Hepatic gene expression discriminates responders and nonresponders in treatment of chronic hepatitis C viral infection

BACKGROUND & AIMS: Pegylated interferon (IFN)-alpha plus ribavirin is the most effective treatment of chronic hepatitis C but has unpleasant side effects and high costs. A large proportion of patients do not respond to therapy for reasons that are unclear. We used gene expression profiling to investigate the molecular basis for treatment failure. METHODS: Expression profiling was performed on percutaneous needle liver biopsy specimens taken before therapy. Gene expression levels were compared among 15 nonresponder, 16 responder, and 20 normal liver biopsy specimens. Differential gene expression was confirmed using real-time polymerase chain reaction. RESULTS: We identified 18 genes whose expression differed significantly between all responders and all nonresponders (P < .005). Many of these 18 genes are IFN sensitive and 2 (ISG15/USP18) are linked in a novel IFN-regulatory pathway, suggesting a possible rationale for treatment resistance. Using a number of independent classifier analyses, an 8-gene subset accurately predicted treatment response for 30 of 31 patients. The classifier analyses were applicable to patients with genotype 1 infection and were not correlated with viral load, disease activity, or fibrosis. CONCLUSIONS: Hepatic gene expression profiling identified consistent differences in patients who subsequently fail treatment with pegylated IFN-alpha plus ribavirin: up-regulation of a specific set of IFN-responsive genes predicts nonresponse to exogenous therapy. These data may be of use in predicting clinical responses to treatment.     

The Health Insurance Portability and Accountability Act (HIPAA): its broad effect on practice

The Health Insurance Portability and Accountability Act (HIPAA), and its final rule, raised fears among practitioners of new and complex regulations that might interfere with medical practice, lead to inadvertent liability and unwanted expense. It generated a dizzying set of health-care administrative activities and a new work for legal consultants. It has extensive scope, and includes most health plans and practitioners. It has regulated both privacy and security, including electronic, paper, and oral communications. However, after a HIPAA compliant office structure is established, and the privacy notice is reviewed and signed by the patient, disclosure of medical information for treatment, payment or "health-care operations" is permitted without recurrent consent forms, thus allowing substantially familiar patterns of doctor-to-doctor communication about treatment. Further, the initial approach to enforcement appears to some legal observers to be more likely corrective rather than punitive, although providers remain uneasy over the mere possibility of criminal penalties. As regards medical research, uncertainties about the application of HIPAA seem less resolved and more variably interpreted by different institutions, with ongoing fear in the research community that important public health and epidemiologic research activity may be compromised by well meaning IRBs using inconsistent, overly strict or erroneous interpretation of the intent of HIPAA regulations.     

Rapid and accurate determination of tissue optical properties using least-squares support vector machines

Diffuse reflectance spectroscopy (DRS) has been extensively applied for the characterization of biological tissue, especially for dysplasia and cancer detection, by determination of the tissue optical properties. A major challenge in performing routine clinical diagnosis lies in the extraction of the relevant parameters, especially at high absorption levels typically observed in cancerous tissue. Here, we present a new least-squares support vector machine (LS-SVM) based regression algorithm for rapid and accurate determination of the absorption and scattering properties. Using physical tissue models, we demonstrate that the proposed method can be implemented more than two orders of magnitude faster than the state-of-the-art approaches while providing better prediction accuracy. Our results show that the proposed regression method has great potential for clinical applications including in tissue scanners for cancer margin assessment, where rapid quantification of optical properties is critical to the performance.     

Narrow-band pass filter array for integrated opto-electronic spectroscopy detectors to assess esophageal tissue

A strategy for spectroscopy tissue diagnosis using a small number of wavelengths is reported. The feasibility to accurately quantify tissue information using only 16 wavelengths is demonstrated with several wavelength reduction simulations of the existing esophageal data set. These results are an important step for the development of a miniaturized, robust and low-cost spectroscopy system. This system is based on a sub-millimeter high-selective filter array that offers prospects for a simplified miniature spectrographic detector for a future diagnostic tool to improve the diagnosis of dysplasia. Several thin-film optical filters are optimized and fabricated and its spectral performance is shown to be sufficient for the selection of specific wavelength bands.     

Future strategies for the treatment of diastolic heart failure

It is estimated that 30% to 50% of heart failure patients have preserved systolic left ventricular (LV) function, often referred to as diastolic heart failure (DHF). Mortality is high in this patient population, and morbidity and rate of hospitalization are similar to those of patients with systolic heart failure. The management of patients with diastolic heart failure is essentially empirical, limited, and disappointing. New drugs, devices, and gene therapy based treatment options are currently under investigation. In this review, future strategies for the treatment of diastolic heart failure are discussed.     

Costs of health care for irritable bowel syndrome, chronic constipation, functional diarrhoea and functional abdominal pain

AIM: To provide estimates of actual costs to deliver health care to patients with functional bowel disorders, and to assess the cost impact of symptom severity, recency of onset, and satisfaction with treatment. METHODS: We enrolled 558 irritable bowel (IBS), 203 constipation, 243 diarrhoea and 348 abdominal pain patients from primary care and gastroenterology clinics at a health maintenance organization within weeks of a visit. Costs were extracted from administrative claims. Symptom severity, satisfaction with treatment and out-of-pocket expenses were assessed by questionnaires. RESULTS: Average age was 52 years, 27% were males, and 59% participated. Eighty percent were seen in primary care clinics. Mean annual direct health care costs were $5049 for IBS, $6140 for diarrhoea, $7522 for constipation and $7646 for abdominal pain. Annual out-of-pocket expenses averaged $406 for treatment of IBS symptoms, $294 for diarrhoea, $390 for constipation and $304 for abdominal pain. Lower gastrointestinal costs comprised 9% of total costs for IBS, 9% for diarrhoea, 6.5% for constipation and 9% for abdominal pain. In-patient care accounted for 17.5% of total costs (15.2% IBS). CONCLUSION: Costs were affected by disease severity (increased), recent exacerbation of bowel symptoms (increased), and whether the patient was consulting for the first time (decreased).     

Pamidronate treatment in rheumatology practice: a comprehensive review

Pamidronate, along with other bisphosphonates, has been used for treatment of bone pain secondary to malignant involvement or metastatic disease for years. Some data, however, have also accumulated on the utility of pamidronate in a variety of benign conditions frequently handled by rheumatologists. This study aims to review the available published data regarding the potential use of pamidronate in rheumatology practice. Methods include the review of relevant articles retrieved by a PUBMED search utilizing the index term “pamidronate”. All available randomized control trials, open trials, and case series, as well as properly reported case studies evaluating usage of pamidronate in rheumatic disorders, have been included in the literature review. The efficacy of pamidronate in patients with spondyloarthropathies; synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome; hypertrophic osteoarthropathy; osteoporotic vertebral fractures; chronic back pain due to disk disease or spinal stenosis; Charcot arthropathy; transient osteoporosis; and complex regional pain syndrome-I, has been demonstrated in more than 40 reports, the majority of which, however, were not controlled studies. In some of reviewed conditions, aside from providing analgesic relief, pamidronate may also have disease-modifying properties. While used in different doses in a variety of rheumatic disorders, pamidronate was generally reported to be well tolerated with an overall good safety profile. Pamidronate may represent an effective and safe choice for a spectrum of rheumatic patients, suffering from intractable musculoskeletal pain, unresponsive to traditionally recommended therapies. Large randomized, controlled studies examining the efficacy of pamidronate in the rheumatic conditions are urgently needed.     

Response Entropy Is More Reactive Than Bispectral Index During Laparoscopic Gastric Banding

Objective. There is a potential use for spectral entropy or bispectral index (BIS) for controlling level of anesthesia, but it is not known how these EEG monitors relate during steady state anesthesia. We compared Response Entropy (RE) and BIS during anesthesia for laparoscopic gastric banding with RE targeted to 45. Methods. Forty patients undergoing laparoscopic gastric banding were randomly assigned to receive either fentanyl or dexmedetomidine infusion, with desflurane concentration adjusted to maintain RE at 45. During anesthesia the average RE and BIS was determined in each patient and the RE-BIS difference plotted as a function of RE every 10 seconds. Fifteen of 40 patients showed activation of RE above 60 during surgery. In these patients RE, BIS and the electromyogram (EMG) were evaluated for the period 10 minutes before and including the peak change in RE. Results. In fentanyl and dexmedetomidine treated patients the average RE was 44–47 with no statistical difference between anesthesia groups or between RE and BIS. In each patient there was a linear relationship between the RE-BIS difference and RE during anesthesia. RE and BIS were similar at a level of 41–44 and RE showed a greater range at higher and lower values compared to BIS. When RE activation was identified during surgery in 15 patients, it was associated with an increase in BIS and EMG. Conclusion. Within the range of 41–44, RE and BIS are equal but the gain of RE is 0.5 greater than BIS with deeper or lighter anesthesia. This is not likely due to increased smoothing with BIS. Identifying periods of RE activation show that BIS, EMG and RE increase together.Feld J, Hoffman WE Park H. Response entropy is more reactive than bispectral index during laparoscopic gastric banding.