bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of COVID-19 vaccination on long COVID: a systematic review and meta-analysis
Authors: Byambasuren Oyungerel , Stehlik Paulina , Clark Justin , Alcorn Kylie , Glasziou Paul 
Published: June 2022

AbstractBackgroundThe impact of COVID-19 vaccination on preventing or treating long COVID is unclear. We aim to assess the impact of COVID vaccinations administered (i) before and (ii) after acute COVID-19, including vaccination after long COVID diagnosis, on the rates or symptoms of long COVID.MethodsWe searched PubMed, Embase, Cochrane COVID-19 trials, and Europe PMC for preprints from 1 Jan 2020 to 16 Feb 2022. We included trials, cohort, and case control studies reporting on long COVID cases and symptoms with vaccine administration both before and after COVID-19 diagnosis as well as after long COVID diagnosis. Risk of bias was assessed using ROBINS-I.ResultsWe screened 356 articles and found no trials, but 6 observational studies from 3 countries (USA, UK, France) that reported on 442,601 patients. The most common long COVID symptoms studied include fatigue, cough, loss of smell, shortness of breath, loss of taste, headache, muscle ache, trouble sleeping, difficulty concentrating, worry or anxiety, and memory loss or confusion. Four studies reported data on vaccination before SARS-CoV-2 infection, of which three showed statistically significant reduction in long COVID: the odds ratio of developing long COVID with one dose of vaccine ranged between OR 0.22 to 1.03; with two doses OR 0.51 to 1; and with any dose OR 0.85 to 1.01. Three studies reported on post-infection vaccination with odds ratios between 0.38 to 0.91. The high heterogeneity between studies precluded any meaningful meta-analysis. Studies failed to adjust for potential confounders such as other protective behaviours, and missing data, thus increasing the risk of bias, and decreasing the certainty of evidence to low.DiscussionCurrent studies suggest that COVID-19 vaccinations may have protective and therapeutic effects on long COVID. However, more robust comparative observational studies and trials are urgently needed to clearly determine effectiveness of vaccines in prevention and treatment of long COVID.
Ethnic inequalities in patient satisfaction with primary health care in the UK: evidence from recent General Practitioner Patient Surveys (GPPS)
Authors: Magadi John Paul , Magadi Monica Akinyi 
Published: June 2022

AbstractAims and objectivesThis paper aims to improve understanding of factors that contribute to persistent ethnic disparities in patient satisfaction in the UK. The specific objectives are to (i) examine ethnic differences in patient satisfaction with their primary care in the UK; (ii) establish recent trends in patient satisfaction by ethnicity; and (iii) examine factors that contribute to ethnic differences in patient satisfaction.Data and methodsThe study is based on secondary analysis of recent General Practitioner Patient Survey (GPPS) datasets of 2019, 2020 and 2021. Descriptive bivariate analysis was used to examine ethnic differences in patient satisfaction across the three years. This was followed with multilevel linear regression, with General Practice (GP) at level-1 and Clinical Commissioning Group (CCG) at level-2 to identify factors contributing to ethnic differences in patient satisfaction.ResultsThe findings show consistent negative correlations between the proportion of patients reporting good (very or fairly good) overall experience and each of the ethnic minority groups. Further examination of the distribution of patient satisfaction by ethnicity, based on combined ethnic minority groups, depicted a clear negative association between ethnic minority group and patient satisfaction at both GP and CCG level. Multilevel regression analysis identified several service-related factors (especially ease of using GP website and being treated with care and concern) that largely explained the ethnic differences in patient satisfaction. Of all factors relating to patient characteristics considered in the analysis, none was significant after controlling for GP service-related factors.ConclusionsEthnic minority patients in the UK continue to consistently report lower satisfaction with their primary health care in recent years. This is largely attributable to supply (service related) rather than demand (patient characteristics) factors. These findings have important implications for health care system policy and practice at both GP and CCG levels in the UK.
Association of Complement C3 Inhibitor Pegcetacoplan with Photoreceptor Degeneration Beyond Areas of Geographic Atrophy
Authors: Pfau Maximilian , Schmitz-Valckenberg Steffen , Ribeiro Ramiro , Safaei Reza , McKeown Alex , Fleckenstein Monika , Holz Frank G. 
Published: June 2022

ABSTRACTPreservation of photoreceptors beyond areas of retinal pigment epithelium atrophy is a critical treatment goal in eyes with geographic atrophy (GA) to prevent vision loss. Thus, we assessed the association of treatment with the complement C3 inhibitor pegcetacoplan with optical coherence tomography (OCT)-based photoreceptor laminae thicknesses in this post hoc analysis of the FILLY trial (NCT02503332).Retinal layers in OCT were segmented using a deep-learning-based pipeline and extracted along evenly spaced contour-lines surrounding areas of GA. The primary outcome measure was change from baseline in (standardized) outer nuclear layer (ONL) thickness at the 5.16°-contour-line at month 12.Participants treated with pegcetacoplan monthly had a thicker ONL along the 5.16° contour-line compared to the pooled sham arm (mean difference [95% CI] +0.29 z-score units [0.16, 0.42],P<.001). The same was evident for eyes treated with pegcetacoplan every other month (+0.26 z-score units [0.13, 0.4],P<.001). Additionally, eyes treated with pegcetacoplan exhibited a thicker photoreceptor inner segment layer along the 5.16°-contour-line at month 12.These findings suggest that pegcetacoplan could slow GA progression and lead to a lesser thinning of photoreceptor layers beyond the GA boundary. Future trials in earlier disease stages, i.e., intermediate AMD, aiming to slow photoreceptor degeneration warrant consideration.
Effectiveness of Subcutaneous Casirivimab and Imdevimab Relative to no COVID-19 Antibody Treatment Among Patients Diagnosed With COVID-19 in the Ambulatory Setting
Authors: Jalbert Jessica J. , Hussein Mohamed , Mastey Vera , Sanchez Robert J. , Wang Degang , Murdock Dana , Farinas Laura , Bussey Jonathan , Duart Carlos , Hirshberg Boaz , Weinreich David M. , Wei Wenhui 
Published: June 2022

AbstractImportanceData on real-world effectiveness of subcutaneous (SC) administration of casirivimab and imdevimab (CAS+IMD) for treatment of COVID-19 are limited.ObjectiveTo assess effectiveness of SC CAS+IMD vs no COVID-19 antibody treatment among patients diagnosed with COVID-19 in ambulatory settings during the Delta-dominant period prior to Omicron emergence.DesignRetrospective cohort study.SettingEncrypted linked data between Komodo Health closed claims database and CDR Maguire Health & Medical database.ParticipantsPatients with COVID-19 in ambulatory settings between August 1, 2021 and October 30, 2021 treated with SC CAS+IMD were exact- and propensity score-matched to up to 5 untreated patients who were treatment-eligible under the Emergency Use Authorization (EUA)ExposureSubcutaneous CAS+IMD.Main Outcomes and MeasuresComposite endpoint of 30-day all-cause mortality or COVID- 19-related hospitalization. Kaplan-Meier estimators were used to calculate composite risk overall and across subgroups including age, COVID-19 vaccination status, immunocompromised, and elevated risk defined as age ≥ 65 years or 55-64 years with body mass index ≥ 35 kg/m2, type 2 diabetes, chronic obstructive pulmonary disease, or chronic kidney disease. Cox proportional- hazards models were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI).ResultsAmong 13 522 patients treated with SC CAS+IMD, 12 972 (95.9%) were matched to 41 848 EUA-eligible untreated patients; patients were 57-58% female, with mean age between 50 and 52 years. The 30-day composite outcome risk was 1.9% (95% CI, 1.7-2.2; 247 events) and 4.4% (95% CI, 4.2-4.6; 1822 events) in the CAS+IMD-treated and untreated cohorts, respectively; CAS+IMD treatment was associated with a 49% lower risk (aHR 0.51; 95% CI, 0.46-0.58). Treatment was also associated with a 67% lower 30-day risk of all-cause mortality (aHR 0.33, 95% CI, 0.18-0.60). Treatment effectiveness was consistent regardless of vaccination status and across subgroups, including those at elevated risk (aHR 0.51, 95% CI 0.42-0.60) or immunocompromised (aHR 0.34, 95% CI 0.17-0.66).Conclusions and RelevanceSubcutaneous treatment with CAS+IMD is effective for reducing all-cause mortality or COVID-19-related hospitalization in patients diagnosed with COVID-19 and managed in real-world outpatient settings during the Delta-dominant period. Effectiveness is maintained among immunocompromised, vaccinated, and elevated risk patients.
Leveraging serology testing to identify children at risk for post-acute sequelae of SARS-CoV-2 infection: An EHR-based cohort study from the RECOVER program
Authors: Mejias Asuncion , Schuchard Julia , Rao Suchitra , Bennett Tellen D. , Jhaveri Ravi , Thacker Deepika , Bailey L. Charles , Christakis Dimitri A. , Pajor Nathan M. , Razzaghi Hanieh , Forrest Christopher B. , Lee Grace M. 
Published: June 2022

ABSTRACTThe impact of post-acute sequelae of SARS-CoV-2 infection (PASC) in children is underrecognized. We developed an EHR-based algorithm across eight pediatric institutions to identify children with COVID-19 based on serology testing from 3/2020 through 4/2022 who had not been identified by PCR. Overall, serology tests were used 100-fold less than PCR. Seroprevalence of IgG anti-nucleocapsid antibodies remained stable, while rates of positive IgG anti-spike antibodies increased in teenagers after COVID-19 vaccine approval. Through data harmonization and after excluding 1,410 serology test results that may have been influenced by vaccines, we identified 2,714 children that were COVID-19 positive exclusively by serology. These patients were frequently tested as inpatients (24% vs. 2%), had chronic conditions more frequently (37% vs 24%), and a MIS-C diagnosis (23% vs. <1%) compared with PCR-positive children. Identification of children that could have been paucisymptomatic, not tested, or missed is critical to define the burden of PASC in children.
Naturally-acquired Immunity Dynamics against SARS-CoV-2 in Children and Adolescents
Authors: Patalon Tal , Saciuk Yaki , Ohayon Hadad Hanit , Perez Galit , Peretz Asaf , Ben-Tov Amir , Gazit Sivan 
Published: June 2022

AbstractObjectivesThere are paucity of studies examining naturally acquired immunity against SARS-CoV-2 in children and adolescents, though they are generally the last group to be afforded the vaccine, and a significant portion of them are still unvaccinated. This study examined the duration of protection conferred by a previous SARS-CoV-2 infection amongst children and adolescents.DesignA retrospective study, applying two complementary approaches: a matched test-negative case control design and a retrospective cohort design.SettingNationally centralized database of Maccabi Healthcare Services, an Israeli national health fund that covers 2.5 million people.ParticipantsThe study population included between 293,743 and 458,959 individuals (depending on the model), 5-18 years of age, who were unvaccinated SARS-CoV-2 naïve persons or unvaccinated convalescent patients.Main outcomes and measuresAnalyses focused on the period of July 1 to December 13, 2021, a Delta-dominant period in Israel. We evaluated three SARS-CoV-2-related outcomes: (1) documented PCR confirmed infection or reinfection, (2) COVID-19 and (3) severe COVID-19.ResultsOverall, children and adolescents who were previously infected acquired durable protection against reinfection (symptomatic or not) with SARS-CoV-2 for at least 18 months. Importantly, no COVID-19 related deaths were recorded in either the SARS-CoV-2 naïve group or the previously infected group. Effectiveness of naturally-acquired immunity against a recurrent infection reached 89.2% (95% CI: 84.7%-92.4%) three to six months after first infection, mildly declining to 82.5% (95% CI, 79.1%-85.3%) nine months to one year after infection, then remaining rather steady for children and adolescents for up to 18 months, with a slight non-significant waning trend. Additionally, we found that ages 5-11 exhibited no significant waning of naturally acquired protection throughout the outcome period, whereas waning protection in the 12-18 age group was more prominent, but still mild.ConclusionsChildren and adolescents who were previously infected with SARS-CoV-2 remain protected against reinfection to a high degree for 18 months. Policy decision makers should consider when and if convalescent children and adolescents should be vaccinated. Nonetheless, further research is needed to examine naturally acquired immunity against emerging variants, including the Omicron.
Forecasting waiting lists for elective procedures and surgery in England: a modelling study
Authors: Nepogodiev Dmitri , Acharya Radhika , Chaudhry Daoud , Glasbey James C , Harris Benjamin , Li Elizabeth , Jolly Kate , Bhangu Aneel 
Published: June 2022

AbstractIntroductionThe aim of this study was to forecast the total need for elective procedures in England by 2030.MethodsWe used publicly available activity data from NHS Digital to estimate procedure- level shortfalls in elective procedures performed during the pandemic period (January 2020 to March 2022) compared to what would be expected based on pre-pandemic trends. We also estimated the procedure-level composition of the NHS waiting list immediately preceding the pandemic (December 2019). The total need for elective procedures in March 2022 was calculated by summing the pandemic shortfall with the pre-pandemic NHS waiting list. We projected the need for elective procedures through to January 2030 for four scenarios: current capacity (surgical volume remains at the same level as in February-March 2022), pessimistic scenario (elective procedure volume increases to pre-pandemic levels by July 2023 followed and remains at this level until 2030), central scenario (elective procedure volume returns to pre-pandemic levels by December 2022 followed by a 2% increase per year), optimistic scenario (elective procedure volume returns to pre-pandemic levels by December 2022 followed by a 4% increase per year)ResultsWe estimated the total need for elective procedures in England in March 2022 was 4,347,469. Of these 4,347,469 patients, 3,304,513 (76.0%) were on a hidden waiting list. The greatest need was for General Surgery (1,522,366), Orthopaedics (976,875), and Ophthalmology (391,683). The procedures with the greatest need were sigmoidoscopy and colonoscopy (568,838), gastroscopy (447,830), cataract surgery (314,790), lower limb joint replacement (224,363), and interventional cardiology (349,300). We projected that at current capacity, the total number of elective procedures needed would increase to 14,608,195 by 2030. In the pessimistic scenario, elective procedure volume total elective procedures needed would increase to 8,507,087, in the central scenario it would increase to 5,420,999, and in the optimistic scenario it would decrease to 2,584,664 procedures.DiscussionThe estimate of 4.3 million elective procedures needed in England is considerably higher than the official NHS waiting list, reflecting a large hidden waiting list. Even in the most optimistic scenarios there will be a substantially larger waiting list in 2030 than pre-pandemic.
A Bayesian hierarchical approach to account for reporting uncertainty, variants of concern and vaccination coverage when estimating the effects of non-pharmaceutical interventions on the spread of infectious diseases
Authors: Rehms Raphael , Ellenbach Nicole , Rehfuess Eva , Burns Jacob , Mansmann Ulrich , Hoffmann Sabine 
Published: June 2022

AbstractCoronavirus disease (COVID-19) has highlighted both the shortcomings and value of modelling infectious diseases. Infectious disease models can serve as critical tools to predict the development of cases and associated healthcare demand and to determine the set of non-pharmaceutical interventions (NPI) that is most effective in slowing the spread of the infectious agent. Current approaches to estimate NPI effects typically focus on relatively short time periods and either on the number of reported cases, deaths, intensive care occupancy or hospital occupancy as a single indicator of disease transmission. In this work, we propose a Bayesian hierarchical model that integrates multiple outcomes and complementary sources of information in the estimation of the true and unknown number of infections while accounting for time-varying under-reporting and weekday-specific delays in reported cases and deaths, allowing us to estimate the number of infections on a daily basis rather than having to smooth the data. Using information from the entire course of the pandemic, we account for the spread of variants of concern, seasonality and vaccination coverage in the model. We implement a Markov Chain Monte Carlo algorithm to conduct Bayesian inference and estimate the effect of NPIs for 20 European countries. The approach shows good performance on simulated data and produces posterior predictions that show a good fit to reported cases, deaths, hospital and intensive care occupancy.
Dissected subgroups predict the risk of recurrence of stage II colorectal cancer and select rational treatment
Authors: Wang Fulong , Lu Shixun , Zhou Xin , Di Xiaotang , Wu Rujia , Chen Gong , Tian Sun 
Published: June 2022

AbstractBackgroundStage II colorectal cancer(CRC) patients after surgery alone have a five-year survival rate of ∼60-80%; the incremental benefit of adjuvant chemotherapy is <5%. Predicting risk of recurrence and selecting effective personalized adjuvant drugs for stage II CRC using formalin-fixed, paraffin-embedded(FFPE) samples is a major challenge.Methods1319 stage II CRC patients who enrolled in 2011-2019 at Sun Yat-sen University Cancer Center were screened. RNAseq data of FFPE tumor samples of 222 stage II MSS CRC patients(n.recurrence=47, n.norecurrence=175, median follow-up=41 months) were used to develop a method TFunctionalProg for dissecting heterogeneous subgroups of recurrence, predicting risk of recurrence and proposing adjuvant drugs.ResultsTFunctionalProg showed significant predictive values in 222 stage II MSS CRCs. The TFunctionalProg low-risk group had significantly better RFS (validation set (HR=4.78, p-value=1e-4, low-risk group three-year RFS=92.6%, high-risk group three-year RFS=59.7%). TFunctionalProg dissected two subgroups of transition states of stage II MSS CRCs at a high risk of recurrence; each state displays distinct levels of hybrid epithelial-mesenchymal traits, cytotoxic cell inhibition and FOLFOX resistance. Based on mechanisms in two subgroups, TFunctionalProg proposed personalized rational adjuvant drug combinations of immunotherapy, chemotherapy and repurposed CNS drugs. The complementary utility of TFunctionalProg and ctDNA-based prognostic biomarkers were presented.ConclusionTFunctionalProg was validated using FFPE samples to predict the risk of recurrence and propose rational adjuvant drug combinations for stage II CRCs.
ERBB4 Drives the Proliferation of BRAF-WT Melanoma Cell Lines
Authors: Lucas L.M. , Cullum R.L. , Woggerman J.N. , Dwivedi V. , Markham J.A. , Kelley C.M. , Knerr E.L. , Cook L.J. , Lucas H.C. , Waits D.S. , Ghosh T.M. , Halanych K.M. , Gupta R.B. , Riese D.J. 
Published: June 2022

AbstractMetastatic skin cutaneous melanomas remain a significant clinical problem. In particular, those melanomas that do not contain a gain-of-functionBRAFallele remain challenging to treat because of the paucity of targets for effective therapeutic intervention. Thus, here we investigate the role of the ERBB4 receptor tyrosine kinase in skin cutaneous melanomas that contain wild-typeBRAFalleles (“BRAFWT melanomas”). We have performedin silicoanalyses of a public repository (The Cancer Genome Atlas - TCGA) of skin cutaneous melanoma gene expression and mutation data (TCGA-SKCM data set). These analyses demonstrate that elevatedERBB4transcription strongly correlates withRASgene orNF1mutations that stimulate RAS signaling. Thus, these results have led us to hypothesize that elevated ERBB4 signaling which cooperates with elevated RAS signaling to driveBRAFWT melanomas. We have tested this hypothesis using commercially availableBRAFWT melanoma cell lines. Ectopic expression of wild-typeERBB4stimulates clonogenic proliferation of the IPC-298, MEL-JUSO, MeWo, and SK-MEL-2BRAFWT melanoma cell lines, whereas ectopic expression of a dominant-negative (K751M)ERBB4mutant allele inhibits clonogenic proliferation of these same cell lines. Ectopic expression of a dominant-negativeERBB4mutant allele inhibits anchorage-independent proliferation of MEL-JUSO cells and ectopic expression of a dominant-negativeERBB2mutant alleles inhibits clonogenic proliferation of MEL-JUSO cells. These data suggest that elevated signaling by ERBB4-ERBB2 heterodimers cooperates with elevated RAS signaling to drive the proliferation of someBRAFWT tumors and that combination therapies that target these two signaling pathways may be effective against theseBRAFWT tumors.
Immediate and Long-Term Effects of Tibial Nerve Stimulation on the Sexual Behavior of Female Rats
Authors: Zimmerman Lauren L. , Mentzelopoulos Georgios , Parrish Hannah , Marcu Vlad I. , Luma Brandon D. , Becker Jill B. , Bruns Tim M. 
Published: June 2022

AbstractObjectivesThere are limited treatment options for female sexual dysfunction (FSD). Percutaneous tibial nerve stimulation (PTNS) has shown improvements in FSD symptoms in neuromodulation clinical studies, but the direct effects on sexual function are not understood. This study evaluated the immediate and long-term effects of PTNS on sexual motivation and receptivity in a rat model of menopausal women. Our primary hypothesis was that long-term PTNS would yield greater changes in sexual behavior than short-term stimulation.Materials and MethodsIn two Experiments, after receiving treatment, we placed ovariectomized female rats in an operant chamber in which the female controls access to a male by nose poking. We used five treatment conditions, which were with or without PTNS and no, partial, or full hormone priming. In Experiment 1, we rotated rats through each condition twice with behavioral testing immediately following treatment for 10 weeks. In Experiment 2, we committed rats to one condition for 6 weeks and tracked sexual behavior over time. We quantified sexual motivation and sexual receptivity with standard measures.ResultsNo primary comparisons were significant in this study. In Experiment 1, we observed increased sexual motivation but not receptivity immediately following PTNS with partial hormone priming, as compared to priming without PTNS. In Experiment 2, we observed trends of increased sexual receptivity and some sexual motivation metrics when PTNS was applied long-term with partial hormone priming, as compared to hormone-primed rats without stimulation.ConclusionsPTNS combined with hormone priming shows potential for increasing sexual motivation in the short-term and sexual receptivity in the long-term in rats. Further studies are needed to examine variability in rat behavior and to investigate PTNS as a treatment for FSD in menopausal women.