Baseline Comorbidities in a Population-Based Cohort of Rheumatoid Arthritis Patients Receiving Biological Therapy: Data from the Australian Rheumatology Association Database

Aims. To describe the baseline characteristics of an Australian population-based cohort of rheumatoid arthritis (RA) patients commencing biological therapy. Methods. Descriptive analysis from the Australian Rheumatology Association Database (ARAD). Results. Up to October 2006, there were 681 RA patients taking biologics enrolled in ARAD. Baseline data were available for 624 (72% female, mean (SD) age 57.0 (12.5) years). Of these, 59.5% reported at least one comorbid condition, most commonly hypertension (35.7%) and osteoporosis (30.4%); 61 (9.8%) had a history of malignancy (35 nonmelanoma skin, 5 breast, 4 bowel, 5 cervix, 3 melanoma, 3 prostate and 1 each of lip, lung, myeloma, testis, uterus, vagina). Self-reported infections within the previous 6 months were common (71.5%). Conclusions. History of comorbidities, including recent infections, is common among Australian RA patients commencing biologics, and 10% have a history of malignancy. This may impact future evaluations of health outcomes among this population, including attribution of adverse events of biologic therapy

Characterising risk of non-steroidal-anti-inflammatory drug related acute kidney injury: a retrospective cohort study

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for pain and inflammation. NSAID complications include acute kidney injury (AKI), causing burden to patients and health services through increased morbidity, mortality, and hospital admissions. AIM: To measure the extent of NSAID prescribing in an adult population, the degree to which patients with potential higher risk of AKI were exposed to NSAIDs, and to quantify their risk of AKI. DESIGN & SETTING: Retrospective 2-year closed-cohort study. METHOD: A retrospective cohort of adults was identified from a pseudonymised electronic primary care database in Hampshire, UK. The cohort had clinical information, prescribing data, and complete GP- and hospital-ordered biochemistry data. NSAID exposure (minimum one prescription in a 2-month period) was categorised as never, intermittent, and continuous, and first AKI using the national AKI e-alert algorithm. Descriptive statistics and logistic regression were used to explore NSAID prescribing patterns and AKI risk. RESULTS: The baseline population was 702 265. NSAID prescription fell from 19 364 (2.8%) to 16 251 (2.4%) over 2 years. NSAID prescribing was positively associated with older age, female sex, greater socioeconomic deprivation, and certain comorbidities (diabetes, hypertension, osteoarthritis, and rheumatoid arthritis) and negatively with cardiovascular disease (CVD) and heart failure. Among those prescribed NSAIDs, AKI was associated with older age, greater deprivation, chronic kidney disease (CKD), CVD, heart failure, diabetes, and hypertension. CONCLUSION: Despite generally good prescribing practice, NSAID prescribing was identified in some people at higher risk of AKI (for example, patients with CKD and older) for whom medication review and NSAID deprescribing should be considered

HPV-Associated Head and Neck Cancer: Molecular and Nano-Scale Markers for Prognosis and Therapeutic Stratification

Over the last 10 years, it has become clear that patients with head and neck cancer can be stratified into two distinct subgroups on the basis of the etiology of their disease. Patients with human papillomavirus-related cancers have significantly better survival rates and may necessitate different therapeutic approaches than those with tobacco and/or alcohol related cancers. This review discusses the various biomarkers currently in use for identification of patients with HPV-positive cancers with a focus on the advantages and limitations of molecular and nano-scale markers

Identifying individuals with persistently normal safety monitoring blood tests whilst taking methotrexate for rheumatoid arthritis or azathioprine for inflammatory bowel disease: a retrospective cohort study.

Background: disease-modifying anti-rheumatic drugs (DMARDs), including methotrexate and azathioprine, are commonly used for rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). Blood test safety monitoring is mainly undertaken in primary care. Normal blood results are common. Aim: to determine the frequency and associations of persistently normal blood tests in RA patients prescribed methotrexate and IBD patients prescribed azathioprine.Design and setting: two-year retrospective cohort study using pseudonymised primary care/laboratory data in Hampshire.Method: RA and IBD patients were identified with associated methotrexate (RA) and azathioprine (IBD) prescriptions. NICE-recommended tests and thresholds were applied and persistent normality defined as a) no abnormalities of any tests, and b) individually for alanine aminotransferase (ALT), estimated glomerular filtration rate (eGFR), white blood count (WBC), and neutrophils. Logistic regression was used to identify associations with test normality. Results: of 702,265 adults, 7102 had RA and 8597 had IBD. 3001 (42.2%) RA patients were prescribed methotrexate and 1162 (13.5%) IBD patients prescribed azathioprine. Persistently normal tests occurred in 1585 (52.8%) of the RA/methotrexate and 657 (56.5%) of the IBD/azathioprine populations. In RA/methotrexate patients 585 (19.5%) had eGFR, 219 (7.3%) ALT, 217 (7.2%) WBC, and 202 (6.7%) neutrophil abnormalities. In IBD/azathioprine patients 138 (4.6%) had WBC, 88 (2.9%) eGFR, 72 (2.4%) ALT and 65 (2.2%) neutrophil abnormalities. Those least likely to have persistent test normality were older and/or had comorbidities.Conclusions: persistent test normality is common in monitoring these DMARDs in primary care, with few hepatic or haematological abnormalities. More stratified monitoring approaches should be explored. <br/

An expression-based site of origin diagnostic method designed for clinical application to cancer of unknown origin

Gene expression profiling offers a promising new technique for the diagnosis and prognosis of cancer. We have applied this technology to build a clinically robust site of origin classifier with the ultimate aim of applying it to determine the origin of cancer of unknown primary (CUP). A single cDNA microarray platform was used to profile 229 primary and metastatic tumors representing 14 tumor types and multiple histologic subtypes. This data set was subsequently used for training and validation of a support vector machine (SVM) classifier, demonstrating 89 % accuracy using a 13-class model. Further, we show the translation of a fiveclass classifier to a quantitative PCR–based platform. Selecting 79 optimal gene markers, we generated a quantitative-PCR low-density array, allowing the assay o

Postoperative concurrent chemoradiotherapy versus postoperative radiotherapy in high-risk cutaneous squamous cell carcinoma of the head and neck: the randomized phase III TROG 05.01 trial

Purpose: To report the results of the Trans Tasman Radiation Oncology Group randomized phase III trial designed to determine whether the addition of concurrent chemotherapy to postoperative radiotherapy (CRT) improved locoregional control in patients with high-risk cutaneous squamous cell carcinoma of the head and neck. Patients and Methods: The primary objective was to determine whether there was a difference in freedom from locoregional relapse (FFLRR) between 60 or 66 Gy (6 to 6.5 weeks) with or without weekly carboplatin (area under the curve 2) after resection of gross disease. Secondary efficacy objectives were to compare disease-free survival and overall survival. Results: Three hundred twenty-one patients were randomly assigned, with 310 patients commencing allocated treatment (radiotherapy [RT] alone, n = 157; CRT, n = 153). Two hundred thirty-eight patients (77%) had high-risk nodal disease, 59 (19%) had high-risk primary or in-transit disease, and 13 (4%) had both. Median follow-up was 60 months. Median RT dose was 60 Gy, with 84% of patients randomly assigned to CRT completing six cycles of carboplatin. The 2- and 5-year FFLRR rates were 88% (95% CI, 83% to 93%) and 83% (95% CI, 77% to 90%), respectively, for RT and 89% (95% CI, 84% to 94%) and 87% (95% CI, 81% to 93%; hazard ratio, 0.84; 95% CI, 0.46 to 1.55; P = .58), respectively, for CRT. There were no significant differences in disease-free or overall survival. Locoregional failure was the most common site of first treatment failure, with isolated distant metastases as the first site of failure seen in 7% of both arms. Treatment was well tolerated in both arms, with no observed enhancement of RT toxicity with carboplatin. Grade 3 or 4 late toxicities were infrequent. Conclusion: Although surgery and postoperative RT provided excellent FFLRR, there was no observed benefit with the addition of weekly carboplatin