Nonregistration, discontinuation, and nonpublication of randomized trials: A repeated metaresearch analysis

BACKGROUND We previously found that 25% of 1,017 randomized clinical trials (RCTs) approved between 2000 and 2003 were discontinued prematurely, and 44% remained unpublished at a median of 12 years follow-up. We aimed to assess a decade later (1) whether rates of completion and publication have increased; (2) the extent to which nonpublished RCTs can be identified in trial registries; and (3) the association between reporting quality of protocols and premature discontinuation or nonpublication of RCTs. METHODS AND FINDINGS We included 326 RCT protocols approved in 2012 by research ethics committees in Switzerland, the United Kingdom, Germany, and Canada in this metaresearch study. Pilot, feasibility, and phase 1 studies were excluded. We extracted trial characteristics from each study protocol and systematically searched for corresponding trial registration (if not reported in the protocol) and full text publications until February 2022. For trial registrations, we searched the (i) World Health Organization: International Clinical Trial Registry Platform (ICTRP); (ii) US National Library of Medicine (ClinicalTrials.gov); (iii) European Union Drug Regulating Authorities Clinical Trials Database (EUCTR); (iv) ISRCTN registry; and (v) Google. For full text publications, we searched PubMed, Google Scholar, and Scopus. We recorded whether RCTs were registered, discontinued (including reason for discontinuation), and published. The reporting quality of RCT protocols was assessed with the 33-item SPIRIT checklist. We used multivariable logistic regression to examine the association between the independent variables protocol reporting quality, planned sample size, type of control (placebo versus other), reporting of any recruitment projection, single-center versus multicenter trials, and industry versus investigator sponsoring, with the 2 dependent variables: (1) publication of RCT results; and (2) trial discontinuation due to poor recruitment. Of the 326 included trials, 19 (6%) were unregistered. Ninety-eight trials (30%) were discontinued prematurely, most often due to poor recruitment (37%; 36/98). One in 5 trials (21%; 70/326) remained unpublished at 10 years follow-up, and 21% of unpublished trials (15/70) were unregistered. Twenty-three of 147 investigator-sponsored trials (16%) reported their results in a trial registry in contrast to 150 of 179 industry-sponsored trials (84%). The median proportion of reported SPIRIT items in included RCT protocols was 69% (interquartile range 61% to 77%). We found no variables associated with trial discontinuation; however, lower reporting quality of trial protocols was associated with nonpublication (odds ratio, 0.71 for each 10% increment in the proportion of SPIRIT items met; 95% confidence interval, 0.55 to 0.92; p = 0.009). Study limitations include that the moderate sample size may have limited the ability of our regression models to identify significant associations. CONCLUSIONS We have observed that rates of premature trial discontinuation have not changed in the past decade. Nonpublication of RCTs has declined but remains common; 21% of unpublished trials could not be identified in registries. Only 16% of investigator-sponsored trials reported results in a trial registry. Higher reporting quality of RCT protocols was associated with publication of results. Further efforts from all stakeholders are needed to improve efficiency and transparency of clinical research

Exploring the Role of Explicit and Implicit Self-Esteem and Self-Compassion in Anxious and Depressive Symptomatology Following Acquired Brain Injury

[EN] Objectives Acquired brain injury (ABI) can lead to the emergence of several disabilities and is commonly associated with high rates of anxiety and depression symptoms. Self-related constructs, such as self-esteem and self-compassion, might play a key role in this distressing symptomatology. Low explicit (i.e., deliberate) self-esteem is associated with anxiety and depression after ABI. However, implicit (i.e., automatic) self-esteem, explicit-implicit self-discrepancies, and self-compassion could also significantly contribute to this symptomatology. The purpose of the present study was to examine whether implicit self-esteem, explicit-implicit self-discrepancy (size and direction), and self-compassion are related to anxious and depressive symptoms after ABI in adults, beyond the contribution of explicit self-esteem. Methods The sample consisted 38 individuals with ABI who were enrolled in a long-term rehabilitation program. All participants completed the measures of explicit self-esteem, implicit self-esteem, self-compassion, anxiety, and depression. Pearson's correlations and hierarchical regression models were calculated. Results Findings showed that both self-compassion and implicit self-esteem negatively accounted for unique variance in anxiety and depression when controlling for explicit self-esteem. Neither the size nor direction of explicit-implicit self-discrepancy was significantly associated with anxious or depressive symptomatology. Conclusions The findings suggest that the consideration of self-compassion and implicit self-esteem, in addition to explicit self-esteem, contributes to understanding anxiety and depression following ABI.Lorena Desdentado is supported by a FPU doctoral scholarship (FPU18/01690) from the Spanish Ministry of Universities. This work was supported by CIBEROBN, an initiative of the ISCIII (ISC III CB06 03/0052).Desdentado, L.; Cebolla, A.; Miragall, M.; Llorens Rodríguez, R.; Navarro, MD.; Baños, RM. (2021). Exploring the Role of Explicit and Implicit Self-Esteem and Self-Compassion in Anxious and Depressive Symptomatology Following Acquired Brain Injury. Mindfulness. 12(4):899-910. https://doi.org/10.1007/s12671-020-01553-wS899910124Anson, K., & Ponsford, J. (2006). Coping and emotional adjustment following traumatic brain injury. The Journal of Head Trauma Rehabilitation, 21(3), 248–259. https://doi.org/10.1097/00001199-200605000-00005.Baños, R. M., & Guillén, V. (2000). Psychometric characteristics in normal and social phobic samples for a Spanish version of the Rosenberg Self-Esteem Scale. Psychological Reports, 87(1), 269–274. https://doi.org/10.2466/pr0.2000.87.1.269.Beadle, E. J., Ownsworth, T., Fleming, J., & Shum, D. (2016). The impact of traumatic brain injury on self-identity: a systematic review of the evidence for self-concept changes. The Journal of Head Trauma Rehabilitation, 31(2), E12–E25. https://doi.org/10.1097/HTR.0000000000000158.Beck, A. T. (1979). Cognitive therapy of depression. New York: Guilford Press.Beevers, C. G. (2005). Cognitive vulnerability to depression: A dual process model. Clinical Psychology Review, 25(7), 975–1002. https://doi.org/10.1016/j.cpr.2005.03.003.Bos, A. E. R., Huijding, J., Muris, P., Vogel, L. R. R., & Biesheuvel, J. (2010). Global, contingent and implicit self-esteem and psychopathological symptoms in adolescents. Personality and Individual Differences, 48(3), 311–316. https://doi.org/10.1016/j.paid.2009.10.025.Bowerman, B. L., & O’Connell, R. T. (1990). Linear statistical models: An applied approach (2nd ed.). Belmont, CA: Duxbury.Brenner, R. E., Heath, P. J., Vogel, D. L., & Credé, M. (2017). Two is more valid than one: examining the factor structure of the self-compassion scale (SCS). Journal of Counseling Psychology, 64(6), 696–707. https://doi.org/10.1037/cou0000211.Brysbaert, M. (2019). How many participants do we have to include in properly powered experiments? A tutorial of power analysis with reference tables. Journal of Cognition, 2(1), 1–38. https://doi.org/10.5334/joc.72.Carroll, E., & Coetzer, R. (2011). Identity, grief and self-awareness after traumatic brain injury. Neuropsychological Rehabilitation, 21(3), 289–305. https://doi.org/10.1080/09602011.2011.555972.Corrigan, P. W., & Watson, A. C. (2002). The paradox of self-stigma and mental illness. Clinical Psychology: Science and Practice, 9(1), 35–53. https://doi.org/10.1093/clipsy/9.1.35.Creemers, D. H. M., Scholte, R. H. J., Engels, R. C. M. E., Prinstein, M. J., & Wiers, R. W. (2012). Implicit and explicit self-esteem as concurrent predictors of suicidal ideation, depressive symptoms, and loneliness. Journal of Behavior Therapy and Experimental Psychiatry, 43(1), 638–646. https://doi.org/10.1016/j.jbtep.2011.09.006.Creemers, D. H. M., Scholt, R. H. J., Engels, R. C. M. E., Prinstein, M. J., & Wiers, R. W. (2013). Damaged self-esteem is associated with internalizing problems. Frontiers in Psychology, 4, 152. https://doi.org/10.3389/fpsyg.2013.00152.Curvis, W., Simpson, J., & Hampson, N. (2018). Factors associated with self-esteem following acquired brain injury in adults: a systematic review. Neuropsychological Rehabilitation, 28(1), 142–183. https://doi.org/10.1080/09602011.2016.1144515.Elbaum, J., & Benson, D. (Eds.). (2007). Acquired brain injury: an integrative neuro-rehabilitation approach. New York: Springer. https://doi.org/10.1007/978-0-387-37575-5.Faul, F., Erdfelder, E., Buchner, A., & Lang, A.-G. (2009). Statistical power analyses using G*Power 3.1: Tests for correlation and regression analyses. Behavior Research Methods, 41(4), 1149–1160. https://doi.org/10.3758/BRM.41.4.1149.FEDACE. (2015). Las personas con daño cerebral adquirido en España. Ministerio de Sanidad, Servicios Sociales e Igualdad. Retrieved May 21, 2020, from: https://fedace.org/index.php?V_dir=MSC&V_mod=download&f=2016-9/26-16-4-11.admin.Informe_FEDACE_RPD_para_DDC-1.pdf.Feigin, V. L., Forouzanfar, M. H., Krishnamurthi, R., Mensah, G. A., Connor, M., Bennett, D. A., Moran, A. E., Sacco, R. L., Anderson, L., Truelsen, T., O’Donnell, M., Venketasubramanian, N., Barker-Collo, S., Lawes, C. M. M., Wang, W., Shinohara, Y., Witt, E., Ezzati, M., & Naghavi, M. (2014). Global and regional burden of stroke during 1990-2010: findings from the Global Burden of Disease Study 2010. The Lancet, 383(9913), 245–254. https://doi.org/10.1016/S0140-6736(13)61953-4.Fennell, M. J. V. (1997). Low self-esteem: a cognitive perspective. Behavioural and Cognitive Psychotherapy, 25(1), 1–26. https://doi.org/10.1017/s1352465800015368.Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975). “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12(3), 189–198. https://doi.org/10.1016/0022-3956(75)90026-6.Garcia-Campayo, J., Navarro-Gil, M., Andrés, E., Montero-Marin, J., López-Artal, L., Marcos, M., & Demarzo, P. (2014). Validation of the Spanish versions of the long (26 items) and short (12 items) forms of the Self-Compassion Scale (SCS). Health and Quality of Life Outcomes, 12(4). https://doi.org/10.1186/1477-7525-12-4.GBD 2016 Traumatic Brain Injury and Spinal Cord Injury Collaborators. (2018). Global, regional, and national burden of traumatic brain injury and spinal cord injury, 1990–2016: A systematic analysis for the Global Burden of Disease Study 2016. The Lancet Neurology, 18(1), 56–87. https://doi.org/10.1016/S1474-4422(18)30415-0.Gould, K. R., Ponsford, J. L., Johnston, L., & Schönberger, M. (2011). Relationship between psychiatric disorders and 1-year psychosocial outcome following traumatic brain injury. The Journal of Head Trauma Rehabilitation, 26(1), 79–89. https://doi.org/10.1097/HTR.0b013e3182036799.Gracey, F., Palmer, S., Rous, B., Psaila, K., Shaw, K., O’Dell, J., Cope, J., & Mohamed, S. (2008). “Feeling part of things”: personal construction of self after brain injury. Neuropsychological Rehabilitation, 18(5–6), 627–650. https://doi.org/10.1080/09602010802041238.Gracey, F., Evans, J. J., & Malley, D. (2009). Capturing process and outcome in complex rehabilitation interventions: a “Y-shaped” model. Neuropsychological Rehabilitation, 19(6), 867–890. https://doi.org/10.1080/09602010903027763.Greenwald, A. G., & Farnham, S. D. (2000). Using the Implicit Association Test to measure self-esteem and self-concept. Journal of Personality and Social Psychology, 79(6), 1022–1038. https://doi.org/10.1037/0022-3514.79.6.1022.Greenwald, A. G., McGhee, D. E., & Schwartz, J. L. K. (1998). Measuring individual differences in implicit cognition: the Implicit Association Test. Journal of Personality and Social Psychology, 74(6), 1464–1480. https://doi.org/10.1037/0022-3514.74.6.1464.Greenwald, A. G., Nosek, B. A., & Banaji, M. R. (2003). Understanding and using the Implicit Association Test: I. An improved scoring algorithm. Journal of Personality and Social Psychology, 85(2), 197–216. https://doi.org/10.1037/0022-3514.85.2.197.Hackett, M. L., Yapa, C., Parag, V., & Anderson, C. S. (2005). Frequency of depression after stroke: a systematic review of observational studies. Stroke, 36(6), 1330–1340. https://doi.org/10.1161/01.STR.0000165928.19135.35.Haeffel, G. J., Abramson, L. Y., Brazy, P. C., Shah, J. Y., Teachman, B. A., & Nosek, B. A. (2007). Explicit and implicit cognition: a preliminary test of a dual-process theory of cognitive vulnerability to depression. Behaviour Research and Therapy, 45(6), 1155–1167. https://doi.org/10.1016/j.brat.2006.09.003.Ingram, R. E. (1984). Toward an information-processing analysis of depression. Cognitive Therapy and Research, 8(5), 443–477. https://doi.org/10.1007/BF01173284.Izuma, K., Kennedy, K., Fitzjohn, A., Sedikides, C., & Shibata, K. (2018). Neural activity in the reward-related brain regions predicts implicit self-esteem: a novel validity test of psychological measures using neuroimaging. Journal of Personality and Social Psychology, 114(3), 343–357. https://doi.org/10.1037/pspa0000114.Khan-Bourne, N., & Brown, R. G. (2003). Cognitive behaviour therapy for the treatment of depression in individuals with brain injury. Neuropsychological Rehabilitation, 13(1–2), 89–107. https://doi.org/10.1080/09602010244000318.Kim, H. S., & Moore, M. T. (2019). Symptoms of depression and the discrepancy between implicit and explicit self-esteem. Journal of Behavior Therapy and Experimental Psychiatry, 63, 1–5. https://doi.org/10.1016/j.jbtep.2018.12.001.Lane, K. A., Banaji, M. R., Nosek, B. A., & Greenwald, A. G. (2007). Understanding and using the Implicit Association Test: IV. What we know (so far) about the method. In B. Wittenbrink & N. Schwarz (Eds.), Implicit measures of attitudes (pp. 59–102). New York: The Guildford Press.Leary, M. R., Tate, E. B., Adams, C. E., Batts Allen, A., & Hancock, J. (2007). Self-compassion and reactions to unpleasant self-relevant events: the implications of treating oneself kindly. Personality Processes and Individual Differences, 92(5), 887–904. https://doi.org/10.1037/0022-3514.92.5.887.Lennon, A., Bramham, J., Carroll, À., McElligott, J., Carton, S., Waldron, B., Fortune, D., Burke, T., Fitzhenry, M., & Benson, C. (2014). A qualitative exploration of how individuals reconstruct their sense of self following acquired brain injury in comparison with spinal cord injury. Brain Injury, 28(1), 27–37. https://doi.org/10.3109/02699052.2013.848378.Longworth, C., Deakins, J., Rose, D., & Gracey, F. (2018). The nature of self-esteem and its relationship to anxiety and depression in adult acquired brain injury. Neuropsychological Rehabilitation, 28(7), 1078–1094. https://doi.org/10.1080/09602011.2016.1226185.MacBeth, A., & Gumley, A. (2012). Exploring compassion: a meta-analysis of the association between self-compassion and psychopathology. Clinical Psychology Review, 32(6), 545–552. https://doi.org/10.1016/j.cpr.2012.06.003.McDonald, S., Saad, A., & James, C. (2011). Social dysdecorum following severe traumatic brain injury: loss of implicit social knowledge or loss of control? Journal of Clinical and Experimental Neuropsychology, 33(6), 619–630. https://doi.org/10.1080/13803395.2011.553586.Milne, E., & Grafman, J. (2001). Ventromedial prefrontal cortex lesions in humans eliminate implicit gender stereotyping. The Journal of Neuroscience, 21(12), 1–6.Moors, A., & De Houwer, J. (2006). Automaticity: a theoretical and conceptual analysis. Psychological Bulletin, 132(2), 297–326. https://doi.org/10.1037/0033-2909.132.2.297.Muris, P., & Petrocchi, N. (2017). Protection or vulnerability? A meta-analysis of the relations between the positive and negative components of self-compassion and psychopathology. Clinical Psychology & Psychotherapy, 24(2), 373–383. https://doi.org/10.1002/cpp.2005.Myers, R. (2000). Classical and modern regression with applications (2nd ed.). Belmont, CA: Duxbury.Neff, K. D. (2003). Self-compassion: an alternative conceptualization of a healthy attitude toward oneself. Self and Identity, 2(2), 85–101. https://doi.org/10.1080/15298860309032.Neff, K. D., & Vonk, R. (2009). Self-compassion versus global self-esteem: two different ways of relating to oneself. Journal of Personality, 77, 23–50. https://doi.org/10.1111/j.1467-6494.2008.00537.x.Neff, K. D., Tóth-Király, I., Yarnell, L. M., Arimitsu, K., Castilho, P., Ghorbani, N., Guo, H. X., Hirsch, J. K., Hupfeld, J., Hutz, C. S., Kotsou, I., Lee, W. K., Montero-Marin, J., Sirois, F. M., De Souza, L. K., Svendsen, J. L., Wilkinson, R. B., & Mantzios, M. (2019). Examining the factor structure of the Self-Compassion Scale in 20 diverse samples: support for use of a total score and six subscale scores. Psychological Assessment, 31(1), 27–45. https://doi.org/10.1037/pas0000629.Norton, P. J., & Paulus, D. J. (2017). Transdiagnostic models of anxiety disorder: theoretical and empirical underpinnings. Clinical Psychology Review, 56, 122–137. https://doi.org/10.1016/j.cpr.2017.03.004.Nosek, B. A., & Banaji, M. R. (2001). The go/no-go association task. Social Cognition, 19(6), 625–664. https://doi.org/10.1521/soco.19.6.625.20886.Oddy, M., & Herbert, C. (2003). Intervention with families following brain injury: evidence-based practice. Neuropsychological Rehabilitation, 13(1–2), 259–273. https://doi.org/10.1080/09602010244000345.Ouimet, A. J., Gawronski, B., & Dozois, D. J. A. (2009). Cognitive vulnerability to anxiety: a review and an integrative model. Clinical Psychology Review, 29(6), 459–470. https://doi.org/10.1016/j.cpr.2009.05.004.Ponsford, J., Kelly, A., & Couchman, G. (2014). Self-concept and self-esteem after acquired brain injury: a control group comparison. Brain Injury, 28(2), 146–154. https://doi.org/10.3109/02699052.2013.859733.Raes, F., Pommier, E., Neff, K. D., & Van Gucht, D. (2011). Construction and factorial validation of a short form of the Self-Compassion Scale. Clinical Psychology & Psychotherapy, 18(3), 250–255. https://doi.org/10.1002/cpp.702.Romero, M., Sánchez, A., Marín, C., Navarro, M. D., Ferri, J., & Noé, E. (2012). Clinical usefulness of the Spanish version of the Mississippi Aphasia Screening Test (MASTsp): validation in stroke patients. Neurología (English Edition), 27(4), 216–224. https://doi.org/10.1016/j.nrleng.2011.06.001.Rosenberg, M. (1965). Rosenberg Self-Esteem Scale (RSE). Acceptance and Commitment Therapy. Measures Package, 61, 52 /S0034-98872009000600009.Sandstrom, M. J., & Jordan, R. (2008). Defensive self-esteem and aggression in childhood. Journal of Research in Personality, 42(2), 506–514. https://doi.org/10.1016/j.jrp.2007.07.008.Schönberger, M., & Ponsford, J. (2010). The factor structure of the Hospital Anxiety and Depression Scale in individuals with traumatic brain injury. Psychiatry Research, 179(3), 342–349. https://doi.org/10.1016/j.psychres.2009.07.003.Schröder-Abé, M., Rudolph, A., & Schütz, A. (2007). High implicit self-esteem is not necessarily advantageous: discrepancies between explicit and implicit self-esteem and their relationship with anger expression and psychological health. European Journal of Personality, 21(3), 319–339. https://doi.org/10.1002/per.626.Scoglio, A. A. J., Rudat, D. A., Garvert, D., Jarmolowski, M., Jackson, C., & Herman, J. L. (2018). Self-compassion and responses to trauma: the role of emotion regulation. Journal of Interpersonal Violence, 33(13), 2016–2036. https://doi.org/10.1177/0886260515622296.Sloan, E., Hall, K., Moulding, R., Bryce, S., Mildred, H., & Staiger, P. K. (2017). Emotion regulation as a transdiagnostic treatment construct across anxiety, depression, substance, eating and borderline personality disorders: a systematic review. Clinical Psychology Review, 57, 141–163. https://doi.org/10.1016/j.cpr.2017.09.002.Smeijers, D., Vrijsen, J. N., van Oostrom, I., Isaac, L., Speckens, A., Becker, E. S., & Rinck, M. (2017). Implicit and explicit self-esteem in remitted depressed patients. Journal of Behavior Therapy and Experimental Psychiatry, 54, 301–306. https://doi.org/10.1016/j.jbtep.2016.10.006.Smith, E. R., & DeCoster, J. (2000). Dual-process models in social and cognitive psychology: conceptual integration and links to underlying memory systems. Personality and Social Psychology Review, 4(2), 108–131. https://doi.org/10.1207/S15327957PSPR0402_01.Sowislo, J. F., & Orth, U. (2013). Does low self-esteem predict depression and anxiety? A meta-analysis of longitudinal studies. Psychological Bulletin, 139(1), 213–240. https://doi.org/10.1037/a0028931.Strack, F., & Deutsch, R. (2004). Reflective and impulsive determinants of social behavior. Personality and Social Psychology Review, 8(3), 220–247. https://doi.org/10.1207/s15327957pspr0803_1.Terol-Cantero, M. C., Cabrera-Perona, V., & Martín-Aragón, M. (2015). Hospital Anxiety and Depression Scale (HADS) review in Spanish samples. Anales de Psicología, 31(2), 494–503. https://doi.org/10.6018/analesps.31.2.172701.Tóth-Király, I., & Neff, K. D. (2020). Is self-compassion universal? Support for the measurement invariance of the Self-Compassion Scale across populations. Assessment. Advance online publication. https://doi.org/10.1177/1073191120926232.Turner-Stokes, L., & Wade, D. (2003). Rehabilitation following acquired brain injury: National Clinical Guidelines. Clinical Medicine, 4(1), 61–65. https://doi.org/10.7861/clinmedicine.4-1-61.Tyerman, A., & Humphrey, M. (1984). Changes in self-concept following severe head injury. International Journal of Rehabilitation Research, 7(1), 11–23. https://doi.org/10.1097/00004356-198403000-00002.Valiente, C., Cantero, D., Vázquez, C., Sanchez, Á., Provencio, M., & Espinosa, R. (2011). Implicit and explicit self-esteem discrepancies in paranoia and depression. Journal of Abnormal Psychology, 120(3), 691–699. https://doi.org/10.1037/a0022856.Vickery, C. D., Sepehri, A., & Evans, C. C. (2008). Self-esteem in an acute stroke rehabilitation sample: a control group comparison. Clinical Rehabilitation, 22(2), 179–187. https://doi.org/10.1177/0269215507080142.Whelan-Goodinson, R., Ponsford, J., & Schönberger, M. (2009). Validity of the Hospital Anxiety and Depression Scale to assess depression and anxiety following traumatic brain injury as compared with the Structured Clinical Interview for DSM-IV. Journal of Affective Disorders, 114(1–3), 94–102. https://doi.org/10.1016/j.jad.2008.06.007.Zeigler-Hill, V. (2006). Discrepancies between implicit and explicit self-esteem: Implications for narcissism and self-esteem instability. Journal of Personality, 74(1), 119–144. https://doi.org/10.1111/j.1467-6494.2005.00371.x.Zessin, U., Dickhäuser, O., & Garbade, S. (2015). The relationship between self-compassion and well-being: a meta-analysis. Applied Psychology. Health and Well-Being, 7(3), 340–364. https://doi.org/10.1111/aphw.12051.Zhang, J. W., Chen, S., & Tomova Shakur, T. K. (2020). From me to you: Self-compassion predicts acceptance of own and others’ imperfections. Personality and Social Psychology Bulletin, 46(2), 228–242. https://doi.org/10.1177/0146167219853846.Zigmond, A. S., & Snaith, R. P. (1983). The Hospital Anxiety and Depression Scale. Acta Psychiatrica Scandinavica, 67(6), 361–370. https://doi.org/10.1111/j.1600-0447.1983.tb09716.x

Oksidacijski stres u lakirera izloženih niskim razinama olova

Lead toxicity is a public health problem particularly to the children and to occupationally exposed adults. Evidence is mounting successively regarding the adverse health effects of lead at low levels. This study was undertaken to assess the antioxidant status of lead-exposed residential and commercial painters of Lucknow city in Uttar Pradesh, India. Thirty-five painters aged 20 to 50 years who had blood lead levels ≤400 µg L-1 were selected for the study from a population of 56 male painters initially screened for blood lead. The control group included an equal number of subjects of the same age group without any occupational exposure to lead. We studied the association between low lead level exposure and antioxidant status and found that blood lead levels in painters were approximately seven times as high as in controls [(219.2 ± 61.9) µg L-1 vs. (30.6±10.1) µg L-1, respectively]. Among the biomarkers of lead toxicity a significant decrease in the level of delta-aminolevulinic acid dehydratase [(9.13±4.62) UL-1 vs. (39.38±5.05) UL-1] and an increase in the level of zinc protoporphyrin [(187.9±49.8) µg L-1 vs. (26.4±5.5) µg L-1] were observed in painters compared to controls. Among antioxidant enzymes, painters showed a significant decrease in catalase [(56.77±11.11) UL-1 vs. (230.30±42.55) UL-1] and superoxide dismutase [(0.64±0.19) UL-1 vs. (2.68±0.62) UL-1] compared to controls. Lipid peroxidation was monitored by measuring thiobarbituric acid reactive substances (TBARS) that were expressed in terms of malondialdehyde (MDA) equivalents. Concentration of MDA in plasma was higher in painters than in controls [(7.48±1.31) nmol mL-1 vs. (3.08±0.56) nmol mL-1]. Significant changes were also observed in reduced and oxidised glutathione levels. The strong association between blood lead levels and oxidative stress markers in this population suggests that oxidative stress should be considered in the pathogenesis of lead-related diseases among people with low level environmental exposure to lead.Toksičnost olova javnozdravstveni je problem, napose u djece i odraslih osoba koje su im izložene profesionalno. Sve je više dokaza o štetnom djelovanju olova pri niskim razinama. Svrha je ovog ispitivanja bila procijeniti antioksidacijski status u lakirera iz grada Lucknowa u indijskoj pokrajini Uttar Pradesh. Iz skupine od 56 muškaraca lakirera u dobi od 20 do 50 godina s pozitivnim početnim nalazima olova u krvi, za ispitivanje su izabrana 35-orica čije su razine iznosile ≤400 µg L-1. Izabran je i jednaki broj kontrolnih ispitanika iz iste dobne skupine, koji nisu bili profesionalno izloženi olovu. Ispitana je povezanost izme|u izloženosti niskim razinama olova i antioksidacijskoga stanja te je utvrđeno da su razine olova u krvi lakirera [(219,2±61,9) µg L-1] bile oko sedam puta više negoli u kontrolnih ispitanika [(30,6±10,1) µg L-1]. Od biopokazatelja toksičnosti olova u lakirera je zamijećen značajan pad razina delta- ALAD [(9,13±4,62) UL-1 prema (39,38±5,05) UL-1] te rast razina cinkova protoporfirina [(187,9±49,8) µg L-1 prema (26,4±5,5) µg L-1] u odnosu na kontrolne ispitanike. Od antioksidacijskih enzima u lakirera je značajno pala aktivnost katalaze [(56,77±11,11) UL-1 prema (230,30±42,55) UL-1] i superoksid dismutaze [(0,64±0.19) UL-1 prema (2,68±0,62) UL-1] u odnosu na kontrolu, dok je produkt lipidne peroksidacije u plazmi (izv. thiobarbituric acid reactive substances, TBARS) izražen kao koncentracija malondialdehida (MDA) porastao [(7,48±1,31) nmol mL-1 prema (3,08±0,56) nmol mL-1]. Značajne su promjene također zamijećene u smanjenim razinama glutationa i njihovoj oksidaciji. Snažna povezanost razina olova u krvi s pokazateljima oksidacijskoga stresa upućuje na to da u osoba s niskom razinom izloženosti olovu iz okoliša kod razmatranja patogeneze bolesti povezane s olovom u obzir valja uzeti oksidacijski stres