Knopka Skachat Fail
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Our prospective study undertaken between June 2006 and May 2007 aimed to collect all antineoplastic medication errors, concerning both unintercepted mistakes that affected patients and intercepted mistakes. Medication errors were defined as a failure in the treatment process, which led to or had the potential to lead to the patient being harmed. The different types of medication errors are defined in Table 1. During routine practice, errors were able to be detected and intercepted at every step of the chemotherapy process, with all health professionals being involved in error detection. Prescription errors were detected by pharmacists using systematic pharmaceutical analysis of all prescribed antineoplastic regimens. Preparation errors were detected during the preparation by the double checked of the fabrication process and by self-reported by pharmacy technicians, or at the time of final pharmaceutical control. Finally, administration errors were reported on a voluntary basis by nurses or physicians.
In total, 341 erroneous prescriptions were reported, with 329 being intercepted. For 191 of the erroneous prescriptions considered to be without impact, the potential severity was assessed by the pharmaceutical team. The remaining 138 cases of intercepted prescriptions (41.9% of erroneous protocols) were analysed by two independent physicians from the haematology, oncology including gastroenterology and radiotherapy, and pneumology wards (Table 5). The concordance of medical judgement was found to vary depending on the medical speciality, being good in haematology (k = 0.75, 53 prescriptions), but moderate in oncology (k = 0.51, 48 prescriptions) and pneumology (k = 0.42, 37 prescriptions). Overall, 81.4% of intercepted medication errors would have had no impact for the patients. However, 13.4% of errors would have resulted in temporary damage and 2.6% in permanent injury, while 2.6% would have compromised the vital prognosis of the patient. The potential injuries from medication errors would have varied, with 40 cases of haematological toxicity, 27 of neurotoxicity, six of hepatic cytolysis, nine of renal failure, three of skin toxicity, and two of cardiac toxicity being avoided. If not intercepted, between four and eight medication errors would have resulted in the patient's death. These avoided incidents related to eight overdosages and one wrong route of administration. The drugs involved in the averted fatal overdosages were vinblastine (592.5 mg prescribed instead of 9.48 mg), vinorelbine (300 mg instead of 30 mg), cisplatin (1, 344 mg instead of 134 mg, a daily dose of 92 mg instead of 34 mg for 5 successive days), doxorubicin (415 mg instead of 41.5 mg), and docetaxel (918 mg instead of 85.5 mg). In addition, two cases of ten-fold dose errors were intercepted with the prescription of 1, 830 mg of etoposide instead of 183 mg and 1, 830 mg of cisplatin instead of 183 mg. The wrong administration route error concerned the erroneous intrathecal administration of intravenous vincristine, which was intercepted just in time in the medical ward.
The stability of temporary anchorage devices (TADs) is critical in orthodontic clinics. The failure of TADs is multifactorial, and the role of the oral microbiome has not been clearly defined. Herein, we attempted to analyze the contribution of the oral microbiome to the failure of TADs.
Next-generation sequencing was adopted for analyzing the microbiome on the TADs from orthodontic patients. 29 TADs (15 failed TADs and 14 successful TADs) were used for 16S rRNA gene sequencing. A total of 135 TADs (62 failed TADs and 73 successful TADs) were collected to conduct metagenomic sequencing. Additionally, 34 verified samples (18 failed TADs and 16 successful TADs) were collected for quantitative real-time polymerase chain reaction analysis (qRT-PCR).
This study illustrated the compositional and functional differences of microorganisms found on successful and failed TADs, indicating that controlling bacterial adhesion on the surface of TADs is essential for their success rate.
The stability of TADs is the premise for their strong anchorage function. However, mobility and failure of TADs are much higher than in dental implants. The failure rate of TADs is 10%-20% [3, 4], posing a great challenge to orthodontists, and the elevated level of failure reduces orthodontic efficacy. Factors that contribute to TAD failure are complicated and ambiguous. Several factors have been reported to be related to TAD failure, including site-related factors, implant-related factors, TAD design, loading force application, and inflammation around the TAD [5,6,7,8,9].
The oral cavity is a unique microenvironment, which harbors distinct microbial communities. The deleterious shift of the microbiota balance is generally recognized as an oral disease driver [10]. In the disease model of periodontitis and peri-implantitis, microbiomes could induce host inflammatory responses and eventually cause bone resorption in surrounding areas. However, TADs differ from the dental implant in the insertion site as well as the non-osseointegration healing process. Therefore, the evidence of microorganisms' negative effects on dental implants might not be applied to TADs. In the case of TADs, it has been suggested that microbiota dysbiosis could hamper the healing process after the insertion of TADs. The insertion process itself triggers host inflammatory responses. If bacterial invasion occurs during the healing process, loss of stability might happen [11]. In order to verify this hypothesis, previous studies have attempted to detect pathogenic bacteria around failed TADs with polymerase chain reaction (PCR) and checkerboard DNA-DNA hybridization technique but failed to build up the connection [12,13,14]. Previous work has only focused on the abundance and detection rate of single bacteria, however, the phylogenetic and functional composition changes of microbiota around failed TADs remain obscure.
Therefore, we hypothesized that there were different microbiota colonized around TADs under different stable conditions. The objective of our study was to reveal the differences in the structure, composition, and function of microbiome colonized around TADs between failed and successful TADs with amplicon sequencing and metagenomic sequencing.
All participants were orthodontic patients under treatment at the Peking University School and Hospital of Stomatology. TADs were applied as anchorage reinforcement during their treatment. Informed consent forms were signed by all participants enrolled in the study. The Ethics Committee of the Peking University School and Hospital of Stomatology approved the study under PKUSSIRB-202060204. TADs were grouped as failed and successful TADs. Failed TADs were defined as TADs showing severe mobility with signs of inflammation and were unable to serve as anchorage devices before the end of the treatment. Successful TADs conversely maintained stability until the end of the treatment. No signs of inflammation or infection were observed.
In metagenomic sequencing, 40 bacterial species were identified with relative abundance greater than 0.5%. Twenty-four bacterial species were found in both the failed TADs and successful TADs. Nine bacterial species were only found in the failed group and 7 bacterial species were only found in the successful group, with a relative abundance greater than 0.5% (Fig. 4A). The most abundant species included Veillonella parvula, Haemophilus parainfluenzae, Actinomyces odontolyticus, Actinomyces israelii, and Streptococcus gordonii.
Differential species between successful and failed TADs. A. The most abundant species was identified through metagenomic sequencing with a relative abundance greater than 0.5%. The blue circle shows species found in failed groups. The red circle shows species found in successful groups. Species found in both groups were depicted in the mutual area. B Differential species with average relative abundance greater than 0.01% between successful and failed TADs based on Wilcoxon's test. C Receiver Operating Characteristic (ROC) analysis of Prevotella intermedia. D Quantitative real-time PCR results of total bacteria load and Prevotella intermedia
We next investigated enriched microbial functions of failed and successful TADs. The heatmap demonstrated the enriched functions of failed TADs. Failed TADs showed enriched KEGG pathways associated with bacterial motility. The flagellar assembly and bacterial chemotaxis-associated genes, including flagellar hook protein FlgE, flagellar motor switch protein FliG, flagellar L-ring protein precursor FlgH, flagellar biosynthetic protein FliP, flagellar basal-body rod protein FlgC, and flagellar biosynthetic protein FliR, were considered pathogenic (Fig. 7A). Failed TADs also showed enriched KEGG pathways associated with oxidative phosphorylation. This mainly included NADH-quinone oxidoreductase subunit J, NADH-quinone oxidoreductase subunit E, and NADH-quinone oxidoreductase subunit K.
Differential functions based on the KEGG database. A Enriched KO pathways in failed groups. KO pathways are depicted in rows. The abundance is shown by the color gradient (blue, not detected; red, most abundant). The sample name is displayed in columns. The blue square circle KO pathways are associated with oxidative phosphorylation. The red square circle KO pathways are associated with flagellar assembly and bacterial chemotaxis. B Dynamics of the microbiome associated with successful and failed TADs. On successful TADs, biofilm exists on the head and the neck of the TAD. The surrounding tissue shows minor signs of inflammation. On failed TADs, biofilm also exists on the body of TAD. Peri-implant inflammation and bone resorption occur on the surrounding tissue. Failed TAD demonstrates enriched functions associated with flagellar assembly, bacterial chemotaxis, and oxidative phosphorylation. The pattern was drafted with reference to KEGG imagery[40, 41] 59ce067264
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