Response to Miles and Mezzich:“Medicine in crisis and a crisis in semantics”

Miles and Mezzich offer a welcome and comprehensive account of historical recent developments in healthcare and the role of its practice models. They identify a ‘crisis’ in medicine, which seems to have occurred in part because the science of medicine has been over-emphasised and the importance of compassion and care de-emphasised.  As they point out, this crisis has been perceived to have evolved over the past one hundred years. Evidence Based Medicine (EBM) is suggested to be inadequate to solve the crisis and it may be the case that EBM, in fact, has precipitated it because it ignores patients qua persons. It is also suggested that Patient Centred Care (PCC) seeks to address the imbalance, but that this is inadequate, too. Between these existing views it is claimed that Person Centred Medicine (PCM) solves the crisis by giving persons and evidence their proper roles and relative importances</jats:p

A Retrospective Evaluation of Critical Care Blood Culture Yield – Do Support Services Contribute to the “Weekend Effect”?

Background The “weekend effect” describes an increase in adverse outcomes for patients admitted at the weekend. Critical care units have moved to higher intensity working patterns to address this with some improved outcomes. However, support services have persisted with traditional working patterns. Blood cultures are an essential diagnostic tool for patients with sepsis but yield is dependent on sampling technique and processing. We therefore used blood culture yield as a surrogate for the quality of support service provision. We hypothesized that blood culture yields would be lower over the weekend as a consequence of reduced support services. Methods We performed a retrospective observational study examining 1575 blood culture samples in a university hospital critical care unit over a one-year period. Results Patients with positive cultures had, on average, higher APACHE II scores (p = 0.015), longer durations of stay (p = 0.03), required more renal replacement therapy (p<0.001) and had higher mortality (p = 0.024). Blood culture yield decreased with repeated sampling with an increased proportion of contaminants. Blood cultures were 26.7% less likely to be positive if taken at the weekend (p = 0.0402). This effect size is the equivalent to the impact of sampling before and after antibiotic administration. Conclusions Our study demonstrates that blood culture yield is lower at the weekend. This is likely caused by delays or errors in incubation and processing, reflecting the reduced provision of support services at the weekend. Reorganization of services to address the “weekend effect” should acknowledge the interdependent nature of healthcare service delivery

Antibiotic Choice and Duration Associate with Repeat Prescriptions in Infective Asthma Exacerbations

Background: Patients with asthma who present with lower respiratory tract infections (LRTIs) often receive antibiotics. There is uncertainty about the need for and consequences of antibiotic administration. Objective: To describe the demographic characteristics of and antibiotic prescriptions for adult patients with asthma with LRTI and investigate factors associated with repeat antibiotic courses. Methods: We analyzed prescriptions of antibiotics for LRTIs in UK primary care from 2010 to 2015 using the Optimum Care Database. The primary outcome was a second antibiotic prescription for an LRTI code within 14 days of index prescription, as a proxy of initial treatment failure. A model for repeat prescriptions was derived using univariable and multivariable logistic regression analyses. Results: We assessed 28,289 cases with complete data sets, 6.5% of which received a second antibiotic course. Amoxicillin and clarithromycin respectively were used most commonly as index and second agents. The most frequent course length was 7 days for both index and repeat prescriptions. Multivariable analysis demonstrated that age, index antibiotic and duration, smoking status, location, and number of consultations and oral steroid courses in the previous year were significantly associated with repeat prescriptions. The derived model predicted the binary outcome adequately (Cox-Snell R2, 0.012; area under curve, 0.62; 95% CI, 0.61-0.63). Comorbidities, vaccinations, asthma treatment, and number of exacerbations were significant only in the univariable analysis. Conclusions: The current index prescribing preference of 7 days of amoxicillin correlated to fewer repeat courses. Baseline asthma treatment was not associated with risk of further prescriptions. Antibiotic administration in older patients with a smoking history could be a target for future studies

Amoxicillin is associated with a lower risk of further antibiotic prescriptions for lower respiratory tract infections in primary care - A database analysis spanning over 30 years.

Antibiotic prescriptions for lower respiratory tract infections occur commonly in primary care but there is uncertainty about the most effective initial treatment strategy. Both increasing antimicrobial resistance and awareness of preventable harm from medicines make resolving this uncertainty a priority. Pragmatic, real-life epidemiological investigations are needed to inform future interventional studies. In this cross-sectional database study we analysed antibiotic prescriptions for non-pneumonic, lower respiratory tract infections (LRTI) in primary care as captured in the Optimum Care Database from 1984 to 2017. The primary outcome was a second antibiotic prescription for a LRTI code within 14 days of index prescription, the secondary outcome further antibiotic prescription for any indication. Only individuals without chronic respiratory diseases were included. We conducted univariable analysis to identify factors associated with repeat prescriptions and generate hypotheses for forthcoming projects. We analysed 367,188 index prescriptions for LRTI. Amoxicillin was the commonest used index drug (65.1%). In 6% a second antibiotic course coded for a further LRTI was prescribed (11.2% without this coding restriction). Further antibiotic prescriptions for LRTI were significantly associated with older age, previous smoking, seven day index courses and not using amoxicillin initially. The largest effect size was seen when amoxicillin was not used as index drug (odds ratio (OR) 1.15, p < 0.001). This would support current prescribing practice for amoxicillin as index drug in those without respiratory disease. Prospective studies are needed to explore the observed differences

Thought disorder in schizophrenia is associated with both executive dysfunction and circumscribed impairments in semantic function.

BACKGROUND: Formal thought disorder (FTD) has long been regarded as a key sign of schizophrenia but little is known about its origins or aetiology. One suggestion is that it is directly related to disordered language functioning; a second is that it is a reflection of poor neurocognitive functioning. A current model posits that it is related to a combination of executive dysfunction and impaired semantic processing. METHOD: To examine these alternative ideas, a heterogeneous group of 30 patients, all carrying a diagnosis of schizophrenia, and 18 non-patient controls completed a series of neurocognitive and psycholinguistic tests, and a clinical review that, inter alia, permitted assessment of thought disorder (TD) using the Thought, Language and Communication Scale (TLC). RESULTS: Patients generally performed at a lower level on most components of the test battery, but there was little evidence of a relationship between TD and syntactic psycholinguistic function. However, schizophrenic patients manifesting higher levels of TD performed at a lower level on tests sensitive to executive dysfunction and semantic impairments. CONCLUSIONS: The origins of TD seem more closely linked to deficits in executive functioning and semantic processing than to impairments in other language functions or general cognition

Asthma control conundrum in clinical practice - Data from a two-stage Delphi survey and literature review

Definitions and measures of asthma control used in clinical trials and practice often vary, as highlighted in the manuscript, "Is asthma control more than just an absence of symptoms? An expert consensus statement". Furthermore, the authors discussed differences between patients and healthcare professionals (HCPs) in terms of understanding and managing asthma. Given these disparities, there is a need for consensus regarding what constitutes well-controlled asthma and, especially, how best it can be measured and recorded. In the current work, we describe our data and provide more detail on the methodology from a two-stage Delphi survey and a structured literature review, which were designed to reach a consensus definition of asthma control and alleviate misalignments between patients and HCPs. Survey data were collected using a two-stage Delphi technique; a method used to collate expert opinions over a series of sequential questionnaires to reach a consensus. The collated Delphi survey data were compared with results from a comprehensive, structured literature review of 216 publications, to assess if there was a correlation between existing guidance and measures of asthma control used in clinical trials and standard clinical practice. In order to collate and interpret findings from the Delphi survey, responses from 82 panelists (73 HCPs and 9 authors) were qualitatively analyzed, quantitatively categorized, and presented as percentages or counts in Excel databases, which are detailed in the current work. Searches conducted using PubMed and Cochrane identified 664 manuscripts, and Embase was used to identify 89 congress abstracts. After applying a stringent screening method using predefined key words, the structured literature review consisted of 185 peer-reviewed manuscripts and 31 congress abstracts, and assessed existing guidance and measures of asthma control used in clinical trials. In this publication, we provide further insight into the predefined keywords, search strings, and strategy applied to identify manuscripts and congress abstracts for inclusion/exclusion, and detail methods for data extraction. Together, the data from the Delphi survey and structured literature review aimed to provide greater insights into challenges and approaches in achieving asthma control in clinical practice, with the potential for results to be used to guide a universally accepted definition and measure of asthma control that can be used and understood by patients, HCPs, and researchers. Qualitative and quantitative methodology and analysis from the Delphi survey and literature review search strategy can potentially be used to identify disparities and explore expert opinion and relevant literature in other therapeutic areas to guide a consensus where disparities exist

Effective deployment of technology-supported management of chronic respiratory conditions:a call for stakeholder engagement

Acknowledgments We are grateful to Joseph Clift, Daisy Ellis, and Dan Poscover for constructive discussions in this area. This manuscript is based on discussions that took place around meetings of the Respiratory Effectiveness Group.Peer reviewedPublisher PD

Identification of novel vascular targets in lung cancer

Background: Lung cancer remains the leading cause of cancer-related death, largely owing to the lack of effective treatments. A tumour vascular targeting strategy presents an attractive alternative; however, the molecular signature of the vasculature in lung cancer is poorly explored. This work aimed to identify novel tumour vascular targets in lung cancer. Methods: Enzymatic digestion of fresh tissue followed by endothelial capture with Ulex lectin-coated magnetic beads was used to isolate the endothelium from fresh tumour specimens of lung cancer patients. Endothelial isolates from the healthy and tumour lung tissue were subjected to whole human genome expression profiling using microarray technology. Results: Bioinformatics analysis identified tumour endothelial expression of angiogenic factors, matrix metalloproteases and cellsurface transmembrane proteins. Predicted novel tumour vascular targets were verified by RNA-seq, quantitative real-time PCR analysis and immunohistochemistry. Further detailed expression profiling of STEAP1 on 82 lung cancer patients confirmed STEAP1 as a novel target in the tumour vasculature. Functional analysis of STEAP1 using siRNA silencing implicates a role in endothelial cell migration and tube formation. Conclusions: The identification of cell-surface tumour endothelial markers in lung is of interest in therapeutic antibody and vaccine development