What is the most cost-effective treatment for patients with low back pain? A systematic review

Economic evaluations of the various interventions available for low back pain will help clinicians and policymakers to identify the most beneficial treatment. This chapter aims to evaluate the most cost-effective treatments for patients with non-specific low back pain. Pubmed, Embase and the Cochrane library were used to search for articles published from 1966 to July 2004 using a variety of keywords. References were checked to identify additional studies. The consensus health economic criteria (CHEC) list was used to assess the methodological quality of the studies. We found 17 studies; six of these concluded that the intervention of interest was superior to the control intervention. However, definite conclusions about the most cost-effective intervention could not be drawn because of the heterogeneity of interventions, controls and study populations. More high-quality economic evaluations are needed before such a conclusion can be made.     

An optimal therapeutic expression level is crucial for suicide gene therapy for hepatic metastatic cancer in mice

The most serious problem in current gene therapy is discrepancies between experimental data and actual clinical outcomes, which may be due to insufficient analyses and/or inappropriate animal models. We have explored suicide gene therapy by using various clinically relevant animal models and doubt the clinical use of maximal suicide gene expression, which has been generally recommended. To explore this subject further, we studied what expression level of suicide gene and what promoter led to the maximal clinical benefit in the case of hepatic metastatic cancer in mice. Therapeutic and adverse side effects of 4 adenoviral vectors that express herpes simplex virus thymidine kinase (HSV-tk) under different promoters were scrupulously investigated in 2 mouse models of hepatic metastasis of gastric cancer that possess clinical characteristics. Surprisingly, increases in HSV-tk expression beyond a certain point, achieved by the Rous sarcoma virus long terminal repeat promoter, not only enhanced the adverse side effects of lethal hepatotoxicity and ganciclovir-independent cytotoxicity but also failed to further increase therapeutic potential. Moreover, the carcinoembryonic antigen (CEA) tumor-specific promoter, the therapeutic potential of which had been underestimated, was much more useful-even in the case of low CEA-producing cancer-than had been previously reported. In conclusion, the optimal therapeutic expression level of a suicide gene is a novel concept and a crucial factor for successful cancer gene therapy. The present results, which contradict those of previous studies, alert researchers about possible problems with ongoing and future clinical trials that lack this concept.     

Mean systolic ejection rate after aortocoronary bypass graft surgery

In 62 patients with coronary artery disease who underwent aortocoronary bypass graft surgery, we measured the mean systolic ejection rate invasively at rest and during upright exercise before and several months after operation. After bypass surgery, mean systolic ejection rate did not show any change at either supine or sitting rest and at submaximal exercise levels of walking on a treadmill. At maximal exercise, only patients with complete revascularization showed a significant increase in heart rate from 105 to 147 (+40%) and mean systolic ejection rate from 339 ml/sec to 404 ml/sec (+19%, P less than 0.001). Patients with incomplete revascularization did not show a substantial change in these variables. Beta-blocker withdrawal did not affect the result significantly.     

Effects of acute NEFA manipulation on incretin-induced insulin secretion in participants with and without type 2 diabetes

Aims/hypothesis

Incretin effect—the potentiation of glucose-stimulated insulin release induced by the oral vs the i.v. route—is impaired in dysglycaemic states. Despite evidence from human islet studies that NEFA interfere with incretin function, little information is available about the effect in humans. We tested the impact of acute bidirectional NEFA manipulation on the incretin effect in humans.

Methods

Thirteen individuals with type 2 diabetes and ten non-diabetic volunteers had a 3 h OGTT, and, a week later, an i.v. isoglycaemic glucose infusion (ISO; OGTT matched). Both pairs of studies were repeated during an exogenous lipid infusion in the non-diabetic volunteers, and following acipimox administration (to inhibit lipolysis) in people with diabetes. Mathematical modelling of insulin secretion dynamics assessed total insulin secretion (TIS), beta cell glucose sensitivity (β-GS), glucose-induced potentiation (P_GLU) and incretin-induced potentiation (P_INCR); the oral glucose sensitivity index was used to estimate insulin sensitivity.

Results

Lipid infusion increased TIS (from 61 [interquartile range 26] to 78 [31] nmol/m² on OGTT and from 29 nmol/m² [26] to 57 nmol/m² [30] on ISO) and induced insulin resistance. P_INCR decreased from 1.6 [1.1] to 1.3 [0.1] (p?<?0.05). β-GS, P_GLU and glucagon, glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP) responses were unaffected. Acipimox (lowering NEFA by ~55%) reduced plasma glucose and TIS and enhanced insulin sensitivity, but did not change β-GS, P_INCR, P_GLU or glucagon, GLP-1 or GIP responses. As the per cent difference, incretin effect was decreased in non-diabetic participants and unchanged in those with diabetes.

Conclusions/interpretation

Raising NEFA selectively impairs incretin effect and insulin sensitivity in non-diabetic individuals, while acute NEFA reduction lowers plasma glucose and enhances insulin sensitivity in people with diabetes but does not correct the impaired incretin-induced potentiation.

     

Cardiac damage in hypertensive patients with inverse white coat hypertension. Hospitalet study

BACKGROUND: Few studies have assessed the relationship between ambulatory blood pressure (BP) and cardiac damage in essential hypertensive patients with inverse white coat hypertension (IWCH). OBJECTIVES: To determine the frequency of IWCH in untreated grade 1-2 hypertension and to assess possible differences in cardiac damage among patients with IWCH, white coat hypertension (WCH) and the rest of patients with grade 1-2 hypertension. PATIENTS AND METHODS: Two hundred and eleven patients with grade 1-2 hypertension were sequentially included. A good quality 24-h ambulatory BP monitoring was obtained in 204 patients (age: 41 +/- 12 years, 56% males). IWCH was defined as a daytime systolic and/or diastolic BP higher than diagnostic office systolic and/or diastolic BP, respectively. WCH was defined as a daytime BP < 135/85 mmHg. A good quality echocardiogram was obtained in 174 patients. We considered left ventricular hypertrophy a left ventricular mass index (LVMI) > or = 125 g/m2. RESULTS: We found IWCH in 29 subjects (14%), and WCH in 68 (33%). Office BP in patients with IWCH was in an intermediate position between WCH and the rest of grade 1-2 hypertension patients. The IWCH patients showed 24-h, daytime and night-time BP higher than the other groups. Left ventricular mass was significantly greater in patients with IWCH than in the other grade 1-2 hypertension patients after adjusting for age, gender, body mass index, smoking and office BP (regression coefficient 28.14, 95%CI: 7.36-48.91). CONCLUSION: IWCH is independently associated with higher values of left ventricular mass in patients with grade 1-2 hypertension.     

Prediction of maximal cardiac output in preoperative patients with coronary artery disease

Of 100 patients (89 men, 11 women) studied preoperatively to determine their aerobic and hemodynamic profiles at rest and during upright treadmill exercise. The mean maximal cardiac output (CO), measured using the direct Fick principle, was 57 ± 14% of average normal values. The reduction in maximal heart rate (63 ± 13% of normal) was a greater factor in the reduction in CO than stroke volume (88 ± 16% of normal). Maximal oxygen consumption (V?O₂max) was 48 ± 15% of normal and the greater reduction in V?O₂₂max compared with CO was due to lower peripheral extraction in the coronary patients. Variables that correlated with maximal CO in a univariate analysis included angina severity (r = ?0.45), V?O₂₂max (r = 0.67), maximal heart rate (r = ?0.31), left ventricular dysfunction (r = ?0.45), maximal systolic blood pressure (r = ?0.31) and number of vessels with ≥ 50% diameter reduction (r = ?0.3). Resting ejection fraction did not correlate with maximal CO. In a multivariate analysis, 4 variables correlated significantly (r = 0.77) with maximal CO: in order, V?O₂₂max, number of vessels with ≥ 50% stenosis, magnitude of ST depression and sex.     

Anti-beta 2 glycoprotein I antibodies in centenarians

BACKGROUND: Non-organ-specific autoantibodies are present in centenarians without evidence of autoimmune diseases but conflicting or no data on anti-phospholipid and anti-phospholipid binding proteins were reported. OBJECTIVE: To investigate the presence and antigen specificity of anti-phospholipid and anti-phospholipid binding proteins in centenarians. METHODS: Seventy-seven centenarians, 70 adult controls, 65 unselected elderly subjects, and 38 old SENIEUR volunteers were investigated. Anti-cardiolipin, anti-human beta 2 glycoprotein I, and lupus anticoagulant were detected. Antigen specificity was assayed against plates coated with anionic, neutral and cationic phospholipids and beta 2 glycoprotein I-dependence was also evaluated. RESULTS: 54.3% of the centenarians were positive for IgG and 8.6% for IgM anti-beta 2 glycoprotein I antibodies, while only 20.7% centenarians were positive for anti-cardiolipin IgG and 2.59% for IgM; none resulted positive for lupus anticoagulant. Anti-cardiolipin positive sera cross-reacted with negatively charged phospholipids and displayed decreased binding to serum-free cardiolipin-coated plates that was restored by human beta 2 glycoprotein I or fetal calf serum. CONCLUSIONS: Centenarians display high reactivity against human beta 2 glycoprotein I but low binding to the bovine molecule in the anti-cardiolipin assay. In spite of the presence of antibodies comparable to those found in patients with the anti-phospholipid syndrome, no vascular events were reported suggesting the presence of unknown protective factors and/or the lack of triggering factors.     

Osteoprotegerin and receptor activator of nuclear factor-kappaB ligand mRNA expression in patients with rheumatoid arthritis and healthy controls

OBJECTIVE: To further understand the role of osteoprotegerin (OPG) and receptor activator of nuclear factor-kappaB ligand (RANK-L) in rheumatoid arthritis (RA), we studied the levels of RANK-L and OPG mRNA in peripheral blood mononuclear cells (PBMC) and synovial tissue of patients with RA and controls. METHODS: RANK-L and OPG mRNA levels were measured in PBMC and CD4+/CD8+ T cell subsets of patients with chronic RA, osteoarthritis (OA), and healthy controls, using quantitative real-time polymerase chain reaction. OPG and RANK-L mRNA levels were measured in paired blood and synovial tissue samples of patients with early, untreated RA at 2 timepoints with an interval of 16 weeks. RESULTS: RANK-L mRNA levels were significantly higher in PBMC of patients with early and chronic RA compared to healthy controls. Contrary to healthy controls, RANK-L mRNA levels in patients with chronic RA were mainly of CD4+ T cell origin. OPG mRNA was observed in the blood of all (17/17) early RA patients, but could not be detected in chronic RA patients (0/14) or in patients with OA (0/8). Three out of 17 healthy controls showed measurable levels of OPG mRNA. The OPG/RANK-L ratio tended to be higher in the synovium than in the PBMC of early RA patients. RANK-L mRNA in synovial tissue was mainly of non-T cell origin. CONCLUSION: Since RANK-L and OPG mRNA levels are elevated in PBMC of RA patients, and CD4+ T cells are the major contributors to RANK-L mRNA expression, mononuclear cells in patients with RA may be involved in the pathways that regulate bone metabolism.