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Review z Depression and

Depression and pain: the need for a new screening tool

Karen Cocksedge BA, PhD, MBChB, Rohit Shankar MBBS, MRCPsych, DPM, PGC-Cl.Research, PGC-Aspergers Chantal Simon PhD, MSc, MA, BM BCh, MRCGP, DRCOG There is a strong association between pain and depression, and the presence of pain negatively affects the recognition and treatment of depression. Here, Dr Cocksedge and colleagues’ explore the neurobiology behind this relationship and propose a new screening tool to assess with either condition for the coexistence of the other, with the potential for significantly better diagnosis, referral and hence treatment.

n both the ICD10 and DSM IV definitions of depres- for a far greater healthcare resource utilisation in both Ision, pain is briefly mentioned as a possible primary and secondary care, since patients with both symptom but is certainly not considered as a defining pain and depression have an increased number of GP symptom such as low or as a somatic symptom. visits, an increased rate of investigations, a higher rate This is surprising since pain symptoms and depres- of drug switching and increased referral sion commonly coexist, as has been demonstrated in to secondary care.3 The combination of both pain and a number of studies (see Table 1). Not only does depression also has an additive effect on the work days there appear to be a clear association between pain lost through both sickness absence and productivity.4 and depression, but furthermore, there is a recog- nised concern that the presence of pain often Aim negatively affects the recognition and treatment of We looked to identify if there were any combined depression: depressed patients have been shown to pain and depression tools by using a comprehensive be far more likely to present with pain symptoms than literature search. We examined our search results to they are to present with affective symptoms1 and it help outline and propose a future mechanism of has been estimated that if all patients from general screening for comorbidity of depression and pain in practice who presented with painful conditions were a primary care setting. evaluated for possible depression, then 60% of previ- ously undetected depressive cases would have been Method recognised.2 Furthermore, when depression is recog- We conducted an extensive literature search to inves- nised to be present in conjunction with pain, tigate if any screening tools simultaneously could clinicians are more likely to focus on treating the pain screen patients for both depression and pain. This was and are less likely to consider psychological treat- undertaken with a systematic MEDLINE, EMBASE and ments, leading to worse outcomes.1 AMED search over the years 1946–2015 using the com- The situation is further complicated by the fact bined terms ‘pain’ AND ‘depression’ combined with that the subjective experience of pain is likely to have the individual terms ‘screening’, ‘checklist’, ‘tool’, cognitive, emotional and behavioural components in ‘questionnaire’, ‘inventory’ or ‘scale’. addition to the underlying biological component and, in some cases, there may be no underlying bio- Results logical component at all. It is likely to be very difficult From our literature search, we found a total of 43 to distinguish between these components, but for the articles but none offered a combined general screen- purposes of considering the effect of pain on depres- ing tool for depression and pain. The articles were sion, the origin of the pain probably makes little analysed and divided into relevant subsections. The difference to the established association. majority focussed on eliciting an altered mental state When pain and depression are recognised and the in conditions with known . Two articles, clinician does focus on treating the depression, the pres- however, did assess for both depression and pain: ence of pain appears to increase the resistance of Tamiya et al.5 looked at pain, and depression depression to treatment (see Table 2 in the online ver- in 145 Japanese women with . sion of this article). As might well be expected, a com- They used visual analogue scales to measure depres- bined diagnosis of both pain and depression accounts sion and anxiety and compared these with standard

26 Progress in Neurology and January/February 2016 www.progressnp.com Depression and pain z Review

Reference Type of study Main findings

Patten 200125 1 year longitudinal study of Non-depressed patients with a long-term medical condi- patients with chronic medical tion were twice as likely to develop major depression in conditions the following year compared with those without such a condition

Painful conditions including , sinusi- tis and back problems were most closely associated with major depression

Ohayon et al. 200326 Cross-sectional study 43% of patients major depression had at least one chronic painful condition, which was four times higher than those without major depression

Bair et al. 20131 Literature review – see Tables Mean prevalence of pain in depression is 65%; mean 1 and 2 in the paper prevalence of depression in pain is 13–85%

Arnow et al. 200627 Primary care patients Disabling chronic pain was present in 41% of those with major depression versus only 10% of those without major depression

Means-Christensen et Primary care patients 2.5–10 times increase in anxiety or major depression in al. 200828 patients with muscle pain, or stomach pain

Demyttenaere et al. 6-month European prospec- 56% of newly diagnosed depressed patients attending 201029 tive observational study psychiatric outpatient clinics were experiencing mod- (FINDER) erate to severe pain, 70% of whom had no physical explanation for their pain

Bair et al. 201030 Prospective cohort study of Pain in is strongly association with depression patients with diabetes (p<0.001)

Beesdo et al. 201031 Nationally representative Pain is strongly associated with depressive disorders community study with odds ratio (OR) in the range 1.9–7.3

Kroenke et al. 201132 Longitudinal study of primary Change in pain was a strong predictor of subsequent care patients with persistent depression severity (p<0.0001) musculoskeletal pain

Gerrits et al. 201433 Netherlands Study of Depres- Onset of depression associated with 6 pain locations sion and Anxiety (p<0.05), increasing number of pain locations (p<0.001) and higher severity of pain (p<0.001)

Table 1. Examples of the studies showing an association between depression and pain measures and to a pain analogue scale. However, their analogue scale to elicit anxiety, depression and study was restricted to patients with rheumatoid arthritis, catastrophising in 45 patients with neck pain.7 Again, a long-term condition where pain is central to the pres- as with Tamiya et al., the study was restricted to a entation, and was not replicated in other populations of single presentation of pain, used small numbers and chronic conditions. Furthermore, the sample population crucially was not tested as a screening tool. was selective and the tools used as diagnostic as opposed In summary, our search did not reveal any to screening. Luppi et al.6 looked at pain, anxiety and validated tool which could be used to screen for depression in 81 patients with leukaemia and 118 patients comorbid pain and clinical depression in primary with solid . They used a Likert scale (0–10) for care. In the absence of such a combined tool, we then pain, depression and anxiety and compared these with considered common screening tools in use for standard measures for depression and anxiety. However, depression and pain separately. again their study was restricted to patients with a specific There are a number of well recognised screening condition – malignancy – and was not replicated in other tools for depression. In the general practice setting, chronic conditions. three tools are recommended in the Quality and We also found a further similar study, not from Outcomes Framework (QOF) guidance for the evalua- within our search criteria, which employed a visual tion of depression. Furthermore, for patients with a www.progressnp.com Progress in Neurology and Psychiatry January/February 2016 27 Review z Depression and pain

Reference Type of study Main findings

Bair et al. 200434 A randomised control trial of pri- The severity of pain was a strong predictor of poor mary care clinics response to antidepressant therapy

Karp et al. 200535 Re-analysis of an archived study of Pain was significant in predicting a longer time patients with major depression to remission, with headaches and muscle soreness independently predicting a slower remission; sub- jects with more pain, even after controlling for the severity of depression, reported more suicidality

DeVeaugh-Geiss et al. Randomised longitudinal effective- Those with severe pain and with moderate pain 201036 ness study comparing selective were both significantly less likely to achieve re- serotonin reuptake inhibitors mission than those without pain (odds ratio [OR] (SSRIs) used in the treatment of 0.11–0.25); those with an early improvement in depression in primary care pain were more likely to achieve remission than those without (OR 1.90)

Table 2. The effect of chronic pain on the efficacy of treatment for depression chronic physical health problem in primary care, NICE and the brainstem.11 Within this relay are serotonergic guidelines recommend two standard questions about and noradrenergic neurons which dampen pain signals depression are asked to all patients and if either answers transmitted from the periphery by depressing the activ- are positive, then to conduct further questioning.8 ity of nociceptive neurons in the spinal dorsal horn.11, These different screening tools can be compared with 12 This system serves to determine our and atten- the ‘ standard’ for rating depression in clinical tion to stimuli and usually modulates this so we are able research, the Hamilton Rating Scale for Depression.9 to focus more on external stimuli rather than those There are also a number of screening tools for pain, from within the body.13 However, in the scenario of a although those designed specifically for use in primary deficiency of serotonin and noradrenaline, this system care settings tend to be specific to particular types of likely loses its modulatory effect such that in depression, pain such as back pain, knee pain or neuropathic pain. multiple pain symptoms are experienced and the pres- ence of pain leads to increased focus on the pain and a Discussion lowered affect. This hypothesis has been demonstrated The neurobiological hypothesis of the coexistence of pain experimentally in a recent study comparing patients and depression with chronic pain in with and without Physical pain can be considered to be a combination depression, which showed that inhibition of pain (via of the sensory component of the pain and the associ- the diffuse noxious inhibitory controls [DNIC]) is fur- ated affective component of the pain. Although psy- ther reduced in comorbid depression.14 chological pain, such as psychological distress, does Recent studies have highlighted that the central not involve a painful stimulus, it still signals a threat nervous system undergoes long-term plasticity in the to the body in the same way as physical pain and thus presence of chronic pain and depression. The underly- the neural mechanisms, including the hypothalam- ing neural circuitry and molecular signalling pathways ic-pituitary axis, are still activated as part of the that underlie this are beginning to be understood.15 response. It has been shown that the nociceptive The molecular signalling pathways include not only the pathway for is in fact similar to the neuropeptides serotonin, noradrenaline and dopamine pathway involved in the processing of the affective as described above, but also include a role for glutamate component of physical pain.10 Through this mecha- signalling, neurotrophic factors (eg brain-derived neu- nism, it is hardly surprising therefore that pain and rotrophic factor [BDNF]) and neuromodulatory lipids depression are associated. (eg endocannabinoids).15 It seems likely that these com- More specifically, the association can be consid- plex changes, which result from chronic pain and ered in terms of commonality of neurotransmitters. depression together, are at the root of why chronic pain It has long been accepted that, biochemically, depres- and depression together are so difficult to treat; but sion can be attributed to a deficiency in serotonin, further work is needed in this area. noradrenaline and dopamine. There is now increas- ing understanding of the descending system of pain Treating the problem modulation whereby the periaqueductal grey acts as If pain and depression share common deficiencies in a relay between forebrain and midbrain structures neurotransmitters, then it seems logical to suggest

28 Progress in Neurology and Psychiatry January/February 2016 www.progressnp.com Depression and pain z Review

that antidepressant therapy, which boosts these neuro- Of course, in patients presenting with chronic pain transmitters, could be used in the treatment of pain. To and depression, an antidepressant is not the only solu- this end, it has long been recognised that tricyclic anti- tion. Many of the cognitive, behavioural and affective have a role in treating chronic pain.16 More factors that are critical in the development of depression recently, an evidence-based review of using antidepres- are also relevant to the development of chronic pain, sants in chronic pain showed that serotonergic-noradr- which helps to further explain their association. Hence, energic appear to be more effective a with both depression and pain needs a multidis- than serotonergic antidepressants.17 One specific sero- ciplinary approach to the problem from psychiatrists, tonergic-noradrenergic antidepressant that is becoming psychologists and pain specialists with an understanding, increasingly popular is duloxetine. The effectiveness of empathetic style and inclusion of education for patients duloxetine in treating chronic pain was reviewed and their families about how the two conditions are likely recently in a 2014 Cochrane review,18 which focussed to be linked.19 There is a wealth of evidence to suggest on the use of this in treating painful neurop- that non-pharmacological interventions such as cognitive athy, chronic pain and fibromyalgia. The authors behavioural therapy, behavioural therapy and accept- concluded that there was a significant improvement in ance-based therapy have some effect in treating chronic pain in all three types of condition, but with the evi- pain and improving mood outcomes.20–22 More recent dence being strongest in diabetic neuropathy. It is of work has demonstrated functional neuroimaging particular that of all the different types of pain, changes in chronic pain patients (in the Default Mode it is neuropathic pain, rather than acute or inflamma- Network) which can be altered by these interventions tory pain, that is most successfully treated with antide- and correlate with clinical outcomes.23 pressants. Using a model of neuropathic pain employing peripheral nerve injury, it has been shown in rodents Addressing the problem: the need for a new screening tool that this type of pain can induce depressive-type symp- Whilst it is encouraging that we are beginning to toms, including and behavioural despair.15 understand the association between depression and

For all patients presenting with long-term physical health problems:

During the last month, have you often been bothered by: No – down, depressed or hopeless? – having little interest or in doing things?

Yes

During the last month have you often During the last month, have you often been bothered by: been bothered by pain? - of worthlessness? -poor concentration? Yes -thoughts of death?

How long have you felt like this? -Where is the pain? -How severe is your pain on a scale of How does it affect your day-to-day 0-10 with 0 being “no pain” and 10 functioning and relationships? being “the worst possible pain”

Do you feel isolated?

Is there any history of psychiatric prob- lems?

Figure 1. Recommended approach for pain and depression screening for patients with long-term physical health conditions presenting to the general practitioner www.progressnp.com Progress in Neurology and Psychiatry January/February 2016 29 Review z Depression and pain

pain, the likely mechanisms involved and possible overlooked. This thereby ensures that in the cases of treatment options, it is of little help to the typical any identified depression complicated by the patient if the coexistence of the two conditions is presence of pain, the treatment of this pain is incor- frequently missed. Instead, what is really needed is a porated into the treatment of the depression and is simple-to-use screening tool for any patient present- therefore more likely to be successful. ing to a general practitioner with either pain or We suggest that this simple screening tool could depression alone, to assess if the two coexist. In the be used by a practice nurse as part of the annual cases where coexistence is demonstrated, the patient review of any chronic illness. Should the three can then be treated appropriately with consideration screening questions or the further questions used of both problems simultaneously. thereafter suggest the existence of newly identified The fact that such a screening tool does not yet chronic pain and / or depression, then the patient exist is surprising since untreated depression may could be referred to the general practitioner for adversely affect ability to treat pain and -spe- further discussion and treatment if necessary. In cific outcomes. Therefore, the argument for future work we plan to test the feasibility of this including pain screening when assessing patients screening tool in correctly identifying new cases of with long-term conditions for depression pain and / or depression in chronic illness and is strong.24 later, the effect that this earlier identification can Work is clearly needed to develop and validate a have on outcomes. combined screening tool for both pain and depres- sion for use with patients suffering from long-term Summary physical health conditions. Here we consider the There is a strong association between pain and patient presenting to primary care with a long-term depression and the presence of pain negatively affects physical health condition. There are separate screen- the recognition and treatment of depression. Their ing tools that could be used to investigate the coexistence suggests a shared neurobiology. Early rec- presence of either depression or pain alone but we ognition and treatment of this comorbidity could suggest that using an integrated, combined tool will have significant impact on patient outcomes and ensure consistency in the primary care approach to health service costs. Failure to do so could lead to long-term health conditions. Our choice of a suitable treatment resistance, negative clinical and social integrated tool must also consider the time pressures impact and increased costs to health and social sec- within general practice where it would not be practi- tors. It is thus imperative that this comorbidity be cal to use a combined version of two lengthy screen- recognised early to allow specialist treatment options ing tools. To this end, we note that since NICE to be considered, including the use of serotoner- recommends that patients with such conditions are gic-noradrenergic antidepressants. all screened for depression, by asking two standard Sadly, at the present time, patients presenting screening questions, we feel that the simplest and with pain alone are not commonly screened for least time-consuming option to incorporate pain depression and conversely, patients presenting with screening for these patients is to add a third screen- depression alone are not commonly screened for ing question about pain. The NICE guidelines fur- the coexistence of pain. It is surprising that a single ther recommend that if either question regarding screening tool to assess patients with either condi- depression screens positive, then further questions tion for the coexistence of the other has not yet are asked to clarify the situation. We therefore recom- been developed. We believe that such a screening mend that an additional two questions could be tool would lead to significantly better diagnosis, added for those who screen positive for pain, which referral and hence treatment. We believe that we ask about the nature and the severity of the pain. have presented the evidence to suggest an easy-to- With consideration of the various pain scales and of use self-reported screening tool for patients pre- the time constraints within general practice, we feel senting to their general practitioner with chronic that the best option is to use the numerical rating illness to screen for both depression and pain. This scale (0–10) as the means to assess the pain severity. could also be used in the context of patients pre- Our recommended approach is illustrated in Figure senting either with pain or depression to screen for 1, the findings of which could be recorded electron- the presence of both conditions. ically within the patient notes. We suggest that includ- ing pain screening as part of depression screening in Tables 3, 4 and 5 are online only, available free to view on patients with long-term physical health conditions the Progress in Neurology and Psychiatry website: http:// will ensure that any potential pain component is not www.progressnp.com

30 Progress in Neurology and Psychiatry January/February 2016 www.progressnp.com Depression and pain z Review

Dr Cocksedge is CT3 in Psychiatry at Cornwall Partner- 20. Bernardy K, Füber N, Köllner V, et al. Efficacy of cognitive-be- ship NHS Foundation ; Dr Shankar is a Consultant havioral therapies in fibromyalgia syndrome — a systematic review and metaanalysis of randomized controlled trials. J Rheumatol Neuropsychiatrist at Cornwall Partnership NHS Founda- 2010;37:1991–2005. tion Trust in Truro, and Honorary Associate Clinical 21. Veehof MM, Oskam MJ, Schreurs KM, et al. -based Professor at Plymouth and Exeter , and Dr interventions for the treatment of chronic pain: a systematic review and meta-analysis. Pain 2011;152:533–42. Simon is a GP at Bearwood Medical Centre in Bourne- 22. Williams AC, Eccleston C, Morley S. Psychological therapies mouth, Executive Editor – Innovait, and Editor, Oxford for the management of chronic pain (excluding headache) in Handbook of General Practice. adults. Cochrane Database Syst Rev 2012;11:CD007407. doi: 10.1002/14651858.CD007407.pub3. 23. 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32 Progress in Neurology and Psychiatry January/February 2016 www.progressnp.com Review z Depression and pain

Category of research article References

Articles that screen for depression in patients with known chronic pain Kent et al. 201437 Kongsted et al. 201438 Lopez et al. 201339 Poole et al. 200940 Cheour et al. 200841 Lee et al. 200842 Sela. 200743 Haggman et al. 200444 Nakaigawa et al. 199545 Wulsin et al. 198846 Turner et al. 198447 Choi et al. 201448

Articles that compare the Beck depression scale with other scales for assess- Olaya-Contreras et al. 201049 ment of depression in patients with known chronic pain Geisser et al. 199750

Articles that use the Beck depression scale alone in patients with known Harris et al. 200851 chronic pain Poole et al. 200652 Morley et al. 200253 Wesley et al. 199954 Novy et al. 199555 Chibnall et al. 199456 Krefetz et al. 200457 Jones. 200858 Riggs. 200759 Bishop et al. 199360 LaVonne et al. 199961

Articles that use the Children’s Depressive Inventory in children with Logan et al. 201362 chronic pain

Articles that use the Hospital Anxiety and Depression scale in patients with Soares-Filho et al. 200963 known chronic pain Castro et al. 200664 Kuijpers et al. 200365 Luppi et al. 20106 Di Vadi et al. 200666 Bagnato et al. 201367 Trudeau et al. 201368 Lynch et al. 201169 Bagnato et al. 201570

Articles that use the Geriatric Depression Scale in known chronic pain Karp et al. 200871

Articles that use the Depression Anxiety Stress Scale in known chronic pain Sarda et al. 200872

Articles that compare the Zung Self-rating scale and the Depression Anxiety Taylor et al. 200573 Stress Scale in known chronic pain

Articles that use the Depression, Anxiety and Positive Outlook Scale in Olaya-Contreras et al. 200974 known chronic pain

Articles that use the Family Drawing Depression Scale in known chronic pain Peek et al. 198875

Articles that assess pain, depression and anxiety in rheumatoid arthritis Tamiya et al. 20025

Articles that screen for pain and for risk of developing post-natal depression Jardri et al. 201076 in women post-delivery Maron et al. 201177

Table 3. The results of the literature search* to investigate if any screening tools simultaneously could screen patients for both depression and pain (*A MEDLINE search was done for articles combining the terms ‘pain’ AND ‘depression’ combined with the individual terms ‘screening’, ‘check- list’, ‘tool’, ‘questionnaire’, ‘inventory’ or ‘scale’. A total of 28 citations were found and are listed, subdivided into categories)

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Screening tool for Type of screening tool Advantages Disadvantages depression

Patient Health Question- Self-reported 9-item ques- • Quick to use • Self-testing carries risk naire (PHQ-9; Kroenke et tionnaire which diagnoses • Self-reported scale of patient adjusting al. 2001)78 depression and assesses • Allows diagnosis of their answers to fit severity; based on DSM-IV major depression and their own agenda79 criteria assessment of severity • Concerns regarding • Well validated and doc- validity of determined umented in a variety of severity8 populations

Hospital Anxiety and Self-reported 14-item • Quick to use • Self-testing carries risk Depression Scale (HADS; questionnaire; assesses both • Self-reported scale of patient adjusting Zigmund et al. 1983) 80 anxiety and depression; has • Allows diagnosis of their answers to fit been validated for use in pri- depression and anxiety their own agenda79 mary care despite its name; separately • Concerns regarding assesses severity validity of determined severity8 • Exclusion of somatic items may represent a reduction in face validity81

Beck Depression Invento- Self-reported 21-item ques- • Quick to use • Self-testing carries risk ry – Second Edition (BDI- tionnaire; diagnoses depres- • Self-reported scale of patient adjusting II; Beck et al. 1996)82 sion and assesses severity; • Allows diagnosis of their answers to fit based on DSM-IV criteria major depression and their own agenda79 assessment of severity • Includes some somatic symptoms • Well validated and doc- umented in a variety of populations

NICE guideline CG91 Two screening questions • Very quick to use • So brief and quick screening for depres- asked by GP to patient. If • Specifically designed for that symptoms may sion in patients with a either positive then further patients with long-term be missed, especially long-term physical health questioning takes place physical health prob- somatic symptoms problem7 lems in the GP setting

Hamilton Rating Scale Clinician-rated 17-item ques- • As clinician-rated, less • Requires clinician to for Depression (HRSD-17; tionnaire used for assessing bias introduced by pa- complete Hamilton. 1960)83 the severity of depression tient’s own agenda • Not intended as a • Useful in assessing the diagnostic instrument effects of drug therapy

Table 4. Three tools used in the general practice setting to screen for depression, as recommended in the Quality and Outcomes Framework (QOF) guidance, and the NICE screening questions for depression in patients with chronic illness, compared with the recognised ‘gold standard’ in clinical research, the Hamilton Rating Scale for Depression

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Pain rating scale Description Advantages Disadvantages

Visual Analogue Scale A self-reported scale. The • Quick and simple to use • Only assesses pain (VAS; reviewed in Wil- patient marks their pain on • Can be parametrically severity liamson, et al. 2005)84 a 100mm line ranging from analysed • Must be administered ‘no pain’ to ‘worst imagina- • Shown to be the most on paper or electroni- ble pain’. This is measured reliable and valid when cally, so difficult to use in mm, giving 101 levels in comparing VAS to VRS in clinical practice pain intensity and NRS • Patients with cognitive • Detects small changes impairment less able in pain to produce consistent scores

Numerical Rating Scale A self-reported scale, using • Quick and simple to use • Only assesses pain (NRS; reviewed in Wil- a 11 (0–10), 21 (0–20) or 101 • Can be parametrically severity liamson, et al. 2005)84 (0–100) point scale with end analysed • Poor reproducibility has points of ‘no pain’ versus • Detects small changes been demonstrated in ‘the worst possible pain’; in pain one study, but lack of can be presented verbally or other studies to confirm graphically this

Verbal Rating Scale (VRS; A self-reported scale in- • Quick and simple to use • Only assesses pain reviewed in Williamson, volving a list of adjectives • Preferred by some pa- severity et al. 2005)84 offered to describe pain tients due to simplicity • Intervals between each intensity and then adjectives rank number are not are assigned numbers necessarily equal, lead- ing to possible misinter- pretation • Can only be analysed using non-parametric statistics • Insensitive to small changes in pain

Brief Pain Inventory – A self-reported scale which • Explores the pain in • Takes longer to com- short form (Cleeland, et includes a severity assess- more detail than just a plete than those above al. 1994)85 ment like the NRS but scores severity scale • Unsuitable for patients pain in the last 24 hours ‘on • High test-retest relia- with cognitive average’, ‘at its worst’, ‘at its bility impairment least’ and ‘right now’. The • Widely used in clinical arithmetic mean of the four research severity items can be used as measures of pain sever- ity. Also assesses location of pain, usage and impact of pain on daily function

Table 5. Examples of common generalised pain scales in use which could be used in a primary care setting

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