Abstract
This study had two objectives: to determine the levels of acceptance and forgiveness reported by patients with borderline personality disorder (BPD) and personality-disordered comparison subjects and recovered vs. non-recovered patients with BPD over 20 years of prospective follow-up. Levels of acceptance and forgiveness were reassessed every two years. Patients with BPD reported levels of these states that were approximately 70% lower than comparison subjects at baseline. These states increased significantly over time for patients with BPD but not for comparison subjects. Recovered patients with BPD reported approximately three times the levels of these states than non-recovered patients with BPD. These levels increased for both groups over time; one state (accepting of myself) increased at a significantly steeper rate for recovered patients with BPD. These results suggest that patients with BPD report becoming more accepting and forgiving over time. Additionally, recovery status is significantly associated with increasing time in these states.
Introduction
Clinical experience suggests that patients with borderline personality disorder (BPD) can be distinguished from patients with other diagnoses by the severity of their dysphoric affects and cognitions. Intense inner states of anger, anxiety, and emptiness as well as the beliefs that one is bad or evil and that others cannot be trusted are frequently encountered in clinical practice (Zanarini, Gunderson, Frankenburg, & Chauncey, 1990; Zanarini, Frankenburg, DeLuca, Henne, Khera, & Gunderson, 1998). More recent research has found that patients with BPD report experiencing positive affects and cognitions even during episodes of acute illness (Reed, & Zanarini, 2011) and that the mean percentage of time they report experiencing these 50 inner states aggregated together increases over time (Reed, Fitzmaurice, & Zanarini, 2012).
Acceptance of one’s past and one’s current inner states is a core element of the comprehensive treatment for BPD with the strongest evidence base—dialectical behavioral therapy (DBT) (Linehan, Armstrong, Suarez, Almon, & Heard, 1991). A recent study found that experiential avoidance (or the opposite of acceptance) decreased significantly more in DBT than in Community Treatment by Experts (CTBE) (Neacsiu, Lungu, Harned, Rizvi, & Linehan, 2014).
Forgiveness is a related concept, which involves the letting go of feelings of bitterness and thoughts of revenge. Another recent study conducted in a sample of primary care patients found that more severe borderline psychopathology was significantly associated with lower ratings of multiple aspects of forgiveness by these community dwelling subjects (Sansone, Kelley, & Forbis, 2013).
The current study, which focuses on these two adaptive or mature inner states, had two main objectives. The first was to determine the levels of acceptance and forgiveness reported by patients with BPD and personality-disordered comparison subjects over 20 years of prospective follow-up. The second was to determine the levels of acceptance and forgiveness reported by patients with BPD who had and who had not recovered (i.e., achieved concurrent symptomatic remission and good psychosocial functioning) over the past two decades.
Method
The current study is part of the McLean Study of Adult Development (MSAD), a multifaceted longitudinal study of the course of borderline personality disorder. The methodology of this study, which was reviewed and approved by the McLean Hospital Institutional Review Board, has been described in detail elsewhere (Zanarini et al., 2003). Briefly, all subjects were initially inpatients at McLean Hospital in Belmont, Massachusetts. Each patient was screened to determine that he or she: (a) was between the ages of 18–35; (b) had a known or estimated IQ of 71 or higher; and (c) had no history or current symptoms of schizophrenia, schizoaffective disorder, bipolar I disorder, or an organic condition that could cause serious psychiatric symptoms (e.g., lupus erythematosus, multiple sclerosis).
After the study procedures were carefully explained, written informed consent was obtained. Each patient then met with a masters-level interviewer blind to the patient’s clinical diagnoses for a thorough psychosocial/treatment history and diagnostic assessment. Four semistructured interviews were administered: (1) the Background Information Schedule (BIS) (Zanarini, Frankenburg, Khera, & Bleichmar, 2001; Zanarini, Frankenburg, Henen, Reich, & Silk, 2005), (2) the Structured Clinical Interview for DSM-III-R Axis I Disorders (SCID-I) (Spitzer, Williams, Gibbon, & First, 1992), (3) the Revised Diagnostic Interview for Borderlines (DIB-R) (Zanarini, Gunderson, Frankenburg, & Chauncey, 1989), and (4) the Diagnostic Interview for DSM-III-R Personality Disorders (DIPD-R) (Zanarini, & Frankenburg, 2001). The inter-rater and test-retest reliability of the BIS (Zanarini et al., 2001; Zanarini et al., 2005) and of the three diagnostic measures (Zanarini & Frankenburg, 2001; Zanarini, Frankenburg, & Vujanovic, 2002) have all been found to be good-excellent.
At each of 10 follow-up waves, separated by 24 months, diagnostic status was reassessed via interview methods similar to the baseline procedures by staff members blind to baseline diagnoses. After informed consent was obtained, our diagnostic battery was readministered. Social and vocational functioning were also assessed at each time period using the follow-up analog of the Background Information Schedule—the Revised Borderline Follow-up Interview (BIF-R) (Zanarini, 1994). The follow-up inter-rater reliability (within one generation of follow-up raters) and follow-up longitudinal reliability (from one generation of raters to the next) of all four interviews were good-excellent (Hörz, Zanarini, Frankenburg, Reich, Fitzmaurice, 2010; Zanarini et al., 2005; Zanarini & Frankenburg, 2001; Zanarini, Frankenburg, & Vujanovic, 2002).
In the current study, inner states reflecting acceptance and forgiveness were assessed using four items from the Positive Affect Scale (PAS) at baseline and each of the 10 waves of follow-up (Zanarini & Deluca, 1994). These items are: “accepting of the past,” “that I can accept myself,” “that I’ve forgiven those who’ve hurt me,” and “that I’ve been able to forgive myself.” The PAS is a self-report measure consisting of 50 items that describe positive inner states of either an affective or cognitive nature found to be common and/or discriminating for borderline personality disorder (Reed & Zanarini, 2011). Participants are asked to report the percentage of the time that they have experienced each positive affect or cognition over the past month and thus, scores range from 0–100% of the time. The psychometric properties of the PAS are excellent, with very high internal consistency (Cronbach’s α = 0.98). The one-week test-retest reliability of the PAS was found to be 0.84 when examined in a sample of 15 nonpsychotic outpatients. The interclass correlation of the items used in this study were found to be r = 0.53 for accepting of the past, r = 0.90 for that I can accept myself, r = 0.85 for that I’ve forgiven those who’ve hurt me, and r = 0.85 for that I’ve been able to forgive myself.
We defined recovery as having three aspects to enhance its reliability and meaning. More specifically, to be rated as recovered, a subject typically had to have achieved a concurrent symptomatic remission, have at least one emotionally sustaining relationship with a close friend or life partner/spouse, and be able to work or go to school consistently, competently, and on a full-time basis (which included being a houseperson) during the two-year interval.
Statistical Analyses
The generalized estimating equations (GEE) approach was used in longitudinal analyses to assess the level of these inner states over 20 years of follow-up. Linear models for change in the mean level over time included the effects of diagnostic (recovery) group, time, and their possible interaction; all analyses included a quadratic time trend to allow for the discernible non-linear increase in the level of these inner states over time. Post-estimation tests were used to determine if the interactions were significant. If not, they were dropped from the final models.
The GEE method used for these analyses appropriately accounts for the correlation among the repeated measures of the PAS over time. Because the PAS variables are positively skewed, these analyses are based on logarithmically transformed scores; consequently, the results when expressed on the original scales of the scores have interpretations in terms of relative, rather than absolute, differences.
The development of the PAS was completed and the measure was introduced into our assessment battery about two-thirds of the way through recruitment of the baseline MSAD sample. As a result, PAS data for 120 of 362 subjects (96 with borderline personality disorder and 24 with non-BPD personality-disordered diagnoses) were collected at baseline. Additionally, 18 subjects at the 18-year and 20-year follow-up assessments did not complete the PAS. A multiple imputation procedure was used to handle missing PAS data and analyses included observed and imputed data. The imputation model incorporated both diagnostic group and follow-up PAS data as predictors of the missing baseline and 18 and 20-year follow-up PAS data. Specifically, the missing baseline, 18-year, and 20-year values were replaced by a set of 10 plausible values randomly drawn from the imputation model. Results from the 10 imputed datasets were then appropriately combined to provide a single estimate of the parameters of interest, together with standard errors and test statistics that reflect the uncertainty inherent in the imputation of the unobserved data.
Participants
The sample and its diagnostic characteristics have been described before (Zanarini et al., 2003). Two hundred and ninety patients met both DIB-R and DSM-III-R criteria for BPD and 72 met DSM-III-R criteria for at least one non-borderline personality disorder (and neither criteria set for BPD). Of these 72 comparison subjects, 4% met DSM-III-R criteria for an odd cluster personality disorder, 33% met DSM-III-R criteria for an anxious cluster personality disorder, 18% met DSM-III-R criteria for a non-borderline dramatic cluster personality disorder, and 53% met DSM-III-R criteria for personality disorder not otherwise specified (which was operationally defined in the DIPD-R as meeting all but one of the required number of criteria for at least two of the 13 personality disorders described in DSM-III-R).
Baseline demographic data have also been reported elsewhere (Zanarini et al., 2003). Briefly, 77% (N=279) of the subjects were female and 87% (N=315) were white. The average age of the subjects was 27 years (SD=6.4), the mean socioeconomic status was 3.3 (SD=1.5) (where 1=highest and 5=lowest), and their mean GAF score was 39.8 (SD=7.8) (indicating major impairment in several areas, such as work or school, family relations, judgment, thinking, or mood).
In terms of continuing participation, 220/258 (85%) of surviving patients with borderline personality disorder (13 died by suicide and 19 died of other causes) were reinterviewed at all ten follow-up waves. A similar rate of participation was found for personality-disordered comparison participants, with 58/70 (83%) of surviving patients in this study group (one died by suicide and one died of other causes) being reassessed at all ten waves of follow-up.
Results
Table 1 details mean scores (based on untransformed data) for four inner states related to acceptance and forgiveness reported by patients with BPD and personality-disordered comparison subjects over 20 years of prospective follow-up. The results of the regression analyses of log transformed scores, presented in the last two columns of Table 1, can be interpreted in terms of relative differences (RD) between diagnostic group and relative change over time. For example, the results for accepting of the past indicate that those with BPD had a mean baseline score that was approximately 70% ([0.30 – 1] x 100%) lower than that reported by personality-disordered comparison subjects. In terms of change over 20 years of follow-up, the relative change over time for comparison subjects was a non-significant increase of 25% ([1.72 × 0.72 −1] x 100% whereas the relative change for patients with BPD was a significant (P<0.001) increase of 112% ([1.72 × 0.72 × 8.15 × 0.21 −1] x 100%) and--a between-group difference in relative change over time that was highly significant (P=0.004, based on a 2 degree of freedom test of diagnostic group by time interaction).
Table 1.
BL | 2 YR FU |
4 YR FU |
6 YR FU |
8 YR FU |
10 YR FU |
12 YR FU |
14 YR FU |
16 YR FU |
18 YR FU |
20 YR FU |
Rel. Diff. Diagnosis Time Time2 Interact. Interact2 |
95% CI Diagnosis Time Time2 Interact. Interact2 |
|
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Accepting of the past | |||||||||||||
BPD OPD |
35.8 (30.8) 65.5 (27.1) |
52.9 (35.5) 70.9 (30.2) |
54.2 (36.1) 72.8 (27.5) |
54.2 (35.4) 72.7 (29.7) |
59.2 (34.0) 78.2 (27.4) |
60.8 (33.0) 76.6 (27.0) |
62.2 (33.4) 82.6 (19.8) |
62.4 (34.4) 77.2 (28.2) |
62.5 (35.2) 73.7 (28.5) |
61.5 (35.0) 77.3 (27.9) |
61.9 (35.1) 77.7 (25.0) |
0.30 1.72 0.72 8.15 0.21 |
0.21, 0.44 0.73, 4.05 0.34, 1.56 2.20, 30.20 0.07, 0.66 |
That I can accept myself | |||||||||||||
BPD OPD |
30.4 (27.4) 61.3 (29.7) |
46.3 (34.2) 66.6 (29.1) |
49.6 (35.3) 72.3 (25.6) |
52.2 (34.7) 71.7 (28.5) |
56.6 (34.7) 77.1 (27.3) |
56.8 (34.4) 72.3 (27.3) |
56.8 (35.5) 80.2 (22.5) |
59.0 (34.3) 76.7 (28.8) |
60.1 (34.7) 70.4 (30.9) |
60.5 (35.0) 74.5 (27.6) |
60.9 (34.4) 74.3 (25.8) |
0.27 2.17 0.58 7.31 0.28 |
0.18, 0.40 0.80, 5.83 0.26, 1.28 1.69, 31.55 0.08, 0.96 |
That I’ve forgiven those who’ve hurt me | |||||||||||||
BPD OPD |
36.4 (30.2) 61.1 (28.6) |
46.2 (35.1) 63.6 (30.8) |
48.3 (35.7) 66.9 (29.5) |
50.2 (35.4) 61.9 (33.7) |
52.0 (34.5) 73.0 (28.7) |
53.4 (35.0) 65.8 (34.2) |
55.2 (34.3) 71.9 (28.1) |
56.9 (34.1) 71.8 (32.5) |
58.4 (34.1) 67.4 (33.3) |
60.6 (34.2) 73.1 (31.3) |
57.9 (28.9) 74.0 (28.9) |
0.31 1.03 1.02 4.81 0.42 |
0.20, 0.48 0.35, 3.03 0.37, 2.80 1.03, 22.50 0.10, 1.68 |
That I’ve been able to forgive myself | |||||||||||||
BPD OPD |
27.6 (25.9) 52.6 (29.7) |
40.9 (34.7) 60.4 (31.7) |
44.1 (35.1) 66.9 (29.1) |
46.3 (34.3) 61.4 (31.4) |
52.1 (34.9) 68.2 (30.2) |
50.2 (34.5) 65.2 (29.7) |
52.2 (35.3) 71.3 (27.4) |
55.3 (33.8) 70.3 (30.5) |
56.2 (34.3) 62.3 (34.0) |
55.1 (34.2) 66.7 (32.8) |
57.1 (34.8) 69.2 (28.6) |
0.28 2.27 0.50 5.82 0.41 |
0.18, 0.44 0.81, 6.37 0.20, 1.23 1.18, 28.84 0.10, 1.66 |
For the other three cognitions studied (that I can accept myself, that I’ve forgiven those who’ve hurt me, that I’ve been able to forgive myself), similar differences between patients with BPD and personality-disordered comparison subjects were found. More specifically, each of these inner states was about 70% lower among patients with BPD than among personality-disordered comparison subjects at baseline. In addition, relative rates of increase over 20 years of follow-up for that I can accept myself and that I’ve been able to forgive myself were significant (p<0.001) (with increases of 161% and 171% respectively) for patients with BPD and non-significant (with increases of 26% and 13% respectively) for comparison subjects—between-group differences in these relative changes were also significant (p=0.004 for accept me and p=0.010 for forgive me). Patients with BPD also exhibited a significant increase (p<0.001) of 112% for that I’ve forgiven those who’ve hurt me, although comparison subjects did not demonstrate a significant increase in this inner state (6%). This between-group difference in relative change was also significant (p<0.01).
Table 2 details mean scores (based on untransformed data) for the same four inner states described above reported by patients with BPD who have (n=152) and have not achieved recovery (N=138). As before, the results of the regression analyses of log transformed scores can be interpreted in terms of relative differences (RD) between recovery status and relative change over time. For example, recovered patients with BPD had scores over time that were around three times higher than those of non-recovered patients with BPD for accepting of the past (2.82), been able to forgive others (3.04), and been able to forgive myself (3.01). Both of these study groups also reported a significant relative increase (p<0.001) for each of these inner states over time—107% increase for accepting of the past, 107% increase for forgiving others, and 164% increase for forgiving myself.
Table 2.
BL | 2 YR FU |
4 YR FU |
6 YR FU |
8 YR FU |
10 YR FU |
12 YR FU |
14 YR FU |
16 YR FU |
18 YR FU |
20 YR FU |
Rel. Diff. Recovery Time Time2 Interact. Interact2 |
95% CI Recovery Time Time2 Interact. Interact2 |
||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Accepting of the past | ||||||||||||||||||||||||||||
Recovered Non-Recovered |
40.1 (29.9) 31.3 (31.1) |
62.3 (32.6) 41.5 (35.6) |
65.8 (32.4) 39.7 (35.3) |
66.2 (32.1) 38.3 (33.3) |
70.4 (28.2) 44.3 (35.3) |
69.8 (28.2) 48.4 (35.1) |
73.8 (27.3) 45.6 (34.3) |
72.7 (36.3) 47.7 (36.3) |
72.3 (31.1) 48.5 (35.9) |
69.2 (31.4) 50.0 (36.9) |
72.6 (30.1) 45.5 (36.1) |
2.82 12.92 0.16 ---- ---- |
2.12, 3.74 4.84, 34.50 0.07, 0.38 ---- ---- |
|||||||||||||||
That I can accept myself | ||||||||||||||||||||||||||||
Recovered Non-Recovered |
34.7 (27.1) 25.8 (26.9) |
56.2 (33.2) 34.4 (31.4) |
63.2 (32.3) 32.3 (31.2) |
64.5 (31.4) 36.0 (32.1) |
67.5 (30.6) 42.0 (34.6) |
67.5 (34.3) 42.1 (34.3) |
67.6 (30.6) 41.6 (36.3) |
69.9 (30.1) 43.5 (33.9) |
70.9 (30.6) 44.7 (34.4) |
68.7 (31.3) 48.3 (36.5) |
69.6 (30.9) 47.6 (35.2) |
2.61 8.15 0.41 2.70 0.24 |
1.58, 4.31 1.49, 44.48 0.09, 1.88 0.44, 16.68 0.05, 1.24 |
|||||||||||||||
That I’ve forgiven those who’ve hurt me | ||||||||||||||||||||||||||||
Recovered Non-Recovered |
42.9 (30.4) 29.4 (28.3) |
55.4 (33.8) 35.2 (33.5) |
61.5 (31.8) 31.7 (33.5) |
61.0 (32.3) 36.0 (34.4) |
63.6 (30.5) 36.5 (33.4) |
61.9 (32.0) 41.8 (35.5) |
65.3 (30.4) 40.9 (34.4) |
66.2 (30.8) 43.8 (34.4) |
68.6 (29.4) 43.8 (34.9) |
69.2 (30.3) 47.6 (35.2) |
64.8 (31.1) 46.9 (36.9) |
3.04 4.57 0.45 --- --- |
2.20, 4.21 1.61, 12.91 0.18, 1.13 --- --- |
|||||||||||||||
That I’ve been able to forgive myself | ||||||||||||||||||||||||||||
Recovered Non-Recovered |
33.4 (26.9) 21.4 (23.2) |
51.6 (34.8) 28.1 (29.9) |
58.4 (33.0) 26.0 (28.6) |
57.4 (33.3) 31.7 (29.7) |
63.2 (31.1) 37.4 (34.2) |
60.2 (32.9) 36.6 (32.9) |
61.5 (32.5) 39.0 (34.9) |
65.9 (30.3) 40.2 (32.9) |
66.6 (29.5) 41.2 (35.0) |
64.4 (31.3) 41.1 (33.6) |
66.9 (31.5) 42.1 (34.4) |
3.00 12.13 0.22 ---- ---- |
2.21, 4.10 3.81, 38.63 0.08, 0.60 ---- ---- |
For the other state studied (being able to accept myself), a more complex picture emerged. Recovered patients with BPD reported baseline scores that were over twice as high as those reported by non-recovered patients with BPD (2.61)—a highly significant difference (p<0.001). For the inner state of accepting myself, the relative increase for non-recovered patients with BPD was 114% (p<0.001) whereas for recovered patients with BPD the relative change was significantly greater (p <0.027) with a 232% increase over time.
Discussion
Two main findings have emerged from this study. The first is that patients with BPD had a significantly different pattern of the percentage of the time that they experienced four inner states related to acceptance and forgiveness than personality-disordered comparison subjects. More specifically, their baseline scores on these cognitions were about 70% lower than comparison subjects. Although their baseline scores were lower, patients with BPD had significant increases in these scores over time whereas comparison subjects did not.
While their average baseline score was about 30% of the time for these inner states, their average score at 20-year follow-up was about 60% of the time. In general, the gap between patients with BPD and personality-disordered comparison subjects grew smaller over the 20 years of prospective follow-up.
It is not surprising that patients with BPD reported significantly lower rates of acceptance and forgiveness at study entrance during their index admission. As noted above, studies have found that their affective and cognitive inner states are more dysphoric than those of a variety of comparison subjects (Zanarini et al., 1990; Zanarini et al, 1998). However, clinicians may be surprised and heartened that they report such improvement in inner states that may be the foundation upon which a more mature adaptation to life can be built.
Acceptance of the past, acceptance of oneself, forgiveness of others who have been hurtful, and forgiveness of oneself are difficult for many people to achieve, with and without psychiatric diagnoses. However, the increase in the percentage of time that patients with BPD experience these states may allow them to accept that the “rules of life” apply to them regardless of what others have done to them or not done for them. It may also allow them to give up “negotiating” the reality of their life. These changes are important for their overall adjustment to adult life as their behavior becomes both more mature and graceful. It also improves their chances for benefiting from treatment as both believing that they deserve special treatment and can negotiate with reality frustrates and annoys many clinicians, leading to countertransference problems that can disrupt the emotional tone of the treatment and even its continuation.
The second main finding is that recovered patients with BPD had a significantly different pattern of the percentage of the time that they experienced these four inner states related to acceptance and forgiveness than patients with BPD who had not achieved recovery over the 20 years of prospective follow-up. More specifically, recovered patients with BPD had scores on these positive cognitions that were 2–3 times higher over time. However, on three of these states (that I can accept my past, that I can forgive those who have hurt me, and that I can forgive myself), both groups of patients with BPD experienced about the same relative increase over time. For the fourth inner state (that I can accept myself), recovered patients with BPD experienced a relative increase over time that was twice as large as non-recovered patients with BPD.
Looked at another way, recovered patients with BPD reported baseline scores on these four inner states of about 40% of the time and scores of about 65% of the time after 20 years of prospective follow-up. In contrast, non-recovered patients with BPD reported baseline scores of about 25% of the time and about 45% of the time after two decades of prospective follow-up. That is, with the exception of the fourth inner state, the gap between recovered and non-recovered patients with BPD remained approximately the same over time.
It is not surprising that patients with BPD who achieved recovery both symptomatically and psychosocially would have higher baseline scores on the four positive states we are studying than patients with BPD who have not achieved this important social and vocational outcome, though they did achieve symptomatic remission (Zanarini, Frankenburg, Reich, & Fitzmaurice, 2012). Both accepting of the past and others as well as forgiving others and oneself are a sign of the emerging ability to empathize about oneself and about others. In contrast, a rigid belief in the malevolence of others and the inability to perceive forgiveness as a source of personal strength rather than a sign of defeat are more common among patients with BPD who have not recovered than they are among patients with BPD who have attained good social and good full-time vocational functioning.
It is not clear whether an increase in these states precedes attaining recovery, follows attaining recovery, or there is some interaction between the two. However, clinical experience suggests that for patients with BPD who achieved recovery, the end result may be a more nuanced view of one’s parents, partners, friends, and colleagues and their “abusive” and “emotionally neglectful” behavior. It may now occur to a borderline patient that perhaps a spouse is preoccupied with a failing business rather than having lost affection for him or her. In a similar manner, it may now occur to a borderline patient that a parent often spoke harshly to him or her during childhood because of his or her own depression rather than hatred for that particular child.
Limitations
Several limitations to this study must be taken into account when interpreting its findings. First, the study was conducted on inpatients with BPD and other personality disorders. Second, about 90% of those in both patient groups were in individual therapy and taking psychotropic medication at baseline and about 70% were in individual therapy and taking standing medications at each wave of follow-up (Zanarini, Frankenburg, Reich, Conkey, & Fitzmaurice, 2015). Therefore, the results may not generalize to less severely ill patients with BPD or to individuals with BPD who are not in treatment—which in almost all cases was treatment as usual in the community and not an evidence-based form of psychotherapy. Third, we used a relatively short four-item scale to assess acceptance and forgiveness. It would have been preferable if we had used a self-report measure that assessed these constructs in a more comprehensive manner; however, potential subject burden and our desire to assess a wide range of positive inner states characteristic of and distinguishing for BPD prevented us from doing so.
Conclusions
Taken together, the results of this study suggest that patients with BPD tend to report becoming more accepting and forgiving of others and themselves over time. These results also suggest that recovery status is significantly associated with the increasing percentage of time that these positive inner states were experienced.
Acknowledgments
This study was supported by NIMH grants MH47588 and MH62169.
Footnotes
The authors report no relevant conflicts of interest.
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