Results Of New Treatment Research Articles

Cost-effectiveness of noninvasive liver fibrosis tests for treatment decisions in patients with chronic hepatitis C.

The cost-effectiveness of noninvasive tests (NITs) as alternatives to liver biopsy is unknown. We compared the cost-effectiveness of using NITs to inform treatment decisions in adult patients with chronic hepatitis C (CHC). We conducted a systematic review and meta-analysis to calculate the diagnostic accuracy of various NITs using a bivariate random-effects model. We constructed a probabilistic decision analytical model to estimate health care costs and outcomes (quality-adjusted life-years; QALYs) using data from the meta-analysis, literature, and national UK data. We compared the cost-effectiveness of four treatment strategies: testing with NITs and treating patients with fibrosis stage ≥F2; testing with liver biopsy and treating patients with ≥F2; treat none; and treat all irrespective of fibrosis. We compared all NITs and tested the cost-effectiveness using current triple therapy with boceprevir or telaprevir, but also modeled new, more-potent antivirals. Treating all patients without any previous NIT was the most effective strategy and had an incremental cost-effectiveness ratio (ICER) of £9,204 per additional QALY gained. The exploratory analysis of currently licensed sofosbuvir treatment regimens found that treat all was cost-effective, compared to using an NIT to decide on treatment, with an ICER of £16,028 per QALY gained. The exploratory analysis to assess the possible effect on results of new treatments, found that if SVR rates increased to >90% for genotypes 1-4, the incremental treatment cost threshold for the “treat all” strategy to remain the most cost-effective strategy would be £37,500. Above this threshold, the most cost-effective option would be noninvasive testing with magnetic resonance elastography (ICER = £9,189). Conclusions: Treating all adult patients with CHC, irrespective of fibrosis stage, is the most cost-effective strategy with currently available drugs in developed countries. (Hepatology 2014;60:832–843)

Open partial nephrectomy: outcomes from two UK centres

To define the current achievable outcomes from open partial nephrectomy (OPN) in the UK at a time when other treatments for small kidney tumours are increasingly being advocated. Current knowledge of the effectiveness of OPN is limited by the fact that published data are almost exclusively derived from a very few centres of established world renown. We retrospectively reviewed 100 consecutive planned OPNs in 90 patients at two UK centres; 93 operations were for suspected cancer. The median (range) tumour size was 3.8 (1.2-9) cm. In all, 42 OPNs were imperative for patients with a single kidney (14), synchronous bilateral tumours (20), or renal impairment alone (eight). In 42 patients with a tumour of < or = 4 cm and a normal contralateral kidney the decision to do OPN was considered elective. There were 10 additional operations in seven patients with Von Hippel-Lindau (VHL) disease. In all, 21 OPNs were in the context of a single kidney. In all, 95 OPNs were successfully completed; one operation was abandoned and there were four nephrectomies, including two for bleeding, one for a positive margin on frozen-section analysis, and one for multifocal tumours. The median warm/cold ischaemia time was 20/33 min. The intraoperative/early complication rate was 36%, including a major complication rate of 11% and re-operation rate for primary bleeding of 3%. Of 36 complications, 30 (83%) were in 23 patients with either an imperative indication or VHL. Complications were more common in the imperative/VHL group (59%) than in the elective/other group (12%). Renal function was preserved in 80 of 100 (80%) OPNs overall. Creatinine levels returned to baseline in 11 of 21 (50%) patients with renal impairment before OPN and in 12 of 20 (60%) with a single kidney, whilst five of 21 (24%) with a single kidney needed dialysis after OPN. The median (range) stay after surgery was 6 (3-50) nights. A malignant diagnosis was confirmed in 76 of 93 (82%) specimens on final histopathology. There were 11 of 100 (11%) positive margins, one managed by immediate conversion to nephrectomy and the remaining 10 managed expectantly. After a median (range) follow-up of 24 (1-69) months there were no deaths from kidney cancer, but three patients had local recurrences and two others had developed metastatic recurrence. OPN is complex surgery, especially in the imperative setting, but very good results are achievable outside established centres of world renown. It provides good cancer control in the short term with low renal morbidity. These results may act as a reference point in the UK by which to compare results of new treatments for kidney cancer.

Results of radiation monotherapy for primary central nervous system lymphoma in the 1990s

Results of radiation therapy for primary central nervous system lymphoma (PCNSL) were poor in the 1970-1980s, with most reported 5-year survival rates being less than 10%. To investigate whether the prognosis of PCNSL patients treated by radiation alone remains still poor, we investigated the results of radiation monotherapy in the 1990s. We collected data on 132 patients with histologically proven PCNSL treated by radiation alone in the 1990s from three nationwide or regional multiinstitutional studies conducted by the Japanese Society for Therapeutic Radiology and Oncology (JASTRO) Lymphoma Study Group or the Chubu Radiation Oncology Group. Follow-up data were updated as far as possible. Eleven patients who did not complete planned radiotherapy were included. The data were analyzed in relation to patient and tumor characteristics. The median patient age was 63 years, and the World Health Organization performance status (PS) was 3 or 4 in 40% of the patients. Multiple tumors were seen in 34%. Whole-brain irradiation with or without focal boost was used in 92%. The median radiation dose to the tumor site was 50 Gy (range, 8-74 Gy). For all 132 patients, the median survival time was 18 months and the 5-year survival rate was 18.0%. For 62 patients with PS 0-3 and aged 16-65 years (i.e., those eligible for the European Organization for Research and Treatment of Cancer 20962 study), the median survival was 26 months and 5-year survival was 24%. The 5-year survival was 25% for patients 63 years old or younger, and 9.8% for those older than 63 years (p = 0.0005). The 5-year survival was 22% for patients with PS 0-2 and 13% for those with PS 3 or 4 (p = 0.0040). Multivariate analysis confirmed the negative influence of higher age on patient prognosis. The results of radiation monotherapy for PCNSL appear to have improved as compared with those reported previously. The results of new treatment should be evaluated in light of this finding. Since most prospective studies on the combined treatment exclude poor PS and high-age patients, the 5-year survival rate of 30% may not be regarded as a marked improvement over radiation alone.

Síndrome de Down y demencia

To review the relationship between Down's syndrome and Alzheimer's disease. Down's syndrome is the commonest autosomopathy. Its clinical features permit easy diagnosis. Control of the more severe complications, such as cardiac malformations have allowed prolonged survival. The presence of neuropathological findings similar to those in Alzheimer's disease is almost constant in the brains of patients aged over 40 years with Down's syndrome. Dementia appears in a third of these patients. In this article we comment on the diagnostic difficulties, possible risk factors and the importance of findings related to chromosome 21. We also evaluate the results of new treatments with cholinesterase inhibitors. The study of the close relationship between Down's syndrome and Alzheimer's disease should allow us to advance understanding of both of these conditions.

Fecundability rates from an infertile male population.

From a computer file of 955 couples attending hospital because of an infertile marriage, 279 were identified where the female partner had normal investigation results. Follow-up information was available for all couples and the fecundability (conception rate per month) for the first year of follow-up has been calculated, stratified according to the husband's investigation results. The fecundability of couples where the wife had normal investigation results but the husband had reduced sperm density ranged from 0.4% for wives with azoospermic husbands to 5.9% when the husband had at least 10 million motile sperm/ml. For any given number of motile sperm the fecundability was also strongly dependent on the duration of involuntary infertility as recorded at the time of initial clinic attendance. In view of the lack of effective treatment for most male infertility the fecundability rates reported herein are likely to represent those that would be found in an untreated population and should be useful as a base line when evaluating results of new treatments.

Psychiatric types: a Q-technique study of 200 patients.

Psychiatry is handicapped in the task of evaluating new methods of treatment because it has had to tackle the problems presented by early and mild cases without modern psychometric methods. There is clearly something wrong when the spontaneous remission rate in schizophrenia can be reported by the New York State Hospitals as 59 per cent. (1944) at a time when the equivalent figure in Kent (Monro, 1950) was 24 per cent. The practical impact of this failure to define terms is that the majority of articles describing the results of new treatments lose most of their force. This happens most obviously when the cases considered are presented simply in diagnostic categories, for example, as x schizophrenics or y hysterics. The trouble can be lessened by giving more clinical detail, but seldom can enough diagnostic and prognostic information be given to enable the reader to arrive at a proper evaluation of the issues presented. New descriptive techniques are therefore an urgent practical necessity, as well as being theoretically desirable.