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1.
Pain ; 161(2): 274-280, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31651575

RESUMO

African Americans experience an increased burden of motor vehicle collision (MVC), post-MVC musculoskeletal pain, and vitamin D insufficiency. In this prospective multicenter study, we tested the hypothesis that African Americans (n = 133) presenting to the emergency department after MVC with low peritraumatic vitamin D levels would have worse chronic musculoskeletal pain outcomes compared to individuals with sufficient vitamin D. Vitamin D levels were assessed in the early aftermath of MVC through enzyme-linked immunosorbent assay, and pain severity was assessed using the 0 to 10 numeric rating scale at 6 weeks, 6 months, and 1 year. In repeated-measures analysis, African American MVC survivors with vitamin D insufficiency experienced more severe chronic pain (ß = 1.18, P = 0.031). In secondary analyses, we assessed for evidence that the effect of vitamin D on post-MVC pain outcomes is mediated, at least in part, by the influence of vitamin D on genetic variants in genes involved in immune system regulation (IL-10 and NLRP3). Genotyping was performed using a genome-wide microarray using collected DNA samples. Secondary analyses suggest that the effect of vitamin D on post-MVC pain outcomes may be influenced by genetic variation in IL-10 and NLRP3. Further studies are needed to assess the impact of vitamin D insufficiency on pain outcomes in African Americans experiencing MVC and other common trauma exposures, to assess factors affecting this relationship, and to assess the efficacy of administering vitamin D in the immediate aftermath of MVC to prevent chronic pain. Such low-cost, nonopioid interventions are urgently needed to address chronic pain development after MVC.

2.
Mol Psychiatry ; 25(2): 283-296, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31745239

RESUMO

Adverse posttraumatic neuropsychiatric sequelae (APNS) are common among civilian trauma survivors and military veterans. These APNS, as traditionally classified, include posttraumatic stress, postconcussion syndrome, depression, and regional or widespread pain. Traditional classifications have come to hamper scientific progress because they artificially fragment APNS into siloed, syndromic diagnoses unmoored to discrete components of brain functioning and studied in isolation. These limitations in classification and ontology slow the discovery of pathophysiologic mechanisms, biobehavioral markers, risk prediction tools, and preventive/treatment interventions. Progress in overcoming these limitations has been challenging because such progress would require studies that both evaluate a broad spectrum of posttraumatic sequelae (to overcome fragmentation) and also perform in-depth biobehavioral evaluation (to index sequelae to domains of brain function). This article summarizes the methods of the Advancing Understanding of RecOvery afteR traumA (AURORA) Study. AURORA conducts a large-scale (n = 5000 target sample) in-depth assessment of APNS development using a state-of-the-art battery of self-report, neurocognitive, physiologic, digital phenotyping, psychophysical, neuroimaging, and genomic assessments, beginning in the early aftermath of trauma and continuing for 1 year. The goals of AURORA are to achieve improved phenotypes, prediction tools, and understanding of molecular mechanisms to inform the future development and testing of preventive and treatment interventions.

3.
Pain ; 161(1): 47-60, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31569141

RESUMO

Posttraumatic widespread pain (PTWP) and posttraumatic stress symptoms (PTSS) are frequent comorbid sequelae of trauma that occur at different rates in women and men. We sought to identify microRNA (miRNA) that may contribute to sex-dependent differences in vulnerability to these outcomes. Monte Carlo simulations (x10,000) identified miRNA in which predicted targeting of PTWP or PTSS genes was most enriched. Expression of the leading candidate miRNA to target PTWP/PTSS-related genes, miR-19b, has been shown to be influenced by estrogen and stress exposure. We evaluated whether peritraumatic miR-19b blood expression levels predicted PTWP and PTSS development in women and men experiencing trauma of motor vehicle collision (n = 179) and in women experiencing sexual assault trauma (n = 74). A sex-dependent relationship was observed between miR-19b expression levels and both PTWP (ß = -2.41, P = 0.034) and PTSS (ß = -3.01, P = 0.008) development 6 months after motor vehicle collision. The relationship between miR-19b and PTSS (but not PTWP) was validated in sexual assault survivors (ß = -0.91, P = 0.013). Sex-dependent expression of miR-19b was also observed in blood and nervous tissue from 2 relevant animal models. Furthermore, in support of increasing evidence indicating a role for the circadian rhythm (CR) in PTWP and PTSS pathogenesis, miR-19b targets were enriched in CR gene transcripts. Human cohort and in vitro analyses assessing miR-19b regulation of key CR transcripts, CLOCK and RORA, supported the potential importance of miR-19b to regulating the CR pathway. Together, these results highlight the potential role that sex-dependent expression of miR-19b might play in PTWP and PTSS development after trauma/stress exposure.

4.
Pain ; 160(3): 670-675, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30507783

RESUMO

Obesity has been found to increase the risk of musculoskeletal pain (MSP) in other settings, but to our knowledge, the influence of increased body mass index on pain outcomes after common trauma exposures such as motor vehicle collision (MVC) has not been assessed. In addition, obesity results in biomechanical changes, as well as physiologic changes including reduced hypothalamic pituitary adrenal axis negative feedback inhibition, but mechanisms by which obesity may result in worse post-traumatic outcomes remain poorly understood. In this study, we evaluated the influence of body mass index on axial and overall MSP severity (0-10 numeric rating scale) 6 weeks, 6 months, and 1 year after MVC among 917 European Americans who presented to the emergency department for initial evaluation. After adjusting for an array of sociodemographic factors, obesity (particularly morbid obesity) was an independent risk factor for worse MSP after MVC (eg, RR 1.41 [95% CI 1.11, 1.80] for moderate or severe MSP 6 months after MVC among morbidly obese vs normal weight MVC survivors). Interestingly, substantial effect modification was observed between obesity risk and a genetic variant known to reduce hypothalamic pituitary adrenal axis negative feedback inhibition (FKBP5 rs9380526). (eg, 41% vs 16% increased risk of moderate or severe MSP at 6 months among obese individuals with and without the risk allele.) Further studies are needed to elucidate mechanisms underlying chronic pain development in obese trauma survivors and to develop interventions that will reduce chronic pain severity among this common, at-risk group.


Assuntos
Acidentes de Trânsito/estatística & dados numéricos , Dor Crônica/epidemiologia , Dor Crônica/etiologia , Obesidade/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Índice de Massa Corporal , Dor Crônica/genética , Feminino , Genótipo , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Obesidade/genética , Polimorfismo de Nucleotídeo Único/genética , Proteínas de Ligação a Tacrolimo/genética , Proteínas de Ligação a Tacrolimo/metabolismo , Adulto Jovem
5.
Am J Med Genet B Neuropsychiatr Genet ; 180(6): 415-427, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30537437

RESUMO

Co-morbid chronic musculoskeletal pain (CMSP) and posttraumatic stress symptoms (PTSS) are frequent sequelae of motor vehicle collision, are associated with greater disability than either outcome alone, and are more prevalent in women than men. In the current study we assessed for evidence that gene transcripts originating from the X chromosome contribute to sex differences in vulnerability to CMSP and PTSS after motor vehicle collision. Nested samples were drawn from a longitudinal study of African American individuals, and CMSP (0-10 numeric rating scale) and PTSS (impact of events scale, revised) outcomes were assessed 6 months following motor vehicle collision. Blood RNA were sequenced (n = 101) and the relationship between X chromosome mRNA expression levels and co-morbid CMSP and PTSS outcomes was evaluated using logistic regression analyses. A disproportionate number of peritraumatic X chromosome mRNA predicting CMSP and PTSS in women were genes previously found to escape X chromosome inactivation (11/40, z = -2.9, p = .004). Secondary analyses assessing gene ontology relationships between these genes identified an enrichment in genes known to influence neuronal plasticity. Further, the relationship of expression of two critical regulators of X chromosome inactivation, X-inactive specific transcript (XIST) and Yin Yang 1 (YY1), was different in women developing CMSP and PTSS. Together, these data suggest that X chromosome genes that escape inactivation may contribute to sex differences in vulnerability to CMSP and PTSS after motor vehicle collision.

6.
BMJ ; 363: k5094, 2018 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-30545967

RESUMO

OBJECTIVE: To determine if using a parachute prevents death or major traumatic injury when jumping from an aircraft. DESIGN: Randomized controlled trial. SETTING: Private or commercial aircraft between September 2017 and August 2018. PARTICIPANTS: 92 aircraft passengers aged 18 and over were screened for participation. 23 agreed to be enrolled and were randomized. INTERVENTION: Jumping from an aircraft (airplane or helicopter) with a parachute versus an empty backpack (unblinded). MAIN OUTCOME MEASURES: Composite of death or major traumatic injury (defined by an Injury Severity Score over 15) upon impact with the ground measured immediately after landing. RESULTS: Parachute use did not significantly reduce death or major injury (0% for parachute v 0% for control; P>0.9). This finding was consistent across multiple subgroups. Compared with individuals screened but not enrolled, participants included in the study were on aircraft at significantly lower altitude (mean of 0.6 m for participants v mean of 9146 m for non-participants; P<0.001) and lower velocity (mean of 0 km/h v mean of 800 km/h; P<0.001). CONCLUSIONS: Parachute use did not reduce death or major traumatic injury when jumping from aircraft in the first randomized evaluation of this intervention. However, the trial was only able to enroll participants on small stationary aircraft on the ground, suggesting cautious extrapolation to high altitude jumps. When beliefs regarding the effectiveness of an intervention exist in the community, randomized trials might selectively enroll individuals with a lower perceived likelihood of benefit, thus diminishing the applicability of the results to clinical practice.


Assuntos
Medicina Aeroespacial/métodos , Morte Súbita/prevenção & controle , Equipamentos de Proteção , Ferimentos e Lesões/prevenção & controle , Acidentes Aeronáuticos/prevenção & controle , Adulto , Aeronaves , Feminino , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Senso de Humor e Humor como Assunto
7.
J Neurosci ; 38(39): 8407-8420, 2018 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-30150364

RESUMO

Previous studies have shown that common variants of the gene coding for FK506-binding protein 51 (FKBP5), a critical regulator of glucocorticoid sensitivity, affect vulnerability to stress-related disorders. In a previous report, FKBP5 rs1360780 was identified as a functional variant because of its effect on gene methylation. Here we report evidence for a novel functional FKBP5 allele, rs3800373. This study assessed the association between rs3800373 and post-traumatic chronic pain in 1607 women and men from two ethnically diverse human cohorts. The molecular mechanism through which rs3800373 affects adverse outcomes was established via in silico, in vivo, and in vitro analyses. The rs3800373 minor allele predicted worse adverse outcomes after trauma exposure, such that individuals with the minor (risk) allele developed more severe post-traumatic chronic musculoskeletal pain. Among these individuals, peritraumatic circulating FKBP5 expression levels increased as cortisol and glucocorticoid receptor (NR3C1) mRNA levels increased, consistent with increased glucocorticoid resistance. Bioinformatic, in vitro, and mutational analyses indicate that the rs3800373 minor allele reduces the binding of a stress- and pain-associated microRNA, miR-320a, to FKBP5 via altering the FKBP5 mRNA 3'UTR secondary structure (i.e., is a riboSNitch). This results in relatively greater FKBP5 translation, unchecked by miR-320a. Overall, these results identify an important gene-miRNA interaction influencing chronic pain risk in vulnerable individuals and suggest that exogenous methods to achieve targeted reduction in poststress FKBP5 mRNA expression may constitute useful therapeutic strategies.SIGNIFICANCE STATEMENT FKBP5 is a critical regulator of the stress response. Previous studies have shown that dysregulation of the expression of this gene plays a role in the pathogenesis of chronic pain development as well as a number of comorbid neuropsychiatric disorders. In the current study, we identified a functional allele (rs3800373) in the 3'UTR of FKBP5 that influences vulnerability to chronic post-traumatic pain in two ethnic cohorts. Using multiple complementary experimental approaches, we show that the FKBP5 rs3800373 minor allele alters the secondary structure of FKBP5 mRNA, decreasing the binding of a stress- and pain-associated microRNA, miR-320a. This results in relatively greater FKBP5 translation, unchecked by miR-320a, increasing glucocorticoid resistance and increasing vulnerability to post-traumatic pain.


Assuntos
Dor Crônica/genética , MicroRNAs/genética , Dor Musculoesquelética/genética , Proteínas de Ligação a Tacrolimo/genética , Regiões 3' não Traduzidas , Adulto , Afro-Americanos/genética , Alelos , Dor Crônica/metabolismo , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Genótipo , Humanos , Masculino , MicroRNAs/metabolismo , Dor Musculoesquelética/metabolismo , Polimorfismo de Nucleotídeo Único , Ligação Proteica , Estrutura Secundária de Proteína , RNA Mensageiro/metabolismo , Receptores de Glucocorticoides/metabolismo , Proteínas de Ligação a Tacrolimo/metabolismo , Adulto Jovem
8.
Pain ; 159(6): 1056-1063, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29438226

RESUMO

African Americans experience a greater burden of acute pain than non-Hispanic white individuals across of variety of acute medical conditions, but it is unknown whether this is the case after trauma. We evaluated pain, pain-related characteristics (eg, peritraumatic distress), and analgesic treatment in 2 cohorts of individuals (African American [n = 931] and non-Hispanic white [n = 948]) presenting to the emergency department (ED) after a motor vehicle collision. We performed a propensity-matched analysis (n = 796 in each group) to assess racial differences in acute pain in the ED. In multivariable models conducted within the matched sample, race was associated with moderate to severe axial pain (odds ratio [OR] 3.2; 95% confidence interval [CI]: 2.1-5.0, P < 0.001) and higher average numerical rating scale scores (1.3; 95% CI: 1.1-1.6; P < 0.001). After adjustment for pain and other covariates, non-Hispanic white patients were more likely to receive an opioid analgesic in the ED (OR 2.0; 95% CI: 1.4-3.0, P < 0.001) or at discharge (OR 4.9; 95% CI: 3.4-7.1, P < 0.001) and also less likely to receive an NSAID in the ED (OR 0.54; 95% CI: 0.38-0.78; P = 0.001) or at discharge (0.31; 95% CI: 0.43-0.84). Racial differences in the severity of acute posttraumatic pain after a motor vehicle collision are not explained by factors such as socioeconomic status or crash characteristics. Despite a higher burden of acute pain, African Americans were less likely to receive opioid analgesics and more likely to receive NSAIDs. Further work is needed to understand the relationship between pain severity, disparities in analgesic treatment, and longer term outcomes, such as post-motor vehicle collision chronic pain.


Assuntos
Acidentes de Trânsito , Dor Aguda/etnologia , Dor Aguda/etiologia , Grupos de Populações Continentais , Dor Aguda/complicações , Dor Aguda/psicologia , Adulto , Afro-Americanos , Catastrofização , Estudos de Coortes , Serviço Hospitalar de Emergência , Grupo com Ancestrais do Continente Europeu , Feminino , Disparidades em Assistência à Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estresse Psicológico/etiologia , Adulto Jovem
9.
Prehosp Emerg Care ; 22(2): 208-213, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28910207

RESUMO

BACKGROUND: To improve survival of patients resuscitated from out of hospital cardiac arrest (OCHA), data is needed to assess and improve inpatient post-resuscitation care. Our objective was to apply probabilistic linkage methodology to link EMS and inpatient databases and evaluate whether it may be used to describe post-arrest care in Michigan. METHODS: We performed a retrospective study to describe post-cardiac arrest care in adult OHCA patients who were transported to Michigan hospitals from July 1, 2010, to June 30, 2013. Using probabilistic linkage methodology we linked two databases, the Michigan EMS Information System (MI_EMSIS) and the Michigan Inpatient Database (MIDB), which describes inpatient care and outcome of all admissions. Rates of case incidence and survival were compared to published literature. We compared the linked dataset to existing cardiac arrest databases from three counties to evaluate the quality of this linkage. RESULTS: Multiple iterations of match strategies were used to create a linked EMS-inpatient dataset. There were 12,838 MI_EMSIS cardiac arrest records of which 1,977 were matched with MIDB records, identifying them as surviving to hospital admission. Of these 590 (30.0%) survived to hospital discharge. The annual survival incidence/100,000 population to admission was 6.93/100,000 and survival incidence to discharge was 2.1/100,000. The matched dataset was compared to county databases identified a limited sensitivity [48.2%, 95% CI 42.1%-55.3%)] and positive predictive value [64.4%, 95% CI 56.8%-71.3%)]. CONCLUSION: Use of the MI_EMSISEMS database and the Michigan Inpatient database was feasible and produced rates of cardiac arrest admission and survival rates similar to published literature. This process yielded a limited match compared to existing county cardiac arrest databases. We conclude that such a linked dataset is useful for descriptive purposes but not as a population based dataset to evaluate statewide post-cardiac arrest care.


Assuntos
Reanimação Cardiopulmonar/normas , Serviços Médicos de Emergência , Parada Cardíaca Extra-Hospitalar/terapia , Melhoria de Qualidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Feminino , Humanos , Masculino , Michigan , Pessoa de Meia-Idade , Alta do Paciente , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
10.
Clin J Pain ; 34(4): 366-374, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28915155

RESUMO

OBJECTIVES: Certain forms of social support have been shown to improve pain-coping behaviors and pain outcomes in older adults with chronic pain, but little is known about the effect of social support on pain outcomes in older adults following trauma exposure. METHODS: We analyzed data from a prospective longitudinal study of adults aged 65 years and older presenting to an emergency department after a motor vehicle collision (MVC) to characterize the relationship between perceived social support and MVC-related pain after trauma overall and by subgroups based on sex, depressive symptoms, and marital status. RESULTS: In our sample (N=176), patients with low perceived social support had higher pain severity 6 weeks after MVC than patients with high perceived social support after adjustment for age, sex, race, and education (4.2 vs. 3.2, P=0.04). The protective effect of social support on pain severity at 6 weeks was more pronounced in men and in married individuals. Patients with low social support were less likely to receive an opioid prescription in the emergency department (15% vs. 32%, P=0.03), but there was no difference in opioid use at 6 weeks (22% vs. 20%, P=0.75). DISCUSSION: Among older adults experiencing trauma, low perceived social support was associated with higher levels of pain at 6 weeks.


Assuntos
Acidentes de Trânsito , Depressão/psicologia , Dor/psicologia , Apoio Social , Ferimentos e Lesões/psicologia , Idoso , Feminino , Humanos , Estudos Longitudinais , Masculino , Estado Civil , Dor/fisiopatologia , Medição da Dor , Estudos Prospectivos , Fatores Sexuais , Ferimentos e Lesões/fisiopatologia
11.
J Am Coll Cardiol ; 70(12): 1467-1476, 2017 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-28911510

RESUMO

BACKGROUND: Gasping is a natural reflex that enhances oxygenation and circulation during cardiopulmonary resuscitation (CPR). OBJECTIVES: This study sought to assess the relationship between gasping during out-of-hospital cardiac arrest and 1-year survival with favorable neurological outcomes. METHODS: The authors prospectively collected incidence of gasping on all evaluable subjects in a multicenter, randomized, controlled, National Institutes of Health-funded out-of-hospital cardiac arrest clinical trial from August 2007 to July 2009. The association between gasping and 1-year survival with favorable neurological function, defined as a Cerebral Performance Category (CPC) score ≤2 was estimated using multivariable logistic regression. RESULTS: The rates of 1-year survival with a CPC score of ≤2 were 5.4% (98 of 1,827) overall, and 20% (36 of 177) and 3.7% (61 of 1,643) for individuals with and without spontaneous gasping or agonal respiration during CPR, respectively. In multivariable analysis, 1-year survival with CPC ≤2 was independently associated with younger age (odds ratio [OR] for 1 SD increment 0.57; 95% confidence interval [CI]: 0.43 to 0.76), gasping during CPR (OR: 3.94; 95% CI: 2.09 to 7.44), shockable initial recorded rhythm (OR: 16.50; 95% CI: 7.40 to 36.81), shorter CPR duration (OR: 0.31; 95% CI: 0.19 to 0.51), lower epinephrine dosage (OR: 0.47; 95% CI: 0.25 to 0.87), and pulmonary edema (OR: 3.41; 95% CI: 1.53 to 7.60). Gasping combined with a shockable initial recorded rhythm had a 57-fold higher OR (95% CI: 23.49 to 136.92) of 1-year survival with CPC ≤2 versus no gasping and no shockable rhythm. CONCLUSIONS: Gasping during CPR was independently associated with increased 1-year survival with CPC ≤2, regardless of the first recorded rhythm. These findings underscore the importance of not terminating resuscitation prematurely in gasping patients and the need to routinely recognize, monitor, and record data on gasping in all future cardiac arrest trials and registries.


Assuntos
Inalação , Parada Cardíaca Extra-Hospitalar/mortalidade , Parada Cardíaca Extra-Hospitalar/fisiopatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Parada Cardíaca Extra-Hospitalar/complicações , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Taquicardia Ventricular/complicações , Fatores de Tempo , Fibrilação Ventricular/complicações , Adulto Jovem
12.
Am J Geriatr Psychiatry ; 25(9): 953-963, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28506605

RESUMO

OBJECTIVE: To characterize risk factors for and consequences of post-traumatic stress disorder (PTSD) among older adults evaluated in the emergency department (ED) following motor vehicle collision (MVC). DESIGN: Prospective multicenter longitudinal study (2011-2015). SETTING: 9 EDs across the United States. PARTICIPANTS: Adults aged 65 years and older who presented to an ED after MVC without severe injuries. MEASUREMENTS: PTSD symptoms were assessed 6 months after the ED visit using the Impact of Event Scale-Revised. RESULTS: Of 223 patients, clinically significant PTSD symptoms at 6 months were observed in 21% (95% CI 16%-26%). PTSD symptoms were more common in patients who did not have a college degree, had depressive symptoms prior to the MVC, perceived the MVC as life-threatening, had severe ED pain, and expected their physical or emotional recovery time to be greater than 30 days. Three factors (ED pain severity [0-10 scale], perceived life-threatening MVC [0-10 scale], and pre-MVC depressive symptoms [yes to either of two questions]), predicted 6-month PTSD symptoms with an area under the curve of 0.76. Compared to patients without PTSD symptoms, those with PTSD symptoms were at higher risk for persistent pain (72% versus 30%), functional decline (67% versus 42%), and new disability (49% versus 18%). CONCLUSIONS: Among older adults treated in the ED following MVC, clinically significant PTSD symptoms at 6 months were present in 21% of patients and were associated with adverse health outcomes. Increased risk for PTSD development can be identified with moderate accuracy using information readily available in the ED.


Assuntos
Acidentes de Trânsito/estatística & dados numéricos , Envelhecimento , Atitude Frente a Saúde , Depressão/epidemiologia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Dor/epidemiologia , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Acidentes de Trânsito/psicologia , Idoso , Envelhecimento/psicologia , Depressão/psicologia , Feminino , Seguimentos , Humanos , Masculino , Dor/etiologia , Dor/psicologia , Fatores de Risco , Transtornos de Estresse Pós-Traumáticos/psicologia
13.
Pain ; 158(2): 289-295, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28092325

RESUMO

Each year millions of Americans present to the emergency department (ED) for care after a motor vehicle collision (MVC); the majority (>90%) are discharged to home after evaluation. Acute musculoskeletal pain is the norm in this population, and such patients are typically discharged to home with prescriptions for oral opioid analgesics or nonsteroidal antiinflammatory drugs (NSAIDs). The influence of acute pain management on subsequent pain outcomes in this common ED population is unknown. We evaluated the effect of opioid analgesics vs NSAIDs initiated from the ED on the presence of moderate to severe musculoskeletal pain and ongoing opioid use at 6 weeks in a large cohort of adult ED patients presenting to the ED after MVC (n = 948). The effect of opioids vs NSAIDs was evaluated using an innovative quasi-experimental design method using propensity scores to account for covariate imbalances between the 2 treatment groups. No difference in risk for moderate to severe musculoskeletal pain at 6 weeks was observed between those discharged with opioid analgesics vs NSAIDs (risk difference = 7.2% [95% confidence interval: -5.2% to 19.5%]). However, at follow-up participants prescribed opioids were more likely than those prescribed NSAIDs to report use of prescription opioids medications at week 6 (risk difference = 17.5% [95% confidence interval: 5.8%-29.3%]). These results suggest that analgesic choice at ED discharge does not influence the development of persistent moderate to severe musculoskeletal pain 6 weeks after an MVC, but may result in continued use of prescription opioids. Supported by NIAMS R01AR056328 and AHRQ 5K12HS022998.


Assuntos
Acidentes de Trânsito/estatística & dados numéricos , Analgésicos Opioides/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Serviço Hospitalar de Emergência/estatística & dados numéricos , Dor/tratamento farmacológico , Dor/epidemiologia , Adolescente , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Autorrelato , Adulto Jovem
14.
Pain ; 158(4): 682-690, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28030471

RESUMO

Posttraumatic stress disorder (PTSD) symptoms and pain after traumatic events such as motor vehicle collision (MVC) have been proposed to be mutually promoting. We performed a prospective multicenter study that enrolled 948 individuals who presented to the emergency department within 24 hours of MVC and were discharged home after evaluation. Follow-up evaluations were completed 6 weeks, 6 months, and 1 year after MVC. Path analysis results supported the hypothesis that axial pain after MVC consistently promotes the maintenance of hyperarousal and intrusive symptoms, from the early weeks after injury through 1 year. In addition, path analysis results supported the hypothesis that one or more PTSD symptom clusters had an influence on axial pain outcomes throughout the year after MVC, with hyperarousal symptoms most influencing axial pain persistence in the initial months after MVC. The influence of hyperarousal symptoms on pain persistence was only present among individuals with genetic vulnerability to stress-induced pain, suggesting specific mechanisms by which hyperarousal symptoms may lead to hyperalgesia and allodynia. Further studies are needed to better understand the specific mechanisms by which pain and PTSD symptoms enhance one another after trauma, and how such mechanisms vary among specific patient subgroups, to better inform the development of secondary preventive interventions.


Assuntos
Acidentes de Trânsito/psicologia , Acidentes de Trânsito/estatística & dados numéricos , Dor/etiologia , Dor/psicologia , Transtornos de Estresse Pós-Traumáticos/etiologia , Adolescente , Adulto , Idoso , Análise Fatorial , Feminino , Técnicas de Genotipagem , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Dor/genética , Medição da Dor , Escalas de Graduação Psiquiátrica , Estudos Retrospectivos , Transtornos de Estresse Pós-Traumáticos/genética , Transtornos de Estresse Pós-Traumáticos/psicologia , Proteínas de Ligação a Tacrolimo/genética , Fatores de Tempo , Adulto Jovem
15.
J Orthop Sports Phys Ther ; 46(10): 911-919, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27690835

RESUMO

Study Design Prospective human cohort study combined with molecular studies. Background A microRNA is a small, noncoding RNA molecule that can play a role in disease onset. Recent studies found that circulating levels of microRNA 320a (miR-320a) are associated with musculoskeletal pain conditions and that miR-320a is stress responsive. Objectives To investigate whether circulating expression levels of miR-320a in the peritraumatic period predict persistent axial musculoskeletal pain 6 months after motor vehicle collision (MVC). Methods We evaluated whether (1) circulating miR-320a and related members of the miR-320a family predict axial musculoskeletal pain and other musculoskeletal pain outcomes 6 months following MVC, and (2) miR-320a regulates stress system and pain-related transcripts in cell culture. Given the wealth of data suggesting that biological mechanisms influencing pain outcomes are often sex and/or stress dependent, interactions between miR-320a, stress, and sex were evaluated. Results In primary analyses (n = 69), a significant crossover interaction was observed between the influence of circulating miR-320a and peritraumatic distress (ß = -0.01, P = .002) on post-MVC axial musculoskeletal pain. Reduced peritraumatic miR-320a expression levels predicted axial musculoskeletal pain in distressed individuals (ß = -0.12, P = .006) but not nondistressed individuals. In secondary analyses, miR-320a predicted widespread musculoskeletal pain, and related members of the miR-320a family also predicted axial and widespread musculoskeletal pain. In cell culture, miR-320a bound stress and pain-associated 3'UTR transcripts (FKBP5, ADCYAP1, PER2, and NR3C1). Conclusion These data suggest that miR-320a may help mediate regional and widespread changes in pain sensitivity after MVC. J Orthop Sports Phys Ther 2016;46(10):911-919. doi:10.2519/jospt.2016.6944.


Assuntos
Acidentes de Trânsito , MicroRNAs/sangue , Dor Musculoesquelética/diagnóstico , Cervicalgia/diagnóstico , Adulto , Feminino , Humanos , Masculino , Dor Musculoesquelética/etiologia , Cervicalgia/etiologia , Estudos Prospectivos
16.
BMJ Open ; 6(9): e012222, 2016 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-27601501

RESUMO

INTRODUCTION: A motor vehicle collision (MVC) is one of the most common life-threatening events experienced by individuals living in the USA. While most individuals recover following MVC, a significant proportion of individuals develop adverse post-traumatic sequelae such as post-traumatic stress disorder or persistent musculoskeletal pain. Adverse post-traumatic sequelae are common, morbid and costly public health problems in the USA and other industrialised countries. The pathogenesis of these disorders following MVC remains poorly understood. In the USA, available data suggest that African-Americans experience an increased burden of adverse post-traumatic sequelae after MVC compared to European Americans, but to date no studies examining the pathogenesis of these disorders among African-Americans experiencing MVC have been performed. METHODS AND ANALYSIS: The African-American CRASH (AA CRASH) study is an NIH-funded, multicentre, prospective study that enrols African-Americans (n=900) who present to the emergency department (ED) within 24 hours of MVC. Participants are enrolled at 13 ED sites in the USA. Individuals who are admitted to the hospital or who report a fracture or tissue injury are excluded. Participants complete a detailed ED interview that includes an assessment of crash history, current post-traumatic symptoms and health status prior to the MVC. Blood samples are also collected in the ED using PAXgene DNA and PAXgene RNA tubes. Serial mixed-mode assessments 6 weeks, 6 months and 1 year after MVC include an assessment of adverse sequelae, general health status and health service utilisation. The results from this study will provide insights into the incidence and pathogenesis of persistent pain and other post-traumatic sequelae in African-Americans experiencing MVC. ETHICS AND DISSEMINATION: AA CRASH has ethics approval in the USA, and the results will be published in a peer-reviewed journal.


Assuntos
Acidentes de Trânsito , Afro-Americanos , Dor Musculoesquelética/etnologia , Transtornos de Estresse Pós-Traumáticos/etnologia , Adulto , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Dor Musculoesquelética/etiologia , Medição da Dor , Aceitação pelo Paciente de Cuidados de Saúde/etnologia , Estudos Prospectivos , Projetos de Pesquisa , Transtornos de Estresse Pós-Traumáticos/etiologia , Fatores de Tempo , Estados Unidos , Adulto Jovem
17.
BMC Geriatr ; 16: 86, 2016 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-27094038

RESUMO

BACKGROUND: Restricted physical activity commonly occurs following acute musculoskeletal pain in older adults and may influence long-term outcomes. We sought to examine the relationship between restricted physical activity after motor vehicle collision (MVC) and the development of persistent pain. METHODS: We examined data from a prospective study of adults ≥65 years of age presenting to the emergency department (ED) after MVC without life-threatening injuries. Restricted physical activity 6 weeks after MVC was defined in three different ways: 1) by a ≥25 point decrease in Physical Activity Scale in the Elderly (PASE) score, 2) by the answer "yes" to the question, "during the past two weeks, have you stayed in bed for at least half a day?", and 3) by the answer "yes" to the question, "during the past two weeks, have you cut down on your usual activities as compared to before the accident?" We examined relationships between each definition of restricted activity and pain severity, pain interference, and functional capacity at 6 months with adjustment for confounders. RESULTS: Within the study sample (N = 164), adjusted average pain severity scores at 6 months did not differ between patients with and without restricted physical activity based on decreased PASE score (2.54 vs. 2.07, p = 0.32). In contrast, clinically and statistically important differences in adjusted average pain severity at 6 months were observed for patients who reported spending half a day in bed vs. those who did not (3.56 vs. 1.91, p < 0.01). In adjusted analyses, both decreased PASE score and cutting down on activity were associated with functional capacity at 6 months, but only decreased PASE score was associated with increased ADL difficulty at 6 months (0.70 vs. -0.01, p = 0.02). CONCLUSIONS: Among older adults experiencing MVC, those reporting bed rest or reduced activity 6 weeks after the collision reported higher pain and pain interference scores at 6 months. More research is needed to determine if interventions to promote activity can improve outcomes after MVC in older adults.


Assuntos
Acidentes de Trânsito/tendências , Limitação da Mobilidade , Atividade Motora , Veículos Automotores , Medição da Dor/tendências , Dor/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Serviço Hospitalar de Emergência/tendências , Feminino , Humanos , Estudos Longitudinais , Masculino , Atividade Motora/fisiologia , Dor/epidemiologia , Medição da Dor/métodos , Estudos Prospectivos
18.
Pain ; 157(2): 438-44, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26808013

RESUMO

Motor vehicle collision (MVC) can trigger chronic widespread pain (CWP) development in vulnerable individuals. Whether such CWP typically develops through the evolution of pain from regional to widespread or through the early development of widespread pain with nonrecovery is currently unknown. We evaluated the trajectory of CWP development (American College of Rheumatology criteria) among 948 European-American individuals who presented to the emergency department (ED) for care in the early aftermath of MVC. Pain extent was assessed in the ED and 6 weeks, 6 months, and 1 year after MVC on 100%, 91%, 89%, and 91% of participants, respectively. Individuals who reported prior CWP at the time of ED evaluation (n = 53) were excluded. Trajectory modeling identified a 2-group solution as optimal, with the Bayes Factor value (138) indicating strong model selection. Linear solution plots supported a nonrecovery model. Although the number of body regions with pain in the non-CWP group steadily declined, the number of body regions with pain in the CWP trajectory group (192/895, 22%) remained relatively constant over time. These data support the hypothesis that individuals who develop CWP after MVC develop widespread pain in the early aftermath of MVC, which does not remit.


Assuntos
Acidentes de Trânsito , Dor Crônica/complicações , Dor Crônica/etiologia , Serviço Hospitalar de Emergência , Adolescente , Adulto , Idoso , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/etiologia , Medição da Dor , Fatores de Risco , Transtornos de Estresse Pós-Traumáticos/etiologia , Adulto Jovem
19.
Ann Emerg Med ; 67(2): 166-176.e1, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26092559

RESUMO

STUDY OBJECTIVE: Motor vehicle crashes are the second most common form of trauma among older adults. We seek to describe the incidence, risk factors, and consequences of persistent pain among older adults evaluated in the emergency department (ED) after a motor vehicle crash. METHODS: We conducted a prospective longitudinal study of patients aged 65 years or older who presented to one of 8 EDs after motor vehicle crash between June 2011 and June 2014 and were discharged home after evaluation. ED evaluation was done through in-person interview; follow-up data were obtained through mail-in survey or telephone call. Pain severity (0 to 10 scale) overall and for 15 parts of the body were assessed at each follow-up point. Principal component analysis was used to assess the dimensionality of the locations of pain data. Participants reporting pain severity greater than or equal to 4 attributed to the motor vehicle crash at 6 months were defined as having persistent pain. RESULTS: Of the 161 participants, 72% reported moderate to severe pain at the ED evaluation. At 6 months, 26% of participants reported moderate to severe motor vehicle crash-related pain. ED characteristics associated with persistent pain included acute pain severity; pain located in the head, neck, and jaw or lower back and legs; poor self-rated health; less formal education; pre-motor vehicle crash depressive symptoms; and patient's expected time to physical recovery more than 30 days. Compared with individuals without persistent pain, those with persistent pain were substantially more likely at 6-month follow-up to have also experienced a decline in their capacity for physical function (73% versus 36%; difference=37%; 95% confidence interval [CI] 19% to 52%), a new difficulty with activities of daily living (42% versus 17%; difference=26%; 95% CI 10% to 43%), a 1-point or more reduction in overall self-rated health on a 5-point scale (54% versus 30%; difference=24%; 95% CI 6% to 41%), and a change in their living situation to obtain additional help (23% versus 8%; difference=15%; 95% CI 2% to 31%). CONCLUSION: Among older adults discharged home from the ED post-evaluation after a motor vehicle crash, persistent pain is common and frequently associated with functional decline and disability.


Assuntos
Acidentes de Trânsito , Dor/epidemiologia , Dor/etiologia , Idoso , Idoso de 80 Anos ou mais , Avaliação da Deficiência , Serviço Hospitalar de Emergência , Feminino , Avaliação Geriátrica , Humanos , Incidência , Escala de Gravidade do Ferimento , Entrevistas como Assunto , Estudos Longitudinais , Masculino , Medição da Dor , Alta do Paciente , Estudos Prospectivos , Fatores de Risco
20.
Pain ; 157(1): 273-9, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26447706

RESUMO

Musculoskeletal pain (MSP) is a common sequela of traumatic stress exposure. While biological factors contributing to chronic MSP after motor vehicle collision (MVC) have traditionally focused on tissue injury, increasing evidence suggests that neuro/stress/immune processes mediated by stress system activation may play a more dominant role. In a previous study, we found that genetic variants in the hypothalamic-pituitary-adrenal (HPA) axis-related gene FKBP5 influence vulnerability to persistent MSP 6 weeks after MVC. In the present cohort study (n = 855), we evaluated whether genetic variants in several other important HPA axis-related genes, including the glucocorticoid receptor (NR3C1), corticotropin-releasing hormone receptor R1 (CRHR1), and corticotropin-releasing hormone-binding protein (CRHBP), influence risk of chronic MSP over time after MVC. Genetic polymorphism rs7718461 in the CRHBP gene showed significant association (P = 0.0012) with overall pain severity during the year after MVC in regression models controlling for multiple comparisons. Two additional CRHBP alleles in high linkage disequilibrium with rs7718461 also showed trend-level significance. In secondary analyses, a significant interaction between this CRHBP locus (minor allele frequency = 0.33) and time was observed (P = 0.015), with increasing effect observed over time following trauma. A significant CRHBP × FKBP5 interaction was also observed, with substantially increased MSP after MVC in those with a risk allele in both genes compared with either gene alone. The results of this study indicate that genetic variants in 2 different HPA axis genes predict chronic MSP severity following MVC and support the hypothesis that the HPA axis is involved in chronic post-MVC MSP pathogenesis.


Assuntos
Acidentes de Trânsito , Proteínas de Transporte/genética , Dor Crônica/etiologia , Dor Musculoesquelética/etiologia , Adulto , Alelos , Dor Crônica/genética , Feminino , Frequência do Gene , Interação Gene-Ambiente , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Dor Musculoesquelética/genética , Polimorfismo de Nucleotídeo Único , Receptores de Hormônio Liberador da Corticotropina/genética , Receptores de Glucocorticoides/genética , Proteínas de Ligação a Tacrolimo/genética , Adulto Jovem
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