A human cadaveric workshop: One solution to competence in the face of rarity

Competent performance of cricothyroidotomy, lateral canthotomy and resuscitative thoracostomy is an expected standard for Australasian emergency physicians, but infrequent exposure to these procedures could impair physician confidence, reducing the likelihood of their execution in a critical timeframe. Training to perform these procedures is a recognised challenge for non‐surgeons, and cadaver‐based training is one method of addressing this need. We describe a 1 day cadaver‐based workshop for emergency medicine doctors and briefly report on its impact on physician confidence. This workshop appeared effective in increasing the confidence of emergency medicine physicians to carry out rarely performed life and sight‐saving procedures and also provides an opportunity for senior clinicians to increase compliance with continuing profession development schemes.     

One‐year metreleptin improves insulin secretion in patients with diabetes linked to genetic lipodystrophic syndromes

Recombinant methionyl human leptin (metreleptin) therapy was shown to improve hyperglycaemia, dyslipidaemia and insulin sensitivity in patients with lipodystrophic syndromes, but its effects on insulin secretion remain controversial. We used dynamic intravenous (i.v.) clamp procedures to measure insulin secretion, adjusted to insulin sensitivity, at baseline and after 1 year of metreleptin therapy, in 16 consecutive patients with lipodystrophy, diabetes and leptin deficiency. Patients, with a mean [± standard error of the mean (s.e.m.)] age of 39.2 (±4) years, presented with familial partial lipodystrophy (n = 11, 10 women) or congenital generalized lipodystrophy (n = 5, four women). Their mean (± s.e.m.) BMI (23.9 ± 0.7 kg/m²), glycated haemoglobin levels (8.5 ± 0.4%) and serum triglycerides levels (4.6 ± 0.9 mmol/l) significantly decreased within 1 month of metreleptin therapy, then remained stable. Insulin sensitivity (from hyperglycaemic or euglycaemic‐hyperinsulinaemic clamps, n = 4 and n = 12, respectively), insulin secretion during graded glucose infusion (n = 12), and acute insulin response to i.v. glucose adjusted to insulin sensitivity (disposition index, n = 12), significantly increased after 1 year of metreleptin therapy. The increase in disposition index was related to a decrease in percentage of total and trunk body fat. Metreleptin therapy improves not only insulin sensitivity, but also insulin secretion in patients with diabetes attributable to genetic lipodystrophies.     

The performance of STA-Liatest D-dimer assay in out-patients with suspected pulmonary embolism

Several studies have shown that d ‐dimer can reliably rule out pulmonary embolism (PE) in out‐patients. However, various assays have different sensitivities and specificities to detect thrombosis. Our aim was to evaluate the performance of STA‐Liatest D‐Di in out‐patients referred for suspected PE in a prospective outcome study. 495 consecutive patients referred to Østfold Hospital Trust‐Fredrikstad, Norway for suspected PE between February 2002 and December 2003, were recruited in a study evaluating a decision‐based algorithm combining clinical probability (CP), d ‐dimer, and multi‐slice computer tomography (MSCT). d ‐dimer was performed as a first step test. No further testing was carried out in patients with d ‐dimer ≤0·4 mg/l and low/intermediate CP. The remaining patients proceeded to MSCT. All patients were followed up for 3 months to assess the 3‐month thromboembolic risk. The final cohort consisted of 432 patients. PE was diagnosed in 102 (23%) patients. At a d ‐dimer cut‐off point of 0·4 mg/l the tests had the highest sensitivity (100%) and specificity (36%). It safely ruled out PE in 120 (28%) patients. Kappa‐coefficients for comparisons versus VIDAS and Asserachrom showed good concordance. STA‐Liatest is a reliable and effective assay that can safely rule out PE in out‐patients with a performance comparable with that of enzyme‐linked immunosorbent assay‐based d ‐dimer levels.     

No evidence that early use of inhaled corticosteroids reduces current asthma at 10 years of age

BACKGROUND: It is debated whether early treatment with inhaled corticosteroids (ICS) can change the natural course of childhood asthma. AIM: To assess if ICS treatment before 2 years of age in children with obstructive airways disease reduces current asthma at 10 years of age. METHODS: Children with (n=233) and without (n=219) recurrent (r) bronchial obstruction (BO) attending clinical examination at 2 years of age in the birth cohort Environment and Childhood Asthma study in Oslo, were reinvestigated at 10 years of age. Current asthma (CA) at 10 years was defined as asthma with either symptoms and/or asthma treatment during the last year, and/or 10% fall in forced expired volume in 1s after standardized treadmill run. The risk of CA was assessed by logistic regression and propensity modelling (including gender, parental atopy and severity score at 2 years) in children with rBO who received ICS or not by 2 years. RESULTS: CA was found in 97 children, more often among rBO children with (56.9%) and without ICS treatment (30.8%) compared to no-BO children (5.5%) (p<0.001). In rBO children logistic regression analyses (adjusted odds ratio aOR (95% confidence interval)) identified male gender (aOR 1.82 (1.01-3.27), p=0.046) and severity score at 2 years 1.14 (1.03-1.28), (p=0.01), as significant and ICS treatment as non-significant 2.00 (0.98-4.12) risk factors for CA. With propensity modelling adjusting for disease severity, ICS treatment by 2 years caused a non-significant increased risk aOR of CA of 1.84 (0.89-3.82). CONCLUSION: No evidence was found that early use of ICS before age two in children with rBO reduces current asthma 8 years later.     

Second‐line treatment in the Malawi antiretroviral programme: high early mortality,but good outcomes in survivors,despite extensive drug resistance at baseline*

Objectives

The Malawi antiretroviral therapy (ART) programme uses the public health approach to identify ART failure. Advanced disease progression may occur before switching to second‐line ART. We report outcomes for patients evaluated and initiated on second‐line treatment in Malawi.

Methods

Patients meeting Malawi immunological or clinical criteria for ART failure in two large urban ART clinics were evaluated for virological failure (viral load >400 HIV‐1 RNA copies/mL) and, if failure was confirmed, initiated on second‐line ART (zidovudine/lamivudine/tenofovir/lopinavir/ritonavir). Patients were seen monthly and laboratory evaluations were performed quarterly and as needed. We performed logistic regression modelling to identify factors associated with mortality, mortality or new HIV illnesses, and virological suppression at 12 months.

Results

Of the 109 patients with confirmed virological failure, five patients died prior to initiation, three declined switching and 101 patients initiated second‐line treatment. Over 12 months, 10 additional patients died, 34 patients experienced 45 HIV‐related events, and 19 patients experienced grade 3 or 4 toxicities. Among survivors, 85.2% had HIV‐1 RNA<400 copies/mL at 12 months. While power to distinguish differences was limited, response rates were similar regardless of baseline resistance level. The median CD4 count increase was 142 cells/μL. World Health Organization clinical failure at baseline [odds ratio (OR) 3.47; 95% confidence interval (CI) 1.14–10.59] and body mass index <18.5 (OR 4.43; 95% CI 1.15–17.12) were risk factors for death. Baseline CD4 count <50 cells/μL was associated with increased risk for death or morbidity at 12 months (OR 2.57; 95% CI 1.01–6.52).

Conclusions

Second‐line treatment in Malawi was associated with substantial mortality, morbidity and toxicity but, among survivors, virological outcomes were favourable.     

Patients with rheumatoid arthritis report greater physical functional deterioration in lower limbs compared to upper limbs over 10 years

OBJECTIVE: To examine the overall magnitude of change in self-reported physical function over a 10-year period in patients with rheumatoid arthritis (RA), and to compare changes in physical function between the lower and upper limbs. METHODS: Self-reported data on physical function were collected from the patients in the Oslo RA register (ORAR) through mail surveys between 1994 and 2004. The change in overall physical function was measured by the Short Form 36 (SF-36), the Modified Health Assessment Questionnaire (MHAQ), and the Arthritis Impact Measurement Scales (AIMS2). The MHAQ and AIMS2 were used to address activities related to lower and upper limb function. The magnitude of changes was expressed as crude and adjusted changes and standardized response means (SRMs). The analyses were adjusted for age, sex, duration of disease, and number of surgical procedures in the lower and upper limbs. RESULTS: A total of 414 patients [323 (78%) females, mean age 54.9 years and median disease duration 11.6 years] were included in these analyses. The overall physical function measured by AIMS2 physical and MHAQ deteriorated during 10 years. The magnitude of change in physical function was generally worse for activities related to lower limbs (SRM for adjusted changes 0.16-0.27) than upper limbs (SRM 0.06-0.08). During the 10-year follow-up period, 231 patients (56%) underwent orthopaedic surgery because of their RA. Findings were consistent after adjusting for surgical procedures. CONCLUSION: Patient-reported lower limb function deteriorated more than upper limb function over a 10-year period in patients with established RA.     

Self reported non-vertebral fractures in rheumatoid arthritis and population based controls: incidence and relationship with bone mineral density and clinical variables

OBJECTIVE: To compare the incidence of self reported non-vertebral fractures after RA diagnosis between female patients with RA and control subjects, and to explore possible associations between non-vertebral fractures and bone mineral density (BMD), disease, and demographic factors. METHODS: 249 women (mean age 63.0 years) recruited from a county register of patients with RA and population controls (n = 249) randomly selected after matching for age, sex, and residential area were studied. Data on previous non-vertebral fractures were obtained from a detailed questionnaire, and BMD was measured at the hip and spine. RESULTS: 53 (21.3%) patients with RA had had 67 fractures after RA diagnosis, the corresponding numbers for controls were 50 (20.1%) and 60 (odds ratio (OR) for paired variables for overall fracture history 1.09, 95% CI 0.67 to 1.77). The overall fracture rates per 100 patient-years were 1.62 and 1.45, respectively, but self reported hip fractures were increased in RA (10 v 2, OR 9.0, 95% CI 1.2 to 394.5). Patients with a positive fracture history had longer disease duration, were more likely to have at least one deformed joint, and had lower age and weight adjusted BMD than those with no fracture history. In logistic regression analysis, fracture history was independently related to BMD only. CONCLUSIONS: With the probable exception of hip fractures, non-vertebral fractures do not seem to be a substantial burden in RA. Similar independent relationships between levels of BMD and fracture history were found in patients with RA and in population based controls.     

Interviews of individuals diagnosed as anti-human immunodeficiency virus-positive through the screening of blood donations in the Paris area to 1994: reflections on the selection of blood donors

BACKGROUND: One of the aims of the medical interview routinely preceding each blood donation is the identification of individuals with a risk factor for infection with the human immunodeficiency virus (HIV). STUDY DESIGN and METHODS: Interviews were performed with individuals diagnosed as being seropositive for HIV through the systematic biologic screening of blood donations in the Paris area to establish, first, the circumstances allowing HIV-seropositive individuals to pass through the predonation medical interview and, second, the motivation of these individuals as blood donors. Risk factors of 30 HIV-infected donors identified between 1991 and 1994 were determined. RESULTS: When asked whether they recognized the eventual risk to recipients of donated blood, 14 (47%) of 30 answered positively. Fifteen (50%) admitted having given their blood to determine their HIV status. CONCLUSION: These individuals did not exclude themselves from blood donation and probably hid their risk factor(s) at the predonation interview in order to be accepted as blood donors.