bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapidly worsening pneumonia in a middle-aged woman: a rare diagnosis and a crucial management decision
Authors: Thomas Liza , Mohammed Asna , Shaikh Niaz Ahmed , Aldaham Tahani Ahmed 
Published: March 2021

A 54-year-old Indian female presented to the hospital with a 4-day history of fever, shortness of breath and blood-streaked sputum. Chest radiograph showed consolidation and she was admitted as a case of bilateral bronchopneumonia. She was started on broad-spectrum antibiotics and antivirals but she continued to deteriorate clinically with increasing oxygen requirement and worsening lung infiltrates. Since lab investigations also revealed significant anaemia and renal impairment, vasculitic workup for pulmonary renal haemorrhagic syndrome was ordered even though she had no haemoptysis in the hospital and haemoglobin was stable after initial blood transfusion. High-resolution computed tomography scan was done on day 5 to assess progression and for any clue to diagnosis. It showed extensive bilateral air space consolidation and ground-glass opacities with suggested radiological differential diagnosis of cryptogenic organising pneumonia or pulmonary haemorrhage. Pulmonology team did not recommend bronchoscopy at the time.In view of the clinical features of rapidly progressing pneumonia despite standard treatment, history of haemoptysis, anaemia, renal impairment and CT scan findings suggestive of pulmonary haemorrhage, pulse intravenous Methylprednisolone was initiated. The patient showed marked clinical and radiological improvement. The vasculitic workup later revealed positive myeloperoxidase antibody and a definitive diagnosis of microscopic polyangiitis was made. She was discharged in a stable condition and advised to follow-up in rheumatology where she continues to follow-up 2 years after her initial diagnosis.This is the first case reported in literature, where treatment was initiated for this rare disease entity within a week of presentation based on highly suggestive clinical, laboratory and radiological evidence without waiting for a confirmatory diagnosis. Delay in this rapidly deteriorating patient could have been fatal and our prompt action was crucial in securing a favourable outcome.
Epidemiological impact of prioritising SARS-CoV-2 vaccination by antibody status: mathematical modelling analyses
Authors: Ayoub Houssein H , Chemaitelly Hiam , Makhoul Monia , Al Kanaani Zaina , Al Kuwari Einas , Butt Adeel A , Coyle Peter , Jeremijenko Andrew , Kaleeckal Anvar Hassan , Latif Ali Nizar , Shaik Riyazuddin Mohammad , Abdul Rahim Hanan F , Nasrallah Gheyath K , Yassine Hadi M , Al Kuwari Mohamed G , Al Romaihi Hamad Eid , Al-Thani Mohamed H , Bertollini Roberto , Al Khal Abdullatif , Abu-Raddad Laith J 
Published: March 2021

BackgroundVaccines against SARS-CoV-2 have been developed, but their availability falls far short of global needs. This study aimed to investigate the impact of prioritising available doses on the basis of recipient antibody status, that is by exposure status, using Qatar as an example.MethodsVaccination impact (defined as the reduction in infection incidence and the number of vaccinations needed to avert one infection or one adverse disease outcome) was assessed under different scale-up scenarios using a deterministic meta-population mathematical model describing SARS-CoV-2 transmission and disease progression in the presence of vaccination.ResultsFor a vaccine that protects against infection with an efficacy of 95%, half as many vaccinations were needed to avert one infection, disease outcome or death by prioritising antibody-negative individuals for vaccination. Prioritisation by antibody status reduced incidence at a faster rate and led to faster elimination of infection and return to normalcy. Further prioritisation by age group amplified the gains of prioritisation by antibody status. Gains from prioritisation by antibody status were largest in settings where the proportion of the population already infected at the commencement of vaccination was 30%–60%. For a vaccine that only protects against disease and not infection, vaccine impact was reduced by half, whether this impact was measured in terms of averted infections or disease outcomes, but the relative gains from using antibody status to prioritise vaccination recipients were similar.ConclusionsMajor health and economic gains can be achieved more quickly by prioritizing those who are antibody-negative while doses of the vaccine remain in short supply.
Biomechanical evaluation of a tool-less external fixator
Authors: Carpanen Diagarajen , Masouros S D , Stinner D J 
Published: March 2021

IntroductionCurrent external fixator systems used by the US and UK military for stabilising extremity fractures require specialised tools to build a construct. The goal of obtaining and maintaining limb length and alignment is not achieved if these tools are misplaced. An alternative, tool-less system is currently available, namely the Dolphix Temporary Fixation System. The aim of this study was to compare the stiffness of the Dolphix system with the existing Hoffmann III system.MethodsThree Hoffmann III and three Dolphix constructs were assembled on a bone (tibia) surrogate. A 30 mm fracture gap was created to simulate a comminuted proximal tibia or distal femur fracture. The constructs were then tested in cyclic axial compression once daily for 3 consecutive days.ResultsThe length and alignment of the surrogate limb was restored following each testing cycle with both external fixation systems. The stiffness of the constructs was maintained throughout each sequential test, with the Dolphix exhibiting 54% the stiffness of the Hoffmann III construct.ConclusionGiven the Dolphix’s performance in mechanical testing and the unique advantage of having a tool-less manual locking clamp mechanism, this tool-less system should be considered for use in the mobile austere environment.
Temporal trends in hyperuricaemia among adults in Wuhan city, China, from 2010 to 2019: a cross-sectional study
Authors: Wan Zhengce , Song Lulu , Hu Liu , Lei Xiaomei , Huang Yuancheng , Lv Yongman 
Published: March 2021

ObjectivesHyperuricaemia is a risk factor for gout attacks, kidney damage and cardiovascular events. Evidence on the trends in hyperuricaemia burden in Wuhan city, China, was limited. The present study aimed to estimate the prevalence of and a decade trend in hyperuricaemia in Wuhan city.DesignCross-sectional study.SettingHealth Management Center of Tongji Hospital.ParticipantsA total of 732 527 adult participants from the general population who took a physical examination in the Health Management Center between 2010 and 2019.Main outcome measuresPrevalence of and trends in hyperuricaemia.ResultsThe overall prevalence of hyperuricaemia was 25.8% (36.6% in men and 10.8% in women) in 2019. The hyperuricaemia prevalence and serum uric acid (SUA) levels were significantly higher in young men, old women and participants with obesity, hypertension, diabetes or dyslipidaemia (p<0.05). SUA levels among men and women gradually increased from 358.0 (313.0–407.0) umol/L and 250.0 (217.0–288.0) umol/L in 2010 to 388.0 (338.0–445.2) umol/L and 270.0 (233.0–314.0) umol/L in 2019, respectively, p<0.05. From 2010 through 2019, hyperuricaemia prevalence significantly increased in each age category and it increased most sharply among participants aged 20–39 years. The multivariate-adjusted prevalence among men was 26.1% (25.4% to 26.7%) in 2010, 30.9% (30.4% to 31.4%) in 2015 and 34.4% (34.1% to 34.8%) in 2019, while among women it was 5.8% (5.4% to 6.2%) in 2010, 7.2% (6.9% to 7.5%) in 2015 and 10.1% (9.9% to 10.3%) in 2019.ConclusionsHyperuricaemia was highly prevalent among adults in Wuhan city. More attention should be paid to the increasing burden of hyperuricaemia, especially for those at higher risks.
Lenient rate control versus strict rate control for atrial fibrillation: a protocol for the Danish Atrial Fibrillation (DanAF) randomised clinical trial
Authors: Feinberg Joshua Buron , Olsen Michael Hecht , Brandes Axel , Raymond llan , Nielsen Walter Bjørn , Nielsen Emil Eik , Stensgaard-Hansen Frank , Dixen Ulrik , Pedersen Ole Dyg , Gang Uffe Jakob Ortved , Gluud Christian , Jakobsen Janus Christian 
Published: March 2021

IntroductionAtrial fibrillation is the most common heart arrhythmia with a prevalence of approximately 2% in the western world. Atrial fibrillation is associated with an increased risk of death and morbidity. In many patients, a rate control strategy is recommended. The optimal heart rate target is disputed despite the results of the the RAte Control Efficacy in permanent atrial fibrillation: a comparison between lenient vs strict rate control II (RACE II) trial.Our primary objective will be to investigate the effect of lenient rate control strategy (<110 beats per minute (bpm) at rest) compared with strict rate control strategy (<80 bpm at rest) on quality of life in patients with persistent or permanent atrial fibrillation.Methods and analysisWe plan a two-group, superiority randomised clinical trial. 350 outpatients with persistent or permanent atrial fibrillation will be recruited from four hospitals, across three regions in Denmark. Participants will be randomised 1:1 to a lenient medical rate control strategy (<110 bpm at rest) or a strict medical rate control strategy (<80 bpm at rest). The recruitment phase is planned to be 2 years with 3 years of follow-up. Recruitment is expected to start in January 2021. The primary outcome will be quality of life using the Short Form-36 (SF-36) questionnaire (physical component score). Secondary outcomes will be days alive outside hospital, symptom control using the Atrial Fibrillation Effect on Quality of Life, quality of life using the SF-36 questionnaire (mental component score) and serious adverse events. The primary assessment time point for all outcomes will be 1 year after randomisation.Ethics and disseminationEthics approval was obtained through the ethics committee in Region Zealand. The design and findings will be published in peer-reviewed journals as well as be made available on ClinicalTrials.gov.Trial registration numberNCT04542785.
Household food insecurity and its association with self-reported male perpetration of intimate partner violence: a survey of two districts in central and western Uganda
Authors: Awungafac George , Mugamba Stephen , Nalugoda Fred , Sjöland Carl Fredrik , Kigozi Godfrey , Rautiainen Susanne , Malyabe Robert Bulamba , Ziegel Leo , Nakigozi Gertrude , Nalwoga Grace Kigozi , Kyasanku Emmanuel , Nkale James , Watya Stephen , Ekström Anna Mia , Kågesten Anna 
Published: March 2021

ObjectivesThis study aimed to determine the lifetime prevalence of male-perpetrated intimate partner violence (IPV), and to assess the association with food insecurity, sociodemographic factors and health risk behaviours in Uganda in the year preceding COVID-19-associated lockdowns.DesignPopulation-based, cross-sectional household survey.SettingUrban, semiurban and rural communities of the Wakiso and Hoima districts in Uganda.ParticipantsA total of N=2014 males aged 13–80 years participated in the survey. The current study included males who reported having ever been in a sexual union and responded to the IPV questions (N=1314).MeasuresData were collected face-to-face from May 2018 to July 2019 using an interviewer-mediated questionnaire. Lifetime IPV perpetration was measured as ‘no physical and/or sexual IPV’, ‘physical’ versus ‘sexual violence only’, and ‘physical and sexual violence’. Past-year food insecurity was measured through the Food Insecurity Experience Scale and categorised into ‘none’, ‘low’ and ‘high’. Multinomial logistic regression was used to determine the crude and adjusted relative risk ratios (aRRRs) of IPV perpetration in relation to self-reported food insecurity, adjusting for sociodemographic and health risk behaviours.ResultsThe prevalence of self-reported lifetime IPV perpetration was 14.6% for physical and 6.5% for sexual violence, while 5.3% reported to have perpetrated both physical and sexual IPV. Most (75.7%) males reported no food insecurity, followed by low (20.7%) and high (3.6%) food insecurity. In adjusted models, food insecurity was associated with increased risk of having perpetrated both physical and sexual violence (aRRR=2.57, 95% CI 1.52 to 4.32). IPV perpetration was also independently associated with having had more than one lifetime sexual partner and drinking alcohol, but not with education level or religion.ConclusionThis study suggests that food insecurity is associated with male IPV perpetration, and more efforts are needed to prevent and mitigate the expected worsening of this situation as a result of the COVID-19 pandemic.
Miles and days until medical abortion via TelAbortion versus clinic in Oregon and Washington, USA
Authors: Beardsworth Kathleen Marie , Doshi Uma , Raymond Elizabeth , Baldwin Maureen K 
Published: March 2021

BackgroundMedical abortion provided via telemedicine is becoming more widely available, potentially decreasing travel time for in-person abortion evaluation.MethodsWe conducted a retrospective chart review of all outpatient medical abortions from October 2016 through December 2019 at our academic medical centre in Portland, Oregon, USA. Using mifepristone administration logs, we identified patients who underwent abortion via direct-to-patient telemedicine or in clinic. Both groups had pre-abortion ultrasound examination. We extracted patient characteristics and geographic data to compare travel distance to clinic, ultrasound facility, and nearest advertised abortion clinic. We compared time from first contact until mifepristone ingestion and gestational age at mifepristone ingestion.ResultsMedian distance from mailing address to clinic for 80 telemedicine and 124 clinic medical abortions was 95 (range 4–377) and 12 (range 0–184) miles (p<0.01). Distance travelled to ultrasound facility was shorter for telemedicine patients (median 7 miles, range 0–150 vs 12 miles, range 0–184; p<0.01) excluding outliers >200 miles. Distance to nearest advertised abortion clinic was equal between groups (median 7 miles, p=0.4). Time to mifepristone administration (ingestion) was longer (11 vs 6 days; p<0.01) and median gestational age was higher (49 vs 44 days; p=0.01) for telemedicine.ConclusionsTelemedicine increases the reach of abortion providers and provides care to more geographically distant patients. Patients chose telemedicine abortion even when they had an equidistant option, suggesting that patients value telemedicine for reasons other than geographic convenience. This telemedicine delivery model that included ultrasound testing prior to abortion resulted in up to a 5-day delay in abortion initiation, which was not clinically significant.
Prediction of severe immune-related adverse events requiring hospital admission in patients on immune checkpoint inhibitors: study of a population level insurance claims database from the USA
Authors: Kalinich Mark , Murphy William , Wongvibulsin Shannon , Pahalyants Vartan , Yu Kun-Hsing , Lu Chenyue , Wang Feicheng , Zubiri Leyre , Naranbhai Vivek , Gusev Alexander , Kwatra Shawn G , Reynolds Kerry L , Semenov Yevgeniy R 
Published: March 2021

BackgroundImmune-related adverse events (irAEs) are a serious side effect of immune checkpoint inhibitor (ICI) therapy for patients with advanced cancer. Currently, predisposing risk factors are undefined but understanding which patients are at increased risk for irAEs severe enough to require hospitalization would be beneficial to tailor treatment selection and monitoring.MethodsWe performed a retrospective review of patients with cancer treated with ICIs using unidentifiable claims data from an Aetna nationwide US health insurance database from January 3, 2011 to December 31, 2019, including patients with an identified primary cancer and at least one administration of an ICI. Regression analyses were performed. Main outcomes were incidence of and factors associated with irAE requiring hospitalization in ICI therapy.ResultsThere were 68.8 million patients identified in the national database, and 14 378 patients with cancer identified with at least 1 administration of ICI in the study period. Patients were followed over 19 117 patient years and 504 (3.5%) developed an irAE requiring hospitalization. The incidence of irAEs requiring hospitalization per patient ICI treatment year was 2.6%, rising from 0% (0/71) in 2011 to 3.7% (93/2486) in 2016. Combination immunotherapy (OR: 2.44, p<0.001) was associated with increased odds of developing irAEs requiring hospitalization, whereas older patients (OR 0.98 per additional year, p<0.001) and those with non-lung cancer were associated with decreased odds of irAEs requiring hospitalization (melanoma OR: 0.70, p=0.01, renal cell carcinoma OR: 0.71, p=0.03, other cancers OR: 0.50, p<0.001). Sex, region, zip-code-imputed income, and zip-code unemployment were not associated with incidence of irAE requiring hospitalization. Prednisone (72%) and methylprednisolone (25%) were the most common immunosuppressive treatments identified in irAE hospitalizations.ConclusionsWe found that 3.5% of patients initiating ICI therapy experienced irAEs requiring hospitalization and immunosuppression. The odds of irAEs requiring hospitalization were higher with younger age, treatment with combination ICI therapy (cytotoxic T lymphocyte-associated 4 and programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1)), and lower for other cancers compared with patients on PD-1 or PD-L1 inhibitors with lung cancer. This evidence from the first nationwide study of irAEs requiring hospitalization in the USA identified the real-world epidemiology, risk factors, and treatment patterns of these irAEs which may guide treatment and management decisions.
Complement C3a and C5a receptor blockade modulates regulatory T cell conversion in head and neck cancer
Authors: Gadwa Jacob , Bickett Thomas E , Darragh Laurel B , Knitz Michael William , Bhatia Shilpa , Piper Miles , Van Court Benjamin , Bhuvane Shiv , Nguyen Diemmy , Nangia Varuna , Kleczko Emily K , Nemenoff Raphael A , Karam Sana D 
Published: March 2021

BackgroundResistance to therapy is a major problem in treating head and neck squamous cell carcinomas (HNSCC). Complement system inhibition has been shown to reduce tumor growth, metastasis, and therapeutic resistance in other tumor models, but has yet to be explored in the context of HNSCC. Here, we tested the effects of complement inhibition and its therapeutic potential in HNSCC.MethodsWe conducted our studies using two Human Papilloma Virus (HPV)-negative HNSCC orthotopic mouse models. Complement C3aR and C5aR1 receptor antagonists were paired with radiation therapy (RT). Tumor growth was measured and immune populations from tumor, lymph node, and peripheral blood were compared among various treatment groups. Genetically engineered mouse models DEREG and C3-/- were used in addition to standard wild type models. Flow cytometry, clinical gene sets, and in vitro assays were used to evaluate the role complement receptor blockade has on the immunological makeup of the tumor microenvironment.ResultsIn contrast to established literature, inhibition of complement C3a and C5a signaling using receptor antagonists accelerated tumor growth in multiple HNSCC cell lines and corresponded with increased frequency of regulatory T cell (Treg) populations. Local C3a and C5a signaling has importance for CD4 T cell homeostasis and eventual development into effector phenotypes. Interruption of this signaling axis drives a phenotypic conversion of CD4+ T cells into Tregs, characterized by enhanced expression of Foxp3. Depletion of Tregs reversed tumor growth, and combination of Treg depletion and C3a and C5a receptor inhibition decreased tumor growth below that of the control groups. Complete knockout of C3 does not harbor the expected effect on tumor growth, indicating a still undetermined compensatory mechanism. Dexamethasone is frequently prescribed to patients undergoing RT and inhibits complement activation. We report no deleterious effects associated with dexamethasone due to complement inhibition.ConclusionsOur data establish Tregs as a pro-tumorigenic driver during complement inhibition and provide evidence that targeted C3a and C5a receptor inhibition may add therapeutic advantage when coupled with anti-Treg therapy.
COVID-19-induced hyperinflammation, immunosuppression, recovery and survival: how causal inference may help draw robust conclusions
Authors: Landewé Robert B M , Ramiro Sofia , Mostard Rémy L M 
Published: March 2021

BackgroundThe CHIC study (COVID-19 High-intensity Immunosuppression in Cytokine storm syndrome) is a quasi-experimental treatment study exploring immunosuppressive treatment versus supportive treatment only in patients with COVID-19 with life-threatening hyperinflammation. Causal inference provides a means of investigating causality in non-randomised experiments. Here we report 14-day improvement as well as 30-day and 90-day mortality.Patients and methodsThe first 86 patients (period 1) received optimal supportive care only; the second 86 patients (period 2) received methylprednisolone and (if necessary) tocilizumab, in addition to optimal supportive care. The main outcomes were 14-day clinical improvement and 30-day and 90-day survival. An 80% decline in C reactive protein (CRP) was recorded on or before day 13 (CRP >100 mg/L was an inclusion criterion). Non-linear mediation analysis was performed to decompose CRP-mediated effects of immunosuppression (defined as natural indirect effects) and non-CRP-mediated effects attributable to natural prognostic differences between periods (defined as natural direct effects).ResultsThe natural direct (non-CRP-mediated) effects for period 2 versus period 1 showed an OR of 1.38 (38% better) for 14-day improvement and an OR of 1.16 (16% better) for 30-day and 90-day survival. The natural indirect (CRP-mediated) effects for period 2 showed an OR of 2.27 (127% better) for 14-day improvement, an OR of 1.60 (60% better) for 30-day survival and an OR of 1.49 (49% better) for 90-day survival. The number needed to treat was 5 for 14-day improvement, 9 for survival on day 30, and 10 for survival on day 90.ConclusionCausal inference with non-linear mediation analysis further substantiates the claim that a brief but intensive treatment with immunosuppressants in patients with COVID-19 and systemic hyperinflammation adds to rapid recovery and saves lives. Causal inference is an alternative to conventional trial analysis, when randomised controlled trials are considered unethical, unfeasible or impracticable.