ABSTRACT
BACKGROUND: Unfortunately, many COPD patients continue to exacerbate despite good adherence to GOLD Class D recommended therapy. Acute exacerbations lead to an increase in symptoms, decline in lung function and increased mortality rate. The purpose of this review is to do a literature search for any prophylactic anti-microbial treatment trials in GOLD class D patients who 'failed' recommended therapy and discuss the role of COPD phenotypes, lung and gut microbiota and co-morbidities in developing a tailored approach to anti-microbial therapies for high frequency exacerbators. MAIN TEXT: There is a paucity of large, well-conducted studies in the published literature to date. Factors such as single-centre, study design, lack of well-defined controls, insufficient patient numbers enrolled and short follow-up periods were significant limiting factors in numerous studies. One placebo-controlled study involving more than 1000 patients, who had 2 or more moderate exacerbations in the previous year, demonstrated a non-significant reduction in exacerbations of 19% with 5 day course of moxifloxacillin repeated at 8 week intervals. In Pseudomonas aeruginosa (Pa) colonised COPD patients, inhaled antimicrobial therapy using tobramycin, colistin and gentamicin resulted in significant reductions in exacerbation frequency. Viruses were found to frequently cause acute exacerbations in COPD (AECOPD), either as the primary infecting agent or as a co-factor. However, other, than the influenza vaccination, there were no trials of anti-viral therapies that resulted in a positive effect on reducing AECOPD. Identifying clinical phenotypes and co-existing conditions that impact on exacerbation frequency and severity is essential to provide individualised treatment with targeted therapies. The role of the lung and gut microbiome is increasingly recognised and identification of pathogenic bacteria will likely play an important role in personalised antimicrobial therapies. CONCLUSION: Antimicrobial therapeutic options in patients who continue to exacerbate despite adherence to guidelines-directed therapy are limited. Phenotyping patients, identification of co-existing conditions and assessment of the microbiome is key to individualising antimicrobial therapy. Given the impact of viruses on AECOPD, anti-viral therapeutic agents and targeted anti-viral vaccinations should be the focus of future research studies.
Subject(s)
Anti-Infective Agents/therapeutic use , Pulmonary Disease, Chronic Obstructive/drug therapy , Bronchoalveolar Lavage Fluid/microbiology , Humans , Microbiota , Nebulizers and Vaporizers , Secondary PreventionABSTRACT
BACKGROUND: Cystic Fibrosis (CF) is an autosomal recessive disease that affects the function of a number of organs, principally the lungs, but also the gastrointestinal tract. The manifestations of cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction in the gastrointestinal tract, as well as frequent antibiotic exposure, undoubtedly disrupts the gut microbiota. To analyse the effects of CF and its management on the microbiome, we compared the gut microbiota of 43 individuals with CF during a period of stability, to that of 69 non-CF controls using 454-pyrosequencing of the 16S rRNA gene. The impact of clinical parameters, including antibiotic therapy, on the results was also assessed. RESULTS: The CF-associated microbiome had reduced microbial diversity, an increase in Firmicutes and a reduction in Bacteroidetes compared to the non-CF controls. While the greatest number of differences in taxonomic abundances of the intestinal microbiota was observed between individuals with CF and the healthy controls, gut microbiota differences were also reported between people with CF when grouped by clinical parameters including % predicted FEV1 (measure of lung dysfunction) and the number of intravenous (IV) antibiotic courses in the previous 12 months. Notably, CF individuals presenting with severe lung dysfunction (% predicted FEV1 ≤ 40%) had significantly (p < 0.05) reduced gut microbiota diversity relative to those presenting with mild or moderate dysfunction. A significant negative correlation (-0.383, Simpson's Diversity Index) was also observed between the number of IV antibiotic courses and gut microbiota diversity. CONCLUSIONS: This is one of the largest single-centre studies on gut microbiota in stable adults with CF and demonstrates the significantly altered gut microbiota, including reduced microbial diversity seen in CF patients compared to healthy controls. The data show the impact that CF and it's management have on gut microbiota, presenting the opportunity to develop CF specific probiotics to minimise microbiota alterations.
Subject(s)
Bacteria/classification , Cystic Fibrosis/complications , Cystic Fibrosis/microbiology , Gastrointestinal Microbiome , Gastrointestinal Tract/microbiology , Administration, Intravenous , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Bacteroidetes , Biodiversity , Classification , DNA, Bacterial , Feces/microbiology , Female , Firmicutes , Gastrointestinal Microbiome/drug effects , Humans , Male , Metagenome , Middle Aged , Phenotype , Probiotics , RNA, Ribosomal, 16S/genetics , Species SpecificityABSTRACT
Clostridium difficile is an anaerobic Gram-positive, spore-forming, toxin-producing bacillus transmitted among humans through the faecal-oral route. Despite increasing carriage rates and the presence of C. difficile toxin in stool, patients with CF rarely appear to develop typical manifestations of C. difficile infection (CDI). In this study, we examined the carriage, toxin production, ribotype distribution and antibiotic susceptibility of C. difficile in a cohort of 60 adult patients with CF who were pre-lung transplant. C. difficile was detected in 50% (30/60) of patients with CF by culturing for the bacteria. C. difficile toxin was detected in 63% (19/30) of C. difficile-positive stool samples. All toxin-positive stool samples contained toxigenic C. difficile strains harbouring toxin genes, tcdA and tcdB. Despite the presence of C. difficile and its toxin in patient stool, no acute gastrointestinal symptoms were reported. Ribotyping of C. difficile strains revealed 16 distinct ribotypes (RT), 11 of which are known to be disease-causing including the hyper-virulent RT078. Additionally, strains RT002, RT014, and RT015, which are common in non-CF nosocomial infection were described. All strains were susceptible to vancomycin, metronidazole, fusidic acid and rifampicin. No correlation was observed between carriage of C. difficile or any characteristics of isolated strains and any recorded clinical parameters or treatment received. We demonstrate a high prevalence of hypervirulent, toxigenic strains of C. difficile in asymptomatic patients with CF. This highlights the potential role of asymptomatic patients with CF in nosocomial transmission of C. difficile.
Subject(s)
Carrier State , Clostridioides difficile/isolation & purification , Cross Infection , Cystic Fibrosis , Enterocolitis, Pseudomembranous , Adult , Bacterial Typing Techniques/methods , Carrier State/diagnosis , Carrier State/epidemiology , Cohort Studies , Cross Infection/diagnosis , Cross Infection/microbiology , Cystic Fibrosis/epidemiology , Cystic Fibrosis/microbiology , Enterocolitis, Pseudomembranous/diagnosis , Enterocolitis, Pseudomembranous/epidemiology , Female , Humans , Ireland/epidemiology , Male , Microbial Sensitivity Tests/methods , PrevalenceSubject(s)
Aminophenols/administration & dosage , Aminophenols/pharmacokinetics , Antifungal Agents/pharmacology , Cystic Fibrosis/drug therapy , Itraconazole/pharmacology , Quinolones/administration & dosage , Quinolones/pharmacokinetics , Siblings , Adult , Antifungal Agents/administration & dosage , Cystic Fibrosis/genetics , Cytochrome P-450 CYP3A Inhibitors/pharmacology , Dose-Response Relationship, Drug , Drug Antagonism , Enzyme Inhibitors , Humans , Itraconazole/administration & dosage , Male , MutationABSTRACT
BACKGROUND: There are no published data on real-life clinical experience comparing inhaled antibiotic therapy via new rapid delivery systems with nebulised antibiotic therapy in CF. This real world study compares safety, effectiveness and tolerability using tobramycin inhaled powder (TIP) versus tobramycin inhaled solution (TIS). METHODS: Adult patients with CF commencing TIP (n=78) completed a questionnaire assessing safety, efficacy, tolerability, patient-satisfaction and self-reported adherence to TIS at baseline and during 12 months of TIP therapy. FEV1% predicted and exacerbation rate were recorded at each visit. RESULTS: There was a significant improvement in adherence scores, with a significant decrease in the number of intravenous antibiotic courses received during 12 months of TIP compared with the preceding 12 months using TIS. 94% of patients who had previously used TIS preferred TIP therapy over TIS. CONCLUSIONS: Inhaled powder tobramycin in CF is associated with improved adherence, tolerability and decreased exacerbation rates compared to nebulised treatment in real-life practice.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Cystic Fibrosis/complications , Nebulizers and Vaporizers , Pseudomonas Infections/drug therapy , Pseudomonas aeruginosa , Tobramycin/administration & dosage , Administration, Inhalation , Adolescent , Adult , Cohort Studies , Female , Forced Expiratory Volume , Humans , Male , Medication Adherence , Middle Aged , Patient Satisfaction , Pseudomonas Infections/complications , Surveys and Questionnaires , Treatment Outcome , Young AdultABSTRACT
Pertussis has shown a striking resurgence in the United States, with a return to record numbers of reported cases as last observed in the 1950s. Bordetella pertussis isolates lacking pertactin, a key antigen component of the acellular pertussis vaccine, have been observed, suggesting that B. pertussis is losing pertactin in response to vaccine immunity. Screening of 1,300 isolates from outbreak and surveillance studies (historical isolates collected from 1935 up to 2009, isolates from the 2010 California pertussis outbreak, U.S. isolates from routine surveillance between 2010-2012, and isolates from the 2012 Washington pertussis outbreak) by conventional PCR and later by Western blotting and prn sequencing analyses ultimately identified 306 pertactin-deficient isolates. Of these pertactin-deficient strains, 276 were identified as having an IS481 in the prn gene (prnIS481 positive). The first prnIS481-positive isolate was found in 1994, and the next prnIS481-positive isolates were not detected until 2010. The prevalence of pertactin-deficient isolates increased substantially to more than 50% of collected isolates in 2012. Sequence analysis of pertactin-deficient isolates revealed various types of mutations in the prn gene, including two deletions, single nucleotide substitutions resulting in a stop codon, an inversion in the promoter, and a single nucleotide insertion resulting in a frameshift mutation. All but one mutation type were found in prn2 alleles. CDC 013 was a predominant pulsed-field gel electrophoresis (PFGE) profile in the pertactin-positive isolates (203/994) but was found in only 5% (16/306) of the pertactin-deficient isolates. Interestingly, PFGE profiles CDC 002 and CDC 237 represented 55% (167/306) of the identified pertactin-deficient isolates. These results indicate that there has been a recent dramatic increase in pertactin-deficient B. pertussis isolates throughout the United States.
Subject(s)
Bacterial Outer Membrane Proteins/analysis , Bacterial Outer Membrane Proteins/genetics , Bordetella pertussis/genetics , Bordetella pertussis/isolation & purification , Mutation , Virulence Factors, Bordetella/analysis , Virulence Factors, Bordetella/genetics , Whooping Cough/epidemiology , Whooping Cough/microbiology , Blotting, Western , Bordetella pertussis/chemistry , Bordetella pertussis/classification , Cluster Analysis , DNA, Bacterial/genetics , Electrophoresis, Gel, Pulsed-Field , Genotype , Humans , Molecular Epidemiology , Molecular Typing , Polymerase Chain Reaction , Prevalence , Sequence Analysis, DNA , United States/epidemiologyABSTRACT
⢠The arbuscular mycorrhizal symbiosis is arguably the most ecologically important eukaryotic symbiosis, yet it is poorly understood at the molecular level. To provide novel insights into the molecular basis of symbiosis-associated traits, we report the first genome-wide analysis of the transcriptome from Glomus intraradices DAOM 197198. ⢠We generated a set of 25,906 nonredundant virtual transcripts (NRVTs) transcribed in germinated spores, extraradical mycelium and symbiotic roots using Sanger and 454 sequencing. NRVTs were used to construct an oligoarray for investigating gene expression. ⢠We identified transcripts coding for the meiotic recombination machinery, as well as meiosis-specific proteins, suggesting that the lack of a known sexual cycle in G. intraradices is not a result of major deletions of genes essential for sexual reproduction and meiosis. Induced expression of genes encoding membrane transporters and small secreted proteins in intraradical mycelium, together with the lack of expression of hydrolytic enzymes acting on plant cell wall polysaccharides, are all features of G. intraradices that are shared with ectomycorrhizal symbionts and obligate biotrophic pathogens. ⢠Our results illuminate the genetic basis of symbiosis-related traits of the most ancient lineage of plant biotrophs, advancing future research on these agriculturally and ecologically important symbionts.
Subject(s)
Glomeromycota/genetics , Mycorrhizae/genetics , Symbiosis/genetics , Transcriptome/genetics , Base Sequence , Colony Count, Microbial , Fungal Proteins/chemistry , Fungal Proteins/genetics , Fungal Proteins/metabolism , Gene Expression Regulation, Fungal , Gene Library , Genes, Fungal/genetics , Glomeromycota/growth & development , Meiosis/genetics , Mycelium/genetics , Mycorrhizae/growth & development , Plants/microbiology , Polymorphism, Single Nucleotide/genetics , Protein Structure, Tertiary , RNA, Messenger/genetics , RNA, Messenger/metabolism , Up-Regulation/geneticsABSTRACT
We tested the hypothesis that carotid atherosclerosis in systemic lupus erythematosus (SLE) is associated with poor health-related quality of life (HRQOL), which is independent of any association with traditional risk factors (TRFs), lifestyle and socioeconomic factors. Women with SLE completed the RAND Medical Outcome Study 36-Item Short-Form Health Survey version 1 (MOS SF-36). B-mode Doppler examination of the carotid arteries determined the presence of atherosclerotic plaque. The association between carotid plaque and HRQOL domains was analysed using logistic regression models with sequential adjustments for age, TRFs, education level and employment status. We studied 181 women, 47 (26%) of whom had carotid plaque. Carotid plaque was significantly associated with lower levels of physical functioning (p = 0.047), vitality (p = 0.04), role emotional (p = 0.04) and mental health subscales (p = 0.01) and lower mental component summary score (MCS) (p = 0.03). These associations were no longer significant after adjustment for age and TRFs, especially smoking. Smokers had lower physical functioning, vitality and mental health and more bodily pain. The association between carotid plaque and HRQOL was not independent of TRFs and smoking was a key mediator of the associations found. Poor HRQOL in smokers will need addressing as part of any smoking cessation strategies in SLE patients.
Subject(s)
Carotid Artery Diseases/physiopathology , Lupus Erythematosus, Systemic/complications , Quality of Life , Smoking/adverse effects , Adult , Carotid Artery Diseases/complications , Carotid Artery Diseases/epidemiology , Female , Health Surveys , Humans , Life Style , Logistic Models , Lupus Erythematosus, Systemic/physiopathology , Middle Aged , Risk Factors , Smoking/epidemiology , Socioeconomic Factors , United KingdomABSTRACT
PURPOSE: Comparative evidence regarding the responsiveness of the EQ-5D and SF-6D in arthritis patients is conflicting and insufficient across the range of disease severity. We examined the comparative responsiveness of the EQ-5D and SF-6D in cohorts of patients with early inflammatory disease through to severe rheumatoid arthritis (RA). METHODS: Responsiveness was tested using the effect size (ES) and standardised response mean (SRM). Correlation of change in EQ-5D and SF-6D with disease specific measures was tested using Pearson correlations and the Steiger's Z test. Treatment response and self-reported change were used as anchors of important change. RESULTS: The EQ-5D was more responsive to deterioration (ES ratio (EQ-5D/SF-6D): 1.6-3.0) and the SF-6D more responsive to improvement (ES ratio (SF-6D/EQ-5D): 1.1-1.8) in health. The SF-6D did not respond well to deterioration in patients with established severe RA (ES and SRM 0.08). The EQ-5D provided larger absolute mean change estimates but with greater variance compared to the SF-6D. CONCLUSIONS: The comparative responsiveness of the EQ-5D and SF-6D differs according to the direction of change. The level of mean change of the EQ-5D relative to the SF-6D has implications for cost-effectiveness analysis. Use of the SF-6D in patients with severe progressive disease may be inappropriate.
Subject(s)
Arthritis, Rheumatoid/psychology , Quality of Life , Surveys and Questionnaires , Adult , Aged , Arthritis, Rheumatoid/physiopathology , Female , Humans , Male , Middle Aged , Outcome Assessment, Health Care , Reproducibility of ResultsABSTRACT
This study classifies the mode of ventilation using respiratory rate, inhaled and exhaled carbon dioxide concentrations in anaesthetised patients. Thirty seven patients were breathing spontaneously (SPONT) and 50 were on a ventilator (intermittent positive pressure ventilation, IPPV). A data-based methodology for rule inference from trained neural networks, orthogonal search-based rule extraction, identified two sets of low-order Boolean rules for differential identification of the mode of ventilation. Combining both models produced three possible outcomes; IPPV, SPONT and 'Uncertain'. The true positive rates were approximately maintained at 96% for IPPV and 93% for SPONT, with false positive rates of 0.4% for each category and 4.3% 'Uncertain' inferences.
Subject(s)
Respiration, Artificial , Respiratory Physiological Phenomena , Case-Control Studies , HumansABSTRACT
Substance abuse continues to be a significant problem amongst anaesthetists. We have investigated a run chart methodology for tracking opioid use that may be used to identify potential personal use by noting a change in usage over time. Included in the data set was a record of an anaesthetist who abused opioids. Opioids signed out from the controlled drugs safe were converted into generic units so that opioid use could be compared. These standardised units of usage were plotted against anaesthetists' theatre time. We show, using run charts--a method used in industrial quality control--how abnormal usage could have been detected. The key to the run chart methodology is detection in a change in personal use rather than demonstrating any change compared with departmental averages. More time series data from anaesthetists known to have abused opioids would be required to validate the system.
Subject(s)
Anesthesiology , Opioid-Related Disorders/diagnosis , Physician Impairment , HumansABSTRACT
Threshold systolic arterial pressure alarms often use pre-operative values as a guide for intra-operative values. Recently, two systems (normalisation and principal component analysis) have been described that use the 'current' systolic arterial pressure and the change in systolic arterial pressure over a preceding time interval to generate an alarm based on units of standard deviation. Normalisation and principal component analysis techniques should prioritize alarms for clinically significant changes and hence reduce overall activation of alarms. Our aim was to measure the change in alarm activation using these techniques compared with standard threshold alarms. Systolic blood pressure data, collected from 10 patients (a total of 2177 min at 100 Hz), were cleaned and submitted to analysis using threshold alarms, normalisation and principal component analysis. With the threshold alarms set at 100 mmHg (low) and 140 mmHg (high), and a 5-min window, the alarms were activated for 557 min; using statistics-based thresholds the alarms were activated for 169 min (normalisation) and 155 min (principal component analysis), a reduction of approximately 70-72%.
Subject(s)
Blood Pressure , Monitoring, Intraoperative/methods , Anesthesia, General , Blood Pressure Determination/methods , Equipment Failure , Humans , Intraoperative Complications/diagnosis , Principal Component Analysis , Signal Processing, Computer-AssistedABSTRACT
BACKGROUND: Anti-tumour necrosis factor (TNF)alpha treatments improve outcome in severe rheumatoid arthritis (RA) and are efficacious in psoriasis and psoriatic arthritis. However recent case reports describe psoriasis occurring as an adverse event in patients with RA receiving anti-TNFalpha therapy. OBJECTIVES: We aimed to determine whether the incidence rate of psoriasis was higher in patients with RA treated with anti-TNFalpha therapy compared to those treated with traditional disease-modifying antirheumatic drugs (DMARDs). We also compared the incidence rates of psoriasis between the three anti-TNFalpha drugs licensed for RA. METHODS: We studied 9826 anti-TNF-treated and 2880 DMARD-treated patients with severe RA from The British Society for Rheumatology Biologics Register (BSRBR). All patients reported with new onset psoriasis as an adverse event were included in the analysis. Incidence rates of psoriasis were calculated as events/1000 person years and compared using incidence rate ratios (IRR). RESULTS: In all, 25 incident cases of psoriasis in patients receiving anti-TNFalpha therapy and none in the comparison cohort were reported between January 2001 and July 2007. The absence of any cases in the comparison cohort precluded a direct comparison; however the crude incidence rate of psoriasis in those treated with anti-TNFalpha therapy was elevated at 1.04 (95% CI 0.67 to 1.54) per 1000 person years compared to the rate of 0 (upper 97.5% CI 0.71) per 1000 person years in the patients treated with DMARDs. Patients treated with adalimumab had a significantly higher rate of incident psoriasis compared to patients treated with etanercept (IRR 4.6, 95% CI 1.7 to 12.1) and infliximab (IRR 3.5, 95% CI 1.3 to 9.3). CONCLUSIONS: Results from this study suggest that the incidence of psoriasis is increased in patients treated with anti-TNFalpha therapy. Our findings also suggest that the incidence may be higher in patients treated with adalimumab.
Subject(s)
Antirheumatic Agents/adverse effects , Arthritis, Rheumatoid/drug therapy , Psoriasis/chemically induced , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Adalimumab , Adult , Aged , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , Antirheumatic Agents/therapeutic use , Etanercept , Female , Humans , Immunoglobulin G/adverse effects , Immunoglobulin G/therapeutic use , Infliximab , Male , Middle Aged , Prospective Studies , Psoriasis/pathology , Receptors, Tumor Necrosis Factor/therapeutic use , RegistriesABSTRACT
Patients with rheumatoid arthritis (RA) are at increased risk of low bone density and fractures. This study identifies predictors of initiation of dual energy X-ray absorptiometry (DXA) testing in RA. We identified RA patients from the CORRONA registry with >or=1 year follow-up without reported DXA at study entry. The primary outcome was report of DXA in the first year of follow-up (DXA initiation). Variables associated with DXA initiation were considered for the multivariate model. Stepwise logistic regression identified independent predictors. Of the 2,717 RA patients without DXA documented at enrollment, 297 (11%) reported DXA initiation. Independent predictors of DXA initiation included age, female sex, history of fracture, steroid use, and physician's assessment of RA activity. In conclusion, DXA initiation in RA patients in the CORRONA cohort is low despite increased risk of osteoporosis. Predictors of DXA initiation include fracture, common risk factors for osteoporosis, and RA-associated factors.
Subject(s)
Arthritis, Rheumatoid/complications , Bone Density , Osteoporosis, Postmenopausal/complications , Practice Patterns, Physicians' , Absorptiometry, Photon , Adult , Age Distribution , Age Factors , Cohort Studies , Female , Follow-Up Studies , Fractures, Bone/etiology , Humans , Logistic Models , Osteoporosis, Postmenopausal/etiology , Osteoporosis, Postmenopausal/metabolism , Predictive Value of Tests , Registries , Risk Factors , Steroids/adverse effectsABSTRACT
OBJECTIVES: To describe changes in the provision of rheumatology services, monitor the pattern of inequalities in UK rheumatology service provision since 2005, and to summarize the 3-yr impact of the new National Health Service (NHS) consultant contract and the Musculoskeletal Services Framework in England and Wales. METHODS: Questionnaires about timetable and working conditions were sent to all consultants on the BSR/ARC UK Workforce Register in January 2007, along with the personal and job-related details currently held about them on the register to update. The questionnaire included a visual analogue scale asking 'how concerned are you that your current post might be under threat' ranging from 0 'Not at all' to 100 'Extremely'. RESULTS: The response rate of the 2005 and 2007 surveys were 89 and 87%, respectively. Levels of optimal provision now exceed 70% in England and Wales, and 50% in Scotland and Northern Ireland. Levels of provision remain substantially higher in London than anywhere else. The median level of perceived job threat in the UK was 31 (interquartile range 11-61). Consultants in areas where provision is highest and a higher proportion of services are run in conjunction with Clinical Assessment and Treatment (CAT) centres report higher perceived job threat. CONCLUSIONS: Provision of rheumatology services has continued to expand over the past decade; however, inequalities persist at national and sub-national level. There is evidence of improvement in regions with the lowest provision, but there are indications of increased perceived job threat in areas with traditionally higher provision and where CAT centres have been introduced.
Subject(s)
Delivery of Health Care/statistics & numerical data , Rheumatology , State Medicine/organization & administration , Consultants/statistics & numerical data , Delivery of Health Care/standards , Health Care Reform , Health Services Research/methods , Humans , Quality of Health Care , Registries , Rheumatology/organization & administration , State Medicine/standards , State Medicine/trends , United Kingdom , Workforce , Workload/statistics & numerical dataABSTRACT
We have developed an anaesthesia alarm system that responds in a more clinically appropriate manner than current threshold alarms. A decrease in systolic arterial pressure of 10 mmHg from a previous value of 70 mmHg has a greater clinical significance than a decrease of 10 mmHg from 150 mmHg. However, it has been difficult to envisage a simple algorithm for the detection of these contextually adverse changes in physiological variables. We have processed systolic arterial pressure data to create a mathematically straightforward statistical tool for sampling intervals up to 5 min. Both the blood pressure and the change in blood pressure over a known time interval are plotted on x and y axes with the units in standard deviations. Some 10 824 measurements were obtained at 10-s intervals in 17 patients. The mean (SD) systolic arterial pressure for all observations in our patients was 118 (17.0) mmHg. The mean (SD) change in systolic arterial pressure over 5 min was - 0.35 (15.2) mmHg. Combining the value for the standard deviation of systolic arterial pressure and the standard deviation of the change in systolic arterial pressure using Pythagoras's theorem creates a value in standard deviations for this particular state. Instead of alarms being set in mmHg, they would be set in standard deviations. This technique was developed further using Principal Component Analysis to isolate uncommon deviations from normal, clinically unimportant physiological variations. These clinically unimportant changes occur in a predictable fashion only if the sampling interval is 90 s or less. This new alarm system is asymmetric - a small decrease in systolic arterial pressure from 90 mmHg may, appropriately, set off an alarm but it would require a much larger increase in systolic arterial pressure to do so.
Subject(s)
Anesthesia, General , Blood Pressure Determination/methods , Intraoperative Complications/diagnosis , Monitoring, Intraoperative/methods , Signal Processing, Computer-Assisted , Algorithms , Blood Pressure , Health Status Indicators , Humans , Principal Component Analysis/methods , Reference Values , SystoleABSTRACT
Systemic lupus erythematosus (SLE) in children is a chronic multisystem disease with wide ranging effects on their quality of life (QOL). While SLE's impact on different arenas of life and well-being has been extensively examined in the adult population, its effect on children has not received adequate attention. This review discusses the multidimensional aspect of QOL, the biopsychosocial implications of SLE, factors complicating QOL measurement in the affected population, and the different generic and disease-specific scales used for measuring QOL and related constructs. Until now, there have not been any pediatric SLE-specific health-related QOL (HRQOL) scales. A section is devoted to a novel instrument developed specifically for measuring QOL in pediatric lupus called the Simple Measure of the Impact of Lupus Erythematosus in Youngsters (SMILEY). SMILEY is a brief, easily understood, valid, reliable and internally consistent pediatric SLE-specific QOL scale and will be a useful adjunct to clinical trials and outcomes research.