Genetic and Biochemical Predictors of Neonatal Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) is a common complication of prematurity with a multifactorial etiology, influenced by both genetic susceptibility and environmental factors on the immature lung. Fibroblast growth factor receptor-3 and -4 (FGFR-3 and FGFR-4) are abundantly expressed in both the epithelium and mesenchyme in the developing mammalian lung. FGFR-4 may play a role in developing BPD as it is associated with airway inflammation and remodeling; studies showed a link between BPD and a polymorphism in the FGFR-4 gene. The aim of this study was to study the significance of FGFR-4 in developing BPD and to investigate the correlation between its serum level and its genetic polymorphism in relation to development of BPD in preterms. This case-control study was performed on 80 preterm neonates (<32 weeks) divided into two groups: group I included 50 preterms with respiratory distress syndrome (RDS) who developed BPD and group II included 30 preterms with RDS only. The mean serum level of FGFR-4 was significantly lower in group I than in group II ( p -value < 0.05). There was no significant correlation between the serum levels of FGFR-4 and the degree of severity of BPD. Allele variation in the FGFR-4 gene was similar in both groups. The serum level of FGFR-4 was significantly lower in preterms with BPD, although the gene polymorphism was not significantly different in the studied groups.

Renal function in small for gestational age preterm infants.

OBJECTIVE: The objective of this study is to compare glomerular and tubular functions in small for gestational age (SGA) and appropriate for gestational age (AGA) preterm infants. STUDY DESIGN: A prospective controlled study was conducted on SGA and AGA infants with gestational ages between 320/7 and 366/7 weeks, who received gentamycin in the first 72 h of life. Glomerular and tubular functions were assessed on days 1 and 5. RESULTS: Fifty (25 SGA and 25 AGA) infants were included. On day of life 1, SGA group had higher serum sodium, serum urea, and urinary creatinine. On day 5, SGA infants had significant increase in serum creatinine (p = 0.04). Urinary NAG and FeNa were comparable among the two groups on days 1 and 5. CONCLUSIONS: Glomerular functions were compromised in SGA preterm infants. Tubular functions were comparable.

Erratum to: Antimicrobials: a global alliance for optimizing their rational use in intra-abdominal infections (AGORA).

[This corrects the article DOI: 10.1186/s13017-016-0089-y.].

The surgical Infection Society Revised Guidelines on the management of intra-abdominal infection

BACKGROUND: Previous evidence-based guidelines on the management of intra-abdominal infection (IAI) were published by the Surgical Infection Society (SIS) in 1992, 2002, and 2010. At the time the most recent guideline was released, the plan was to update the guideline every five years to ensure the timeliness and appropriateness of the recommendations. METHODS: Based on the previous guidelines, the task force outlined a number of topics related to the treatment of patients with IAI and then developed key questions on these various topics. All questions were approached using general and specific literature searches, focusing on articles and other information published since 2008. These publications and additional materials published before 2008 were reviewed by the task force as a whole or by individual subgroups as to relevance to individual questions. Recommendations were developed by a process of iterative consensus, with all task force members voting to accept or reject each recommendation. Grading was based on the GRADE (Grades of Recommendation Assessment, Development, and Evaluation) system; the quality of the evidence was graded as high, moderate, or weak, and the strength of the recommendation was graded as strong or weak. Review of the document was performed by members of the SIS who were not on the task force. After responses were made to all critiques, the document was approved as an official guideline of the SIS by the Executive Council. RESULTS: This guideline summarizes the current recommendations developed by the task force on the treatment of patients who have IAI. Evidence-based recommendations have been made regarding risk assessment in individual patients; source control; the timing, selection, and duration of antimicrobial therapy; and suggested approaches to patients who fail initial therapy. Additional recommendations related to the treatment of pediatric patients with IAI have been included. SUMMARY: The current recommendations of the SIS regarding the treatment of patients with IAI are provided in this guideline.(AU)

Does positioning affect tracheal aspiration of gastric content in ventilated infants?

OBJECTIVES: Gastroesophageal reflux and aspiration can occur in premature infants who are supported with mechanical ventilation. The relation between physical positioning and gastric aspiration in ventilated infants has not been studied. Pepsin measured in tracheal aspirate (TA) emerged as a specific marker for aspiration. The objective of our study was to assess pepsin in TA of ventilated infants at 2 different positions: supine and right lateral. METHODS: We conducted a randomized controlled trial on premature infants who were enterally fed and supported with mechanical ventilation. Patients were randomized into intervention and control groups. In the intervention group, infants were placed supine for 6 hours before a sample of TA was obtained. A second sample was collected 6 hours later while lying in the right lateral position. In the control group, the 2 samples of TA were obtained while infants remained in the supine position during the entire study time. Pepsin in TA was measured while blinded to the group assignment. RESULTS: A total of 34 patients were enrolled and randomized to intervention (n = 17) and control (n = 17) groups. Gestational age was 32.7 ± 2.7 weeks, and birth weight was 1617 ± 526 g; both groups had similar demographic and clinical characteristics. Pepsin concentration did not differ between groups at baseline. In the intervention group, pepsin concentration significantly declined from 13 ng/mL (interquartile range [IQR] 11.9-38.7) to 10 ng/mL (IQR 7-12; P < 0.001), whereas it did not change in the control group (P = 0.42). CONCLUSIONS: The right lateral positioning is associated with decreased TA pepsin. The implications of the present study on hospital practice and clinical outcomes need further investigations.

Pneumothorax in the neonatal intensive care unit in Cairo University Hospital.

Pneumothorax is more frequent in the neonatal period than at any other time in life and the incidence increases in neonates who have concurrent underlying lung disease or who require mechanical ventilation. This cross sectional study was performed in the inborn NICU in Cairo University Hospitals over one year from September 2010 to August 2011. All neonates admitted were included; their data were collected and observed for pneumothorax occurrence. A total of 59 neonates (9.1%) developed pneumothorax with highest incidence in ELBW and gestational ages less than 32 weeks. RDS and MAS were the most common coexisting lung pathologies. 89.83% of the cases with pneumothorax were on mechanical ventilation. Pneumothorax occurred on the right side in 64.4% of cases, on the left in 18.6% and bilateral in 16.95% of the cases. The mortality was higher (62.7%) in the neonates with pneumothorax than the mortality of the total admissions. The mortality was significantly higher with lower birth weights and gestational ages. Apgar score at one and five minutes and the associated medical diagnosis showed no significant differences between the neonates who died and those who survived.

Trauma-specific intensive care units can be cost effective and contribute to reduced hospital length of stay.

Our hypothesis was that clinical outcomes are improved and cost and hospital length of stay (LOS) reduced as a result of the opening of a closed trauma intensive care unit (ICU). We conducted a cross-sectional study in a university-affiliated Level I trauma center. Our study population comprised trauma patients admitted to the ICU between June 1, 1996 and July 1, 1998 for at least 24 hours and with an Injury Severity Score (ISS) >16 (excluding those with severe brain injury). The main outcome measures were changes in LOS and number of ventilator days, prevalence of complications, changes in patient charges, and hospital costs. Two hundred four patients were included [trauma ICU (TICU) 60, surgical ICU 144]. The two groups were not statistically different in age, ISS, mechanism of injury, infection rate, and mortality; however, the TICU patients had a lower number of ventilator hours (83.1 vs 100.0; P = 0.007), lower ICU LOS (9.4 vs 12.1 days; P = 0.06), and lower total hospital LOS (15.6 vs 22.3 days; P = 0.01). Although this was not of statistical significance TICU patients had lower hospital charges ($125,383 vs $152,994; P = 0.06) and lower cost per case ($42,306 vs $47,548; P = 0.35) for a net savings of $314,520 during the first 6 months of operation of the TICU. This study suggests that improved clinical outcomes and decreases in cost and LOS are directly related to the opening of a closed trauma ICU.

Recurrent trauma in elderly patients.

HYPOTHESIS: Older patients (those aged > or = 70 years) who have experienced trauma have an increased risk of recurrent trauma. Demographic, medical, and functional factors are potential contributors to the risk of subsequent trauma among injured elderly patients. DESIGN: Retrospective follow-up study. PARTICIPANTS: Study participants were derived from the Longitudinal Study of Aging, an extension of the 1984 National Health Interview Survey focusing on persons who were aged 70 years and older in 1984. A cohort of elderly patients participating in the Longitudinal Study of Aging and hospitalized for injury in 1985 (n = 100) was identified using Medicare hospital discharge data. An uninjured cohort (n = 401) was also identified from the Longitudinal Study of Aging and matched for age (1 year) and sex. MAIN OUTCOME MEASURES: Risk of admission for trauma among the injured cohort compared with the uninjured cohort and associations between demographic, medical, and functional characteristics and trauma recurrence. RESULTS: Following adjustment for potential confounding factors, the injured cohort was 3.25 times more likely (95% confidence interval, 1.99-5.31) to be hospitalized for injury during the follow-up period compared with the uninjured cohort. Among the injured cohort, those at greatest risk of subsequent trauma included women and those with chronic medical conditions or functional impairments, the latter being the only factor independently associated with recurrence. CONCLUSIONS: Elderly patients who have experienced trauma are at increased risk of subsequent injury. Interventions to reduce the likelihood of trauma recurrence should focus on those with chronic illnesses and functional impairments.

Reduction of vancomycin-resistant enterococcal infections by limitation of broad-spectrum cephalosporin use in a trauma and burn intensive care unit.

Both vancomycin and third-generation cephalosporin use are believed to contribute to a rise in vancomycin-resistant enterococci (VRE) infections. In 1998, the largest number of VRE infections in our hospital occurred in the trauma/burn intensive care unit (TBICU), accounting for nearly 20% of hospital infections. In an attempt to control the VRE infection rate, antibiotic protocols for prophylaxis, empiric, and definitive therapy were initiated during the final quarter of 1998 to minimize cephalosporin use by the introduction of piperacillin/tazobactam. Therefore, we undertook a study of the VRE infection rate for the TBICU in relation to vancomycin, piperacillin/tazobactam, piperacillin, third-generation cephalosporin, and total cephalosporin use before and after efforts to limit cephalosporins. These data were compared to those in the medical and surgical intensive care units. During 1998, seven VRE infections occurred in the TBICU. Following initiation of antibiotic protocols, one case of VRE infection occurred in the subsequent month and no cases in the 17 months since. The decrease in the VRE infection rate corresponded with a significant increase in the use of piperacillin/tazobactam and a reduction in third-generation and total cephalosporin use. In contrast, cephalosporin use in the medical and surgical intensive care units remains significantly higher than in the TBICU, and neither unit has had a reduction in their VRE infection rates.

Long-term survival in the elderly after trauma.

BACKGROUND: In the elderly, trauma has been associated with increased, long-term, all-cause mortality. Functional limitations secondary to injury may be responsible for the reduced survival rate. The objective of this study was to test this hypothesis using data from the Longitudinal Study of Aging (LSOA). METHODS: The LSOA is an extension of the 1984 National Health Interview Survey, which focused on 7,527 persons who were 70 years and older in 1984. Using data from the LSOA, a cohort of elderly patients hospitalized for injury in 1985 (N = 102) was identified from Medicare hospital discharge data. An uninjured cohort (N = 408) was also identified using the LSOA and matched by age (within 1 year) and sex. Deaths in both cohorts were identified using the National Death Index. Hazard ratios (HRs) for mortality within 6 years subsequent to injury, adjusted for demographic, health status, and functional characteristics, were calculated. RESULTS: The injured cohort had a significantly reduced rate of survival compared with the uninjured cohort (HR = 1.5; 95% confidence interval [CI] 1.1-2.2), and this relationship persisted after adjusting for demographic and health characteristics (HR = 1.4; 95% CI 1.0-2.0). After additional adjustment for measures of functional decline, the association diminished (HR = 1.2; 95% CI 0.8-1.7). Functional decline remained a strong, independent factor for the risk of mortality. CONCLUSION: Trauma in the elderly has both an acute and long-term influence on mortality; the latter seems to be mediated through a decline in function resulting from the injury. This study suggests that strategies to return the elderly patient to preinjury functional status are of paramount importance. Future research should explore the impact of these interventions on long-term survival.

The April 8, 1998 tornado: assessment of the trauma system response and the resulting injuries.

BACKGROUND: On April 8, 1998, an F5 tornado touched down in two counties of Alabama producing a wide path of destruction. The presence of a regional trauma system in this area presents an opportunity to evaluate the effectiveness of the system in responding to the victims of this natural disaster. METHODS: Emergency room logs and the regional trauma system database were searched for all patients treated for injuries sustained from the tornado, and medical records were reviewed for demographic information, mode of transportation to hospital, injuries, treatment, and outcome. Fatalities were identified by means of the coroner's office. RESULTS: A total of 224 patients were evaluated at nine area hospitals, of whom 63 (28%) required admission. There were 32 deaths: 30 persons were dead at the scene, and 2 patients subsequently died at Level I trauma centers. Among patients with nonfatal injuries, 39% were managed at Level I facilities, 46% at Level III facilities, and 15% at nontrauma facilities. Forty patients (55%) seen at Level I facilities required admission compared with 15 patients (17%) at Level III facilities and 8 patients (29%) at nontrauma facilities; Level I facilities also had the highest Injury Severity Score. Of patients requiring admission, 83% were transported by emergency medical services; these patients also had the highest Injury Severity Score. CONCLUSION: The regional trauma system facilitated appropriate and efficient triage to system hospitals, routing the most severely injured patients to the Level I centers without overwhelming them with the more numerous, less severely injured patients.

Contribution of Escherichia coli alpha-hemolysin to bacterial virulence and to intraperitoneal alterations in peritonitis.

Alpha-hemolysin (Hly) is a common exotoxin produced by Escherichia coli that enhances virulence in a number of clinical infections. The addition of hemolysin production to laboratory bacterial strains is known to increase the lethality of E. coli peritonitis. However, the mechanisms involved have not been determined and the contribution of hemolysin to the alterations in the host intraperitoneal environment and the leukocyte response is not known. Utilizing a rat peritonitis model, we show that wild-type hemolytic E. coli strains have a significant competitive advantage over nonhemolytic strains within the peritoneum. To examine the specific contribution of Hly to E. coli-induced virulence and alterations within the peritoneum, a mixed peritonitis model of E. coli, Bacteroides fragilis, and sterile fecal adjuvant was used. Three transformed E. coli strains were utilized: one strongly secretes active hemolysin (WAF 270), a second secretes active hemolysin but a reduced amount (WAF 260), and the third does not produce hemolysin (WAF 108). After an equal inoculum of each of the three strains, WAF 270 produced a markedly increased lethality and an increased recovery of both E. coli and B. fragilis from the host relative to the other strains. Changes in the intraperitoneal pH, degree of erythrocyte lysis, and recruitment and viability of leukocytes within the peritoneum following the induction of peritonitis differed significantly between the strongly hemolytic and nonhemolytic strains. Induction of peritonitis with WAF 270 caused a pronounced decrease in intraperitoneal pH, lysis of most of the intraperitoneal erythrocytes, and a marked decrease in recoverable viable leukocytes compared to WAF 108. Thus, hemolysin production by E. coli within the peritoneum may alter not only the host's ability to control the hemolytic strain itself but also other organisms.

Endovascular therapy of traumatic injuries of the extracranial cerebral arteries.

The field of neuroendovascular therapy is rapidly growing. New technology and operators' expertise are developing at a pace that will make this discipline progressively more available and successful. For patients who have traumatic injuries of the extracranial arteries, endovascular therapy offers a new dimension to the treatment of these injuries and the prevention of stroke. Because many of these patients are likely to be critically ill, it is important to keep in mind the principles of their management before, during, and after the procedure, thus assuring the best chance for a successful outcome. Furthermore, some of the issues related to their neurointensive care will serve as guides for the need for endovascular therapy, as well as its timing.

Prognostic factors in patients with inferior vena cava injuries.

Inferior vena cava (IVC) injuries are potentially devastating insults that continue to be associated with high mortality despite advances in prehospital and in-hospital critical care. Between 1987 and 1996, 37 patients (32 males and 5 females; average age, 30 years) were identified from the trauma registry as having sustained IVC trauma. Overall mortality was 51 per cent (n = 19), with 13 intraoperative deaths and five patients dying within the first 48 hours. Blunt IVC injuries (n = 8) had a higher associated mortality than penetrating wounds (63% versus 48%). Of the 29 patients with penetrating IVC trauma, the wounding agent influenced mortality (shotgun-100% versus gunshot-43% versus stab-0%). Anatomical location of injury was also predictive of death [suprahepatic (n = 3)-100% versus retrohepatic (n = 9)-78% versus suprarenal (n = 6)-33% versus juxtarenal (n = 2)-50% versus infrarenal (n = 15)-33%]. A direct relationship existed between outcome and the number of associated injuries: nonsurvivors averaged four and survivors averaged three. Eighty per cent of patients sustaining four or more associated injuries died, by contrast to a 33 per cent mortality in those suffering less than four injuries. Physiological factors were also predictive of outcome. Patients in shock (systolic blood pressure < 80) on arrival had a higher mortality than those who were hemodynamically stable (76% versus 30%). Preoperative lactate levels were of prognostic value for death (> or = 4.0-59% versus < 4.0-0%), as was base deficit (< 4-22%, > or = 4, and < 10-36%, > or = 10-73%). Interestingly, neither time from injury to hospital arrival (47.4 minutes versus 33.0 minutes) nor time in the emergency department before surgery (45.6 minutes versus 42.6 minutes) differed between survivors and fatalities. Mortality remained high in the 34 patients who had operative control of their IVC injuries [lateral repair (n = 27)-44% versus ligation (n = 6)-66% versus Gortex graft (n = 1)-0%]. As wounding agent, anatomical location, associated injuries, and physiological status seem to most directly impact mortality, future efforts must focus both on establishing prevention programs directed at reducing the incidence of this injury, as well as on advancing the management of those who do survive to hospitalization, if we are to improve on the outcome of these devastating injuries.

Diagnosis of blunt rupture of the right hemidiaphragm by technetium scan.

Traumatic rupture of the diaphragm, particularly of the right hemidiaphragm, may be occult and can be difficult to diagnose if laparotomy is not required for concomitant injury. Missed or delayed diagnosis of such injuries can produce life-threatening complications, such as intestinal herniation, ischemia, and necrosis. We present a case of traumatic rupture of the right hemidiaphragm that demonstrates the typically occult nature of this injury. The majority of right-sided injuries are diagnosed during laparotomy performed for other injuries. In those patients not requiring laparotomy, the diagnosis is usually delayed because this injury seldom produces clinical or radiographic findings that are either sensitive or specific. In this case, intraperitoneal injection of technetium sulfur colloid was used to establish the diagnosis of right diaphragm rupture, and an uncomplicated repair was undertaken.

Combined blunt cardiac and pericardial rupture: review of the literature and report of a new diagnostic algorithm.

The spectrum of blunt cardiac injury varies from the asymptomatic cardiac concussion to the immediately fatal cardiac rupture. Although the majority of victims sustaining blunt cardiac rupture die before receiving medical attention, some survive to evaluation. The diagnosis of cardiac rupture, if established, typically results from the signs and symptoms of pericardial tamponade. However, some patients may have remarkably few signs and symptoms suggestive of cardiac injury and represent a significant diagnostic challenge. We provide two cases of cardiac rupture in which the diagnosis was delayed by the presence of an associated pericardial tear with decompression into the mediastinum and pleural space. In neither of the cases did existing institutional algorithms for blunt cardiac injury assist in establishing the diagnosis before the acute demise of the patient. The presence of a coexisting pericardial injury in these patients with blunt cardiac rupture obscured the diagnosis, leading to the deaths of these patients. A discussion of these two cases and review of the literature is provided with recommendations for diagnostic algorithms in patients sustaining blunt thoracic trauma with possible cardiac and pericardial injury.

Determining anatomic injury with computed tomography in selected torso gunshot wounds.

BACKGROUND: Changes in the management of torso gunshot wounds (TGSWs) have evolved in recent years as a result of differences between military and civilian injuries and increasing interest in avoiding nontherapeutic invasive procedures. The objective of this study was to establish the utility and accuracy of computed tomography (CT) in the evaluation of selected patients with TGSWs. METHODS: Retrospective review for a 6-year period of patients who sustained TGSWs and underwent CT solely for the purpose of trajectory determination. Patients had complete physical examinations and plain radiographic evaluations by a dedicated group of in-house trauma surgeons. When trajectory was indeterminate after evaluation, CT was performed. In some cases, CT was used when trajectory was determined to be intracavitary but organ injury was believed to be unlikely or amenable to nonoperative management. RESULTS: Fifty TGSW patients underwent 52 computed tomographic scans. Abdominal/pelvic CT was performed in 37 patients, and thoracic CT was performed in 15 patients. All patients were stable and none sustained complications attributable to CT or delay in therapy. Twenty of 37 abdominal/pelvic computed tomographic scans excluded transabdominal or pelvic trajectory. Seventeen of 37 scans proved transabdominal or pelvic trajectory; nine laparotomies were performed, and eight patients were observed. Nine of 15 thoracic computed tomographic scans excluded transmediastinal trajectory. Six of 15 scans suggested vascular proximity and prompted further workup, which was positive in two cases. CONCLUSION: CT of selected TGSW patients is safe and may reduce the incidence of invasive diagnostic procedures. A prospective evaluation of CT for TGSW patients is warranted.

Hemolytically active (acylated) alpha-hemolysin elicits interleukin-1beta (IL-1beta) but augments the lethality of Escherichia coli by an IL-1- and tumor necrosis factor-independent mechanism.

Many pathogenic Escherichia coli produce the toxin alpha-hemolysin (Hly), and lipopolysaccharide (LPS), interleukin-1 (IL-1), and tumor necrosis factor (TNF) have all been recognized as important effector molecules during infections by gram-negative organisms. Despite the characterization of many in vitro effects of hemolysin, no direct relationship has been established between hemolysin, LPS, proinflammatory cytokine production, and E. coli-induced mortality. Previously, we have shown in vivo that hemolysin elicits a distinct IL-1alpha spike by 4 h into a lethal hemolytic E. coli infection. Using three transformed E. coli strains, WAF108, WAF270, and WAH540 (which produce no Hly [Hlynull], acylated Hly [Hlyactive], or nonacylated Hly [Hlyinactive], respectively), we sought to determine the specific roles of hemolysin acylation, LPS, IL-1, and TNF in mediating the lethality of E. coli infection in mice. WAF270 was 100% lethal in BALB/c, C3H/HeJ, and C57BL/6 mice; in mice pretreated with antibody to the type 1 IL-1 receptor; in type 1 IL-1 receptor-deficient mice; and in dual (type 1 IL-1 receptor-type 1 TNF receptor)-deficient mice at doses which were nonlethal (0%) with both WAF108 and WAH540. At lethal doses, WAF270 killed by 6 +/- 2.3 h while WAF108 and WAH540 killed at 36 +/- 9.4 and 36 +/- 13.8 h, respectively. These differences in mortality were not due to IL-1 or TNF release, and the enhanced expression of LPS, which corresponded to Hly expression, was not likely the primary factor causing mortality. We demonstrate that bacterial fatty acid acylation of hemolysin is required in order for it to elicit IL-1 release by monocytes and to confer its virulence on E. coli.

Emerging evidence of selection of fluconazole-tolerant fungi in surgical intensive care units.

OBJECTIVE: To determine whether increased use of fluconazole has coincided with a shift in the relative proportion of fluconazole-tolerant species isolated from critically ill surgical patients in 2 university hospitals. DESIGN: Microbiological data and fluconazole administration frequencies were reviewed among patients treated in the surgical intensive care units (SICUs) from January 1, 1990, through December 31, 1995. SETTING: The SICUs of the University of Virginia Medical Center, Charlottesville, and the Hospital of the University of Pennsylvania, Philadelphia. MAIN OUTCOME MEASURES: The number and species types of all fungal isolates and the number of patients treated with fluconazole for each of the 6 years were determined. RESULTS: A sharp increase in the use of fluconazole among critically ill surgical patients has occurred at both medical centers from 1990-1995. The culture results of most patients treated with fluconazole were negative for fungi (73% and 63% at the University of Virginia Medical Center and the Hospital of the University of Pennsylvania, respectively); there was a greater tendency to use fluconazole at the University of Virginia Medical Center compared with the Hospital of the University of Pennsylvania (2.2% vs 1.8% of patients admitted to the SICU received it, respectively; P = .007). There was a significant increase in the proportion of Candida glabrata isolated at the University of Virginia Medical Center (P < .01) from 1990-1995, but a similar change was not detectable at the Hospital of the University of Pennsylvania. CONCLUSIONS: These data justify concern that the increased use of fluconazole in SICUs may be promoting a shift in the fungal flora that cause nosocomial infections toward species that are more difficult to treat. Prospective studies about the use of fluconazole for prophylaxis and empirical therapy among SICU patients are warranted before its widespread use in these settings continues.