Defining Natural History: Assessment of the Ability of College Students to Aid in Characterizing Clinical Progression of Niemann-Pick Disease, Type C

Niemann-Pick Disease, type C (NPC) is a fatal, neurodegenerative, lysosomal storage disorder. It is a rare disease with broad phenotypic spectrum and variable age of onset. These issues make it difficult to develop a universally accepted clinical outcome measure to assess urgently needed therapies. To this end, clinical investigators have defined emerging, disease severity scales. The average time from initial symptom to diagnosis is approximately 4 years. Further, some patients may not travel to specialized clinical centers even after diagnosis. We were therefore interested in investigating whether appropriately trained, community-based assessment of patient records could assist in defining disease progression using clinical severity scores. In this study we evolved a secure, step wise process to show that pre-existing medical records may be correctly assessed by non-clinical practitioners trained to quantify disease progression. Sixty-four undergraduate students at the University of Notre Dame were expertly trained in clinical disease assessment and recognition of major and minor symptoms of NPC. Seven clinical records, randomly selected from a total of thirty seven used to establish a leading clinical severity scale, were correctly assessed to show expected characteristics of linear disease progression. Student assessment of two new records donated by NPC families to our study also revealed linear progression of disease, but both showed accelerated disease progression, relative to the current severity scale, especially at the later stages. Together, these data suggest that college students may be trained in assessment of patient records, and thus provide insight into the natural history of a disease

Pruritus in patients treated with targeted cancer therapies: Systematic review and meta-analysis

BACKGROUND: Pruritus has been anecdotally described in association with targeted cancer therapies. The risk of pruritus has not been systematically ascertained. OBJECTIVE: A systematic review and meta-analysis of the literature was conducted for axitinib, cetuximab, dasatinib, erlotinib, everolimus, gefitinib, imatinib, ipilimumab, lapatinib, nilotinib, panitumumab, pazopanib, rituximab, sorafenib, temsirolimus, tositumomab, vandetanib, and vemurafenib. METHODS: Databases from PubMed, Web of Science (01/1998–07/2012), and American Society of Clinical Oncology abstracts (2004–2012) were searched. Incidence and risk (RR) of pruritus were calculated using random or fixed effects model. RESULTS: The incidences of all-grade and high-grade pruritus were 17.4% (95% confidence interval (CI): 16.0%−19.0%) and 1.4% (95% CI: 1.2%−1.6%), respectively. There was an increased risk of all-grade pruritus (RR=2.90 (95% CI: 1.76–4.77, p<0.001)); and variation among different drugs (P<0.001). LIMITATIONS: The reporting of pruritus may vary, resulting from concomitant medications, comorbidities, and underlying malignancies. We found a higher incidence of pruritus in patients with solid tumors, concordant with those targeted therapies with the highest pruritus incidences. CONCLUSION: There is a significant risk of developing pruritus in patients receiving targeted therapies. In order to prevent suboptimal dosing and decreased quality of life, patients should be counseled and treated against this untoward symptom