This volume is the first detailed, book-length study of Middle English medical recipes in their literary, imaginative, social, and codicological contexts. Analysing recipe collections in over seventy ...late medieval manuscripts, this book explores how the words and structures of recipes could contribute to those texts’ healing purpose, but could also confuse, impede, exceed, and redefine that purpose. The study therefore presents a challenge to recipes’ traditional reputation as mundane, unartful texts written and read solely for the sake of directing practical action. Crucially, it also relocates these neglected texts and overlooked manuscripts within the complex networks forming medieval textual culture, demonstrating that—though marginalized in modern scholarship—medical recipes were actually linguistically, formally, materially, and imaginatively interconnected with many other late medieval discourses, including devotional writings, romances, fabliaux, and Chaucerian poetry. The monograph thus models for readers modes of analysis and close reading that might be deployed in relation to recipes in order to understand better their allusive, fragmentary, and playful qualities as well as their wide-ranging influence on medieval imaginations.
This article tells the story of an eighteenth-century medical pamphlet called
This was written by John Morley (d. 1776/7), a wealthy Essex landowner who advertised free medical treatments. The ...pamphlet is one of many short tracts on scrofula produced after the ceremony of 'the royal touch' ceased with the death of Queen Anne. However, it merits special attention from historians of medicine and historians of the book because it was edited and reprinted many more times than other surviving scrofula tracts: 42 editions appeared between 1760 and 1824. This suggests significant popularity. The
is also of interest because the first 15 editions display changes and additions completed by Morley before his death in late 1776 or early 1777. Between these versions, Morley consistently refashioned his identity as practitioner and author. He also adjusted his portrayal of the intended readers of the pamphlet: in later editions, readers are recorded using the
in increasingly complex and autonomous ways to design their own medical treatments. The pamphlet is therefore testimony to the fluid relationship between practitioner and patient. It shows that seemingly simple, formulaic and easy-to-read forms like pamphlets and case studies could play a variety of complex and shifting roles in eighteenth-century medical encounters and the construction of healing knowledge.
This study introduces a novel method for estimating the variance of life expectancy since diagnosis (LE
) and loss in life expectancy (LLE) for cancer patients within a relative survival framework in ...situations where life tables based on the entire general population are not accessible. LE
and LLE are useful summary measures of survival in population-based cancer studies, but require information on the mortality in the general population. Our method addresses the challenge of incorporating the uncertainty of expected mortality rates when using a sample from the general population.
To illustrate the approach, we estimated LE
and LLE for patients diagnosed with colon and breast cancer in Sweden. General population mortality rates were based on a random sample drawn from comparators of a matched cohort. Flexible parametric survival models were used to model the mortality among cancer patients and the mortality in the random sample from the general population. Based on the models, LE
and LLE together with their variances were estimated. The results were compared with those obtained using fixed expected mortality rates.
By accounting for the uncertainty of expected mortality rates, the proposed method ensures more accurate estimates of variances and, therefore, confidence intervals of LE
and LLE for cancer patients. This is particularly valuable for older patients and some cancer types, where underestimation of the variance can be substantial when the entire general population data are not accessible.
The method can be implemented using existing software, making it accessible for use in various cancer studies. The provided example of Stata code further facilitates its adoption.
A relative survival approach is often used in population-based cancer studies, where other cause (or expected) mortality is assumed to be the same as the mortality in the general population, given a ...specific covariate pattern. The population mortality is assumed to be known (fixed), i.e. measured without uncertainty. This could have implications for the estimated standard errors (SE) of any measures obtained within a relative survival framework, such as relative survival (RS) ratios and the loss in life expectancy (LLE). We evaluated the existing approach to estimate SE of RS and the LLE in comparison to if uncertainty in the population mortality was taken into account.
The uncertainty from the population mortality was incorporated using parametric bootstrap approach. The analysis was performed with different levels of stratification and sizes of the general population used for creating expected mortality rates. Using these expected mortality rates, SEs of 5-year RS and the LLE for colon cancer patients in Sweden were estimated.
Ignoring uncertainty in the general population mortality rates had negligible (less than 1%) impact on the SEs of 5-year RS and LLE, when the expected mortality rates were based on the whole general population, i.e. all people living in a country or region. However, the smaller population used for creating the expected mortality rates, the larger impact. For a general population reduced to 0.05% of the original size and stratified by age, sex, year and region, the relative precision for 5-year RS was 41% for males diagnosed at age 85. For the LLE the impact was more substantial with a relative precision of 1286%. The relative precision for marginal estimates of 5-year RS was 3% and 30% and for the LLE 22% and 313% when the general population was reduced to 0.5% and 0.05% of the original size, respectively.
When the general population mortality rates are based on the whole population, the uncertainty in the estimates of the expected measures can be ignored. However, when based on a smaller population, this uncertainty should be taken into account, otherwise SEs may be too small, particularly for marginal values, and, therefore, confidence intervals too narrow.
Introduction
The aim of this work is to evaluate baricitinib safety with respect to venous thromboembolism (VTE), major adverse cardiovascular events (MACE), and serious infection relative to tumor ...necrosis factor inhibitors (TNFi) in patients with rheumatoid arthritis (RA).
Methods
Patients with RA from 14 real-world data sources (three disease registries, eight commercial and three government health insurance claims databases) in the United States (
n
= 9), Europe (
n
= 3), and Japan (
n
= 2) were analyzed using a new user active comparator design. Propensity score matching (1:1) controlled for potential confounding. Meta-analysis of incidence rate ratios (IRR) and incidence rate differences (IRD) for each outcome, from each data source was executed using modified Poisson regression and Cochran–Mantel–Haenszel analysis.
Results
Of 9013 eligible baricitinib-treated patients, 7606 were propensity score-matched with TNFi-treated patients, contributing 5879 and 6512 person-years of baricitinib and TNFi exposure, respectively. Across data sources, 97 patients (56 baricitinib) experienced VTE during follow-up, 93 experienced MACE (54 baricitinib), and 321 experienced serious infection (176 baricitinib). Overall IRRs comparing baricitinib with TNFi treatment were 1.51 (95% CI 1.10, 2.08) for VTE, 1.54 (95% CI 0.93, 2.54) for MACE, and 1.36 (95% CI 0.86, 2.13) for serious infection. IRDs for VTE, MACE, and serious infection, respectively, were 0.26 (95% CI −0.04, 0.57), 0.22 (95% CI −0.07, 0.52), and 0.57 (95% CI −0.07, 1.21) per 100 person-years greater for baricitinib than TNFi.
Conclusions
Overall results suggest increased risk of VTE with baricitinib versus TNFi, with consistent point estimates from the two largest data sources. A numerically greater risk was observed for MACE and serious infection when comparing baricitinib versus TNFi, with different point estimates from the two largest data sources. Findings from this study and their impact on clinical practice should be considered in context of limitations and other evidence regarding the safety and efficacy of baricitinib and other Janus kinase inhibitors.
Trial registration:
EU PAS Register (
http://encepp.eu
), identifier #32271.
There are situations when we need to model multiple time-scales in survival analysis. A usual approach in this setting would involve fitting Cox or Poisson models to a time-split dataset. However, ...this leads to large datasets and can be computationally intensive when model fitting, especially if interest lies in displaying how the estimated hazard rate or survival change along multiple time-scales continuously.
We propose to use flexible parametric survival models on the log hazard scale as an alternative method when modelling data with multiple time-scales. By choosing one of the time-scales as reference, and rewriting other time-scales as a function of this reference time-scale, users can avoid time-splitting of the data.
Through case-studies we demonstrate the usefulness of this method and provide examples of graphical representations of estimated hazard rates and survival proportions. The model gives nearly identical results to using a Poisson model, without requiring time-splitting.
Flexible parametric survival models are a powerful tool for modelling multiple time-scales. This method does not require splitting the data into small time-intervals, and therefore saves time, helps avoid technological limitations and reduces room for error.
The Sample Analysis at Mars (SAM) instrument suite detected SO2, H2S, OCS, and CS2 from approx.450 to 800 C during evolved gas analysis (EGA) of materials from the Rocknest aeolian deposit in Gale ...Crater, Mars. This was the first detection of evolved sulfur species from a Martian surface sample during in situ EGA. SO2(approx. 3-22 micro-mol) is consistent with the thermal decomposition of Fe sulfates or Ca sulfites, or evolution/desorption from sulfur-bearing amorphous phases. Reactions between reduced sulfur phases such as sulfides and evolved O2 or H2O in the SAM oven are another candidate SO2 source. H2S (approx.41-109 nmol) is consistent with interactions of H2O, H2 and/or HCl with reduced sulfur phases and/or SO2 in the SAM oven. OCS (approx.1-5 nmol) and CS2(approx.0.2-1 nmol) are likely derived from reactions between carbon-bearing compounds and reduced sulfur. Sulfates and sulfites indicate some aqueous interactions, although not necessarily at the Rocknest site; Fe sulfates imply interaction with acid solutions whereas Ca sulfites can form from acidic to near-neutral solutions. Sulfides in the Rocknest materials suggest input from materials originally deposited in a reducing environment or from detrital sulfides from an igneous source. The presence of sulfides also suggests that the materials have not been extensively altered by oxidative aqueous weathering. The possibility of both reduced and oxidized sulfur compounds in the deposit indicates a nonequilibrium assemblage. Understanding the sulfur mineralogy in Rocknest materials, which exhibit chemical similarities to basaltic fines analyzed elsewhere on Mars, can provide insight in to the origin and alteration history of Martian surface materials.
Couplets, though, tend towards unity as well as fragmentation: they continue to bind the two responses of glee and wretchedness into a cohesive unit sealed by rhyme.6 This is fitting, although ...references to splitting, tearing, and fracturing proliferate across Jack and bis Stepdame, dividing bodies and minds, one also finds across the different versions of the poem that survive a simultaneous - and related - interest in unity, an insistence that, in some ways, the wondrous, funny, and unusual spectacles Jack brings about have the potential to unite those who watch and participate in them. In recent decades, medieval scholarship has been increasingly preoccupied with the relationship between community, emotions, and display: work on the history of affects and emotions has stressed communities' capacity to structure the experience, categorization, and articulation of emotions, but it has also emphasized the boundaries and differences isolating communal experiences and dividing them from within.7 Similarly, though many scholars have affirmed the unifying potential of political, religious, and communal spectacles, Claire Sponsler and other thinkers have challenged unity as the default position, suggesting that 'recent theories of divergent response in mass culture criticism' can help open up more flexible interpretative horizons for medieval drama, spectacle, and display.8 She suggests that those flexible horizons would better suit 'the overlapping socioeconomic groups that made up urban life' (and urban audiences) since those groups 'tended to spin out a nearly endless chain of fragmentations and unifications' as individuals participated in, and stood apart from, multiple communities at once.9 Jack and bis Stepdame has not fed into these discussions of spectacle but it is revealing that the main marvel that Jack performs - the playing of a magic pipe which compels everyone who hears it to dance - is multisensory, appealing to spectators' hearing, sight, and touch along with their capacity to experience wonder, laughter, pain, and pleasure. ...the variations between these witnesses add another dimension to the tale's persistent concern with tearing, dividing, and fragmenting: variations sometimes cluster around those lines that are concerned with subjective emotional responses to Jack's tricks, reproducing the divisions within the tale at the level of textual transmission as scribes and printers take different - and often polarized - attitudes to the most appropriate crowd response to Jack's spectacular but violent shenanigans. Melissa Furrow's edition of the poem and careful outlining of these different manuscript and print groups, their relationship to one another, and the different endings they contain constitutes some of the most detailed scholarly attention that this understudied comic poem has received.11 Developing Furrows observations and rectifying this critical neglect, my article suggests that this lively manuscript and print tradition can also help to illuminate the poems central concern with feeling both united and fragmented.
ObjectivesTo investigate whether the relative effectiveness of janus kinase inhibitors (JAKis) versus tumour necrosis factor inhibitors (TNFi) or other biological disease-modifying antirheumatic ...drugs in rheumatoid arthritis differ by the presence or absence of risk factors for cardiovascular (CV) disease, age, sex and smoking.MethodsThrough Swedish registers, we identified 13 493 individuals with 3166 JAKi, 5575 non-TNFi and 11 286 TNFi treatment initiations 2016–2022. All lines of therapy were included, with the majority in second line or higher. Treatment response was defined as the proportion reaching European Alliance of Associations for Rheumatology (EULAR) good response and Clinical Disease Activity Index (CDAI) remission, respectively, within 6 months. Crude percentage point differences in these proportions (JAKis, and non-TNFis, vs TNFis) overall and by risk factors were observed, and adjusted for confounders using linear regression models. Predicted probabilities of response and remission were estimated from adjusted Poisson models, and presented across CV risk and age.ResultsOverall, adjusted percentage point differences indicated higher response (+5.0%, 95% CI 2.2% to 7.9%) and remission (+5.8%, 95% CI 3.2% to 8.5%) with JAKis versus TNFis. The adjusted percentage point differences for response in those above 65, at elevated CV risk, and smokers were +5.9% (95% CI 2.7% to 9.0%), +8.3% (95% CI 5.3% to 11.4%) and +6.0% (95% CI 3.3% to 8.7%), respectively. The corresponding estimates for remission were +8.0% (95% CI 5.3% to 10.8%), +5.6% (95% CI 3.0% to 8.2%) and +7.6% (95% CI 5.5% to 9.7%).ConclusionsAs used in clinical practice, response and remission at 6 months with JAKis are higher than with TNFi. Among patients with risk factors of concern, effectiveness is similar or numerically further increased. For individualised benefit-to-risk ratios to guide treatment choice, safety and effectiveness in specific patient segments should be considered.
ObjectivesTo compare risks for COVID-19-related outcomes in inflammatory joint diseases (IJDs) and across disease-modifying antirheumatic drugs (DMARDs) during the first two waves of the pandemic and ...to assess effects of the pandemic on rheumatology care provision.MethodsThrough nationwide multiregister linkages and cohort study design, we defined IJD and DMARD use annually in 2015–2020. We assessed absolute and relative risks of hospitalisation or death listing COVID-19. We also assessed the incidence of IJD and among individuals with IJD, rheumatologist visits, DMARD use and incidence of selected comorbidities.ResultsBased on 115 317 patients with IJD in 2020, crude risks of hospitalisation and death listing COVID-19 (0.94% and 0.33% across both waves, respectively) were similar during both waves (adjusted HR versus the general population 1.33, 95% CI 1.23 to 1.43, for hospitalisation listing COVID-19; 1.23, 95% CI 1.08 to 1.40 for death listing COVID-19). Overall, biological disease-modifying antirheumatic drugs (bDMARDs)/targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) did not increase risks of COVID-19 related hospitalisation (with the exception of a potential signal for JAK inhibitors) or death. During the pandemic, decreases were observed for IJD incidence (−7%), visits to rheumatology units (−16%), DMARD dispensations (+6.5% for bDMARD/tsDMARDs and −8.5% for conventional synthetic DMARDs compared with previous years) and for new comorbid conditions, but several of these changes were part of underlying secular trends.ConclusionsPatients with IJD are at increased risk of serious COVID-19 outcomes, which may partially be explained by medical conditions other than IJD per se. The SARS-CoV-2 pandemic has exerted measurable effects on aspects of rheumatology care provision demonstrated, the future impact of which will need to be assessed.
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