Small and large fiber sensory polyneuropathy in type 2 diabetes: Influence of diagnostic criteria on neuropathy subtypes

Diabetic polyneuropathy (DPN) can be classified based on fiber diameter into three subtypes: small fiber neuropathy (SFN), large fiber neuropathy (LFN), and mixed fiber neuropathy (MFN). We examined the effect of different diagnostic models on the frequency of polyneuropathy subtypes in type 2 diabetes patients with DPN. This study was based on patients from the Danish Center for Strategic Research in Type 2 Diabetes cohort. We defined DPN as probable or definite DPN according to the Toronto Consensus Criteria. DPN was then subtyped according to four distinct diagnostic models. A total of 277 diabetes patients (214 with DPN and 63 with no DPN) were included in the study. We found a considerable variation in polyneuropathy subtypes by applying different diagnostic models independent of the degree of certainty of DPN diagnosis. For probable and definite DPN, the frequency of subtypes across diagnostic models varied from: 1.4% to 13.1% for SFN, 9.3% to 21.5% for LFN, 51.4% to 83.2% for MFN, and 0.5% to 14.5% for non‐classifiable neuropathy (NCN). For the definite DPN group, the frequency of subtypes varied from: 1.6% to 13.5% for SFN, 5.6% to 20.6% for LFN, 61.9% to 89.7% for MFN, and 0.0% to 6.3% for NCN. The frequency of polyneuropathy subtypes depends on the type and number of criteria applied in a diagnostic model. Future consensus criteria should clearly define sensory functions to be tested, methods of testing, and how findings should be interpreted for both clinical practice and research purpose.     

Thrombopoietin-receptor agonists in haematological disorders: the Danish experience

The objective of this study was to investigate the use of thrombopoietin-receptor agonists (TPO-ra) in patients with refractory primary immune thrombocytopenia (ITP) as well as off-label use of TPO-ra in Danish haematology departments. Hospital medical records from 32 of the 39 patients having received TPO-ra from 2009 to 1 May 2011 were available for data collection and included in the study. Of these patients, 15 received TPO-ra for refractory primary ITP, 7 for secondary ITP (chronic lymphatic leukaemia, systemic lupus erythematosus, Evans syndrome, human immunodeficiency virus and celiac disease) and 10 were treated for non-ITP (chemotherapy-induced, acute myeloid leukaemia, myelodysplastic syndrome, hereditary spherocytosis and suspected chemically induced thrombocytopenia). Initial response to TPO-ra defined as platelet counts >30 × 10(9)/l after 4 weeks of treatment was found in 59% of primary ITP patients, 57% of patients with secondary ITP and 40% of patients with non-ITP. There were four deaths in the cohort, three of which were related to pre-existing medical conditions. Otherwise adverse effects were in general mild. This Danish retrospective registration study has demonstrated that in the off-protocol setting, the use of TPO-ra is associated with response rates largely similar to those seen in previous protocol-monitored studies and no new adverse events were reported.     

Recommendations for an update of 2003 European regulatory requirements for registration of drugs to be used in the treatment of RA

Since 2003, the European Medicines Agency (EMA) document, 'Points to consider on clinical investigation of medicinal products other than NSAIDs (nonsteroidal anti-inflammatory drugs) for the treatment of rheumatoid arthritis' has provided guidance for the clinical development of both biologic and non-biologic disease-modifying antirheumatic drugs (DMARDs). In the last few years, several new products have been developed or are in development for the treatment of RA, which offer significant efficacy with regard to disease control, including prevention of structural damage and disability. Concurrently, novel insights have been gained with respect to the assessment of disease activity, joint damage and disability. New treatment strategies have been established which relate to early therapy, tight control and rapid switching of medication. Accordingly, several new EULAR/ACR recommendations have been or are being developed. Several important additions and changes are needed in the 2003 guidance to incorporate the current scientific knowledge into clinical trial design for the development of future products. Under the auspices of the Group for the Respect of Ethics and Excellence in Science (GREES), a group of experts in the field of RA and clinical trial design met to provide a consensus recommendation for an update to the 2003 EMA guidance document.     

The prevalence of chronic obstructive pulmonary disease in Uppsala, Sweden--the Burden of Obstructive Lung Disease (BOLD) study: cross-sectional population-based study

Objectives: To estimate chronic obstructive pulmonary disease (COPD) prevalence in Uppsala and the impact of risk factors on disease prevalence using the standardised methods of the Burden of Obstructive Lung Disease (BOLD) study initiative. Methods: Randomly selected participants, aged 40 years or more (n = 548) responded to a questionnaire regarding smoking habits, respiratory symptoms, medical history, and exposure to airway irritants. Spirometry, with a post‐bronchodilator test, was performed and COPD defined as post‐bronchodilatory forced expiratory volume in 1 s (FEV₁)/forced vital capacity (FVC) < 0.70 or FEV₁/FVC < lower limit of normality (LLN). Circulatory inflammatory markers were measured. Results: COPD prevalence was 16.2%, which was the fourth lowest prevalence of COPD, compared with 12 other BOLD centres. Main risk factors for COPD were increasing age [odds ratio (OR) = 2.08 per 10 years] and smoking (OR = 1.33 per 10 pack years). Higher education was protective (OR = 0.70 per 5 years). Previous tuberculosis was an almost significant risk factor for COPD (P = 0.08). Subjects with COPD reported more respiratory symptoms but only 29% had previous doctor diagnosed COPD, asthma, chronic bronchitis or emphysema. Participants with COPD had higher levels of C‐reactive protein (P = 0.01), but no difference was observed in interleukin 6 (IL‐6) levels. Using LLN instead of the fixed FEV₁/FVC ratio reduced the prevalence of COPD to 10%. Conclusion: COPD prevalence in Uppsala was similar to other BOLD centres in high‐income countries. Apart from known COPD risk factors (age, smoking, lower educational level), a history of tuberculosis may be associated with COPD even in high‐income countries. COPD remains under‐diagnosed, as only 29% of subjects with COPD had a previously diagnosed lung disorder. Please cite this paper as: Danielsson P, Ólafsdóttir IS, Benediktsdóttir B, Gíslason T and Janson C. The prevalence of chronic obstructive pulmonary disease in Uppsala, Sweden – the Burden of Obstructive Lung Disease (BOLD) study: cross‐sectional population‐based study. Clin Respir J 2012; 6: 120–127.     

Inverse relationship between circulating levels of leptin and bone mineral density in chronic liver disease

Background and Aim: The pathophysiology of osteoporosis complicating chronic liver disease is unknown. Recent animal studies have found leptin to be a potent inhibitor of bone formation. The aim of this study was to investigate the relationship between serum leptin levels and bone mineral density in patients with chronic liver disease. Methods: Fifty‐eight patients, 39 females and 19 males, and age‐ and gender‐matched controls were included. Bone mineral density was measured by using dual energy X‐ray absorptiometry. Serum leptin was measured by using a radioimmunoassay. Results: The mean serum leptin concentration was 10.4 ± 11.3 and 15.2 ± 17.9 ng/mL; P = 0.11, in the patients and controls, respectively. Leptin correlated positively with body mass index in patients (r = 0.40; P = 0.003) and in controls (r = 0.55; P < 0.0001). In patients classified as Child–Pugh grade B and C, serum leptin correlated negatively with bone mineral density in females at both the lumbar spine and the femoral neck (r = –0.78; P = 0.04 and r = –0.86; P = 0.03, respectively). In male patients, the correlation was only significant at the lumbar spine (r = –0.99; P = 0.002 and r = –0.86; P = 0.06, at the lumbar spine and femoral neck, respectively). No correlation was found between serum leptin and bone mineral density in the controls. Conclusion: An inverse relationship between serum leptin and bone mineral density was found in patients with advanced chronic liver disease. The reasons for these findings are uncertain, but a pathophysiological role of circulating leptin in osteoporosis in chronic liver disease is possible.     

Circulating levels of insulin‐like growth factors and their binding proteins in patients with chronic liver disease: lack of correlation with bone mineral density

Abstract: Background/Aims: Insulin‐like growth factor‐I (IGF‐I) levels are low in patients with chronic liver disease (CLD) and have been found to correlate with measurements of bone mineral density (BMD) in men with viral cirrhosis. The aim of this study was to investigate the relationship between circulating IGF‐I levels and BMD in patients with CLD of other causes. Methods: Fifty‐eight patients with CLD were included. Age‐ and sex‐matched normal individuals served as controls. Serum levels of IGF‐I and IGF‐II and their binding proteins (IGFBP‐1–3) were measured by radioimmunoassay. BMD was measured by dual energy X‐ray absorptiometry. Results: IGF‐I levels were 57±33 and 136±48 ng/ml; p<0.0001 in patients and controls, respectively. IGF‐II and IGFBP‐3 levels were lower (p<0.0001) and IGFBP‐1 and IGFBP‐2 levels were higher in patients compared with controls (p<0.0005 and p<0.0001, respectively). All growth factors, except for IGFBP‐2, correlated with parameters of liver function. In a multiple regression analysis, adjusting for age, no correlation was found between IGF‐I, IGF‐II, IGFBP‐1–3 and BMD in either patients or controls. Conclusion: Patients with CLD have low levels of IGF‐I, IGF‐II and IGFBP‐3 that correlate with liver function. No relationship was found between low levels of growth factors and BMD.     

Development of a competency-based approach to teaching preventive medicine

A collaborative project to develop a competency-based curriculum and associated instructional materials for teaching preventive medicine to medical students has been undertaken by the Association of Teachers of Preventive Medicine in cooperation with the Center for Educational Development in Health at Boston University. A general model of physician responsibilities in the preventive dimension of clinical practice was elaborated and specific performance objectives were delineated. Specifications of physician performance were verified through Delphi and questionnaire surveys among approximately 100 practicing physicians. Three facets of physician performance emerged as warranting special attention: planning a practice-based program of clinical prevention, adapting the program to the needs of individual patients, and assisting patients to modify behavior patterns. Competency-based educational objectives were derived from the physician performance objectives. An instructional system to facilitate attainment of these objectives is under development. It incorporates five modules based on the following themes: the epidemiologic basis of clinical prevention, methods of clinical prevention, management planning for preventive services, clinical health and risk appraisal, and intervention for behavior change. Each module consists of units of instruction which specify expected learning outcomes, provide guidelines for evaluation of student performance, and recommend appropriate learning activities and resources.     

Exercise leads to faster postural reflexes, improved balance and mobility, and fewer falls in older persons with chronic stroke

OBJECTIVES: To determine the effect of two different community-based group exercise programs on functional balance, mobility, postural reflexes, and falls in older adults with chronic stroke. DESIGN: A randomized, clinical trial. SETTING: Community center. PARTICIPANTS: Sixty-one community-dwelling older adults with chronic stroke. INTERVENTION: Participants were randomly assigned to an agility (n=30) or stretching/weight-shifting (n=31) exercise group. Both groups exercised three times a week for 10 weeks. MEASUREMENTS: Participants were assessed before, immediately after, and 1 month after the intervention for Berg Balance, Timed Up and Go, step reaction time, Activities-specific Balance Confidence, and Nottingham Health Profile. Testing of standing postural reflexes and induced falls evoked by a translating platform was also performed. In addition, falls in the community were tracked for 1 year from the start of the interventions. RESULTS: Although exercise led to improvements in all clinical outcome measures for both groups, the agility group demonstrated greater improvement in step reaction time and paretic rectus femoris postural reflex onset latency than the stretching/weight-shifting group. In addition, the agility group experienced fewer induced falls on the platform. CONCLUSION: Group exercise programs that include agility or stretching/weight shifting exercises improve postural reflexes, functional balance, and mobility and may lead to a reduction of falls in older adults with stroke.