Microdiscectomy compared with transforaminal epidural steroid injection for persistent radicular pain caused by prolapsed intervertebral disc: the NERVES RCT

Background Sciatica is a common condition reported to affect > 3% of the UK population at any time and is most often caused by a prolapsed intervertebral disc. Currently, there is no uniformly adopted treatment strategy. Invasive treatments, such as surgery (i.e. microdiscectomy) and transforaminal epidural steroid injection, are often reserved for failed conservative treatment. Objective To compare the clinical effectiveness and cost-effectiveness of microdiscectomy with transforaminal epidural steroid injection for the management of radicular pain secondary to lumbar prolapsed intervertebral disc for non-emergency presentation of sciatica of < 12 months’ duration. Interventions Patients were randomised to either (1) microdiscectomy or (2) transforaminal epidural steroid injection. Design A pragmatic, multicentre, randomised prospective trial comparing microdiscectomy with transforaminal epidural steroid injection for sciatica due to prolapsed intervertebral disc with < 1 year symptom duration. Setting NHS services providing secondary spinal surgical care within the UK. Participants A total of 163 participants (aged 16–65 years) were recruited from 11 UK NHS outpatient clinics. Main outcome measures The primary outcome was participant-completed Oswestry Disability Questionnaire score at 18 weeks post randomisation. Secondary outcomes were visual analogue scores for leg pain and back pain; modified Roland–Morris score (for sciatica), Core Outcome Measures Index score and participant satisfaction at 12-weekly intervals. Cost-effectiveness and quality of life were assessed using the EuroQol-5 Dimensions, five-level version; Hospital Episode Statistics data; medication usage; and self-reported cost data at 12-weekly intervals. Adverse event data were collected. The economic outcome was incremental cost per quality-adjusted life-year gained from the perspective of the NHS in England. Results Eighty-three participants were allocated to transforaminal epidural steroid injection and 80 participants were allocated to microdiscectomy, using an online randomisation system. At week 18, Oswestry Disability Questionnaire scores had decreased, relative to baseline, by 26.7 points in the microdiscectomy group and by 24.5 points in the transforaminal epidural steroid injection. The difference between the treatments was not statistically significant (estimated treatment effect –4.25 points, 95% confidence interval –11.09 to 2.59 points). Nor were there significant differences between treatments in any of the secondary outcomes: Oswestry Disability Questionnaire scores, visual analogue scores for leg pain and back pain, modified Roland–Morris score and Core Outcome Measures Index score up to 54 weeks. There were four (3.8%) serious adverse events in the microdiscectomy group, including one nerve palsy (foot drop), and none in the transforaminal epidural steroid injection group. Compared with transforaminal epidural steroid injection, microdiscectomy had an incremental cost-effectiveness ratio of £38,737 per quality-adjusted life-year gained and a probability of 0.17 of being cost-effective at a willingness to pay threshold of £20,000 per quality-adjusted life-year. Limitations Primary outcome data was invalid or incomplete for 24% of participants. Sensitivity analyses demonstrated robustness to assumptions made regarding missing data. Eighteen per cent of participants in the transforaminal epidural steroid injection group subsequently received microdiscectomy prior to their primary outcome assessment. Conclusions To the best of our knowledge, the NErve Root Block VErsus Surgery trial is the first trial to evaluate the comparative clinical effectiveness and cost-effectiveness of microdiscectomy and transforaminal epidural steroid injection. No statistically significant difference was found between the two treatments for the primary outcome. It is unlikely that microdiscectomy is cost-effective compared with transforaminal epidural steroid injection at a threshold of £20,000 per quality-adjusted life-year for sciatica secondary to prolapsed intervertebral disc

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

A blood flow model for sickle cell anemia

A mathematical model has been developed to simulate the time average blood flow throughout the circulatory system of the human body. It was assumed that whole blood obeyed Cassons equation and the flow properties were calculated by means of this relationship. The model is a complete computer simulation designed to calculate the steady flow rates, average pressure gradients, and mean hemoglobin flow rates over the entire vascular system. Pertinent shear stress and shear rate data were submitted to the model to determine the extent to which the above properties were affected by the disease, sickle cell anemia. Possible extension of the model for evaluation of proposed theraputics for sickle cell anemia are discussed

Bistratene A induces a microtubule-dependent block in cytokinesis and altered stathmin expression in HL60 cells

Bistratene A is a cyclic polyether which affects cell cycle progression and can induce phosphorylation of cellular proteins. Treatment of HL60 cells with 100 ng/ml bistratene A was found to inhibit cytokinesis but had no effect on DNA synthesis and nuclear division. Consequently, bistratene A-treated cells became polyploid and multinucleate. In association with the development of this phenotype, the cytoplasmic protein stathmin was biphasically phosphorylated and levels of expression were doubled. Immunostaining of binucleate cells (bistratene A for 24 h) revealed increased alpha-tubulin localization where the cleavage furrow might be expected to form, i.e., along the equatorial plane. Treatment of these binucleate cells with the microtubule depolymerizing agent nocadazole promoted cleavage furrow formation and partially ameliorated the bistratene A-induced block in cell division. These findings implicate the polymerization status of microtubules and stathmin function in the regulation of cytokinesis. (C) 1999 Academic Press

Surveying the RHIO landscape. A description of current RHIO models, with a focus on patient identification

Across the country, new RHIOs are being formed every day. The 21 RHIOs studied by the work group illustrate the variety of purposes, funding, and record linking methods RHIOs may adopt. As this trend continues to evolve and improve, RHIOs may prove to be a valuable stepping stone on the road to a national system in which a patient\u27s medical data will be available anywhere, anytime. Accurate patient identification and linking are the foundation of health technology that is implemented in a RHIO or any similar network that shares patient information. Without accurate patient identification, patient safety and quality of care are compromised. When high percentages of duplication or overlaying of records occurs in electronic health record databases, physician trust in the system is lost. As HIM professionals, we must be involved in addressing the security and confidentiality of RHIO databases and in defining the record linking method appropriate to the RHIO. As professionals skilled in patient identification methods and possessing significant organizational skills and personnel management experience, HIM professionals should become involved in this process at the earliest opportunity in the RHIO formation. HIM professionals can participate in long-term planning, business plan development, and organizational structure definition. Future articles will address how HIM professionals can become involved, what particular attributes and skills they can bring to the table, and job descriptions appropriate to HIM professionals in the healthcare information sharing industry. The work group urges all HIM professionals to become involved personally in this exciting new field