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Summary: Multiple myeloma is associated with significant early morbidity and mortality, with considerable end organ damage often present at diagnosis. The Tackling EArly Morbidity and Mortality in Multiple Myeloma (TEAMM) trial was used to evaluate routes to diagnosis in patients with myeloma and the relationship between diagnostic pathways, time to diagnosis and disease severity. A total of 915 participants were included in the study. Fifty‐one per cent were diagnosed by direct referral from primary care to haematology; 29% were diagnosed via acute services and 20% were referred via other secondary care specialties. Patients diagnosed via other secondary care specialties had a longer diagnostic interval (median 120 days vs. 59 days) without an increase in features of severe disease, suggesting they had a relatively indolent disease. Marked intrahospital delay suggests possible scope for improvement. A quarter of those diagnosed through acute services reported >30 days from initial hospital consultation to haematology assessment. Participants diagnosed through acute services had poorer performance status (P < 0·0001) and higher burden of end organ damage (P < 0·0001) with no difference in the overall length of diagnostic pathway compared to those diagnosed by direct referral (median 59 days). This suggests that advanced disease in patients presenting through acute services predominantly reflects disease aggression. [ABSTRACT FROM AUTHOR]

Background Lack of agreement about criteria and terminology for children's language problems affects access to services as well as hindering research and practice. We report the second phase of a study using an online Delphi method to address these issues. In the first phase, we focused on criteria for language disorder. Here we consider terminology. Methods The Delphi method is an iterative process in which an initial set of statements is rated by a panel of experts, who then have the opportunity to view anonymised ratings from other panel members. On this basis they can either revise their views or make a case for their position. The statements are then revised based on panel feedback, and again rated by and commented on by the panel. In this study, feedback from a second round was used to prepare a final set of statements in narrative form. The panel included 57 individuals representing a range of professions and nationalities. Results We achieved at least 78% agreement for 19 of 21 statements within two rounds of ratings. These were collapsed into 12 statements for the final consensus reported here. The term 'Language Disorder' is recommended to refer to a profile of difficulties that causes functional impairment in everyday life and is associated with poor prognosis. The term, 'Developmental Language Disorder' ( DLD) was endorsed for use when the language disorder was not associated with a known biomedical aetiology. It was also agreed that (a) presence of risk factors (neurobiological or environmental) does not preclude a diagnosis of DLD, (b) DLD can co-occur with other neurodevelopmental disorders (e.g. ADHD) and (c) DLD does not require a mismatch between verbal and nonverbal ability. Conclusions This Delphi exercise highlights reasons for disagreements about terminology for language disorders and proposes standard definitions and nomenclature. [ABSTRACT FROM AUTHOR]

Background There are variations in the proportions of head and neck cancers caused by the human papillomavirus (HPV) between countries and regions. It is unclear if these are true variations or due to different study designs and assays. Methods We tested formalin-fixed paraffin-embedded diagnostic biopsies for p16 immunohistochemistry and HPV-DNA (by polymerase chain reaction [PCR] and in situ hybridization [ISH]) using validated protocols on samples from 801 patients with head and neck cancer recruited prospectively between 2006 and 2011 in 4 randomized controlled trials (RCTs). Results Twenty-one percent of patients (170 of 801) showed both HPV-DNA and p16-positivity, detected almost exclusively in oropharyngeal cancer (55%; 15 of 302); and only 1% of the patients (5 of 499) with nonoropharyngeal cancer were HPV positive. HPV-positive oropharyngeal cancer differed between Western and Eastern Europe (37%, 155 of 422 vs 6%, 8 of 144; p < .0001) and between Western Europe and Asia (37% vs 2%; 4 of 217; p < .0001). Other independent determinants of HPV positivity were tumor site and smoking. Conclusion This is the first study to establish geographic variability as an independent risk factor in HPV-positive oropharyngeal cancer prevalence, with higher prevalence in Western Europe. © 2016 The Authors Head & Neck Published by Wiley Periodicals, Inc. Head Neck 38: E1863-E1869, 2016 [ABSTRACT FROM AUTHOR]

The article discusses the teaching strategy to undergraduate students with the use of peer-reviewed journals. Topics mentioned include the undergraduate students lack of direct experience with academic journals, the clear understanding of where scholarly results can be found, and the learning about peer-reviewed journals while illustrating the use of citations and references.

Breast cancer can be classified into molecular sub-types that have distinct survival patterns. We evaluated the prognostic significance of breast cancer sub-types in a cohort of women taking part in the NEAT and BR9601 clinical trials comparing cyclophosphamide, methotrexate and fluorouracil (CMF) with ECMF (epirubicin and CMF). Furthermore, we evaluated whether the sub-types were predictive of the added benefit of epirubicin in these trials. Tumour tissue microarrays were stained and scored for ER, PR, HER2, EGFR and CK5/6. These were used to classify the tumours into six intrinsic sub-types. We used Cox regression to compare overall survival (OS), breast cancer-specific survival (BCSS) and relapse-free survival (RFS) in the different sub-groups. We also compared the effect of ECMF with CMF by sub-group. Immunohistochemistry data were available for 1,725 cases of whom 805 were luminal 1-basal negative. Median follow-up time was 7 years. The luminal 1-basal negative tumours were associated with the best prognosis in five years after surgery and the HER2-like tumours were associated with the poorest prognosis. There was little evidence for significant heterogeneity of this effect by tumour sub-type (OS p = 0.40, BCSS p = 0.53 RFS p = 0.50) - the largest additional benefit of epirubicin was in women with tumours of the 5-negative phenotype (OS HR = 0.39 95% CI: 0.21-0.73) and the smallest was in Luminal 1-basal negative tumours (OS HR = 0.86 95% CI: 0.64-1.16). We confirmed that breast cancer sub-types show distinct behaviour with differences in short- and long-term survival. The benefit of ECMF over CMF was statistically similar in all disease sub-types. [ABSTRACT FROM AUTHOR]

Objectives To compare patient and tumour characteristics at presentation from two large bladder cancer cohorts, with recruitment separated by 15-20 years, To identify significant differences in the West Midlands' urothelial cancer of the bladder ( UCB) population during this period., Patients and Methods Data were collected prospectively from 1478 patients newly diagnosed with UCB in the West Midlands from January 1991 to June 1992 ( Cohort 1), and from 1168 patients newly diagnosed with UBC within the same region from December 2005 to April 2011 ( Cohort 2)., Gender, age, smoking history, and tumour grade, stage, type, multiplicity and size at presentation were compared using a Pearson chi-square test or Cochran- Armitage trend test, as appropriate., Result Cohort 2 had a higher proportion of male patients ( P = 0.021), elderly patients ( P < 0.001), grade 3 tumours ( P < 0.001), Ta/ T1 tumours ( P = 0.008), multiple tumours ( P < 0.001), and tumours of ≤2 cm in diameter ( P < 0.001)., Conclusions There were significant differences between the cohorts., These differences are potentially explained by an ageing population, changes in grading practices, improved awareness of important symptoms, improved cystoscopic technology, and reductions in treatment delays., Regional cohorts remain important for identifying changes in tumour and patient characteristics that may influence disease management in the UK and beyond. [ABSTRACT FROM AUTHOR]

Syndecan-1 (CD138) is a heparin sulphate proteoglycan that is over expressed on the surface of both normal and malignant plasma cells and actively shed from the cell surface (soluble syndecan-1). Soluble syndecan-1 has been shown to be an independent prognostic factor in myeloma but its role in prognostic classification requires further investigation. We have retrospectively measured soluble syndecan-1 in 324 presentation samples and 154 plateau phase samples from the UK Medical Research Council Myeloma VIth trial. Log-rank analysis showed that the presentation value of soluble syndecan-1 is a highly significant prognostic factor when assessing survival from entry ( χ2 = 14·92, P < 0·0001) and remains an important independent prognostic factor when considered in Cox regression models ( P ≤ 0·02) with known independent factors. The magnitude of fall in soluble syndecan-1 from presentation to plateau also had prognostic value when assessing overall survival from plateau ( χ2 = 3·79, P = 0·05). In conclusion, this large study confirms that soluble syndecan-1 level is a powerful independent prognostic factor both at diagnosis and at plateau phase. [ABSTRACT FROM AUTHOR]

To investigate the relationship between deprivation, delay and survival from bladder cancer in the West Midlands, as socio-economic deprivation is associated with worse survival in many malignancies, and it has been suggested that treatment differences and delay in seeking care are major contributing causes. Data were prospectively collected on 1537 newly diagnosed cases of urothelial cancer presenting in the West Midlands between January 1991 and June 1992. Survival was censored at 31 July 2000, when 785 (51%) patients had died. The influence of deprivation on survival was explored using cause-specific and all-cause mortality. Patients in less affluent groups had significantly worse survival than patients in more affluent groups when considering deaths from all causes ( P = 0.02), which held true when adjusting for independent prognostic factors (age, smoking history, and tumour grade, stage, type and size). Bladder cancer-specific mortality showed no significant difference between socio-economic groups ( P = 0.30). Socio-economic deprivation is a significant predictor of survival when death from all causes is considered. However, this does not hold true for bladder cancer-specific death. The perceived differences in treatment and delay between socio-economic groups do not seem to occur for bladder cancer in the West Midlands. [ABSTRACT FROM AUTHOR]

Oral clodronate (1600 mg/d) has been shown to significantly reduce the incidence of skeletal complications in multiple myeloma. Preliminary analysis of a double-blind placebo-controlled trial of this treatment indicated that clodronate might prolong survival in patients without vertebral fractures at presentation. This issue was re-examined after further follow-up of the patients recruited into the Medical Research Council (MRC) VIth Myeloma Study. The trial examined the effects of clodronate on the natural history of skeletal disease in multiple myeloma; 619 patients were randomized between June 1986 and May 1992 commencing 15 d after the start of ABCM [adriamycin, BCNU (carmustine), cyclophosphamide, melphalan] chemotherapy or 43 d after ABCMP (ABCM + prenisolone); 535 patients who received clodronate or placebo were included in the analysis. The presence or absence of spinal fractures was assessed centrally from spinal X-rays; long-bone fractures were assessed locally. With a median follow-up of 8·6 years, there was no overall significant difference in survival between the two treatment groups (O/E, χ2 = 0·78, P = 0·38). Among the subgroup of 153 patients with no skeletal fractures at presentation there was a significant survival advantage (O/E, χ2 = 7·52, P = 0·006) in favour of the 73 patients receiving clodronate, with median survivals being, respectively, 59 months (95% CI 43–71 months) and 37 months (95% CI 31–52 months), and 5-year survivals being 46% and 35%. The original analysis of this study shows that there is a benefit in taking 1600 mg clodronate daily for patients with myelomatosis to prevent the development of new skeletal disease. Bearing in mind the limitations of subgroup analysis, the present study indicates that treatment may prolong survival in patients without overt skeletal disease at diagnosis. These observations, however, require confirmation in prospective clinical trials. [ABSTRACT FROM AUTHOR]

Plateau phase has been achieved in 64% of all newly diagnosed patients with multiple myeloma treated with the ABCM (adriamycin, BiCNU, cyclophosphamide and melphalan) regimen in the Medical Research Council (MRC) trials; this stable clinical stage of the disease is associated with no more than minimal symptoms. Several studies have found that α-interferon (α-IFN) maintenance therapy increases the duration of plateau phase, but it is less clear if this translates into prolonged survival. We report the effect of α-IFN on the duration of plateau phase and overall survival in a trial with 284 patients who were randomized to receive α2b-IFN (Intron-A) or no maintenance therapy during first plateau phase. The minimum follow-up after randomization was 21 months. There was no significant difference in the overall survival between the two treatment groups (χ2 = 0.32, P = 0.57). There was a trend towards longer relapse-free survival in the patients allocated α-IFN, but this trend to longer plateau phase was not statistically significant (χ2 = 1.62, P = 0.2). Disease progression at relapse on α-IFN appears to be more severe with greater elevations from plateau levels of serum paraprotein (P = 0.06) and β2-microglobulin (P = 0.03) levels. Physicians tended to start chemotherapy sooner after diagnosis of relapse when patients had received α-IFN (P = 0.16). Although, in common with most other studies, there is a trend for patients treated with α-IFN to have a longer plateau phase, this is counteracted by morbidity attributable to the treatment and a somewhat shortened survival post relapse. Meta-analysis of interferon trials is required to assess whether the minor trend for longer survival in patients maintained on α-IFN found in some studies is significant and, if so, the extent of this advantage. [ABSTRACT FROM AUTHOR]

The article offers information on bezafibrate and medroxyprogesterone acetate related to endemic Burkitt lymphoma in Malawi. It mentions that endemic burkitt lymphoma (eBL) lead to childhood cancers from malaria. It states that medroxyprogesterone acetate (MPA) has potent anti-eBL activity and that provide affordable, non-toxic therapy .