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In 1436 Duke Philip of Burgundy was advised by Hue de Lannoy that, after heavy expenditure and loss of life over twenty years, the entire community of the realm in England was so weary of the war that they had lost all hope in it. This appraisal appears in a preamble to proposals for Burgundian diplomatic initiatives in September, but it almost certainly informed the duke's decision earlier in the year to launch an attack on Calais. The English response to the siege of Calais, however, was neither lethargic nor half-hearted. In spring 1436 the government issued proclamations warning of the attack and preparing the ground for the mobilisation of the nation in defence of its honour and interests. When the siege began, Humphrey, duke of Gloucester, was appointed to command the relief expedition and soon found himself at the head of the largest army assembled in England since 1385. Many lords and knights raised companies and Londoners volunteered for service. Although there are few surviving records of the men who served in 1436, it cannot be doubted that Lancashire was well represented. Sir John Radcliffe, a native of Lancashire, was sent ahead to organise the defence of Calais. By chance, too, it is known that Thomas Harrington, a Lancashire squire, raised, at his own expense, a company of six men-at-arms and 120 archers. Even before Gloucester's expedition crossed the Channel, the duke of Burgundy's Flemish army decided to abandon the siege. After disembarking in Calais, the expeditioners joined in the rout of the Flemings and the rapine in Flanders. In England the relief of Calais, along with the defeat of a Scots incursion, was celebrated as a great victory. In addition to triumphalist poems and ballads, a Latin poem crowed the nation's chauvinism: ‘England crushes realms, Burgundy buys dishonour / Fractured France trembles, conquered Scotland groans.’
While acknowledging the bombast in 1436, historians would probably agree with Lannoy's appraisal of English attitudes to the war. They have observed a decline in the readiness of the political nation to support the war through taxation, military service and even prayer. In explaining parliament's reluctance to fund the war in France, they have clarified the sheer intractability of the fiscal problem. The decline in participation by noble and gentle families between 1415 and 1450 has been documented in some detail.
The public sphere should be regulated so the distribution of political speech does not correlate with the distribution of income or wealth. A public sphere where people can fund any political speech from their private holdings is epistemically defective. The argument has four steps. First, if political speech is unregulated, the rich predictably contribute a disproportionate share. Second, wealth tends to correlate with substantive political perspectives. Third, greater quantities of speech by the rich can “drown out” the speech of the poor, because of citizens’ limited attention span for politics. Finally, the normative problem with all this is that it reduces the diversity of arguments and evidence citizens become familiar with, reducing the quality of their political knowledge. The clearest implication of the argument is in favour of strict contribution limits and/or public funding for formal political campaigns, but it also has implications for more informal aspects of the public sphere.
Background: Antibiotic time outs (ABTOs), formal reassessments of all new antimicrobial regimens by the care team, can optimize antimicrobial regimens, reducing antimicrobial overuse and potentially improving outcomes. Implementation of ABTOs is a substantial challenge. We used quality improvement methods to implement robust, meaningful, team-driven ABTOs in general medicine ward services. Methods: We identified and engaged stakeholders to serve as champions for the quality improvement initiative. On October 1, 2018, 2 internal medicine teaching services (services A and B), began conducting ABTOs on all patients admitted to their services receiving systemic antimicrobials for at least 36 hours. Eligible patients were usually identified by the team pharmacist. ABTOs were completed within 72 hours of antibiotic initiation and were documented in the electronic medical record (EMR) by providers using a template. The process was modified as necessary in response to feedback from frontline clinicians using plan-do-study-act (PDSA) methods. We subsequently spread the project to 2 additional internal medicine services (services C and D); 2 family medicine teams (services E and F); and 1 general pediatric service (service G). The project is ongoing. We collected data for the following metrics: (1) proportion of ABTO-eligible patients with an ABTO; (2) proportion of ABTOs conducted within the recommended time frame; (3) documented plan changes as a result of ABTO (eg, change IV antibiotics to PO); (4) proportion of documented plan changes actually completed within 24 hours. Results: Within 12 weeks, services A and B were successfully completing time outs in >80% of their patients. This target was consistently reached by services C, D, E, F, and G almost immediately following launch on those services. As of June 29, 2019, >80% of eligible patients across all participating services have had a time out conducted for 16 consecutive weeks. ABTOs have resulted in a change in management in 35% of cases, including IV-to-PO change in 19% of cases and discontinuation in 5%. Overall, 77% of time outs occurred during the 36–72-hour window. Ultimately, 95% of documented plan changes were completed within 24 hours. Conclusions: ABTOs are effective but implementation is challenging. We achieved high compliance with ABTOs without using electronic reminders. Our results suggest that ABTOs were impactful in the non–critical-care general medicine setting. Next steps include (1) development of EMR-based tools to facilitate identifying eligible patients and ABTO documentation; (2) continued spread through our health care system; and (3) analysis of ABTO impact using ABTO-unexposed patients as a control group.
Many studies document cognitive decline following specific types of acute illness hospitalizations (AIH) such as surgery, critical care, or those complicated by delirium. However, cognitive decline may be a complication following all types of AIH. This systematic review will summarize longitudinal observational studies documenting cognitive changes following AIH in the majority admitted population and conduct meta-analysis (MA) to assess the quantitative effect of AIH on post-hospitalization cognitive decline (PHCD).
We followed Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Selection criteria were defined to identify studies of older age adults exposed to AIH with cognitive measures. 6566 titles were screened. 46 reports were reviewed qualitatively, of which seven contributed data to the MA. Risk of bias was assessed using the Newcastle–Ottawa Scale.
The qualitative review suggested increased cognitive decline following AIH, but several reports were particularly vulnerable to bias. Domain-specific outcomes following AIH included declines in memory and processing speed. Increasing age and the severity of illness were the most consistent risk factors for PHCD. PHCD was supported by MA of seven eligible studies with 41,453 participants (Cohen’s d = −0.25, 95% CI [−0.02, −0.49] I2 35%).
There is preliminary evidence that AIH exposure accelerates or triggers cognitive decline in the elderly patient. PHCD reported in specific contexts could be subsets of a larger phenomenon and caused by overlapping mechanisms. Future research must clarify the trajectory, clinical significance, and etiology of PHCD: a priority in the face of an aging population with increasing rates of both cognitive impairment and hospitalization.
Outbreaks of cyclosporiasis, a food-borne illness caused by the coccidian parasite Cyclospora cayetanensis have increased in the USA in recent years, with approximately 2300 laboratory-confirmed cases reported in 2018. Genotyping tools are needed to inform epidemiological investigations, yet genotyping Cyclospora has proven challenging due to its sexual reproductive cycle which produces complex infections characterized by high genetic heterogeneity. We used targeted amplicon deep sequencing and a recently described ensemble-based distance statistic that accommodates heterogeneous (mixed) genotypes and specimens with partial genotyping data, to genotype and cluster 648 C. cayetanensis samples submitted to CDC in 2018. The performance of the ensemble was assessed by comparing ensemble-identified genetic clusters to analogous clusters identified independently based on common food exposures. Using these epidemiologic clusters as a gold standard, the ensemble facilitated genetic clustering with 93.8% sensitivity and 99.7% specificity. Hence, we anticipate that this procedure will greatly complement epidemiologic investigations of cyclosporiasis.
Chapter 5 explores the early spread of vaccination in continental Europe. If news of Jenner’s discovery quickly spread abroad, the delivery of vaccine in a viable state proved a major challenge. Diplomatic and medical networks explain its early arrival in Germany and Austria. From 1799, Dr De Carro made Vienna a major centre for the spread of the practice, with the samples sent to Lord Elgin in Istanbul seeding the practice in Greece. The British military build-up in the Mediterranean opened new channels for the dissemination of English cowpox. By vaccinating sailors aboard ship, Drs Marshall and Walker brought fresh vaccine to Gibraltar and Malta and Marshall established vaccination in Sicily and southern Italy early in 1801. Dr Sacco’s discovery of a local source of cowpox in cattle in Lombardy in late 1800 led to important trials and, over the following decade, an impressive vaccination programme in northern Italy. In the interstices of war in Europe, the practice developed as an international enterprise with several important new hubs.
Chapter 3 focuses on Jenner and the discovery of vaccination, specifically his translation of the vague notion that cowpox prevented smallpox into a more precise body of knowledge which could distinguish between varieties of cowpox and be the basis for the development of protocols for its effective use. Given the rarity of cowpox, his use of humanised cowpox (vaccine), propagated on children, was to prove critical to the success and viability of the practice. Publishing his findings in 1798, Jenner had to wait a year for his new mode of prophylaxis to gain acceptance. Initially, London-based physicians – Woodville conducting clinical trials and Pearson distributing vaccine – made much of the running. Jenner, however, reasserted his leadership in the field and made championship of vaccination his principal occupation. After considering reports on Jenner’s discovering of cowpox inoculation and making it available to the world, the British parliament granted him a premium in 1802. The Royal Jennerian Society was established in 1803 to promote and support the practice.
Chapter 8 discusses the arrival of vaccination in Portugal and Spain. An early recipient of cowpox, Portugal proved barren ground until the Prince Regent promoted the practice. Given its long rejection of smallpox inoculation, Spain moved surprisingly rapidly to embrace the new prophylaxis, with the first vaccination at the end of 1800, with vaccine sent from Paris. During 1801, vaccination was established in Madrid and other major centres and there was a flurry of publications on the procedure, some original, others customised translations. Grandees patronised vaccination in the provinces and local initiatives led to good coverage in Barcelona and Navarra. In 1803, the Royal and Philanthropic Vaccine Expedition was organised to extend the practice through the Spanish empire, beginning in the Canary Islands. War and political upheaval frustrated measures to consolidate vaccination in Spain and Portugal, but the authorities, political and medical, and some communities retained their commitment to the practice.
Chapter 9 charts the fortunes of vaccination in the Russian empire. Emulating Catherine the Great’s patronage of inoculation, Dowager Empress Maria sponsored its introduction and establishment in the Foundling Houses in Moscow and St Petersburg in 1801. Early in 1802, Tsar Alexander commended the practice and supported a plan for a vaccine expedition through the empire, using children under vaccination to deliver vaccine from one district to the next. Projecting an image of paternalism and philanthropy, the expedition required local notables and medical men to assist in extending and embedding the practice. The Russian embassy to China in 1805–6 included a vaccination arm that helped to consolidate and further extend the practice in Siberia. By a variety of means, including promotional prints (lubki) addressed to the peasantry, pressure from the nobility and direct coercion in 1811, large numbers of vaccinations were achieved. The French invasion of Russia only briefly halted the progress of the practice. After the defeat of Napoleon, Tsar Alexander visited London, congratulating Jenner in person.
Chapter 2 discusses smallpox inoculation (variolation) in the late eighteenth century. The development of a light form of the procedure, which reduced its risks and costs, made it increasingly familiar in Britain and the English-speaking world from the 1760s. The practice likewise gained new credit, as a calculated risk, in elite and enlightened circles in continental Europe. Rulers like Catherine the Great promoted the practice, recognising its potential value to the state as well as the individual. In England, the emergence of specialist inoculators seeking the commercial edge, the practice of ‘general inoculations’ in villages, and the public health risks of popular recourse to the practice in urban settings brought to light cases of individuals previously infected with cowpox being resistant to smallpox and provided the technology and incentive to explore the possible advantages of inoculating cowpox as a safe alternative. In the meantime, the rapid expansion of smallpox inoculation, not least in European colonies, provided a launching pad for the global spread of vaccination in the decade after 1800.
Chapter 4 discusses the expansion of vaccination in the British Isles during the Napoleonic Wars. The rapid extension of the practice from 1800, involving hundreds of thousands of people, represented a mobilisation of opinion and action that paralleled the mobilisation of the nation for war. Medical men took up vaccination with alacrity, seeking to make their name and serve their communities. Members of the aristocracy and gentry, with women often in the lead, accepted it in their families and supported it in their spheres of influence. Clergymen promoted it from the pulpit. Reckless practice led to adverse outcomes that encouraged anxieties about inoculating cowpox and provided ammunition for an anti-vaccination movement in London in 1805–7. Instructed to conduct an enquiry, the College of Physicians fully endorsed vaccination in 1807. After receiving the report, Parliament broke new ground in health provision by funding a National Vaccine Establishment to distribute vaccine and have oversight of the practice.
Chapter 7 discusses the spread of vaccination in northern Europe. Familiarity with smallpox inoculation, its disadvantages as well as its advantages, assured a strong constituency of interest in the Netherlands, Germany and Scandinavia and a generally positive response to the potential of the new prophylaxis. Medical men in Germany, well-networked professionally, conducted trials of the new prophylaxis, rapidly achieved consensus as to its value and collaborated in extending it nationally. They invested culturally in vaccination, celebrating the ‘guardian pox’ in festivals and promoting a cult of Jenner. In the Netherlands, most German states and in the kingdoms of Denmark and Sweden, rulers acted on the advice of their physicians to endorse and support vaccination. Government officials and the clergy, Catholic as well as Lutheran, needed little prompting to assist in establishing it in their spheres of influence. Vaccination put down strong roots across northern Europe, becoming compulsory in Bavaria in 1805, Denmark in 1810–11 and Sweden in 1816.
Chapter 12 discusses the severity of smallpox in the New World and the use of smallpox inoculation to control smallpox in the West Indies and suppress epidemics in Spanish America. Early attempts to introduce cowpox in Jamaica and elsewhere led to disappointment, but local initiatives began to bear fruit prior to the arrival of the Spanish Royal and Philanthropic Vaccine Expedition in 1804. This well documented expedition, in which children under vaccination were escorted to go arm-to-arm with others along the way, naturally commands centre stage. Projecting an image of professional expertise and imperial benevolence, Dr Balmis and his assistants brought vaccination to Venezuela and helped to set the practice on a firmer organisational footing in Cuba, Guatemala and Mexico. In the meantime, Salvany, his deputy, headed south through Colombia and Peru, vaccinating on an epic scale. Although Lima was already supplied with vaccine from Brazil by way of Buenos Aires, Salvany continued his work in the remote districts of Peru until his death in 1810. His assistant, Grajales, remained in harness in Chile until 1812.
Chapter 13 completes the study of vaccine’s encirclement of the globe by examining its introduction in Mauritius, Cape Colony and New South Wales in 1804, Indonesia in 1804–5 and the Philippines and Canton (Guangzhou) in 1805. The seeding of vaccination around the Indian Ocean, in the southern latitudes and around the South China Sea reveals a complex pattern of movements, with vaccine from India brought to Mauritius and Cape Town, with carefully packed cowpox sent directly from London to Sydney and with Mexican boys going arm-to-arm with Filipinos. The spread of vaccination around this vast region rarely led to continuity of practice, except in European enclaves, in Mauritius and parts of the Indonesia and the Philippines, where enslaved or subject populations were available to maintain the vaccine supply. Vaccination nonetheless saved lives, helped to suppress smallpox in gateway cities, laid foundations on which the practice could be rebuilt and extended and show-cased the benefits and costs of colonial medicine.