Possible association between beclomethasone diproprionate aerosol and cataracts

Posterior subcapsular cataracts may be associated with corticosteroid administration. I report a nine-year-old girl who developed transient bilateral posterior subcapsular cataracts whilst on long-term beclomethasone diproprionate aerosol, having in this time a total of only three weeks prednisone orally. The literature is reviewed regarding the possible absorption of beclomethasone diproprionate. The role and frequency of corticosteroids in causing cataracts is discussed. Suggestions are made about the role of beciomethasone diproprionate aerosol in the management of childhood asthma.     

Long-term follow-up of people who have survived cancer during childhood

Substantial improvements in survival after treatment for malignant disease in childhood are leading to a rapidly increasing number of long-term survivors, many of whom are now adults. However, late chronic adverse effects of treatment are common, and have potentially severe effects on survivors' future physical, cognitive, or psychosocial health. The aim of long-term follow-up is to facilitate timely diagnosis and appropriate management of late adverse effects, thereby reducing the frequency of severe complications. Although the delivery of long-term follow-up care varies substantially--particularly in terms of who provides it, where, and how--recognition of the importance of appropriate multidisciplinary care and cross-speciality care is increasing, especially for adolescent and adult survivors of cancer during childhood. Several models of long-term follow-up care have been developed to address this need. This review discusses the present provision of long-term follow-up, and summarises information that might facilitate design and implementation of future models of long-term follow-up care.     

Guidelines for supportive care in multiple myeloma 2011

Supportive care plays an increasingly important role in the modern management of multiple myeloma. While modern treatments have significantly prolonged overall and progression free survival through improved disease control, the vast majority of patients remain incurable, and live with the burden of the disease itself and the cumulative side effects of treatments. Maintenance of quality of life presents challenges at all stages of the disease from diagnosis through the multiple phases of active treatment to the end of life. Written on behalf of the British Committee for Standards in Haematology (BCSH) and the UK Myeloma Forum (UKMF), these evidence based guidelines summarize the current national consensus for supportive and symptomatic care in multiple myeloma in the following areas; pain management, peripheral neuropathy, skeletal complications, infection, anaemia, haemostasis and thrombosis, sedation, fatigue, nausea, vomiting, anorexia, constipation, diarrhoea, mucositis, bisphosphonate-induced osteonecrosis of the jaw, complementary therapies, holistic needs assessment and end of life care. Although most aspects of supportive care can be supervised by haematology teams primarily responsible for patients with multiple myeloma, multidisciplinary collaboration involving specialists in palliative medicine, pain management, radiotherapy and surgical specialities is essential, and guidance is provided for appropriate interdisciplinary referral. These guidelines should be read in conjunction with the BCSH/UKMF Guidelines for the Diagnosis and Management of Multiple Myeloma 2011.     

Reevaluation of the interaction between HLA–DRB1 shared epitope alleles,PTPN22, and smoking in determining susceptibility to autoantibody‐positive and autoantibody‐negative rheumatoid arthritis in a large UK Caucasian population

Objective

To define interactions between the HLA–DRB1 shared epitope (SE), PTPN22, and smoking in cyclic citrullinated peptide (CCP) antibody– and rheumatoid factor (RF)–positive and –negative rheumatoid arthritis (RA).

Methods

Data on ∼5,000 RA patients and ∼3,700 healthy controls recruited from 6 centers in the UK were analyzed; not all centers had both genotype data and smoking data available for study. The magnitude of association was assessed in autoantibody‐positive and ‐negative subgroups. The effect of smoking on antibody status among cases was assessed following adjustment for year of birth and center, using Mantel‐Haenszel analysis. Analyses of the combined effects of PTPN22, HLA–DRB1 SE, and smoking were performed using additive and multiplicative models of interaction within a logistic regression framework.

Results

The combined effects of PTPN22, HLA–DRB1 SE, and smoking were defined, with no evidence of departure from a multiplicative model. Within the case population, all 3 factors were independently associated with the generation of CCP antibodies (odds ratio [OR] 11.1, P < 0.0001), whereas only HLA–DRB1 SE and smoking were independently associated with RF production (OR 4.4, P < 0.0001). There was some evidence of increasing likelihood of antibody positivity with heavier smoking. Finally, we demonstrated that smoking was associated with the generation of both CCP and RF antibodies (OR 1.7, P = 0.0001).

Conclusion

PTPN22 appears to be primarily associated with anticitrulline autoimmunity, whereas HLA–DRB1 SE is independently associated with RF. This study has confirmed associations of specific gene–environment combinations with a substantially increased risk of developing RA. Further work is needed to determine how these data can be used to inform clinical practice.

     

Optimizing the management of patients with spinal myeloma disease

Myeloma is one of the most common malignancies that results in osteolytic lesions of the spine. Complications, including pathological fractures of the vertebrae and spinal cord compression, may cause severe pain, deformity and neurological sequelae. They may also have significant consequences for quality of life and prognosis for patients. For patients with known or newly diagnosed myeloma presenting with persistent back or radicular pain/weakness, early diagnosis of spinal myeloma disease is therefore essential to treat and prevent further deterioration. Magnetic resonance imaging is the initial imaging modality of choice for the evaluation of spinal disease. Treatment of the underlying malignancy with systemic chemotherapy together with supportive bisphosphonate treatment reduces further vertebral damage. Additional interventions such as cement augmentation, radiotherapy, or surgery are often necessary to prevent, treat and control spinal complications. However, optimal management is dependent on the individual nature of the spinal involvement and requires careful assessment and appropriate intervention throughout. This article reviews the treatment and management options for spinal myeloma disease and highlights the value of defined pathways to enable the proper management of patients affected by it.     

UK prospective diabetes study (UKPDS)

Summary The UK Prospective Diabetes Study (UKPDS) is a multi-centre, prospective, randomised, intervention trial of 5100 newly-diagnosed patients with Type 2 (non-insulin-dependent) diabetes mellitus which aims to determine whether improved blood glucose control will prevent complications and reduce the associated morbidity and mortality. Newly presenting Type 2 diabetic patients aged 25–65 years inclusive, median age 53 years, median body mass index 28 kg/m² and median fasting plasma glucose 11.3 mmol/l, were recruited and treated initially by diet. Ninety five percent remained hyperglycaemic (fasting plasma glucose > 6 mmol/l) and were randomly allocated to different therapies. In the main randomisation, those who were asymptomatic and had fasting plasma glucose under 15 mmol/l were allocated either to diet policy, or to active policy with either insulin or sulphonylurea aiming to reduce the fasting plasma glucose to under 6 mmol/l. Over 3 years, the median fasting plasma glucose in those allocated to diet policy was 8.9 mmol/l compared with 7.0 mmol/l in those allocated to active policy. The Hypertension in Diabetes Study has been included in a factorial design to assess whether improved blood pressure control will be advantageous. Patients with blood pressure 160/90 mm Hg were randomly allocated to tight control aiming for < 150/85 mm Hg with either an angiotensin-converting enzyme inhibitor or a Beta-blocker or to less tight control aiming for < 200/105 mm Hg. The endpoints of the studies are major clinical events which affect the life and well-being of patients, such as heart attacks, angina, strokes, amputations, blindness and renal failure. To date, 728 patients have had at least one clinical endpoint. Surrogate endpoints include indices of macrovascular and microvascular disease detected by ECG with Minnesota Coding, retinal colour photography and microalbuminuria. The studies also aim to evaluate potential risk factors for the development of diabetic complications such as smoking, obesity, central adiposity, plasma LDL-and HDL-cholesterol, triglyceride, insulin, urate and other biochemical variables. The studies are planned to terminate in 1994, with a median follow-up of 9 years (range 3–16 years) for the glucose study and 5 years (range 2–6 years) for the hypertension study.