Periosteal Osteosarcoma: A Review of 17 Cases with Mean Follow-up of 52 Months

Purpose: Periosteal osteosarcomas are rare cartilage-rich bone tumours characterized by a juxtacortical eccentric position and are normally regarded oncologically as of intermediate to high grade.Their low incidence is mirrored by a small number of reported cases in the world literature. While there is general agreement that wide surgical excision is required, there is a paucity of evidence regarding adjuvant therapy. Previous reports have not indicated any consistent approach to this to allow appraisal

3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial

Background: Liraglutide 3·0 mg was shown to reduce bodyweight and improve glucose metabolism after the 56-week period of this trial, one of four trials in the SCALE programme. In the 3-year assessment of the SCALE Obesity and Prediabetes trial we aimed to evaluate the proportion of individuals with prediabetes who were diagnosed with type 2 diabetes. Methods: In this randomised, double-blind, placebo-controlled trial, adults with prediabetes and a body-mass index of at least 30 kg/m2, or at least 27 kg/m2 with comorbidities, were randomised 2:1, using a telephone or web-based system, to once-daily subcutaneous liraglutide 3·0 mg or matched placebo, as an adjunct to a reduced-calorie diet and increased physical activity. Time to diabetes onset by 160 weeks was the primary outcome, evaluated in all randomised treated individuals with at least one post-baseline assessment. The trial was conducted at 191 clinical research sites in 27 countries and is registered with ClinicalTrials.gov, number NCT01272219. Findings: The study ran between June 1, 2011, and March 2, 2015. We randomly assigned 2254 patients to receive liraglutide (n=1505) or placebo (n=749). 1128 (50%) participants completed the study up to week 160, after withdrawal of 714 (47%) participants in the liraglutide group and 412 (55%) participants in the placebo group. By week 160, 26 (2%) of 1472 individuals in the liraglutide group versus 46 (6%) of 738 in the placebo group were diagnosed with diabetes while on treatment. The mean time from randomisation to diagnosis was 99 (SD 47) weeks for the 26 individuals in the liraglutide group versus 87 (47) weeks for the 46 individuals in the placebo group. Taking the different diagnosis frequencies between the treatment groups into account, the time to onset of diabetes over 160 weeks among all randomised individuals was 2·7 times longer with liraglutide than with placebo (95% CI 1·9 to 3·9, p<0·0001), corresponding with a hazard ratio of 0·21 (95% CI 0·13–0·34). Liraglutide induced greater weight loss than placebo at week 160 (–6·1 [SD 7·3] vs −1·9% [6·3]; estimated treatment difference −4·3%, 95% CI −4·9 to −3·7, p<0·0001). Serious adverse events were reported by 227 (15%) of 1501 randomised treated individuals in the liraglutide group versus 96 (13%) of 747 individuals in the placebo group. Interpretation: In this trial, we provide results for 3 years of treatment, with the limitation that withdrawn individuals were not followed up after discontinuation. Liraglutide 3·0 mg might provide health benefits in terms of reduced risk of diabetes in individuals with obesity and prediabetes. Funding: Novo Nordisk, Denmark

Ten-year mortality, disease progression, and treatment-related side effects in men with localised prostate cancer from the ProtecT randomised controlled trial according to treatment received

Background The ProtecT trial reported intention-to-treat analysis of men with localised prostate cancer randomly allocated to active monitoring (AM), radical prostatectomy, and external beam radiotherapy. Objective To report outcomes according to treatment received in men in randomised and treatment choice cohorts. Design, setting, and participants This study focuses on secondary care. Men with clinically localised prostate cancer at one of nine UK centres were invited to participate in the treatment trial comparing AM, radical prostatectomy, and radiotherapy. Intervention Two cohorts included 1643 men who agreed to be randomised and 997 who declined randomisation and chose treatment. Outcome measurements and statistical analysis Analysis was carried out to assess mortality, metastasis and progression and health-related quality of life impacts on urinary, bowel, and sexual function using patient-reported outcome measures. Analysis was based on comparisons between groups defined by treatment received for both randomised and treatment choice cohorts in turn, with pooled estimates of intervention effect obtained using meta-analysis. Differences were estimated with adjustment for known prognostic factors using propensity scores. Results and limitations According to treatment received, more men receiving AM died of PCa (AM 1.85%, surgery 0.67%, radiotherapy 0.73%), whilst this difference remained consistent with chance in the randomised cohort (p = 0.08); stronger evidence was found in the exploratory analyses (randomised plus choice cohort) when AM was compared with the combined radical treatment group (p = 0.003). There was also strong evidence that metastasis (AM 5.6%, surgery 2.4%, radiotherapy 2.7%) and disease progression (AM 20.35%, surgery 5.87%, radiotherapy 6.62%) were more common in the AM group. Compared with AM, there were higher risks of sexual dysfunction (95% at 6 mo) and urinary incontinence (55% at 6 mo) after surgery, and of sexual dysfunction (88% at 6 mo) and bowel dysfunction (5% at 6 mo) after radiotherapy. The key limitations are the potential for bias when comparing groups defined by treatment received and changes in the protocol for AM during the lengthy follow-up required in trials of screen-detected PCa. Conclusions Analyses according to treatment received showed increased rates of disease-related events and lower rates of patient-reported harms in men managed by AM compared with men managed by radical treatment, and stronger evidence of greater PCa mortality in the AM group. Patient summary More than 95 out of every 100 men with low or intermediate risk localised prostate cancer do not die of prostate cancer within 10 yr, irrespective of whether treatment is by means of monitoring, surgery, or radiotherapy. Side effects on sexual and bladder function are better after active monitoring, but the risks of spreading of prostate cancer are more common

Functional and quality of life outcomes of localised prostate cancer treatments (prostate testing for cancer and treatment [ProtecT] study)

Objective To investigate the functional and quality of life (QoL) outcomes of treatments for localised prostate cancer and inform treatment decision-making. Patients and Methods Men aged 50–69 years diagnosed with localised prostate cancer by prostate-specific antigen testing and biopsies at nine UK centres in the Prostate Testing for Cancer and Treatment (ProtecT) trial were randomised to, or chose one of, three treatments. Of 2565 participants, 1135 men received active monitoring (AM), 750 a radical prostatectomy (RP), 603 external-beam radiotherapy (EBRT) with concurrent androgen-deprivation therapy (ADT) and 77 low-dose-rate brachytherapy (BT, not a randomised treatment). Patient-reported outcome measures (PROMs) completed annually for 6 years were analysed by initial treatment and censored for subsequent treatments. Mixed effects models were adjusted for baseline characteristics using propensity scores. Results Treatment-received analyses revealed different impacts of treatments over 6 years. Men remaining on AM experienced gradual declines in sexual and urinary function with age (e.g., increases in erectile dysfunction from 35% of men at baseline to 53% at 6 years and nocturia similarly from 20% to 38%). Radical treatment impacts were immediate and continued over 6 years. After RP, 95% of men reported erectile dysfunction persisting for 85% at 6 years, and after EBRT this was reported by 69% and 74%, respectively (P < 0.001 compared with AM). After RP, 36% of men reported urinary leakage requiring at least 1 pad/day, persisting for 20% at 6 years, compared with no change in men receiving EBRT or AM (P < 0.001). Worse bowel function and bother (e.g., bloody stools 6% at 6 years and faecal incontinence 10%) was experienced by men after EBRT than after RP or AM (P < 0.001) with lesser effects after BT. No treatment affected mental or physical QoL. Conclusion Treatment decision-making for localised prostate cancer can be informed by these 6-year functional and QoL outcomes

Metallo-β-lactamase-producing Clinical Isolates from Patients of a Tertiary Care Hospital

Background: The growing increase in the rates of antibiotic resistance is a major cause for concern in both non-fermenting bacilli and isolates of the Enterobacteriaceae family. β-lactams have been the mainstay of treatment for serious infections, and the most active of these are the carbapenems. Acquired metallo-β-lactamases (MBL) have recently emerged as one of the most worrisome resistance mechanisms owing to their capacity to hydrolyze all β-lactams, including carbapenems. We have undertaken this investigation to ascertain the prevalence of MBL-producing non-fermenting bacilli and Enterobacteriaceae. Materials and Methods: The study was conducted over a period of 4 months in a 1200-bedded teaching hospital. Isolates included in the study were screened for imipenem resistance both by conventional methods and mini analytical profile index (miniAPI). The isolates that showed imipenem resistance were tested for MBL production by imipenem (IMP)-ethylenediaminetetraacetic acid combined disc test. Imipenem-resistant non-MBL isolates also tested for Modified Hodge test and AmpC β-lactamases production to detect other mechanisms of carbapenem resistance. Results: Of 638 gram negative bacilli isolates and 3.39% showed imipenem resistance, 2.9% showed MBL production, of which 1.7% were non-fermenters and 1.25% were Enterobacteriaceae, 0.3% showing non-MBL KPC carbapenemas. Most isolates were from the intensive care unit and from post-operative patients. Our findings show that there are significant numbers of isolates having MBL production along with multidrug resistance. There is a need for active surveillance to detect MBL producers

The West Midlands bladder cancer prognosis programme : rationale and design

Objective: To describe the rationale and design of the Bladder Cancer Prognosis Programme (BCPP), and to demonstrate the capability of this design. Methods: There is a need to understand the determinants of bladder cancer to help reduce recurrence, progression, morbidity, mortality and related costs. We previously showed that lifestyle factors are important for determining the risk of bladder cancer, but little is known about their importance in determining the risk of recurrence or progression after diagnosis. Also, histopathological factors alone provide only crude prognostication; the analysis of molecular markers represents a method for refinement but research in this area has not been useful in informing therapeutic decisions or prognostication. The BCPP is a prospective longitudinal cohort study of all patients with newly diagnosed bladder cancer within the West Midlands (UK), investigating the influence of lifestyle factors on recurrence and progression, health-related quality of life, the predictive effect of a panel of molecular markers on recurrence or progression, and the establishment of Europe’s largest comprehensive bladder cancer bio-repository. It also incorporates the first randomized clinical trial on the efficacy of selenium and vitamin E on bladder cancer. The numbers and proportions of eligible patients recruited, questionnaires completed and specimens obtained were all recorded. Results: Since December 2005, 771 patients have been recruited (68% of eligible patients) and of these, 331 are currently being followed up by questionnaires. We have obtained blood, urine and tumour tissues from 92%, 80% and 80% of patients, respectively. Conclusions: The design of the BCPP has allowed this study to be incorporated into routine clinical work throughout the West Midlands, achieving high levels of recruitment, and data and specimen collection. This might represent a model for the future investigation of urological and other malignancies