Background The coordination between different levels of care is essential for the management of obstructive sleep apnea (OSA). The objective of this multicenter project was to develop a screening model for OSA in the primary care setting. Methods Anthropometric data, clinical history, and symptoms of OSA were recorded in randomly selected primary care patients, who also underwent a home sleep apnea test (HSAT). Respiratory polygraphy or polysomnography were performed at the sleep unit to establish definite indication for continuous positive airway pressure (CPAP). By means of cross-validation, a logistic regression model (CPAP yes/no) was designed, and with the clinical variables included in the model, a scoring system was established using the β coefficients ( PASHOS Test ). In a second stage, results of HSAT were added, and the final accuracy of the model was assessed. Results 194 patients completed the study. The clinical test included the body mass index, neck circumference and observed apneas during sleep (AUC 0.824, 95% CI 0.763–0.886, P < 0.001). In a second stage, the oxygen desaturation index (ODI) of 3% (ODI3% ≥ 15%) from the HSAT was added (AUC 0.911, 95% CI 0.863–0.960, P < 0.001), with a sensitivity of 85.5% (95% CI 74.7–92.1) and specificity of 67.8% (95% CI 55.1–78.3). Conclusions The use of this model would prevent referral to the sleep unit for 55.1% of the patients. The two-stage PASHOS model is a useful and practical screening tool for OSA in primary care for detecting candidates for CPAP treatment. Clinical Trial Registration Registry: ClinicalTrials.gov; Name: PASHOS Project: Advanced Platform for Sleep Apnea Syndrome Assessment; URL: https://clinicaltrials.gov/ct2/show/NCT02591979 ; Identifier: NCT02591979. Date of registration: October 30, 2015.
Background The incidence of high-risk human papillomavirus (hrHPV)-driven head and neck squamous cell carcinoma, in particular oropharyngeal cancers (OPC), is increasing in high-resource countries. Patients with HPV-induced cancer respond better to treatment and consequently have lower case-fatality rates than patients with HPV-unrelated OPC. These considerations highlight the importance of reliable and accurate markers to diagnose truly HPV-induced OPC. Methods The accuracy of three possible test strategies, i.e. (a) hrHPV DNA PCR (DNA), (b) p16 (INK4a) immunohistochemistry (IHC) (p16), and (c) the combination of both tests (considering joint DNA and p16 positivity as positivity criterion), was analysed in tissue samples from 99 Belgian OPC patients enrolled in the HPV-AHEAD study. Presence of HPV E6*I mRNA (mRNA) was considered as the reference, indicating HPV etiology. Results Ninety-nine OPC patients were included, for which the positivity rates were 36.4%, 34.0% and 28.9% for DNA, p16 and mRNA, respectively. Ninety-five OPC patients had valid test results for all three tests (DNA, p16 and mRNA). Using mRNA status as the reference, DNA testing showed 100% (28/28) sensitivity, and 92.5% (62/67) specificity for the detection of HPV-driven cancer. p16 was 96.4% (27/28) sensitive and equally specific (92.5%; 62/67). The sensitivity and specificity of combined p16 + DNA testing was 96.4% (27/28) and 97.0% (65/67), respectively. In this series, p16 alone and combined p16 + DNA missed 1 in 28 HPV driven cancers, but p16 alone misclassified 5 in 67 non-HPV driven as positive, whereas combined testing would misclassify only 2 in 67. Conclusions Single hrHPV DNA PCR and p16 (INK4a) IHC are highly sensitive but less specific than using combined testing to diagnose HPV-driven OPC patients. Disease prognostication can be encouraged based on this combined test result.
Background and Aims Clinical trials and real-life studies with ustekinumab in Crohn's disease (CD) have shown a good efficacy and safety profile. However, these data are scarcely available in elderly patients. Therefore, we aim to assess the effectiveness and safety of ustekinumab in elderly patients with CD. Methods Elderly patients (>60 years old) from the prospectively maintained ENEIDA registry treated with ustekinumab due to CD were included. Every patient was matched with two controls under 60 years of age, according to anti-TNF use and smoking habit. Values for the Harvey-Bradshaw Index (HBI), endoscopic activity, C-reactive protein (CRP), and faecal calprotectin (FC) were recorded at baseline and at weeks 16, 32 and 54. Results 648 patients were included, 212 elderlies. Effectiveness was similar between young and elderly patients during the follow-up. Steroid-free remision was similar at week 16 (54.6 vs 51.4%, p=0.20), 32 (53.0% vs 54.5%, p=0.26) and 54 (57.8% vs 51.1%, p=0.21). Persistence of ustekinumab as maintenance therapy was similar in both age groups (log-rank test; p=0.91). There was no difference in the rate of adverse effects (14.2% vs 11.2%, p=0.350), including severe infections (7.1% vs 7.3%, p=1.00), except for the occurrence of de novo neoplasms, which was higher in older patients (0.7% vs 4.3%, p= 0.003). Conclusions Ustekinumab is as effective in elderly patients with CD, as it is in non-elderly. Safety profile seems to be also similar but for a higher rate of de novo neoplasms, probably related to the age of the elderly patients.
Background The objective of this study was to determine the minimum number of cultures needed to detect Cutibacterium acnes in primary reverse shoulder arthroplasties (RSA). Methods It is a prospective study including 160 primary RSA. Exclusion criteria included an active infection, an invasive shoulder treatment in the last six months before surgery, an Arthro-SCAN or Arthro-MRI in the last six months before surgery, previous shoulder surgeries and revision cases. In 90 cases, 11 cultures were obtained. Another 10 cultures were obtained in the other 70 cases (culture #10 was a sterile sponge to detect false positives). To determine the minimum number of cultures needed to detect C. acnes, the prevalence of C. acnes contamination of the 160 patients included was determined. Results There were 128 females and 32 males, with a mean age of 74 years. There were 1690 cultures obtained from the 160 primary RSA surgeries, and 132 of them turned out to be positive for C. acnes. There were 42 patients with positive cultures. Twenty of them were males and 22 females. When considering the skin and the deep tissue cultures altogether, the prevalence of positive cultures for C. acnes was of 26.25%. If only deep tissues cultures were considered, the prevalence of positive cultures for C. acnes was of 23.13%. When considering the skin and the deep tissue cultures together, the sensitivity to detect the C. acnes is 19% if only 1 culture is obtained, 31% if 2 cultures are obtained, 50% if 3 cultures are obtained, 59.5% if 4 cultures are obtained, 66.7% if 5 cultures are obtained, 73.8% if 6 cultures are obtained, 85.7% if 7 cultures are obtained and that sensitivity is 92.9% if 8 cultures are obtained. When considering only the deep tissue cultures, if only 1 culture is obtained the sensitivity to detect the C. acnes is 24.3%, 40.5% if 2 cultures are obtained, 54.1% if 3 cultures are obtained, 73% if 4 cultures are obtained, 89.2% if 5 cultures are obtained, and 97.3% sensitivity if 6 or 7 cultures are obtained. Discussion A minimum number of 8 cultures are needed to detect C. acnes in skin and in deep tissues. Moreover, a minimum of 6 cultures are needed to detect it in deep tissues when performing an RSA.
Introduction The analysis of the core biomarkers of Alzheimer's Disease (AD) in the cerebrospinal fluid (CSF) is recommended in the clinical units where it is available. Because of the absence of universal validated values, the determination of specific cut-off points for each center and its population is recommended. The main objective of the CORCOBIA study was to determine the cut-off points of core AD CSF biomarkers for several centers (Parc de Salut Mar, Barcelona and Hospital General de Granollers), which work with the same reference laboratory (Laboratori de Referència de Catalunya). Methods Prospective study including cognitively healthy subjects (HC, n = 42), subjects with amnestic mild cognitive impairment (aMCI, n = 35) and patients with dementia due to Alzheimer's Disease (AD, n = 48), in whom clinical and neuropsychological assessment, neuroimaging, APOE genotyping and lumbar puncture to analyze amyloid beta peptides (Aβ42, Aβ40), total tau (tTau) and phosphorylated Tau (pTau181) using the Lumipulse G600II (Fujirebio) was performed. The values of Sensitivity (Se), Specificity (Sp), predictive values and area under the curve (AUC) were calculated, determining the cut-off point according to the Youden index by comparing the groups of HC and AD. Results The resulting cut-offs and their AUC were the following: Aβ42 750 pg/ml (AUC 0.809); Aβ42/Aβ40 0.062 (AUC 0.78); pTau181 69.85 pg/ml (AUC 0.81); tTau 522.0 pg/ml (AUC 0.79); Aβ42/tTau 1.76 (AUC 0.86); Aβ42/pTau181 10.25 (AUC 0.86). Conclusions The determination of cut-off points of core AD CSF biomarkers for the participating centers allows a better diagnostic accuracy. The ratio CSF Aβ42/pTau181 shows the highest AUC and better balance between sensitivity and specificity.
Objectives: To evaluate the feasibility of contrast-enhanced mammography (CEM)-guided biopsy at Hospital del Mar, a Spanish university hospital. Methods: We retrospectively reviewed all consecutive women with a suspicious enhancing finding eligible for CEM-guided biopsy, who were prospectively enrolled in a pre-marketing clinical validation and feasibility study (October 2019 to September 2021). CEM-guided biopsy is a stereotactic-based procedure that, by using intravenous iodinated contrast media administration and dual-energy acquisition, provides localisation of enhancing lesions. All the biopsies were performed using a vacuum-assisted device. We collected procedural characteristics (patient position and type of approach), and histopathological results. Feasibility endpoints included success (visualisation of the enhancing lesion, post-procedural biopsy changes and clip placement), procedural time, number of scout acquisitions and complications. Results: A total of 66 suspicious enhancing lesions (18.0% foci, 44.0% mass, 38.0% non-mass enhancement; median size 8.5 mm) in 64 patients (median age 59 years, mostly minimal [48.4%] or mild [32.8%] background parenchymal enhancement) were referred for CEM-guided biopsy in the study period. The success rate was 63/66 (95.4%). Amongst successful procedures, patients were most frequently seated (52/63, 82.5%) and the preferred approach was horizontal (48/63, 76.2%). Median total time per procedure was 15 min. Median number of acquisitions needed before targeting was 2 (range 1-4). Complications consisted of hematoma (17/63, 27%) and vasovagal reaction (2/63, 3.2%). At histology, the malignancy rate was 25/63 (39.7%). Conclusion: In this first patient series, CEM-guided breast biopsy was feasible, with success and complication rates similar to those previously reported for magnetic resonance guidance. Key points: • CEM may be used to guide biopsy of enhancing lesions through a stereotactic-based procedure combined with intravenous iodinated contrast media administration and dual-energy acquisition. • In this first patient series (n = 64), the success rate of CEM-guided biopsy was above 95%, the only complications were hematoma (22.2%) and vasovagal reaction (3.2%), and median total time per procedure was 15 min. • CEM-guided biopsy is feasible and could potentially be a widely available biopsy technique for enhancing-only lesions.
An expert survey was designed to support the development of a workplace-based multi-country intervention tackling depression, anxiety, and mental illness-related stigma in small- and medium-sized enterprises (SMEs). Academic experts and representatives of SME organisations, specific sector organisations, labour or advocacy groups, and occupational health organisations, were contacted across eight European countries and Australia. The survey comprised closed and open text questions to assess expert opinion about interventions for employees with mental health difficulties, interventions supporting their managers, and anti-stigma interventions. The survey was available in six languages. The online platform Qualtrics was used for data collection. Quantitative data was analysed through descriptive statistics and qualitative data was analysed through thematic analysis. Sixty-five of 146 experts responded, representing a 42% response rate. Results showed only 26.2% of experts agreed that employees could speak openly about mental health issues, and 81.5% of experts indicated a large or medium unmet need for support for employees with mental health issues. Psychoeducational materials, face-to-face workshops and interventions based on cognitive behavioural therapy were ranked most likely to be taken up by employees. Experts rated as most useful for managers’ guidelines on how to act if an employee has mental health issues (67.7%). The greatest number of experts indicated workshops of people with lived experience of mental illness (80.0%) and awareness campaigns (78.5%) were most required to tackle stigma. Responses were consistent between experts from different countries and areas of expertise. Experts in this multinational survey assessed that interventions supporting mental health in the workplace and tackling stigma are greatly needed. A multicomponent intervention with a wide range of materials and tools is supported.
Background and Objectives: Previous studies demonstrated a huge variability among surgeons when it comes to reproducing the position of an acetabular cup in total hip arthroplasty. Our main objective is to determine if orthopedic surgeons can replicate a given orientation on a pelvic model better than untrained individuals. Our secondary objective is to determine if experience has any influence on their ability for this task. Materials and Methods: A group of specialist orthopedic hip surgeons and a group of volunteers with no medical training were asked to reproduce three given (randomly generated) acetabular cup orientations (inclination and anteversion) on a pelvic model. Error was measured by means of a hip navigation system and comparisons between groups were made using the appropriate statistical methods. Results: The study included 107 individuals, 36 orthopedic surgeons and 71 untrained volunteers. The mean error among surgeons was slightly greater as regards both inclination (7.84 ± 5.53 vs. 6.70 ± 4.03) and anteversion (5.85 ± 4.52 vs. 5.48 ± 3.44), although statistical significance was not reached (p = 0.226 and p = 0.639, respectively). Similarly, although surgeons with more than 100 procedures a year obtained better results than those with less surgical experience (8.01 vs. 7.67 degrees of error in inclination and 5.83 vs. 5.87 in anteversion), this difference was not statistically significant, either (p = 0.852 and p = 0.981). Conclusions: No differences were found in the average error made by orthopedic surgeons and untrained individuals. Furthermore, the surgeons’ cup orientation accuracy was not seen to improve significantly with experience.
Objective To evaluate the cost-effectiveness of a secondary prevention programme in patients admitted to the emergency department due to drug-related problems (DRPs). Methods A decision model compared costs and outcomes of patients with DRPs admitted to the emergency department. Model variables and costs, along with their distributions, were obtained from the trial results and literature. The study was performed from the perspective of the National Health System including only direct costs. Key findings The implementation of a secondary prevention programme for DRPs reduces costs associated with emergency department revisits, with an annual net benefit of €87 639. Considering a mortality rate attributable to readmission of 4.7%, the cost per life-years gained (LYG) with the implementation of this programme was €2205. In the short term, the reduction in the number of revisits following the programme implementation was the variable that most affected the model, with the benefit threshold value corresponding to a relative reduction of 12.4% of the number of revisits of patients with DRPs to obtain benefits. Conclusions Implementing a secondary prevention programme is cost-effective for patients with DRPs admitted to the emergency department. Implementation costs will be exceeded by reducing revisits to the emergency department.
Introduction: One of the most important aims in the management of systemic lupus erythematosus (SLE) is to avoid or delay the accumulation of organ damage. The first five years after diagnosis are crucial for prognosis. Areas covered: This manuscript reviews available data on organ damage accrual in SLE and early therapeutic intervention as a possible strategy to prevent its long-term accrual. Expert opinion: Organ damage can be minimized by controlling disease activity and risk of flares, reducing the dose of glucocorticoids, and ensuring a proper therapeutic intervention with an early introduction of the right therapies. The current standard treatment cannot provide clinical remission in all patients with SLE. Therefore, there is a clinical need for introducing new therapeutic strategies able to achieve the main therapeutic objectives. The addition of biologic and other therapeutic agents to the standard of care is effective for controlling disease activity and for preventing severe flares, enabling a reduced use of glucocorticoids, and presumably reducing organ damage progression. Considering its efficacy and safety, early inclusion of biologic agents in the first lines of the treatment algorithm, at least in certain patients, could be considered as an innovative treatment approach to decrease disease burden in SLE patients.
Myeloproliferative neoplasms (MPN) are uncommon in children/young adults. Here we present data on unselected patients diagnosed before 25 years of age included from 38 centres in 15 countries. Sequential patients were included. We identified 444 patients, with median follow up 9.7 years (0-47.8). Forty-nine (11.1%) had a history of thrombosis at diagnosis, 49 new thrombotic events were recorded (1.16 % pt/year), peri-hepatic vein thromboses were most frequent (47.6% venous events) and logistic regression identified JAK2V617F mutation (p=0.016) and hyperviscosity symptoms (visual disturbances, dizziness, vertigo, headache) as risk factors (p=0.040). New hemorrhagic events occurred in 44 patients (9.9%, 1.04 % pt/y). Disease transformation occurred in 48 patients (10.9%, 1.13 % pt/year), usually to myelofibrosis (7.5%) with splenomegaly as a novel risk factor for transformation in ET (p= 0.000) in logistical regression. Eight deaths (1.8%) were recorded, three after allogeneic stem cell transplantation. Concerning conventional risk scores: IPSET-T and IPSET-NT differentiated ET patients in terms of thrombotic risk. Both scores identified high-risk patients with the same median thrombosis-free survival of 28.5y. No contemporary scores were able to predict survival for young ET or PV patients. Our data represents the largest real-world study of MPN patients age <25 years at diagnosis). Rates of thrombotic events and transformation were higher than expected compared with the previous literature. Our study provides new and reliable information as a basis for prospective studies, trials, and development of harmonized international guidelines for the specific management of young patients with MPN.
The objective of the study was to analyze the factors associated with chronic bronchial infection (CBI) due to methicillin-susceptible Staphylococcus aureus (SA) and assess the clinical impact on severity, exacerbations, hospitalizations, and loss of lung function compared to patients with no isolation of PPMs in a large longitudinal series of patients from the Spanish bronchiectasis registry (RIBRON). Material and methods: A prospective, longitudinal, multicenter study was conducted with patients included in the RIBRON registry between January 2015 and October 2020. The inclusion criteria were an age of 18 years or older and an initial diagnosis of bronchiectasis. Patients recorded in the registry had a situation of clinical stability in the absence of an exacerbation in the four weeks before their inclusion. All patients were encouraged to provide a sputum sample at each visit for microbiological culture. Annual pulmonary function tests were performed according to the national spirometry guidelines. Results: A total of 426 patients were ultimately included in the study: 77 patients (18%) with CBI due to SA and 349 (82%) who did not present any isolation of PPMs in sputum. The mean age was 66.9 years (16.2), and patients 297 (69.7%) were female, with an average BMI of 25.1 (4.7) kg/m2 and an average Charlson index of 1.74 (1.33). The mean baseline value of FEV1 2 L was 0.76, with a mean FEV1% of 78.8% (23.1). One hundred and seventy-two patients (40.4%) had airflow obstruction with FEV1/FVC < 0.7. The mean predictive FACED score was 1.62 (1.41), with a mean value of 2.62 (2.07) for the EFACED score and 7.3 (4.5) for the BSI score. Patients with CBI caused by SA were younger (p < 0.0001), and they had a lower BMI (p = 0.024) and more exacerbations in the previous year (p = 0.019), as well as in the first, second, and third years of follow-up (p = 0.020, p = 0.001, and p = 0.018, respectively). As regards lung function, patients with CBI due to SA had lower levels of FEV1% at the time of inclusion in the registry (p = 0.021), and they presented more frequently with bronchial obstruction (p = 0.042). A lower age (OR: 0.97; 95% CI: 0.94-0.99; p < 0.001), lower FEV1 value% (OR: 0.98; 95% CI: 0.97-0.99; p = 0.035), higher number of affected lobes (OR: 1.53; 95% CI: 1.2-1.95; p < 0.001), and the presence of two or more exacerbations in the previous year (OR: 2.33; 95% CI: 1.15-4.69; p = 0.018) were observed as independent factors associated with CBI due to SA. The reduction in FEv1% in all patients included in the study was -0.31%/year (95% CI: -0.7; -0.07) (p = 0.110). When the reduction in FEv1% is analyzed in the group of patients with CBI due to SA and the group without pathogens, we observed that the reduction in FEV1% was -1.19% (95% CI: -2.09, -0.69) (p < 0.001) in the first group and -0.02% (95% CI: -0.07, -0.01) (p = 0.918) in the second group. According to a linear regression model (mixed effects) applied to determine which factors were associated with a more pronounced reduction in FEv1% in the overall group (including those with CBI due to SA and those with no PPM isolation), age (p = 0.0019), use of inhaled corticosteroids (p = 0.004), presence of CBI due to SA (p = 0.007), female gender (p < 0.001), and the initial value of FEV1 (p < 0.001) were significantly related. Conclusions: Patients with non-CF bronchiectasis with CBI due to SA were younger, with lower FEV1% values, more significant extension of bronchiectasis, and a higher number of exacerbations of mild to moderate symptoms than those with no PPM isolation in respiratory secretions. The reduction in FEV1% was -1.19% (95% CI: -2.09, -0.69) (p < 0.001) in patients with CBI caused by SA.
Introduction COVID-19 patients admitted to critical care units present an intense inflammatory response and the need to replace organs or systems for long periods of time, which facilitates the presence of infectious complications. Objectives To present the national rates of infections related to invasive devices (IRDI) in COVID-19 patients, as well as the rates of multi-resistant bacteria (MBR) acquired during their stay in critical care units. Method Retrospective analysis of COVID-19 patients included during the first, second and fourth waves of the pandemic in a national observational and multicenter database (ENVIN-HELICS). Pneumonias related to mechanical ventilation (N-MV), urinary tract infections related to urethral catheter (UTI-SU) and primary bacteremia related to central venous catheters (BP-CVC) were recorded, whose rates are presented as incidence density (ID). The BMRs acquired during the stay in the critical care units were recorded and presented as cumulative incidence (CI). Results 7,778 patients were included, 1,525 (19.6%) in the first wave of the pandemic, 3,484 (44.8%) in the second, and 2,769 (35.6%) in the fourth. ICU stay of 21 days in the first and second waves and 19.7 days in the fourth. Intra-ICU mortality in the first wave, decreasing from 31% to 26.3% in the second and 18.9% in the fourth. N-MV rates of 14.31, 13.56, and 19.99 episodes per 1,000 days of MV in each wave. UTI-SU rates of 6.54, 5.63 and 7.97 episodes per 1000 days of SU. BP-CVC rates of 12.42, 7.95, and 8.13 per 1,000 CVC days. The BMR rate was 22.9, 15.3, and 15.3 BMR per 100 admitted patients. Conclusions . High rates of the different IRDI in COVID patients that are maintained in the three waves analyzed. High rates of BMR acquired during the stay in critical care units with a tendency to decrease in the fourth wave.
Introduction: The current literature has not yet provided a definitive conclusion on the best emergency groin hernia repair. The aim of this study was first to compare the short and long-term outcomes between open preperitoneal and anterior approach in emergency groin hernia repair and second to identify risk factors for postoperative complications, mortality, and recurrence. Materials and Methods: This retrospective cohort study included patients who underwent emergency groin hernia repair between January 2010 and December 2018. Short and long-term outcomes were analyzed comparing approach and repair techniques. The predictors of complications and mortality were investigated using multivariate logistic regression. Cox regression multivariate analysis were used to explore risk factors of recurrence. Results: A total of 316 patients met the inclusion criteria. The most widely used surgical techniques were open preperitoneal mesh repair (34%) and mesh plug (34%), followed by Lichtenstein (19%), plug and patch (7%) and tissue repair (6%). Open preperitoneal mesh repair was associated with lower rates of recurrence ( p = 0.02) and associated laparotomies ( p < 0.001). Complication and 90-day mortality rate was similar between the techniques. Multivariable analysis identified patients aged 75 years or older (OR, 2.08; 95% CI, 1.14–3.80; p = 0.016) and preoperative bowel obstruction (OR, 2.11; 95% CI, 1.20–3.70; p = 0.010) as risk factors for complications and Comprehensive Complication Index ≥26.2 as risk factor for 90-day mortality (OR, 44.76; 95% CI, 4.51–444.59; p = 0.01). Female gender was the only risk factor for recurrence. Conclusion: Open preperitoneal mesh repair may be superior to other techniques in the emergency setting, because it can avoid the morbidity of associated laparotomies, with a lower long-term recurrence rate.
Infections caused by multidrug resistant Gram-negative bacteria are becoming a worldwide problem due to their increasing incidence and associated high mortality. Carbapenem-resistant bacteria such as Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii are the most important in clinical practice. The objective of these guidelines is to update the recommendations for the diagnosis and treatment of infections caused by these multidrug resistant bacteria. Although ‘old’ antibiotics such as aminoglycosides, colistin, or tigecycline are frequently used for therapy of these bacteria, the ‘new’ beta-lactams such as ceftazidime–avibactam, ceftolozane–tazobactam, meropenem–vaborbactam, imipenem–cilastatin–relebactam or cefiderocol are progressively becoming the first-line therapy for most of these microorganisms. The Spanish Society of Infectious Diseases and Clinical Microbiology (Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica) designated a panel of experts in the field to provide evidence-based recommendations in response to common clinical questions. This document is primarily focused on microbiological diagnosis, clinical management, and targeted antimicrobial therapy of these infections, with special attention to defining the role of the new antimicrobials in the treatment of these bacteria.
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