Simultaneous and Consecutive Drainage of Bilateral Chronic Subdural Hematoma: A Randomized Controlled Trial

Abstract

Chronic subdural hematoma (CSDH) is one of the most common types of intracranial hemorrhage, particularly in elderly individuals. Although most patients present with unilateral CSDH, bilateral involvement is not rare. Furthermore, bilateral CSDHs are associated with rapid deterioration and poorer outcomes because of a higher risk of brain herniation than unilateral hematomas. The most contentious issue is the potential herniation of the medial temporal lobe, which remains on the unevacuated side during the brief interval between right and left procedures. We compared simultaneous burr-hole craniostomy with consecutive burr-hole craniostomy for treating bilateral CSDH and to determine whether consecutive evacuation is riskier in terms of brain stem complications.

Over a 6.5-year period, patients with bilateral CSDH who had an indication for operation were allocated into two groups randomly. The first group (n = 18) underwent simultaneous evacuation, and the second group (n = 25) underwent consecutive evacuation. Glasgow Coma Scale and Markwalder grades were recorded during the postoperative period. Patients were followed up during the inpatient period and postoperatively at 1, 3, 6, and 12 months after discharge. Mortality, morbidity, surgical complications, reoperation, and, as a combination of all of these, treatment success rates were compared. Treatment success rates were worse in patients with mixed-density hematomas and in female patients at the end of 12 months, but there was no significant difference between the simultaneous and consecutive evacuation groups at any time. Therefore, the choice of technique can be decided by the surgeon.

Introduction

Chronic subdural hematoma (CSDH) arises at the dural border cell layer and is characterized by a pathological collection of blood, fibrin, and degradation products between the dura and arachnoid mater with an insidious onset and progression.^1,2) Theories of the formation and expansion of CSDH have evolved over time and suggested traumatic and inflammatory components that contribute to membrane formation and the development of permeable neovessels.^1-3) Surgical evacuation of CSDH via burr-hole craniostomy appears to be the most widely practiced treatment technique worldwide, and outcomes are generally favorable.^4-11)

Although most patients present with unilateral CSDH, approximately 16%-25% of CSDHs are bilateral. In previous reports, bilateral CSDH was raised as a predictor of rapid deterioration and worse outcomes attributable to brain herniation compared with unilateral ones.^12-14) In 1999, Okuchi et al. reported right oculomotor nerve paresis and hemiparesis in a case of “bilateral CSDH” after consecutive evacuation. Saying that this was caused by herniation of the unilateral medial temporal lobe during the short time between the right and left procedures, he suggested simultaneous removal.¹⁵⁾ However, this theory has not been confirmed. In recent years, similar issues have been discussed in other case reports.^14,16,17) Nevertheless, the optimal surgical considerations for bilateral CSDH remain controversial. Thus, this study primarily aimed to determine whether consecutive removal of bilateral CSDH poses a risk of complications. The secondary objectives of the study were to obtain information about the 1-year prognosis of bilateral CSDH and to determine other factors that affect the prognosis, if any.

Materials and Methods

The study was conducted as a prospective randomized controlled trial (ClinicalTrials.gov identifier: NCT06337851). Approval for the study was obtained from the local ethics committee (institutional review board) of Izmir Ataturk Training and Research Hospital under decision number 2003/9. The recruitment period was 6.5 years.

Inclusion criteria

Symptomatic adult (≥18 years old) patients with bilateral hemispheric CSDH who presented to the Neurosurgery Department of our tertiary hospital were included in the study.

Exclusion criteria

Patients with hematoma thickness smaller than 10 mm on either side and those who previously underwent any cranial surgery were excluded.

Randomization

Simple randomization, without blocking was used to divide patients into two groups: simultaneous (group 1) and consecutive (group 2) burr-hole craniostomy. Written consent was obtained from each patient or his/her relatives for the surgery and the use of data in this study.

Clinical evaluation

Evaluation was based on the Glasgow Coma Scale (GCS), motor examination, Babinski sign, and headache.^7,18)

Radiological evaluation

For preoperative computed tomography (CT) images of CSDHs, Nakaguchi's classification¹⁹⁾ of laminar, separated, and trabecular types was used as is, whereas the homogeneous group was divided into three subgroups: homogeneous hypodense, homogeneous isodense, and homogeneous hyperdense, as suggested by Gökmen et al.⁸⁾ The term mixed density was used, as suggested by Gökmen et al., to describe de novo hyperdense hemorrhagic foci in previous hypodense hemorrhage.⁸⁾ However, unlike the ones in the separated type, these foci do not accumulate at the underside due to gravity but have mixed presence within the subdural hematoma cavity.

CT scan was used to calculate the hemorrhage thickness, hemorrhage volume, and midline shift of CSDHs (Fig. 1). Axial sections crossing the pineal gland and septum pellucidum were used to measure hemorrhage thickness because the axial CT sections at the upper calvarium were not perpendicular but were oblique to the hemorrhage. The inner table was used to measure the distance from the thickest point of the hematoma to the brain parenchyma (Fig. 2). Bilateral hemorrhage volumes were calculated in the CT sections of all patients using the XYZ/2 formula.²⁰⁾

Fig. 1.

Preoperative shift measurement for patient no. 30. The lines indicate the midline, septum pellucidum shift, and pineal gland shift.

Fig. 2.

Measurement of hematoma thickness on the (a) right and (b) left sides on preoperative computed tomography scan of patient no. 37.

Operation

Patients were operated under general or local anesthesia based on the recommendations of anesthesiologists and the patient's general medical status. First-generation cephalosporins were used as preoperative prophylactic antibiotics (cefazolin). Patients in group 1 were fixed in the supine position with their heads in the neutral and flexion positions. Bilateral burr holes were made one after another, the dural surfaces were exposed simultaneously, and outer membranes of both sides were opened, and the hematomas were evacuated simultaneously. All patients underwent drainage system, which was performed by inserting a silicone tube into the subdural space and tunneling under the scalp to the exit point. In group 2, the hematoma with the greatest thickness was removed first. (If thickness was equal on both sides, the first incision was made on the right side.) The head in the supine position was rotated to the side with a smaller hemorrhage thickness. A burr hole was created, the dural surface was exposed, the outer membrane was opened, and the hematoma was evacuated at one side. Then, drainage system was inserted into the subdural space. After the procedure on the first side was completed, as a consecutive process, the head was rotated to the other side, and the same procedure was repeated. The contralateral hematoma was evacuated. For postoperative drainage in both groups, 12-gauge soft drainage sets with secretion bags were used. Depending on the subdural fluid collected, all drains were removed within 36-48 h postoperatively. Only those patients with epileptic history and who are on epileptic medication received postoperative antiepileptics.

Follow-up

In the postoperative period, a comprehensive evaluation encompassing neurological examinations and CT imaging was performed. This evaluation protocol was executed immediately following the surgical procedure; after the removal of surgical drains (usually on the second postoperative day); and at designated intervals of the 1st, 3rd, 6th, and 12th months to monitor patient progress and recovery. Surgical success was defined as follows: patients with no surgery-related complications, no recurrence requiring redo surgery, and good clinical outcomes, means: GCS score of 15, improvement in paresis and headache.

Variables

The independent variables were evacuation sequence, preoperative GCS score, preoperative Babinski sign, age, sex, and CT appearance of the hematoma. The dependent variable was surgical success.

Primary and secondary outcome measures

In this study, the primary outcome measure was to determine whether there is a difference in success rates between simultaneous and consecutive burr-hole craniostomy. The secondary outcome measure was to determine the ones that affect the success rate among other independent variables, if any.

Statistics

The independent samples t-test was used for continuous variables, and the Mann-Whitney U test was used for categorical variables. Chi-squared statistics or Fisher's exact test was used for nominal variables. Results were considered significant if p < 0.05. All statistical analyses were performed using IBM SPSS software.

Results

On the basis of the aforementioned criteria, 43 patients (38 male, 5 female) were included in the study. Eighteen and 25 patients were assigned to groups 1 and 2, respectively.

Preoperative findings of all cases

All patients had at least a 10-mm thick bilateral CSDH localized in the convex portion, with possibly associated symptoms.

The patients' ages varied between 22 and 89 (mean 67.98, SD 15.82) years, and 18 patients had a trauma history. Of the 43 patients, 21 were diagnosed with hypertension, 8 had a history of ischemic cerebrovascular disease, 7 had cardiac pathologies, 3 had epilepsy, 1 had a hematologic disorder, and 1 had a hepatic pathology. The feature distribution by group is shown in Table 1.

Table 1.

Comparisons of demographic and clinical features between the simultaneous and consecutive groups

	Simultaneous group (n = 18)	Consecutive group (n = 25)	p-value
Mean age (years)	67.11 ± 15.81	68.60 ± 16.13	0.833*
Gender (male/female)	17/1	21/4	0.292†
Trauma history	9	9	0.359††
Hypertension	10	11	0.455††
Cardiac pathologies	3	4	0.634†
Hematologic disorder	1	0	0.429†
Hepatic pathology	0	1	0.581†
Ischemic cerebrovascular disease	4	4	0.447†
Epilepsy	1	2	0.624†
Symptom/sign
Presence of headache	13	13	0.278†
Median headache scores	1 (min 1, max 2)	1 (min 0, max 2)	0.586**
Presence of paresis	4	6	0.456†
Mental change	12	14	0.480††
Median GCS at admission	13.5 (min 6, max 15)	14.0 (min 6, max 15)	0.838**
Interval between ictus and surgery (days)	0.17 ± 0.38	0.48 ± 1.76	0231*

*Independent samples Student t-test. **Mann-Whitney U test. ^†Fisher’s exact test. ^††Pearson chi-squared test. GCS, Glasgow Coma Scale

The elapsed time between ictus and surgery was 0.35 (SD 1.36) days.

The total GCS varied between 6 and 15 (median 14). There were 17 patients who had a preoperative GCS score of 15. Six of the 17 patients had unilateral or bilateral paresis. All 11 remaining patients complained of headache.

Eight and 11 patients had unilateral and bilateral positive Babinski's signs, respectively.

CT revealed that of the hemorrhages evaluated, 27 were homogeneous isodense, 20 were separated, 16 were homogeneous hypodense, 13 presented a mixed density, 2 displayed a trabecular pattern, 1 was laminar, and 1 was homogeneous hyperdense. Because three patients were operated with preoperative MRI, CT imaging was not available of them.

The mean right-sided bleeding thickness was 1.85 cm (SD 0.64), and the mean left-sided bleeding thickness was 1.85 cm (SD 0.58). The difference in the hematoma thickness between the right and left sides of the same patient was 0.00-2.70 cm, and the mean value was 0.67 cm (SD 0.54). The mean of the sum of the right and left bleeding thickness in the same patient was 3.70 cm (SD 0.85).

The mean right- and left-sided bleeding volume was 40.25 cm³ (SD 20.64) and 44.00 cm³ (SD 21.93), respectively. The difference in the hematoma volume between the right and left sides of the same patient was 1-64.0 cm³, and the mean value was 18.75 cm³ (SD 16.92). The mean sum of the right- and left-sided bleeding volumes in the same patient was 84.28 cm³ (SD 34.34).

The preoperative septum pellucidum shift toward the right and left sides was up to 10.0 mm (mean 1.35, SD 2.93) and 12 mm (mean 1.09, SD 2.70), respectively. The pineal gland shift toward the right and left sides was up to 6.0 mm (mean 0.70, SD 1.82) and 9.0 mm (mean 0.55, SD 1.72), respectively.

Preoperative findings according to the groups

There were no differences between consecutive and simultaneous surgery groups in terms of age and time elapsed between ictus and surgery (Table 1). The rate of having at least one additional pathology was slightly higher in the simultaneous group (100%) than in the consecutive group (80%) (p = 0.044; Pearson's chi-squared test).

There was no difference between these two surgical groups in terms of right or left bleeding thickness, right or left bleeding volume, bleeding thickness and volume differences between the right and left sides, and the sum of right and left bleeding volumes (p = 0.147, 0.350, 0.058, 0.509, 0.355, 0.465, and 0.063 respectively; independent samples t-test). Furthermore, there was no difference between these two surgical groups in terms of septum pellucidum and pineal gland shift presence (p = 0.616 and 0.746; Pearson's chi-squared test).

Unsuccessful cases

By the end of the 12th postoperative month, 10 patients had died, 4 required reoperations, and 12 patients underwent reoperation and/or died (Tables 2 and 3). One patient died of ARDS that developed after pneumonia, and another five patients died because of the surgical procedure (mortality rate 11.6%) within 30 days postoperatively. As the follow-up period increased, deaths occurred for reasons unrelated to surgery.

Table 2.

Comparisons of follow-up clinical features between the simultaneous and consecutive groups

	Postop		1st M		3rd M		6th M		12th M
	SG	CG	SG	CG	SG	CG	SG	CG	SG	CG
Median GCS Median (min/max)	15 (7/15)	15 (8/15)	15 (14/15)	15 (14/15)	15 (15/15)	15 (15/15)	15 (15/15)	15 (15/15)	15 (15/15)	15 (15/15)
Median headache score Median (min/max)	2 (0/2)	2 (0/2)	1 (0/2)	1 (0/2)	0 (0/2)	0 (0/2)	0 (0/1)	0 (0/1)	0 (0/1)	0 (0/0)
Presence of paresis (n)	3	4	0	0	0	0	0	0	0	0
Reoperation (n)	1	0	0	2	0	1	0	0	0	0

GCS, Glasgow Coma Scale; SG, simultaneous group; CG, consecutive group; Postop, early postoperative period; M, month

Table 3.

Mortality rates and causes in the simultaneous and consecutive groups

	Relation	Simultaneous group (n = 18)	Consecutive group (n = 25)	Total	p-value†
Within 7 days of surgery	Total*	1 (%5.56) - Sudden cardiac arrest on the 2nd day	2 (%8.00) - Ovarian cancer, GIS metastasis, poor general condition, and sudden cardiac arrest on the 6th day - Postoperative CT: bilateral thick ASDH	3 (%6.98)	0.624
Within 30 days of surgery	SP	0	2 - Discharged on the 3rd postoperative day. 10 days later, GCS: 5, ASDH on the right side - Discharged on the 7th postoperative day. 5 days later, unconsciousness, bilateral subdural empyema	2	0.503
	OP	1 - Pneumonia-ARDS	0	1
	Total**	2 (%11.1)	4 (%16.00)	6 (%13.95)
3rd month	SP	0	0	0	0.634
	OP	1 -Pulmonary embolism	0	1
	Total**	3 (%16.67)	4 (%16.00)	7 (%16.28)
6th month	SP	0	0	0	0.425
	OP	0	2 - Cardiac pathologies	2
	Total**	3 (%16.67)	6 (%24.00)	9 (%20.93)
12th month	SP	0	0	0	0.594
	OP	1 - Gastric cancer and GIS bleeding	0	1
	Total**	4 (%22.2)	6 (%24.00)	10 (%23.26)

* All deaths occurring within the first 7 days postoperatively were considered surgery-related mortality. **All deaths occurring up to the specified time. ^†Fisher’s exact test. SP, surgery-related deaths; AP, deaths related to other pathologies; GIS, gastrointestinal system; CT, computed tomography; ASDH, acute subdural hematoma; GCS, Glasgow Coma Scale

General follow-up data

One patient was unreachable. The remaining 30 patients were contacted via telephone and scheduled for follow-up. Twenty-four patients visited the hospital for clinical and radiological evaluations. The other 6 patients were clinically evaluated via telephone according to the information received from them and their relatives.

All 30 patients who were reached via telephone had a GCS score of 15. None of the patients experienced paresis or headache. No motor deficit was detected in any of the 24 patients who came to the hospital for control, except for 1 patient with SVA sequela left hemiparesis (patient no. 16).

Results by evacuation sequence

The groups were compared in terms of success during each control period. No significant differences were observed between the two groups in any period (p = 0.818, 0.605, 0.834, 0.612, and 0.921 in the postoperative early period and 1st, 3rd, 6th, and 12th month, respectively; Pearson's chi-squared test).

Results by preoperative GCS score

At the end of the 12th month, successful results were obtained in 19 (86%) of 22 patients with preoperative GCS scores of 14 or 15, and successful results were obtained in 11 (55%) of 20 patients with GCS scores of ≤13 (p = 0.025; Pearson's chi-squared test).

Results by preoperative Babinski's sign

In the postoperative 1st month follow-up of 13 patients with preoperative bilateral positive Babinski's sign, unsuccessful results were obtained in 5 (38.5%) patients. Unsuccessful results were obtained in 3 (10%) of the 30 patients without bilateral positive Babinski's sign. In the 6th month controls, 6 (46.2%) of 13 patients with bilateral positive Babinski's sign had unsuccessful results. In the same period, unsuccessful results were observed in 5 (17.2%) of 29 patients (1 patient lost to follow-up) without bilateral positive Babinski's sign. These results were statistically significant (p = 0.028 and 0.049; Pearson's chi-squared test).

Results by age

There were no statistically significant relationships between age and results (control months: p = 0.079/1st, 0.065/3rd, 0.408/6th, 0.625/12th; independent samples t-test).

Results by gender

The success rate was lower in female patients in the early postoperative period at the 6th and 12th control months (p = 0.011, 0.011, and 0.04; Pearson's chi-squared, Pearson's chi-squared, and Fisher's exact tests, respectively). There were no successful results in five female patients in the early postoperative period. One of the five female patients was lost to follow-up after the 1-month follow-up. There were no successful outcomes in the other four female patients.

Results by hematoma type

When we divide the appearance of hematomas on CT into two groups: mixed-type and others, In the 6-month follow-up, 5 (50%) of 10 mixed-type hematomas were unsuccessful, and 6 (18.8%) of 32 hemorrhages in other types were unsuccessful (p = 0.0498; Pearson's chi-squared test). At the end of 1 year, 6 (60%) of 10 mixed-density hematomas were unsuccessful (5 died and 1 was reoperated), and only 6 (18.8%) of the other 32 hematomas were unsuccessful (5 died and 1 reoperated) (p = 0.012, Pearson's chi-squared test).

Discussion

Previous studies have shown that bilateral CSDHs are susceptible to rapid deterioration and are associated with poor prognosis.^12,13) This has been sometimes attributed to brain herniation, resulting from the relatively unbalanced increase in contralateral hematoma pressure during evacuation or acute hemorrhage triggered by a sudden increase in cerebral blood flow following supratentorial decompression.^15,17) No study in the literature has compared the simultaneous and consecutive evacuation of bilateral CSDHs and assessed their respective success rates. In our study, no statistically significant difference was found between the type of surgical procedure performed and the success rate in the early and none of the other periods.

Preoperative GCS scores of the patients in this study corresponded to poor prognosis (p = 0.025; Pearson's chi-squared test). GCS is an indicator of injury severity and inherently indicates more severe brain damage and poorer prognosis.^21-24) Therefore, this finding is not surprising. The same applies to Babinski's sign.

Of the 17 patients with a preoperative GCS score of 15, 8 and 9 had mild and severe headaches, respectively. There were no patients who did not describe a headache. Because headache is mainly considered to determine success in patients with a preoperative GCS score of 15 and no history of paresis, these patients were considered failures. Surgical site pain or postoperative pneumocephalus may also be responsible for not being considered successful in the early period (Fig. 3). In randomized clinical studies, no difference was shown between evacuation techniques (burr hole vs. twist drill) in terms of pneumocephalus.^4-6,8)

Fig. 3.

CT images of patient no. 2 in the (a) early postoperative period and (b) after drainage.

Two potential etiologies of CSDH have been proposed. The first etiology is acute subdural hematomas that develop after trauma becomes chronic and result in CSDH.^22,25) The second etiology is that CSDHs, especially bilateral CSDHs, can develop from chronic hygromas.^26-29) Elderly patients with brain atrophy typically have bilateral chronic hygroma. It has been reported that the presence of recurrent microhemorrhages into the chronic hygroma due to trauma or even without any trauma may play a role in the development of CSDHs.^26,30,31) Bilateral CSDHs are more common among elderly patients (>75) who already have brain atrophy compared with unilateral CSDHs (mean age 65 years).^30,31) However, this study's mean age is close to that of patients with unilateral CSDH reported in the literature compared with that of patients with bilateral CSDH. This might be due to the relatively high number of young patients in our series who had bilateral CSDH and concomitant pathologies (13 of the 15 patients under 68 years manifested concomitant pathology, whereas only 3 of the 28 patients over 68 years had concomitant pathology). Moreover, in this study, 18 of 43 patients (41.8%) described trauma history. Studies in the literature reporting that recurrence and morbidity rates increase with advancing age assert that there will be no adequate postoperative reexpansion among elderly patients because their brains are atrophic, which will increase the recurrence rates while decreasing the success rates.^{6,10,14,19,30,32,33)} Nevertheless, this study did not determine such a negative relationship between age and success.

One of the critical appraisals of this study may be spontaneous intracranial hypotension (SIH), a condition often neglected by neurosurgeons because of the infrequent encounters during neurosurgical practice. SIH is sometimes complicated by CSDH.³⁴⁾ The reported incidence of subdural hematoma among patients with SIH ranges from 16% to 57%, and many cases have bilateral SDHs.^35-39) From another perspective, in the prospective cohort study by Kim et al., SIH was also confirmed in 8 of 62 patients with subdural fluid collection.⁴⁰⁾ Different treatment strategies, such as conservative, hydration, Trendelenburg position, and epidural blood patch, can be required in SDH cases with SIH.⁴¹⁾ Although surgical drainage of subdural hematoma is recommended in cases of acute clinical deterioration besides other SIH treatments, some reports in the literature indicate that it may lead to serious complications if performed before correcting CSF leaks.⁴²⁾ Takahashi et al. stated that the intracranial pressure was low, and hematomas did not bulge out in these cases.³⁹⁾ From this perspective, none of the patients in our study exhibited diencephalic or brainstem sagging on imaging, and pressurized evacuation of chronic subdural fluid was observed during surgeries. However, no prior SIH was examined. It is difficult to consider SIH as an underlying cause. Therefore, a careful evaluation should be performed to ensure that the superimposed SIH is not overlooked.

In the literature, the postoperative mortality rate of bilateral CSDH ranges from 3.8% to 5%.^12,13,43) The mortality rate in the first 7 days of this study (6.98%) was slightly higher than that reported in the literature. The authors attributed this to the lower GCS scores of patients upon admission and their poor general condition resulting from additional medical problems (Table 3). All deaths occurring after the first 1-month period were observed in patients who had undergone successful surgery, remained neurologically intact, showed no recurrence of CDSH, and were caused by issues unrelated to CDSH.

In a study on the evaluation of CT scans of CSDHs, Nakaguchi et al. claimed that bleeding that appeared to be in the form of separation on CT scan revealed de novo bleeding, and this type of bleeding resulted in the highest recurrence risk.¹⁹⁾ Separation means that the anterior (frontal) side appears to be hypodense (fluid content), whereas the occipital area seems to be hyperdense (erythrocytes, leukocytes, etc.) because of the formed elements of blood precipitate on the posterior side (occipital area) of the head when the patient lies in the supine position for CT scanning. Most of the time, these two zones can be clearly distinguished. However, this study showed a lack of association with separated hematomas and poor prognosis, contrary to Nakaguchi's findings for at least the bilateral CSDHs.¹⁹⁾

The reason for selecting simple randomization in this study was to minimize bias by eliminating predictability. This study preserved complete randomness and independence regarding the treatment applied. However, due to the relatively low incidence of bilateral CSDH,¹⁴⁾ enrolling a many patients was challenging during the 6.5-year recruitment period. This resulted in unequal numbers of participants between the two groups (i.e., 25 and 18). This can be considered a limitation of this study.

The prognosis of female patients was poor. However, among the patients who participated in the study, only 5 of 43 were female, making it difficult to confirm that whether the findings were significant. The challenge in achieving an adequate female patient population is attributed to the higher prevalence of bilateral CSDH in males. Other studies in the literature suggest a female-to-male ratio of approximately 1:4.¹³⁾

Conclusion

This study found no significant differences in prognosis and complications between simultaneous and consecutive drainage of CSDHs. Therefore, the choice of technique can be decided by the surgeon. The authors believe that bilateral CSDHs do not require simultaneous drainage, which may hinder the surgeon's ergonomic work due to the position of the patient's head during the procedure. The secondary findings revealed that young and old patients had similar prognoses for bilateral subdural hematoma, contrary to expectations, as younger patients had more accompanying pathologies. Additionally, in this study, a suspicion was raised that female gender may be associated with poor prognosis. Nevertheless, bilateral CSDH in young and female patients might be an indication for early intervention and close follow-up. Therefore, it is recommended that a larger population be studied.

Funding

No funding, grants, or other support was received.

Availability of Data and Materials

The dataset can be shared if requested by the journal.

Code Availability

Not applicable.

Consent to Participate and Publication

Consent for surgery, participation in this study, and publication were obtained from patients or their relatives (for unconscious patients).

Conflicts of Interest Disclosure

The authors declare no relevant financial or nonfinancial interests.