ORIGINAL RESEARCH article
Sec. Autonomic Neuroscience
Volume 9 - 2018 | https://doi.org/10.3389/fphys.2018.01199
Postoperative Pain Assessment Indices Based on Photoplethysmography Waveform Analysis
- 1Interdisciplinary Program in Biomedical Engineering, Chonnam National University, Gwangju, South Korea
- 2Department of Biomedical Engineering, Chonnam National University, Yeosu, South Korea
- 3Department of Clinical Pharmacology and Therapeutics, University of Ulsan College of Medicine, Seoul, South Korea
- 4Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
The purpose of this study was to derive parameters that might reflect postoperative pain from photoplethysmography (PPG) and verify the derived parameters in postoperative pain assessment. We obtained preoperative and postoperative PPG and 100-mm visual analog scale (VAS) from 65 surgical patients and extracted a total of 51 PPG morphology-based parameters and their normalized parameters from these PPGs obtained. Pain discrimination performances of these derived parameters were assessed by statistical analyses, including Wilcoxon signed rank test with Bonferroni correction, classification accuracy based on logistic regression, and 4-fold cross validation. After comparing these parameters derived from PPG in pre- and post-operative conditions, statistically significant difference was found in 36 of the 51 parameters. Using logistic classification, dynamic between-pulse parameters such as normalized systolic amplitude variation and normalized diastolic amplitude variation showed better pain classification performance than the static within-pulse parameters. VAS score was 0 in every pre-operation condition, but >60 VAS was observed in the post-operative condition. Systolic peak amplitude variation normalized by PPG AC amplitude showed the best performance in classifying post-operative pain, with accuracy, sensitivity, specificity, and positive predictivity values of 79.5, 74.0, 86.0, and 84.5%, respectively. These results are superior to those of the surgical pleth index (SPI, GE Healthcare, Chicago, IL, United States) at 65.9, 65.9, 66.5, and 66.5%, respectively.
Up to 50% of surgical patients are known to experience moderate or even severe pain immediately after surgery (Boselli et al., 2013; Gerbershagen et al., 2013). While opioids are widely used as effective analgesics, opioid sensitivity is well known to vary widely among individuals. Pain sensitivity and analgesic susceptibility are major factors limiting the objectivity of post-operative pain management. Opioids can result in underdose or overdose of medication. Overdosing of analgesics is a life-threatening condition with disadvantageous effects such as prolonged sedation or prolonged respiratory insufficiency (Macintyre et al., 2011; Apfel et al., 2012). In addition, opioid analgesic overdose encompasses a range of clinical findings such as respiratory depression, miosis, stupor, hepatic injury from acetaminophen or hypoxemia, myoglobinuric renal failure, rhabdomyolysis, absent or hypoactive bowel sounds, compartment syndrome, and hypothermia (Boyer, 2012).
Therefore, the challenge for an effective analgesic strategy is to estimate the dose that can exactly counterbalance the amount of ongoing nociception with respect to individual susceptibility to analgesics and individual sensitivity to pain (Ip et al., 2009). Maintaining an appropriate level of analgesics is very important to improve the patient’s prognosis (Musizza and Ribaric, 2010). However, it is difficult to judge the adequate amount of opioid because the degree of pain experienced during surgery varies depending on the patient as well as the environmental and emotional factors of the same patient. This is because indices such as anxiety, sensitivity, and distress tolerance closely related to pain experience can vary greatly among individuals.
To quantify surgical pain, previous studies have focused on autonomic nervous system responses such as changes in heart rate (HR) and blood pressure, amount of tears, changes in pupil size, respiratory rate and volume, and patient movement (Russell, 1989; Moerman et al., 1993). Among these responses, the surgical pleth index (SPI, GE Healthcare, Chicago, IL, United States), an index based on photoplethysmography (PPG), is a promising surgical pain quantification index. SPI is a non-invasive, dimensionless score (0–100), which allows an estimate of intraoperative nociception. SPI is a model of PPG amplitude (PPGA) and heart beat interval (HBI). It is modeled as SPI = 100 × (0.67 × PPGAnorm+0.33 × HBInorm) (Huiku et al., 2007). PPGA is known to be strongly correlated with sympathetic response by surgical stimulation while HBI is known to correlate with opioid effect (Huiku et al., 2007). The value of SPI ranges from 0 to 100, with a value of 0 indicating weaker surgical stimulus, while a value closer to 100 indicated stronger surgical stimulus. In addition, SPI 50 can be used to differentiate a patient’s pain intensity in general anesthesia (Chen et al., 2010). It has been reported that SPI can vary with pain-stimuli or anesthetic concentration in propofol-remifentanil anesthesia (Huiku et al., 2007). SPI has demonstrated excellent performance compared to various other pain estimation methods based on HR, blood pressure, or response entropy (Wennervirta et al., 2008). Several studies have reported that SPI is a potential indicator for pain assessment in unconscious patients (Ahonen et al., 2007; Huiku et al., 2007; Kallio et al., 2008). However, according to Ledowski et al. (2009), SPI has limited accuracy in assessing conscious subjects. In fact, the manufacturer recommends the use of SPI only during anesthesia; this is presumably because SPI is normalized with data from anesthesia patients only. At present, SPI are frequently used in the clinical setting. However, a complete assessment technique for pain is not available, especially for post-operative pain.
In this study, we proposed new indicators in post-operative pain assessment by deriving characteristic features not presented in previous studies through PPG waveform analysis. We then verified the pain correlation of the derived candidate parameters. In particular, in the previous studies, pain caused by specific stimuli was evaluated, such as incision during surgery (Ahonen et al., 2007; Huiku et al., 2007; Kallio et al., 2008; Boselli et al., 2013), but this may include changes due to various factors such as the effect of an electrosurgical unit other than the pain itself. Moreover, in a clinical setting, it is important to distinguish pain from non-pain because the specified dose is repeatedly administered depending on the presence or absence of pain without adjusting the dose according to the pain intensity. Therefore, in order to observe the pure changes due to pain, in this study, two conditions were defined rather than the various pain intensities: preoperative condition as a state without pain and post-operative condition as a state of pain.
Materials and Methods
Ethics and Dataset
This study was approved by the Asan Medical Center Institutional Review Board (approval number: 2016-0477) and registered on the international clinical trials registry platform (1KCT0002080). A total of 81 subjects were enrolled. All experiments were approved by the Human Research Ethics Committee of Asan Medical Center and all methods were performed in accordance with the relevant guidelines and regulations. All participants gave written informed consent for their participation in the study. Finally, data from 65 subjects (28 males, 37 females, mean age of 50.5 ± 10.5 years) were used for analysis, excluding data from 16 subjects: data from 2 subjects had recording errors, 1 subject had severe arrhythmia; and data from 13 subjects were recorded without SPI. Patient’s information and type of surgery are described in Table 1.
Photoplethysmography data were recorded at pre-operation and post-operation. All surgeries included skin incision, and were performed under general anesthesia to reduce surgical pain. Pre-operative data were recorded in the surgery waiting room immediately before surgery. First, the 100 mm visual analog scale (VAS) was recorded and the PPG and SPI were simultaneously recorded for 6 min. Post-operative data were recorded after transfer of the patient to the recovery room immediately after the operation. At this time, PPG and SPI were recorded for 6 min after first recording VAS. Opioid was not used for 6 min immediately after surgery, and it was administrated after signal measurement was completed.
The VAS consists of a straight line with endpoints defining the extreme limits of the signal. For pain intensity, the scale is most commonly anchored by “no pain” (score of 0) and “pain as bad as it could be” or “worst imaginable pain” [score of 100 (100 mm scale)] (Haefeli and Elfering, 2006). PPG was recorded on the index finger of the opposite arm with intravenous therapy at a sampling frequency of 300 Hz for 6 min in each period. SPI was simultaneously recorded every 10 s. A GE Datex-Ohmeda S/5 Anesthesia Monitor, disposable PPG sensor, and a portable computer running the S/5 Collect software (GE Healthcare, Chicago, IL, United States) were used for monitoring and recording, respectively. Every recording is performed at room temperature.
The obtained PPG was filtered using a finite impulse response (FIR) bandpass filter at 0.5–10 Hz. Systolic and diastolic peak points were detected using the adaptive threshold method (Shin et al., 2009). The detected peak position was verified by experienced researchers and manually corrected for false detected or missed peaks. In the case of post-operative measurements, motion artifact may also occur, which can distort the data, even rendering it impossible to analyze. Therefore, the section where motion noise occurred was manually excluded from the analysis. Matlab 2016b (Mathworks, Inc., MA, United States) was used for all procedures of peak detection and signal analysis.
Pain affects the autonomic nervous system, leading to the vasoconstriction of sympathetic nerves (Huiku et al., 2007). Most parameters of this study were derived based on this clinical fact. We derived 23 parameters from PPG morphology analysis. These parameters were based on the spatial characteristic, amplitude, temporal characteristic, and the length or interval of PPG. Each parameter for each condition was calculated by averaging the values obtained for each pulse for 6 min. Graphical representation of derived parameters is shown in Figure 1. Detailed descriptions are summarized in Table 2.
Amplitudes of PPG have arbitrary units (a.u.) because they are affected by various factors such as skin color of the subject, human body composition of the measurement site, anatomical structure, nail condition, ambient light, and sensor wearing condition at the time of measurement (Allen, 2007). Therefore, amplitude-based characteristics should not be quantified, and normalization for arbitrary units was considered. The parameters of the baseline-systolic amplitude of PPG (ACAbl) and the adjacent diastolic-systolic amplitude (ACAdia) had arbitrary units that required normalization. Area-related parameters related to ACAbl and ACAdia also had arbitrary units. Calculating the ratio between parameters including arbitrary units could give a dimensionless parameter instead of arbitrary units. Therefore, individual or measured conditional characteristics related to amplitude were removed. Time unit parameters are affected by HR, which has an inter-individual difference. Therefore, the inter-individual difference due to HR needs to be corrected. By calculating the ratio between time unit parameters, it is possible to eliminate inter-individual differences. Therefore, time unit parameters were normalized to adjacent diastolic peak interval or systolic peak-diastolic peak interval in the present study. Consequently, 28 normalized parameters including 27 non-dimensional parameters were derived by normalization. These normalized parameters are listed in Table 3.
Logistic classification has been used in binary classification problems. Logistic function is a monotonic, continuous function between 0 and 1. Mathematical expression of logistic function is represented in Eq. 1. Sigmoid function is a representative example of logistic function (L = 1, k = 1, x0 = 0). In logistic classification, output is a probability. In our study, preoperative data were set as class 0 while post-operative data were set as class 1, and we used a 0.5 as a classification criterion of pain or non-pain assessment. This means that we classified the result is a pain if f(x) > 0.5, and non-pain if f(x) < 0.5.
Validation was obtained using two methods: statistical significance test and accuracy evaluation of pain classification. Statistical tests were performed to determine if the derived parameters had significant changes due to pain. In statistical analysis, proposed parameters extracted from data obtained in pre- and post-operation were analyzed for statistical significance. To determine inter-subject variance, we calculated the coefficient of variance (CV). For testing normality, the Kolmogorov–Smirnov test was used. Because all data do not have normality, we used the Wilcoxon signed rank test to verify the significant difference between parameters derived with PPG measured on pre- and post-operation. In multiple comparisons, the Bonferroni correction was used. P < 0.05 was considered statistically significant.
The accuracy of pain classification was evaluated by applying logistic classification. For the random partitioning of samples into a training set and a test set, we used 4-fold cross validation. Classification performance was evaluated based on accuracy (AC), sensitivity (SE), specificity (SP), and positive predictivity value (PPV). AC indicates the proportion of correctly classified numbers in the total case. SE is the probability that a classification result will indicate pain among those with pain. SE is the fraction of those without pain who have a negative classification result. PPV is the probability of actual pain among those classified as pain.
In our experiment, we confirmed that 0 VAS was observed in the pre-operation condition, while >60 VAS was observed in the post-operative condition. Table 4 shows the mean, SD, CV, and P-value for each parameter before and after surgery. The results showed that SPI was significantly increased after the operation. Among the derived parameters, area-based indices such as A, Asys, Adia, TriA, TriAsys, and TriAdia were significantly decreased in the post-operative condition. Amplitude-based indices, ACAdia and ACAbl were also significantly decreased in the post-operation. For temporal indices, Lsys was significantly increased in post-operation while Ldia was not significantly changed. Slope-based parameters, RS, LRS, RSmax, FS, and LFS were decreased significantly in post-operation. Pulse widths, PW30, PW50, and PW70 showed no significant change. However, PW90 were increased significantly in post-operation. Normalized area-based indices, Asys/A, Adia/A, Asys/Adia, TriAsys/TriA, TriAdiai/TriA, and TriAdia/TriA, were found to have significant differences among the derived dimensionless parameters. The area of systolic phase was relatively increased, while the area of diastolic phase was decreased in post-operation. Similarly, Asys/ACAbl showed a significant increase in the post-operation, whereas Adia/ACAbl was not significantly changed. All of the RS/FS and RS/ACAbl calculated as slope ratios were significantly decreased in the post-operative condition. However, the ratio of maximum rising slope to average rising slope, RSmax/RS, was not significantly changed. This might be due to an increase in the systolic interval caused by postoperative pain, consistent with the results of parameters derived from area ratio. In addition, parameters (A/ACAbl)/Lsys, (A/ACAbl)/Ldia, (Asys/ACAbl)/Lsys, and (Asys/ACAbl)/Ldia showed significant differences between pre- and post-operation. Results showed that a total of 15 parameters (Ldia, PPIsys, PPIdia, ACVsys, ACVdia, PW30, PW50, PW70, A/ACAbl, Adia/ACAbl, RSmax/RS, (A/ACAbl)/Lsys, (A/ACAbl)/PPIdia, (Adia/ACAbl)/Ldia, and (Adia/ACAbl)/PPIdia) were not significantly changed after the operation. For parameters representing dynamic inter-pulse variation, a significant increase was observed in the parameters of ACVsys/ACAdia, ACVsys/ACAbl, ACVdia/ACAdia, and ACVdia/ACAbl. This suggests that the fluctuation of amplitude is increased with pain.
Figure 2 shows a boxplot of the top 10 parameters with high accuracy. The lighter box in the figure shows preoperative results, while the darker box shows post-operative results. The boxplot in Figure 2 graphically depicts the groups of values of each parameter through their quartiles. Lines extending vertically from these boxes indicate variability outside the upper and lower quartiles. The cross mark (“×”) represents an outlier. Crosses on the right side refer to the outliers of more than 3/2 times the size of the upper quartile. Crosses on the left-side refer to the outliers of less than 3/2 times the size of the lower quartile. The spacing between different parts of the box indicates the degree of dispersion and skewness in the data.
FIGURE 2. Boxplot of the top 10 accuracy parameters and SPI before and after surgery. The lighter box shows pre-operative results while the darker box shows post-operative results. Cross mark (“×”) represents the outlier. Crosses on the right side refer to outliers of more than 1.5 times the interquartile range above the third quartile. Crosses on the left-side refer to outliers of less than 3/2 times the size of the lower quartile. The spacings between different parts of the box indicate the degree of dispersion (spread) and skewness in the data. Every parameter shows a significant difference by surgical stress (∗∗∗P < 0.001, ∗∗P < 0.01).
Thirteen out of the 51 indices showed better performance than SPI in post-operative pain classification accuracy. Among these, the four indicators normalizing the difference of the adjacent pulse amplitudes, ACVsys/ACAdia, ACVsys/ACAbl, ACVdia/ACAdia, and ACVdia/ACAbl, showed remarkably high performance. The remaining top 10 accuracy of classification was higher in the order of pulse amplitude from the adjacent diastolic peak (ACAdia), normalized diastolic waveform area (Adia/A), pulse amplitude from baseline (ACAbl), normalized systolic waveform area (Asys/A), average slope of systolic interval (RS), and maximum value of systolic slope (RSmax). Table 5 shows the classification of the performance of parameters with statistically significant differences.
Possibility of PPG as a Post-operative Pain Indicator
Photoplethysmography is an optical technique used to determine the blood volume changes by measuring the amount of light that is transmitted, reflected, or scattered after the light has been irradiated to the peripheral site of the body. PPG is mainly measured at the fingertips, tips of toes, or earlobes. PPG has a larger or smaller value depending on the amount of blood ejected from the heart. It generally defines the upward convex pole as the systolic peak and the downward convex pole as the diastolic peak (Allen, 2007). Previous studies using PPG waveform analysis for surgical pain assessment have found that the PPG amplitude and systolic peak interval are significantly reduced according to the skin incision during propofol-remifentanil anesthesia (Rantanen et al., 2006). In another study it was found that the maximum slope between the diastolic pole and the systolic pole is significantly reduced according to the skin incision during fentanyl, propofol, and sevoflurane anesthesia (Seitsonen et al., 2005). Huiku et al. (2007) extracted normalized PPGA (PPGAnorm), pulse transit time (PTT), systolic blood pressure (SBP), normalized heart beat interval (HBInorm), RE, and sympatho-vagal ratio (SVR) from PPG or other signals. After analyzing pain relevance with these parameters, they found that PPGnorm, PTT, and SBP were highly correlated with pain stimuli (Huiku et al., 2007). Moreover, studies using state and RE, HR, and PPGA (Rantanen et al., 2006) or using HBI, SD1, SD2, SD1/SD2 of HRV Poincaré analysis results, RE, difference of RE and state entropy, PPGA, PPG notch amplitude, and PPG notch y position (Rantanen et al., 2006) have shown that SPI is superior to other indices.
Previous studies have revealed the relationship between PPG waveform characteristics and pain. However, further analytical methods are needed for pain assessment using PPG. The waveform of PPG can provide a range of hemodynamic information. For example, the perfusion index (the ratio of AC amplitude and DC level of PPG) is sensitive to proximal sympathectomy (Klodell et al., 2005), peripheral perfusion in critically ill patients (Lima et al., 2002), and neonatal left heart obstruction (Granelli and Östman-Smith, 2007). Stiffness index (defined as the amplitude ratio of the systolic peak and notch point) and reflection index (defined as systolic pole-to-notch position interval proposed by Millasseau et al. (2006) can be used to indirectly estimate the stiffness of the vessel. It has been reported that the ratio of the inflection points of the second derivative photoplethysmography (SDPTG) reflects the vascular stiffness due to aging (Takazawa et al., 1998). Thus, PPG morphology analysis reveals the possibility of extracting pain parameters with high significance, besides the parameters used in existing PPG-pain studies.
Effectiveness of PPG-Based Parameters in Post-operative Pain Assessment
Similar to previous studies, A, Asys, and Adia were significantly decreased after the operation (Seitsonen et al., 2005). Considering that the area-related parameter of the waveform reflects changes in blood volume at the measurement point, the reduction in area might be due to the contraction of blood vessels through sympathetic activation by pain. RSmax, RS, LRS, FS, and LFS associated with the up and down slopes of ACAdia, ACAbl, and PPG representing PPG amplitudes were also significantly reduced after the operation, which is consistent with the results of previous studies (Seitsonen et al., 2005; Rantanen et al., 2006; Kallio et al., 2008). These results can be explained by increased blood vessel resistance shown in pulse area change or decreased maximum blood volume due to vasoconstriction. From a similar viewpoint, significant increase in Lsys indicates that contracted vessels might have increased the vascular resistance due to vasoconstriction of the sympathetic nerves (Jaryal et al., 2009; Hickey et al., 2016). TriA, TriAsys, and TriAdia in the area of a triangle where the waveform of the high frequency component such as harmonics was removed showed similar patterns as those of A, Asys, and Adia, respectively. This might indicate the lack of significant correlation between pain and the high frequency component of PPG. HBI derived from systolic and diastolic extremes known to be pain-related was increased after the operation but in our study the increase was not statistically significant. While this result is not common, the previous research also showed that HBI has relatively low sensitivity and specificity compared with combined feature of PPG (Seitsonen et al., 2005; Rantanen et al., 2006).
In the case of PW, PW30, PW50, and PW70 showed no significant change between pre- and post-operation. However, PW90 was significantly increased in post-operation. Changes in PW90 might be due to the narrowing of the waveform at the upper part of the amplitude when pain occurred. This can be interpreted in terms of increasing systolic interval length. Physiologically, the increase of systolic length increased the severity of vascular flow resistance (Angius et al., 2012; Wang et al., 2015).
The normalization in this study is divided into two types: that for the spatial-domain of PPG such as amplitude and that for the temporal domain of the PPG waveform such as interval or length. First, on the spatial domain, since the amplitude has an arbitrary value as mentioned above, it has an inter-individual difference as well as an intra-individual difference for each measurement. Thus, we derived ratio-based indices that could compensate for the arbitrary change of the amplitude. Secondly, on the temporal dimension, since the basal heart has individual difference, it is impossible to determine whether or not the pain is based on a specific HR. Moreover, every temporal value such as the systolic and diastolic lengths also depends on the beat-to-beat interval. However, the percentage of systolic interval during HR may be uniform for every person compared with the HR.
As a result of normalization, we confirmed that CVs were decreased in most of the indices. In the spatial domain, CV of Asys and Adia was decreased by dividing with A from 62.1 to 15.8% and from 70.0 to 6.1%, respectively. In the temporal domain, the CV of Ldia was decreased from 20.1 to 5.2%. Interestingly, the CV of the Lsys was increased by normalization (7.5–16.8%). This result could suggest that systolic length is less effected by the pulse length, and this concurs with the result of previous research that investigates systolic length change according to the exercises (Franculescu et al., 1982). In ACVsys and ACVdia, CVs were decreased by normalization from 65.9 to 41.9% and from 67.5 to 41.8%, respectively. These results suggest that the normalization could reduce the intra-individual and inter-individual differences. However, for a more generalized result, normalization with a massive dataset is needed.
The results of pain classification using these proposed parameters showed that parameters derived from pulse-to-pulse analysis and normalized parameters were superior to those derived from single pulse analysis. For example, the classification accuracy of parameters such as ACVsys/ACAbl, ACVsys/ACAdia, ACVdia/ACAbl, and ACVdia/ACAdia reflecting the dynamic changes between pulses was about 80%, which was more than 10% higher than the accuracy when single parameters were used without normalization. These dynamic parameters can resemble blood pressure variability (BPV). BPV is known to reflect blood pressure variations in very short-term analysis (beat-to-beat), which influences the central and reflex autonomic modulation in short term analysis (<24 h) (Conway et al., 1984; Mancia et al., 1986; Parati et al., 1995) and the elastic properties of arteries (reduced arterial compliance) (Parati, 2005; Kotsis et al., 2011; Fukui et al., 2013). However, the relationship between BPV and pain has not yet been reported. Therefore, it is more reasonable to conclude that dynamic parameters of amplitude variation can distinguish the pain better than static parameters, since stroke volume variability (SVV), a dynamic parameter, can reflect volume responses more effectively than the static parameters HR and BP in hemodynamic analysis.
Collinearity Between Features
The aim of this study is to analyze the many features of PPG, and to identify the indicators that correlate with pain. Thus, a total of 51 indicators were derived, which include interdependent indicators. Indicator collinearity does not need to be treated as important when single indicators are used to classify pain. However, as in the case of the SPI, if collinearity is used to generate a combined indicator with some indicators, it may be necessary to evaluate the collinearity between the two indicators, since this may lead to errors in accuracy evaluation. The index collinearity is usually assessed using the condition number, variance inflation factor (VIF) or correlation coefficient. In this study, the collinearity between each index was calculated from the correlation coefficient, and is shown in Figure 3. In the figure, blue is the positive correlation coefficient and red is the negative correlation coefficient. The color concentration reflects the magnitude of the correlation coefficient. The results of this collinearity evaluation can be used in developing combined indicators using single indicators.
FIGURE 3. Collinearity test result between 51 features. Blue and red represents positive and negative correlation, respectively. The darker the color, the higher the correlation. 1: A, 2: Asys, 3: Adia, 4: TriA, 5: TriAsys, 6: TriAdia, 7: Lsys, 8: Ldia, 9: PPIsys, 10: PPIdia, 11: ACAdia, 12: ACAbl, 13: ACVsys, 14: ACVdia, 15: RS, 16: LRS, 17: RSmax, 18: FS, 19: LFS, 20: PW30, 21: PW50, 22: PW70, 23: PW90, 24: Asys/A, 25: Adia/A, 26: Asys/Adia, 27: TriAsys/TriA, 28: TriAdia/TriA, 29: TriAsys/TriAdia, 30: A/ACAbl, 31: Asys/ACAbl, 32: Adia/ACAbl, 33: Lsys/PPIdia, 34: Ldia/PPIdia, 35: Lsys/Ldia, 36: ACVsys/ACAdia, 37: ACVsys/ACAbl, 38: ACVdia/ACAdia, 39: ACVdia/ACAbl, 40: RSmax/RS, 41: RS/FS, 42: RS/ACAbl, 43: (A/ACAbl)/Lsys, 44: (A/ACAbl)/Ldia, 45: (A/ACAbl)/PPIdia, 46: (Asys/ACAbl)/Lsys, 47: (Asys/ACAbl)/Ldia, 48: (Asys/ACAbl)/PPIdia, 49: (Adia/ACAbl)/Lsys, 50: (Adia/ACAbl)/Ldia, 51: (Adia/ACAbl)/PPIdia
The aim of our study is to evaluate individual predictors rather than regression by combining multiple predictors. If we develop a combination feature that combines individual features in the future, we should perform a multicollinearity test between the features found in this study. Also, in order for the study to be a useful index in clinical practice, it is necessary to derive a pain index discriminant formula that can express the pain score as a normalized value. Finally, this study does not include an assessment of the pain situation suppressed by analgesics. Therefore, it is necessary to verify whether the post-operative pain candidate index reflects real-time pain change following analgesic administration in order to be used clinically in post-operative pain evaluation. Moreover, a composite test for a specific age, disease, etc., is required to improve reliability.
Results of this study demonstrated that dynamic parameters obtained by inter-pulse analysis were more sensitive to pain than static parameters obtained from single pulse analysis. Considering that existing surgical pain assessment studies are performed mainly on the above mentioned static indicators, dynamic indicators found in this study can be used to develop more sophisticated pain assessment algorithms in the future. However, further studies are needed before these new pain parameters identified in this study can be applied to clinical practice, including evaluation in general anesthesia. First, this study was based on a statistical analysis of total signals for 6 min obtained before and after surgery without observing changes in pain in real-time. Therefore, it is necessary to determine whether real-time pain change estimation is possible. In addition, this study only dealt with single parameters obtained from PPG waveforms. Further studies with multivariate models using multiple indicators are needed for more sophisticated pain assessment. Finally, since the pain assessment technique must be provided as a formula that can quantify the degree of pain, further research is needed to determine the normalization technique to correct inter-individual differences.
B-MC and G-JN collected the data. HS designed the data analysis scheme. YLY, HSS, and HS performed the data analysis. B-MC and HS interpreted the results. All authors contributed to the writing of the manuscript, provided critical revisions, and approved the final version.
This research was supported by a grant (NRF-2015R1C1A1A02036535) from the Basic Science Research Program through the National Research Foundation (NRF) of Korea, funded by the Ministry of Science, ICT and Future Planning, Republic of Korea and by the Bio & Medical Technology Development Program of the NRF funded by the Korean government, MSIP (NRF-2016M3A9F1941328).
Conflict of Interest Statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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Klodell, C. T., Lobato, E. B., Willert, J. L., and Gravenstein, N. (2005). Oximetry-derived perfusion index for intraoperative identification of successful thoracic sympathectomy. Ann. Thorac. Surg. 80, 467–470. doi: 10.1016/j.athoracsur.2005.02.075
Kotsis, V., Stabouli, S., Karafillis, I., Papakatsika, S., Rizos, Z., Miyakis, S., et al. (2011). Arterial stiffness and 24h ambulatory blood pressure monitoring in young healthy volunteers: the early vascular ageing Aristotle University Thessaloniki Study (EVA–ARIS Study). Atherosclerosis 219, 194–199. doi: 10.1016/j.atherosclerosis.2011.07.111
Ledowski, T., Ang, B., Schmarbeck, T., and Rhodes, J. (2009). Monitoring of sympathetic tone to assess postoperative pain: skin conductance vs surgical stress index. Anaesthesia 64, 727–731. doi: 10.1111/j.1365-2044.2008.05834.x
Lima, A. P., Beelen, P., and Bakker, J. (2002). Use of a peripheral perfusion index derived from the pulse oximetry signal as a noninvasive indicator of perfusion. Crit. Care Med. 30, 1210–1213. doi: 10.1097/00003246-200206000-00006
Mancia, G., Parati, G., Pomidossi, G., Casadei, R., Di Rienzo, M., and Zanchetti, A. (1986). Arterial baroreflexes and blood pressure and heart rate variabilities in humans. Hypertension 8, 147–153. doi: 10.1161/01.HYP.8.2.147
Millasseau, S. C., Ritter, J. M., Takazawa, K., and Chowienczyk, P. J. (2006). Contour analysis of the photoplethysmographic pulse measured at the finger. J. Hypertens. 24, 1449–1456. doi: 10.1097/01.hjh.0000239277.05068.87
Parati, G., Saul, J. P., Di Rienzo, M., and Mancia, G. (1995). Spectral analysis of blood pressure and heart rate variability in evaluating cardiovascular regulation. Hypertension 25, 1276–1286. doi: 10.1161/01.HYP.25.6.1276
Rantanen, M., Yli-Hankala, A., Van Gils, M., Yppärilä-Wolters, H., Takala, P., Huiku, M., et al. (2006). Novel multiparameter approach for measurement of nociception at skin incision during general anaesthesia. Br. J. Anaesth. 96, 367–376. doi: 10.1093/bja/ael005
Russell, I. F. (1989). Conscious awareness during general anaesthesia: relevance of autonomic signs and isolated arm movements as guides to depth of anaesthesia. Baillières Clin. Anaesthesiol. 3, 511–532. doi: 10.1016/S0950-3501(89)80016-9
Seitsonen, E., Korhonen, I., Van Gils, M., Huiku, M., Lötjönen, J., Korttila, K., et al. (2005). EEG spectral entropy, heart rate, photoplethysmography and motor responses to skin incision during sevoflurane anaesthesia. Acta Anaesthesiol. Scand. 49, 284–292. doi: 10.1111/j.1399-6576.2005.00654.x
Takazawa, K., Tanaka, N., Fujita, M., Matsuoka, O., Saiki, T., Aikawa, M., et al. (1998). Assessment of vasoactive agents and vascular aging by the second derivative of photoplethysmogram waveform. Hypertension 32, 365–370. doi: 10.1161/01.HYP.32.2.365
Wang, A., Yang, L., Liu, C., Cui, J., Li, Y., Yang, X., et al. (2015). Athletic differences in the characteristics of the photoplethysmographic pulse shape: effect of maximal oxygen uptake and maximal muscular voluntary contraction. Biomed Res. Int. 2015:752570. doi: 10.1155/2015/752570
Wennervirta, J., Hynynen, M., Koivusalo, A. M., Uutela, K., Huiku, M., and Vakkuri, A. (2008). Surgical stress index as a measure of nociception/antinociception balance during general anesthesia. Acta Anaesthesiol. Scand. 52, 1038–1045. doi: 10.1111/j.1399-6576.2008.01687.x
Keywords: anesthesia, pain quantification, photoplethysmography, post-operative pain, surgical pain
Citation: Yang YL, Seok HS, Noh G-J, Choi B-M and Shin H (2018) Postoperative Pain Assessment Indices Based on Photoplethysmography Waveform Analysis. Front. Physiol. 9:1199. doi: 10.3389/fphys.2018.01199
Received: 21 April 2018; Accepted: 08 August 2018;
Published: 28 August 2018.
Edited by:Bernhard Schaller, Universität Zürich, Switzerland
Reviewed by:Roberto Maestri, IRCCS Istituti Clinici Scientifici Maugeri (ICS Maugeri), Italy
Vlasta Bari, Policlinico San Donato (IRCCS), Italy
Copyright © 2018 Yang, Seok, Noh, Choi and Shin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Hangsik Shin, firstname.lastname@example.org
†These authors have contributed equally to this work


Modulation of motor cortical excitability following rapid-rate transcranial magnetic stimulation.Clin Neurophysiol. 2007 Jan; 118(1):140-5.CN
To investigate the effect of high frequency rTMS (25 Hz at 90-100% of resting motor threshold) on the excitability of the motor cortex of healthy human subjects.
Resting and active motor threshold, MEP recruitment curve (I/O curve), short interval intracortical inhibition (SICI) and facilitation (ICF), and the duration of the silent period (SP) were tested in the right first dorsal interosseous muscle (FDI) before and twice after the end of 1500 pulses in 16 normal young adult male volunteers.
Twenty-five Hertz rTMS decreased motor thresholds, reduced the duration of the silent period and had a tendency to increase the slope of the I/O curve. Most of these effects lasted for the duration of the two post-testing sessions (at least 30 min) and had returned to normal by 2h. There were no significant effects on SICI/ICF.
Twenty-five Hertz rTMS can produce a long lasting increase in cortical excitability in healthy subjects.
This method may prove useful for the study of normal human physiology and for therapeutic manipulation of brain plasticity.


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All Zignature recipes are based on a meat-first philosophy because dogs are carnivores and require high-quality animal protein to thrive. The first listed ingredient in any pet food is vitally important because there’s more of that ingredient than any other. Not only is meat the first ingredient in all our recipes, but we also include meat or fish meal as the second ingredient. Compare this to many well-known pet foods that use high-starch carbohydrate fillers as their first or second ingredient, and you’ll quickly see why Zignature offers your pet the correct nutrition for enhanced vitality.


- 1 Chinese Herbs To Lower Blood Sugar
- 2 How To Treat High Blood Sugar Naturally
- 3 How To Treat Diabetes 2
- 4 Natural Herbal Medicines For Diabetes
- 5 Side Effects Of High Blood Sugar In Pregnancy
- 6 Lower A1C In A Week
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This drink is suggested by a lot of holistic doctors, plus it has been believed that all of the girls from Norway consume this drink and that is the main reason for their beauty.
English farmer called Thomas Parr, was believed to have consumed whey and that is why he lived for unbelievable 152 years. It is a type of beverage that a lot of medicinal experts suggest in order to have healthier and linger life.
The following are the properties and health benefits that whey has:
It is a type of beverage which can be used by everyone, regardless of the age. The taste is very familiar because it is like the breast milk, that is the reason why everyone is allowed to consume it including the babies.
A 100 % natural whey is consisted of 1% proteins and 93% water. Plus, the most important elements in the whey milk are the following: phosphorus, manganese, magnesium, sodium, copper, phosphorus, zinc, iron, potassium, vitamins and cobalt.
This is the best and healthiest beverage for liver which is damaged.
The most important thing in order to have a perfectly good health is if your liver is in perfect condition. So, this beverage is suggested for using in the case of eliminating all the toxins from the liver. This is the main reason why people affected of liver disease are suggested to use this beverage.
Whey is full with beta-lactoglobulins which actually give to the body amino acids also known with the name BCAA (branched-chain amino acids). These are confirmed for helping even in case with more advantaged liver disease. Plus, the amino acids are very helpful when it comes to situations like insomnia and bad mood.
Also, we have to mention that whey are full with immunoglobulins and lysosome. They improve the immune system and lactoferrin, which keep the body safe from infections and other toxins.
Furthermore, it is important to say that whey is consisted of glutathione, which is very useful when it comes to treatments against cancer, issues with the thyroid, multiple sclerosis, chronic inflammation, and Parkinson’s diseases.
Whey is used for losing weight
Whey is the perfect thing to use if a person has the desire to reduce its weight and stress, as well as to fight against several serious health situations. By using this a person will have enough energy and the body is going to be hydrated always.
Moreover, whey is essential when it comes to normal function of the nerves, plus for keeping normal the blood pressure, levels of the sugar and tiredness.
A folk medicine when it comes to indigestion.
Whey is consisted of lactic acid. With this characteristic it will be used to fight against bacteria and fungi in the bowels.
So people dealing with cramps, constipation, bloating, chronic inflammation are suggested to drink this beverage.
Also, we have to mention that besides these type of problems this old medicine are useful against:
- Excessive eating
- High blood pressure
- Eliminating toxins from the body
- Weak immune system
- Candida overgrowth
- Issues with the abdomen
- Issues with the liver
The process of preparation and the way to use it:
It is a beverage which is possible to prepare at home by using fresh milk, or if you don’t have it, you may buy it at any market of eco-food from the local producer. The best and full with benefits is the whey from the goats. However, it is possible to use cow whey as well. It is important to mention that people should be aware for their milk to be free of hormones or antibiotics.
First of all, begin by consuming 1.5 deciliters, 3 times in one day. Then as the day goes by you can use a bigger dose.
If a person has issues with the digestive system, then the right thing to do is to prepare a combination of whey and water. And before eating to consume the mixture.
Plus, if a person wants shiny, beautiful hair and skin whey is the right thing to be used.
Source and image source: healthiestalternative.com


Soft drinks are made with the carbohydrates that contains carbon dioxide which makes the water bubbly it is known to be healthy as the normal water we drink but i do not feel that it has any kind of benefits. Soft drink is a beverage that is non-alcoholic, carbonated drinks that contains many ingredients such as sweetener, flavoring, carbonated water and others as the carbon dioxide is dissolved, it gives the soft drink a distinctive taste and texture. The advantages of drinking liquor (including beer, wine and distilled spirits) in moderation is that it improves health and increases longevity. Soft drink consumption has increased substantially over the last 50 years and it has been established that using large amounts of soft drinks regularly can be detrimental to your health if used in moderation soft drinks can have some beneficial effects on your body. Even sweetened soft drinks have less sugar than some fruit juices for instance, grape juice contains 50 percent more sugar than coca cola bad for your tooth enamel – one study found that drinking orange juice for only 5 days was enough to reduce the hardness of tooth enamel by as much as 84 percent.
Advantages and disadvantages of alcohol are based on how we use it and at what limits it precipitates and denatures surface proteins making tissues soft in long-term bedridden patients, it is used to harden bony surfaces of the back hi friendsi think alcohol has more disadvantages to advantages in our lifeit has advantages for. What is a sugar tax a sugar tax is a tax on sugary drinks, also called a sugar sweetened beverage tax (ssbt) public health advocates say an ssbt in australia and new zealand could help reduce consumption of ssbs and thereby reduce obesity and other associated diseases. The pros and cons of taxing sweetened beverages based on sugar content 1 taxing sugar content is the least costly way to reduce sugar consumption 3 sugar content 3 soft drink volumes, prices, and sugar content 16 pass-through 17 outcomes of interest 17 tax designs 18 results 19.
Energy drinks are marketed with the claim that they will boost your energy different energy drinks contain different ingredients and these are the primary disadvantage of these beverages. 6 disadvantages of diet soda sponsored links diet drinks are harmful to your health and here is the list of 6 reasons why you should get exclude zero-calorie drinks from your menu 1 artificial sweeteners cause headaches aspartame is said to cause headaches the chemical is still being studied. Before the 1950s, 65 ounces was the standard size for soda bottles now 20-ounce bottles are standard, but even larger 42-ounce bottles are available, meaning soft drink consumption continues to rise. Soft drink consumption has increased substantially over the last 50 years and it has been established that people have large amounts of soft drinks regularly caffeine benefits caffeine is a stimulant that is found in soft drinks.
The caffeine content of 12-ounce soft drinks, for instance, varies from none to about 60 milligrams cspi is in support of labels that tell the amount, in milligrams, of caffeine in foods and. Best answer: soft drinks taste good that is the main advantage another advantage is that they are convenient it is easy to just pop open a can of soda soft drinks are also readily available just about anywhere. Advantages and disadvantages of cocacola coca-cola is a carbonated soft drink sold in stores, restaurants, and vending machines in more than 200 countries cocacola is one of the most popular soft drink in the world, so i will mention some of advantages of drinking cocacola for our life.
The disadvantages of soft drinks : pepsi - coca cola - sprite etc some injurious health effects of soft drinks: pepsi - 7 up - coca cola etc before the 1950s, 65 ounces was the standard size for soda bottles. Health benefits of soda & carbonated water by ireland wolfe soda, also known as pop, is a sugary, carbonated soft drink soda has more health dangers than pluses however, it can provide some benefits upset stomach carbonated water and some types of soda can help to relieve stomach problems, such as indigestion or nausea a 2002 study. Much ado is made about the disadvantages of soft drinks -- namely, their high sugar content however, soft drinks do carry certain advantages, from convenient energy boosts to, possibly, protection against disease.
To day i am going to share with you , what are the advantages and disadvantages of drinking soft drinks follow us on. Following are some advantages and disadvantages of consuming sports drinks after looking at the pros and cons, you can decide for yourself if sports drinks are the best way to replenish your body. Advantages and disadvantages of soft drinks global soft drink industry is currently expanding quite rapidly this is due to two major factors first, markets are expanding rapidly in developing countries and second people are turning toward natural, healthy, and low-calorie drinks. Soft drink regular drinking is a significant risk factor for developing of metabolic syndrome 18, a combination of the symptoms such as high blood pressure, obesity, high cholesterol, and insulin resistance.


Sitka residents are invited to join their community in honoring our local wellness champions and planning our health priorities for the next year during the fourth annual Sitka Health Summit, “Working Together for a Healthier Sitka,” on Monday and Tuesday, Oct. 4-5, at Harrigan Centennial Hall.
The Sitka Local Foods Network got its start as two community food security projects from the 2008 Sitka Health Summit — to create a local foods market and to create a community greenhouse/expand local community gardens. In 2009 the Sitka Local Foods Network received a community wellness champion award for nutrition.
There are two main community events during the Sitka Health Summit — the Sitka Community Dessert and Awards Ceremony on Monday, Oct. 4, and the Planning Day: Real Ideas Into Action on Tuesday, Oct. 5.
Doors open for Monday’s program at 6 p.m., with the program starting at 6:30 p.m. The event features a selection of free local and organic desserts provided by Sitka Spuce Catering for the first 200 people. The keynote presentation will be by Dr. Julien Naylor, an internal medicine/diabetes specialist at SEARHC Mt. Edgecumbe Hospital who will speak about the importance of creating a healthy community in Sitka and how to help people move toward a more healthful life. Following the presentation will be an awards ceremony honoring our community wellness champions. This event is free, but donations will be accepted for the Sitka Health Summit’s new Health Initiatives Fund. Also, raffle tickets for a watercolor by local artist Pat Kehoe and other prizes are being sold for $5 each to raise money for the Health Initiatives Fund.
Tuesday’s program from 9 a.m. to 4 p.m. will allow Sitka residents to set the community’s health and wellness goals for 2010-11. Some of our recent past goals were to make Sitka more bicycle friendly and to start a market for local foods, and they resulted in Sitka becoming Alaska’s first official Bicycle Friendly Community in 2008 and the creation of the Sitka Farmers Market. This year’s top goals and priorities will receive seed money from the new Health Initiatives Fund. There also will be a community health and wellness resource room open to the public from 10 a.m. to 5 p.m. in the Exhibit Room. Snacks and lunch will be available.
The Sitka Health Summit is brought to you by Sitka Community Hospital and the SouthEast Alaska Regional Health Consortium (SEARHC), with major financial help from Premera Blue Cross Blue Shield of Alaska, the City and Borough of Sitka, Scott Insurance Services, White’s Inc./Harry Race Pharmacy/White’s Pharmacy and the University of Alaska Southeast-Sitka Campus. The Sitka Health Summit’s vision is “to serve our great state as a model for community wellness by creating a healthy community where all Sitkans strive for and enjoy a high quality of life.”
For more information about the Sitka Health Summit, contact Holly Keen at 738-2707 or firstname.lastname@example.org, or go to our Web site at http://www.sitkahealthsummit.org/.


Babies Fall When Carried?
Tonight, I want to ask. my baby was 1 month old when he was dropped, because the person carrying him slipped. But the baby is still held tightly in the sling, not touching the floor held by the hand. The condition of the baby is sleeping, the baby does not cry .. Is it dangerous?
Hello, thank you for the question to HealthReplies.com
Basically, if the baby does not bump, does not experience excessive traction in the hands or feet, the baby does not cry even the baby does not wake up from sleep in a sling, you have nothing to worry about, meaning that the impact caused by the person holding him falls does not affect the baby at all. There will not be certain complications that occur in infants.
Consider again when the baby wakes up later, if the baby is still active as usual, the baby moves his hands and feet as usual, the baby can drink as usual. If your baby does look like he usually does, then you have nothing to worry about or do. Make sure your home environment is safe for the people around you (for your baby or for people who live in it) so that it does not happen again slip or stumble and fall in your home.
If you notice certain changes in your baby, take it to the pediatrician for further examination.
So much information from me, hopefully enough answer


The Trump Administration Just Rolled Back An Essential Piece of Our Healthcare Infrastructure, and Medical Professionals Are Speaking Out
Trump’s administration recently enacted another blow to the American healthcare system. Early in July, it was announced that they would be deleting 20 years' worth of critical medical guidelines. This vast database of guidelines has been a treasure trove of critical information used by doctors and other medical professionals for the last two decades. The database went “dark” on July 16th, due to lack of funding.
As part of the Department of Health and Human Services, the Agency for Healthcare Research and Quality (AHRQ) maintained the database known as the National Guideline Clearinghouse (NGC).
$1,000,000 in Medical Debt Owed by Seattle Area Residents Was Just Wiped Away Thanks to a Local News Station
A Seattle-based news station has purchased $1,000,000 in medical debt, in an effort to secure medical debt forgiveness for individuals within their coverage area.
According to The Hill, KIRO spent approximately $12,000 to purchase $1,000,000 in medical debt owed to Seattle-based providers. The station collaborated with a charity named “RIP Medical Debt, which locates, buys and forgives medical debt across America.”
For perhaps the first time, patients suffering from Huntington’s disease have cause for hope. A recent trial conducted by researchers at University College London (UCL) indicates that an experimental drug may significantly suppress a mutated gene related to Huntington’s devastating degenerative effects.
It is estimated that about 30,000 people in the United States and 8,500 people in the UK currently suffer from Huntington's. The disease, which some patients describe as a mix of Alzheimer’s, Parkinson’s and ALS, is responsible for a dizzying array of symptoms. Patients first experience severe mood swings and depression, then face ever-worsening dementia and a gradual loss of motor control that ends in paralysis; the majority die about 10 to 20 years following its onset.


THIS ISN’T GOING TO HAPPEN OVERNIGHT! I just want to scream that at the top of my lungs when it comes to people wanting to get into better shape. There are so many false promises and lies still being distributed throughout all forms of media claiming that people can take this magic pill or get the body they want in 30 days. I see it and hear it all the time (I currently work in a health food store). So many people have such an unreasonable expectation. Then they get upset and want to quit when they don’t see results on day one. If it took you 30 years of living an unhealthy lifestyle to get the body you have now, what makes you think that you’re going to have your dream body in 60 days? Will you make progress within that time, yes. Will you reach your goal within that time frame, no. We live during a time where everybody wants it right now. Instead of putting something in the oven and allowing it to properly cook for 3-4 hours, we’d rather throw it in the microwave and have it ready in 3-4 minutes. We want to apply that same concept to other areas of our lives and it just does not work. It took me years to put on weight and develop the body that I wanted naturally. A lot of people think there is some big secret that people like me are not sharing. There is no secret. If you want to know the two main keys to success, I’ll gladly share them with you.
The proper diet and right amount of exercise are your main keys to success. Yes, there are other factors but everything revolves around those two things. For the record, diet refers to eating actual food and not just taking supplements. You’d be surprised how many people still ask what supplements they should take and they have no clue about their diet. What you put into your body matters. Even if you are in the gym working out consistently, the results you want are going to take significantly longer to come if you are not fueling your body properly. The journey to getting into better shape is a marathon, not a sprint. It will take a lifestyle change. If you’re doing it naturally, it’s going to take years. But those years will produce a much healthier and better version of you. I do understand that a lot of people need help just getting started. Yes, you could search on google for workout and diet programs. But me personally, I would recommend that you invest in a proven coach or trainer. They can design workouts and a nutrition plan specifically for you. They will also hold you accountable since you do have to check in with them. There are the two main keys to success on how you can transform your body. It’s hard, but it is worth it. Health is wealth.
When it comes to your health, don’t take shortcuts. Yes, there are performance enhancing drugs (PEDs) that can help you reach your goals quicker. It is very tempting, but you are possibly sacrificing your long-term health for immediate satisfaction. The goal is to extend your life, not cut it short. Be willing to put in the work. It is going to take blood, sweat, and years to get where you want to go. It will be hard. There will be times where you will want to cheat on your diet or just skip a workout because you just don’t want to go to the gym. And if you fail on that day or in that moment, do not let it stop you. It’s just a setback. Get back up, and keep moving forward. The results are worth it. It is a great feeling to look good and to be healthy. Everyone has the ability to improve their health. It all comes down to the choices you make. Change will not happen overnight. But if you are consistent and will put in the work, I promise you that the results will come. No more excuses, make it happen.


Chips that are paleo are hard to come by. Either they use junky oils that are high in Omega-6 fatty acids like canola, safflower, sunflower, or something similar, or they have a ridiculous amount of ingredients that were probably never meant to be consumed.
But, I found these Boulder Canyon Sea Salt chips at the grocery store a few weeks ago, and they are awesome! I know that white potatoes are a gray area food because of the insulin response that they create when compared to sweet potatoes, but I am healthy enough now where I don’t have as many blood sugar issues and can eat white potatoes without issue.
So, what are the ingredients in these?
That’s it. That’s all that is in each and every wonderful chip. And the avocado oil gives a smoothness that is hard to describe when compared to regular chips. I wouldn’t say eat a bag a week or anything like that, but for those times when you need some crunch or want to eat just a few as you walk by the pantry, I think they would be just fine. And they obviously would be so much better for you than anything from Frito-Lays. They do have a couple of other flavors like Sea Salt and Black Pepper, and Sea Salt and Malt Vinegar, but the ingredient list is substantially bigger, and Malt Vinegar is derived from Barley Malt, so it makes me a little bit nervous about the amount of gluten that could be in that, and apparently I’m not the only one.
But I would wholeheartedly give a thumbs up to the basic Sea Salt wavy and kettle cooked chips as they are basic and use solid ingredients as the labeling says Non-GMO ingredients are used as well. Very solid line in the sand Boulder Canyon. I approve.


Brain Architecture (website) - From Harvard University's Center on the Developing Child, this site provides information on brain development in the early years.
Brain Development (webpage) - Zero to Three provides resources about a variety of topics supporting brain development, including a Baby Brain Map, which demonstrates how a human brain develops during specific age ranges.
Adverse Childhood Experiences in Wisconsin (pdf) - An ACES report from the Wisconsin Children's Trust Fund & Children's Hospital of Wisconsin including findings from the 2011-12 Behavioral Risk Factor Survey.
Institute for Child Success (webpage) - This research and policy group provides several briefs connecting research on a variety of topics associated with child development.
Steps for Brain Building: Serve & Return (website) - From Harvard's Center on the Developing Child, this site describes simple ways to build a strong foundation in a child's brain for all other learning.
© 2010-2018 | Wisconsin Early Childhood Collaborating Partners | All rights reserved.


Flossing can be an important part of keeping teeth squeaky clean, fighting cavities, and protecting teeth for the long haul; so the earlier kids can learn to floss, the more natural the habit will be for the rest of their lives.
STRONG: Helping Kids Learn about their Core As people get older, they begin to recognize the importance of a strong core. It helps people prevent back pain, increase flexibility, and improve posture. The younger we are when we start working on having a strong core, the more benefits someone has from that work. Even kids
For growing bodies, incorporating appropriate types and levels of exercise is important for facilitating growth and for preventing injuries that could have long-lasting impacts.
Sometimes it can be difficult to get kids to get up and move their bodies, which is so critical for them to grow up healthy and strong. It can be frustrating when they won’t stretch, don’t want to go on a walk, and just sit at the playground rather than get goofy on the equipment. Stretch-n-Grow encourages movement through play!
What are the Types of Muscles? The body is full of muscles that continue to grow and get stronger as kids grow every year. They work better the more they are used. At Stretch-n-Grow, we love to focus on different muscle groups, working out our arms and legs to help them do their best. But
One of the most important things we believe here at Stretch-n-Grow is that fitness should be fun, and that stretching the body is an important part of growing up happy and healthy. Engaging the mind is just as important though! Children get that through school, teaching moments, and creativity. Did you know that exercise can
12 Yoga Poses to Master in the New Year As we set off on the adventure of a new year, our focus returns to creating new habits. For families, especially families with children, it can be easy to start a lot of projects to try and sign the kids up for a bunch of new
Go Wild: Exercise Like Wild Animals Sometimes you just have to go wild – and exercise like a wild animal! Kids seem full of energy, and even when you think they’re ready to slow down, they seem to tap into another fuel reserve and can keep going wild for another hour! Releasing the inner animal and
So what is risky play anyway? Usually found outdoors, risky play happens when children are allowed the time and space to explore and experience variables. These variables include height, speed and use of tools. Risky play also includes exploration of rough and tumble play, incorporation of elements such as water, and concepts like getting lost. The key to successful risky play is that all of these things are tested on the child’s own terms.


KGH Hospital is a General Health clinic in Dilsukhnagar, Hyderabad. The clinic is visited by doctors like Dr. Gopinath Kumar, Dr. Laxmi and Dr. N. Surendar (PT). The timings of KGH Hospital are: Mon to Sun: 12:00 AM-11:30 PM. Some of the services provided by the clinic are: Intra-Uterine Insemination (IUI), Amniocentesis, Cordocentesis, Quad Screen and In-Vitro Fertilization (IVF). Click on map to find directions to reach KGH Hospital.


AirBands- The future of BFR training is here!
Blood flow restriction training (BFR) involves reducing blood flow to the exercising muscles through the application of specially designed cuffs.
The cuffs are inflated to the point where blood flow is impaired partially in the limbs, subsequent blood pooling in the limb, leads to increase in metabolic waste build up, leading to a cascade of beneficial physiological mechanisms in the body, stimulating exacerbated increases in strength and muscle size through:
- Higher recruitment of fast twitch muscle fibres
- Systemic and localised hormone production
- Increased muscle protein synthesis
Research has demonstrated blood flow restriction training can significantly increase muscle size and strength using low training loads. This makes blood flow restriction training an excellent rehabilitation tool.
AirBands are the worlds first wireless, automated BFR cuffs that are run via an app on your smartphone/tablet. This allows users the ability to inflate/deflate the cuffs at the press of a button and does not require any cords or attachments to get int the way of your workout/rehabilitation.
Click the link below to purchase your own AirBands and use the code: MOVEMENTRX for free shipping!


By age 45, three in ten women in the United States has had at least one abortion – many women suffer silently in self-contempt and fear the judgment of others.
Abortion is supposed to be a “quick solution,“ but that “solution” can have lasting effects. Some experience low self-esteem, difficulty sleeping, depression, eating disorders, increased drug/alcohol use or even have thoughts of suicide.
If you are experiencing hurts like these, there is hope for healing. PEACE Ministry offers a non-judgmental, confidential environment in which you will find counseling, acceptance and support from women or men who have experienced these hurts and have found healing and peace.
PEACE Ministry exists to help women and men who have suffered the physical, emotional, psychological or spiritual trauma from abortion find forgiveness, freedom and healing through Jesus Christ.
We minister with complete confidentiality through the use of Support Groups, Bible Studies, Personal Testimonies, Speaking Engagements and Media while broadening our outreach by networking with Community and Church Organizations, Pastors, Women's Groups and those who are transparent about their abortion experience.
Our goals are not only to support those in need of recovery from the trauma of abortion, but also to raise awareness in our area churches about issues related to abortion recovery and of the need to provide a safe, healing environment for those who have been hurt by abortion.
"Where there was once despair, there can be hope. Where there was shame,
there can be freedom. Where there was once pain, there can be peace."
Contact Lori@options-now.com for more information


There are unwanted effects of CBD Oil. Together with medical studies pending from the U.S. as well as in Europe, finding out whether CBD Oil truly works will likely be an ongoing quest.
One popular medical study from the U.S. has studied the anti-anxiety, anti-spasticity, and the anticancer ramifications of CBD. However, despite the CBD being non-psychoactive and being a pure substance, researchers found,”kiddies were no more anxious than normal, but did report spasticity.” While these were findings that are likely, it won’t signify that CBD is safe for use with adults or children.
Because they fear that CBD isn’t safe enough for human 21, Many people may be concerned about these side effects. If you’re worried about yourself taking CBD because of its negative effects or your child, then there are other options out there. Keep reading to learn more about where to find rest out of the sideeffects of CBD Oil.
CBD Oil could be purchased over the counter. It’s very important to talk to your doctor before taking CBD because of its potential side effects.
You can get relief from these sideeffects, as you may observe. The ideal method to get relief is to come across something which contains an oral pill using CBD. The capsule can help reduce or get rid of the negative effects of CBD Oil in a oral type.
There are things which you could perform in order to get rest out of the sideeffects of CBD Oil. You are able to begin to use a topical lotion to decrease the discomfort which you just feel. But some unwanted effects of CBD Oil are permanent.
You might want to use CBD Drops to help relieve the side effects of CBD Oil. This really is 1 alternative that you may consider in the event that you want to block the sideeffects of CBD Oil without using CBD Capsules.
While CBD Drops are an effective way to relieve the negative effects of CBD Oil, then you also ought to bear in mind that not all side effects are irreversible. By way of example, you will experience.
Might require https://thecbddosage.com/ therapy. May require the intervention of your doctor.
Yet another means to treat CBD Oil’s negative effects is to modify your diet plan program. Using Oral ointments CBD Capsules, and more will not make the side effects of CBD Oil go a way.
So you can live a life that is more 16, these changes will bring your pain under control. Whether move on into this next procedure or you decide to keep on this regimen, these options will assist you to reduce or eliminate the unwanted effects of CBD Oil.
Once you learn how to find rest finding rest out of the negative ramifications of CBD Oil will be easier. There are many distinct techniques that you can utilize to help relieve your symptoms of stress and depression.
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Insights On No-Hassle Advice In asian women for marriage
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Want to help your ADHD naturally without the use of ADHD medication? Then watch my FREE ADHD Training here: 👉 👈
A lot of people will write off alternative natural treatments for ADHD because either they have tried several and failed or they hear from others that it does not work. And I don’t blame you if you are one of those people because there is a lot of information out there on ADHD treatment but it is hard to know what actually works and what does not.
That’s why on this livestream I am going to go over what ADHD medication alternatives are out there that actually work. These are the natural alternative treatments I use with my ADHD patients and clients that get results.
So Join Me Live Thursday January 20th At 12pm PST 3pm EST To find out what ADHD alternative treatment work and to get your ADHD questions answered Live with Dr. LeGrand!
Join our FREE ADHD Natural Solution Facebook Support Group here: s
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DISCLAIMER: This content is strictly the opinion of Dr. LeGrand and is for informational and educational purposes only. It is not intended to provide medical advice or to take the place of medical advice or treatment from a personal physician. All viewers of this content are advised to consult their doctors or qualified health professionals regarding specific health questions. Neither Dr. LeGrand nor the publisher of this content takes responsibility for possible health consequences of any person or persons reading or following the information in this educational content. All viewers of this content, especially those taking prescription or over-the-counter medications, should consult their physicians before beginning any nutrition, supplement or lifestyle program.


Find the best places near you to buy premium quality CBD in Bon Aqua, TN
There are actually hundreds of CBD sellers in Bon Aqua Tennessee however just a couple of sell CBD products with any type of clinical efficiency. There are some really crucial questions to ask before deciding where to get
What is CBD?
Hemp oil is much more widely understood to be in the Cannabis plant family members. Nonetheless, hemp does not offer the customer with high volumes of THC (like its relative equivalent does). Instead, it shares its mass quantities of cannabidiol, or CBD, with the customer.
For very first time buyers of CBD oil, it can be a little a challenge, as there are numerous things to take into consideration as CBD oil can can be found in several types. There is also a substantial number of different items as well as brand names on the market.
Where to Buy CBD Cream Near Me in Bon Aqua
To get the CBD oil that best matches your requirements, the two essential points to think about are the strength and concentration. Other elements to think about consist of purity and the quantity of CBD oil within the item itself.
The initial thing you require to know about selecting a CBD Oil product is that they can be made from removes from either Hemp Plants or Marijuana Plants. And, currently, those from marijuana plants are not legal in lots of states, neither can they be delivered across many state lines.
if you want to purchase cannabidiol (CBD) oil products, you have to dig deep to locate precise and current details. That’s because, while CBD is increasing in popularity, reliable details is commonly scattered throughout the web.
What’s even more, CBD is among the most misunderstood dietary substances offered today. Lots of people confuse it with THC, the major psychedelic active ingredient in marijuana.
As opposed to these typical false impressions, CBD is both legal as well as totally secure. It has no psychedelic components, so there’s no opportunity of “obtaining high.”
Even if you’re absolutely clear on the difference in between CBD and also THC, there are still lots of various other factors to consider prior to buying, consisting of brand names, focus, sorts of items, as well as above all, your very own demands.
One typical mistaken belief some people have regarding hemp oil is to assume this is cannabis. Despite the fact that hemp is part of the marijuana family members of species, it is extremely different from cannabis in many means.
CBD Oil available contains 0.3% THC (the legal limitation for this product) and also sometimes much less. As a result of the low consistency of THC, CBD products are not psychotropic as well as does not create any effects in the individual whatsoever.
Hemp also contains fats which have actually been recognized to be terrific for the body. Unlike its cannabis equivalent, hemp includes high amounts of CBD and low quantities of THC for which its expanded. While cannabis is unlawful to consume in many states, hemp is gradually ending up being extra popular as well as extra states are legalizing usings hemp oil for its residents.
Find Pure CBD Oil Near Your Area In Bon Aqua Tennessee
CBD derived hemp oil is a natural compound grown for numerous purposes, amongst which are the well-being benefits attached to this plant. Produce your very own opportunities and also learn for yourself exactly how CBD acquired products can benefit your everyday life.
When looking for the best CBD product, you’ll see 2 kinds mainly about, offered on the market; complete range CBD and also CBD isolate. The differences in between the two are fairly visible. However the technique of usage, quantitative dose, and time intervals can play a vital function in the efficiency of CBD. As full-spectrum CBD is much more preferred, isolate has specific benefits that might not be negated.
What do individuals mean by Separated CBD?
CBD isolate clarifies its name quite possibly. It refers to pure CBD that has been isolated from all various other compounds in the cannabis plant, having nothing else. A 2014 research study likewise demonstrated that CBD isolate can be helpful as there is no opportunity of THC inadvertently making its method into the product. The people that stay in states where THC is strictly forbidden, it might also benefit them. Separate is likewise valuable for sensitive to various other cannabinoids such as THC. Separate products are generally taken into consideration as having 99+% pure CBD.
What is meant by Complete Range CBD?
Complete range CBD describes CBD items containing CBD along with all various other energetic cannabinoids in the plant such as THC, CBG, CBN, terpenes and also all the other nutrients located in Cannabis plant. Usually these are in normally taking place ratios in the removed form, from the details pressure of the plant. They are additionally added purposefully into items to elevate the effectiveness. Full Range needs to be taken with some precautions by those who obtain their drugs checked. The THC found much less than 0.3% in full spectrum hemp items can make medicine tests positive.
Are you wanting to acquire CBD-rich oil? Discovering the ideal CBD oil can be a complicated job, especially if you are a rookie. There are lots of methods of getting your Cannabinoid (CBD) oil. You can acquire the item online, from brick and mortar store, co-ops, dispensaries, and natural herbalists. CBD oil items can be made from essences of either hemp plants or Marijuana Plant kingdoms. Relying on your recommended setting of ingestion, the hemp-extracted oil is available in a variety of applications consisting of casts, topicals, vaporizers, vape pens, transdermal spots and as infused edibles.
CBD oil is legal in 30 states where medical and/or leisure marijuana is legal, according to Governing publication.
Seventeen additional states have CBD-specific legislations on guides, according to Avoidance magazine. Those are Alabama, Georgia, Indiana, Iowa, Kentucky, Mississippi, Missouri, North Carolina, Oklahoma, South Carolina, South Dakota, Tennessee, Texas, Utah, Virginia, Wisconsin and also Wyoming.
- Where to buy CBD Oil in Bon Aqua TN
- Where to buy CBD Gummies in Bon Aqua TN
- Where to buy CBD Cream in Bon Aqua TN
- Where to buy CBD Vape Oil in Bon Aqua TN
CBD Shop Locations Near You
Bon Aqua, TN 37025
Hickman, Tennessee (TN)