Patient characteristics associated with risk of first hospital admission and readmission for acute exacerbation of chronic obstructive pulmonary disease (COPD) following primary care COPD diagnosis: a cohort study using linked electronic patient records.

OBJECTIVES: To investigate patient characteristics of an unselected primary care population associated with risk of first hospital admission and readmission for acute exacerbation of chronic obstructive pulmonary disease (AECOPD). DESIGN: Retrospective open cohort using pseudonymised electronic primary care data linked to secondary care data. SETTING: Primary care; Lothian (population approximately 800,000), Scotland. PARTICIPANTS: Data from 7002 patients from 72 general practices with a COPD diagnosis date between 2000 and 2008 recorded in their primary care record. Patients were followed up until 2010, death or they left a participating practice. MAIN OUTCOME MEASURES: First and subsequent admissions for AECOPD (International Classification of Diseases (ICD) 10 codes J44.0, J44.1 in any diagnostic position) after COPD diagnosis in primary care. RESULTS: 1756 (25%) patients had at least 1 AECOPD admission; 794 (11%) had at least 1 readmission and the risk of readmission increased with each admission. Older age at diagnosis, more severe COPD, low body mass index (BMI), current smoking, increasing deprivation, COPD admissions and interventions for COPD prior to diagnosis in primary care, and comorbidities were associated with higher risk of first AECOPD admission in an adjusted Cox proportional hazards regression model. More severe COPD and COPD admission prior to primary care diagnosis were associated with increased risk of AECOPD readmission in an adjusted Prentice-Williams-Peterson model. High BMI was associated with a lower risk of first AECOPD admission and readmission. CONCLUSIONS: Several patient characteristics were associated with first AECOPD admission in a primary care cohort of people with COPD but fewer were associated with readmission. Prompt diagnosis in primary care may reduce the risk of AECOPD admission and readmission. The study highlights the important role of primary care in preventing or delaying a first AECOPD admission.

The cost of walking downhill: is the preferred gait energetically optimal?

Humans tend to prefer walking patterns that minimize energetic cost, but must also maintain stability to avoid falling over. The relative importance of these two goals in determining the preferred gait pattern is not currently clear. We investigated the relationship between energetic cost and stability during downhill walking, a context in which gravitational energy will assist propulsion but may also reduce stability. We hypothesized that humans will not minimize energetic cost when walking downhill, but will instead prefer a gait pattern that increases stability. Simulations of a dynamic walking model were used to determine whether stable downhill gaits could be achieved using a simple control strategy. Experimentally, twelve healthy subjects walked downhill at 1.25 m/s (0, 0.05, 0.10, and 0.15 gradients). For each slope, subjects performed normal and relaxed trials, in which they were instructed to reduce muscle activity and allow gravity to maximally assist their gait. We quantified energetic cost, stride timing, and leg muscle activity. In our model simulations, increase in slope reduced the required actuation but also decreased stability. Experimental subjects behaved more like the model when using the relaxed rather than the normal walking strategy; the relaxed strategy decreased energetic cost at the steeper slopes but increased stride period variability, an indicator of instability. These results indicate that subjects do not take optimal advantage of the propulsion provided by gravity to decrease energetic cost, but instead prefer a more stable and more costly gait pattern.

Opioid peptides and dipeptidyl peptidase in autism.

It has been hypothesized that autism results from an 'opioid peptide excess'. The aims of this study were to (1) confirm the presence of opioid peptides in the urine of children with autism and (2) determine whether dipeptidyl peptidase IV (DPPIV/CD26) is defective in children with autism. Opioid peptides were not detected in either the urine of children with autism (10 children; nine males, one female; age range 2 years 6 months to 10 years 1 month) or their siblings (10 children; seven males, three females; age range 2 years 3 months to 12 years 7 months) using liquid chromatography-ultraviolet-mass spectrometric analysis (LC-UV-MS). Plasma from 11 normally developing adults (25 years 5 months to 55 years 5 months) was also tested. The amount and activity of DPPIV in the plasma were quantified by an ELISA and DPPIV enzyme assay respectively; DPPIV was not found to be defective. The percentage of mononuclear cells expressing DPPIV (as CD26) was determined by flow cytometry. Children with autism had a significantly lower percentage of cells expressing CD3 and CD26, suggesting that they had lower T-cell numbers than their siblings. In conclusion, this study failed to replicate the findings of others and questions the validity of the opioid peptide excess theory for the cause of autism.

Systemic antibodies to Clostridium botulinum type C: do they protect horses from grass sickness (dysautonomia)?

The aetiology of equine grass sickness (EGS) is still unknown. There is increasing evidence that toxicoinfection with Clostridium botulinum type C is involved. Epidemiological evidence shows that resistance to EGS can occur in older horses and those that have been on a particular pasture for longer or have been in prior contact with the disease. This resistance may be in the form of an immune response to the aetiological agent. Levels of systemic antibodies to the surface antigens of C. botulinum type C (using the closely related and safe C. novyi type A as a phenotypic marker) and to the botulinum type C neurotoxin (BoNT/C) were investigated in horses with and without EGS. Horses with grass sickness were found to have significantly lower levels of systemic IgG to both surface antigens and BoNT/C. Horses with low levels of systemic immunity to these antigens may be more susceptible to developing EGS. There were no significant differences in antibody levels between the different categories of EGS, suggesting systemic immunity to C. botulinum type C does not play a significant role in influencing the severity of the disease. However, horses that had been in contact with EGS or that were grazing land where it had occurred frequently in the past had significantly higher antibody levels to these antigens. These horses may have been exposed to subclinical doses of C. botulinum type C and BoNT/C, resulting in the production of a protective immune response against the putative aetiological agent. This finding is of potential significance for the prospect of prevention of EGS by vaccination against C. botulinum type C.

The association of Clostridium botulinum type C with equine grass sickness: a toxicoinfection?

The cause of grass sickness, an equine dysautonomia, is unknown. The disease usually results in death. Gastrointestinal (GI) dysfunction is a common clinical manifestation in all forms of the disease. It is generally thought that equine grass sickness (EGS) is caused by an ingested or enterically produced neurotoxin which is absorbed through the GI tract. Clostridium botulinum was first implicated as a causative agent when it was isolated from the GI tract of a horse with EGS in 1919. The aim of the present study was to investigate the hypothesis that EGS results from toxicoinfection with C. botulinum type C: growth of the bacterium in the GI tract with production of toxin (BoNT/C). Ileum contents and faeces from horses with EGS were investigated for BoNT/C, and indirectly for the presence of C. botulinum type C, and compared with control samples from horses without EGS. BoNT/C was detected directly by ELISA in the ileum of 45% (13/29) of horses with EGS compared to 4% (1/28) of controls, and in the faeces of 44% (20/45) of horses with EGS compared to 4% (3/77) of controls. Levels of up to 10 Mlg toxin/g wet weight of gut contents were observed. The one control horse with detectable toxin in the ileum had been clinically diagnosed as having acute EGS, but this was not confirmed by histopathology. The organism was detected indirectly by assaying for BoNT/C by ELISA after enrichment in culture medium. C. botulinum type C was shown to be present in 48% (14/29) of ileum samples and 44% (20/45) of faecal samples from horses with EGS, compared with 7% (2/27) of ileum samples and 8% (6/72) of faecal samples from controls. These results support the hypothesis that EGS results from a C. botulinum type C toxicoinfection.