Use of the day 6 bone marrow to alter remission induction therapy in patients with acute myeloid leukaemia: a leukemia intergroup study

Patients with acute myeloid leukaemia who fail to show substantial bone marrow cytoreduction by day 6 of induction therapy enter complete remission (CR) less frequently than patients with good bone marrow leukaemic cytoreduction. The objective of the current study was to determine whether an increase in the intensity of therapy on days 8, 9 and 10 ('augmentation' of remission induction therapy) for patients with poor bone marrow cytoreduction detected in the day 6 bone marrow could improve the complete remission rate without increasing the number of toxic deaths. Patients from six centres were entered and treated with standard dose ara-C for 7 or 10 d and an anthracycline for the first 3 d. Patients aged less than 60 years and with greater than 30% bone marrow biopsy cellularity or greater than 10% abnormal cells on the aspirate obtained 6 d after the start of therapy were augmented with cytosine arabinoside 3 g/m2 every 12 h on days 8, 9 and 10. Therapy was augmented in 116 of the 252 patients less than 60 years. There was a highly statistically significant difference between augmented and nonaugmented patients (P less than 0.001) for the per cent biopsy cellularity and per cent abnormal cells in the day 6 marrow. The CR rate for augmented patients was 69% and for nonaugmented patients 60% suggesting that augmentation therapy abrogated the prognostic significance of more extensive residual leukaemia in the day 6 bone marrow. The results suggest that augmentation of remission induction for patients with poor bone marrow cytoreduction detected 6 d after initiation of therapy, may salvage patients who are destined to fail remission induction because of resistant disease without producing excessive toxicity.     

High-dose cytosine arabinoside in the treatment of preleukemic disorders: a leukemia intergroup study

Fifteen patients with myelodysplastic/myeloproliferative disorders were treated with high-dose cytosine arabinoside therapy. While severe toxicity was produced in every patient, only two of the 15 patients entered complete remission and two achieved partial remission status. The therapeutic responses were confined to patients who had severe myelofibrosis of apparently recent onset.     

Treatment of osteoporosis: facing the challenges in the Asia‐Pacific

The prevalence of osteoporosis and fractures is projected to increase rapidly in the Asia‐Pacific region in coming decades. At the societal level, healthcare providers will face the challenges of paucity of information, lack of awareness among physicians, resource constraints, lack of organization, absence of policies of cost reimbursement, insufficient representation of the problem in curricula and lack of effective, inexpensive and convenient therapy. Poverty, illiteracy, lack of awareness and interest in future quality of life, and co‐morbidities with seemingly greater importance, will all act as challenges at the level of individual patients. Lack of compliance is a function of lack of awareness and motivation, cost, complexity of administration, side‐effects and absence of immediately perceivable benefit. The challenges may be overcome through systematic collection of data, formation or activation of national osteoporosis planning and coordinating groups, development of national guidelines, programs of education of healthcare providers, patients and the general public, adoption of a population‐based prevention strategy, cost‐effective opportunistic screening using clinical decision rules like the osteoporosis self‐assessment tool for Asians, use of the fracture risk assessment tool for therapeutic decision‐making, giving due emphasis to the problem in curricula and development of mechanisms for cost reimbursement. The Asia‐Pacific League of Associations for Rheumatology may take a lead in stimulating, organizing and coordinating these activities.     

Use of Faropenem as an Indicator of Carbapenemase Activity in the Enterobacteriaceae

The aim of this study was to determine the ability of a disc susceptibility test using faropenem (10 μg) to predict carbapenemase activity in Enterobacteriaceae. A collection of 166 isolates of carbapenemase-producing Enterobacteriaceae (CPE) and 82 isolates of Enterobacteriaceae that produced other β-lactamases was compiled from diverse sources. Disc susceptibility testing was performed using the CLSI/EUCAST methodology with discs of faropenem (10 μg), temocillin (30 μg), and four carbapenems (each 10 μg). A further prospective evaluation of the faropenem disc susceptibility test was performed using 205 consecutive isolates referred to a United Kingdom reference laboratory in parallel with molecular methods for carbapenemase detection. Of 166 isolates of CPE, 99% showed growth up to the edge of a 10-μg faropenem disc compared with only 6% of other β-lactamase producers (sensitivity, 99%; specificity, 94%). A “double zone” around 10-μg faropenem discs was frequently associated with OXA-48 producers. Of the carbapenems, the most useful agent was imipenem, where a zone diameter of ≤23 mm as a predictor of carbapenemase activity had a sensitivity of 99% and a specificity of 85%. The presence of no zone of inhibition around a 30-μg temocillin disc was a consistent feature of strains producing OXA-48 carbapenemase. For 205 isolates of Enterobacteriaceae referred to a United Kingdom reference laboratory, growth up to a 10-μg faropenem disc correctly identified 84 of 86 carbapenemase producers (98% sensitivity), with a specificity of 87%. Disc susceptibility testing using faropenem (10 μg) is a simple, convenient, and highly predictive screening test for carbapenemase-producing Enterobacteriaceae.     

Aberrant retropharyngeal (submucosal) internal carotid artery: an under-recognized, clinically significant variant

We present a case of a 71-year-old woman who was incidentally found to have aberrant retropharyngeal internal carotid artery, lying very close to the pharyngeal mucosa, on imaging. Radiologists, otolaryngologists and anaesthetists should be aware of this clinically significant variant which can result in life-threatening bleeding during procedures in the oral cavity or oropharynx.     

Joint ESCMID,FEMS, IDSA,ISID and SSI position paper on the fair handling of career breaks among physicians and scientists when assessing eligibility for early-career awards

BackgroundThough women increasingly make up the majority of medical-school and other science graduates, they remain a minority in academic biomedical settings, where they are less likely to hold leadership positions or be awarded research funding. A major factor is the career breaks that women disproportionately take to see to familial duties. They experience a related, but overlooked, hurdle upon their return: they are often too old to be eligible for ‘early-career researcher’ grants and ‘career-development’ awards, which are stepping stones to leadership positions in many institutions and which determine the demographics of their hierarchies for decades to come. Though age limits are imposed to protect young applicants from more experienced seniors, they have an unintended side effect of excluding returning workers, still disproportionately women, from the running.MethodsIn this joint effort by the European Society of Clinical Microbiology and Infectious Diseases, the Federation of European Microbiological Societies, the Infectious Disease Society of America, the International Society for Infectious Diseases and the Swiss Society for Infectious Diseases, we invited all European Congress of Clinical Microbiology and Infectious Diseases-affiliated medical societies and funding bodies to participate in a survey on current ‘early-career’ application restrictions and measures taken to provide protections for career breaks.RecommendationsThe following simple consensus recommendations are geared to funding bodies, academic societies and other organizations for the fair handling of eligibility for early-career awards: 1. Apply a professional, not physiological, age limit to applicants. 2. State clearly in the award announcement that career breaks will be factored into applicants' evaluations such that: ? Time absent is time extended: for every full-time equivalent of career break taken, the same full-time equivalent will be extended to the professional age limit. ? Opportunity costs will also be taken into account: people who take career breaks risk additional opportunity costs, with work that they did before the career break often being forgotten or poorly documented, particularly in bibliometric accounting. Although there is no standardized metric to measure additional opportunity costs, organizations should (a) keep in mind their existence when judging applicants' submissions, and (b) note clearly in the award announcement that opportunity costs of career breaks are also taken into account. 3. State clearly that further considerations can be undertaken, using more individualized criteria that are specific to the applicant population and the award in question.The working group welcomes feedback so that these recommendations can be improved and updated as needed.     

Chikungunya infection in Malaysia: Comparison with dengue infection in adults and predictors of persistent arthralgia

BackgroundChikungunya virus (CHIKV) and dengue virus (DENV) co-circulate in areas endemic with the Aedes mosquito vectors. Both viruses cause similar illnesses which may be difficult to distinguish clinically. CHIKV is also associated with persistent arthralgia.ObjectivesTo compare and describe factors which differentiate between DENV and CHIKV infections on presentation; and to describe predictors of persistent arthralgia in CHIKV patients.Study designPatients aged >14 years diagnosed with acute CHIKV and DENV infections in Kuala Lumpur, Malaysia were retrospectively identified. Clinical and laboratory data were obtained from medical records, and compared. CHIKV patients were telephoned 15–24 months later and interviewed about persistent symptoms. Logistic regression analysis was performed.ResultsA total of 53 CHIKV and 113 DENV patients were included. CHIKV patients were older and more likely to be female. CHIKV was independently associated with arthralgia and rash, while DENV was associated with myalgia, raised aspartate transaminase, and leucopaenia. Forty CHIKV patients were followed up, with a median duration of self-reported arthralgia of 3 months (range, 0–24 months). Eighteen (45%) had persistent arthralgia beyond 4 months, for which age >40 years was an independent predictor. At 1 year, 9 (22.5%) patients had arthralgia.ConclusionIn Kuala Lumpur, selected clinical and laboratory predictors help to distinguish between DENV and CHIKV infections. Persistent arthralgia was a frequent sequel of CHIKV infection in this cohort.