Project description:Ventilator-associated tracheobronchitis (VAT) is associated with increased duration of mechanical ventilation. We hypothesized that, in patients with VAT, antibiotic treatment would be associated with reduced duration of mechanical ventilation.We conducted a prospective, randomized, controlled, unblinded, multicenter study. Patients were randomly assigned (1:1) to receive or not receive intravenous antibiotics for 8 days. Patients with ventilator-associated pneumonia (VAP) prior to VAT and those with severe immunosuppression were not eligible. The trial was stopped early because a planned interim analysis found a significant difference in intensive care unit (ICU) mortality.Fifty-eight patients were randomly assigned. Patient characteristics were similar in the antibiotic (n = 22) and no antibiotic (n = 36) groups. Pseudomonas aeruginosa was identified in 32% of VAT episodes. Although no difference was found in mechanical ventilation duration and length of ICU stay, mechanical ventilation-free days were significantly higher (median [interquartile range], 12 [8 to 24] versus 2 [0 to 6] days, P < 0.001) in the antibiotic group than in the no antibiotic group. In addition, subsequent VAP (13% versus 47%, P = 0.011, odds ratio [OR] 0.17, 95% confidence interval [CI] 0.04 to 0.70) and ICU mortality (18% versus 47%, P = 0.047, OR 0.24, 95% CI 0.07 to 0.88) rates were significantly lower in the antibiotic group than in the no antibiotic group. Similar results were found after exclusion of patients with do-not-resuscitate orders and those randomly assigned to the no antibiotic group but who received antibiotics for infections other than VAT or subsequent VAP.In patients with VAT, antimicrobial treatment is associated with a greater number of days free of mechanical ventilation and lower rates of VAP and ICU mortality. However, antibiotic treatment has no significant impact on total duration of mechanical ventilation.ClinicalTrials.gov, number NCT00122057.

Project description:ImportancePediatric ventilator-associated events (PedVAEs, defined as a sustained worsening in oxygenation after a baseline period of stability or improvement) are useful for surveillance of complications from mechanical ventilation. It is unclear whether interventions to mitigate known risk factors can reduce PedVAE rates.ObjectiveTo assess whether adherence to 1 or more test factors in a quality improvement bundle was associated with a reduction in PedVAE rates.Design, setting, and participantsThis multicenter quality improvement study obtained data from 2017 to 2020 for patients who were mechanically ventilated and cared for in neonatal, pediatric, and cardiac intensive care units (ICUs). These ICUs were located in 95 hospitals participating in the Children's Hospitals' Solutions for Patient Safety (SPS) network in North America. Data analyses were performed between September 2021 and April 2023.InterventionA quality improvement bundle consisted of 3 test factors: multidisciplinary apparent cause analysis, daily discussion of extubation readiness, and daily discussion of fluid balance goals. This bundle was distributed to a subgroup of hospitals that volunteered to participate in a collaborative PedVAE prevention initiative under the SPS network guidance in July 2018.Main outcomes and measuresEach SPS network hospital submitted monthly PedVAE rates from January 1, 2017, to May 31, 2020, and test factor data were submitted from July 1, 2018, to May 31, 2020. Analyses focused on hospitals that reliably submitted PedVAE rate data, defined as outcomes data submission through May 31, 2020, for at least 80% of the baseline and postbaseline periods.ResultsOf the 95 hospitals in the SPS network that reported PedVAE data, 21 were grouped in the Pioneer cohort and 74 in the non-Pioneer cohort. Only 12 hospitals (57%) from the 21 Pioneer hospitals and 33 (45%) from the 74 non-Pioneer hospitals were considered to be reliable reporters of outcome data. Among the 12 hospitals, the PedVAE rate decreased from 1.9 to 1.4 events per 1000 ventilator days (absolute rate difference, -0.6; 95% CI, -0.5 to -0.7; P < .001). No significant change in the PedVAE rate was seen among the 33 hospitals that reliably submitted PedVAE rates but did not implement the bundle. Of the 12 hospitals, 3 that reliably performed daily discussion of extubation readiness had a decrease in PedVAE rate from 2.6 to 1.2 events per 1000 ventilator days (absolute rate difference, -1.4; 95% CI, -1.0 to -1.7; P < .001), whereas the other 9 hospitals that did not implement this discussion did not have a decrease.Conclusions and relevanceThis study found that a multicenter quality improvement intervention targeting PedVAE risk factors was associated with a substantial reduction in the rate of PedVAEs in hospital ICUs. The findings suggest that ICU teams seeking to reduce PedVAEs incorporate daily discussion of extubation readiness during morning rounds.

Project description:BackgroundGel-forming mucins (GFMs) play important roles in otitis media (OM) pathogenesis. Increased mucin expression is activated by pathogens and proinflammatory cytokines. Bacterial biofilms influence inflammation and resolution of OM and may contribute to prolonged mucin production. The influence of specific pathogens on mucin expression and development of chronic OM with effusion (OME) remains an area of significant knowledge deficit.ObjectivesTo assess the relationship between GFM expression, specific pathogens, middle ear mucosal (MEM) changes, biofilm formation, and antibiotic utilization.MethodsMixed gender chinchillas were inoculated with nontypeable Haemophilus influenzae (NTHi) strain 86028NP or Streptococcus pneumoniae (SP) strain TIGR4 via transbulla injection. Antibiotic was administered on day 3-5 post inoculation. GFM expression was measured by quantitative PCR. Biofilm formation was identified and middle ear histologic changes were measured.ResultsSP infection resulted in higher incidence of biofilm and ME effusion compared with NTHi infection. However, NTHi persisted in the ME longer than SP with no substantive bacterial clearance detected on day 10 compared with complete bacterial clearance on day 10 for 50-60% of the SP-infected chinchillas. Both infections increased MEM inflammatory cell infiltration and thickening. NTHi upregulated the Muc5AC, Muc5B and Muc19 expression on day 10 (p = 0.0004, 0.003, and 0.002 respectively). SP-induced GFM upregulations were trended toward significant. In both NTHi and SP infections, the degree of GFM upregulation had a direct relationship to increased MEM hypertrophy, inflammatory cell infiltration and biofilm formation. Antibiotic treatment reduced the incidence of ME effusion and biofilm, limited the MEM changes and reversed the GFM upregulation. In NTHi infection, the rate of returning to baseline level of GFMs in treated chinchillas was quicker than those without treatment.ConclusionsIn an animal model of OM, GFM genes are upregulated in conjunction with MEM hypertrophy and biofilm formation. This upregulation is less robust and more quickly ameliorated to a significant degree in the NTHi infection with appropriate antibiotic therapy. These findings contribute to the understanding of pathogen specific influences on mucin expression during OM pathogenesis and provide new data which may have implications in clinical approach for OM treatment.

Project description:BackgroundRadical prostatectomy reduces mortality among men with localized prostate cancer; however, important questions regarding long-term benefit remain.MethodsBetween 1989 and 1999, we randomly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy and followed them through the end of 2012. The primary end points in the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) were death from any cause, death from prostate cancer, and the risk of metastases. Secondary end points included the initiation of androgen-deprivation therapy.ResultsDuring 23.2 years of follow-up, 200 of 347 men in the surgery group and 247 of the 348 men in the watchful-waiting group died. Of the deaths, 63 in the surgery group and 99 in the watchful-waiting group were due to prostate cancer; the relative risk was 0.56 (95% confidence interval [CI], 0.41 to 0.77; P=0.001), and the absolute difference was 11.0 percentage points (95% CI, 4.5 to 17.5). The number needed to treat to prevent one death was 8. One man died after surgery in the radical-prostatectomy group. Androgen-deprivation therapy was used in fewer patients who underwent prostatectomy (a difference of 25.0 percentage points; 95% CI, 17.7 to 32.3). The benefit of surgery with respect to death from prostate cancer was largest in men younger than 65 years of age (relative risk, 0.45) and in those with intermediate-risk prostate cancer (relative risk, 0.38). However, radical prostatectomy was associated with a reduced risk of metastases among older men (relative risk, 0.68; P=0.04).ConclusionsExtended follow-up confirmed a substantial reduction in mortality after radical prostatectomy; the number needed to treat to prevent one death continued to decrease when the treatment was modified according to age at diagnosis and tumor risk. A large proportion of long-term survivors in the watchful-waiting group have not required any palliative treatment. (Funded by the Swedish Cancer Society and others.).

Dataset Information

VATICAN (Ventilator-Associated Tracheobronchitis Initiative to Conduct Antibiotic Evaluation): protocol for a multicenter randomized open-label trial of watchful waiting versus antimicrobial therapy for ventilator-associated tracheobronchitis

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