biomarker of visual dysfunction.
Universal prevention through a digital health platform reduces injury incidence in youth athletics (track and field): a cluster randomised controlled trial
Authors: Jacobsson Jenny , Kowalski Jan , Timpka Toomas , Hansson Per-Olof , Spreco Armin , Dahlstrom Orjan 
Published: December 2022

ObjectivesTo examine whether universal prevention via a digital health platform can reduce the injury incidence in athletics athletes aged 12–15 years and if club size had an influence on the effect of the intervention.MethodsThis was a cluster randomised trial where young athletics athletes were randomised through their club following stratification by club size into intervention (11 clubs; 56 athletes) and control (10 clubs; 79 athletes) groups. The primary endpoint was time from baseline to the first self-reported injury. Intervention group parents and coaches were given access to a website with health information adapted to adolescent athletes and were encouraged to log in and explore its content during 16 weeks. The control group continued training as normal. Training exposure and injury data were self-reported by youths/parents every second week, that is, eight times. The primary endpoint data were analysed using the log-rank test. Cox proportional hazards regression was used to analyse the second study aim with intervention status and club size included in the explanatory models.ResultsThe proportion of completed training reports was 85% (n=382) in the intervention group and 86% (n=545) in the control group. The injury incidence was significantly lower (HR=0.62; χ2=3.865; p=0.049) in the intervention group. The median time to first injury was 16 weeks in the intervention group and 8 weeks in the control group. An interaction effect between the intervention and stratification factor was observed with a difference in injury risk between athletes in the large clubs in the intervention group versus their peers in the control group (HR 0.491 (95% CI 0.242 to 0.998); p=0.049).ConclusionsA protective effect against injury through universal access to health information adapted for adolescent athletes was observed in youth athletics athletes. The efficacy of the intervention was stronger in large clubs.Trial registration numberNCT03459313.
Contactless monitoring of respiratory rate (RR) and heart rate (HR) in non-acuity settings: a clinical validity study
Authors: Varma Muralidhar , Sequeira Trevor , Naidu Navaneetha Krishnan S , Mallya Yogish , Sunkara Amarendranath , Patil Praveen , Poojary Nagaraj , Vaidyanathan Manikanda Krishnan , Balmaekers Benoît , Thomas Joseph , Prasad N Shankar , Badagabettu Sulochana 
Published: December 2022

ObjectivePatient monitoring in general wards primarily involves intermittent observation of temperature, heart rate (HR), respiratory rate (RR) and blood pressure performed by the nursing staff. Several hours can lapse between such measurements, and the patient may go unobserved. Despite the growing widespread use of sensors to monitor vital signs and physical activities of healthy individuals, most acutely ill hospitalised patients remain unmonitored, leaving them at an increased risk. We investigated whether a contactless monitoring system could measure vital parameters, such as HR and RR, in a real-world hospital setting.DesignA cross-sectional prospective study.Setting and participantsWe examined the suitability of employing a non-contact monitoring system in a low-acuity setup at a tertiary care hospital in India. Measurements were performed on 158 subjects, with data acquired through contactless monitoring from the general ward and dialysis unit.Outcome measuresVital parameters (RR and HR) were measured using a video camera in a non-acuity setting.ResultsThree distinct combinations of contactless monitoring afforded excellent accuracy. Contactless RR monitoring was linearly correlated with Alice NightOne and manual counts, presenting coefficients of determination of 0.88 and 0.90, respectively. Contactless HR monitoring presented a coefficient of determination of 0.91. The mean absolute errors were 0.84 and 2.15 beats per minute for RR and HR, respectively.ConclusionsCompared with existing Food and Drug Administration-approved monitors, the findings of the present study revealed that contactless monitoring of RR and HR accurately represented study populations in non-acuity settings. Contactless video monitoring is an unobtrusive and dependable method for monitoring and recording RR and HR. Further research is needed to validate its dependability and utility in other settings, including acute care.Trial registration numberCTRI/2018/11/016246.
Improving access to primary care and annual health checks for people who have a learning disability: a multistakeholder qualitative study
Authors: Wigham Sarah , Bourne Jane , McKenzie Karen , Rowlands Gill , Petersen Katharine , Hackett Simon 
Published: December 2022

ObjectivesTo investigate key stakeholders’ views on how to improve access to primary care in general practice settings for people with learning disabilities (or intellectual disabilities). Further to explore how inequalities and barriers in specific areas including annual health checks might be addressed.DesignA qualitative study design was used with data collected during focus groups, interviews and open-response surveys; data analysis was thematic and informed by stakeholder consultation. Processes to facilitate quality included triangulation of stakeholder perspectives, triangulation of data collection methods and checking interpretation of findings with participants.SettingUK regional services including learning disability organisations, primary care general practitioner (GP) clinical practice networks and supported housing organisations.ParticipantsSixteen people participated in the study: four people with learning disabilities participated in a focus group; four relatives completed an interview or survey; eight GPs, practice nurses and supported housing managers participated in interviews.ResultsFive overarching themes describing approaches to improve primary care access for people with learning disabilities were identified including: prioritisation, proactivity, innovation and improvement, personalisation and prevention and follow-up. Definitions of themes were described and illustrated with quotes. Ten recommendations informed by the thematic analysis, stakeholder consultation, research and primary care guidance were codeveloped with people with learning disabilities.ConclusionsAll stakeholders identified problems, with primary care interfaces being misaligned with the needs of people with learning disabilities. The recommendations informed by all stakeholders can be used to guide development of service provision to better meet the needs of people with learning disabilities in primary care. Future research should explore professionals’ understanding of reasonable adjustments.
Mobile health-based remote interaction management intervention for patients with low anterior resection syndrome: study protocol for a randomised controlled trial
Authors: Li Hui , Zhou Peng , Pang Xueying , Wang Ting , Yin Danqiao , Fu Min , He Hongye , Zhu Degang , Yu Shihui , Hu Shaohua 
Published: December 2022

IntroductionLow anterior resection syndrome (LARS) involves bowel dysfunction after sphincter-preserving surgery for rectal resection that significantly impacts patients’ quality of life (QoL). The improvement of LARS largely depends on patient self-management behaviour; however, insufficient information about supportive care and weak awareness of self-management lead to poor self-management behaviour. Motivational interviewing (MIs) explore and change patients’ ambivalence during the conversation, thereby changing and maintaining healthy behaviours to enhance effective participation. In recent years, mobile health has been widely used in clinical practice, providing continuous information support and remote interaction. However, current online information on LARS is suboptimal, websites are highly variable, important content is often lacking and the material is too complex for patients. Therefore, this study will evaluate the impacts of a remote LARS interaction management intervention based on a WeChat applet (‘e-bowel safety’) and MIs on patients with LARS.Methods and analysisThis study will be a single-blind, two-arm randomised controlled trial involving patients with LARS in three tertiary grade A general hospitals who will be randomised into two groups. The intervention group will use the ‘e-bowel safety’ applet and the intervention team will conduct a monthly MI about syndrome management. The control group will receive an information booklet that contains the same information as that provided in the ‘e-bowel safety’ informational module. The intervention will last for 3 months, followed by 3 months of follow-up. The primary outcome will be global QoL; the secondary outcomes will include bowel function, social support, self-management measured at the baseline, 3 months and 6 months for three times and patients’ thinkings at the end of the intervention (at 3 months).Ethics and disseminationEthics approval was granted by the Clinical Medical Research Ethics Committee of the First Affiliated Hospital of Anhui Medical University (PJ2022-07-53).Trial registration numberChinese Clinical Trial Registry (ChiCTR2200061317).
Obesity among those newly diagnosed with Crohn’s disease and ulcerative colitis compared with the general population
Authors: Sehgal Priya , Shen Bo , Li Jianhua , Freedberg Daniel E 
Published: December 2022

ObjectiveObesity is a potentially modifiable risk factor for inflammatory bowel disease (IBD). We aimed to evaluate the body mass index (BMI) of those diagnosed with IBD early versus late in life in the context of age-adjusted background population.Design/methodPatients with a new diagnosis of IBD from 2000 to 2021 were included. Early-onset IBD was classified as age <18 and late-onset IBD classified as age ≥65. Obesity was classified as BMI ≥30 kg/m2. Population data were obtained from community surveys.ResultsIncluded were 1573 patients (56.0%) with Crohn’s disease (CD) and 1234 (44.0%) with ulcerative colitis (UC). Overall, the median BMI at IBD diagnosis was 20 kg/m2(IQR 18–24) among those diagnosed at age <18 vs 26.9 kg/m2(IQR 23.1–30.0) among those diagnosed at age ≥65 (rank-sum p<0.01). In all age groups, BMI was stable during the 1-year preceding IBD diagnosis. At age <18, 11.5% of the background population was obese compared with 3.8% of those with newly diagnosed CD (p<0.01) and 4.8% of those with newly diagnosed UC (p=0.05). At age ≥65, 23.6% of the population was obese compared with 24.3% of those with newly diagnosed CD (p=0.78) and 29.5% of those with newly diagnosed UC (p=0.01).ConclusionPatients with IBD diagnosed at age <18 were less likely to be obese compared with the age-adjusted background population whereas those diagnosed at age ≥65 were more likely to be obese. Future prospective studies should investigate obesity as a modifiable risk factor for late-life IBD.
Efficient preclinical treatment of cortical T cell acute lymphoblastic leukemia with T lymphocytes secreting anti-CD1a T cell engagers
Authors: Jiménez-Reinoso Anaïs , Tirado Néstor , Martinez-Moreno Alba , Díaz Víctor M , García-Peydró Marina , Hangiu Oana , Díez-Alonso Laura , Albitre Ángela , Penela Petronila , Toribio Maria L , Menéndez Pablo , Álvarez-Vallina Luis , Sánchez Martínez Diego 
Published: December 2022

BackgroundThe dismal clinical outcome of relapsed/refractory (R/R) T cell acute lymphoblastic leukemia (T-ALL) highlights the need for innovative targeted therapies. Although chimeric antigen receptor (CAR)-engineered T cells have revolutionized the treatment of B cell malignancies, their clinical implementation in T-ALL is in its infancy. CD1a represents a safe target for cortical T-ALL (coT-ALL) patients, and fratricide-resistant CD1a-directed CAR T cells have been preclinically validated as an immunotherapeutic strategy for R/R coT-ALL. Nonetheless, T-ALL relapses are commonly very aggressive and hyperleukocytic, posing a challenge to recover sufficient non-leukemic effector T cells from leukapheresis in R/R T-ALL patients.MethodsWe carried out a comprehensive study using robustin vitroandin vivoassays comparing the efficacy of engineered T cells either expressing a second-generation CD1a-CAR or secreting CD1a x CD3 T cell-engaging Antibodies (CD1a-STAb).ResultsWe show that CD1a-T cell engagers bind to cell surface expressed CD1a and CD3 and induce specific T cell activation. Recruitment of bystander T cells endows CD1a-STAbs with an enhancedin vitrocytotoxicity than CD1a-CAR T cells at lower effector:target ratios. CD1a-STAb T cells are as effective as CD1a-CAR T cells in cutting-edgein vivoT-ALL patient-derived xenograft models.ConclusionsOur data suggest that CD1a-STAb T cells could be an alternative to CD1a-CAR T cells in coT-ALL patients with aggressive and hyperleukocytic relapses with limited numbers of non-leukemic effector T cells.
Exploiting the immunogenic potential of standard of care radiation or cisplatin therapy in preclinical models of HPV-associated malignancies
Authors: Kowalczyk Joshua T , Fabian Kellsye P , Padget Michelle R , Lopez Diana C , Hoke Austin TK , Allen Clint T , Hermsen Mario , London, Nyall R , Hodge James W 
Published: December 2022

BackgroundWhile radiation and chemotherapy are primarily purposed for their cytotoxic effects, a growing body of preclinical and clinical evidence demonstrates an immunogenic potential for these standard therapies. Accordingly, we sought to characterize the immunogenic potential of radiation and cisplatin in human tumor models of HPV-associated malignancies. These studies may inform rational combination immuno-oncology (IO) strategies to be employed in the clinic on the backbone of standard of care, and in so doing exploit the immunogenic potential of standard of care to improve durable responses in HPV-associated malignancies.MethodsRetroviral transduction with HPV16 E7 established a novel HPV-associated sinonasal squamous cell carcinoma (SNSCC) cell line. Three established HPV16-positive cell lines were also studied (cervical carcinoma and head and neck squamous cell carcinoma). Following determination of sensitivities to standard therapies using MTT assays, flow cytometry was used to characterize induction of immunogenic cell stress following sublethal exposure to radiation or cisplatin, and the functional consequence of this induction was determined using impedance-based real time cell analysis cytotoxicity assays employing HPV16 E7-specific cytotoxic lymphocytes (CTLs) with or without N803 (IL-15/IL-15-Rα superagonist) or exogenous death receptor ligands. In vitro observations were translated using an in vivo xenograft NSG mouse model of human cervical carcinoma evaluating cisplatin in combination with CTL adoptive cell transfer.ResultsWe showed that subpopulations surviving clinically relevant doses of radiation or cisplatin therapy were more susceptible to CTL-mediated lysis in four of four tumor models of HPV-associated malignancies, serving as a model for HPV therapeutic vaccine or T-cell receptor adoptive cell transfer. This increased killing was further amplified by IL-15 agonism employing N803. We further characterized that radiation or cisplatin induced immunogenic cell stress in three of three cell lines, and consequently demonstrated that upregulated surface expression of Fas and TRAIL-R2 death receptors at least in part mediated enhanced CTL-mediated lysis. In vivo, cisplatin-induced immunogenic cell stress synergistically potentiated CTL-mediated tumor control in a human model of HPV-associated malignancy.ConclusionStandard of care radiation or cisplatin therapy induced immunogenic cell stress in preclinical models of HPV-associated malignancies, presenting an opportunity poised for exploitation by employing IO strategies in combination with standard of care.
SARS-CoV-2 omicron breakthrough infections in patients with multiple sclerosis
Authors: van Kempen Zoé L E , Stalman Eileen W , Steenhuis Maurice , Kummer Laura Y L , van Dam Koos P J , Wilbrink Maarten F , ten Brinke Anja , van Ham S Marieke , Kuijpers Taco , Rispens Theo , Eftimov Filip , Wieske Luuk , Killestein Joep 
Published: December 2022

BackgroundIt is unclear which patients with multiple sclerosis (MS) are most susceptible for omicron breakthrough infections.MethodsWe assessed omicron breakthrough infections in vaccinated patients with MS with and without disease-modifying therapies enrolled in an ongoing large prospective study. We longitudinally studied humoral responses after primary and booster vaccinations and breakthrough infections.ResultsOmicron breakthrough infections were reported in 110/312 (36%) patients with MS, and in 105/110 (96%) infections were mild. Omicron breakthrough infections occurred more frequently in patients treated with anti-CD20 therapies and sphingosine-1 phosphate receptor (S1PR) modulators, patients with impaired humoral responses after primary immunisation (regardless of treatment) and patients without prior SARS-CoV-2 infections. After infection, antibody titres increased in patients on S1PR modulator treatment while anti-CD20 treated patients did not show an increase.ConclusionsSARS-COV-2 omicron breakthrough infections are more prevalent in patients with MS on anti-CD20 therapies and S1PR modulators compared with other patients with MS, which correlated with decreased humoral responses after vaccination. Humoral responses after infection were higher in S1PR modulator-treated patients in comparison to patients on anti-CD20 therapies, suggesting that immunological protection from contracting infection or repeated exposures may differ between these therapies.
Metaphors and decision making in parental blogs about their children with life-limiting diseases: who’s afraid of the war metaphor?
Authors: Neefjes Veronica 
Published: December 2022

The use of metaphors aids understanding by allowing us to think of complex problems in terms of relatively simple and more concrete information. As such, metaphors shape thought and guide future action. While metaphors are known to play a role in medical treatment decision-making, the effect of particular metaphors is unknown.This paper explores the metaphors West-European parents use for their child suffering from a life-limiting condition by analysing 15 blogs from Dutch, German and English and Welsh parents. The analysis found that all parents use war metaphors to describe their child and their disease. Describing their child in war metaphors, for example, ‘fighter’, ‘hero’ or ‘trooper’ allows parents to express their pride in their child. To describe the familial situation parents use both ‘life as a fight’ and a ‘time as space’ metaphor. Time is conceptualised as a space to be filled with positive experiences to allow the child to live as full a life as possible. In medical treatment decisions, parents balance ‘fighting the disease’ against their child’s ability to live a good life. No evidence was found that the use of war metaphors increase a tendency to treat when benefit is unlikely. Instead, parents primarily use war metaphors as a conduit to express their love for their child and to empower them to manage the familial situation.
Haematological malignancies in patients with psoriatic arthritis overall and treated with TNF inhibitors: a Nordic cohort study
Authors: Cordtz Rene Lindholm , Askling Johan , Delcoigne Benedicte , Smedby Karin E , Baecklund Eva , Ballegaard Christine , Isomäki Pia , Aaltonen Kalle , Gudbjornsson Bjorn , Love Thorvardur Jon , Provan Sella Aarrestad , Michelsen Brigitte , Sexton Joseph , Dreyer Lene , Hellgren Karin 
Published: December 2022

ObjectivesTo evaluate the risk of haematological malignancies in patients with psoriatic arthritis (PsA) overall, and in relation to treatment with tumour necrosis factor inhibitors (TNFi).MethodsWe identified that patients with PsA starting a first TNFi from the clinical rheumatology registers (CRR) in the five Nordic countries (n=10 621) and biologics-naïve PsA patients from (1) the CRR (n=18 705) and (2) the national patient registers (NPR, n=27 286, Sweden and Denmark) from 2006 through 2019. For Sweden and Denmark, general population comparators were matched 5:1 to PsA patients on birth year, year at start of follow-up and sex. By linkage to the national cancer registers in all countries, we collected information on haematological malignancies overall, and categorised into lymphoid or myeloid types. We estimated incidence rate ratios (IRRs) with 95% CIs using modified Poisson regression for TNFi-treated versus biologics-naïve PsA patients and versus the general population adjusted for age, sex, calendar period and country.ResultsDuring 59 827 person-years, 40 haematological malignancies occurred among TNFi-treated patients with PsA resulting in a pooled IRR of 0.96 (0.68–1.35) versus biologics-naïve PsA from CRR and an IRR of 0.84 (0.64–1.10) versus biologics-naïve PsA from NPR. The IRR of haematological malignancies in PsA overall versus general population comparators was 1.35 (1.17–1.55). The estimates were largely similar for lymphoid and myeloid malignancies.ConclusionsTreatment with TNFi in patients with PsA was not associated with an increased incidence of haematological malignancies. Conversely, a moderately increased underlying risk was seen in patients with PsA compared with the general population.