High versus standard doses interferon-alpha in the treatment of naïve chronic hepatitis C patients in Taiwan: a 10-year cohort study

BACKGROUND: Interferon-alpha monotherapy is effective in less than one-third patients with chronic hepatitis C. The dose-effect, tolerability and durability of interferon-alpha treatment and its long-term effect on the prevention of cirrhosis and hepatocellular carcinoma in naïve Taiwanese patients with chronic hepatitis C have not been well investigated. We conducted the present cohort study treated with high and standard interferon-alpha to illustrate the issues. METHODS: We performed a long-term virologic and histological follow-up of 214 chronic hepatitis C patients treated with interferon-alpha, 3 million units (3-MU, n = 80) or 6-MU (n = 134) thrice weekly for 24 weeks, in Taiwan between 1992 and 2001. RESULTS: There was no difference in the incidence of discontinuation between 3-MU and 6-MU groups (4/80, 5.0% versus 10/134. 7.5%). The 6-MU group had similar incidence of adverse events with the 3-MU group, except that 6-MU group had significantly higher incidence of psychological manifestations, mainly presented as irritability. The rates of sustained virological response (SVR) were significantly higher in 6-MU regimen (37.1%) than in 3-MU regimen (23.7%, p < 0.05) in per protocol analysis. Based on multivariate analysis, baseline viral load was strongly associated with SVR, followed by hepatitis C virus genotype, interferon-alpha regimen, and liver fibrosis. A histological improvement in necroinflammatory activity, but not in fibrosis was observed in the follow-up biopsy performed 0.5–5.5 years (mean: 1.9 years, n = 51) after end-of-treatment. Among patients without SVR, there was more activity improvement in 6-MU group. The durability of SVR was 100% (18/18) and 97.8% (45/46) for 3-MU and 6-MU group, respectively, in a mean follow-up period of 6.81 years (5.25–9.18 years). For 163 baseline non-cirrhotic patients, 9 of 84 (10.7%) non-responders and 3 of 79 (3.8%) sustained responders progressed to cirrhosis during a mean follow-up period of 5.52 and 5.74 years, respectively (p = 0.067, Kaplan-Meier survival analysis, log-rank test). For all 200 patients, hepatocellular carcinoma was detected in 12 of 113 (10.6%) non-responders and one of 87 (1.1%) sustained responders during a mean follow-up period of 5.67 and 5.73 years, respectively (p < 0.01, Kaplan-Meier survival analysis, log-rank test). CONCLUSION: We confirm the dose effect of interferon-alpha in chronic hepatitis C. Six-MU regimen had better efficacy than 3-MU regimen in virologic and histological responses. Both regimens had good tolerability and durability in Taiwan. Sustained response could reduce the incidence of cirrhotic change and hepatocarcinogenesis

The Glasgow Outcome Scale -- 40 years of application and refinement

The Glasgow Outcome Scale (GOS) was first published in 1975 by Bryan Jennett and Michael Bond. With over 4,000 citations to the original paper, it is the most highly cited outcome measure in studies of brain injury and the second most-cited paper in clinical neurosurgery. The original GOS and the subsequently developed extended GOS (GOSE) are recommended by several national bodies as the outcome measure for major trauma and for head injury. The enduring appeal of the GOS is linked to its simplicity, short administration time, reliability and validity, stability, flexibility of administration (face-to-face, over the telephone and by post), cost-free availability and ease of access. These benefits apply to other derivatives of the scale, including the Glasgow Outcome at Discharge Scale (GODS) and the GOS paediatric revision. The GOS was devised to provide an overview of outcome and to focus on social recovery. Since the initial development of the GOS, there has been an increasing focus on the multidimensional nature of outcome after head injury. This Review charts the development of the GOS, its refinement and usage over the past 40 years, and considers its current and future roles in developing an understanding of brain injury

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

A contemporary population-based study of testicular sex cord stromal tumours: Presentation, treatment patterns, and predictors of outcome.

INTRODUCTION:We aimed to characterize demographic distribution, patient outcomes, and prognostic features of testicular sex cord stromal tumours (SCST) using a large statewide database. METHODS:Adult male patients diagnosed with SCST between 1988 and 2010 were identified within the California Cancer Registry (CCR). Baseline demographic variables and disease characteristics were reported. Primary outcome measures were cancer-specific survival (CSS) and overall survival (OS). Bivariate and multivariate Cox proportional hazards models were employed to identify predictors of survival. RESULTS:A total of 67 patients with SCST were identified, of which 45 (67%) had Leydig cell and 19 (28%) had Sertoli cell tumours. Median age was 40 years and the majority of patients (84%) presented with localized disease. Following orchiectomy, nine patients (15%) underwent retroperitoneal lymph node dissection (RPLND), whereas 54 patients (80%) had no further treatment. With a median followup of 75 months, two-year OS and CSS was 91% and 95%, respectively, for those presenting with stage I disease. For those presenting with stage II disease, two-year OS and CSS was 30%. Predictors of worse OS included age &gt;60 (hazard ratio [HR] 5.64; p&lt;0.01) and metastatic disease (HR 8.56; p&lt;0.01). Presentation with metastatic disease was the only variable associated with worse CSS (HR 13.36; p&lt;0.01). Histology was not found to be a significant predictor of either CSS or OS. CONCLUSIONS:We present the largest reported series to date for this rare tumour and provide contemporary epidemiological and treatment data. The primary driver of prognosis in patients with SCST is disease stage, emphasizing the importance of early detection and intervention

A contemporary population-based study of testicular sex cord stromal tumours: Presentation, treatment patterns, and predictors of outcome.

INTRODUCTION:We aimed to characterize demographic distribution, patient outcomes, and prognostic features of testicular sex cord stromal tumours (SCST) using a large statewide database. METHODS:Adult male patients diagnosed with SCST between 1988 and 2010 were identified within the California Cancer Registry (CCR). Baseline demographic variables and disease characteristics were reported. Primary outcome measures were cancer-specific survival (CSS) and overall survival (OS). Bivariate and multivariate Cox proportional hazards models were employed to identify predictors of survival. RESULTS:A total of 67 patients with SCST were identified, of which 45 (67%) had Leydig cell and 19 (28%) had Sertoli cell tumours. Median age was 40 years and the majority of patients (84%) presented with localized disease. Following orchiectomy, nine patients (15%) underwent retroperitoneal lymph node dissection (RPLND), whereas 54 patients (80%) had no further treatment. With a median followup of 75 months, two-year OS and CSS was 91% and 95%, respectively, for those presenting with stage I disease. For those presenting with stage II disease, two-year OS and CSS was 30%. Predictors of worse OS included age &gt;60 (hazard ratio [HR] 5.64; p&lt;0.01) and metastatic disease (HR 8.56; p&lt;0.01). Presentation with metastatic disease was the only variable associated with worse CSS (HR 13.36; p&lt;0.01). Histology was not found to be a significant predictor of either CSS or OS. CONCLUSIONS:We present the largest reported series to date for this rare tumour and provide contemporary epidemiological and treatment data. The primary driver of prognosis in patients with SCST is disease stage, emphasizing the importance of early detection and intervention

Diagnosing the GOSE : structural and psychometric properties using item response theory, a TRACK-TBI pilot study

The Glasgow Outcome Scale-Extended (GOSE) was designed to assess global outcome after traumatic brain injury (TBI). Since its introduction, several empirically founded criticisms of the GOSE have been raised, including poor reliability; an insensitivity to small, but potentially meaningful, changes; a tendency to produce ceiling effects; inconsistent associations with neurocognitive, psychological, and quality-of-life measures; and an inability to assess the multi-dimensional nature of TBI outcome. The current project took a diagnostic approach to identifying the underlying causes of reported limitations by exploring the internal construct validity of the GOSE at 3 and 6 months post-injury using item response theory (IRT) techniques. Data were from the TRACK-TBI Pilot Study, a large (N = 586), prospective, multi-site project that included TBI cases of all injury severity levels. To assess the level of latent functional "impairment" captured by GOSE items independent of the assigned outcome category or GOSE total score, items were modified so that higher scores reflected greater impairment. Results showed that although the GOSE's items capture varying levels of impairment across a broad disability spectrum at 3 and 6 months, there was also evidence at each time point of item redundancy (multiple items capturing similar levels of impairment), item deficiency (lack of items capturing lower levels of impairment), and item inefficiency (items only capturing minimal impairment information). The findings illustrate the value of IRT to illuminate strengths and weaknesses of clinical outcome assessment measures and provide a framework for future measure refinement