Objective: To describe the drugs and types of medicine management problems most frequently associated with preventable drug related admissions to an acute medical admissions unit. Design: Observation study. Setting: Medical admissions unit in a teaching hospital in Nottingham, UK. Participants: 4093 patients seen by pharmacists on the medical admissions unit between 1 January and 30 June 2001. Main outcome measures: Proportion of admissions that were drug related and preventable, classification of the underlying causes of preventable drug related admissions, and identification of drugs most commonly associated with preventable drug related admissions. Results: Of the admissions seen by pharmacists, 265 (6.5%) were judged to be drug related and 178 (67%) of these were judged to be preventable. Preventable admissions were mainly due to problems with prescribing (63 cases (35%)), monitoring (46 cases (26%)), and adherence to medication (53 cases (30%)). The drugs most commonly implicated were NSAIDs, antiplatelets, antiepileptics, hypoglycaemics, diuretics, inhaled corticosteroids, cardiac glycosides, and beta-blockers. Conclusions: Potentially preventable drug related morbidity was associated with 4.3% of admissions to a medical admissions unit. In 91% of cases these admissions were related to problems with either prescribing, monitoring, or adherence. R ecent reports in the USA 1 and the UK 2 highlight the problem of drug related morbidity and the need to find ways to prevent medical errors. These reports suggest that preventable drug related admissions require particular attention and, in 2002, two systematic reviews were published on this topic.3 4 Winterstein et al 3 identified 15 studies of preventable drug related hospital admissions and found a median of 7.1% of admissions to be drug related, and 59% of these to be preventable. Beijer et al 4 reviewed 68 studies, 12 of which looked at preventable admissions. This review highlighted some of the limitations of previous research and emphasised the need for further studies looking at the preventability of drug related admissions and documentation of the drugs responsible for these admissions. This sort of information is needed if we are to develop effective strategies to prevent drug related admissions. In addition, it is important to identify some of the underlying causes of preventable admissions.We have addressed some of these issues by conducting a large study of drug related morbidity detected by pharmacists on a medical admissions unit in the UK. We have defined drug related morbidity as adverse drug reactions, 5 failure to optimise treatment, unintentional overdose, and adherence problems. Admissions associated with intentional overdoses and drugs of abuse were excluded.The objectives of our study were to: • estimate the proportion of admissions to an acute medical admissions unit that were associated with drug related morbidity and the proportion of these admissions that were potentially preventable; • identify the drugs associated with the preventable ...

Oral Diseases (2011) 17 (Suppl. 1), 7–22 Squamous cell carcinoma (SCC) of the oral and oropharyngeal region is the sixth most common malignancy in the world today. Despite numerous advances in treatment, long‐term survival from this disease remains poor. Early detection can decrease both morbidity and mortality associated with this neoplasm. However, screening for potentially malignant disease is typically confounded by difficulty in discriminating between reactive/inflammatory lesions vs those lesions that are premalignant in nature. Furthermore, the histologic diagnosis of dysplasia can be subjective and is thus prone to a considerable range of interpretation. Similarly, no definitive, validated criteria exist for predicting which dysplastic lesions are most likely to progress to cancer over time. Given this state of science, the presence of dysplasia can only be used to indicate that an oral lesion may have an increased risk of malignant transformation. Molecular biomarkers capable of identifying the subset of lesions likely to progress to cancer are required to eliminate this clinical diagnostic dilemma. The purpose of this review is to assess the current state of knowledge regarding genetic/epigenetic alterations observed in oral mucosal premalignancy. In addition, recommendations for future research studies directed at defining the predictive capacity of specific biomarkers in this modeling are presented.

Heterogeneity of carcinoma-associated fibroblasts (CAF) has long been recognized, but the functional significance remains poorly understood. Here, we report the distinction of two CAF subtypes in oral squamous cell carcinoma (OSCC) that have differential tumor-promoting capability, one with a transcriptome and secretome closer to normal fibroblasts (CAF-N) and the other with a more divergent expression pattern (CAF-D). Both subtypes supported higher tumor incidence in nonobese diabetic/severe combined immunodeficient (NOD/SCID) Ilγ2(null) mice and deeper invasion of malignant keratinocytes than normal or dysplasia-associated fibroblasts, but CAF-N was more efficient than CAF-D in enhancing tumor incidence. CAF-N included more intrinsically motile fibroblasts maintained by high autocrine production of hyaluronan. Inhibiting CAF-N migration by blocking hyaluronan synthesis or chain elongation impaired invasion of adjacent OSCC cells, pinpointing fibroblast motility as an essential mechanism in this process. In contrast, CAF-D harbored fewer motile fibroblasts but synthesized higher TGF-β1 levels. TGF-β1 did not stimulate CAF-D migration but enhanced invasion and expression of epithelial–mesenchymal transition (EMT) markers in malignant keratinocytes. Inhibiting TGF-β1 in three-dimensional cultures containing CAF-D impaired keratinocyte invasion, suggesting TGF-β1–induced EMT mediates CAF-D–induced carcinoma cell invasion. TGF-β1–pretreated normal fibroblasts also induced invasive properties in transformed oral keratinocytes, indicating that TGF-β1–synthesizing fibroblasts, as well as hyaluronan-synthesizing fibroblasts, are critical for carcinoma invasion. Taken together, these results discern two subtypes of CAF that promote OSCC cell invasion via different mechanisms. Cancer Res; 73(13); 3888–901. ©2013 AACR.

The application of SC and GO algorithms to HNSCC microarray data identified gene sets highly significant for predicting patient outcome. Further large-scale studies will establish the usefulness of these gene sets in the clinical management of HNSCC.