Variability of cortisol assays can confound the diagnosis of adrenal insufficiency in the critically ill population

Objective: To compare the total plasma cortisol values obtained from three widely used immunoassays and a high pressure liquid chromatography (HPLC) technique on samples obtained from patients with sepsis. Design and setting: Observational interventional in the general intensive care unit of a metropolitan hospital. Patients and participants: Patients admitted to the intensive care unit with a diagnosis of sepsis and fulfilling criteria of systemic inflammatory response syndrome. Interventions: Standard short synacthen test performed with 250 mu g cosyntropin. Measurements and results: Two of the three immunoassays returned results significantly higher than those obtained by HPLC: Immulite by 95% (95%CI 31-188%) and TDx by 79% (21-165%). The limits of agreement for all three immunoassays with HPLC ranged from -62% to 770%. In addition, by classifying the patients into responders and non-responders to ACTH by standard criteria there was concordance in all assays in only 44% of patients. Conclusions: Immunoassay estimation of total plasma cortisol in septic patients shows wide assay related variation that may have significant impact in the diagnosis of relative adrenal insufficiency.

Dimensional changes in the ageing cornea

The study investigated the central and peripheral corneal characteristics of groups of subjects from 20 to 90 years of age to assist the understanding of ageing changes in the cornea, and to see whether relationships between ocular parameters were revealed. After age 45 the corneal horizontal radius of curvature gradually decreased with age. This trend was shown by the Aston University subjects (group B). The effect was very significant for the hospital patients undergoing biometry before cataract extraction operation (group D). Vertical radius of curvature showed a slight decrease with age after age 45, but similar to corneal eccentricity, this showed no significant age effect. Corneal astigmatism progressed from with the rule towards against the rule, particularly after age 60. The shift seemed mainly due to the decreasing horizontal corneal curvature. In biometry no significant age relation was found for axial length, but a significant relation was found between curvature and axial length in the larger group D. Lens thickness showed a very significant relation to age and to axial length, but no significant relation to corneal curvature. Anterior chamber depth showed a very significant relation to age, lens thickness and axial length, but no significant relation to corneal curvature. A significant age effect was found for corneal thickness decreasing with age for the central, nasal and temporal regions of the right eye. Analysis of the biometry results indicated the influence of two major factors. Firstly, the natural growth of the eye in youth, leading to greater values of axial length, radius of corneal curvature, lens thickness and anterior chamber depth. Secondly, the typical ageing changes where the increasing lens thickness caused a reduction in anterior chamber depth. The decrease in corneal thickness with age shown in some corneal regions may be a sign of ageing changes in the tissue proteins and hydration balance.

Molecular and genetic evidence for abnormalities in the nodes of Ranvier in schizophrenia

Context: Genetic, neuroimaging, and molecular neurobiological evidence support the hypothesis that the disconnectivity syndrome in schizophrenia (SZ) could arise from failures of saltatory conduction and abnormalities at the nodes of Ranvier (NOR) interface where myelin and axons interact. Objective: To identify abnormalities in the expression of oligodendroglial genes and proteins that participate in the formation, maintenance, and integrity of the NOR in SZ. Design: The messenger RNA (mRNA) expression levels of multiple NOR genes were quantified in 2 independent postmortem brain cohorts of individuals with SZ, and generalizability to protein expression was confirmed. The effect of the ANK3 genotype on the mRNA expression level was tested in postmortem human brain. Case-control analysis tested the association of the ANK3 genotype with SZ. The ANK3 genotype's influence on cognitive task performance and functional magnetic resonance imaging activation was tested in 2 independent cohorts of healthy individuals. Setting: Research hospital. Patients: Postmortem samples from patients with SZ and healthy controls were used for the brain expression study (n=46) and the case-control analysis (n=272). Healthy white men and women participated in the cognitive (n=513) and neuroimaging (n=52) studies. Main Outcome Measures: The mRNA and protein levels in postmortem brain samples, genetic association with schizophrenia, cognitive performance, and blood oxygenation level-dependent functional magnetic resonance imaging. Results: The mRNA expression of multiple NOR genes was decreased in schizophrenia. The ANK3 rs9804190 C allele was associated with lower ANK3 mRNA expression levels, higher risk for SZ in the case-control cohort, and poorer working memory and executive function performance and increased prefrontal activation during a working memory task in healthy individuals. Conclusions: These results point to abnormalities in the expression of genes and protein associated with the integrity of the NOR and suggest them as substrates for the disconnectivity syndrome in SZ. The association of ANK3 with lower brain mRNA expression levels implicates a molecular mechanism for its genetic, clinical, and cognitive associations with SZ. ©2012 American Medical Association. All rights reserved.

"Customer" knowledge management in healthcare

This paper reports on a work-in-progress project on the management of patient knowledge in a UK general hospital. Greater involvement of patients is generally seen as crucial to the effective provision of healthcare in the future. However, this presents many challenges, especially in the light of the ageing population in most developed countries and the consequent increasing demand for healthcare. In the UK, there have been many attempts to increase patient involvement by the systematisation of patient feedback, but typically they have not been open to academic scrutiny or formal evaluation, nor have they used any knowledge management principles. The theoretical foundations for this project come first from service management and thence from customer knowledge management. Service management stresses the importance of the customer perspective. Healthcare clearly meets the definitions of a service even though it may also include some tangible elements such as surgery and provision of medication. Although regarding hospital patients purely as "customers" is a viewpoint that needs to be used with care, application of the theory offers potential benefits in healthcare. The two main elements we propose to use from the theory are the type of customer knowledge and its relationship to attributes of the quality of the service provided. The project is concerned with investigating various knowledge management systems (KMS) that are currently in use (or proposed) to systematise patient feedback in an NHS Trust hospital, to manage knowledge from and to a lesser extent about patients. The study is a mixed methods (quantitative and qualitative) action research investigation intended to answer the following three research questions: • How can a KMS be used as a mechanism to capture and evaluate patient experiences to provoke patient service change • How can the KMS assist in providing a mechanism for systematising patient engagement? • How can patient feedback be used to stimulate improvements in care, quality and safety?

Adaptive regulation or governmentality: patient safety and the changing regulation of medicine

Studies from across the world have shown that clinical mistakes are a major threat to the safety of patient care (World Health Organisation 2004). For the National Health Service (NHS) of England and Wales it is estimated that one in ten hospital patients experience some form of error, and each year these cost the service over £2billion in remedial care (Department of Health 2000). Unsurprisingly, ‘patient safety’ is now a major international health policy priority, questioning the efficacy of existing regulatory practices and proposing a new ethos of learning. Within England and Wales, the National Patient Safety Agency (NPSA) has been created to lead policy development and champion service-wide learning, whilst throughout the NHS the National Reporting and Learning System (NRLS) has been introduced to enable this learning (NPSA 2003). This paper investigates the extent to which, in seeking to better manage the threats to patient safety, this policy agenda represents a transition in medical regulation.

Economic evaluations of clinical pharmacy services in Ireland, 2007-2015

Introduction The concept of this thesis was driven by stagnation within the Irish healthcare system. Multiple reports from pharmacy organisations had outlined possible future directions for the profession but progress was minimal, especially in comparison with other countries. The author’s directive was to evaluate the economic impact of a series of clinical pharmacy services (CPS) in hospital and community settings. Methods A systematic review of economic evaluations of clinical pharmacy services in hospital patients was undertaken to gain insight into recent research in the field. Eligible studies were evaluated using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS), to establish the quality, consistency and transparency of relevant research. A retrospective analysis of an internal hospital pharmacy interventions database was conducted. A method first described by Nesbit et al. was implemented to estimate the level of cost avoidance achieved. A cost-effectiveness analysis based on data from a randomised controlled trial of a pharmacist-supervised patient self-testing (PST) of warfarin therapy is presented. Outcome measure was the incremental cost associated with six months of intervention management. A similar cost-effectiveness analysis based on previously published RCT data was used to evaluate a novel structured pharmacist review of medication in older hospitalised patients. Cost-effectiveness analysis was presented in the form of an incremental cost-effectiveness ratio (ICER). An ICER is an additional cost per unit effect, in the case of this study, the cost of preventing an additional non-trivial ADR in hospital. A method described by Preaud et al. was adapted to estimate the clinical and economic benefit gained from vaccination of patients by a community pharmacist in Ireland in 2013/14. Sample demographic data was obtained from a national chain of community pharmacies and applied to overall national vaccination data. Results Systematic review identified twenty studies which were eligible for inclusion. Overall, pharmacist interventions had a positive impact on hospital budgets. Only three studies (15%) were deemed to be “good-quality” studies. No ‘novel’ clinical pharmacist intervention was identified during the course of this review. Analysis of internal hospital database identified 4,257 interventions documented on 2,147 individual patients over a 12 month period. Substantial cost avoidance of €710,000 was generated over a 1 year period from the perspective of the health care provider. Mean cost avoidance of €166 per intervention was generated. The cost of providing these interventions was €82,000. Substantial net cost-benefits of €626,279 and a cost-benefit ratio of 8.64 : 1 were generated based on this evaluation of pharmacist interventions. Results from an evaluation of a novel pharmacist-led form of warfarin management indicated indicated that on a per patient basis, PST was slightly more expensive than established anticoagulant management. On a per patient basis over a six month period, PST resulted in an incremental cost of €59.08 in comparison with routine care. Overall cost of managing a patient through pharmacist-supervised PST for a six month period is €226.45. However, for this increase in cost a clinically significant improvement in care was provided. Patients achieved a significantly higher time in therapeutic range during the PST arm in comparison with routine care, (72 ± 19.7% vs 59 ± 13.5%). Difference in overall cost was minimal and PST was the dominant strategy in some scenarios examined during sensitivity analysis. Structured pharmacist review of medication was determined to be dominant in comparison to usual pharmaceutical care. Even if the healthcare payer was unwilling to pay any money for the prevention of an ADR, the intervention strategy is still likely to be cost-effective (probability of being determined cost-effective = 0.707). Implementation of pharmacist-led influenza vaccination has resulted in substantial clinical and economic benefits to the healthcare system. The majority of patients (64.9%) who availed of this service had identifiable influenza-related risk factors. Of patients with influenza-related risk factors, age ≥65 year was the most commonly cited risk factor. Pharmacist vaccination services averted a total of 848 influenza cases across all age groups during the 2013/2014 influenza season. Due to receipt of vaccination in a pharmacy setting, 444 influenza-related GP visits were prevented. In terms of more serious influenza-associated events, 11 hospitalisations and five influenza-related deaths were averted. Costs averted were approximately €305,000. These were principally wider societal-related costs associated with lost productivity. Conclusion Overall, clinical pharmacy services are adding value to the Irish healthcare system in both hospital and community settings, but provision of additional funding for new services would enable them to offer a great deal more.

Memoria de los consumidores expuestos a la publicidad

La psicología y la publicidad son dos disciplinas que se han complementado, la publicidad se ha visto beneficiada con esta alianza, ya que el principal aporte que le hace la psicología a la publicidad es poder determinar aquellos factores o estrategias que generan en el consumidor: atención, asociación entre marca y producto, para luego almacenarse en la memoria y así generar una posible conducta de compra en el individuo. Los medios de comunicación cumplen un papel importante en la transmisión de la información publicitaria, dependiendo del medio utilizado se enfoca la información teniendo en cuenta el campo perceptivo que recibirá la información, para lograr asociación y posterior almacenamiento en la memoria. Para poder medir la jerarquía del recuerdo en la memoria de los individuos ante la mención de una categoría de servicio de un producto, la publicidad y el mercadeo hacen uso de la prueba Top of Mind.

Physical activity profile in heart failure patients from a Brazilian tertiary cardiology hospital

Background: Physical activity (PA) has proven benefits in the primary prevention of heart diseases such as heart failure (HF). Although it is well known, HF PA habits and physicians` advice have been poorly described. The aim of this study was to investigate if physicians were advising HF patients to exercise and to quantify patients` exercise profiles in a complex cardiology hospital. Methods: All 131 HF patients (80 male, average age 53 +/- 10 years, NYHA class I-V, left ventricular ejection fraction 35 +/- 11%, 35 ischemic, 35 idiopatic , 32 hypertensive and 29 with Chagas disease) went to the hospital for a HF routine check-up. On this occasion, after seeing the physician, we asked the patients if the physician had advised them about PA. Then, we asked them to fill in the international physical activity questionnaire (IPQA) Short Form to classify their PA level. Results: Our data showed a significant difference between patients who had received any kind of PA advice from physicians (36%) and those who had not (64%, p<0.0001). Using the IPAQ criteria, of the 36% of patients who had received advice, 12.4% were classified as low and 23.6% as moderate. Of the 64% of patients who did not receive advice, 26.8% were classified as lowand 37.2% as moderate. Etiology (except Chagas), functional class, ejection fraction, sex and age did not influence the PA profile. Conclusions: Physicians at a tertiary cardiology hospital were not giving patients satisfactory advice as to PA. Our data supports the need to strengthen exercise encouragement by physicians and for complementary studies on this area. (Cardiol J 2010; 17, 2: 143-148)

Can ECG changes predict the long-term outcome in patients admitted to hospital for suspected acute myocardial infarction?

7,028 patients with suspected acute myocardial infarction and discharged alive from hospital were followed in a 10-year community-based study. The long-term prognosis was relatively good if the electrocardiograms (ECGs) were normal (5-year all-cause death rate 5%), poor with uncodable ECGs showing rhythm or conduction disturbances (37%), and intermediate with new Q wave, new ST elevation, new T wave inversion or ischemic ECG (17-21%), and with new ST depression (27%). Similar patterns were found for ischemic cardiac death and reinfarction. The long-term prognosis of patients with suspected acute myocardial infarction is relatively good if the ECGs are normal and poor if ECGs are uncodable. ST depression may be a marker for a worse long-term outcome.

Treatment of obstructive sleep apnea syndrome in patients from a teaching hospital in Brazil: is it possible?

The aim of this study was to evaluate the efficacy of a cost-effective intra-oral appliance for obstructive sleep apnea syndrome built into a large teaching hospital. Out of 20 evaluated and treated patients, 14 concluded the study: eight men and six women, with a mean age of 42-46 (mean + SD) years and mean body mass index of 27.66. Inclusion criteria were mild or moderate apnea-hypopnea index (AHI) according to a polysomnographic study. All patients were treated with the monobloco intra-oral appliance. They were then submitted to a follow-up polysomnographic study after 60 days using the appliance. An orofacial clinical evaluation was carried out with the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) questionnaire and with clinical evaluation questionnaire devised by the Orofacial Pain Team before and 60 days after fitting the intra-oral appliance. The AHI showed a statistically meaningful (p = 0.002) reduction from 15.53 to 7.82 events per hour, a non-statistically significant oxygen saturation increase from 83.36 to 84.86 (p = 0.09), and Epworth`s sleepiness scale reduction from 9.14 to 6.36 (p = 0.001). Three patients did not show any improvement. The most common side effect during the use of the appliance/device was pain and facial discomfort (28.57%), without myofascial or temporomandibular joint pain as evaluated by the RDC/TMD questionnaire. The intra-oral device produced a significant reduction of the apnea-hypopnea index during the study period with the use of the monobloco intra-oral appliance. Patients did not show prior myofascial pain or 60 days after use of the intra-oral appliance.

Predicting Hospital Mortality in Critically Ill Cancer Patients according to Acute Kidney Injury Severity

Background: Acute kidney injury (AKI) is a frequent complication in hospitalized patients, especially in those in intensive care units (ICU). The RIFLE classification might be a valid prognostic factor for critically ill cancer patients. The present study aims to evaluate the discriminatory capacity of RIFLE versus other general prognostic scores in predicting hospital mortality in critically ill cancer patients. Methods: This is a single-center study conducted in a cancer-specialized ICU in Brazil. All of the 288 patients hospitalized from May 2006 to June 2008 were included. RIFLE classification, APACHE II, SOFA, and SAPS II scores were calculated and the area under receiver operating characteristic (AROC) curves and logistic multiple regression were performed using hospital mortality as the outcome. Results: AKI, defined by RIFLE criteria, was observed in 156 (54.2%) patients. The distribution of patients with any degree of AKI was: risk, n = 96 (33.3%); injury, n = 30 (10.4%), and failure, n = 30 (10.4%). Mortality was 13.6% for non-AKI patients, 49% for RIFLE `R` patients, 62.3% for RIFLE `I` patients, and 86.8% for RIFLE `F` patients (p = 0.0006). Logistic regression analysis showed that RIFLE criteria, APACHE II, SOFA, and SAPS II were independent factors for mortality in this population. The discrimination of RIFLE was good (AROC 0.801, 95% CI 0.748-0.854) but inferior compared to those of APACHE II (AROC 0.940, 95% CI 0.915-0.966), SOFA (AROC 0.910, 95% CI 0.876-0.943), and SAPS II (AROC 0.869, 95% CI 0.827-0.912). Conclusion: AKI is a frequent complication in ICU patients with cancer. RIFLE was inferior to commonly used prognostic scores for predicting mortality in this cohort of patients. Copyright (C) 2011 S. Karger AG, Basel

Outcome of stroke patients admitted to intensive care: Experience from an Australian teaching hospital

The objective of this study was to determine the mortality rate and the functional outcomes of stroke patients admitted to the intensive care unit (ICU) and to identify predictors of poor outcome in this population. The records of all patients admitted to the ICU with the diagnosis of stroke between January 1994 and December 1999 were reviewed. Patients with subarachnoid haemorrhage were excluded. Data were collected on clinical and biological variables, risk factors for stroke and the presence of comorbidities. Mortality (ICU, in-hospital and three-month) and functional outcome were used as end-points. In the six-year-period, 61 patients were admitted to the ICU with either haemorrhagic or ischaemic stroke. Medical records were available for only 58 patients. There were 23 ischaemic and 35 haemorrhagic strokes. The ICU, in-hospital and three-month mortality rates were 36%, 47% and 52% respectively. There were no significant differences in the prevalence of premorbid risk factors between survivors and non-survivors. The mean Barthel score was significantly different between the independent and dependent survivors (94 +/- 6 vs 45 +/- 26, P < 0.001). A substantial number of patients with good functional outcomes had lower Rankin scores (92% vs 11%, P < 0.001). Only 46% of those who were alive at three months were functionally independent. Intensive care admission was associated with a high mortality rate and a high likelihood of dependent lifestyle after hospital discharge. Haemorrhagic stroke, fixed dilated pupil(s) and GCS < 10 during assessment were associated with increased mortality and poor functional outcome.

Evaluation of cyclooxygenase 2 inhibitor use in patients admitted to a large teaching hospital

Background: The heavy usage of coxibs in Australia far outstrips the predicted usage that was based on the treatment of patients with risk factors for upper gastro-intestinal adverse events from conventional anti--inflammatory agents. This raises questions regarding the appropriateness of prescribing. Aims: To determine: (i) the relationship between prescriptions for cyclooxygenase 2 (COX-2) inhibitors and objective evidence of inflammatory arthritis, (ii) prior experience with paracetamol and/or conventional non-steroidal anti-inflammatory drugs (NSAIDs), and (iii) contraindications to the use of NSAIDs. Methods: Drug utilization evaluation and rheumato-logical assessment was conducted on 70 consecutive patients admitted on COX-2 inhibitors to a 480-bed metropolitan hospital. The main outcome measures were: the indication for COX-2 inhibitor; objective -evidence of inflammatory arthritis; previous trial of -paracetamol or conventional NSAIDs; and patient -satisfaction. Results: Only 11 patients (16%) had symptoms or signs of an inflammatory arthropathy, and met Pharmaceut-ical Benefits Schedule criteria for prescribing a COX-2 inhibitor. Fifty-nine patients (84%) had chronic osteo-arthritis, degenerative spinal disease, injury or malignancy, without overt active inflammation. Fourteen patients (20%) had trialled regular paracetamol prior to using any NSAID treatment. Conventional NSAIDs had been previously used by 51 patients (73%). Eleven patients (16%) reported previous adverse gastrointestinal effects from conventional NSAIDs. On the basis of significant renal impairment (creatinine clearance 5/10). Conclusions: Drug utilization data indicate that COX-2 inhibitors are frequently used first line for degenerative osteoarthritis in the absence of overt inflammation, without prior adequate trial of paracetamol and with disregard for the cautions and contraindications of these agents. These findings may explain the unprecedented Pharmaceutical Benefits Schedule expenditure on COX-2 inhibitors in Australia.

Survival of adult AIDS patients in a reference hospital of a metropolitan area in Brazil

OBJECTIVE: To evaluate the influence of sociodemographic, clinical, and epidemiological factors in AIDS patients survival in a reference hospital. METHODS: A sample of 502 adult AIDS patients out of 1,494 AIDS cases registered in a hospital in Fortaleza, Brazil, was investigated between 1986 and 1998. Sixteen cases were excluded due to death at the moment of the AIDS diagnosis and 486 were analyzed in the study. Socioeconomic and clinical epidemiological were the variables studied. Statistical analysis was conducted using the Kaplan-Meier survival analysis and the Cox proportional hazards model. RESULTS: Three hundred and sixty two out of the 486 patients studied took at least one antiretroviral drug and their survival was ten times longer than those who did not take any drug (746 and 79 days, respectively, p <0.001). Patients who took two nucleoside reverse transcriptase inhibitors (NRTI) plus protease inhibitor were found to have higher survival rates (p <0.001). The risk of dying in the first year was significantly lower for patients who took NRTI and a protease inhibitor compared to those who took only NRTI. In addition, this risk was much lower from the second year on (0.10; 95%CI: 0.42-0.23). The risk of dying in the first year was significantly higher for less educated patients (15.58; 95%CI: 6.64-36.58) and those who had two or more systemic diseases (3.03; 95%CI: 1.74-5.25). After the first year post-diagnosis, there was no risk difference for these factors. CONCLUSIONS: Higher education revealed to exert a significant influence in the first-year survival. Antiretroviral drugs had a greater impact in the survival from the second year on. A more aggressive antiretroviral therapy started earlier could benefit those patients.