Viruses without borders and the medical research agenda.

The COVID-19 pandemic has shown us that there are numerous research questions-empirical, political, and philosophical-that need addressing both prior to, during, and after a pandemic. The current organisation of medical research has hindered our ability to efficiently answer these questions. This in turn suggests that there ought to be changes to how the medical research agenda is set.

Evidence of effectiveness.

There are two competing views regarding the role of mechanistic knowledge in inferences about the effectiveness of interventions. One view holds that inferences about the effectiveness of interventions should be based only on data from population-level studies (often statistical evidence from randomised trials). The other view holds that such inferences must be based in part on mechanistic evidence. The competing views are local principles of inference, the plausibility of which can be assessed by a more general normative principle of inference. Bayesianism tells us to base inferences on both the 'likelihood' and the 'prior'. The likelihood represents statistical evidence. One influence on the prior probability of a hypothesis like 'd causes x' is mechanistic knowledge of how d causes x. Thus, reasoning about such inferences by appealing to both statistical and mechanistic evidence is vindicated by our best general theory of inference. The primary contribution of this paper is to assess the merits and weaknesses of the arguments on both sides of the debate, using the Bayesian framework. This analysis lends support to those who argue that we should base our causal inferences about interventions in part on mechanistic evidence.

Measuring effectiveness.

Measuring the effectiveness of medical interventions faces three epistemological challenges: the choice of good measuring instruments, the use of appropriate analytic measures, and the use of a reliable method of extrapolating measures from an experimental context to a more general context. In practice each of these challenges contributes to overestimating the effectiveness of medical interventions. These challenges suggest the need for corrective normative principles. The instruments employed in clinical research should measure patient-relevant and disease-specific parameters, and should not be sensitive to parameters that are only indirectly relevant. Effectiveness always should be measured and reported in absolute terms (using measures such as 'absolute risk reduction'), and only sometimes should effectiveness also be measured and reported in relative terms (using measures such as 'relative risk reduction')-employment of relative measures promotes an informal fallacy akin to the base-rate fallacy, which can be exploited to exaggerate claims of effectiveness. Finally, extrapolating from research settings to clinical settings should more rigorously take into account possible ways in which the intervention in question can fail to be effective in a target population.

Effectiveness of medical interventions.

To be effective, a medical intervention must improve one's health by targeting a disease. The concept of disease, though, is controversial. Among the leading accounts of disease-naturalism, normativism, hybridism, and eliminativism-I defend a version of hybridism. A hybrid account of disease holds that for a state to be a disease that state must both (i) have a constitutive causal basis and (ii) cause harm. The dual requirement of hybridism entails that a medical intervention, to be deemed effective, must target either the constitutive causal basis of a disease or the harms caused by the disease (or ideally both). This provides a theoretical underpinning to the two principle aims of medical treatment: care and cure.

Is meta-analysis the platinum standard of evidence?

An astonishing volume and diversity of evidence is available for many hypotheses in the biomedical and social sciences. Some of this evidence-usually from randomized controlled trials (RCTs)-is amalgamated by meta-analysis. Despite the ongoing debate regarding whether or not RCTs are the 'gold-standard' of evidence, it is usually meta-analysis which is considered the best source of evidence: meta-analysis is thought by many to be the platinum standard of evidence. However, I argue that meta-analysis falls far short of that standard. Different meta-analyses of the same evidence can reach contradictory conclusions. Meta-analysis fails to provide objective grounds for intersubjective assessments of hypotheses because numerous decisions must be made when performing a meta-analysis which allow wide latitude for subjective idiosyncrasies to influence its outcome. I end by suggesting that an older tradition of evidence in medicine-the plurality of reasoning strategies appealed to by the epidemiologist Sir Bradford Hill-is a superior strategy for assessing a large volume and diversity of evidence.

The chemical characterization of the gene: vicissitudes of evidential assessment.

The chemical characterization of the substance responsible for the phenomenon of "transformation" of pneumococci was presented in the now famous 1944 paper by Avery, MacLeod, and McCarty. Reception of this work was mixed. Although interpreting their results as evidence that deoxyribonucleic acid (DNA) is the molecule responsible for genetic changes was, at the time, controversial, this paper has been retrospectively celebrated as providing such evidence. The mixed and changing assessment of the evidence presented in the paper was due to the work's interpretive flexibility--the evidence was interpreted in various ways, and such interpretations were justified given the neophytic state of molecular biology and methodological limitations of Avery's transformation studies. I argue that the changing context in which the evidence presented by Avery's group was interpreted partly explains the vicissitudes of the assessments of the evidence. Two less compelling explanations of the reception are a myth-making account and an appeal to the wartime historical context of its publication.

Infection control and antimicrobial restriction practices for antimicrobial-resistant organisms in Canadian tertiary care hospitals.

In 2003, a survey examining infection control and antimicrobial restriction policies and practices for preventing the emergence and transmission of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (VRE), and extended spectrum beta-lactamase (ESBL) was performed within Canadian teaching hospitals as part of the Canadian Nosocomial Infection Surveillance Program. Twenty-eight of 29 questionnaires were returned. The majority of facilities conducted admission screening for MRSA (96.4%) and VRE (89.3%) but only 1 site screened for ESBL/AmpC. Rates of MRSA, VRE, and ESBL remain low in Canada. It is believed that these lower rates may be due to intense admission screening protocols and stringent infection control policies for antimicrobial-resistant organisms (AROs) within Canadian institutions. Few (MRSA: 14.8%; VRE: 12.0%) recorded the number of patients screened. Regular prevalence surveys were done for MRSA (21.4%), VRE (35.7%), and ESBL/AmpC (3.8%). Pre-emptive precautions were applied for MRSA by 60.7% and for VRE by 75.0% of facilities. All facilities flagged patients previously identified with MRSA and VRE but only 46.2% flagged ESBL and 15.4% flagged AmpC patients. Barrier precautions varied by ARO and patient-care setting. In the inpatient non-ICU setting, more than 90% wore gowns and gloves for MRSA and VRE but only 50% for ESBL; and 57.1% wore masks for MRSA. Attempts to decolonize MRSA patients had been made by 82.1%, largely in order to place them in another facility. Policies restricting antimicrobial prescribing were reported by 21 facilities (75.0%). Further studies examining hospital infection control policies and corresponding rates of ARO infections would help in identifying and refining best practice guidelines within Canadian institutions.

The role of nurse understaffing in nosocomial viral gastrointestinal infections on a general pediatrics ward.

OBJECTIVE: To examine the relationship between nurse staffing levels and the rate of nosocomial viral gastrointestinal infections (NVGIs) in a general pediatrics population. DESIGN: Retrospective descriptive study. SETTING: A general pediatrics ward at The Hospital for Sick Children in Toronto, Ontario, Canada, a 320-bed, tertiary-care pediatric institution. RESULTS: Forty-three NVGIs were detected in 37 patients of 2,929 admissions (1.3%). The monthly NVGI rate correlated significantly with the monthly night patient-to-nurse ratio (r = 0.56) and the monthly day patient-to-nurse ratio (r = 0.50). The nursing hours per patient-day during the preinfection period (PIP) were significantly lower than those during the nonpreinfection period (NPIP; 12.5 vs 13.0). There was no difference between the PIP and the NPIP day patient-to-nurse ratios (3.31 vs 3.32), but there was a significant difference between the PIP and the NPIP night patient-to-nurse ratios (3.26 vs 3.16). The incidence of NVGIs in the 72-hour period after any day when the nursing hours per patient-day were less than 10.5 was 6.39 infections per 1,000 patient-days, compared with 2.17 infections per 1,000 patient-days in periods with more than 10.5 nursing hours per patient-day (rate ratio, 2.94; 95% confidence interval, 2.16 to 4.01). CONCLUSION: Nurse understaffing contributed to an increased NVGI rate in our general pediatrics population, and should be assessed as a risk factor in outbreak investigations.