High throughput screening aids clinical decision-making in refractory acute myeloid leukaemia.

BACKGROUND: Despite advances in therapeutics for adverse-risk acute myeloid leukaemia (AML), overall survival remains poor, especially in refractory disease. Comprehensive tumour profiling and pre-clinical drug testing can identify effective personalised therapies. CASE: We describe a case of ETV6-MECOM fusion-positive refractory AML, where molecular analysis and in vitro high throughput drug screening identified a tolerable, novel targeted therapy and provided rationale for avoiding what could have been a toxic treatment regimen. Ruxolitinib combined with hydroxyurea led to disease control and enhanced quality-of-life in a patient unsuitable for intensified chemotherapy or allogeneic stem cell transplantation. CONCLUSION: This case report demonstrates the feasibility and role of combination pre-clinical high throughput screening to aid decision making in high-risk leukaemia. It also demonstrates the role a JAK1/2 inhibitor can have in the palliative setting in select patients with AML.

Health-care workers' understanding of and barriers to palliative care services to Aboriginal children with cancer.

AIM: To identify barriers in the understanding and provision of optimal palliative care to Aboriginal children with cancer by health-care staff, with the aim to support education and training that highlights the importance of cultural, physical and spiritual needs at end-of-life. METHODS: Medical and nursing staff working in Departments of Palliative Care, Metabolic Medicine and Haematology/Oncology at the Women's and Children's Hospital in Adelaide, South Australia, were asked to complete a survey regarding their experience in treating Aboriginal children receiving palliative care. The survey addressed the understanding of cultural and spiritual needs, barriers encountered and opinions for improved services. RESULTS: The survey was completed by 34 participants. 91.2% (n = 31) had provided care to Aboriginal children who were receiving care during palliative and end-of-life phases for a diagnosis of cancer, 58.8% (n = 20) of which had supported children returning home. Only 23.5% of participants reported comfort in communicating about spiritual/cultural needs with patients and families. There was minimal previous exposure to education (17.6%), yet all participants were interested in future education opportunities. CONCLUSION: This study highlights a paucity in understanding and comfort among health-care workers in treating Aboriginal children at end-of-life. New models, including the training of staff, educational resources and involvement of Aboriginal health-care workers, may improve care.

Marginal traction alopecia severity score: development and test of reliability.

BACKGROUND: Traction alopecia (TA) is common in African females. Although hairstyles are thought to be causal, the contribution of individual hairstyling variables to TA severity has not been quantified. The aim of the current study was to develop a severity scoring system (M-TAS score) for marginal TA, the commonest form of this disorder, and to test its reliability. METHOD: The margins of the scalp were divided into anterior and posterior with an imaginary line joining the tips of both ears. The anterior and posterior hairlines were further divided into three using the temporalis muscles and mastoid processes at the hairline as landmarks, respectively. Each examiner assessed each of the six areas. If any were found to have TA, the severity was scored using an examiner assessed system (tested once) or a picture matched score (tested twice). Ten and eight female patients with TA of varying severity were assessed by 11 and 9 examiners (dermatologists, dermatology trainees, and nurses), respectively. RESULTS: The intraclass correlation coefficient (ICC) for interobserver agreement was larger with photograph-matched scores than with examiner estimated scores reaching substantial (0.61-0.80) and excellent (0.81-100) agreement for both anterior and posterior scores irrespective of level of skill of examiner. The ICC for intraobserver agreement with the photograph matched scores was 0.99. LIMITATIONS: The diagnosis of normal margin was excellent for the anterior yet poor for the posterior margin with photograph scores. The M-TAS score is not for diagnosis but to assess severity. CONCLUSION: The photograph-based M-TAS score requires validation with larger samples but could be a useful research tool for elucidating disease prevalence and determinants of TA as well for monitoring response to treatment.

Hairdressing and the prevalence of scalp disease in African adults.

BACKGROUND: Anecdotal reports suggest that certain scalp disorders are common in Africans and may be associated with hairstyles. OBJECTIVES: This study of 874 African adults in Cape Town was performed to test this hypothesis. METHODS: A questionnaire was administered and scalp examinations performed, after ethics approval. RESULTS: Participants included 30.9% men and 69.1% women (median age 36.1 years, range 18-99). Most men had natural hair: 91.7% vs. 24.3% women. The majority of men had recent haircuts (< 4 weeks): 74.8% vs. 9.9% women. The overall prevalence of acne (folliculitis) keloidalis nuchae (AKN) was 3.5%: higher in men than women (10.5% vs. 0.3%). AKN prevalence was not associated with whether clippers or blades were used. However, it was associated with haircut symptoms. Haircut-associated symptoms, i.e. at least one episode of transient pimples (or crusts) and bleeding (however small) were reported in 37% and 18.9% of men, respectively. The latter may have implications for disease transmission. Most women (58.7%) had chemically treated hair (49.2% relaxed and 9.6% permed hair) vs. 2.3% men. The prevalences of traction alopecia (TA) and central centrifugal cicatricial alopecia (CCCA) were 22.6% and 1.9%: higher in women (31.7% vs. 2.2% and 2.7% vs. 0%, respectively). CCCA was highest in women > 50 years (6.7% vs. 1.2%). TA prevalence was highest if the usual hairstyle was extensions attached to relaxed hair (48%). CONCLUSION: We found associations between specific scalp diseases, hairstyles, gender, and age. These associations need further study, better to elucidate determinants and to improve disease prevention and treatment.

Hairdressing is associated with scalp disease in African schoolchildren.

BACKGROUND: Anecdotal reports suggest that certain disorders are common in African hair and may be associated with hairstyles. OBJECTIVES: A cross-sectional study of 1042 schoolchildren was performed to test this hypothesis. METHODS: A questionnaire was administered and scalp examinations performed, after ethics approval. RESULTS: Participants included 45% boys and 55% girls. The majority of boys, 72.8%, kept natural hair with frequent haircuts (within 4 weeks). The prevalence of acne (folliculitis) keloidalis nuchae (AKN) was 0.67% in the whole group and highest (4.7%) in boys in the final year of high school, all of whom had frequent haircuts. The majority of girls (78.4%) had chemically relaxed hair, which was usually combed back or tied in ponytails, vs. 8.6% of boys. Traction alopecia (TA) was significantly more common with relaxed than natural hair, with an overall prevalence of 9.4% (98 of 1042) and of 17.1% in girls, in whom it increased with age from 8.6% in the first year of school to 21.7% in the last year of high school. The proportion with TA in participants with a history of braids on natural hair was lower (22.9%), but not significantly, than among those with a history of braids on relaxed hair (32.1%). No cases of central centrifugal cicatricial alopecia were identified. CONCLUSIONS: We found associations between hairstyle and disease in our population of schoolchildren. AKN appears to be associated with frequently cut natural hair and TA with relaxed hair. These associations need further study for purposes of disease prevention.

Major flares in women with SLE on combined oral contraception.

Two recent trials concluded that the use of oral contraceptives (OC) did not induce flares in lupus patients. We record our experience with OC in patients with stable lupus. Eight patients were enrolled in an open trial. Six received a combined contraceptive pill and two were allocated to the control arm. During a 12 month follow-up, 3 patients in the active arm experienced 4 major flares. One patient died as a result of uncontrolled disease complicated by sepsis. At this point, we abandoned the trial. The 2 patients in the control arm experienced no disease exacerbation during the 7 months of observation. We would urge that patients who are placed on OC be closely monitored.

Ovarian reserve tests for predicting fertility outcomes for assisted reproductive technology: the International Systematic Collaboration of Ovarian Reserve Evaluation protocol for a systematic review of ovarian reserve test accuracy.

BACKGROUND: The presence of a wide range of tests of ovarian reserve suggests that no single test provides a sufficiently accurate result. Many tests are used without reference to an evidence base. So far, individual studies conducted on these tests are too small to give precise estimates of prognostic accuracy. OBJECTIVES: To systematically assess the accuracy of the available tests of ovarian reserve in terms of prediction of fertility outcomes. SEARCH STRATEGY: The search will be conducted using the name of the respective index test being studied (as listed on the MESH database), if more than 2000 citations are listed, 'ovary' and or 'ovarian', 'fertility' and or 'reserve' will be combined with the original search term as required. Studies of the accuracy of tests of ovarian reserve will be obtained without language restrictions from 1980 to 2005 using the following electronic databases and Ovid software: MEDLINE, EMBASE, PUBmed, Biological extracts, Pascal, Cochrane Library (CDSR, DARE, CCTR, HTA), Best Evidence databases, SCISEARCH, Conference Proceedings (ISI Proceedings, Healthstar, Current Contents, Science Citation Index, Cancerlit and Econlit and NHS Economic Evaluation database. The National Research Register, the Medical Research Council's Clinical Trials Register, MEDION, DARE, and the US Clinical Trials register. SELECTION CRITERIA: Studies will be selected if accuracy of tests are compared with a reference standard and include data that can be abstracted into a two-by-two table to calculate sensitivity and specificity. The studies to be included in this review will examine one of the following index 'tests' within a study population of women undergoing assisted reproductive technology: * Clinical variables--age, history of cancelled cycles. * Basal blood tests--follicle-stimulating hormone (FSH), lutenising hormone (LH), FSH:LH ratios, estradiol (E(2)), inhibin A and B, progesterone (P(4)), P(4):E(2) ratios, antimullerian hormone, testosterone, vascular endothelial growth factor, insulin-like growth factor-1:insulin-like growth factor binding protein-1 ratios. * Dynamic tests--clomiphene citrate challenge test, gonadotropin analogue stimulating test, exogenous FSH ovarian reserve test. * Ultrasound tests-antral follicle count, ovarian volume, ovarian stromal peak systolic velocity, including waveform and pulsatility index, ovarian follicular vascularity. * Histology--ovarian biopsy. Data collection and analysis Two independent reviewers will perform quality assessment and data extraction. Prognostic accuracy will be determined by calculating positive and negative likelihood ratios for the following outcomes or reference standards: live birth, ongoing pregnancy, clinical pregnancy, biochemical pregnancy, embryos available for transfer, eggs obtained at oocyte retrieval, cycles cancelled prior to oocyte retrieval. Main results and conclusions N/A.

Drugs for discoid lupus erythematosus.

BACKGROUND: Discoid lupus erythematosus is a chronic form of cutaneous (skin) lupus which can cause permanent scarring if treatment is inadequate. Many drugs have been used to treat this disease and some of these are potentially very toxic. OBJECTIVES: To assess the effects of drugs for discoid lupus erythematosus. SEARCH STRATEGY: We searched the Cochrane Clinical Trials Register (December 1999), MEDLINE (January 1966 to December 1999), EMBASE (January 1980 to January 2000), and the reference lists of relevant reviews. Index Medicus (1956 to 1966) was handsearched and 7 experts in the field were approached for information about unpublished trials. SELECTION CRITERIA: Randomised trials of drugs to treat people with discoid lupus erythematosus. Drugs included in the search were azathioprine, chloroquine, clofazimine, corticosteroids, (oral and topical), dapsone, gold, interferon alpha-2a, methotrexate, phenytoin, retinoids, sulphasalazine and thalidomide. DATA COLLECTION AND ANALYSIS: Two reviewers independently examined each retrieved study for eligibility. MAIN RESULTS: Two trials involving 136 participants were included. In a cross-over study of twelve weeks duration fluocinonide 0.05% cream (a potent topical corticosteroid), appeared to be markedly better than hydrocortisone 1% cream ( a mild corticosteroid). Clearing or excellent improvement was seen in 27% of people using fluocinonide and in 10% of those using hydrocortisone, giving a 17% absolute benefit in favour of fluocinonide (95% CI 4.5 to 29.5% and NNT 6). In the second trial, hydroxychloroquine was compared with acitretin in 58 people. There was marked improvement or clearing in 46% of people using acitretin and in 50% of those on hydroxychloroquine, a nonsignificant 4% absolute gain with hydroxychloroquine (95%CI -23% to 30%). The adverse effects were more frequent and more severe in the acitretin group. REVIEWER'S CONCLUSIONS: Fluocinonide cream may be more effective than hydrocortisone in treating people with discoid lupus erythematosus. Hydroxychloroquine and acitretin appear to be of equal efficacy, although adverse effects are more frequent and more severe with acitretin. There is not enough reliable evidence about other drugs used to treat discoid lupus erythematosus.

Cutaneous leucocytoclastic vasculitis: a clinical and aetiological study.

Cutaneous vasculitis may be the presenting sign in many different clinical disorders. The aetiology and clinical and laboratory findings were recorded in 69 consecutive patients with cutaneous leucocytoclastic vasculitis. Underlying connective tissue disease or malignancy was found in 19 patients. Evidence of recent streptococcal infection was detected in 24 patients. Application of the classification criteria proposed by the American College of Rheumatology (ACR) identified 35 patients with Henoch-Schonlein purpura (HSP) and 42 with hypersensitivity vasculitis (HSV). Thirty-three subjects fulfilled criteria for both HSP and HSV.

Loss of trabecular bone mineral density in systemic lupus erythematosus.

OBJECTIVE: To evaluate trabecular bone mineral density (BMD) in young ambulatory female patients with systemic lupus erythematosus (SLE). METHODS: Bone mineral density (gm/cm2) at the lumbar vertebrae (L1-L4) and at the left femur (neck, trochanter, intertrochanter, and Ward's triangle) was measured by dual x-ray absorptiometry in 46 SLE patients (mean age 31 years, mean disease duration 76 months) and in 108 healthy female controls (mean age 32 years). Twenty-two of the SLE patients were receiving corticosteroids (CS) at the time of the study. RESULTS: Lumbar BMD in the SLE patients was less severely reduced than was BMD at the femoral sites, but the SLE group was closer to the lumbar fracture threshold of 0.812 gm/cm2 than was the control group (P = 0.0009). There were no significant differences between the SLE patients currently being treated with corticosteroids and those who were not (P > 0.3). BMD at Ward's triangle and at the femoral neck was not significantly reduced in the SLE patients. Total femoral BMD had a sensitivity of 76% and specificity of 62% in differentiating the SLE group from the controls. The positive predictive value was 61% and the negative predictive value was 89%. The prevalence of osteopenia in the SLE patients was 25%. CONCLUSION: SLE causes significant trabecular bone loss, which is not due to corticosteroid therapy.

[Rheumatism--a disease of civilization? Incidence of inflammatory rheumatic diseases in South Africa]. / Rheuma--eine Zivilisationskrankheit? Häufigkeit entzündlicher rheumatischer Krankheiten in Südafrika.

The population of Southern Africa is currently estimated at least 40 million and comprises people of 3 major--groups Negroid, Khoisan and Caucasoid. In addition to these, there are also smaller groups whose origin is Asiatic or Oriental, and a mixed group (coloured) which has resulted from the miscegenation between the Negroid-Caucasoid and other groups [1]. This great diversity of peoples and cultures permits unique opportunities for studies in comparative medicine which may provide valuable information about the pathogenesis and natural history of disease. The rheumatic diseases have not been looked at in this comparative way until recently. This is, in part, because the demands of infective and nutritional diseases on medical services have tended to overshadow the rheumatic diseases. This paper reviews the investigation of inflammatory rheumatic disease in Southern Africa.

The epidemiology of rheumatic disease in a rural and an urban population over the age of 65 years.

The prevalence of rheumatic disease in subjects over 65 years of age was measured in a rural and an urban population in the Western Cape by means of a questionnaire and a clinical/radiological investigation. The completion rates were 88% and 85% for the rural and the urban groups respectively. Recall of previous arthritis/backache and shoulder pain/shoulder disease and osteo-arthrosis was more frequent in the urban population, and osteoporosis occurred with equal frequency in both populations. The relevance of these findings is discussed in terms of their actual and potential impact on the treatment of elderly persons.

False-positive test results for syphilis in relatives of a patient with systemic lupus erythematosus.

In a family of nine members, two had systemic lupus erythematosus and seven positive serological test results for syphilis. None of the affected subjects had a history or physical signs of syphilis, but two had positive results to the Treponema pallidum immobilisation test. The explanation for these findings is not known, but possibily they were all false-positive reactions.

Erythrocyte electrolyte content and sodium efflux in chronic renal failure.

The cation content of the eythrocyte was studied in 36 patients with chronic renal failure; A normal or high erythrocyte potassium was found. Erythrocytes sodium values showed a wide range, from very high to very low, and the rate constant for Na efflux was found to be higher than normal. The interpretation of these findings is discussed. It is suggested that the higher than normal. The interpretation of these findings is discussed. It is suggested that the high erythrocyte K content may reflect abnormal total body K, may be explained on the basis of a young red cell population or may be related to abnormal function of the erythrocyte cation pump. It is probable that the development of these changes in chronic renal failure depends on many factors.

Multicentric reticulohistiocytosis. A case report.

A patient with multicentric reticulohistiocytosis is reported, and the clinical and pathological features of the condition are discussed.