Subject(s)
Clinical Trials as Topic/statistics & numerical data , Glucocorticoids/adverse effects , Immunosuppressive Agents/adverse effects , Immunotherapy/statistics & numerical data , Neoplasms/drug therapy , Neoplasms/immunology , Glucocorticoids/administration & dosage , Humans , Immunosuppressive Agents/administration & dosage , Immunotherapy/adverse effects , Immunotherapy/methods , Registries , Treatment OutcomeABSTRACT
BACKGROUND: The optimal method for diagnosing ventilator-associated pneumonia (VAP) is controversial and its effect on reported incidence uncertain. This study aimed to model the impact of using either endotracheal aspirate or bronchoalveolar lavage on the reported incidence of pneumonia and then to test effects suggested from theoretical modelling in clinical practice. METHODS: A three-part single-centre study was undertaken. First, diagnostic performance of aspirate and lavage were compared using paired samples from 53 patients with suspected VAP. Secondly, infection surveillance data were used to model the potential effect on pneumonia incidence and antibiotic use of using exclusively aspirate or lavage to investigate suspected pneumonia (643 patients; 110 clinically suspected pneumonia episodes). Thirdly, a practice change initiative was undertaken to increase lavage use; pneumonia incidence and antibiotic use were compared for the 12 months before and after the change. RESULTS: Aspirate overdiagnosed VAP compared with lavage (89% vs 21% of clinically suspected cases, p<0.0001). Modelling suggested that changing from exclusive aspirate to lavage diagnosis would decrease reported pneumonia incidence by 76% (95% CI 67% to 87%) and antibiotic use by 30% (95% CI 20% to 42%). After the practice change initiative, lavage use increased from 37% to 58%. Although clinically suspected pneumonia incidence was unchanged, microbiologically confirmed VAP decreased from 18 to 9 cases per 1000 ventilator days (p = 0.001; relative risk reduction 0.61 (95% CI 0.46 to 0.82)), and mean antibiotic use fell from 9.1 to 7.2 antibiotic days (21% decrease, p = 0.08). CONCLUSIONS: Diagnostic technique impacts significantly on reported VAP incidence and potentially on antibiotic use.
Subject(s)
Pneumonia, Ventilator-Associated/diagnosis , Anti-Bacterial Agents/administration & dosage , Bronchoalveolar Lavage Fluid/microbiology , Critical Care/methods , Drug Utilization/statistics & numerical data , Female , Humans , Incidence , Male , Microbiological Techniques/methods , Middle Aged , Models, Biological , Pneumonia, Ventilator-Associated/drug therapy , Pneumonia, Ventilator-Associated/epidemiology , Prospective Studies , Scotland/epidemiology , Trachea/microbiologyABSTRACT
We describe a case of cytomegalovirus colitis in a critically ill but otherwise immunocompetent 61-year-old male. Infection was demonstrated by histology and confirmed by plasma polymerase chain reaction and detection of cytomegalovirus IgM antibody. The patient was treated with ganciclovir with resolution of the cytomegalovirus viraemia. Cytomegalovirus colitis may be an under-recognised problem in immunocompetent patients who are critically ill. Quantification of plasma cytomegalovirus DNA by polymerase chain reaction is a non-invasive method of supporting the diagnosis and can be used to monitor the treatment of cytomegalovirus infection in the immunocompetent.
Subject(s)
Aortic Aneurysm, Abdominal/surgery , Colitis/diagnosis , Colitis/virology , Cytomegalovirus/isolation & purification , Elective Surgical Procedures/methods , Antiviral Agents/therapeutic use , Cerebral Infarction , Clostridioides difficile/isolation & purification , Colitis/drug therapy , Critical Illness , Diagnosis, Differential , Diarrhea/microbiology , Diarrhea/virology , Fatal Outcome , Ganciclovir/therapeutic use , Humans , Male , Middle Aged , Polymerase Chain Reaction , Postoperative Complications/diagnosis , Postoperative Complications/drug therapy , Postoperative Complications/virology , Respiratory InsufficiencyABSTRACT
Chromosome translocations in the common epithelial cancers are abundant, yet little is known about them. They have been thought to be almost all unbalanced and therefore dismissed as mostly mediating tumour suppressor loss. We present a comprehensive analysis by array painting of the chromosome translocations of breast cancer cell lines HCC1806, HCC1187 and ZR-75-30. In array painting, chromosomes are isolated by flow cytometry, amplified and hybridized to DNA microarrays. A total of 200 breakpoints were identified and all were mapped to 1 Mb resolution on bacterial artificial chromosome (BAC) arrays, then 40 selected breakpoints, including all balanced breakpoints, were further mapped on tiling-path BAC arrays or to around 2 kb resolution using oligonucleotide arrays. Many more of the translocations were balanced at 1 Mb resolution than expected, either reciprocal (eight in total) or balanced for at least one participating chromosome (19 paired breakpoints). Second, many of the breakpoints were at genes that are plausible targets of oncogenic translocation, including balanced breaks at CTCF, EP300/p300 and FOXP4. Two gene fusions were demonstrated, TAX1BP1-AHCY and RIF1-PKD1L1. Our results support the idea that chromosome rearrangements may play an important role in common epithelial cancers such as breast cancer.
Subject(s)
Breast Neoplasms/genetics , Chromosome Breakage , Chromosome Painting/methods , Genes, Neoplasm , Tissue Array Analysis/methods , Translocation, Genetic , Cell Line, Tumor , Chromosome Mapping/methods , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Gene Frequency , Genome, Human , Humans , Membrane Proteins/genetics , Oligonucleotide Array Sequence Analysis , Oncogene Proteins, Fusion/analysis , Oncogene Proteins, Fusion/genetics , Oncogenes/physiology , Telomere-Binding Proteins/geneticsABSTRACT
We use t, b, tau Yukawa unification to constrain supersymmetry parameter space. We find a narrow region survives for mu>0 (suggested by b-->sgamma and the anomalous magnetic moment of the muon) with A0 approximately -1.9m(16), m(10) approximately 1.4m(16), m(16) approximately 1200-3000 GeV and muM(1/2) approximately 100-500 GeV. Demanding Yukawa unification thus makes definite predictions for Higgs and sparticle masses.
