Creation, Contingency, and Early Modern Science: The Impact of Voluntarist Theology on Seventeenth-Century Natural Philosophy

Could God have made it true that 2 + 2 = 5? Was he bound to make the best of all possible worlds? Is he able at this moment to alter the course of nature, either in whole or in part? Questions like these are often associated with medieval theology, not with early modern science. But science is done by people, and people have not always practiced the rigorous separation of science and theology that has come to characterize the modern world. Although many 17th century scientists sought validity for their work apart from revelation, divorcing science from religion was something they never intended. Indeed most natural philosophers of the scientific revolution assumed without question that the world and the human mind had been created by God. This was no small admission, for it meant that both the manner in which and the degree to which the world could be understood depended upon how God had acted in creating it and how he continued to act in sustaining it. Fifty years ago the late British philosopher M.B. Foster identified two different theologies of creation which differ profoundly in their implications for natural science. Rationalist theology, which assigns to God the activity of pure reason, involves both a rationalist X philosophy of nature and a rationalist theory of knowledge of nature. Voluntarist theology, which attributes to God an activity of will not wholly determined by reason, implies that the products of his creative activity are contingent and can be known only empirically. By a careful analysis of four natural philosophies of the early modern period--those of Galileo, Descartes, Boyle, and Newton--! intend to show that there was indeed a connection between theological voluntarism and empirical science in the 17th century

Building toolkits for COPD exacerbations: lessons from the past and present

In the nineteenth century, it was recognised that acute attacks of chronic bronchitis were harmful. 140 years later, it is clearer than ever that exacerbations of chronic obstructive pulmonary disease (ECOPD) are important events. They are associated with significant mortality, morbidity, a reduced quality of life and an increasing reliance on social care. ECOPD are common and are increasing in prevalence. Exacerbations beget exacerbations, with up to a quarter of in-patient episodes ending with readmission to hospital within 30 days. The healthcare costs are immense. Yet despite this, the tools available to diagnose and treat ECOPD are essentially unchanged, with the last new intervention (non-invasive ventilation) introduced over 25 years ago. An ECOPD is ’an acute worsening of respiratory symptoms that results in additional therapy’. This symptom and healthcare utility-based definition does not describe pathology and is unable to differentiate from other causes of an acute deterioration in breathlessness with or without a cough and sputum. There is limited understanding of the host immune response during an acute event and no reliable and readily available means to identify aetiology or direct treatment at the point of care (POC). Corticosteroids, short acting bronchodilators with or without antibiotics have been the mainstay of treatment for over 30 years. This is in stark contrast to many other acute presentations of chronic illness, where specific biomarkers and mechanistic understanding has revolutionised care pathways. So why has progress been so slow in ECOPD? This review examines the history of diagnosing and treating ECOPD. It suggests that to move forward, there needs to be an acceptance that not all exacerbations are alike (just as not all COPD is alike) and that clinical presentation alone cannot identify aetiology or stratify treatment

Assessment of a rapid liquid-based cytology method for measuring sputum cell counts

Differential sputum cell counting is not widely available despite proven clinical utility in the management of asthma. We compared eosinophil counts obtained using liquid-based cytology (LBC), a routine histopathological processing method, and the current standard method. Eosinophil counts obtained using LBC were a strong predictor of sputum eosinophilia (≥3%) determined by the standard method suggesting LBC could be used in the management of asthma

Infection, inflammation and intervention: mechanistic modelling of epithelial cells in COVID-19

While the pathological mechanisms in COVID-19 illness are still poorly understood, it is increasingly clear that high levels of pro-inflammatory mediators play a major role in clinical deterioration in patients with severe disease. Current evidence points to a hyperinflammatory state as the driver of respiratory compromise in severe COVID-19 disease, with a clinical trajectory resembling acute respiratory distress syndrome, but how this ‘runaway train’ inflammatory response emerges and is maintained is not known. Here, we present the first mathematical model of lung hyperinflammation due to SARS-CoV-2 infection. This model is based on a network of purported mechanistic and physiological pathways linking together five distinct biochemical species involved in the inflammatory response. Simulations of our model give rise to distinct qualitative classes of COVID-19 patients: (i) individuals who naturally clear the virus, (ii) asymptomatic carriers and (iii–v) individuals who develop a case of mild, moderate, or severe illness. These findings, supported by a comprehensive sensitivity analysis, point to potential therapeutic interventions to prevent the emergence of hyperinflammation. Specifically, we suggest that early intervention with a locally acting anti-inflammatory agent (such as inhaled corticosteroids) may effectively blockade the pathological hyperinflammatory reaction as it emerges

Identification of key opportunities for optimising the management of high-risk COPD patients in the UK using the CONQUEST quality standards: an observational longitudinal study

Background: This study compared management of high-risk COPD patients in the UK to national and international management recommendations and quality standards, including the COllaboratioN on QUality improvement initiative for achieving Excellence in STandards of COPD care (CONQUEST). The primary comparison was in 2019, but trends from 2000 to 2019 were also examined. / Methods: Patients identified in the Optimum Patient Care Research Database were categorised as newly diagnosed (≤12 months after diagnosis), already diagnosed, and potential COPD (smokers having exacerbation-like events). High-risk patients had a history of ≥2 moderate or ≥1 severe exacerbations in the previous 12 months. / Findings: For diagnosed patients, the median time between diagnosis and first meeting the high-risk criteria was 617 days (Q1-Q3: 3246). The use of spirometry for diagnosis increased dramatically after 2004 before plateauing and falling in recent years. In 2019, 41% (95% CI 39–44%; n = 550/1343) of newly diagnosed patients had no record of spirometry in the previous year, and 45% (95% CI 43–48%; n = 352/783) had no record of a COPD medication review within 6 months of treatment initiation or change. In 2019, 39% (n = 6893/17,858) of already diagnosed patients had no consideration of exacerbation rates, 46% (95% CI 45–47%; n = 4942/10,725) were not offered or referred for pulmonary rehabilitation, and 41% (95% CI 40–42%; n = 3026/7361) had not had a COPD review within 6 weeks of respiratory hospitalization. / Interpretation: Opportunities for early diagnosis of COPD patients at high risk of exacerbations are being missed. Newly and already diagnosed patients at high-risk are not being assessed or treated promptly. There is substantial scope to improve the assessment and treatment optimisation of these patients

Standardisation of clinical assessment, management and follow-up of acute hospitalised exacerbation of copd: A europe-wide consensus

Background: Despite hospitalization for exacerbation being a high-risk event for morbidity and mortality, there is little consensus globally regarding the assessment and management of hospitalised exacerbations of COPD. We aimed to establish a consensus list of symptoms, physiological measures, clinical scores, patient questionnaires and investigations to be obtained at time of hospitalised COPD exacerbation and follow-up. Methods: A modified Delphi online survey with pre-defined consensus of importance, feasibility and frequency of measures at hospitalisation and follow-up of a COPD exacerbation was undertaken. Findings: A total of 25 COPD experts from 18 countries contributed to all 3 rounds of the survey. Experts agreed that a detailed history and examination were needed. Experts also agreed on which treatments are needed and how soon these should be delivered. Experts recommended that a full blood count, renal function, C-reactive protein and cardiac blood biomarkers (BNP and troponin) should be measured within 4 hours of admission and that the modified Medical Research Council dyspnoea scale (mMRC) and COPD assessment test (CAT) should be performed at time of exacerbation and follow-up. Experts encouraged COPD clinicians to strongly consider discussing palliative care, if indicated, at time of hospitalisation. Interpretation: This Europe-wide consensus document is the first attempt to standardise the assessment and care of patients hospitalised for COPD exacerbations. This should be regarded as the starting point to build knowledge and evidence on patients hospitalised for COPD exacerbations

Development and validation of a new algorithm for improved cardiovascular risk prediction

QRISK algorithms use data from millions of people to help clinicians identify individuals at high risk of cardiovascular disease (CVD). Here, we derive and externally validate a new algorithm, which we have named QR4, that incorporates novel risk factors to estimate 10-year CVD risk separately for men and women. Health data from 9.98 million and 6.79 million adults from the United Kingdom were used for derivation and validation of the algorithm, respectively. Cause-specific Cox models were used to develop models to predict CVD risk, and the performance of QR4 was compared with version 3 of QRISK, Systematic Coronary Risk Evaluation 2 (SCORE2) and atherosclerotic cardiovascular disease (ASCVD) risk scores. We identified seven novel risk factors in models for both men and women (brain cancer, lung cancer, Down syndrome, blood cancer, chronic obstructive pulmonary disease, oral cancer and learning disability) and two additional novel risk factors in women (pre-eclampsia and postnatal depression). On external validation, QR4 had a higher C statistic than QRISK3 in both women (0.835 (95% confidence interval (CI), 0.833–0.837) and 0.831 (95% CI, 0.829–0.832) for QR4 and QRISK3, respectively) and men (0.814 (95% CI, 0.812–0.816) and 0.812 (95% CI, 0.810–0.814) for QR4 and QRISK3, respectively). QR4 was also more accurate than the ASCVD and SCORE2 risk scores in both men and women. The QR4 risk score identifies new risk groups and provides superior CVD risk prediction in the United Kingdom compared with other international scoring systems for CVD risk

Successful awake proning is associated with improved clinical outcomes in patients with COVID-19: single-centre high-dependency unit experience

The SARS-CoV-2 can lead to severe illness with COVID-19. Outcomes of patients requiring mechanical ventilation are poor. Awake proning in COVID-19 improves oxygenation, but on data clinical outcomes is limited. This single-centre retrospective study aimed to assess whether successful awake proning of patients with COVID-19, requiring respiratory support (continuous positive airways pressure (CPAP) or high-flow nasal oxygen (HFNO)) on a respiratory high-dependency unit (HDU), is associated with improved outcomes. HDU care included awake proning by respiratory physiotherapists. Of 565 patients admitted with COVID-19, 71 (12.6%) were managed on the respiratory HDU, with 48 of these (67.6%) requiring respiratory support. Patients managed with CPAP alone 22/48 (45.8%) were significantly less likely to die than patients who required transfer onto HFNO 26/48 (54.2%): CPAP mortality 36.4%; HFNO mortality 69.2%, (p=0.023); however, multivariate analysis demonstrated that increasing age and the inability to awake prone were the only independent predictors of COVID-19 mortality. The mortality of patients with COVID-19 requiring respiratory support is considerable. Data from our cohort managed on HDU show that CPAP and awake proning are possible in a selected population of COVID-19, and may be useful. Further prospective studies are required