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.     

Bone Mineral Density in the Proximal Femur and Contralateral Knee After Total Knee Arthroplasty

Osteoarthrosis (OA) is often associated with pain and disability, which are relieved after total knee arthroplasty (TKA), but the nature of bone changes associated with OA is controversial. We examined preoperative hip and contralateral knee bone mineral density (BMD) in patients requiring TKA and monitored the BMD changes postoperatively. Sixty-nine patients, scheduled to have TKA for osteoarthrotic knees, had both hips and contralateral knee BMD measured by dual-energy X-ray absorptiometry (DXA) at the time of operation (baseline) and at 1 yr after operation. X-rays of the knee joints were also taken to evaluate the severity of OA. Preoperatively, 27% and 38% of the patients had total hip BMD Z-score more than 1 SD in the operated side and contralateral hips, respectively. In all regions of interest (ROI), the mean baseline BMD of the affected side proximal femur was significantly lower than that of the contralateral side (p < 0.0005-0.019). The severity of OA was not associated with BMD. During 1-yr follow-up, the postoperative knee status and the physical activity of the patients (AKS score) improved. However, neither the hip nor the nonoperated knee BMDs increased. Knee OA is associated with significantly lower BMD values in the affected side compared with the contralateral hip, and these levels remained similar or decreased during a 1-yr follow-up. We conclude that improved mobility after TKA does not improve the effects of preoperative disuse-associated bone loss in the short term.     

Potency variation of small-molecule chymase inhibitors across species

Chymases (EC 3.4.21.39) are mast cell serine proteinases that are variably expressed in different species and, in most cases, display either chymotryptic or elastolytic substrate specificity. Given that chymase inhibitors have emerged as potential therapeutic agents for treating various inflammatory, allergic, and cardiovascular disorders, it is important to understand interspecies differences of the enzymes as well as the behavior of inhibitors with them. We have expressed chymases from humans, macaques, dogs, sheep (MCP2 and MCP3), guinea pigs, and hamsters (HAM1 and HAM2) in baculovirus-infected insect cells. The enzymes were purified and characterized with kinetic constants by using chromogenic substrates. We evaluated in vitro the potency of five nonpeptide inhibitors, originally targeted against human chymase. The inhibitors exhibited remarkable cross-species variation of sensitivity, with the greatest potency observed against human and macaque chymases, with K_i values ranging from ∼0.4 to 72 nM. Compounds were 10-300-fold less potent, and in some instances ineffective, against chymases from the other species. The X-ray structure of one of the potent phosphinate inhibitors, JNJ-18054478, complexed with human chymase was solved at 1.8 Å resolution to further understand the binding mode. Subtle variations in the residues in the active site that are already known to influence chymase substrate specificity can also strongly affect the compound potency. The results are discussed in the context of selecting a suitable animal model to study compounds ultimately targeted for human chymase.     

Comparison of four different sampling methods for detecting pharyngeal carriage of Streptococcus pneumoniae and Haemophilus influenzae in children.

Samples from 96 children with acute respiratory infection were obtained simultaneously with nasal, nasopharyngeal, and oropharyngeal swabs and by nasopharyngeal aspiration and were cultured on chocolate and blood agar plates. The rates of isolation of Streptococcus pneumoniae and Haemophilus influenzae detected by the four sampling methods were compared. Nasopharyngeal aspirates were optimal for the detection of both S. pneumoniae (isolation rate, 33%) and H. influenzae (isolation rate, 31%). When a nasopharyngeal aspirate is not available, such as for healthy children or children with no obtainable secretions, the nasopharyngeal swab seems optimal for the detection of both S. pneumoniae and H. influenzae among children younger than 13 months of age. Among older children, similarly, the nasopharyngeal swab seems optimal for the detection of S. pneumoniae; however, for H. influenzae, the oropharyngeal swab seems optimal.     

Acute infections in children are accompanied by oxidative modification of LDL and decrease of HDL cholesterol, and are followed by thickening of carotid intima-media.

BACKGROUND: Atherosclerosis begins early in life. Infections might contribute to the pathogenesis of atherosclerosis. In this study, we investigated whether acute infections in children could alter the carotid wall morphology and the lipid profile. METHODS: Mean carotid intima-media thickness (IMT) was measured by high-resolution ultrasound in 28 hospitalised children (mean age: 5+/-2 years), who fulfilled the diagnostic criteria of acute infections (body temperature, >38 degrees C; C-reactive protein, >15mg/ml, and clinical), and in 20 age- and gender-matched controls. Antibodies against oxidised low-density lipoprotein (anti-oxLDL antibodies), as well as total and high-density lipoprotein cholesterol (HDL-C) were analysed in all children. The infection group was investigated both during the acute illness and 3 months after clinical recovery (post-infection). RESULTS: During the acute illness, the infection group had elevated anti-oxLDL antibodies and decreased HDL-C, as compared to those obtained at 3 months and in controls (p<0.05). These changes in the infection group were followed, at 3 months, by thickening of carotid intima-media. Those who received antibiotics during their acute illness had less carotid thickening than those who were not treated with antibiotics (p<0.05). CONCLUSION: Acute infections in children seem to be accompanied by enhanced oxidative modification of LDL and by decrease in HDL-C. These lipid changes may be followed by thickening of carotid artery intima-media. These findings suggest that, in childhood, acute infections could be associated with increased risk of atherosclerosis, and warrant further studies on this topic.     

Periodontal treatment needs in populations under 20 years of age in Espoo, Finland and Chiangmai, Thailand

The aim of this study was to assess the periodontal treatment needs at under 20 yr of age in the affluent area of Espoo, Finland, offering comprehensive public dental health care, as compared to a less advantaged area in Chiangmai, Thailand. In Espoo, 50 girls and 50 boys were examined in each age group of 7, 12 and 17 yr. In Chiangmai equal numbers of girls and boys were examined to obtain a group of 89 subjects aged 18.5 + 0.6 yr. According to the Community Periodontal Index of Treatment Needs (CPITN) the need of scaling increased in Espoo from 6% of the 7-yr-olds to 39% of the 17-yr-olds. Moderate pocketing (4-5 mm) occurred in one subject at age 12 and in three subjects at age 17. In Chiangmai, deep pockets (6 mm and over) were recorded for 1%, moderate pockets for a total of 44%, and dental calculus as the highest treatment need indicator in the remaining 55%, indicating a need for professional treatment in 100% of the group examined. The mean number of sextants requiring scaling was 0.6 per person at age 17 in Espoo as compared to 4.5 at 18.5 yr of age in Chiangmai. Three or more healthy sextants per subject were recorded for 47% of the 17-yr-olds in Espoo and for only 6% of the 18.5-yr-olds in Chiangmai. It was concluded that already at young age vast differences occur between periodontal treatment needs in industrialized and developing countries.     

Postoperative parenteral nutrition with high supply of branched-chain amino acids: effects on nitrogen balance and liver protein synthesis

Branched-chain amino acids (BCAA) stimulate muscle and liver protein synthesis in vitro. The significance of this action in catabolic conditions in vivo remains controversial. The effects of a high supply of BCAA in total parenteral nutrition (TPN) on nitrogen balance and liver protein synthesis were studied in a postoperative rat model. After standard operative trauma TPN was commenced with one of two isocaloric programs (I: 20.1% BCAA and II: 50% BCAA) and continued for 48 hr. The relative rate of liver protein synthesis, measured after TPN in vitro by perfusion with 14C-leucine, was similar in both groups (I: 53.4 +/- 17.3 and II: 49.0 +/- 27.3 arbitrary units of synthesis rate, mean +/- SD). The cumulative nitrogen balance was positive with both regimens and was not improved by the high supply of BCAA (I: 2.02 +/- 0.81 and II: 1.87 +/- 0.63 gN/kg/48 hr mean +/- SD). We conclude that after moderate surgical trauma TPN with a high supply of BCAA offers no advantage over conventional TPN.