Intravenous dexamethasone for extubation of newborn infants

Abstract

Background

Endotracheal tubes are foreign bodies that may injure the upper airway causing laryngeal edema. This in turn may result in failure of extubation in preterm infants. Corticosteroids have been used prophylactically to reduce upper airway obstruction and facilitate extubation.

Objectives

To determine the effects of intravenous corticosteroids on the incidence of endotracheal reintubation, stridor, atelectasis and adverse side effects in newborn infants having their endotracheal tube removed following a period of intermittent positive pressure ventilation (IPPV).

Search methods

Searches were made of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library) (dexamethasone and extub*), MEDLINE (MeSH search terms "dexamethasone", "extubat*" and "exp infant, newborn"), previous reviews including cross references, abstracts of conferences and symposia proceedings, expert informants and journal handsearching mainly in the English language. These searches were updated in August 2007.

Selection criteria

Trials were included that used random or quasi‐random patient allocation and compared intravenous steroids given immediately prior to a planned extubation with placebo.

Data collection and analysis

Data were extracted independently by the two authors and analysed in RevMan for all trials. Prespecified subgroup analyses were performed to examine differences in response between infants at high risk for upper airway edema and those receiving routine prophylaxis prior to extubation.

Main results

Administration of dexamethasone prior to extubation significantly reduced the need for reintubation of the trachea. This result applies to both the high‐risk group and to the total population of infants enrolled. However, the incidence of extubation failure was zero in the trial that attempted to exclude infants at high risk of airway edema. The side effects of higher blood sugar levels and glycosuria were found in the two trials where these were sought.

Authors' conclusions

Implications for practice 
 Dexamethasone reduces the need for endotracheal reintubation of neonates after a period of IPPV. In view of the lack of effect in low‐risk infants and the documented and potential side effects, it appears reasonable to restrict its use to infants at increased risk for airway edema and obstruction, such as those who have received repeated or prolonged intubations.

Implications for research 
 Issues of dosage and applicability to the extremely low birthweight population could be addressed in future trials. Outcomes such as chronic lung disease, duration of assisted ventilation and length of hospital stay as well as long‐term neurodevelopment should also be examined.

Plain language summary

Intravenous dexamethasone for extubation of newborn infants

Dexamethasone may help babies at high risk of complications when being taken off mechanical breathing support. The tube that is placed in the baby's airway to enable mechanical ventilation (machine‐assisted breathing) can cause injury. This can lead to complications when the tube is removed (extubation). This review found that giving dexamethasone (a corticosteroid drug) around the time of extubation can help prevent swelling in the baby's throat that might require reinsertion of the tube. However, the review found that there are adverse effects of dexamethasone. The benefits only outweigh the risks for babies at high risk of complication (such as those who have received several, or prolonged, intubations).

Background

Endotracheal intubation is used to provide intermittent positive pressure ventilation (IPPV) for a number of neonatal conditions. The presence of a foreign body in contact with delicate upper airway mucosa can lead to injury. This may take the form of laryngeal oedema, vocal cord injury or subglottic stenosis, all of which may present clinically as upper airway obstruction after extubation (Arensman, 1988). This may in turn lead to increasing respiratory distress requiring reintubation of the trachea. Factors that may increase the likelihood of damage include repeated passage of an endotracheal tube, prolonged intubation and the presence of a large tube relative to the size of the glottis. Various agents including systemic corticosteroids have been used both prophylactically and as treatment to reduce upper airway obstruction and facilitate extubation (Carlo 1992).

In addition, corticosteroids may also have a beneficial effect on the lower airways by decreasing oedema and secretions due to the toxic effects of oxygen and IPPV. Increased compliance of the lung has been observed following corticosteroid treatment (Durand 1995). A reduction of respiratory distress and consequent pressure gradients across the upper airway may decrease the tendency towards upper airway narrowing during extubation.

Systemic corticosteroids are not without side‐effects. Halliday 2003 reported increased rates of short‐term (hyperglycemia and hypertension) and long‐term (neurological abnormalities including cerebral palsy) adverse effects in infants treated with early corticosteroids to prevent chronic lung disease.

This review updates the existing review of intravenous dexamethasone in neonates being extubated which was published in the Cochrane Library (Davis 1999).

Objectives

To determine whether the use of intravenous corticosteroids improves the post‐extubation course of newborn infants as evidenced by effects on the incidence of endotracheal reintubation, stridor, atelectasis and adverse side effects. Subgroup analysis was performed to determine whether there was a difference in response between the group of newborn infants as a whole and those thought to be at high risk of upper airway obstruction because of prolonged intubation or traumatic or multiple intubations. Sensitivity analysis was planned to investigate the role of potential confounding variables such as the use of nasal CPAP post‐extubation.

Methods

Criteria for considering studies for this review

Types of studies

All trials utilising random or quasi‐random patient allocation were included.

Types of participants

Newborn infants who received Intermittent Positive Pressure Ventilation (IPPV) and were about to have their endotracheal tube removed.

Types of interventions

Intravenous administration of corticosteroid.

Types of outcome measures

The primary outcome of interest was the need for reintubation of the trachea. Secondary outcomes included:

• the presence of clinical signs suggestive of upper airway obstruction (stridor, respiratory distress, atelectasis) and

• adverse effects such as hyperglycemia and hypertension.

Search methods for identification of studies

Searches were made of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2007) dexamethasone and extub*), MEDLINE (1966 ‐ August 2007, MeSH search terms "dexamethasone", "extubat*" and "exp infant, newborn"), previous reviews including cross references, abstracts of conferences and symposia proceedings, expert informants, journal handsearching mainly in the English language.

Data collection and analysis

Criteria and methods used to assess the methodological quality of the included trials: 
 The standard method of the Cochrane Collaboration and its Neonatal Review Group were used. The methodological quality of each trial was reviewed by the second author blinded to trial authors and institutions. Methodological quality assessment was based on 1) blinding of randomisation, 2) blinding of intervention, 3) completeness of follow‐up and 4) blinding of outcome measurement.

Methods used to collect data from the included trials: 
 Each review author extracted data separately before comparison and resolution of differences.

Methods used to synthesize data: 
 Standard method of the Neonatal Review Group with the use of relative risk (RR), risk difference (RD) and number needed to treat (NNT). Heterogeneity was examined using the I squared test.

Subgroup analysis was performed to determine whether there was a difference in response between the group of newborn infants as a whole and those thought to be at high risk of upper airway obstruction because of prolonged intubation or traumatic or multiple intubations. Sensitivity analysis was planned to investigate the role of potential confounding variables such as the use of nasal CPAP post‐extubation.

Results

Description of studies

Three randomized trials were identified which addressed the effects of treatment with dexamethasone to facilitate extubation of newborn infants following a period of IPPV. A full description of each is included in the Table, Characteristics of Included Studies. No trials were excluded from the review and no ongoing trials were identified.

The participants in the three trials differed with respect to risk of airway edema. Couser 1992 selected a population considered at high risk because of either traumatic or multiple intubations or intubation for more than 14 days. This group had a mean weight at entry of around 1200g. Ferrara 1989 specifically excluded patients intubated more than once and enrolled infants with a mean duration of intubation of less than a week. His patients comprised a heavier (mean > 2kg) and more mature (mean > 33 weeks) population. The trial of Courtney 1992 also studied a heavier (mean extubation weight 2200 ‐ 2400g), more mature population (mean 32 ‐ 34 weeks gestational age). There was no effort to include or exclude infants on the basis of perceived risk of airway edema although an upper limit of 30 days of intubation was placed to minimise the effect of subglottic stenosis.

All three trials used dexamethasone intravenously. Courtney 1992 used three doses of 0.5 mg/kg, Couser 1992 3 doses of 0.25mg/kg and Ferrara 1989 used a single dose of 0.25 mg.

The primary outcome, need for endotracheal intubation, was assessed in all trials. The presence of stridor was noted by Couser 1992 and Ferrara 1990 and atelectasis on CXR reported by Ferrara 1989 and Courtney 1992. Side effects of dexamethasone including hypertension and hyperglycemia were evaluated by Couser 1992 and Courtney 1992.

Risk of bias in included studies

All the trials are of high quality and full details are provided in the Table, Characteristics of Included Studies.

Method of subject allocation: 
 All three included studies were randomized controlled trials. Only Courtney 1992 specified the use of a random number table and this trial and Couser 1992 used off site randomization.

Masking of caregivers: 
 The use of a normal saline placebo ensured caregivers were unaware of group of assignment. In view of the systemic side effects it is possible that the actual treatment group could have been suspected in some cases.

Completeness of outcome assessment: 
 Couser 1992 and Ferrara 1989 had complete follow‐up of all randomized infants for all outcomes. Courtney 1992 excluded nine randomized infants from studies of pulmonary mechanics. However, all were included for the clinically important outcomes of endotracheal reintubation and atelectasis.

Masking of outcome assessors: 
 Masking of outcome assessment was achieved in all trials.

Effects of interventions

There was no disagreement between reviewers with respect to quality assessment done independently. After discussion, there was also no disagreement regarding data extraction.

PRIMARY OUTCOME 
 
 ENDOTRACHEAL REINTUBATION (OUTCOMES 01.01, 02.01): 
 
 For the population as a whole, dexamethasone prior to extubation reduced the use of endotracheal reintubation [typical RR 0.18 (0.04, 0.97), typical RD ‐0.09 (‐0.16, ‐0.01)]. Since number needed to treat (NNT) is the inverse of RD, on average twelve infants would need to be treated to prevent 1 reintubation, although confidence intervals are wide [NNT 12 (6, 100)]. In the subset of those thought to be at high risk of upper airway edema, a trend favouring dexamethasone did not reach statistical significance (confidence intervals surrounding RR include 1). However the RD does reach significance [RD ‐0.17 (‐0.034, ‐0.004)] and on average six high‐risk infants need to be treated to prevent one reintubation, with very wide confidence intervals [NNT 6 (3, 250)].

The drug is not without side‐effects and defining the group of infants in whom it is most likely to be effective is desirable. The trial in which infants with one risk factor for upper airway edema (multiple intubations) were excluded (Ferrara 1989) had a reintubation rate in the total study population of 0 of 59 infants. The overall treatment effect is therefore derived from the high‐risk population of Couser 1992 and the population including all intubated infants of Courtney 1992.

SECONDARY OUTCOMES

POST EXTUBATION STRIDOR (OUTCOMES 01.02, 02.02, 03.01, 04.01): 
 Dexamethasone was also effective in reducing the incidence of postextubation stridor [typical RR 0.39 (0.16,0.93), typical RD ‐0.17 (‐0.31, ‐0.03), NNT 6 (3, 37)]. This result is heavily influenced by the trial of Couser 1992. Post hoc analysis on the basis of the dose of dexamethasone administered shows that while the multiple dose strategy of Couser reduced the incidence of stridor, the single dose regime of Ferrara 1989 did not. 
 The long‐term outcome of subglottic stenosis was reported only by Couser and the low incidence of this complication means caution should be exercised in interpreting the trend favouring dexamethasone (Outcome 01.05).

POST EXTUBATION ATELECTASIS (OUTCOME 01.03): 
 A trend exists towards a reduction in the rate of postextubation atelectasis with dexamethasone but once again the low risk population of Ferrara 1989 recorded no cases of this adverse outcome.

GLYCOSURIA (OUTCOME 01.04): 
 Glycosuria occurred only in infants treated with dexamethasone (7 of 27) in the only trial evaluating this outcome (Couser 1992). Using the measure of RD, this finding is statistically significant [typical RD 0.26 (0.08,0.44)] and the number needed to treat to produce this harm is 4 (2, 13). Bedside monitoring also showed a statistically significantly higher glucose level in the dexamethasone group (Courtney 1992). The clinical importance of these findings is not fully examined. In each of the two trials recording blood pressure as an outcome (Couser 1992 and Courtney 1992), the authors reported no differences between groups. No details are presented to allow meta‐analysis of this outcome.

OTHER OUTCOMES: 
 Two studies recorded pulmonary function tests before and after extubation. Couser 1992 demonstrated significant differences between dexamethasone and placebo groups with respect to total respiratory resistance, dynamic compliance and tidal volumes, all favouring dexamethasone. In the lower risk population of Courtney 1992, no such differences were found. Couser 1992 also reported pCO2 values postextubation that were statistically lower in the dexamethasone group. The absolute difference of 5 mm Hg was of limited clinical importance.

An a priori subgroup analysis was planned to examine the confounding variable, use of postextubation NCPAP. This was unable to be performed as the two trials in which this cointervention was used (Couser 1992 and Ferrara 1989) did so on an ad hoc basis and did not report outcomes related to NCPAP administration.

Discussion

The outcome, requirement for endotracheal reintubation, is of modest clinical importance in the spectrum of those relating to neonatal intensive care. In addition to its implications of instability for the infant, reintubation has economic consequences, the presence of an endotracheal tube significantly increasing the cost of intensive care. Dexamethasone is a potent glucocorticoid with many effects beyond reducing airway edema. The disturbance to glucose metabolism is well demonstrated by two of the included studies. In combination, these facts suggest that it is important to define both a group at low risk of requiring reintubation, in whom dexamethasone may not be justified and a high‐risk group that will benefit from administration of the drug before extubation.

Description of the study populations of Courtney 1992 and Ferrara 1989 does not allow definition of their risk factors as outlined by Couser 1992. However, it is likely that the latter study included a population at substantially higher risk of requiring reintubation compared with the other two. In a high‐risk population, the equation of treating six infants with dexamethasone in order to prevent one reintubation seems to favour treatment. The absence of infants requiring reintubation in the Ferrara 1989 trial in larger infants having had only one endotracheal tube suggests treatment is not indicated in this group. Interestingly, in a randomized trial of the routine use of dexamethasone prior to extubation in older children (Tellez 1991), no benefit could be demonstrated.

Since we regard the avoidance of intubation and other pulmonary benefits as having greater clinical importance than glycosuria, we believe the use of dexamethasone can be justified for infants at high risk of upper‐airway edema and obstruction after extubation. 
 
 Some uncertainty exists about the clinical importance of the benefit attributed to dexamethasone by the limited time of follow‐up reported by these studies. The need for reintubation beyond 24 hours after ETT removal is not reported. It is possible that the benefits of dexamethasone derive, at least in part, from the improvements in pulmonary compliance demonstrated by Couser 1992, an effect that may have diminished over a longer period. Longer courses of corticosteroids to reduce chronic lung disease were linked to increased risk of neurodevelopmental problems (Halliday 2003). No trials of short‐course corticosteroids for extubation have followed up infants after discharge and long‐term safety remains undetermined.

An additional limitation of this review results from the changes in neonatal intensive care since these studies were performed. The use of exogenous surfactant, increased use of antenatal steroids and the trend to extubate early to NCPAP have reduced the duration of endotracheal intubation. In addition, an increasing number of survivors at 22 to 24 weeks forms a new population in whom this treatment may have a different safety/efficacy profile.

Two dosage regimens were used by trials in this review. Meaningful comparison is only possible with respect to the outcome of stridor. An apparent advantage of the higher, multiple dose strategy requires further investigation.

Epinephrine has been used topically to reduce airway oedema and to facilitate extubation and is the subject of another systematic review (Davies,1998).

Authors' conclusions

Implications for practice.

Dexamethasone reduces the need for endotracheal reintubation of neonates after a period of IPPV. In view of the lack of effect in low‐risk infants and the documented and potential side effects, it appears reasonable to restrict its use to infants at increased risk for airway edema and obstruction, such as those who have received repeated or prolonged intubations.

Implications for research.

Issues of dosage and applicability to the extremely low birthweight population should be evaluated. Outcomes such as chronic lung disease, duration of assisted ventilation and length of hospital stay as well as long‐term neurodevelopment should also be examined.

What's new

Date	Event	Description
14 January 2008	Amended	Converted to new review format.

History

Protocol first published: Issue 2, 1997
 Review first published: Issue 1, 1999

Date	Event	Description
23 October 2007	New search has been performed	This review updates the review "Intravenous dexamethasone for extubation of newborn infants" published in The Cochrane Library, Issue 4, 2001 (Davis 2001). A repeat literature search showed no new trials eligible for inclusion and there have been no substantive changes to the review.
4 July 2001	New citation required and conclusions have changed	Substantive amendment

Data and analyses

Comparison 1. Dexamethasone vs Placebo (all infants).

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Endotracheal reintubation	3	160	Risk Ratio (M‐H, Fixed, 95% CI)	0.18 [0.04, 0.97]
2 Postextubation stridor	2	109	Risk Ratio (M‐H, Fixed, 95% CI)	0.39 [0.16, 0.93]
3 Postextubation atelectasis	2	110	Risk Ratio (M‐H, Fixed, 95% CI)	0.54 [0.19, 1.53]
4 Glycosuria	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	12.86 [0.77, 213.62]
5 Subglottic stenosis	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	0.28 [0.03, 2.55]

1.1. Analysis.

Comparison 1 Dexamethasone vs Placebo (all infants), Outcome 1 Endotracheal reintubation.

1.2. Analysis.

Comparison 1 Dexamethasone vs Placebo (all infants), Outcome 2 Postextubation stridor.

1.3. Analysis.

Comparison 1 Dexamethasone vs Placebo (all infants), Outcome 3 Postextubation atelectasis.

1.4. Analysis.

Comparison 1 Dexamethasone vs Placebo (all infants), Outcome 4 Glycosuria.

1.5. Analysis.

Comparison 1 Dexamethasone vs Placebo (all infants), Outcome 5 Subglottic stenosis.

Comparison 2. Dexamethasone vs Placebo (high risk patients).

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Endotracheal reintubation	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	0.10 [0.01, 1.68]
2 Stridor	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	0.17 [0.04, 0.70]
3 Subglottic stenosis	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	0.28 [0.03, 2.55]

2.1. Analysis.

Comparison 2 Dexamethasone vs Placebo (high risk patients), Outcome 1 Endotracheal reintubation.

2.2. Analysis.

Comparison 2 Dexamethasone vs Placebo (high risk patients), Outcome 2 Stridor.

2.3. Analysis.

Comparison 2 Dexamethasone vs Placebo (high risk patients), Outcome 3 Subglottic stenosis.

Comparison 3. Dexamethasone vs Placebo (multiple dose).

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Postextubation stridor	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	0.17 [0.04, 0.70]

3.1. Analysis.

Comparison 3 Dexamethasone vs Placebo (multiple dose), Outcome 1 Postextubation stridor.

Comparison 4. Dexamethasone vs Placebo (single dose).

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Postextubation stridor	1	59	Risk Ratio (M‐H, Fixed, 95% CI)	0.97 [0.27, 3.51]

4.1. Analysis.

Comparison 4 Dexamethasone vs Placebo (single dose), Outcome 1 Postextubation stridor.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Courtney 1992.

Methods	1) Blinding of randomization ‐ yes: random number table, cards drawn by pharmacy personnel 2) Blinding of intervention ‐ yes 3) Complete followup ‐ yes for the important outcome of endotracheal reintubation, incomplete for some secondary outcomes 4) Blinding of outcome measurement ‐ yes
Participants	Included: infants > 1000g, intubated for 3 to 30 days. Primary conditions comprised RDS (38), pneumonia (8), airleak (2), asphyxia (1), meconium aspiration (1) and persistent fetal circulation (1). Excluded: anomalies of the airway or lungs, evidence of active infection, hypertension, hyperglycemia or bleeding diathesis or had received steroids (including maternal) within 5 days of extubation.
Interventions	Dexamethasone 0.5 mg/kg in 3 doses, 8 hours apart, the last dose given 1 hour before extubation or normal saline placebo.
Outcomes	Reintubation within 24 hours of extubation. Postextubation atelectasis within 24 hours on CXR. Pulmonary mechanics using an esophageal balloon and a heated pneumotachometer. Side effects of dexamethasone: BP and bedside glucose estimations every 4 hours, observation over 1 week for evidence of sepsis (documented on blood, urine, CSF cultures)
Notes	Larger infants ‐ mean weight at extubation = 2.43 kg, intubated for mean of 9 to 11 days. No sample size calculations provided. 9 of 51 (18%) were excluded after randomization although data available on all for the outcome of endotracheal reintubation.
Risk of bias
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Low risk	A ‐ Adequate

Couser 1992.

Methods	1) Blinding of randomization ‐ Yes: method unspecified, performed by hospital pharmacy 2) Blinding of intervention ‐ Yes 3) Complete followup ‐ Yes 4) Blinding of outcome measurement ‐ Yes
Participants	Included: infants at high risk for airway edema: traumatic or multiple endotracheal intubations. Excluded: congenital central airway or lung parenchymal anomalies, open use of dexamethasone for CLD, sedative or muscle relaxant medication within 12 hours of extubation. Reached predetermined minimal levels of respiratory support with no atelectasis on CXR and normal blood gases.
Interventions	Dexamethasone 0.25 mg/kg per dose at 8 hourly intervals for 3 doses beginning 4 hours before extubation or normal saline placebo.
Outcomes	Reintubation: for severe stridor plus bradycardia, oxygen saturation <85% in > 80% inspired oxygen and unresponsive to racemic epinephrine or required frequent bag and mask ventilation. Stridor: defined as a high‐pitched inspiratory sound associated with signs of upper airway obstruction. Atelectasis apparent on CXR performed within 24 hours postextubation. Blood gas analysis at 2 to 4 hours and 18 to 24 hours postextubation. Pulmonary mechanics using heated pneumotachometer. Side effects of dexamethasone: BP estimations every 3 to 4 hours, screening for glycosuria followed by bedside and formal blood glucose estimations as required.
Notes	High risk infants with mean weight at entry ˜ 1200g. NCPAP and methylxanthine use at discretion of attending neonatologist. Sample size calculation performed on the basis of rates of extubation failure.
Risk of bias
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Low risk	A ‐ Adequate

Ferrara 1989.

Methods	1) Blinding of randomization ‐ yes: method unspecified 2) Blinding of intervention ‐ yes 3) Complete followup ‐ yes 4) Blinding of outcome measurement ‐ yes
Participants	Included: Single intubation, ventilated for at least 48 hours (mean = 6 days), larger infants (mean birthweight ˜2200g. Extubated from low ventilator settings ‐ <35% oxygen, rate < 6 breaths/minute, PEEP < 4cm. Excluded:respiratory acidosis (pH < 7.30, pCO2 > 50), > 1 intubation, already receiving steroids, congenital anomalies.
Interventions	Dexamethasone as a single 0.25 mg/kg dose, 30 minutes before extubation or saline placebo.
Outcomes	Assessed at 30 minutes, 6 hours and 24 hours postextubation: audible stridor, blood gas estimations, oxygen requirements, Downes' score, the need for reintubation, apnea and bradycardic episodes. Assessed at 4 and 24 hours: CXR for lobar atelectasis
Notes	Infants < 1500g managed with NCPAP postextubation One infant excluded after randomization because of central hypoventilation syndrome. Sample size calculations performed on the basis of rates of "respiratory complications"
Risk of bias
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Low risk	A ‐ Adequate

CLD = chronic lung disease; BP = blood pressure; CXR = chest xray; RDS = respiratory distress syndrome; NCPAP = nasal continuous positive airway pressure, PEEP = positive end expiratory pressure.

Contributions of authors

Each review author independently searched the literature and extracted data from trials meeting inclusion criteria. 
 PGD wrote the review with assistance from DHS.

Sources of support

Internal sources

• University of Melbourne, Australia.

• NSW Centre for Perinatal Health Services Research, Sydney, Australia.

• Royal Prince Alfred Hospital, Sydney, Australia.

• Royal Women's Hospital, Melbourne, Australia.

• Murdoch Children's Research Institute, Melbourne, Australia.

External sources

• Department of Health and Aging, Commonwealth Government, Canberra, Australia.

• National Health and Medical Research Council, Australia.

Declarations of interest

None

Edited (no change to conclusions)