Citations

Objective The study aimed to define thresholds of clinically significant change in 17‐item Hamilton Depression Rating Scale (HDRS‐17) scores using the Clinical Global Impression‐Improvement (CGI‐I) Scale as a gold standard. Methods We conducted a secondary analysis of individual patient data from the Pharmacogenomic Research Network Antidepressant Medication Pharmacogenomic Study, an 8‐week, single‐arm clinical trial of citalopram or escitalopram treatment of adults with major depression. We used equipercentile linking to identify levels of absolute and percent change in HDRS‐17 scores that equated with scores on the CGI‐I at 4 and 8 weeks. Additional analyses equated changes in the HDRS‐7 and Bech‐6 scale scores with CGI‐I scores. Results A CGI‐I score of 2 (much improved) corresponded to an absolute decrease (improvement) in HDRS‐17 total score of 11 points and a percent decrease of 50–57%, from baseline values. Similar results were observed for percent change in HDRS‐7 and Bech‐6 scores. Larger absolute (but not percent) decreases in HDRS‐17 scores equated with CGI‐I scores of 2 in persons with higher baseline depression severity. Conclusions Our results support the consensus definition of response based on HDRS‐17 scores ( > 50% decrease from baseline). A similar definition of response may apply to the HDRS‐7 and Bech‐6. Copyright © 2016 John Wiley & Sons, Ltd.

Abstract During the past decade, a conceptual shift occurred in the field of Alzheimer's disease (AD) considering the disease as a continuum. Thanks to evolving biomarker research and substantial discoveries, it is now possible to identify the disease even at the preclinical stage before the occurrence of the first clinical symptoms. This preclinical stage of AD has become a major research focus as the field postulates that early intervention may offer the best chance of therapeutic success. To date, very little evidence is established on this “silent” stage of the disease. A clarification is needed about the definitions and lexicon, the limits, the natural history, the markers of progression, and the ethical consequence of detecting the disease at this asymptomatic stage. This article is aimed at addressing all the different issues by providing for each of them an updated review of the literature and evidence, with practical recommendations.

Previously regarded as an obscure disorder, nonalcoholic steatohepatitis (NASH) has recently emerged as an important chronic liver disease. NASH is within a spectrum of disorders characterized by excessive accumulation of fat in the liver, including simple hepatic steatosis (fatty liver), inflammation and necrosis (steatohepatitis), and fibrosis. Collectively, the disorders are called nonalcoholic fatty liver disease (NAFLD). Estimates of the prevalence of these individual conditions are suspect because liver biopsy is required for definitive diagnosis and is not generally performed. Although these conditions have traditionally been thought of as diseases of obese women, and are frequently associated with diabetes mellitus and hypertriglyceridemia, they have also been identified in lean men. Insulin resistance appears to be a common factor. These conditions are difficult to distinguish from each other clinically, and no biochemical or radiological test reliably establishes the diagnosis. A ratio of serum aspartate to alanine aminotransferase levels of less than one can distinguish NAFLD from alcoholic liver disease, but this is a nonspecific finding. Fatty infiltration imparts a diffuse echogenicity to the liver at ultrasonography, but this test cannot easily distinguish fat from fibrous tissue or identify cases of NASH. Only histological examination can establish the diagnosis of NASH, grade its severity, determine the prognosis and guide treatment.

Hepatitis C is a prevalent infection in North America. However, the natural history of hepatitis C virus (HCV) infection in the general population is not fully understood. Available cohortbased studies suggest that only a relative minority of patients develop significant liver disease, such as cirrhosis and/or hepatocellular carcinoma. Other studies, mostly conducted based on referral patients with established disease, portray much more serious consequences of HCV infection. Although a substantial improvement has been made in the treatment for HCV, the overall impact of antiviral therapy in altering the natural course of HCV infection remains uncertain. Therapeutic trials involve narrow selection criteria that would exclude the majority of hepatitis C patients in the community, and are conducted in ideal settings that may not be generalizable to the average practice setting. Demographic groups that are at high risk of developing severe liver disease include older male patients who consume alcohol. In contrast, antiviral therapy is more effective in young and female patients and those who do not drink alcohol. Thus, patients who appear to be successfully treated may not be those for whom clearance of the virus would be beneficial. Cost-effectiveness studies published to date have not been able to fully address the complex and heterogeneous matrix of the factors that influence the natural history of HCV infection and treatment response.In summary, there is a significant degree of uncertainty about many assumptions that are necessary in creating computer models to estimate the cost-effectiveness of HCV therapy. When interpreting the results of cost effectiveness analyses regarding the treatment of HCV infection, it is important to be aware of the underlying assumptions that are incorporated in the model and the data on which they are based. Given these limitations, vis-à-vis the expense, toxicity and yet limited effectiveness of the currently available antiviral agents, one should not blindly accept a conclusion that treatment for hepatitis C is cost effective.

OBJECTIVE: To present recently published material comparing the performance of endosonography relative to other imaging modalities when evaluating the patient with a suspected or known pancreas carcinoma.METHODS: Medline was searched using the terms ‘endosonography’ and ‘pancreas neoplasms’. References from retrieved papers were reviewed to identify other reports. Emphasis was placed on peer-reviewed material published within the past three years that included comparison with other imaging modalities.RESULTS: Despite advances in cross-sectional imaging modalities, endosonography remains the most sensitive and specific method for identifying pancreatic mass lesions. The resectability of pancreatic carcinoma is best determined with dual-phase helical computed tomography, although endosonography may be slightly more accurate for lymph node assessment. Endoscopic ultrasound-guided fine needle aspiration biopsy has a high sensitivity (93%) and specificity (100%) when used in patients with masses in whom pancreatic cancer is suspected but prior biopsies have been negative.CONCLUSIONS: Endosonography helps in the diagnosis of pancreatic neoplasms through definitive inclusion or exclusion of a mass lesion as well as biopsy confirmation of malignancy. The role of endosonography in the determination of resectability has been eclipsed by dual-phase helical computed tomography. However, endoscopic ultrasound with fine needle aspiration of nonperitumoral lymph nodes may identify advanced disease with sufficient frequency to justify its routine use in patients with lesions that are thought to be resectable based on helical computed tomography.

AbstractGenetic risk scores were used as unconfounded instruments for specific lipid traits (Mendelian randomization) to assess whether circulating lipids causally influence prostate cancer risk. Data from 22,249 prostate cancer cases and 22,133 controls from 22 studies within the international PRACTICAL consortium were analyzed. Allele scores based on single nucleotide polymorphisms (SNPs) previously reported to be uniquely associated with each of low‐density lipoprotein (LDL), high‐density lipoprotein (HDL), and triglyceride (TG) levels, were first validated in an independent dataset, and then entered into logistic regression models to estimate the presence (and direction) of any causal effect of each lipid trait on prostate cancer risk. There was weak evidence for an association between the LDL genetic score and cancer grade: the odds ratio (OR) per genetically instrumented standard deviation (SD) in LDL, comparing high‐ (≥7 Gleason score) versus low‐grade (<7 Gleason score) cancers was 1.50 (95% CI: 0.92, 2.46; P = 0.11). A genetically instrumented SD increase in TGs was weakly associated with stage: the OR for advanced versus localized cancer per unit increase in genetic risk score was 1.68 (95% CI: 0.95, 3.00; P = 0.08). The rs12916‐T variant in 3‐hydroxy‐3‐methylglutaryl‐CoA reductase (HMGCR) was inversely associated with prostate cancer (OR: 0.97; 95% CI: 0.94, 1.00; P = 0.03). In conclusion, circulating lipids, instrumented by our genetic risk scores, did not appear to alter prostate cancer risk. We found weak evidence that higher LDL and TG levels increase aggressive prostate cancer risk, and that a variant in HMGCR (that mimics the LDL lowering effect of statin drugs) reduces risk. However, inferences are limited by sample size and evidence of pleiotropy.