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1.
J Neurodev Disord ; 11(1): 19, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31426750

RESUMO

BACKGROUND: Children with neurodevelopmental disorders (NDDs) exhibit a shared phenotype that involves executive dysfunctions including impairments in mental flexibility (MF). It is of interest to understand if this phenotype stems from some shared neurobiology. METHODS: To investigate this possibility, we used magnetoencephalography (MEG) neuroimaging to compare brain activity in children (n = 88; 8-15 years) with autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD), as they completed a set-shifting/mental flexibility task. RESULTS: Neuroimaging results revealed a similar parietal activation profile across the NDD, groups suggesting a link to their shared phenotype. Differences in frontal activity differentiated the three clinical groups. Brain-behaviour analyses showed a link with repetitive behaviours suggesting shared dysfunction in the associative loop of the corticostriatal system. CONCLUSION: Our study supports the notion that NDDs may exist along a complex phenotypic/biological continuum. All NDD groups showed a sustained parietal activity profile suggesting that they share a strong reliance on the posterior parietal cortices to complete the mental flexibility task; future studies could elucidate whether this is due to delayed brain development or compensatory functioning. The differences in frontal activity may play a role in differentiating the NDDs. The OCD group showed sustained prefrontal activity that may be reflective of hyperfrontality. The ASD group showed reduced frontal activation suggestive of frontal dysfunction and the ADHD group showed an extensive hypoactivity that included frontal and parietal regions. Brain-behaviour analyses showed a significant correlation with repetitive behaviours which may reflect dysfunction in the associative loop of the corticostriatal system, linked to inflexible behaviours.

2.
Front Psychol ; 9: 1960, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30369900

RESUMO

During speech, how does the brain integrate information processed on different timescales and in separate brain areas so we can understand what is said? This is the language binding problem. Dynamic functional connectivity (brief periods of synchronization in the phase of EEG oscillations) may provide some answers. Here we investigate time and frequency characteristics of oscillatory power and phase synchrony (dynamic functional connectivity) during speech comprehension. Twenty adults listened to meaningful English sentences and non-sensical "Jabberwocky" sentences in which pseudo-words replaced all content words, while EEG was recorded. Results showed greater oscillatory power and global connectivity strength (mean phase lag index) in the gamma frequency range (30-80 Hz) for English compared to Jabberwocky. Increased power and connectivity relative to baseline was also seen in the theta frequency range (4-7 Hz), but was similar for English and Jabberwocky. High-frequency gamma oscillations may reflect a mechanism by which the brain transfers and integrates linguistic information so we can extract meaning and understand what is said. Slower frequency theta oscillations may support domain-general processing of the rhythmic features of speech. Our findings suggest that constructing a meaningful representation of speech involves dynamic interactions among distributed brain regions that communicate through frequency-specific functional networks.

3.
Clin Neurophysiol ; 129(12): 2642-2649, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30150028

RESUMO

OBJECTIVES: The objective of this study was to review our experience with intra-operative "train of five" stimulation using subdural grid for motor mapping in children undergoing epilepsy surgery evaluation. METHODS: Twenty consecutive children below 18-years of age with drug-refractory epilepsy who underwent invasive-EEG monitoring using subdural-grid placement and intra-operative motor mapping using direct cortical stimulation by sub-dural grid electrodes (IODCS-SDG) at our institution between January-2016 and June-2017 were reviewed. Stimulation was delivered through the subdural-grid electrodes using a train-of-five pulses and muscle responses were recorded by motor-evoked-potentials (MEPs). Intra-operative direct cortical stimulation delivered through a ball-tipped probe (IODCS-probe) and extra-operative motor-mapping (EODCS-SDG) were also performed. RESULTS: IODCS-SDG was completed in 20 patients and subsequent EODCS-SDG was done in 17/20 patients. MEP responses were more commonly obtained in the deltoid (19/20), extensor-digitorum-communis (20/20) and first-dorsal-interosseus (19/20). The median thresholds varied between 40 V and 60 V for the six muscle groups. The respective IODCS-probe thresholds tended to be similar. No stimulation-provoked seizures or anaesthesia-related complications were noted during IODCS-SDG. EODCS-SDG could not be completed in 4/17 children and mapping data obtained was frequently inadequate. Nine patients demonstrated 100% concordance between IODCS-SDG and EODCS-SDG for the common mapped body regions. Stimulation-provoked seizures during EODCS-SDG were seen in 6/17 (35.3%) and after-discharges in 7/17 (41.2%) children. CONCLUSIONS: IODCS-SDG could be performed safely in children with drug refractory epilepsy undergoing invasive EEG monitoring. SIGNIFICANCE: IODCS-SDG may be a useful adjunct to EODCS-SDG in motor mapping for children.


Assuntos
Eletroencefalografia/métodos , Epilepsia/cirurgia , Monitorização Neurofisiológica Intraoperatória/métodos , Córtex Motor/cirurgia , Espaço Subdural/cirurgia , Adolescente , Criança , Pré-Escolar , Eletrodos/efeitos adversos , Eletroencefalografia/instrumentação , Feminino , Humanos , Monitorização Neurofisiológica Intraoperatória/instrumentação , Masculino , Córtex Motor/fisiopatologia , Estimulação Transcraniana por Corrente Contínua/instrumentação , Estimulação Transcraniana por Corrente Contínua/métodos
4.
Epilepsy Behav ; 87: 83-88, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30131223

RESUMO

OBJECTIVE: Limited evidence on the relationship between antiepileptic drug (AED) tapering and the likelihood of a seizure during an Epilepsy Monitoring Unit (EMU) admission is available, and no evidence specific to the pediatric population has been published. Our study sought to determine whether AED tapering leads to increased seizure likelihood in a pediatric EMU setting. METHODS: We performed a retrospective chart review of children admitted to the pediatric EMU at the Hospital for Sick Children in Toronto between June 1, 2014 and June 1, 2016. Data collected included demographics, reason for EMU referral, and epilepsy and medical characteristics. Among those with nondaily seizures, Kaplan-Meier curves were fit to compare probability of EMU seizure in those who were tapered fully from at least one AED to those not tapered. A Cox proportional hazards model was fit to evaluate this relationship after adjustment for subject sex, distance traveled to hospital, epilepsy duration, seizure frequency, time since last seizure, whether EMU referral was part of presurgical planning, magnetic resonance imaging (MRI) findings, and number of prescribed AEDs. An interaction between medication taper and number of prescribed AEDs was also included. Terms not significant at p < 0.3 were removed from the model, and the reduced model was recomputed. RESULTS: Of the 281 children included in the study, 159 had nondaily seizures. Kaplan-Meier curves indicated fully tapering at least one AED was associated with increased likelihood of seizure during EMU; however, after adjustment for confounding variables, this association was not preserved. Abnormal MRI findings, referral for presurgical evaluation, and shorter (≤3 months) time since last seizure were associated with increased likelihood of seizure during EMU. SIGNIFICANCE: Short-term AED tapering in pediatric patients may not be effective for increasing seizure likelihood in the EMU.


Assuntos
Anticonvulsivantes/administração & dosagem , Monitoramento de Medicamentos/métodos , Epilepsia/diagnóstico por imagem , Epilepsia/tratamento farmacológico , Unidades Hospitalares , Adolescente , Criança , Pré-Escolar , Esquema de Medicação , Monitoramento de Medicamentos/tendências , Feminino , Unidades Hospitalares/tendências , Hospitalização/tendências , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Estudos Retrospectivos , Convulsões/diagnóstico por imagem , Convulsões/tratamento farmacológico , Resultado do Tratamento
5.
Epilepsy Res ; 145: 123-126, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29957568

RESUMO

OBJECTIVES: The risk of drowning is reported to be 15-19 times greater in people with epilepsy compared to the general population. Despite this disproportionate burden, there is limited data about the circumstances surrounding drowning deaths in people with epilepsy. This population-based case series characterizes drowning deaths in people with epilepsy. METHODS: Postmortem data from coroner-ordered autopsies conducted in Ontario between 2014 and 2016 were screened for cases of drowning in people with a history of seizures. Demographic information, epilepsy characteristics, and circumstances surrounding death were extracted from post mortem reports. The incidence of drowning in people with epilepsy was calculated using government estimates of the Ontario population and the number of people with epilepsy. RESULTS: Twenty-five people with epilepsy drowned during the three-year study period, giving an estimated incidence of 1.5 per 10,000 epilepsy person-years (95% CI: 0.98, 2.23). Decedents were mostly young (mean age 36 years) and without physical or developmental disability. Approximately one-third had psychiatric comorbidities. Epilepsy severity ranged from well-controlled to drug refractory. Only 3 people had alcohol or illicit drugs detected on toxicological analysis. Forty-four percent of deaths were the result of an unwitnessed drowning in a bathtub. CONCLUSIONS: This population-based case series confirms people with epilepsy drown at a rate nearly ten times greater than the general population (1.5 per 10,000 epilepsy person-years compared to the estimated provincial average of 0.13 per 10,000). Drowning deaths in people with epilepsy most often occur in the bathtub. These deaths are only rarely associated with intoxication. People with epilepsy should receive counseling on the increased risk of drowning, including information regarding the significant risk associated with bathtub use, the potential protective roles of anti-epileptic drug (AED) adherence and supervision when in or around water, and the fact that all people with epilepsy remain at an increased risk of drowning regardless of their apparent seizure control.


Assuntos
Afogamento/epidemiologia , Epilepsia/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Criança , Planejamento em Saúde Comunitária , Diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
6.
Neurology ; 91(2): e107-e111, 2018 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-29884734

RESUMO

OBJECTIVE: To determine the incidence of sudden unexpected death in epilepsy (SUDEP) in children in Ontario, Canada. METHODS: Cases of suspected pediatric SUDEP occurring between January 1, 2014, and December 31, 2015, in Ontario, Canada, were eligible for inclusion. Potential cases were identified through 3 sources: a national pediatrician surveillance program, child neurologist report, and screening of provincial forensic autopsies. Cases were classified as definite, definite plus, probable, possible, and near/near plus according to criteria described by Nashef et al. (Epilepsia 2012). Overall crude pediatric SUDEP incidence and the incidence of definite or probable pediatric SUDEP were calculated using estimates of the prevalence of pediatric epilepsy in Canada drawn from government survey data and the number of children living in Ontario. Capture-recapture analysis was used to estimate the number of missing cases and determine an adjusted definite/probable SUDEP incidence. RESULTS: Seventeen cases of pediatric SUDEP resulted in an overall incidence of 1.17 (95% confidence interval 0.68-1.88) per 1,000 pediatric epilepsy person-years. The definite/probable incidence, including definite (n = 11), definite plus (n = 2), or probable (n = 3) SUDEP cases, was 1.11 (0.63-1.79). Capture-recapture analysis indicated an estimated 21 (16-39) definite/probable SUDEP cases occurred during the study period, giving an adjusted incidence of definite/probable SUDEP of 1.45 (0.90-2.22) per 1,000 pediatric epilepsy person-years. CONCLUSION: SUDEP may be more common in children than widely reported, with the incidence rate of definite/probable SUDEP in children being similar to rates reported in adults.


Assuntos
Morte Súbita/epidemiologia , Epilepsia/epidemiologia , Adolescente , Criança , Pré-Escolar , Epilepsia/mortalidade , Feminino , Humanos , Incidência , Lactente , Masculino , Ontário/epidemiologia
7.
Oncoimmunology ; 7(4): e1303584, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29632710

RESUMO

VXM01 is a first-in-kind orally applied tumor vaccine based on live attenuated Salmonella typhi carrying an expression plasmid encoding VEGFR2, an antigen expressed on tumor vasculature and a stable and accessible target for anti-angiogenic intervention. A recent randomized, placebo-controlled, phase I dose-escalation trial in advanced pancreatic cancer patients demonstrated safety, immunogenicity and transient, T-cell response-related anti-angiogenic activity of four priming vaccinations applied within one week. We here evaluated whether monthly boost vaccinations are safe and can sustain increased frequencies of vaccine-specific T cells. Patients with advanced pancreatic cancer were randomly assigned at a ratio of 2:1 to priming with VXM01 followed by up to six monthly boost vaccinations, or placebo treatment. Vaccinations were applied orally at two alternative doses of either 106 colony-forming units (CFU) or 107 CFU, and concomitant treatment with standard-of-care gemcitabine during the priming phase, and any treatment thereafter, was allowed in the study. Immunomonitoring involved interferon-gamma (IFNγ) ELIspot analysis with long overlapping peptides spanning the entire VEGFR2 sequence. A total of 26 patients were treated. Treatment-related adverse events preferentially associated with VXM01 were decreases in lymphocyte numbers in the blood, increased frequencies of neutrophils and diarrhea. Eight out of 16 patients who received at least one boosting vaccination responded with pronounced, i.e. at least 3-fold, increase in VEGFR2-specific T cell response over baseline levels. In the VXM01 vaccination group, VEGFR2-specific T cells peaked preferentially during the boosting phase with an average 4-fold increase over baseline levels. In conclusion, prime/boost vaccination with VXM01 was safe and immunogenic and increased vaccine specific T cell responses compared with placebo treatment.

8.
Hum Brain Mapp ; 39(7): 2907-2916, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29573366

RESUMO

Emotion regulation mediates socio-cognitive functions and is essential for interactions with others. The capacity to automatically inhibit responses to emotional stimuli is an important aspect of emotion regulation; the underlying neural mechanisms of this ability have been rarely investigated. Forty adults completed a Go/No-go task during magnetoencephalographic (MEG) recordings, where they responded rapidly to either a blue or purple frame which contained angry or happy faces. Subjects responded to the target color in an inhibition (75% Go trials) and a vigilance condition (25% Go trials). As expected, inhibition processes showed early, sustained activation (200-450 ms) in the right inferior frontal gyrus (IFG). Emotion-related inhibition processes showed greater activity with angry faces bilaterally in the orbital-frontal gyri (OFG) starting at 225 ms and temporal poles from 250 ms, with right hemisphere dominance. The presence of happy faces elicited earlier activity in the right OFG. This study demonstrates that the timing of inhibition processes varies with the emotional context and that there is much greater activation in the presence of angry faces. It underscores the importance of the right IFG for inhibition processes, but the OFG in automatic emotion regulation.


Assuntos
Emoções/fisiologia , Função Executiva/fisiologia , Reconhecimento Facial/fisiologia , Neuroimagem Funcional/métodos , Magnetoencefalografia/métodos , Córtex Pré-Frontal/fisiologia , Autocontrole , Percepção Social , Adulto , Feminino , Humanos , Masculino , Córtex Pré-Frontal/diagnóstico por imagem , Adulto Jovem
9.
Brain Cogn ; 120: 58-66, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29065995

RESUMO

Mental flexibility is a core property of cognitive executive functions, relying on an extended frontoparietal network in the brain. fMRI research comparing typically developing children and adults has found that children from an early age recruit the same "classic" brain areas associated with mental flexibility as adults; however, there is evidence that the timing of activation may be different. To investigate the temporal dynamics of brain activity associated with mental flexibility in children, we recruited 22 typically developing children (8-15 years) to complete a set-shifting task in the MEG. Our results showed that while the children relied on the same frontoparietal network of mental flexibility, there was a different emphasis on active brain regions, with children preferentially using their posterior parietal cortices. Additional areas such as the temporal pole and the premotor areas were also recruited, potentially playing a supporting role. Although children shared the same window of peak activity as adults, 75-350ms, we found a significant decrease in activation latency with increasing age, suggesting the presence of developmental differences in timing of brain activity in areas supporting mental flexibility during childhood.


Assuntos
Mapeamento Encefálico/métodos , Desenvolvimento Infantil/fisiologia , Função Executiva/fisiologia , Magnetoencefalografia/métodos , Lobo Parietal/fisiologia , Desempenho Psicomotor/fisiologia , Adolescente , Criança , Feminino , Humanos , Masculino
10.
BMC Musculoskelet Disord ; 18(1): 145, 2017 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-28376754

RESUMO

BACKGROUND: Evidence is lacking on whether fat infiltration in the multifidus muscles affects outcomes after total disc replacement (TDR) surgery and if it develops after surgery. The aims of this study were 1) to investigate whether pre-treatment multifidus muscle fat infiltration predicts outcome 2 years after treatment with TDR surgery or multidisciplinary rehabilitation, and 2) to compare changes in multifidus muscle fat infiltration from pre-treatment to 2-year follow-up between the two treatment groups. METHODS: The study is secondary analysis of data from a trial with 2-year follow-up of patients with chronic low back pain (LBP) and degenerative disc randomized to TDR surgery or multidisciplinary rehabilitation. We analyzed (aim 1) patients with both magnetic resonance imaging (MRI) at pre-treatment and valid data on outcome measures at 2-year follow-up (predictor analysis), and (aim 2) patients with MRI at both pre-treatment and 2-year follow-up. Outcome measures were visual analogue scale (VAS) for LBP, Oswestry Disability Index (ODI), work status and muscle fat infiltration on MRI. Patients with pre-treatment MRI and 2-year outcome data on VAS for LBP (n = 144), ODI (n = 147), and work status (n = 137) were analyzed for prediction purposes. At 2-year follow-up, 126 patients had another MRI scan, and change in muscle fat infiltration was compared between the two treatment groups. Three radiologists visually quantified multifidus muscle fat in the three lower lumbar levels on MRI as <20% (grade 0), 20-50% (grade 1), or >50% (grade 2) of the muscle cross-section containing fat. Regression analysis and a mid-P exact test were carried out. RESULTS: Grade 0 pre-treatment multifidus muscle fat predicted better clinical results at 2-year follow-up after TDR surgery (all outcomes) but not after rehabilitation. At 2-year follow-up, increased fat infiltration was more common in the surgery group (intention-to-treat p = 0.03, per protocol p = 0.08) where it was related to worse pain and ODI. CONCLUSIONS: Patients with less fat infiltration of multifidus muscles before TDR surgery had better outcomes at 2-year follow-up, but findings also indicated a negative influence of TDR surgery on back muscle morphology in some patients. The rehabilitation group maintained their muscular morphology and were unaffected by pre-treatment multifidus muscle fat. TRIAL REGISTRATION: NCT 00394732 (retrospectively registered October 31, 2006).


Assuntos
Adiposidade , Degeneração do Disco Intervertebral/patologia , Vértebras Lombares/cirurgia , Músculos Paraespinais/patologia , Substituição Total de Disco , Adulto , Feminino , Seguimentos , Humanos , Degeneração do Disco Intervertebral/reabilitação , Degeneração do Disco Intervertebral/cirurgia , Masculino , Pessoa de Meia-Idade
11.
PLoS One ; 12(2): e0171548, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28182642

RESUMO

BACKGROUND: Parastomal hernia (PH) is the most common complication after ostomy formation. Prophylactic mesh placement may be effective in reducing the rate of PH at the stoma site. The aims of this systematic review were to summarize the evidence with regard to the safety and effectiveness in comparison with the standard procedure without mesh placement and to identify important risk constellations. METHOD: A systematic literature search was performed in PubMed, EMBASE and the Cochrane library with no language or date restrictions. Randomized (RCTs) and non-randomized controlled trials (nRCTs) were included. The main outcomes of interest were PH (primary outcome) rate and stoma-related complications (secondary outcomes) such as stenosis or fistula. Statistical analysis included meta-analyses of pooled data and subgroup analyses. RESULTS: Eleven trials (eight RCTs; three nRCTs) with a total of 755 patients were included. PH rate varied from 0% to 59% in the intervention and from 20% to 94% in the control group. RCTs showed a significant reduction of PH rate in the mesh group (OR 0.24; 95% CI 0.10 to 0.58, p = 0.034), whereas included nRCTs did not. No significant differences were observed in postoperative complication rates. Subgroup analyses showed superiority of non-absorbable meshes and sublay mesh positioning in open surgery. CONCLUSION: Prophylactic mesh placement is safe and reduces PH rate. A recommendation for prophylactic non-absorbable meshes in a sublay position can be made for patients undergoing open colorectal operations with end-ostomies. Further research endeavors should focus on patient-oriented outcomes, not only PH rate, with respect to tailored treatment in specific patient populations.


Assuntos
Hérnia/prevenção & controle , Estomia/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Telas Cirúrgicas/efeitos adversos , Estudos de Casos e Controles , Hérnia/epidemiologia , Humanos , Estomia/métodos , Complicações Pós-Operatórias/epidemiologia , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
Stroke ; 47(10): 2503-10, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27531345

RESUMO

BACKGROUND AND PURPOSE: Neurocognitive deficits are common among survivors of aneurysmal subarachnoid hemorrhage, even among those with good outcomes and no structural lesions. This study aims to probe the neurophysiological underpinnings of cognitive dysfunction among patients with ruptured intracranial aneurysms using magnetoencephalography (MEG). METHODS: Thirteen patients who had undergone uncomplicated coiling for aneurysmal subarachnoid hemorrhage and 13 matched controls were enrolled. Neuropsychological tests were done before magnetoencephalography scans. Magnetoencephalography data were acquired in a 151-channel, whole-head magnetoencephalography system for resting state and 2 cognitive tasks (go-no-go and set-shifting). Mean time from treatment to test was 18.8 months. RESULTS: Cognitive tasks of inhibition (go-no-go) indicated greater activation in the right anterior cingulate and inferior frontal gyrus, and cognitive set-shifting tasks (mental flexibility) indicated greater activity in the bilateral anterior cingulate cortex and right medial frontal gyrus among aneurysmal subarachnoid hemorrhage patients, with significantly different timing of activation between groups. Resting-state, beta-band connectivity of the anterior cingulate correlated negatively with Montreal Cognitive Assessment scores (left: r=-0.56; P<0.01 and right: r=-0.55; P<0.01): higher connectivity of this region was linked to poorer cognitive test performance. CONCLUSIONS: We have shown increased activation in areas of the anterior cingulate gyrus and frontobasal regions during the execution of more demanding tasks in good grade. The degree of activation in the anterior cingulate gyrus has a negative correlation with cognitive (Montreal Cognitive Assessment) scores. These subtle differences may be related to the common neurocognitive and behavioral complaints seen in this patient population.


Assuntos
Encéfalo/diagnóstico por imagem , Cognição/fisiologia , Disfunção Cognitiva/diagnóstico por imagem , Hemorragia Subaracnóidea/diagnóstico por imagem , Adulto , Idoso , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/psicologia , Feminino , Humanos , Magnetoencefalografia , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/psicologia
13.
Oncoimmunology ; 4(4): e1001217, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26137397

RESUMO

VEGFR-2 is expressed on tumor vasculature and a target for anti-angiogenic intervention. VXM01 is a first in kind orally applied tumor vaccine based on live, attenuated Salmonella bacteria carrying an expression plasmid, encoding VEGFR-2. We here studied the safety, tolerability, T effector (Teff), T regulatory (Treg) and humoral responses to VEGFR2 and anti-angiogenic effects in advanced pancreatic cancer patients in a randomized, dose escalation phase I clinical trial. Results of the first 3 mo observation period are reported. Locally advanced or metastatic, pancreatic cancer patients were enrolled. In five escalating dose groups, 30 patients received VXM01 and 15 placebo on days 1, 3, 5, and 7. Treatment was well tolerated at all dose levels. No dose-limiting toxicities were observed. Salmonella excretion and salmonella-specific humoral immune responses occurred in the two highest dose groups. VEGFR2 specific Teff, but not Treg responses were overall increased in vaccinated patients. We furthermore observed a significant reduction of tumor perfusion after 38 d in vaccinated patients together with increased levels of serum biomarkers indicative of anti-angiogenic activity, VEGF-A, and collagen IV. Vaccine specific Teff responses significantly correlated with reductions of tumor perfusion and high levels of preexisting VEGFR2-specific Teff while those showing no antiangiogenic activity had low levels of preexisting VEGFR2 specific Teff, showed a transient early increase of VEGFR2-specific Treg and reduced levels of VEGFR2-specific Teff at later time points - pointing to the possibility that early anti-angiogenic activity might be based at least in part on specific reactivation of preexisting memory T cells.

14.
Spine (Phila Pa 1976) ; 39(24): 1999-2006, 2014 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-25271499

RESUMO

STUDY DESIGN: Multicenter randomized trial with patients listed as sick for 1 to 12 months due to neck or back pain and referred to secondary care. OBJECTIVE: To compare the return-to-work (RTW) rate among patients offered work-focused rehabilitation or multidisciplinary rehabilitation. SUMMARY OF BACKGROUND DATA: A growing number of studies have focused on the RTW processes associated with patients with back pain. Many studies have combined a workplace focus with multidisciplinary treatments; however, this focus has not been evaluated in Norway among patients with neck and back pain thus far. METHODS: A total of 405 patients who were referred to the spine clinics at 2 university hospitals in Norway were randomly assigned into work-focused and control intervention groups. The existing treatments at each hospital were used as the control interventions, which entailed either a comprehensive multidisciplinary intervention or a brief multidisciplinary intervention. The RTW rates and proportions were compared at 12 months. RESULTS: During the first 12 months after inclusion, 142 (70%) participants in the work-focused rehabilitation group and 152 (75%) participants in the control group returned to work. The median time to RTW was 161 days in the work-focused group and 158 days in the control group. A comparison of the work-focused and control interventions revealed a relative RTW probability (hazard ratio) of 0.94 (95% confidence interval = 0.75-1.17) after adjusting for age, sex, and education. CONCLUSION: The results suggest that a focus on the workplace in specialist care does not substantially alter the RTW rate compared with standard multidisciplinary treatments.


Assuntos
Dor nas Costas/reabilitação , Cervicalgia/reabilitação , Retorno ao Trabalho , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reabilitação/métodos , Licença Médica , Fatores de Tempo
15.
Front Cell Neurosci ; 8: 174, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24987335

RESUMO

A growing number of studies indicate that 3-alpha reduced neurosteroids are remarkable analgesics in various pain states. This is the case for allopregnanolone (AP), one of the most potent endogenous positive allosteric modulators of GABAA receptor function. From the pioneering work of Hans Selye, who described the sedative properties of steroids, synthetic compounds resembling the progesterone metabolite AP have been developed. If some of them have been used as anesthetics, it seems difficult to propose them as a therapeutic option for pain since they display several adverse side effects such as sedation, amnesia and functional tolerance. An alternative strategy, chosen by few laboratories around the world, is aimed at stimulating the local production of 3-alpha reduced neurosteroids in order to limit these well-known side effects. This pharmacological approach has the advantage of targeting specific structures, fully equipped with the necessary biosynthetic enzymatic machinery, where neurosteroids already act as endogenous pain modulators. The various pharmacological trials which attempted to treat pain symptoms by stimulating the production of 3-alpha reduced neurosteroids are reviewed here, as well as novel neurotransmitter systems possibly regulating their endogenous production.

16.
BMC Musculoskelet Disord ; 14: 329, 2013 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-24261336

RESUMO

BACKGROUND: Neck and back pain are common and often account for absenteeism at work. Factors at work as well as fear-avoidance beliefs may influence sick-leave in these patients. The aims of this study were to assess: (1) how sick-listed patients in specialised care perceive demand, control, support, effort, reward, and overcommitment at work compared to a general reference group of workers; (2) if women and men report demand, control, support, effort, reward, and overcommitment differently; and (3) the association between psychological and social factors at work and fear-avoidance beliefs about work. METHODS: A cross-sectional multicentre study was carried out in 373 patients on sick leave due to neck and back pain. Psychosocial work factors were measured by demand, control, and support, (Nordic Questionnaire for Psychological and Social Factors at Work), and effort, reward and overcommitment (Effort Reward Imbalance Questionnaire). Fear avoidance beliefs about work were measured by the Fear-Avoidance Belief Questionnaire Work subscale (FABQ-W). RESULTS: Although the patients differed significantly from a reference working group regarding several subscales of demand, control, support, effort, reward, and overcommitment, the magnitude of these differences were small. The study population also reported significantly higher scores for 'demand for physical endurance' than the reference population, and Cohen's d = 0.55 here indicated a medium degree of difference. Female patients reported significantly higher on support, whereas male patients reported significantly higher demand for physical endurance, quantitative demand, effort, and overcommitment. Demand for physical endurance, job control, job support, high reward, and overcommitment were significantly associated with FABQ-W. CONCLUSIONS: Perceived psychological and social factors at work were strongly associated with fear-avoidance beliefs about work in sick-listed neck and back patients. The demand for physical endurance, control, support, high reward, as well as overcommittment at work outweighed pain and added to the burden of emotional distress and disability regarding fear-avoidance beliefs.


Assuntos
Absenteísmo , Dor nas Costas/psicologia , Medo , Comportamentos Relacionados com a Saúde , Conhecimentos, Atitudes e Prática em Saúde , Cervicalgia/psicologia , Percepção , Licença Médica , Local de Trabalho/psicologia , Adulto , Dor nas Costas/diagnóstico , Dor nas Costas/terapia , Estudos Transversais , Cultura , Avaliação da Deficiência , Emoções , Feminino , Humanos , Descrição de Cargo , Masculino , Pessoa de Meia-Idade , Cervicalgia/diagnóstico , Cervicalgia/terapia , Noruega , Medição da Dor , Resistência Física , Recompensa , Apoio Social , Inquéritos e Questionários
17.
Spine J ; 13(12): 1849-57, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24060231

RESUMO

BACKGROUND CONTEXT: Little is known about the prognostic factors for work-related outcomes of sciatica caused by disc herniation. PURPOSE: To identify the prognostic factors for return to work (RTW) during a 2-year follow-up among sciatica patients referred to secondary care. STUDY DESIGN/SETTING: Multicenter prospective cohort study including 466 patients. Administrative data from the National Sickness Benefit Register were accessed for 227 patients. PATIENT SAMPLE: Two samples were used. Sample A comprised patients who at the time of inclusion in the cohort reported being on partial sick leave or complete sick leave or were undergoing rehabilitation because of back pain/sciatica. Sample B comprised patients who, according to the sickness benefit register, at the time of inclusion received sickness benefits or rehabilitation allowances because of back pain/sciatica. OUTCOME MEASURES: In Sample A, the outcome was self-reported return to full-time work at the 2-year follow-up. In Sample B, the outcome was time to first sustained RTW, defined as the first period of more than 60 days without receiving benefits from the register. METHODS: Significant baseline predictors of self-reported RTW at 2 years (Analysis A) were identified by multivariate logistic regression. Significant predictors of time to sustained RTW (Analysis B) were identified by multivariate Cox proportional hazard modeling. Both analyses included adjustment for age and sex. To assess the effect of surgery on the probability of RTW, analyses similar to A and B were performed, including the variable surgery (yes/no). RESULTS: One-fourth of the patients were still out of work at the 2-year follow-up. In Sample A (n=237), younger age, better general health, lower baseline sciatica bothersomeness, less fear-avoidance work, and a negative straight-leg-raising test result were significantly associated with a higher probability of RTW at the 2-year follow-up. Surgery was not significantly associated with the outcome. In Sample B (n=125), history of sciatica, duration of the current sciatica episode more than 3 months, greater sciatica bothersomeness, fear-avoidance work, and back pain were significantly associated with a longer time to sustained RTW. Surgery was significantly negatively associated with time to sustained RTW both in univariate (hazard ratio [HR] 0.60; 95% confidence interval [CI] 0.39, 0.93; p=.02) and in multivariate (HR 0.49; 95% CI 0.31, 0.79; p=.003) analyses. CONCLUSIONS: The baseline factors associated with RTW identified in multivariate analysis were age, general health, history of sciatica, duration of the current episode, baseline sciatica bothersomeness, fear-avoidance work, back pain, and the straight-leg-raising test result. Surgical treatment was associated with slower RTW, but surgical patients were more severely affected than patients treated without surgery; so, this finding should be interpreted with caution.


Assuntos
Avaliação da Deficiência , Deslocamento do Disco Intervertebral/complicações , Deslocamento do Disco Intervertebral/reabilitação , Retorno ao Trabalho/estatística & dados numéricos , Ciática/etiologia , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Licença Médica/estatística & dados numéricos
18.
BMC Musculoskelet Disord ; 13: 183, 2012 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-22999108

RESUMO

BACKGROUND: Few studies have investigated prognostic factors for patients with sciatica, especially for patients treated without surgery. The aim of this study was to identify factors associated with non-success after 1 and 2 years of follow-up and to test the prognostic value of surgical treatment for sciatica. METHODS: The study was a prospective multicentre observational study including 466 patients with sciatica and lumbar disc herniation. Potential prognostic factors were sociodemographic characteristics, back pain history, kinesiophobia, emotional distress, pain, comorbidity and clinical examination findings. Study participation did not alter treatment considerations for the patients in the clinics. Patients reported on the questionnaires if surgery of the disc herniation had been performed. Uni- and multivariate logistic regression analyses were used to evaluate factors associated with non-success, defined as Maine-Seattle Back Questionnaire score of ≥5 (0-12) (primary outcome) and Sciatica Bothersomeness Index ≥7 (0-24) (secondary outcome). RESULTS: Rates of non-success were at 1 and 2 years 44% and 39% for the main outcome and 47% and 42% for the secondary outcome. Approximately 1/3 of the patients were treated surgically. For the main outcome variable, in the final multivariate model non-success at 1 year was significantly associated with being male (OR 1.70 [95% CI; 1.06 - 2.73]), smoker (2.06 [1.31 - 3.25]), more back pain (1.0 [1.01 - 1.02]), more comorbid subjective health complaints (1.09 [1.03 - 1.15]), reduced tendon reflex (1.62 [1.03 - 2.56]), and not treated surgically (2.97 [1.75 - 5.04]). Further, factors significantly associated with non-success at 2 years were duration of back problems >; 1 year (1.92 [1.11 - 3.32]), duration of sciatica >; 3 months (2.30 [1.40 - 3.80]), more comorbid subjective health complaints (1.10 [1.03 - 1.17]) and kinesiophobia (1.04 [1.00 - 1.08]). For the secondary outcome variable, in the final multivariate model, more comorbid subjective health complaints, more back pain, muscular weakness at clinical examination, and not treated surgically, were independent prognostic factors for non-success at both 1 and 2 years. CONCLUSIONS: The results indicate that the prognosis for sciatica referred to secondary care is not that good and only slightly better after surgery and that comorbidity should be assessed in patients with sciatica. This calls for a broader assessment of patients with sciatica than the traditional clinical assessment in which mainly the physical symptoms and signs are investigated.


Assuntos
Ciática/cirurgia , Adulto , Distribuição de Qui-Quadrado , Comorbidade , Feminino , Humanos , Degeneração do Disco Intervertebral/complicações , Degeneração do Disco Intervertebral/diagnóstico , Degeneração do Disco Intervertebral/cirurgia , Deslocamento do Disco Intervertebral/complicações , Deslocamento do Disco Intervertebral/diagnóstico , Deslocamento do Disco Intervertebral/cirurgia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Noruega , Razão de Chances , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Ciática/etiologia , Inquéritos e Questionários , Fatores de Tempo , Falha de Tratamento
19.
Spine (Phila Pa 1976) ; 37(25): 2063-73, 2012 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-22706091

RESUMO

STUDY DESIGN: Randomized clinical trial with 2-year follow-up. OBJECTIVE: To assess the development of adjacent level degeneration (ALD) and index level facet arthropathy (FA) in patients treated with disc prosthesis compared with patients treated with rehabilitation. SUMMARY OF BACKGROUND DATA: There is controversy about the natural history of disc degeneration and the development of ALD and FA in patients who undergo disc prosthesis surgery. METHODS: The study included 116 patients with a history of low back pain for at least 1 year, Oswestry Disability Index 30 points or more, and degenerative changes in 1 or 2 lower lumbar spine levels. Magnetic resonance imaging was performed before treatment and at the 2-year follow-up. ALD and index level FA were determined on the basis of the majority assessment of 3, independent, experienced radiologists. ALD was assessed by evaluating Modic changes, posterior high intensity zone in the disc, nucleus pulposus signal, disc height, disc contour, and FA. Data were analyzed with Fischer exact test and t test. RESULTS: ALD developed with similar frequencies in patients who were (n = 59) and were not (n = 57) treated with surgery. In patients treated with surgery, index level FA appeared or increased in 20 patients (34%) and decreased in 1 patient. In patients treated with rehabilitation, 2 (4%) had new or increased FA at the index/degenerated disc level and 1 had decreased FA (P < 0.001). The development of ALD and FA was not related to clinical outcome. CONCLUSION: In this first study that compared the courses of degeneration after treatment with disc prosthesis surgery or rehabilitation, ALD was observed at similar frequencies at the 2-year follow-up. However, the surgery group had increased FA at the implant level.


Assuntos
Dor Crônica/terapia , Degeneração do Disco Intervertebral/terapia , Disco Intervertebral/cirurgia , Dor Lombar/terapia , Vértebras Lombares/cirurgia , Complicações Pós-Operatórias/etiologia , Sacro/cirurgia , Substituição Total de Disco/efeitos adversos , Articulação Zigapofisária/patologia , Adulto , Dor Crônica/diagnóstico , Dor Crônica/etiologia , Dor Crônica/reabilitação , Dor Crônica/cirurgia , Avaliação da Deficiência , Feminino , Humanos , Disco Intervertebral/patologia , Degeneração do Disco Intervertebral/diagnóstico , Degeneração do Disco Intervertebral/etiologia , Degeneração do Disco Intervertebral/reabilitação , Degeneração do Disco Intervertebral/cirurgia , Dor Lombar/diagnóstico , Dor Lombar/etiologia , Dor Lombar/reabilitação , Dor Lombar/cirurgia , Vértebras Lombares/patologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Noruega , Medição da Dor , Complicações Pós-Operatórias/patologia , Valor Preditivo dos Testes , Sacro/patologia , Fatores de Tempo , Resultado do Tratamento
20.
Eur Spine J ; 21(12): 2531-8, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22669708

RESUMO

PURPOSE: To compare the 9-year outcome in patients with chronic low back pain treated by instrumented lumbar fusion versus cognitive intervention and exercises. METHODS: The main outcome measure was the Oswestry Disability Index (ODI). Secondary outcome measures included pain, fear-avoidance beliefs, trunk muscle strength, medication, and return to work. RESULTS: One-third of the patients randomized to cognitive intervention and exercises had crossed over and been operated and one-third of the patients allocated to lumbar fusion had been re-operated. The intention-to-treat analysis detected no differences between the two groups. The mean adjusted treatment effect for ODI was 1.9 (95 % CI -7.8 to 11.6). Analysed according to the treatment received, more operated patients used pain medication and were out of work. CONCLUSIONS: The outcome at 9 years was not different between instrumented lumbar fusion and cognitive intervention and exercises.


Assuntos
Dor Lombar/reabilitação , Dor Lombar/cirurgia , Adulto , Dor Crônica/reabilitação , Dor Crônica/cirurgia , Terapia Cognitivo-Comportamental , Terapia por Exercício , Feminino , Humanos , Vértebras Lombares , Masculino , Pessoa de Meia-Idade , Fusão Vertebral , Resultado do Tratamento
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