Factors associated with pain pressure threshold in both local and remote sites in knee osteoarthritis.

BACKGROUND: Knee osteoarthritis (KOA) is a prevalent condition, and its most frequent symptom is pain that often leads to disability. Pain sensitization is a core feature of KOA, and it can be measured through quantitative sensory testing protocols such as pain pressure threshold (PPT). However, there is a lack of understanding about the factors that may influence changes in PPTs in the KOA population. OBJECTIVE: To explore the clinical and functional factors associated with PPTs in a sample of people with chronic KOA pain and to compare models of local (knees) and remote (thenar regions) sites. DESIGN: Cross-sectional analysis of a prospective cohort. SETTING: Primary care in public institution. PARTICIPANTS: 113 adults with KOA. INTERVENTION: N/A. MAIN OUTCOME MEASURES: Multivariable regression analyses evaluating demographic, clinical, and functional variables that could be associated with local and remote PPTs (main outcomes) were performed. RESULTS: Both thenar region (adjusted-R2 : 0.29) and knee (adjusted-R2 : 0.45) models had the same significant negative association with being a female, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain levels (thenar: ß: -0.15, p = .002; knee: ß: -0.2, p < .001), and the 10-Meter Walking Test (thenar: ß: -0.05, p = .038; knee: ß: -0.08, p = .004). A small significant positive association with depressive symptoms was identified in both models, which acted as a confounder for WOMAC pain and was likely affected by unmeasured confounders. CONCLUSIONS: PPTs in KOA pain are associated with functional outcomes such as the 10-Meter Walking Test and activity-related pain intensity; thus more disability is associated with smaller pain thresholds. Similarity between models may suggest central sensitization.

Functional and Neural Correlates Associated with Conditioned Pain Modulation in Patients with Chronic Knee Osteoarthritis Pain: A Cross-Sectional Study.

Background: In this study, we aimed to assess the factors that predict a dysfunctional conditioned pain modulation (CPM) in chronic knee OA. Methods: This is a cross-sectional analysis of patients with chronic knee OA from a prospective cohort study in Brazil (n = 85). We performed linear and logistic multivariate regression models using the purposeful selection approach to test the relationship between the CPM in both knees (average) as a dependent variable and demographics, clinical, and neurophysiological as independent variables. Results: A significant negative association between WOMAC pain scores and CPM (ß: -0.13) was found. This association was modified by the subjects' race, being stronger in the non-white subjects. In our logistic regression models, pain intensity indexed with the WOMAC pain scale remained a significant association with dichotomized CPM. Furthermore, a significant CPM association with balance, indexed with the Berg Balance score, was evidenced (ß: 0.04). Neurophysiological variables showed a significant negative relationship with CPM, such as the relative power of delta oscillations in the frontal area (ß: -3.11) and central area (ß: -3.23). There was no significant relationship between CPM and the following domains: cognitive, emotion, sleep, opioid receptor polymorphisms, and intrinsic variables of OA disease. There was no association of CPM with TMS-indexed inhibitory markers. Conclusions: These results may indicate that less function of the pain descending inhibitory system in patients with OA is correlated with higher activity-related pain (WOMAC), less balance, and cortical plasticity especially with increased low-frequency (delta) brain oscillations. These associations seem modified by race.

The role of symptoms severity, heart rate, and central sensitization for predicting sleep quality in patients with fibromyalgia.

BACKGROUND: Clinical predictors of sleep quality in patients with fibromyalgia syndrome (FMS) are still unknown. By identifying these factors, we could raise new mechanistic hypotheses and guide management approaches. We aimed to describe the sleep quality of FMS patients and to explore the clinical and quantitative sensory testing (QST) predictors of poor sleep quality and its subcomponents. METHODS: This study is a cross-sectional analysis of an ongoing clinical trial. We performed linear regression models between sleep quality (Pittsburgh Sleep Quality Index [PSQI]) and demographic, clinical, and QST variables, controlling for age and gender. Predictors for the total PSQI score and its seven subcomponents were found using a sequential modeling approach. RESULTS: We included 65 patients. The PSQI score was 12.78 ± 4.39, with 95.39% classified as poor sleepers. Sleep disturbance, use of sleep medications, and subjective sleep quality were the worst subdomains. We found poor PSQI scores were highly associated with symptom severity (FIQR score and PROMIS fatigue), pain severity, and higher depression levels, explaining up to 31% of the variance. Fatigue and depression scores also predicted the subjective sleep quality and daytime dysfunction subcomponents. Heart rate changes (surrogate of physical conditioning) predicted the sleep disturbance subcomponent. QST variables were not associated with sleep quality or its subcomponents. CONCLUSIONS: Symptom severity, fatigue, pain, and depression (but no central sensitization) are the main predictors of poor sleep quality. Heart rate changes independently predicted the sleep disturbance subdomain (the most affected one in our sample), suggesting an essential role of physical conditioning in modulating sleep quality in FMS patients. This underscores the need for multidimensional treatments targeting depression and physical activity to improve the sleep quality of FMS patients.

Association of Mu opioid receptor (A118G) and BDNF (G196A) polymorphisms with rehabilitation-induced cortical inhibition and analgesic response in chronic osteoarthritis pain

Background/objective: Chronic pain due to osteoarthritis (OA) is a prevalent cause of global disability. New biomarkers are needed to improve treatment allocation, and genetic polymorphisms are promising candidates. Method: We aimed to assess the association of OPRM1 (A118G and C17T) and brain-derived neurotrophic factor (BDNF [G196A]) polymorphisms with pain-related outcomes and motor cortex excitability metrics (measured by transcranial magnetic stimulation) in 113 knee OA patients with chronic pain. We performed adjusted multivariate regression analyses to compare carriers versus non-carriers in terms of clinical and neurophysiological characteristics at baseline, and treatment response (pain reduction and increased cortical inhibitory tonus) after rehabilitation. Results: Compared to non-carriers, participants with polymorphisms on both OPRM1 (A118G) and BDNF (G196A) genes were less likely to improve pain after rehabilitation (85 and 72% fewer odds of improvement, respectively). Likewise, both carriers of OPRM1 polymorphisms (A118G and C17T) were also less likely to improve cortical inhibition (short intracortical inhibition [SICI], and intracortical facilitation [ICF], respectively). While pain and cortical inhibition improvement did not correlate in the total sample, the presence of OPRM1 (A118G) and BDNF (G196A) polymorphisms moderated this relationship. Conclusions: These results underscore the promising role of combining genetic and neurophysiological markers to endotype the treatment response in this population. (AU)

Association of Mu opioid receptor (A118G) and BDNF (G196A) polymorphisms with rehabilitation-induced cortical inhibition and analgesic response in chronic osteoarthritis pain.

Background/objective: Chronic pain due to osteoarthritis (OA) is a prevalent cause of global disability. New biomarkers are needed to improve treatment allocation, and genetic polymorphisms are promising candidates. Method: We aimed to assess the association of OPRM1 (A118G and C17T) and brain-derived neurotrophic factor (BDNF [G196A]) polymorphisms with pain-related outcomes and motor cortex excitability metrics (measured by transcranial magnetic stimulation) in 113 knee OA patients with chronic pain. We performed adjusted multivariate regression analyses to compare carriers versus non-carriers in terms of clinical and neurophysiological characteristics at baseline, and treatment response (pain reduction and increased cortical inhibitory tonus) after rehabilitation. Results: Compared to non-carriers, participants with polymorphisms on both OPRM1 (A118G) and BDNF (G196A) genes were less likely to improve pain after rehabilitation (85 and 72% fewer odds of improvement, respectively). Likewise, both carriers of OPRM1 polymorphisms (A118G and C17T) were also less likely to improve cortical inhibition (short intracortical inhibition [SICI], and intracortical facilitation [ICF], respectively). While pain and cortical inhibition improvement did not correlate in the total sample, the presence of OPRM1 (A118G) and BDNF (G196A) polymorphisms moderated this relationship. Conclusions: These results underscore the promising role of combining genetic and neurophysiological markers to endotype the treatment response in this population.

Transcutaneous auricular vagus nerve stimulation effects on inflammatory markers and clinical evolution of patients with COVID-19: a pilot randomized clinical trial.

OBJECTIVE: To evaluate the effects of transcutaneous auricular vagus nerve stimulation (taVNS) on inflammatory markers and clinical outcomes in patients with COVID-19. METHODS: A randomized blinded pilot study was carried out with 21 individuals hospitalized with COVID-19 who received 14 sessions of active (a-taVNS) or sham taVNS (s-taVNS). The level of interleukin-6 (IL-6), interleukin-10 (IL-10), cortisol, and C-reactive protein (CRP) in plasma and clinical evolution pre- and post-intervention were evaluated. The memory and attention levels were evaluated 14 days after the end of the treatment. RESULTS: After treatment, significant intragroup differences were found in the CRP (p = 0.01), IL-6 (p = 0.01), and cortisol (p = 0.01) levels; however, in the comparison between the groups, only the CRP level was statistically lower for the a-taVNS (p = 0.04). The impression of improvement in memory and attention was greater in the a-taVNS than in the s-taVNS (p = 0.01, p = 0.04, respectively). There was no difference between the other clinical outcomes. CONCLUSIONS: taVNS is a viable and safe intervention in the acute care of patients with COVID-19, which can modulate their inflammatory profile and improve cognitive symptoms. However, improvements in overall clinical outcomes were not detected. Larger sample sizes and longer follow-ups are needed to confirm the anti-inflammatory and clinical effects of taVNS in patients with COVID-19. TRIALS REGISTRY: The Brazilian Registry of Clinical Trials (RBR-399t4g5).

Immune checkpoint inhibitor therapy and outcomes from SARS-CoV-2 infection in patients with cancer: a joint analysis of OnCovid and ESMO-CoCARE registries.

BACKGROUND: As management and prevention strategies against COVID-19 evolve, it is still uncertain whether prior exposure to immune checkpoint inhibitors (ICIs) affects COVID-19 severity in patients with cancer. METHODS: In a joint analysis of ICI recipients from OnCovid (NCT04393974) and European Society for Medical Oncology (ESMO) CoCARE registries, we assessed severity and mortality from SARS-CoV-2 in vaccinated and unvaccinated patients with cancer and explored whether prior immune-related adverse events (irAEs) influenced outcome from COVID-19. FINDINGS: The study population consisted of 240 patients diagnosed with COVID-19 between January 2020 and February 2022 exposed to ICI within 3 months prior to COVID-19 diagnosis, with a 30-day case fatality rate (CFR30) of 23.6% (95% CI 17.8 to 30.7%). Overall, 42 (17.5%) were fully vaccinated prior to COVID-19 and experienced decreased CFR30 (4.8% vs 28.1%, p=0.0009), hospitalization rate (27.5% vs 63.2%, p<0.0001), requirement of oxygen therapy (15.8% vs 41.5%, p=0.0030), COVID-19 complication rate (11.9% vs 34.6%, p=0.0040), with a reduced need for COVID-19-specific therapy (26.3% vs 57.9%, p=0.0004) compared with unvaccinated patients. Inverse probability of treatment weighting (IPTW)-fitted multivariable analysis, following a clustered-robust correction for the data source (OnCovid vs ESMO CoCARE), confirmed that vaccinated patients experienced a decreased risk of death at 30 days (adjusted OR, aOR 0.08, 95% CI 0.01 to 0.69).Overall, 38 patients (15.8%) experienced at least one irAE of any grade at any time prior to COVID-19, at a median time of 3.2 months (range 0.13-48.7) from COVID-19 diagnosis. IrAEs occurred independently of baseline characteristics except for primary tumor (p=0.0373) and were associated with a significantly decreased CFR30 (10.8% vs 26.0%, p=0.0462) additionally confirmed by the IPTW-fitted multivariable analysis (aOR 0.47, 95% CI 0.33 to 0.67). Patients who experienced irAEs also presented a higher median absolute lymphocyte count at COVID-19 (1.4 vs 0.8 109 cells/L, p=0.0098). CONCLUSION: Anti-SARS-CoV-2 vaccination reduces morbidity and mortality from COVID-19 in ICI recipients. History of irAEs might identify patients with pre-existing protection from COVID-19, warranting further investigation of adaptive immune determinants of protection from SARS-CoV-2.

The Economic Burden of Localized Prostate Cancer and Insights Derived from Cost-Effectiveness Studies of the Different Treatments.

Prostate cancer has huge health and societal impacts, and there is no clear consensus on the most effective and efficient treatment strategy for this disease, particularly for localized prostate cancer. We have reviewed the scientific literature describing the economic burden and cost-effectiveness of different treatment strategies for localized prostate cancer in OECD countries. We initially identified 315 articles, studying 13 of them in depth (those that met the inclusion criteria), comparing the social perspectives of cost, time period, geographical area, and severity. The economic burden arising from prostate cancer due to losses in productivity and increased caregiver load is noticeable, but clinical decision-making is carried out with more subjective variability than would be advisable. The direct cost of the intervention was the main driver for the treatment of less severe cases of prostate cancer, whereas for more severe cases, the most important determinant was the loss in productivity. Newer, more affordable radiotherapy strategies may play a crucial role in the future treatment of early prostate cancer. The interpretation of our results depends on conducting thorough sensitivity analyses. This approach may help better understand parameter uncertainty and the methodological choices discussed in health economics studies. Future results of ongoing clinical trials that are considering genetic characteristics in assessing treatment response of patients with localized prostate cancer may shed new light on important clinical and pharmacoeconomic decisions.

An International Comparison of Presentation, Outcomes and CORONET Predictive Score Performance in Patients with Cancer Presenting with COVID-19 across Different Pandemic Waves.

Patients with cancer have been shown to have increased risk of COVID-19 severity. We previously built and validated the COVID-19 Risk in Oncology Evaluation Tool (CORONET) to predict the likely severity of COVID-19 in patients with active cancer who present to hospital. We assessed the differences in presentation and outcomes of patients with cancer and COVID-19, depending on the wave of the pandemic. We examined differences in features at presentation and outcomes in patients worldwide, depending on the waves of the pandemic: wave 1 D614G (n = 1430), wave 2 Alpha (n = 475), and wave 4 Omicron variant (n = 63, UK and Spain only). The performance of CORONET was evaluated on 258, 48, and 54 patients for each wave, respectively. We found that mortality rates were reduced in subsequent waves. The majority of patients were vaccinated in wave 4, and 94% were treated with steroids if they required oxygen. The stages of cancer and the median ages of patients significantly differed, but features associated with worse COVID-19 outcomes remained predictive and did not differ between waves. The CORONET tool performed well in all waves, with scores in an area under the curve (AUC) of >0.72. We concluded that patients with cancer who present to hospital with COVID-19 have similar features of severity, which remain discriminatory despite differences in variants and vaccination status. Survival improved following the first wave of the pandemic, which may be associated with vaccination and the increased steroid use in those patients requiring oxygen. The CORONET model demonstrated good performance, independent of the SARS-CoV-2 variants.

Temporal Summation in Fibromyalgia Patients: Comparing Phasic and Tonic Paradigms.

Introduction: Fibromyalgia (FM) is associated with dysfunctional pain modulation mechanisms, including central sensitization. Experimental pain measurements, such as temporal summation (TS), could serve as markers of central sensitization and have been previously studied in these patients, with conflicting results. Our objective in this study was to explore the relationships between two different protocols of TS (phasic and tonic) and test the associations between these measures and other clinical variables. Materials and Methods: In this cross-sectional analysis of a randomized clinical trial, patients were instructed to determine their pain-60 test temperature, then received one train of 15 repetitive heat stimuli and rated their pain after the 1st and 15th stimuli: TSPS-phasic was calculated as the difference between those. We also administered a tonic heat test stimulus at the same temperature continuously for 30 s and asked them to rate their pain levels after 10 s and 30 s, calculating TSPS-tonic as the difference between them. We also collected baseline demographic data and behavioral questionnaires assessing pain, depression, fatigue, anxiety, sleepiness, and quality of life. We performed univariable analyses of the relationship between TSPS-phasic and TSPS-tonic, and between each of those measures and the demographic and clinical variables collected at baseline. We then built multivariable linear regression models to find predictors for TSPS-phasic and TSPS-tonic, while including potential confounders and avoiding collinearity. Results: Fifty-two FM patients were analyzed. 28.85% developed summation during the TSPS-phasic protocol while 21.15% developed summation during the TSPS-tonic protocol. There were no variables associated TSPS phasic or tonic in the univariable analyses and both measures were not correlated. On the multivariate model for the TSPS-phasic protocol, we found a weak association with pain variables. BPI-pain subscale was associated with more temporal summation in the phasic protocol (ß = 0.38, p = 0.029), while VAS for pain was associated with less summation in the TSPS-tonic protocol (ß = -0.5, p = 0.009). Conclusion: Our results suggest that, using heat stimuli with pain-60 temperatures, a TSPS-phasic protocol and a TSPS-tonic protocol are not correlated and could index different neural responses in FM subjects. Further studies with larger sample sizes would be needed to elucidate whether such responses could help differentiating subjects with FM into specific phenotypes.

Motor cortex inhibition as a fibromyalgia biomarker: a meta-analysis of transcranial magnetic stimulation studies.

Fibromyalgia (FM) is a common and refractory chronic pain condition with multiple clinical phenotypes. The current diagnosis is based on a syndrome identification which can be subjective and lead to under or over-diagnosis. Therefore, there is a need for objective biomarkers for diagnosis, phenotyping, and prognosis (treatment response and follow-up) in fibromyalgia. Potential biomarkers are measures of cortical excitability indexed by transcranial magnetic stimulation (TMS). However, no systematic analysis of current evidence has been performed to assess the role of TMS metrics as a fibromyalgia biomarker. Therefore, this study aims to evaluate evidence on corticospinal and intracortical motor excitability in fibromyalgia subjects and to assess the prognostic role of TMS metrics as response biomarkers in FM. We conducted systematic searches on PubMed/Medline, Embase, and Cochrane Central databases for observational studies and randomized controlled trials on fibromyalgia subjects that used TMS as an assessment. Three reviewers independently selected and extracted the data. Then, a random-effects model meta-analysis was performed to compare fibromyalgia and healthy controls in observational studies. Also, to compare active versus sham treatments, in randomized controlled trials. Correlations between changes in TMS metrics and clinical improvement were explored. The quality and evidence certainty were assessed following standardized approaches. We included 15 studies (696 participants, 474 FM subjects). The main findings were: (1) fibromyalgia subjects present less intracortical inhibition (mean difference (MD) = -0.40, 95% confidence interval (CI) -0.69 to -0.11) and higher resting motor thresholds (MD = 6.90 µV, 95% CI 4.16 to 9.63 µV) when compared to controls; (2) interventions such as exercise, pregabalin, and non-invasive brain stimulation increased intracortical inhibition (MD = 0.19, 95% CI 0.10 to 0.29) and cortical silent period (MD = 14.92 ms, 95% CI 4.86 to 24.98 ms), when compared to placebo or sham stimulation; (3) changes on intracortical excitability are correlated with clinical improvements - higher inhibition moderately correlates with less pain, depression, and pain catastrophizing; lower facilitation moderately correlates with less fatigue. Measures of intracortical inhibition and facilitation indexed by TMS are potential diagnostic and treatment response biomarkers for fibromyalgia subjects. The disruption in the intracortical inhibitory system in fibromyalgia also provides additional evidence that fibromyalgia has some neurophysiological characteristics of neuropathic pain. Treatments inducing an engagement of sensorimotor systems (e.g., exercise, motor imagery, and non-invasive brain stimulation) could restore the cortical inhibitory tonus in FM and induce clinical improvement.

Establishment of CORONET, COVID-19 Risk in Oncology Evaluation Tool, to Identify Patients With Cancer at Low Versus High Risk of Severe Complications of COVID-19 Disease On Presentation to Hospital.

PURPOSE: Patients with cancer are at increased risk of severe COVID-19 disease, but have heterogeneous presentations and outcomes. Decision-making tools for hospital admission, severity prediction, and increased monitoring for early intervention are critical. We sought to identify features of COVID-19 disease in patients with cancer predicting severe disease and build a decision support online tool, COVID-19 Risk in Oncology Evaluation Tool (CORONET). METHODS: Patients with active cancer (stage I-IV) and laboratory-confirmed COVID-19 disease presenting to hospitals worldwide were included. Discharge (within 24 hours), admission (≥ 24 hours inpatient), oxygen (O2) requirement, and death were combined in a 0-3 point severity scale. Association of features with outcomes were investigated using Lasso regression and Random Forest combined with Shapley Additive Explanations. The CORONET model was then examined in the entire cohort to build an online CORONET decision support tool. Admission and severe disease thresholds were established through pragmatically defined cost functions. Finally, the CORONET model was validated on an external cohort. RESULTS: The model development data set comprised 920 patients, with median age 70 (range 5-99) years, 56% males, 44% females, and 81% solid versus 19% hematologic cancers. In derivation, Random Forest demonstrated superior performance over Lasso with lower mean squared error (0.801 v 0.807) and was selected for development. During validation (n = 282 patients), the performance of CORONET varied depending on the country cohort. CORONET cutoffs for admission and mortality of 1.0 and 2.3 were established. The CORONET decision support tool recommended admission for 95% of patients eventually requiring oxygen and 97% of those who died (94% and 98% in validation, respectively). The specificity for mortality prediction was 92% and 83% in derivation and validation, respectively. Shapley Additive Explanations revealed that National Early Warning Score 2, C-reactive protein, and albumin were the most important features contributing to COVID-19 severity prediction in patients with cancer at time of hospital presentation. CONCLUSION: CORONET, a decision support tool validated in health care systems worldwide, can aid admission decisions and predict COVID-19 severity in patients with cancer.

Association Between Step Count Measured With a Smartphone App (Pain-Note) and Pain Level in Patients With Chronic Pain: Observational Study.

BACKGROUND: Chronic pain is the leading cause of disability, affecting between 20% and 50% of the global population. The key recommended treatment is physical activity, which can be measured in daily life using a pedometer. However, poor adherence to pedometer use can result in incorrect measurements. Furthermore, only a few studies have investigated a possible curvilinear association between physical activity and chronic pain. OBJECTIVE: In this study, we developed the Pain-Note smartphone app to collect real-world data on step count, using the smartphone's built-in pedometer. The aims of our research are (1) to evaluate the association between daily step count and pain level among patients with chronic pain and (2) determine if the association between daily step count and pain level was curvilinear. METHODS: We conducted a cross-sectional study based on step count data collected with the app and on the results of questionnaires, which measured the duration and intensity of pain, the widespread pain index, the symptom severity score, and the insomnia severity scale, including 7 questions for symptoms of depression. We analyzed the association between step count and pain level as a nonlinear relationship using a restricted cubic spline model. A prespecified subgroup analysis was also conducted based on fibromyalgia criteria. RESULTS: Between June 1, 2018, and June 11, 2020, a total of 6138 records were identified, of which 1273 were analyzed. The mean age of the participants was 38.7 years, 81.9% (1043/1273) were female, and chronic pain was present for more than 5 years in 43.2% (550/1273) of participants. Participants in the third and fourth quartiles for step count (more than 3045 and 5668 steps a day, respectively) showed a significant positive association between higher step count and lower numerical pain rating scale (mean difference -0.43, 95% CI -0.78 to -0.08, P=.02; -0.45; 95% CI -0.8 to -0.1, P=.01, respectively) than those in the first quartile (less than or equal to 1199 steps a day). The restricted cubic spline model for the association between step count and pain scale displayed a steep decline followed by a moderate decrease as the step count increased; the inflection point was 5000 steps. However, this association was not observed among participants who met the fibromyalgia criteria (491/1273), who showed a steep positive increase below 2000 steps. Data were collected between June 1, 2018, and June 11, 2020, and were analyzed on November 18, 2021. CONCLUSIONS: Step count measured with the Pain-Note app showed a nonlinear association with pain level. Although participants with and without fibromyalgia showed a negative correlation between step count and pain level, participants who meet the criteria for fibromyalgia may present a different relationship between walking and pain perception compared to those in the general chronic pain population.

Safety of Direct Oral Anticoagulants Compared to Warfarin for Atrial Fibrillation after Cardiac Surgery: A Systematic Review and Meta-Analysis.

The evidence for use of direct oral anticoagulants (DOACs) in the management of post-operative cardiac surgery atrial fibrillation is limited and mostly founded on clinical trials that excluded this patient population. We performed a systematic review and meta-analysis of clinical trials and observational studies to evaluate the hypothesis that DOACs are safe compared to warfarin for the anticoagulation of patients with post-operative cardiac surgery atrial fibrillation. We searched PubMed, EMBASE, Web of Science, clinicaltrials.gov, and the Cochrane Library for clinical trials and observational studies comparing DOAC with warfarin in patients ≥18 years old who had post-cardiac surgery atrial fibrillation. Primary outcomes included stroke, systemic embolization, bleeding, and mortality. We performed a random-effects meta-analysis of all outcomes. The meta-analysis for the primary outcomes showed significantly lower risk of stroke with DOAC use (6 studies, 7143 patients, RR 0.64; 95% CI 0.50-0.81, I2: 0.0%) compared to warfarin, a trend towards lower risk of systemic embolization (4 studies, 7289 patients, RR 0.64, 95% CI 0.41-1.01, I2: 31.99%) and similar risks of bleeding (14 studies, 10182 patients, RR 0.91; 95% CI 0.74-1.10, I2: 26.6%) and mortality (12 studies, 9843 patients, relative risk [RR] 1.01; 95% CI 0.74-1.37, I2: 26.5%). Current evidence suggests that DOACs, compared to warfarin, in the management of atrial fibrillation after cardiac surgery is associated with lower risk of stroke and a strong trend for lower risk of systemic embolization, and no evidence of increased risk for hospital readmission, bleeding and mortality.

Specific Electroencephalographic Signatures for Pain and Descending Pain Inhibitory System in Spinal Cord Injury.

OBJECTIVES: The pain related to spinal cord injury (SCI) is difficult to treat, and it is associated with significant morbidity. One aspect to improve therapeutics is to explore markers of pain and its correlates in SCI. METHODS: In this cross-sectional neurophysiological analysis of a randomized, double-blind controlled trial, 39 patients with SCI were included. We analyzed conditioned pain modulation (CPM) efficiency as the index of the descending pain inhibitory system, EEG variables, and clinical pain levels as measured by the Visual Analogue Scale. Regression analyses were performed to assess the relationship among EEG variables, pain levels, and CPM. RESULTS: We included 39 SCI patients, 74% reported SCI-related pain. We found that (1) less alpha and beta power are related to pain presence, (2) less alpha and beta power are associated with higher pain levels among patients with pain, (3) patients with pain have decreased peak alpha-theta frequency compared to no-pain group, (4) more relative theta power are related to the presence of low CPM efficiency, (5) higher relative theta power is associated with lower CPM efficiency. CONCLUSIONS: Our results confirm and provide additional data on the relationship between decreased alpha and beta frequencies and higher pain levels. One important finding, though, was a specific and different EEG signature for the descending inhibitory pain system, as we showed that increased theta EEG power is related to decreased CPM efficiency; suggesting that, although low CPM efficiency plays a major role in pain in these participants, it does seem to be associated with a specific oscillatory brain rhythm different from clinical pain. These findings have significant implications for future research on EEG-based biomarkers of pain in post-SCI and new interventions as neurofeedback to manage pain in this population.

Recruitment characteristics and non-adherence associated factors of fibromyalgia patients in a randomized clinical trial: A retrospective survival analysis.

INTRODUCTION: Fibromyalgia is a complex pain condition that affects mostly women. Given the disease's lack of understanding, patients report poor adherence to medication and mistrust of medical services. This study aims to describe the recruitment characteristics and non-adherence associated factors of fibromyalgia patients to an RCT. METHODS: We performed a retrospective longitudinal analysis with data from our ongoing RCT. We investigated characteristics of subjects recruited, consented, and randomized. Adherence was studied using survival analysis techniques, and its associated factors were identified using Cox proportional hazards regression model. RESULTS: 524 subjects were contacted, 269 were eligible, 61 consented and 40 subjects were randomized. Thirty-eight percent were non-adherent to the protocol with a median of visits of five. The recruitment survey reported that 90% would likely participate in RCTs, 52% had previous participation, and 19% were aware of RCTs by their physicians. Some barriers were investigator-related (staff's friendliness and receiving the results of their trial participation) and center-related (privacy-confidentiality issues and the institution's reputation), without difference between adherent and non-adherent participants. We report significant factors for non-adherence as VAS anxiety score of 5 or more (5.3 HR, p = 0.01), Body Mass Index (BMI) (0.91 HR, p = 0.041) and Quality of Life (QoL) - Personal development subdomain (0.89 HR, p = 0.046). CONCLUSION: Recruitment and adherence of fibromyalgia patients is a challenge; however, they seem eager to participate in RCTs. We recommend creating a comfortable, friendly and trusting environment to increase the recruitment rate. Higher anxiety, lower BMI and lower quality of life were associated with a higher attrition rate.

Barriers and facilitators for clinical trial participation of underrepresented and non-underrepresented fibromyalgia patients: A cross-sectional internet survey.

BACKGROUND: There is a need of well-powered randomized clinical trials in fibromyalgia. However, challenges for recruitment are presented. This study aims to describe and assess the perception of barriers and facilitators and the associated factors for the participation of underrepresented and non-underrepresented fibromyalgia patients. METHODS: We performed an online survey through REDCap (Research Electronic Data Capture) targeting fibromyalgia patients from April 7 to July 3, 2020 during the COVID-19 stay home mandate and it was restricted to the United States of America. We described and compared the survey characteristics between underrepresented and non-underrepresented participants, and we performed logistic regression models to assess the associated factors with clinical trial participation. RESULTS: In total, 481 completed the survey including 168 underrepresented fibromyalgia patients. Only (1) 11.09 % reported previous participation in clinical trials and the significant perceived barriers were investigator-related (lack of friendliness of research staff and the opportunity to receive the results) and center-related (privacy and confidentiality policies, and the institution's reputation); (2) the participation rate and perceived barriers and facilitators were similar between underrepresented and non-underrepresented patients; and was positively associated with low income, higher age, and clinical trial awareness from their physician; and negatively associated with the perception of investigator-related barriers; and (4) for the underrepresented population, the presence of emotional support. CONCLUSION: Our findings suggest low rates of participation, regardless of underrepresented population status. Strategies as involving their physician as liaison to increase the awareness of clinical trials, as well as improving patient-researcher communication should be considered in this population.

Therapeutic Approaches With Immune Checkpoint Inhibitors in Head and Neck Cancers and the Role of PD-L1 as a Biomarker.

Head and neck squamous cell carcinoma (HNSCC) is a potential curative disease at its localized stage, by the use of multimodal treatment including surgery, radiation, and chemotherapy. While the metastatic stage is considered incurable and is characterized by poor prognosis. Conventional cytotoxic chemotherapy in addition to cetuximab were the only available systemic treatment with limited efficacy and modest median overall survival barely crossing the 1 year limit. Immunotherapy with PD-1 and PD-L1 inhibitors has revolutionized the treatment of multiple cancers. Recently, Immunotherapy is being extensively explored in head and neck cancer and clinical trials have shown impressive results that allowed to immune check point inhibitors to be the new standard of care. In this article we tried to explain the rationale and mechanisms of targeting the immune system in head and neck carcinoma and to report the results from the phase III clinical trials that put the immunotherapy as a new standard of care for head and neck cancer.