Prolonged time of after-sensation after experimental pain stimuli despite efficient conditioned pain modulation in patients with chronic neuropathic pain after traumatic nerve injuries in upper extremity

Background:  As yet, there is limited research that can identify factors that differentiate between painful and nonpainful neuropathies after traumatic nerve injury. The aim of this study was to compare subjects with pain and without pain, all after operative nerve repair in the upper extremities. Methods:  Subjects in both groups (pain, n = 69; painless, n = 62) underwent clinical assessment of sensory nerve function and psychophysical tests: quantitative sensory testing and conditioned pain modulation (CPM). Conditioned pain modulation was assessed by pain ratings to 120 seconds pressure stimuli administered before and after a 60 seconds noxious 4°C cold conditioning stimulus (CS). Time of recovery (time off) of pain intensity from peak VASmaxc after CS was recorded. Questionnaires about the quality of life (RAND-36) and disability of the extremity (QuickDash) were completed. Results:  There were no significant differences between groups for CPM (P = 0.19). Time off was 42 seconds in subjects with pain in comparison with 28 seconds in those without pain (P < 0.0001). Compared with individuals reporting no pain, participants with neuropathic pain after nerve injuries had 1.8 times the odds of recovering later after CS, gain of function findings at sensory examination (P < 0.0001), lower scores of the physical component of RAND-36 (P < 0.0001), and increase arm disability (P < 0.0001). Hyperesthesia to cold pain stimulation (P = 0.03) and lowered pain pressure threshold (P = 0.01) were found in the pain group. Conclusion:  Recovery after the pain induced by cold CS indicates changes in central processing of pain and provides a potential measurement of endogenous pain modulation in individuals with chronic neuropathic pain

Sensor-Based Measurement of Nociceptive Pain : An Exploratory Study with Healthy Subjects

Valid assessment of pain is essential in daily clinical practice to enhance the quality of care for the patients and to avoid the risk of addiction to strong analgesics. The aim of this paper is to find a method for objective and quantitative evaluation of pain using multiple physiological markers. Data was obtained from healthy volunteers exposed to thermal and ischemic stimuli. Twelve subjects were recruited and their physiological data including skin conductance, heart rate, and skin temperature were collected via a wrist-worn sensor together with their selfreported pain on a visual analogue scale (VAS). Statistically significant differences (p &lt; 0.01) were found between physiological scores obtained with the wearable sensor before and during the thermal test. Test-retest reliability of sensor-based measures was good during the thermal test with intraclass correlation coefficients ranging from 0.22 to 0.89. These results support the idea that a multi-sensor wearable device can objectively measure physiological reactions in the subjects due to experimentally induced pain, which could be used for daily clinical practice and as an endpoint in clinical studies. Nevertheless, the results indicate a need for further investigation of the method in real-life pain settings.</p

Evaluating the Appropriate Use Criteria for Coronary Revascularization in Stable Ischemic Heart Disease Using Randomized Data From the ISCHEMIA Trial

BACKGROUND: The appropriate use criteria for revascularization of stable ischemic heart disease have not been evaluated using randomized data. Using data from the randomized ISCHEMIA trial (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches; July 2012 to January 2018, 37 countries), the health status benefits of an invasive strategy over a conservative one were examined within appropriate use criteria scenarios. METHODS: Among 1833 participants mapped to 36 appropriate use criteria scenarios, symptom status was assessed using the Seattle Angina Questionnaire-7 at 1 year for each scenario and for each of the 6 patient characteristics used to define the scenarios. Coronary anatomy and SYNTAX(Synergy between percutaneous coronary intervention with Taxus and cardiac surgery) scores were measured using coronary computed tomography angiography. Treatment effects are expressed as an odds ratio for a better health status outcome with an invasive versus conservative treatment strategy using Bayesian hierarchical proportional odds models. Differences in the primary clinical outcome were similarly examined. RESULTS: The mean age was 63 years, 81% were male, and 71% were White. Diabetes was present in 28% and multivessel disease in 51%. Most clinical scenarios favored invasive for better 1-year health status. The benefit of an invasive strategy on Seattle Angina Questionnaire angina frequency scores was reduced for asymptomatic patients (odds ratio [95% credible interval], 1.16 [0.66-1.71] versus 2.26 [1.75-2.80]), as well as for those on no antianginal medications. Diabetes, number of diseased vessels, proximal left anterior descending coronary artery location, and SYNTAX score did not effectively identify patients with better health status after invasive treatment, and minimal differences in clinical events were observed. CONCLUSIONS: Applying the randomization scheme from the ISCHEMIA trial to appropriate clinical scenarios revealed baseline symptoms and antianginal therapy to be the primary drivers of health status benefits from invasive management. Consideration should be given to reducing the patient characteristics collected to generate appropriateness ratings to improve the feasibility of future data collection

Health-status outcomes with invasive or conservative care in coronary disease

BACKGROUND In the ISCHEMIA trial, an invasive strategy with angiographic assessment and revascularization did not reduce clinical events among patients with stable ischemic heart disease and moderate or severe ischemia. A secondary objective of the trial was to assess angina-related health status among these patients. METHODS We assessed angina-related symptoms, function, and quality of life with the Seattle Angina Questionnaire (SAQ) at randomization, at months 1.5, 3, and 6, and every 6 months thereafter in participants who had been randomly assigned to an invasive treatment strategy (2295 participants) or a conservative strategy (2322). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate differences between the treatment groups. The primary outcome of this health-status analysis was the SAQ summary score (scores range from 0 to 100, with higher scores indicating better health status). All analyses were performed in the overall population and according to baseline angina frequency. RESULTS At baseline, 35% of patients reported having no angina in the previous month. SAQ summary scores increased in both treatment groups, with increases at 3, 12, and 36 months that were 4.1 points (95% credible interval, 3.2 to 5.0), 4.2 points (95% credible interval, 3.3 to 5.1), and 2.9 points (95% credible interval, 2.2 to 3.7) higher with the invasive strategy than with the conservative strategy. Differences were larger among participants who had more frequent angina at baseline (8.5 vs. 0.1 points at 3 months and 5.3 vs. 1.2 points at 36 months among participants with daily or weekly angina as compared with no angina). CONCLUSIONS In the overall trial population with moderate or severe ischemia, which included 35% of participants without angina at baseline, patients randomly assigned to the invasive strategy had greater improvement in angina-related health status than those assigned to the conservative strategy. The modest mean differences favoring the invasive strategy in the overall group reflected minimal differences among asymptomatic patients and larger differences among patients who had had angina at baseline

Initial invasive or conservative strategy for stable coronary disease

BACKGROUND Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, 121.8 percentage points; 95% CI, 124.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used