Association between intraoperative opioid administration and 30-day readmission: a pre-specified analysis of registry data from a healthcare network in New England.

BACKGROUND: The use of intraoperative opioids may influence the rate of postoperative complications. This study evaluated the association between intraoperative opioid dose and the risk of 30-day hospital readmission. METHODS: We conducted a pre-specified analysis of existing registry data for 153 902 surgical cases performed under general anaesthesia at Massachusetts General Hospital and two affiliated medical centres. We examined the association between total intraoperative opioid dose (categorised in quintiles) and 30-day hospital readmission, controlling for several patient-, anaesthetist-, and case-specific factors. RESULTS: Compared with low intraoperative opioid dosing [quintile 1, median (inter-quartile range): 8 (4-9) mg morphine equivalents], exposure to high-dose opioids during surgery [quintile 5: 32 (27-41) equivalents] is an independent predictor of 30-day readmission [odds ratio (OR) 1.15 (95% confidence interval 1.07-1.24); P<0.001]. Ambulatory surgery patients receiving high opioid doses were found to have the greatest adjusted risk of readmission (OR 1.75; P<0.001) with a clear dose-response effect across quintiles (P for trend <0.05), and were more likely to be readmitted early (postoperative days 0-2 vs 3-30; P<0.001). Opioid class modified the association between total opioid dose and readmission, with longer-acting opioids demonstrating a stronger influence (P<0.001). We observed significant practice variability across individual anaesthetists in the utilisation of opioids that could not be explained by patient- and case-specific factors. CONCLUSIONS: High intraoperative opioid dose is a modifiable anaesthetic factor that varies in the practice of individual anaesthetists and affects postoperative outcomes. Conservative standards for intraoperative opioid dosing may reduce the risk of postoperative readmission, particularly in ambulatory surgery.

Association between intraoperative non-depolarising neuromuscular blocking agent dose and 30-day readmission after abdominal surgery.

BACKGROUND: We hypothesised that intraoperative non-depolarising neuromuscular blocking agent (NMBA) dose is associated with 30-day hospital readmission. METHODS: Data from 13,122 adult patients who underwent abdominal surgery under general anaesthesia at a tertiary care hospital were analysed by multivariable regression, to examine the effects of intraoperatively administered NMBA dose on 30-day readmission (primary endpoint), hospital length of stay, and hospital costs. RESULTS: Clinicians used cisatracurium (mean dose [SD] 0.19 mg kg-1 [0.12]), rocuronium (0.83 mg kg-1 [0.53]) and vecuronium (0.14 mg kg-1 [0.07]). Intraoperative administration of NMBAs was dose-dependently associated with higher risk of 30-day hospital readmission (adjusted odds ratio 1.89 [95% Confidence Interval (CI) 1.26-2.84] for 5th quintile vs 1st quintile; P for trend: P<0.001), prolonged hospital length of stay (adjusted incidence rate ratio [aIRR] 1.20 [95% CI 1.11-1.29]; P for trend: P<0.001) and increased hospital costs (aIRR 1.18 [95% CI 1.13-1.24]; P for trend: P<0.001). Admission type (same-day vs inpatient surgery) significantly modified the risk (interaction term: aOR 1.31 [95% CI 1.05-1.63], P=0.02), and the adjusted odds of readmission in patients undergoing ambulatory surgical procedures who received high-dose NMBAs vs low-dose NMBAs amounted to 2.61 [95% CI 1.11-6.17], P for trend: P<0.001. Total intraoperative neostigmine dose increased the risk of 30-day readmission (aOR 1.04 [1.0-1.08], P=0.048). CONCLUSIONS: In a retrospective analysis, high doses of NMBAs given during abdominal surgery was associated with an increased risk of 30-day readmission, particularly in patients undergoing ambulatory surgery.

Trace metal contents of three tricalcium silicate materials: MTA Angelus, Micro Mega MTA and Bioaggregate.

AIM: To investigate the levels of nine metals [aluminium (Al), antimony (Sb), arsenic (As), beryllium (Be), cadmium (Cd), chromium (Cr), iron (Fe), lead (Pb) and molybdenum (Mo)] in MTA Angelus, Micro Mega MTA and Bioaggregate using inductively coupled plasma-optical emission spectrometry (ICP-OES). METHODOLOGY: Each material (0.2 g) was digested using a mixture of hydrochloric and nitric acids and then filtered. The levels of nine metals in the resulting filtrates were measured by ICP-OES. The results were statistically analysed using one-way anova and the Bonferroni test. RESULTS: MTA Angelus contained more aluminium, beryllium and chromium than Micro Mega MTA (P < 0.05), whilst their levels of arsenic, cadmium and iron were similar. Antimony, lead and molybdenum were not detected in any of the three tested cements. Bioaggregate contained trace amounts of aluminium. CONCLUSIONS: MTA Angelus and Micro Mega MTA contained small amounts of seven tested metal oxides. Bioaggregate only contained trace amounts of aluminium.

Antimicrobial efficacy of a human ß-defensin-3 peptide using an Enterococcus faecalis dentine infection model.

AIM: To assess the antibacterial efficacy of a human ß-defensin-3 (HBD3) peptide against Enterococcus faecalis biofilms. METHODOLOGY: Standardized human dentine blocks were infected with E. faecalis ATCC 29212 for 3 weeks. Aqueous calcium hydroxide paste (n = 12, CH), a 2% chlorhexidine gel (n = 12, CHX), an HBD3 peptide gel (n = 12) and saline (n = 12) were tested as experimental groups. A mismatched peptide gel group (n = 12, MP) and sterilized but noninoculated block group (n = 12) were included as controls. After 1 week of medication, the dentinal samples at the depth of 200 and 400 µm were collected from medicated canal lumens. Bacterial growth was assessed by spectrophotometric analysis of optical density (OD) after 72 h of incubation. Statistical analysis was performed with repeated-measures anova and Tukey's post hoc test. RESULTS: The HBD3 group was associated with significantly lower OD values (P < 0.05) than the CH or CHX groups at both depths. The CH group did not differ significantly from MP or Saline group at either depth (P > 0.05). There was no significant difference (P > 0.05) in the OD values of the inner (200 µm) and outer (400 µm) dentinal samples for any group. CONCLUSIONS: The HBD3 peptide inhibited the growth of E. faecalis biofilms in infected dentine blocks.

Data resources for epidemiology of skin diseases.

Among existing data sets the First National Health and Nutrition Examination Survey (NHANES-I) stands out for its large sample size and detailed examination of the skin. However, because NHANES-I employed many different examiners and no uniform diagnostic criteria, the quality of the data is variable. Furthermore, the survey was conducted in the 1970s and does not contain information necessary to answer some currently relevant epidemiologic questions. Future data collection efforts will have to be planned to address specific hypotheses. In addition, future dermato-epidemiologic studies will have to pay careful attention to diagnostic accuracy.

Incidence of alopecia areata in Olmsted County, Minnesota, 1975 through 1989.

OBJECTIVE: To assess the incidence and natural history of alopecia areata (AA) among unselected patients from a community. DESIGN: We conducted a retrospective population-based descriptive study of AA among residents of Olmsted County, Minnesota, for the period from 1975 through 1989. MATERIAL AND METHODS: After identifying 292 Olmsted County residents first diagnosed with AA during the 15-year study period, we reviewed their complete (inpatient and outpatient) medical records in the community and statistically analyzed the effects of gender and age-group. RESULTS: The overall incidence of AA was 20.2 per 100,000 person-years and did not change with time. Rates were similar in the two genders and over all ages, and lifetime risk was estimated at 1.7%. Eighty-seven percent of patients were examined by a dermatologist who diagnosed AA, and 29% of cases were confirmed by biopsy. Most patients had mild or moderate disease, but alopecia totalis or universalis developed at some point during the clinical course in 21 patients. CONCLUSION: This study of the incidence and natural history of AA in a community shows that this disorder is fairly common and can be seen at all ages. Although spontaneous resolution is expected in most patients, a small but significant proportion of cases (probably approximately 7%) may evolve into severe and chronic hair loss, which may be psychosocially devastating for affected persons.

Effects of a bacterial cell wall fragment on monocyte inflammatory function.

Gram-negative bacteria recovered from necrotic pulps of teeth with periapical lesions have been shown to promote bone resorption through the effects of their lipopolysaccharide (LPS). Recently, it was shown that microflora of root-filled teeth with persisting periapical lesions consisted mainly of single species of Gram-positive bacteria. But Gram-positive bacteria do not contain LPS and their role in the development of periapical lesions is not clearly understood. The purpose of this study was to evaluate the effects of muramyl dipeptide (MDP), a cell wall component of both Gram-negative and Gram-positive bacteria, on cytokine release from monocytes. Human monocyte cultures were treated with MDP or LPS and interleukin-1 beta, and tumor necrosis factor-alpha levels in the supernatants were estimated. MDP and LPS stimulated cytokine release, but the effect of MDP was significantly less than that of LPS.

Influence of mixing vehicle on dissociation of calcium hydroxide in solution.

The antimicrobial effects of aqueous preparations of calcium hydroxide have been demonstrated in the past. Calcium hydroxide, when dissolved in water, dissociates into hydroxide and calcium ions. The presence of hydroxide ions in a solution makes it antimicrobial. Recently it was shown that the use of glycerin as a mixing vehicle facilitates placement of calcium hydroxide in the root canals. The influence of nonaqueous mixing vehicles on the dissociation of calcium hydroxide is not clearly understood. In this study the conductivity of aqueous and nonaqueous solutions of calcium hydroxide was measured. The conductivity values for saturated solutions of calcium hydroxide in water was 7.3+/-3 mS/cm. The conductivity of calcium hydroxide in pure glycerin or propylene glycol was essentially zero. It was concluded that use of nonaqueous mixing vehicles may impede the effectiveness of calcium hydroxide as a root canal dressing.

Effect of calcium hydroxide on bacterial lipopolysaccharide.

Apical periodontitis and its concomitant periapical osteolysis is caused by pulpal infection, and bacterial lipopolysaccharide (LPS) is known to play a major role in the bone resorption process. Little is known concerning the effect of root canal intervisit dressings on residual LPS in root canals after bacterial cell lysis. The purpose of this study was to evaluate the effects of calcium hydroxide on bacterial LPS. Free hydroxy fatty acids were quantified in samples of LPS treated with calcium hydroxide. Calcium hydroxide treatment of LPS was shown to release elevated quantities of hydroxy fatty acids. It was concluded that calcium hydroxide hydrolyzed the lipid moiety of bacterial LPS, resulting in the release of free hydroxy fatty acids. This result suggests that calcium hydroxide-mediated degradation of LPS may be an important reason for the beneficial effects obtained with calcium hydroxide use in clinical endodontics.

Alteration of biological properties of bacterial lipopolysaccharide by calcium hydroxide treatment.

Bacterial lipopolysaccharide (LPS) plays a major role in the development of periapical bone resorption. Although the chemical properties of LPS are altered by treatment with an alkali such as calcium hydroxide, the effects of calcium hydroxide on the biological properties of LPS are not known. The purpose of this study was to investigate whether treatment of LPS with calcium hydroxide alters its biological action as measured by human monocyte secretion of prostaglandin E2. Monocyte cell cultures were stimulated with LPS or calcium hydroxide-treated LPS and culture supernatants were analyzed for prostaglandin E2 content using gas chromatography-mass spectrometry. Prostaglandin E2 was identified in supernatants of LPS-stimulated monocytes but not in those stimulated with calcium hydroxide-treated LPS. It was concluded that the treatment with calcium hydroxide may alter biological properties of bacterial LPS.

Tumor necrosis factor identified in periapical tissue exudates of teeth with apical periodontitis.

Root canal samples, taken from periapical tissue exudates during routine root canal treatment procedures, were processed for identification of tumor necrosis factor using a mouse anti-human monoclonal antibody and enzyme-linked immunosorbent assay. Detectable levels of tumor necrosis factor were identified in periapical tissue exudates in chronic apical periodontitis.

Adherence of enamel matrix derivatives on root-end filling materials.

It was recently shown that application of enamel matrix derivatives (EMDs) on denuded root dentin promotes periodontal regeneration. EMD is shown to adhere to the etched dentin, but its adherence to root-end filling materials is not known. The purpose of this study was to evaluate the adherence of a commercially available EMD product to root-end filling materials. Dentin sections were embedded in blocks made of acrylic resin. Cavities were prepared in similar acrylic resin blocks and were filled with amalgam, IRM, or composite resin. EMD was labeled with radioactive iodine and applied to the surfaces of the dentin sections, freshly made fillings, or acrylic resin controls. The specimens were rinsed, and the amount of radioactive iodine was determined in a gamma counter. Substantial amounts of EMD adhered to dentin sections. EMD adherence to amalgam and IRM was significantly less than to dentin or composite resin.

Integrin expression in human dental pulp cells and their role in cell attachment on extracellular matrix proteins.

Integrins are a family of heterodimeric glycoproteins consisting of alpha and beta subunits that noncovalently interact to form cell surface adhesion receptors. The objective of this study was to identify integrins in human dental pulp cells and determine their role in human dental pulp cell attachment to the biological active molecules, laminin and fibronectin. Integrin expression was studied by immunoblot and immunoprecipitation using monoclonal integrin antibodies. The role of integrin in human dental pulp cell adhesion on laminin and fibronectin was determined by inhibition of cell adhesion with those antibodies. This study found human dental pulp cells expressed alpha 1, alpha 3, alpha 5, alpha 6, alpha v, and beta 1 integrin subunits. The adhesion of human dental pulp cells to laminin and fibronectin was not inhibited by monoclonal antibody to any subunit, except that anti-beta 1 antibody inhibited pulp cells adhesion on laminin. These data provide information for further studying the role of integrins in dental pulp cell biological function.

Cytotoxic evaluation of root-end filling materials in cultures of human osteoblast-like cells and periodontal ligament cells.

The cytotoxicity of three root-end filling materials (amalgam, IRM, and Super-EBA) was evaluated in cultures of human periodontal ligament cells and human osteoblast-like cells. Ten-millimeter-long plastic test tubes were filled with 3 mm of freshly mixed root-end filling materials at one end (1.5 mm diameter). The opposite end was sealed and attached by heat to a 35-mm cell culture dish. Human periodontal ligament cells and human osteoblast-like cells were seeded in the dishes. The size of cell-free zones around the root-end filling materials and the total cell number per dish were calculated after 3 and 7 days. Empty test tubes used as controls did not influence the growth and distribution of the cultured cells. Cell density increased in all groups in the test period. Amalgam had a larger cell-free zone, compared with IRM and Super-EBA and showed a reduction in total cell number per dish for both tested cell types. IRM and Super-EBA also had a cell-free inhibition zone for both cell types, but no significant reduction in total cell number per dish. This study showed that amalgam had a higher cell toxicity to human periodontal ligament cells and human osteoblast-like cells than IRM and Super-EBA.

Root canal dentinal tubule disinfection.

Dentinal tubules of the root canal walls of human teeth were infected in vitro with a known bacterial isolate. The roots were exposed to either calcium hydroxide or iodine potassium-iodide for various periods of time and the viability of microorganisms was determined by incubation of entire root samples in a culture medium. The effects of the two agents on microbial viability were evaluated and compared. Iodine potassium-iodide disinfected dentin effectively. In contrast, bacteria remained viable in the dentin after relatively extended periods of calcium hydroxide treatment.

Adhesion of human osteoblasts on root-end filling materials.

Adhesion of human osteoblasts to root-end filling materials (mineral trioxide aggregate (MTA), IRM, composite, and amalgam) was observed by scanning electron microscopy. Root-end filling materials were inserted into 96-well flat-bottomed plates and condensed to disks of approximately 1 mm thick and the same diameter as the wells. After the disks were set, they were placed in the bottom of Nunc four-well culture plates at one disk per well. Then human osteoblasts were seeded into the wells at 1.5 x 10(5) cells per well. After 1 day in culture the disks of root-end filling materials along with cells grown on their surface were examined with a scanning electron microscopy. Results showed that osteoblasts attached and spread on MTA and composite by forming a monolayer. Osteoblasts also attached on amalgam, but with few cells spreading. In the presence of IRM, osteoblasts appeared rounded with no spreading. These results indicate that osteoblasts have a favorable response to MTA and composite resin compared with IRM and amalgam.

An in vitro method for longitudinal evaluation of toxicity of endodontic sealers.

An in vitro method for longitudinal evaluation of root canal sealers was developed and applied. A newly introduced cell culture chamber was used to evaluate the cytotoxic effects of test samples immediately after mixing and for an extended period of time thereafter. A ranking of the test materials, based on their cytotoxicity, was allowed by the method.

Antifungal effects of sodium hypochlorite and chlorhexidine in root canals.

The purpose of this study was to evaluate the antifungal properties of 0.12% chlorhexidine, 1% NaOCl, and 5% NaOCl. Root sections were enlarged and the smear layer was removed in half of the specimens. The specimens were fixed in the wells of tissue culture plates. Each root canal was dispensed with an inoculum of Candida albicans. After 10 days, the root sections were treated with 3 ml of either disinfectant solution for 1 min, 5 min, 30 min, and 1 h. Then, root sections were incubated in test tubes having Sabouraud's Dextrose Broth at 37 degrees C for 24 h. In the presence of the smear layer, antifungal activity was observed only in 1-h treatment groups for all solutions. However, in the absence of the smear layer, 5% NaOCl alone started to show antifungal activity after 30 min. The antimicrobial effectiveness of irrigating solutions should be re-evaluated, particularly in patients predisposed to oral candidiasis.

Enamel matrix derivative prolongs primary osteoblast growth.

Enamel matrix derivative (EMD) secreted by cells of the epithelial root sheath plays an important role in cementogenesis and periodontal tissue formation. The mechanisms by which EMD influences cell function are not known. The purpose of this study was to determine the effect of EMD on cell growth of primary mouse osteoblasts. Osteoblasts were digested from 6- to 8-day-old mouse calvaria and plated into 6-well cell culture plates at an initial density of 5000 cells/cm2. After 24-h incubation with Dulbecco's modified eagle medium (DMEM) supplemented with 10% fetal bovine serum, cells were incubated in three different groups of media: DMEM only as control, DMEM with 25 microg/ml EMD, and DMEM with 100 microg/ml EMD. At days 3, 7, 10, and 14, the total cell number per well was calculated, and cell morphology was examined. At each observation period the number of cells in the EMD groups was significantly greater (ANOVA, p < 0.01) than that in the control group. EMD had a greater effect on osteoblast survivor in the higher concentration than in the lower concentration. Furthermore normal morphology of the primary osteoblasts was maintained in the EMD groups. These results suggest that EMD prolongs primary osteoblast growth and may have an effect on osteoblasts during periodontal regeneration.

Colonization of Candida albicans on cleaned human dental hard tissues.

Candida albicans is a fungus that commonly infects oral mucosal surfaces. Limited data exist on biofilm formation by C. albicans on dental surfaces. Human premolar teeth were infected with C. albicans for 10 days and hard-tissue surfaces were examined with a scanning electron microscope. Enamel, cementum and dentine, in the absence or presence of a smear layer, were readily colonized by this micro-organism. Hyphae penetrated into cracks, followed the ridges of the cavities and migrated into dentinal tubules. Blastospores and hyphae were embedded in an extracellular material. These findings suggest that dental hard tissues may be invaded by C. albicans and thus can potentially present a reservoir for disseminating candidal infections.