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PURPOSE OF REVIEW: Inflammatory Bowel Disease (IBD) is a chronic GI inflammatory condition induced by a dysregulated immune system activation, whereas HIV infection causes depletion of the immune system, inducing immunosuppression. Given the increasing incidence of IBD across the globe, including in developing countries, the co-prevalence of both conditions is expected to increase. Herein, we systematically review the data describing disease course when both pathologies co-exist. RECENT FINDINGS: Overall, the co-prevalence of IBD and HIV is around 0.1 to 2%. While IBD does not seem to affect HIV course, the opposite is controversial, as some studies report milder IBD phenotype, with fewer disease relapses especially when CD4 + counts are lower than 200 cells/µL. Despite growing evidence to support the safety of the use of immunosuppressants and biologics in IBD-HIV infected patients, these classes of drugs are used in less than 50% of patients, as compared to non-HIV infected IBD patients. There is a need for more studies on disease course and safety of IBD medications in the setting of IBD.
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Colite Ulcerativa , Infecções por HIV , Doenças Inflamatórias Intestinais , Humanos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/tratamento farmacológico , Imunossupressores/efeitos adversos , Terapia de Imunossupressão , Colite Ulcerativa/complicaçõesRESUMO
Rapid bone loss can occur after spinal cord injury (SCI) and a standard of care to prevent or treat this phenomenon is an active area of research. Using advanced analysis techniques, this study demonstrates that zoledronic acid, a possible treatment, prevented loss of bone strength at the hip following SCI. INTRODUCTION: Bone loss below the level of neurological lesion is a well-known complication of spinal cord injury (SCI), and effective preventive treatment for this phenomenon is an active area of research. Zoledronic acid has demonstrated efficacy to attenuate bone loss at the hip after SCI, but previous studies relied on measurements from dual-energy X-ray absorptiometry. The purpose of this investigation was to more thoroughly characterize changes to bone mineral and strength at the proximal femur in individuals receiving zoledronic acid in the acute SCI stage; we also examined the influence of ambulatory ability on bone outcomes. METHODS: Participants randomized to either zoledronic acid (n = 29) or placebo (n = 30) received computed tomography (CT) scans and ambulatory assessments at baseline and 6 and 12 months following drug infusion. CT-based finite element (FE) modeling was used to predict changes in proximal femoral strength associated with treatment. RESULTS: After 12 months, FE-predicted bone strength was reduced by a mean (SD) of 9.6 (17.9)% in the zoledronic acid group versus 24.6 (24.5)% in the placebo group (p = 0.007). These differences in strength were explained by reductions in CT measurements of both trabecular (p < 0.001) and cortical (p ≤ 0.021) bone at the femoral neck and trochanteric region. Ambulation ability influenced select trabecular and cortical parameters, but we were unable to detect an impact on FE-predicted bone strength. CONCLUSION: These findings demonstrate that treatment with zoledronic acid in acute SCI attenuates losses in proximal femoral strength, which may reduce the risk of hip fractures across patients with varying degrees of ambulatory abilities.
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Doenças Ósseas Metabólicas , Traumatismos da Medula Espinal , Humanos , Ácido Zoledrônico/uso terapêutico , Ácido Zoledrônico/farmacologia , Densidade Óssea , Fêmur/patologia , Absorciometria de Fóton , Doenças Ósseas Metabólicas/prevenção & controle , Colo do Fêmur , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/tratamento farmacológico , CaminhadaRESUMO
Osteoarthritis (OA) manifests with chronic pain, motor impairment, and proprioceptive changes. However, the role of the brain in the disease is largely unknown. Here, we studied brain networks using the mathematical properties of graphs in a large sample of knee and hip OA (KOA, n = 91; HOA, n = 23) patients. We used a robust validation strategy by subdividing the KOA data into discovery and testing groups and tested the generalizability of our findings in HOA. Despite brain global topological properties being conserved in OA, we show there is a network wide pattern of reorganization that can be captured at the subject-level by a single measure, the hub disruption index. We localized reorganization patterns and uncovered a shift in the hierarchy of network hubs in OA: primary sensory and motor regions and parahippocampal gyrus behave as hubs and insular cortex loses its central placement. At an intermediate level of network structure, frontoparietal and cingulo-opercular modules showed preferential reorganization. We examined the association between network properties and clinical correlates: global disruption indices and isolated degree properties did not reflect clinical parameters; however, by modeling whole brain nodal degree properties, we identified a distributed set of regions that reliably predicted pain intensity in KOA and generalized to hip OA. Together, our findings reveal that while conserving global topological properties, brain network architecture reorganizes in OA, at both global and local scale. Network connectivity related to OA pain intensity is dissociated from the major hub disruptions, challenging the extent of dependence of OA pain on nociceptive signaling.
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Artralgia/fisiopatologia , Córtex Cerebral/fisiopatologia , Dor Crônica/fisiopatologia , Conectoma , Rede Nervosa/fisiopatologia , Osteoartrite do Quadril/fisiopatologia , Osteoartrite do Joelho/fisiopatologia , Idoso , Artralgia/diagnóstico por imagem , Artralgia/etiologia , Córtex Cerebral/diagnóstico por imagem , Dor Crônica/diagnóstico por imagem , Dor Crônica/etiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Osteoartrite do Quadril/complicações , Osteoartrite do Joelho/complicaçõesRESUMO
Hydrothermal areas are potentially hazardous to humans as volcanic gases such as radon (222Rn) are continuously released from soil diffuse degassing. Exposure to radon is estimated to be the second leading cause of lung cancer, but little is known about radon health-associated risks in hydrothermal regions. This cross-sectional study was designed to evaluate the DNA damage in the buccal epithelial cells of individuals chronically exposed to indoor radon in a volcanic area (Furnas volcano, Azores, Portugal) with a hydrothermal system. Buccal epithelial cells were collected from 33 individuals inhabiting the hydrothermal area (Ribeira Quente village) and from 49 individuals inhabiting a non-hydrothermal area (Ponta Delgada city). Indoor radon was measured with Ramon 2.2 detectors. Chromosome damage was measured by micronucleus cytome assay, and RAPD-PCR was used as a complementary tool to evaluate DNA damage, using three 10-mer primers (D11, F1 and F12). Indoor radon concentration correlated positively with the frequency of micronucleated cells (r s = 0.325, p = 0.003). Exposure to radon is a risk factor for the occurrence micronucleated cells in the inhabitants of the hydrothermal area (RR = 1.71; 95% CI, 1.2-2.4; p = 0.003). One RAPD-PCR primer (F12) produced differences in the banding pattern, a fact that can indicate its potential for detecting radon-induced specific genomic alterations. The observed association between chronic exposure to indoor radon and the occurrence of chromosome damage in human oral epithelial cells evidences the usefulness of biological surveillance to assess mutations involved in pre-carcinogenesis in hydrothermal areas, reinforcing the need for further studies with human populations living in these areas.
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Poluentes Radioativos do Ar/toxicidade , Poluição do Ar em Ambientes Fechados/análise , Dano ao DNA , Mucosa Bucal/efeitos da radiação , Radônio/toxicidade , Adulto , Idoso , Poluentes Radioativos do Ar/análise , Açores , Estudos Transversais , Monitoramento Ambiental/métodos , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Células Epiteliais/efeitos da radiação , Feminino , Humanos , Masculino , Testes para Micronúcleos , Pessoa de Meia-Idade , Mucosa Bucal/citologia , Mucosa Bucal/metabolismo , Portugal , Radônio/análise , Técnica de Amplificação ao Acaso de DNA Polimórfico , Erupções VulcânicasRESUMO
Total knee replacement (TKR) is the gold-standard treatment for end-stage chronic osteoarthritis pain, yet many patients report chronic postoperative pain after TKR. The search for preoperative predictors for chronic postoperative pain following TKR has been studied with inconsistent findings. This study investigates the predictive value of quantitative sensory testing (QST) and PainDETECT for postoperative pain 3, 6, and 12 months post-TKR. We assessed baseline and postoperative (3- and 6-months) QST measures in 77 patients with knee OA (KOA) and 41 healthy controls, along with neuropathic pain scores in patients (PainDETECT). QST parameters included pressure pain pressure threshold (PPT), pain tolerance threshold (PTT), conditioned pain modulation (CPM), and temporal summation (TS) using cuff algometry, alongside mechanical hyperalgesia, and mechanical temporal summation to repeated pinprick stimulation. Compared to healthy controls, KOA patients at baseline demonstrated hyperalgesia to pinprick stimulation at the medial OA-affected knee and cuff pressure on the ipsilateral calf. Lower cuff algometry PTT and mechanical pinprick hyperalgesia were associated with baseline KOA pain intensity. Moreover, baseline pinprick pain hyperalgesia explained 25% of variance in pain intensity 12 months post-TKR and preoperative neuropathic pain scores also captured 30% and 20% of the variance in postoperative pain at 6- and 12-months, respectively. A decrease in mechanical pinprick hyperalgesia from before surgery to 3 months after TKR was associated with lower postoperative pain at the 12 months post-TKR follow-up, and vice-versa. Our findings suggest that preoperative pinprick hyperalgesia and PainDETECT neuropathic-like pain symptoms show predictive value for the development of chronic post-TKR pain.
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BACKGROUND: Total knee replacement (TKR) is the gold standard treatment for end-stage chronic osteoarthritis pain, yet many patients report chronic postoperative pain after TKR. The search for preoperative predictors for chronic postoperative pain following TKR has been studied with inconsistent findings. METHODS: This study investigates the predictive value of quantitative sensory testing (QST) and PainDETECT for postoperative pain 3, 6 and 12 months post-TKR. We assessed preoperative and postoperative (3 and 6 months) QST measures in 77 patients with knee OA (KOA) and 41 healthy controls, along with neuropathic pain scores in patients (PainDETECT). QST parameters included pressure pain pressure threshold (PPT), pain tolerance threshold (PTT), conditioned pain modulation (CPM) and temporal summation (TS) using cuff algometry, alongside mechanical hyperalgesia and temporal summation to repeated pinprick stimulation. RESULTS: Compared to healthy controls, KOA patients at baseline demonstrated hyperalgesia to pinprick stimulation at the medial knee undergoing TKR, and cuff pressure at the calf. Lower cuff algometry PTT and mechanical pinprick hyperalgesia were associated with preoperative KOA pain intensity. Moreover, preoperative pinprick pain hyperalgesia explained 25% of variance in pain intensity 12 months post-TKR and preoperative neuropathic pain scores also captured 30% and 20% of the variance in postoperative pain at 6 and 12 months respectively. A decrease in mechanical pinprick hyperalgesia from before surgery to 3 months after TKR was associated with lower postoperative pain at the 12 months post-TKR follow-up. CONCLUSION: Our findings suggest that preoperative pinprick hyperalgesia and neuropathic-like pain symptoms show predictive value for the development of chronic post-TKR pain. SIGNIFICANCE STATEMENT: This study's findings hold significant implications for chronic pain management in knee osteoarthritis patients, particularly those undergoing total knee replacement surgery (TKR). Mechanical hyperalgesia and neuropathic pain-like characteristics predict postoperative pain 1 year after TKR, emphasizing the importance of understanding pain phenotypes in OA for selecting appropriate pain management strategies. The normalization of hyperalgesia after surgery correlates with better long-term outcomes, further highlighting the therapeutic potential of addressing abnormal pain processing mechanisms pre- and post-TKR.
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Artroplastia do Joelho , Hiperalgesia , Neuralgia , Osteoartrite do Joelho , Medição da Dor , Limiar da Dor , Dor Pós-Operatória , Humanos , Artroplastia do Joelho/efeitos adversos , Hiperalgesia/fisiopatologia , Hiperalgesia/etiologia , Hiperalgesia/diagnóstico , Masculino , Neuralgia/etiologia , Neuralgia/diagnóstico , Feminino , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/etiologia , Idoso , Pessoa de Meia-Idade , Osteoartrite do Joelho/cirurgia , Medição da Dor/métodos , PrognósticoRESUMO
INTRODUCTION: We sought to predict analgesic response to daily oral nonsteroidal anti-inflammatory drugs (NSAIDs) or subcutaneous tanezumab 2.5 mg (every 8 weeks) at week 16 in patients with moderate-to-severe osteoarthritis, based on initial treatment response over 8 weeks. METHODS: Data were derived from three randomized controlled trials of osteoarthritis. A two-step, trajectory-focused, analytics approach was used to predict patients as responders or non-responders at week 16. Step 1 identified patients using a data-element combination method (based on pain score at baseline, pain score at week 8, pain score monotonicity at week 8, pain score path length at week 8, and body site [knee or hip]). Patients who could not be identified in step 1 were predicted in step 2 using a k-nearest neighbor method based on pain score and pain response level at week 8. RESULTS: Our approach predicted response with high accuracy in NSAID-treated (83.2-90.2%, n = 931) and tanezumab-treated (84.6-91.0%, n = 1430) patients regardless of the efficacy measure used to assess pain, or the threshold used to define response (20%, 30%, or 50% improvement from baseline). Accuracy remained high using 50% or 20% response thresholds, with 50% and 20% yielding generally slightly better negative and positive predictive value, respectively, relative to 30%. Accuracy was slightly better in patients aged ≥ 65 years relative to younger patients across most efficacy measure/response threshold combinations. CONCLUSIONS: Analyzing initial 8-week analgesic responses using a two-step, trajectory-based approach can predict future response in patients with moderate-to-severe osteoarthritis treated with NSAIDs or 2.5 mg tanezumab. These findings demonstrate that prediction of treatment response based on a single dose of a novel therapeutic is possible and that predicting future outcomes based on initial response offers a way to potentially advance the approach to clinical management of patients with osteoarthritis. GOV IDENTIFIERS: NCT02528188, NCT02709486, NCT02697773.
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Osteoartrite do Quadril , Osteoartrite do Joelho , Humanos , Analgésicos , Anti-Inflamatórios não Esteroides/uso terapêutico , Osteoartrite do Quadril/tratamento farmacológico , Osteoartrite do Joelho/tratamento farmacológico , Dor/tratamento farmacológico , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
INTRODUCTION: Assessing functional improvement after intensive care unit discharge is particularly challenging. The aim of this study was to measure the association between (1) changes in knee extension muscle strength or quadriceps femoris and rectus femoris muscle thickness and (2) changes in functionality/function-related measurements in post-intensive care unit patients. METHODS: This prospective cohort study included adult patients without previous disability, consecutively selected after intensive care unit discharge. Some parameters, such as Short-Form 36, 6-min walking test, 1-min sit-to-stand, and Short Physical Performance Battery, were measured at baseline and 3 and 6 mos after discharge. Correlations were assessed and regression models were built to assess the association between evolution in knee extension strength or muscle thickness and evolution in functional tests. RESULTS: Thirty patients completed the follow-up. Moderate correlation was found between knee extension strength change and Short-Form 36 physical functioning (correlation coefficient [ ρ ] = 0.53), 6-min walking test ( ρ = 0.38), 1-min sit-to-stand ( ρ = 0.52), and Short Physical Performance Battery ( ρ = 0.38). Baseline values and changes in knee extension strength moderately predicted evolution in Short-Form 36 physical functioning ( r2 = 0.32, P = 0.006). Changes in muscle thickness were overall not associated with changes in functional variables. CONCLUSION: Changes in knee extension muscle strength may inform on functional progression over time after intensive care unit discharge, although confirmatory studies are needed.
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Articulação do Joelho , Alta do Paciente , Adulto , Humanos , Estudos Prospectivos , Extremidade Inferior , Força Muscular/fisiologia , Unidades de Terapia IntensivaRESUMO
ABSTRACT: The neural mechanisms for the persistence of pain after a technically successful arthroplasty in osteoarthritis (OA) remain minimally studied, and direct evidence of the brain as a predisposing factor for pain chronicity in this setting has not been investigated. We undertook this study as a first effort to identify presurgical brain and clinical markers of postarthroplasty pain in knee OA. Patients with knee OA (n = 81) awaiting total arthroplasty underwent clinical and psychological assessment and brain magnetic resonance imagining. Postoperative pain scores were measured at 6 months after surgery. Brain subcortical anatomic properties (volume and shape) and clinical indices were studied as determinants of postoperative pain. We show that presurgical subcortical volumes (bilateral amygdala, thalamus, and left hippocampus), together with shape deformations of the right anterior hippocampus and right amygdala, associate with pain persistence 6 months after surgery in OA. Longer pain duration, higher levels of presurgical anxiety, and the neuropathic character of pain were also prognostic of postsurgical pain outcome. Brain and clinical indices accounted for unique influences on postoperative pain. Our study demonstrates the presence of presurgical subcortical brain factors that relate to postsurgical persistence of OA pain. These preliminary results challenge the current dominant view that mechanisms of OA pain predominantly underlie local joint mechanisms, implying novel clinical management and treatment strategies.
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Artroplastia do Joelho , Osteoartrite do Joelho , Humanos , Artroplastia do Joelho/efeitos adversos , Medição da Dor/métodos , Osteoartrite do Joelho/complicações , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/cirurgia , Dor Pós-Operatória/diagnóstico por imagem , Dor Pós-Operatória/etiologia , Encéfalo/diagnóstico por imagem , Biomarcadores , Resultado do TratamentoRESUMO
INTRODUCTION: The Handheld Dynamometer (HHD) has the potential to overcome some of the logistic and economic limitations of isokinetic dynamometers for measuring knee extension muscle strength. However, its reliability has not been fully assessed. The purpose of this study is to measure intra and inter-rater reliability of HHD for knee extension strength in patients receiving rehabilitation treatment, as well as to understand in which conditions is the reliability higher. METHODS: Twenty-nine patients admitted in an inpatient Physical Medicine and Rehabilitation unit were consecutively included in this cross-sectional study. Two experienced and two inexperienced physicians made two assessments of knee extension strength with HHD, separated by three hours. Intraclass Correlation Coefficients (ICC), absolute differences between assessments, and correlations between strength and functional variables were calculated. RESULTS: Intra and inter-rater ICC were overall high (≥ 0.950 and 0.927, respectively). Higher values were found when average of two measurements were made for estimating intra-rater ICC (ICC = 0.978; 95%CI = 0.969-0.985) but not for inter-rater ICC. ICC were not statistically significantly different when calculated based on measurements performed by inexperienced physicians and experienced ones. There was a moderate correlation between strength and functional variables. CONCLUSION: Handheld Dynamometer seems to be a reliable option to measure knee extension muscle strength, particularly when two measurements are performed and their average is reported.
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Articulação do Joelho , Joelho , Estudos Transversais , Humanos , Joelho/fisiologia , Articulação do Joelho/fisiologia , Força Muscular/fisiologia , Dinamômetro de Força Muscular , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Point-of-care ultrasound can be used to assess muscle thickness. However, its reliability has not been fully evaluated. AIM: This study aimed to assess the intrarater and inter-rater reliability of point-of-care ultrasound for the estimation of quadriceps and rectus femoris thickness in patients from a rehabilitation setting. DESIGN: This is a cross-sectional study. SETTING: This study was conducted at the Department of Physical Medicine and Rehabilitation of a tertiary care hospital. POPULATION: Twenty-nine inpatients consecutively selected after admission. METHODS: Four observers, two trained and two untrained, used point-of-care ultrasound to measure quadriceps femoris and rectus femoris thickness. Each observer performed two measurements followed by a second set of two measurements three hours later. Intraclass correlation coefficients (ICC) were then calculated. RESULTS: Both intrarater and inter-rater ICC were higher than 0.888 for both quadriceps and rectus femoris measurements. Reliability was highest when ICC were calculated based on the average of two measurements, with the intrarater ICC being of 0.956 (95% CI: 0.937-0.970) for rectus femoris and of 0.966 (95% CI: 0.951-0.976) for quadriceps femoris; and with the inter-rater ICC being of 0.919 (95% CI: 0.863-0.957) for rectus femoris and 0.945 (95% CI: 0.907- 0.971) for quadriceps femoris. Trained and untrained observers did not have significantly different ICC values. CONCLUSIONS: These results suggest that point-of-care ultrasound is a reliable option to measure muscle thickness of knee extensors by the same or different observers. CLINICAL REHABILITATION IMPACT: Measuring knee extensors thickness may aid to adequately modulate treatment choices in patients with disability. This study suggests that quadriceps and rectus femoris muscle thickness measured after a short training course, by either an experienced or inexperienced clinician, presents high reliability. Reliability can be increased if the average of two measurements is used. Besides being inexpensive and portable, point-of-care ultrasound is a reliable tool for measuring knee extensors' thickness, rendering it potentially adequate to be used in clinical practice.
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Sistemas Automatizados de Assistência Junto ao Leito , Músculo Quadríceps , Estudos Transversais , Humanos , Músculo Quadríceps/diagnóstico por imagem , Músculo Quadríceps/fisiologia , Reprodutibilidade dos Testes , Ultrassonografia/métodosRESUMO
INTRODUCTION: We sought to identify and characterize distinct responder profiles among osteoarthritis (OA) subjects treated with tanezumab, nonsteroidal anti-inflammatory drugs (NSAIDs), or placebo. METHODS: Subject-level data were derived from three randomized, double-blind, placebo- or NSAID-controlled trials of tanezumab in subjects with moderate-to-severe OA. Subjects received subcutaneous tanezumab (2.5 mg, n = 1527; 5 mg, n = 1279) every 8 weeks, oral NSAIDs (n = 994) daily, or placebo (n = 513). Group-based trajectory modeling (GBTM, an application of finite mixture statistical modeling that uses response trajectory to identify and summarize complex patterns in longitudinal data) was used to identify subgroups of subjects following similar patterns of response in each treatment arm, based on daily pain intensity scores from baseline through Week 16. We then examined whether subject-related variables were associated with any of the subgroups using multinomial logistic regression. RESULTS: A three-subgroup/four-inflection point trajectory model was selected based on clinical and statistical considerations. The subgroups were high responders (substantial pain improvement and a large majority of members achieved ≥ 30% improvement before Week 16), medium responders (gradual pain improvement and a majority of members achieved ≥ 30% improvement by Week 16), and non-responders (little to no pain improvement over 16 weeks). Across all treatments, fluctuation in pain intensity in the week prior to treatment was consistently associated with treatment response. Other variables were positively (age, body mass index, days of rescue medication use) or negatively (severity of disease based on Kellgren-Lawrence grading) associated with response but effects were small and/or varied across treatments. CONCLUSIONS: Across all treatments, GBTM identified three subgroups of subjects that were characterized by extent of treatment response (high, medium, and non-responders). Similar analyses (e.g., grouping of subjects based on response trajectory and identification of subgroup-related variables) in other studies of OA could inform clinical trial design and/or treatment approaches. (NCT02697773; NCT02709486; NCT02528188).
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Osteoartrite do Quadril , Osteoartrite do Joelho , Anti-Inflamatórios não Esteroides/uso terapêutico , Método Duplo-Cego , Humanos , Osteoartrite do Quadril/tratamento farmacológico , Osteoartrite do Joelho/tratamento farmacológico , Medição da Dor , Preparações Farmacêuticas , Resultado do TratamentoRESUMO
Chronic pain is a leading cause of disability worldwide and its prevalence is likely to increase over the next decades. Treatment for chronic pain remains insufficient and therapeutical advances have not made comparable progress with that for many chronic disorders, thus amplifying the concern on the future burden of the disease. At the same time, and even after decades of intense research, the underlying pathophysiology of chronic pain remains minimally understood. We believe advancing our current understanding of chronic pain requires mechanistically explicit, hypothesis-driven, and clinically focused models. In this review we highlight some of the main findings over the last decades that have contributed to the present knowledge of brain mechanisms of chronic pain, and how such advances were possible due to a reverse translational research approach. We argue that this approach is essential in the chronic pain field, in order to generate new scientific hypotheses, probe physiological mechanisms, develop therapeutic strategies and translate findings back into promising human clinical trials.
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Encéfalo/fisiopatologia , Dor Crônica/etiologia , Animais , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Dor Crônica/diagnóstico por imagem , Dor Crônica/fisiopatologia , Humanos , Aprendizagem , Memória , Motivação , Recompensa , Roedores , Pesquisa Translacional BiomédicaRESUMO
A single infusion of zoledronic acid (ZOL) after acute spinal cord injury (SCI) attenuates bone loss at the hip (proximal femur) and knee (distal femur and proximal tibia) for at least 6 months. The objective of this study was to examine the effects of timing and frequency of ZOL over 2 years. In this double-blind, placebo-controlled trial, we randomized 60 individuals with acute SCI (<120 days of injury) to receive either ZOL 5-mg infusion (n = 30) or placebo (n = 30). After 12 months, groups were again randomized to receive ZOL or placebo, resulting in four treatment groups for year 2: (i) ZOL both years; (ii) ZOL year 1, placebo year 2; (iii) placebo year 1, ZOL year 2; and (iv) placebo both years. Our primary outcome was bone loss at 12 months; compared to placebo, a single infusion of ZOL attenuated bone loss at the proximal femur, where median changes relative to baseline were -1.7% to -2.2% for ZOL versus -11.3% to -12.8% for placebo (p < 0.001). Similarly, the distal femur and proximal tibia showed changes of -4.7% to -9.6% for ZOL versus -8.9% to -23.0% for placebo (p ≤ 0.042). After 24 months, differences were significant at the proximal femur only (-3.2% to -6.0% for ZOL vs. -16.8% to -21.8% for placebo; p ≤ 0.018). Although not statistically significant, median bone density losses suggested some benefit from two annual infusions compared to a single baseline infusion, as well as from a single infusion 12 months after baseline compared to 2 years of placebo; therefore, further investigation in the 12-month to 24-month treatment window is warranted. No unanticipated adverse events associated with drug treatment were observed. In summary, ZOL 5-mg infusion after acute SCI was well-tolerated and may provide an effective therapeutic approach to prevent bone loss in the first few years following SCI. © 2021 American Society for Bone and Mineral Research (ASBMR).
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Conservadores da Densidade Óssea , Traumatismos da Medula Espinal , Densidade Óssea , Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Humanos , Imidazóis/uso terapêutico , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/tratamento farmacológico , Tempo para o Tratamento , Ácido ZoledrônicoRESUMO
INTRODUCTION: The opiate epidemic has severe medical and social consequences. Opioids are commonly prescribed in patients with chronic pain, and are a main contributor to the opiate epidemic. The adverse effects of long-term opioid usage have been studied primarily in dependence/addiction disorders, but not in chronic pain. Here, we examine the added iatrogenic effects, psychology, and brain morphology of long-term opioid use in matched patients with chronic pain with and without opioid use (case-controlled design). METHODS: We compared psychosocial, functional, and psychological measures between patients with chronic back pain (CBP) who were managing their pain with or without opioids, thereby controlling for the effect of pain on these outcomes. In addition, we investigated brain morphological differences associated with long-term opioid usage. We recruited 58 patients with CBP, 29 of them on long-term opioids and 29 who did not use opioids, and who were matched in terms of age, sex, pain intensity, and pain duration. Questionnaires were used to assess pain quality, pain psychology, negative and positive emotions, physical, cognitive, sensory, and motor functions, quality of life, and personality traits. RESULTS: Patients with CBP on opioids displayed more negative emotion, poorer physical function, and more pain interference (p < 0.001), whereas there were no statistical differences in cognitive and motor functions and personality traits. Voxel-based morphometry using structural brain imaging data identified decreased gray matter density of the dorsal paracingulate cortex (family-wise error-corrected p < 0.05) in patients with opioids, which was associated with negative emotion (p = 0.03). Finally, a volumetric analysis of hippocampal subfields identified lower volume of the left presubiculum in patients on opioids (p < 0.001). CONCLUSION: Long-term opioid use in chronic pain is associated with adverse negative emotion and disabilities, as well as decreased gray matter volumes of specific brain regions.
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ABSTRACT: The interaction between osteoarthritis (OA) pain and brain properties remains minimally understood, although anatomical and functional neuroimaging studies suggest that OA, similar to other chronic pain conditions, may impact as well as partly be determined by brain properties. Here, we studied brain gray matter (GM) properties in OA patients scheduled to undergo total joint replacement surgery. We tested the hypothesis that brain regional GM volume is distinct between hip OA (HOA) and knee OA (KOA) patients, relative to healthy controls and moreover, that these properties are related to OA pain. Voxel-based morphometry group contrasts showed lower anterior cingulate GM volume only in HOA. When we reoriented the brains (flipped) to examine the hemisphere contralateral to OA pain, precentral GM volume was lower in KOA and HOA, and 5 additional brain regions showed distortions between groups. These GM changes, however, did not reflect clinical parameters. Next, we subdivided the brain into larger regions, approximating Brodmann areas, and performed univariable and machine learning-based multivariable contrasts. The univariable analyses approximated voxel-based morphometry results. Our multivariable model distinguished between KOA and controls, was validated in a KOA hold-out sample, and generalized to HOA. The multivariable model in KOA, but not HOA, was related to neuropathic OA pain. These results were mapped into term space (using Neurosynth), providing a meta-analytic summary of brain anatomical distortions in OA. Our results indicate more subtle cortical anatomical differences in OA than previously reported and also emphasize the interaction between OA pain, namely its neuropathic component, and OA brain anatomy.
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Dor Crônica , Substância Cinzenta , Encéfalo/diagnóstico por imagem , Estudos Transversais , Substância Cinzenta/diagnóstico por imagem , Humanos , Imageamento por Ressonância MagnéticaRESUMO
A significant proportion of osteoarthritis (OA) patients continue to experience moderate to severe pain after total joint replacement (TJR). Preoperative factors related to pain persistence are mainly studied using individual predictor variables and distinct pain outcomes, thus leading to a lack of consensus regarding the influence of preoperative parameters on post-TJR pain. In this prospective observational study, we evaluated knee and hip OA patients before, 3 and 6 months post-TJR searching for clinical predictors of pain persistence. We assessed multiple measures of quality, mood, affect, health and quality of life, together with radiographic evaluation and performance-based tasks, modeling four distinct pain outcomes. Multivariate regression models and network analysis were applied to pain related biopsychosocial measures and their changes with surgery. A total of 106 patients completed the study. Pre-surgical pain levels were not related to post-surgical residual pain. Although distinct pain scales were associated with different aspects of post-surgical pain, multi-factorial models did not reliably predict post-surgical pain in knee OA (across four distinct pain scales) and did not generalize to hip OA. However, network analysis showed significant changes in biopsychosocial-defined OA personality post-surgery, in both groups. Our results show that although tested clinical and biopsychosocial variables reorganize after TJR in OA, their presurgical values are not predictive of post-surgery pain. Derivation of prognostic markers for pain persistence after TJR will require more comprehensive understanding of underlying mechanisms.
Assuntos
Osteoartrite do Quadril/cirurgia , Osteoartrite do Joelho/cirurgia , Manejo da Dor , Dor Pós-Operatória/terapia , Idoso , Artroplastia de Substituição/efeitos adversos , Artroplastia de Quadril/efeitos adversos , Artroplastia de Quadril/métodos , Artroplastia do Joelho/efeitos adversos , Artroplastia do Joelho/métodos , Feminino , Humanos , Articulação do Joelho/fisiopatologia , Articulação do Joelho/cirurgia , Masculino , Pessoa de Meia-Idade , Osteoartrite do Quadril/fisiopatologia , Osteoartrite do Joelho/fisiopatologia , Medição da Dor/métodos , Dor Pós-Operatória/epidemiologia , Dor Pós-Operatória/fisiopatologia , Índice de Gravidade de DoençaRESUMO
INTRODUÇAO: A tuberculose multirresistente é uma ameaça ao controle da tuberculose em todo o mundo. Tratamento inadequado é freqüentemente apontado como fator de risco para tuberculose multirresistente. OBJETIVO: Identificar fatores associados ao tratamento inadequado em portadores de tuberculose multirresistente. MÉTODO: Foram levantados e identificados os testes de sensibilidade para tuberculose, realizados no Laboratório Central do Estado do Ceará de 1990 a 1999. Foi realizado um estudo retrospectivo e prospectivo, em grupo de portadores de tuberculose multirresistente, comparando as características dos pacientes com tratamento adequado com as dos com tratamentos inadequados. Foi considerado multirresistente o bacilo resistente a pelo menos rifampicina + isoniazida e utilizado o método das proporções. RESULTADOS: Dos 1.500 testes de sensibilidade realizados, 266 eram multirresistentes. Destes, identificaram-se apenas 153 pacientes, dos quais 19 foram excluídos, restando, no estudo, 134 pacientes. Pela análise univariada os fatores associados significativamente ao tratamento inadequado foram: não-adesão ao tratamento, pobreza extrema, intolerância medicamentosa, falha no atendimento, falta de medicação, dois ou mais tratamentos anteriores, lesões radiológicas bilaterais e grandes cavidades pulmonares. Foi encontrada ainda associação (p < 0,001) de alcoolismo e/ou tabagismo com a não-adesão. Na análise multivariada, permaneceram associados ao tratamento inadequado: dois ou mais tratamentos anteriores (p < 0,0001, OR = 5,9; IC 95 por cento: 2,5-13,7), grandes cavidades pulmonares (p < 0,0217, OR = 2,7; IC 95 por cento: 1,2-6,1) e lesões radiológicas bilaterais (p < 0,0226, OR = 3,2; IC 95 por cento: 1,4-7,4). CONCLUSAO: Neste estudo, observou-se que os fatores associados aos tratamentos inadequados são de grande abrangência. Deve existir uma tentativa para controlar melhor a doença, principalmente nos pacientes em retratamento e nos portadores de grandes cavidades e/ou lesões bilaterais na radiografia torácica.