Higher Preimplantation Opioid Doses Associated With Long‐Term Spinal Cord Stimulation Failure in 211 Patients With Failed Back Surgery Syndrome

ObjectiveSpinal cord stimulation (SCS) is an effective treatment in failed back surgery syndrome (FBSS). We studied the effect of preimplantation opioid use on SCS outcome and the effect of SCS on opioid use during a two-year follow-up period.Materials and methodsThe study cohort included 211 consecutive FBSS patients who underwent an SCS trial from January 1997 to March 2014. Participants were divided into groups, which were as follows: 1) SCS trial only (n = 47), 2) successful SCS (implanted and in use throughout the two-year follow-up period, n = 131), and 3) unsuccessful SCS (implanted but later explanted or revised due to inadequate pain relief, n = 29). Patients who underwent explantation for other reasons (n = 4) were excluded. Opioid purchase data from January 1995 to March 2016 were retrieved from national registries.ResultsHigher preimplantation opioid doses associated with unsuccessful SCS (ROC: AUC = 0.66, p = 0.009), with 35 morphine milligram equivalents (MME)/day as the optimal cutoff value. All opioids were discontinued in 23% of patients with successful SCS, but in none of the patients with unsuccessful SCS (p = 0.004). Strong opioids were discontinued in 39% of patients with successful SCS, but in none of the patients with unsuccessful SCS (p = 0.04). Mean opioid dose escalated from 18 ± 4 MME/day to 36 ± 6 MME/day with successful SCS and from 22 ± 8 MME/day to 82 ± 21 MME/day with unsuccessful SCS (p < 0.001).ConclusionsHigher preimplantation opioid doses were associated with SCS failure, suggesting the need for opioid tapering before implantation. With continuous SCS therapy and no explantation or revision due to inadequate pain relief, 39% of FBSS patients discontinued strong opioids, and 23% discontinued all opioids. This indicates that SCS should be considered before detrimental dose escalation.     

Long-term use of probucol in the multifactorial primary prevention of vascular disease

Over 1,200 middle-aged men with no apparent vascular disease participated in a 5-year multifactorial primary prevention trial, in which 612 received dietetic, hygienic and—when indicated—pharmacologic treatment for the following risk factors: hyperlipidemia, hypertension, smoking, obesity and abnormal glucose tolerance. Pharmacologic therapy included hypolipidemic agents (mainly probucol and clofibrate) and antihypertensive drugs (mainly diuretics and β blockers). At the end of the 5 years, results in these men were compared with findings in 610 high risk and 593 low risk control subjects, none of whom had received treatment. Although intervention decreased the mean risk factor status of the treated men by 33%, their 5-year coronary incidence exceeded that of the high risk control subjects (3.1 % vs 1.5%). Stroke incidence, however, was markedly reduced in the treated subjects (0% vs 1.3%). Multivariate analysis showed that the coronary events occurred in patients taking β blockers or clofibrate, while few occurred in those receiving probucol or the diuretics. The decrease in mean serum cholesterol was 15% in men receiving only probucol, and ranged from 0% to 13% in those receiving different drug combinations, including clofibrate plus probucol (11%). Probucol also markedly decreased high density lipoprotein cholesterol levels, especially when combined with clofibrate.

It is possible that adverse drug effects offset the probable benefit of an improved risk profile in the treated men, thereby explaining the greater than expected occurrence of cardiac events in this group. The probucol data, however, suggest that it may not be harmful to lower the high density lipoprotein cholesterol level when there is a significant decrease in total cholesterol as well.     

Amphoterin as an extracellular regulator of cell motility: from discovery to disease

Amphoterin is a ubiquitous and highly conserved protein previously considered solely as a chromatin-associated, nuclear molecule. Amphoterin is released into the extracellular space by various cell types, and plays an important role in the regulation of cell migration, differentiation, tumorigenesis and inflammation. This paper reviews recent research on the mechanistic background underlying the biology of secreted amphoterin, with an emphasis on the role of amphoterin as an autocrine/paracrine regulator of cell migration.     

Micronutrients and other microconstituents

Many furan‐containing natural products that induce increased activity of the glutathione S‐transferase (GST) enzyme system have been found to inhibit tumorigenesis in laboratory animals. 2‐n‐Heptylfuran (HF) and 2‐n‐butylthiophene (BT), a sulfur analogue of furan, are two of the many furans and thiophenes formed during the roasting process of meat. BT and HF, when administered by gavage at doses that ranged from 11 to 90 μmol, induced increased GST activity in various tissues of A/J mice. At 90 μmol/dose, BT induced increased GST in the liver, small bowel mucosa, and lung. No increase in enzyme activity was found in the forestomach. HF was an enzyme inducer in the liver, small bowel mucosa, and forestomach but was inactive in the lung. The acid‐soluble sulfhydryl level, a good measure of glutathione contents in tissues, was examined in tissue homogenates from mice treated with BT and HF. BT induced significant increase of GSH in the liver and lung at the higher doses. No change was observed in either the small bowel mucosa or the forestomach. A 50‐μmol dose of HF was found to increase GSH level in all four tissues studied. The inhibition of lung and forestomach tumorigenesis was carried out with A/J mice using benzo[a]pyrene as the carcinogen. BT treatment resulted in a reduction of tumor multiplicity in the lung and forestomach. The tumor incidence in the forestomach was reduced significantly. The potency of HF as inhibitor of carcinogenesis was similar to that of BT in the forestomach of mice. In the lung, HF was found to be ineffective as an inhibitor of pulmonary adenoma formation. These results suggest that furan‐ and thiophene‐containing compounds may be effective inhibitors of chemical carcinogenesis.     

From biomedical teaching to biopsychosocial education: a process of change in a Finnish medical school

A group of clinicians, teachers and researchers in the University of Oulu have been worried for years about the predominantly biomedical orientation in the local Faculty of Medicine. Therefore, a project group was founded in 1992 to develop the medical degree programme towards a more comprehensive model. This article introduces the main strategies used in the process of change and describes the challenges encountered during the process. There are still many problems in the education of medical students towards a patient and family orientation and in the effort to change the whole medical culture of the university from a biomedical to a biopsychosocial approach. However, in the postgraduate education of general practitioners, we no longer prefer to teach only doctors, but education on the biopsychosocial model will also be arranged to the interdisciplinary teams working in the municipalities in the Province of Oulu in Finland.     

Relation between baseline lipid and lipoprotein values and the incidence of coronary heart disease in the Helsinki Heart Study

A 34% reduction in the incidence of definite coronary heart disease events was observed in dyslipidemic men treated with gemfibrozil in the Helsinki Heart Study, a controlled 5-year, double-blind primary prevention trial for coronary heart disease. Over the entire study period, gemfibrozil therapy induced mean decreases of 10% in serum total cholesterol levels, 11% in low-density lipoprotein (LDL) cholesterol, 35% in triglyceride levels, and a mean increase of 11% in high-density lipoprotein (HDL) cholesterol level, compared with placebo. The differences in percentage changes in LDL cholesterol between gemfibrozil- and placebo-treated men varied among Fredrickson hyperlipoproteinemia types; after 1 year of treatment the difference was greatest for type IIA hyperlipoproteinemia (14 percentage units) and smallest for IIB hyperlipoproteinemia (3 percentage units). The treatment-associated changes in HDL cholesterol and triglycerides did not differ materially between the 3 hyperlipoproteinemia types, when calculated in the same way. The gemfibrozil-associated reduction in incidence of definite coronary events varied among Fredrickson types and among tertiles of baseline HDL cholesterol and triglycerides. The greatest rate reductions were seen in subjects with type IIB hyperlipoproteinemia, low initial HDL level or high initial triglycerides. These results suggest that subjects with low HDL cholesterol and type IIB hyperlipoproteinemia (and possibly type IV hyperlipoproteinemia) would benefit from treatment with gemfibrozil.     

Evaluation of pure-tone audiometric protocols in vestibular schwannoma screening

The objective was to evaluate the pure-tone audiogram-based screening protocols in VS diagnostics. We retrospectively analyzed presenting symptoms, pure tone audiometry and MRI finding from 246 VS patients and 442 controls were collected to test screening protocols (AAO-HNS, AMCLASS-A/B, Charing Cross, Cueva, DOH, Nashville, Oxford, Rule3000, Schlauch, Seattle, Sunderland) for sensitivity and specificity. Results were pooled with data from five other studies, and analysis of sensitivity, specificity and positive likelihood ratio (LR+) for each protocol was performed. Our results show that protocols with significantly higher sensitivity (AMCLASS-A/B, Nashville) show also significantly lowest specificity, and tend to have low association (positive likelihood ratio, LR+) to the VS. The highest LR+ was found for protocols AAO-HNS, Rule3000 and Seattle. In conclusions, knowing their properties, screening protocols are simple decision-making tools in VS diagnostic. To use the advantage of the highest sensitivity, protocols AMCLASS-A + B or Nashville can be of choice. For more reasonable approach, applying the protocols with high LR+ (AAO-HNS, Rule3000, Seattle) may reduce the overall number of MRI scans at expense of only few primarily undiagnosed VS.