The PerPAIN trial: a pilot randomized controlled trial of personalized treatment allocation for chronic musculoskeletal pain-a protocol.

BACKGROUND: The therapy of chronic musculoskeletal pain (CMSP) is complex and the treatment results are often insufficient despite numerous therapeutic options. While individual patients respond very well to specific interventions, other patients show no improvement. Personalized treatment assignment offers a promising approach to improve response rates; however, there are no validated cross-disease allocation algorithms available for the treatment of chronic pain in validated personalized pain interventions. This trial aims to test the feasibility and safety of a personalized pain psychotherapy allocation with three different treatment modules and estimate initial signals of efficacy and utility of such an approach compared to non-personalized allocation. METHODS: This is a randomized, controlled assessor-blinded pilot trial with a multifactorial parallel arm design. CMSP patients (n = 105) will be randomly assigned 1:1 to personalized or non-personalized treatment based on a cluster assignment of the West Haven-Yale Multidimensional Pain Inventory (MPI). In the personalized assignment condition, patients with high levels of distress receive an emotional distress-tailored intervention, patients with pain-related interference receive an exposure/extinction-tailored treatment intervention and patients who adapt relatively well to the pain receive a low-level smartphone-based activity diary intervention. In the control arm, patients receive one of the two non-matching interventions. Effect sizes will be calculated for change in core pain outcome domains (pain intensity, physical and emotional functioning, stress experience, participant ratings of improvement and satisfaction) after intervention and at follow-up. Feasibility and safety outcomes will assess rates of recruitment, retention, adherence and adverse events. Additional data on neurobiological and psychological characteristics of the patients are collected to improve treatment allocation in future studies. CONCLUSION: Although the call for personalized treatment approaches is widely discussed, randomized controlled trials are lacking. As the personalization of treatment approaches is challenging, both allocation and intervention need to be dynamically coordinated. This study will test the feasibility and safety of a novel study design in order to provide a methodological framework for future multicentre RCTs for personalized pain psychotherapy. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00022792 ( https://www.drks.de ). Prospectively registered on 04/06/2021.

A phase III randomized controlled study on the efficacy and improved bowel function of prolonged-release (PR) oxycodone-naloxone (up to 160/80 mg daily) vs oxycodone PR.

BACKGROUND: Oxycodone/naloxone (OXN PR) is a prolonged-release formulation containing oxycodone and naloxone in a 2:1 ratio. This study aimed to evaluate the tolerability and efficacy of doses up to OXN160/80 mg PR compared with oxycodone prolonged-release formulation (OxyPR) in a randomised controlled trial. METHODS: Two hundred and forty-three patients were randomised to treatment with OXN PR (n = 123) or OxyPR (n = 120) during the 5-week double-blind study. Measured were: opioid-induced constipation [bowel function index score (BFI)]; analgesic efficacy (NRS 0-10); daily laxative rescue medication use; rescue medication use, and the number of complete spontaneous bowel movements (CSBMs) per week. A subanalysis was conducted in cancer patients. RESULTS: Greater reductions in mean BFI scores were reported for the OXN PR group compared with OxyPR from Week 1 onwards; at Week 5 the mean change from baseline was -32.5 versus -14.2. Average 24-h pain scores were low and remained stable in the range 3-4 in both treatment groups. Analgesic rescue medication use was similar between the groups. Patients receiving OXN PR used significantly lower mean daily doses of laxative rescue medication than those receiving OxyPR (P = 0.006). The number of CSBM in the OXN PR group approximately doubled compared with a 25% decrease in the OxyPR group. Comparable results to the total study population were reported in the cancer patient subgroup. CONCLUSIONS: OXN PR in daily doses of up to 160/80 mg significantly improves bowel function compared with equivalent doses of OxyPR while still providing comparable analgesic efficacy. SIGNIFICANCE: Effective analgesia can be achieved using oxycodone/naloxone PR up to 160/80 mg daily without compromising bowel function. A similar outcome was reported in cancer and non-cancer patients.

Long-term efficacy and safety of oxycodone-naloxone prolonged-release formulation (up to 180/90 mg daily) - results of the open-label extension phase of a phase III multicenter, multiple-dose, randomized, controlled study.

BACKGROUND: The inclusion of naloxone with oxycodone in a fixed combination prolonged-release formulation (OXN PR) improves bowel function compared with oxycodone (Oxy) alone without compromising analgesic efficacy. In a recent 5-week, randomized, double-blind comparative trial of OXN PR and OxyPR, it could be shown that the beneficial properties of OXN PR extend to doses up to 160/80 mg. METHODS: Bowel function, pain, quality of life (QoL) and safety of OXN PR up to 180/90 mg daily were evaluated in a 24-week open-label extension phase of the 5-week randomized comparative study in patients with non-malignant or malignant pain requiring opioids and suffering from opioid-induced constipation. RESULTS: During treatment with a mean (SD) daily dose OXN PR of 130.7 (26.56) mg (median, maximum: 120 and 180 mg), the Bowel Function Index (BFI) decreased from 45.3 (26.37) to 26.7 (21.37) with the largest decrease seen in the first week. The average pain over the last 24 h remained stable (median Pain Intensity Scale score 4.0) and QoL was maintained throughout the study. Adverse events were consistent with the known effects of OXN PR and no new safety concerns emerged. Equivalent efficacy and safety benefits were observed in cancer patients. CONCLUSIONS: The OXN PR in doses up to 180/90 mg provides effective analgesia with maintenance of bowel function during long-term treatment. The beneficial effects of such dose levels of OXN PR contribute to stable patient-reported QoL and health status despite serious underlying pain conditions, such as cancer. SIGNIFICANCE: In patients with pain requiring continuous opioid therapy at doses above 80 mg of oxycodone, stable and effective long-term analgesia can be achieved using OXN PR up to 180/90 mg daily without compromising bowel function and may be preferential to supplemental oxycodone.

Long-term evaluation of combined prolonged-release oxycodone and naloxone in patients with moderate-to-severe chronic pain: pooled analysis of extension phases of two Phase III trials.

BACKGROUND: While opioids provide effective analgesia, opioid-induced constipation (OIC) can severely impact quality of life and treatment compliance. This pooled analysis evaluated the maintenance of efficacy and safety during long-term treatment with combined oxycodone/naloxone prolonged-release tablets (OXN PR) in adults with moderate-to-severe chronic pain. METHODS: Patients (N = 474) received open-label OXN PR during 52-week extension phases of two studies, having completed 12-week, double-blind, randomized treatment with oxycodone prolonged-release tablets (Oxy PR) or OXN PR. Analgesia and bowel function were assessed at each study visit using 'Average pain over last 24 h scale and Bowel Function Index (BFI), respectively. Treatment Satisfaction Questionnaire for Medication was assessed at study end only. KEY RESULTS: Improvement in bowel function was particularly marked in patients who switched from Oxy PR in the double-blind phase to OXN PR during the extension phase, resulting in a clinically meaningful reduction (≥12 points) in BFI score: at the start of the extension phases, mean (SD) BFI score was 44.3 (28.13), and was 29.8 (26.36) for patients who had received OXN PR in the double-blind phase. One week later, BFI scores were similar for the two groups (26.5 [24.40] and 27.5 [25.60], respectively), as was observed throughout the following months. Fewer than 10% of patients received laxatives regularly. Mean 24-h pain scores were low and stable throughout the extension phases. No unexpected adverse events were observed. CONCLUSIONS & INFERENCES: Pooled data demonstrate OXN PR is an effective long-term therapy for patients with chronic non-cancer pain, and can address symptoms of OIC. No new safety issues were observed which were attributable to the long-term administration of OXN PR.

Observational, nonintervention, multicenter study for validation of the Bowel Function Index for constipation in European countries.

OBJECTIVE: Constipation is a common adverse event of treatment with opioids for chronic non-malignant pain and may result in a considerable reduction in health-related quality of life. The aim of this study was to assess the psychometric properties of the Bowel Function Index (BFI) in european patients suffering from constipation secondary to opioid analgesic treatment for chronic, non-malignant pain. METHODS: This was a multinational study conducted at 15 clinical sites in the Czech Republic, Germany, Italy, and the United Kingdom. Patients suffering from constipation secondary to opioid analgesic treatment for chronic, non-malignant pain were recruited to complete a series of questionnaires including a socio-demographic form, the BFI, the Patient Assessment of Constipation - Symptoms (PAC-SYM), a global frequency item, and a clinical form. RESULTS: A total of 131 patients were included in this study. Inter-item correlations of the BFI were statistically significant in the moderate to large range and the analysis indicated a strong degree of internal consistency (Cronbach's alpha = 0.86). All correlations between the BFI and the global item were statistically significant in the moderate to high range (r = 0.59 to 0.69; p < 0.0001). Correlations between the BFI and the PAC-SYM were moderate and statistically significant (p < 0.01 to 0.0001). CONCLUSIONS: Although this study was limited by the relatively small sample size, it is a part of an extensive validation program. This study suggests that the BFI is a reliable and valid measure of constipation-related symptomatology in chronic pain patients. This measure may be a valuable indicator of patients' experience of symptoms of opioid treatment of chronic pain in future trials.

Long-term efficacy and safety of combined prolonged-release oxycodone and naloxone in the management of non-cancer chronic pain.

OBJECTIVE: The aim of this study was to assess safety and efficacy of fixed combination oxycodone prolonged release (PR)/naloxone PR in terms of both analgesia and improving opioid-induced bowel dysfunction (OIBD) and associated symptoms, such as opioid-induced constipation (OIC), in adults with chronic non-cancer pain. STUDY DESIGN: These were open-label extension studies in which patients who had previously completed a 12-week, double-blind study received oxycodone PR/naloxone PR for up to 52 weeks. The analgesia study assessed pain using the modified Brief Pain Inventory-Short Form (BPI-SF). The bowel function study assessed improvements in constipation using the Bowel Function Index (BFI). RESULTS: At open-label baseline in the analgesia study (n = 379), mean score [+/- standard deviation (SD)] for the BPI-SF item 'average pain over the last 24 h' was 3.9 +/- 1.52, and this remained low at 6 months (3.7 +/- 1.59) and 12 months (3.8 +/- 1.72). Mean scores for BPI-SF item 'sleep interference', and the BPI-SF 'pain' and 'interference with activities' subscales also remained low throughout the 52-week study. In the bowel function study (n = 258), mean BFI score (+/- SD) decreased from 35.6 +/- 27.74 at the start of the extension study to 20.6 +/- 24.01 after 12 months of treatment with oxycodone PR/naloxone PR. Pain scores also remained low and stable during this study. Adverse events in both extension phases were consistent with those associated with opioid therapy; no additional safety concerns were observed. CONCLUSION: Results from these two open-label extension studies demonstrate the long-term efficacy and tolerability of fixed combination oxycodone PR/naloxone PR in the treatment of chronic pain. Patients experienced clinically relevant improvements in OIBD while receiving effective analgesic therapy.

Combined prolonged-release oxycodone and naloxone improves bowel function in patients receiving opioids for moderate-to-severe non-malignant chronic pain: a randomised controlled trial.

BACKGROUND: This randomised, double-blind, double-dummy, parallel-group multicentre study assessed the impact of a total daily dose of 60-80 mg oral oxycodone prolonged-release (PR)/naloxone PR (OXN PR) as fixed-ratio combination for patients with opioid-induced constipation (OIC) having moderate-to-severe, non-malignant pain. METHODS: During pre-randomisation patients receiving opioids for moderate-to-severe non-malignant pain were converted to oxycodone PR (OXY PR) and titrated to an effective analgesic dose. During randomisation 265 patients on a stable OXY PR dose (60-80 mg/day) and with OIC were included in the full analysis population to receive OXN PR or OXY PR alone. Primary outcome was improvement in symptoms of constipation as measured by the Bowel Function Index (BFI). Secondary/exploratory outcomes examined analgesic efficacy and other bowel function parameters. RESULTS: After 4 weeks of treatment, patients receiving OXN PR showed a significant improvement in bowel function compared with those in the OXY PR group (-14.9; 95% CI: -17.9, -11.9; p<0.0001) as measured by BFI which was seen after only 1 week of treatment continuing to the end of the study. After 4 weeks of treatment, patients receiving OXN PR had a median number of 3.0 complete spontaneous bowel movements (CSBM) per week compared with only 1.0 for OXY PR alone. Laxative intake was lower in the OXN PR than the OXY PR group. Furthermore, improvements in bowel function were achieved without loss of analgesic efficacy; pain intensity scores were comparable between the groups and consistent for duration of the study. Most frequently reported adverse events were consistent with those reported for opioid analgesics; no new or unexpected adverse reactions attributable to OXN PR used in higher doses were observed. CONCLUSION: This study shows that the fixed-ratio combination of OXN PR is superior to OXY PR alone in terms of bowel function, while providing effective equivalent analgesia.

Fixed-ratio combination oxycodone/naloxone compared with oxycodone alone for the relief of opioid-induced constipation in moderate-to-severe noncancer pain.

OBJECTIVE: Opioid therapy is frequently associated with treatment-limiting constipation. Naloxone is an opioid antagonist with low oral systemic bioavailability. This Phase III clinical trial assessed the safety and efficacy of an oral fixed-ratio combination of oxycodone prolonged-release (PR) and naloxone PR compared with oxycodone PR in relieving opioid-induced constipation. STUDY DESIGN: This double-blind, multicenter trial was conducted in specialist and primary care centers in four European countries in an out-patients setting. The study included 322 adult patients with moderate-to-severe, noncancer pain requiring opioid therapy in a range of >or=20 mg/day and

Patient assessment of a novel therapeutic approach for the treatment of severe, chronic pain.

BACKGROUND AND OBJECTIVES: Opioid-induced constipation can have a major negative impact on patients' quality of life. This randomised clinical trial evaluated patient assessment of the efficacy and tolerability of oral prolonged-release (PR) oxycodone when co-administered with oral naloxone PR. METHODS: Two hundred and two patients with chronic cancer- or non-cancer-related pain undergoing stable oxycodone PR therapy (40, 60 or 80 mg/day) were randomised to one of four intervention groups: 10, 20 or 40 mg/day naloxone PR or placebo. Following a 4-week maintenance phase, patients were followed-up for 2 weeks in which time they received oxycodone PR only. At the end of the maintenance phase, patients and investigators were asked to assess treatment efficacy and tolerability, as well as preference for the titration or maintenance phase. RESULTS: Patient and investigator global assessment of efficacy and tolerability improved with increasing naloxone dose. Efficacy was ranked as 'good' or 'very good' by 50.0%, 67.4% and 72.5% of patients in the 10, 20 and 40 mg naloxone PR dose groups, respectively, compared with 43.5% of patients in the placebo group. Patient assessment of tolerability was similar between treatment groups and placebo, being ranked as 'good' or 'very good' by 83.3%, 79.1% and 82.5% of patients in the 10, 20 and 40 mg/day naloxone PR dose groups, respectively, compared with 71.7% of patients in the placebo group. The maintenance treatment phase was preferred by patients in the naloxone groups. A 2 : 1 dose ratio of oxycodone to naloxone was also assessed. Efficacy was ranked as 'good' or 'very good' by 70.4% of patients treated with the 2 : 1 dose ratio compared with 43.5% of patients receiving placebo. Tolerability of the 2 : 1 dose ratio was ranked as being 'good' or 'very good' by 81.5% of patients compared with 71.1% for the placebo group and patients preferred the maintenance phase. CONCLUSIONS: The co-administration of oral naloxone PR with oxycodone PR improves patient assessment of analgesic opioid therapy for severe chronic pain, in terms of both efficacy and tolerability.

[Local therapy of grade IIa burns: efficacy and tolerability of a new hydrosome wound gel for the local treatment of grade IIa burns as compared with silver sulfadiazine ointment]. / Lokale Behandlung von Grad-IIa-Verbrennungen : Wirksamkeit und Verträglichkeit eines neuartigen hydrosomalen Wundgels im Vergleich zu Silbersulfadiazin-Creme.

BACKGROUND: A new hydrosome wound gel is based on a new mechanism of action. It contains hydrosomes that penetrate to the wound bed and supply the wound with phospholipids, which are identical to membrane phospholipids of human cells. In this manner it supports the proliferative processes during wound healing. PATIENTS AND METHODS: In a randomized, controlled, intraindividual comparative study of 47 patients with grade IIa burns, the hydrosome wound gel was tested against silver sulfadiazine cream. Digital pictures of the burn wounds were taken daily, and the wounds were analyzed in terms of their reepithelization rate. RESULTS: Wounds receiving the hydrosome wound gel healed 1.5-2 days faster than wounds treated with sulfadiazine cream (9.9+/-4.5 days vs. 11.3+/-4.9 days, p=0.015). In 66% of the patients, faster epithelization was observed with the hydrosome wound gel treatment. The hydrosome gel guaranteed secure prophylaxis against infection, and it was well tolerated and easy to apply. CONCLUSION: In this study, the treatment of grade IIa burn wounds with hydrosome wound gel led to faster wound closure compared with treatment with sulfadiazine cream. Therefore, hydrosome gel represents a good alternative to sulfadiazine cream.

Repithel: removing the barriers to wound healing.

BACKGROUND: Various standardized and/or validated models exist to test wound healing products. This article discusses their usefulness in clinical practice. OBJECTIVES: Major barriers to wound healing have been identified after intense interaction of research and practitioners. Although extensively tested, wound healing products are still associated with trial and error due to the high variability and complexity associated with the treatment of wounds. Therefore, the results of preclinical testing are compared and contrasted with clinical observations of a liposomal hydrogel containing 3% povidone-iodine (Repithel, PVP-ILH) to assess their expressiveness and to give the practitioner more guidance in application. METHODS: Testing of PVP-ILH included physicochemical testing according to ISO norms, testing in in vitro and in vivo models. The obtained results are compared to the clinical profile of the obtained product in randomized controlled trials and ultimately expressive case studies. RESULTS: PVP-ILH displays good local tolerance, the basis for use in sensitive and predamaged tissue. As observed in laboratory testing, it readily provides moisture and takes up limited amounts of moisture. This was also seen in the clinical testing, as the ability to keep wounds moist and incorporate a certain -- but not large -- amount of exudates. Clinical results also show clean, well-debrided wounds, an effect that (in the absence of an established model for wound cleansing) was traced to the hydrogel component carbomer. DISCUSSION: Recent consensus advocates the concept of wound bed preparation as a systematic approach to removing barriers to healing (TIME). Based on the results, tissue (removing non-viable tissue and debris) and moisture (balance) can now be better understood, and infection/inflammation (control) and edge (progressing, non-advancing or undermining wound edges) are reviewed together with previously published data to assess all aspects potentially impeding wound healing. CONCLUSION: PVP-ILH successfully removes barriers to wound healing, thus laying the foundation to high-quality wound closure. Results from many scientific disciplines can help the user to better understand a product, standardization of testing is the only way of making results comparable.

Membranes for biohybrid liver support: the behaviour of C3A hepatoblastoma cells is dependent on the composition of acrylonitrile copolymers.

Co-polymers based on acrylonitrile, N-vinylpyrrolidone, aminoethylmethacrylate and sodium methallylsulfonate were used to prepare flat membranes by phase inversion. The surface properties of membranes were characterised by water contact angle measurements, atomic force microscopy and X-ray photoelectron spectroscopy (XPS). Membrane permeability was estimated by porosity measurements with water as test liquid. Human C3A hepatoblastoma cells were plated on these materials. Cell-material interaction was characterised by overall cell morphology, formation of focal adhesion contacts and intercellular junctions. Furthermore, cell proliferation was measured and compared with the functional activity of cells as indicated by 7-ethoxycoumarin-O-deethylation. More hydrophilic materials reduced spreading of cells, formation of focal adhesion and subsequent proliferation while homotypic cell adhesion was facilitated in correlation with stronger expressions of intercellular junctions and improved functional activity. In contrast, membranes with stronger adhesivity enhanced cell proliferation but reduced the functional activity of cells. It was concluded that the co-polymerisation of acrylonitrile with hydrophilic co-monomers, such as N-vinylpyrrolidone, could be used to tailor membrane materials for the application in biohybrid liver support systems.

Testing the cytotoxicity of metal alloys used as magnetic prosthetic devices.

Technical magnetic materials are increasingly used for the development of magnetic retained dental prosthetic and orofacial epithetic devices. Since most of the magnets based on rare earth metals, such as samarium-cobalt based alloys have a high tendency for corrosion they were first coated by tin and then encapsulated by titanium. However, the high mechanical load particularly on dental devices may cause a rupture of the titanium capsule and the alloys contact directly biological fluids. Hence, it is important to know the cytotoxicity of these magnets to assess their potential effects on the surrounding tissue. In this study, the cytotoxicity of neodymium-iron-boron and samarium-cobalt (plain, tin and titanium coated) magnets was tested. First, magnets were incubated up to 7 days in culture medium to prepare extracts for cytotoxicity measurements. Changes in the surface morphology due to corrosion were visualized by scanning electron microscopy and analysis of the elemental composition. 3T3 mouse fibroblasts were cultured in the presence of extracts and their viability measured by neutral red and metabolic assays. To learn more about a possible toxic activity of the main components of magnets, salt solutions of different concentrations resembling those elements, which are main constituents of the magnets, were used. 3T3 fibroblasts were also cultured in direct contact with the materials and material induced effects on cell morphology and growth monitored by microscopy. As a result of this study it was found that samarium-cobalt magnets have a strong tendency for corrosion and exert a considerable cytotoxicity. Neodymium-iron-boron magnets have a lesser tendency for corrosion and are only moderate cytotoxic. Coating of samarium-cobalt magnets with tin or titanium makes the materials non-toxic. Application of salt solutions shows that cobalt has a tendency to be cytotoxic at higher concentrations, but enhances cell metabolism and proliferation at lower concentrations while the other magnet constituents had a lower or negligible cytotoxic potential.

First isolation of Trichophyton raubitschekii (syn. T. rubrum) in Europe.

Trichophyton raubitschekii is a rare dermatophyte which belongs to the Trichophyton rubrum species complex. Since 1981, only a few cases of dermatophytosis due to this anthropophilic causative agent were published. In this paper the authors report the first cases of Tinea corporis caused by Trichophyton raubitschekii (syn. T. rubrum) in Europe. The patients, one immigrant from Ghana and three from Cameroon, had typical lesions of tinea corporis. Four strains were isolated and characterized by conventional and molecular methods. On morphological and physiological grounds the isolates were identified as T. raubitschekii by the following phenotypical features: (1) velvety colony texture; (2) brown pigment; (3) abundant macroconidia and (4) positive urease activity. Molecular diagnostics were performed by single strand conformation polymorphism (SSCP) and sequence analysis of the ATPase9 intron of the mitochondrial (mt) DNA and the internal transcribed spacer (ITS) region of the rDNA, respectively. The ITS sequences and SSCP patterns of the ATPase9 intron were found to be identical among the four strains and also when compared to reference strains of T. rubrum. As shown in the present paper, T. raubitschekii is genetically identical to T. rubrum but differs in some phenotypical characteristics. Since misidentification with other dark-coloured dermatophyte variants is possible, medical mycologists should bear in mind the special morphological characteristics of T. raubitschekii (syn. T. rubrum) for future identifications.

Advanced integrated mouse YAC map including BAC framework.

Functional characterization of the mouse genome requires the availability of a comprehensive physical map to obtain molecular access to chromosomal regions of interest. Positional cloning remains a crucial way of linking phenotype with particular genes. A key step and frequent stumbling block in positional cloning is making a contig of a genetically defined candidate region. The most efficient first step is isolating YAC (Yeast Artificial Chromosome) clones. A robust, detailed YAC contig map is thus an important tool. Employing Interspersed Repetitive Sequence (IRS)-PCR genomics, we have generated an advanced second-generation YAC contig map of the mouse genome that doubles both the depth of clones and the density of markers available. In addition to the primarily YAC-based map, we located 1942 BAC (Bacterial Artificial Chromosome) clones. This allows us to present for the first time a dense framework of BACs spanning the genome of the mouse, which, for instance, can serve as a nucleus for genomic sequencing. Four large-insert mouse YAC libraries from three different strains are included in our data, and our analysis incorporates the data of Hunter et al. and Nusbaum et al. There is a total of 20,205 markers on the final map, 12,033 from our own data, and a total of 56,093 YACs, of which 44,401 are positive for more than one marker.

Candida africana sp. nov., a new human pathogen or a variant of Candida albicans?

Atypical Candida strains were isolated from patients in Madagascar, Angola and Germany. These isolates were slow growing and were unable to produce chlamydospores. They had atypical carbohydrate assimilation profiles. All strains were unable to assimilate the amino sugars N-acteylglucosamine and glucosamine as well as the disaccharide trehalose and the organic acid DL-lactate. They were germ-tube-positive in serum, but only some of these organisms produced pseudohyphae after a long incubation. As shown by Fourier transform infrared spectroscopy the atypical Candida isolates clustered as a monophyletic group different from C. albicans and C. dubliniensis. All strains belonged to C. albicans serotype B. Considering all data presented here, this group of Candida strains differs from any other known member of the genus Candida. Therefore, it is suggested to represent a new species within the genus Candida for which the name Candida africana is proposed.

Morphological study of Osteoplate 2000-extension implants after bending.

Unfavorable anatomical conditions of implant sites often require the insertion of implants in a direction that may interfere with the positioning of suprastructural elements in a functionally and esthetically satisfying manner. In some implant systems, bending of the implant neck is one of the possible methods for optimizing the insertion angle for the superimposed prosthesis. The aim of this study was to investigate whether bending procedures of the implant neck cause changes in the surface properties at the implant neck area. After bending of the implant neck up to 30 degrees, scanning electron microscopy revealed changes in the surface texture of the titanium. Superficial rips approximately 5 microns wide and 100 microns long had formed. These findings were confirmed by metallographic examinations. Values of Vickers hardness testing in the implant neck area after bending of 30 degrees showed significant differences between the compression or stretched zone and the neutral zone of the bending area. Bending of the implant neck between 0 and 20 degrees may influence the surface morphology, promoting superficial rips. Plaque accumulation and mechanically induced mucosal irritations due to changes of surface morphology and properties by bending should be further analyzed.

Percutaneous dilatational tracheostomy: still a surgical procedure.

Although percutaneous dilatational tracheostomy (PDT) has been shown to be a cost-effective bedside alternative to open tracheostomy (OT), prior reports of the complications of the procedure are contradictory. Reported complications range from minor events to fatal ones, in varying percentages. This prospective study was designed to identify the type and severity of complications accompanying the introduction of PDT to a tertiary medical center. Surgical and medical intensive care unit (ICU) patients requiring elective tracheostomy were identified as appropriate for PDT using approved institutional criteria. All procedures were performed at an ICU bedside in the presence of a surgeon privileged to perform OT. Demographic data, procedural information, and patient outcome (including minor and major complications, length of stay, and survival) were collected. PDT was performed in 96 ICU patients, with complete data available for 95 patients. PDT was performed in an average of 13.1+/-1.0 minutes. Twenty-three major and minor complications occurred, including two perioperative deaths, in 15 patients (15.8%). A total of 37 PDT patients (38.9%) died in the hospital, indicative of the severity of illness of patients requiring tracheostomy. Based on the experience to date, Cedars-Sinai Medical Center (Los Angeles, CA) continues to require a surgeon privileged to perform OT to participate in all PDT procedures.