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Abstract Background: Heart Rate Variability (HRV) analysis is a non-invasive method of assessing autonomic tone and has been studied in conjunction with.

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Presentation on theme: "Abstract Background: Heart Rate Variability (HRV) analysis is a non-invasive method of assessing autonomic tone and has been studied in conjunction with."— Presentation transcript:

1 Abstract Background: Heart Rate Variability (HRV) analysis is a non-invasive method of assessing autonomic tone and has been studied in conjunction with acupuncture in a number of contexts. Acupuncture can lower sympathetic tone and enhance vagal activity, i.e decrease the stress reponse. In contrast to the research setting, there are time and efficiency constraints in the private acupuncture practice. In addition there can be monitoring artifacts which make frequency and time domain HRV analysis unreliable. The author hypothesizes that analysis using nonlinear HRV analysis in addition to the aforementioned analysis methods will give a more sensitive and dependable evaluation of the patients autonomic state and show a more consistent correlation with clinical outcomes. The ultimate goal is to use HRV as an additional feedback in the clinic to achieve better results and hence, better outcomes. Objective: To correlate patients responses to acupuncture treatment with their intra- treatment HRV measurements across time, frequency and nonlinear domains. Design, Setting, and Patients: Case study of 20 patients representing 80 treatment sessions. The presenting diagnoses were varied including hypertension(3), low back pain/sciatica (3), headache/migraine(5), depression/anxiety(4), peripheral neuropathy (2), allergy (1), IBS(1), PCOS (1). Intervention: All patients received body acupuncture according Traditional Chinese Medicine principles. Electro-acupuncture was used if following a protocol (PCOS), or if manual acupuncture was not proving effective. HRV data was collected after needle placement for 20 minutes, and analyzed after treatment. Main Outcome Measure: Patients were assessed by symptom resolution. Their HRV data were compared for the time framesa (60 to 360 sec) andb ( 360 to 660 sec) using Kubios shareware for: 1. Time series: pnn50 % 2. Frequency Domain: FFT (LFR/HFR) ratios and HFR% 3. Nonlinear results: Poincaré Plots (SD1/SD2) and Sample entropy Results: Patients who responded to their acupuncture treatment tended to exhibit a decrease in LFR/HFR in the segmenta, compared tob by at least 30% and/or an increase froma tob in the nonlinear measurement SD1/SD2 by at least 20%. Non-responders, or patients who were aggravated by a particular treatment tended to show no change or an increase in their LFR/HFR froma tob and a decrease in their SD1/SD2 froma tob. Conclusions: In this study the correlation between increased HRV during acupuncture treatment and positive response to acupuncture was supported. Use of nonlinear analysis in addition to frequency domain measures added to the sensitivity of HRV outcome measures.

2 Introduction The goal of these studies is to develop a system of 1. Reliable measurement of HRV (Heart Rate Variability) during acupuncture treatment to help guide and inform treatment. 2. To establish the utility of acupuncture as a stress reducing treatment. 3. To develop a dependable system of measurement to be used to correlate with more invasive and expensive measures of stress and health such as cortisol measurements, fMRI, EEG, and telomere evaluations. The Autonomic Nervous System and Acupuncture: Autonomic balance has been implicatedin acupunctures results [i][ii]. Increased parasympathetic activity and decreased sympathetic activity can be beneficial to the patient in that increased stress and elevated cortisol levels coincide with increased sympathetic tone and have an incalculable negative impact on pain, mood, immunity, longevity, and health in general.7,8 HRV and Autonomic Nervous System: The basic concept in HRV is that more complexity is a sign of greater health. HRV is often measured after a physiological intervention, such as postural change, a cardiac stressor, or even mental challenges. Acupuncture and HRV: Acupuncture is a subtle intervention that achieves its results by triggering multiple neurotransmitters including local and central effects, and it may be possible to detect some of those changes by subtle changes in HRV. HRV has been studied with acupuncture in the laboratory setting, on healthy volunteers, and in the clinic on specific patients. HRV has been explored in conjunction with fMRI[iii] and EEG[iv] in the acupuncture context also. There are a few studies correlating HRV with positive clinical outcomes[v][vi][vii], but in general, HRV is for the most part relegated to studies, not as a practical tool to be used in the clinic. There is good reason for this,There are multiple confounds in combining the acupuncture and HRV, including the constraints of clinical practice and the propensity to artifact in cardiac monitoring. The author hypothesized that with the newer capabilities of Kubios shareware to analyze HRV with nonlinear methods, inclusion of nonlinear parameters could prove to be more reliable and sensitive to subtle shifts in HRV than linear methods. With a decrease in the stress reponse, one would expect to see the following. Fast Fourier Transform. A Decrease in the LFR/HFR from segment a (1 minute to 6 minutes) and b (minutes 6 to 11.) Poincare Plots (SD1/SD2) are a valuable method which is a simple visualization tool, can identify ectopic beats so is less dependent on a pristine heart tracing.[viii] Would expect to see an increase in the SD1/SD2 between a and b segments. Sample Entropy, SampEn is widely accepted as a more consistent and less biased complexity measure than Approximate Entropy. You would expect to see an increase in Sample Entropy from the first to the second time window.

3 Abstract Heart Rate Variability Analysis in the Acupuncture Clinic: Correlation with Clinical Outcomes Kristen Sparrow, MD Private Practice San Francisco, California Background: Heart Rate Variability (HRV) analysis is a non-invasive method of assessing autonomic tone and has been studied in conjunction with acupuncture in a number of contexts. Acupuncture can lower sympathetic tone and enhance vagal activity, i.e decrease the stress reponse. In contrast to the research setting, there are time and efficiency constraints in the private acupuncture practice. In addition there can be monitoring artifacts which make frequency and time domain HRV analysis unreliable. The author hypothesizes that analysis using nonlinear HRV analysis in addition to the aforementioned analysis methods will give a more sensitive and dependable evaluation of the patients autonomic state and show a more consistent correlation with clinical outcomes. The ultimate goal is to use HRV as an additional feedback in the clinic to achieve better results and hence, better outcomes. Objective: To correlate patients responses to acupuncture treatment with their intra- treatment HRV measurements across time, frequency and nonlinear domains. Design, Setting, and Patients: Case study of 20 patients representing 80 treatment sessions. The presenting diagnoses were varied including hypertension(3), low back pain/sciatica (3), headache/migraine(5), depression/anxiety(4), peripheral neuropathy (2), allergy (1), IBS(1), PCOS (1). Intervention: All patients received body acupuncture according Traditional Chinese Medicine principles. Electro-acupuncture was used if following a protocol (PCOS), or if manual acupuncture was not proving effective. HRV data was collected after needle placement for 20 minutes, and analyzed after treatment. Main Outcome Measure: Patients were assessed by symptom resolution. Their HRV data were compared for the time frames a (60 to 360 sec) and b (360 to 660 sec) using Kubios shareware for: 1. Time series: pnn50 % 2. Frequency Domain: FFT (LFR/HFR) ratios and HFR% 3. Nonlinear results: Poincaré Plots (SD1/SD2) and Sample entropy Results: Patients who responded to their acupuncture treatment tended to exhibit a decrease in LFR/HFR in the segment a, compared to b by at least 30% and/or an increase from a to b in the nonlinear measurement SD1/SD2 by at least 20%. Non-responders, or patients who were aggravated by a particular treatment tended to show no change or an increase in their LFR/HFR from a to b and a decrease in their SD1/SD2 from a to b. Conclusions: In this study the correlation between increased HRV during acupuncture treatment and positive response to acupuncture was supported. Use of nonlinear analysis in addition to frequency domain measures added to the sensitivity of HRV outcome measures.

4 Introduction The goal of these studies is to develop a system of 1. Reliable measurement of HRV (Heart Rate Variability) during acupuncture treatment to help guide and inform treatment. 2. To establish the utility of acupuncture as a stress reducing treatment. 3. To develop a dependable system of measurement to be used to correlate with more invasive and expensive measures of stress and health such as cortisol measurements, fMRI, EEG, and telomere evaluations. The Autonomic Nervous System and Acupuncture: Autonomic balance has been implicatedin acupunctures results [i][ii]. Increased parasympathetic activity and decreased sympathetic activity can be beneficial to the patient in that increased stress and elevated cortisol levels coincide with increased sympathetic tone and have an incalculable negative impact on pain, mood, immunity, longevity, and health in general.7,8[i][ii] HRV and Autonomic Nervous System: The basic concept in HRV is that more complexity is a sign of greater health. HRV is often measured after a physiological intervention, such as postural change, a cardiac stressor, or even mental challenges. Acupuncture and HRV: Acupuncture is a subtle intervention that achieves its results by triggering multiple neurotransmitters including local and central effects, and it may be possible to detect some of those changes by subtle changes in HRV. HRV has been studied with acupuncture in the laboratory setting, on healthy volunteers, and in the clinic on specific patients. HRV has been explored in conjunction with fMRI[iii] and EEG[iv] in the acupuncture context also. There are a few studies correlating HRV with positive clinical outcomes[v][vi][vii], but in general, HRV is for the most part relegated to studies, not as a practical tool to be used in the clinic. There is good reason for this,There are multiple confounds in combining the acupuncture and HRV, including the constraints of clinical practice and the propensity to artifact in cardiac monitoring. The author hypothesized that with the newer capabilities of Kubios shareware to analyze HRV with nonlinear methods, inclusion of nonlinear parameters could prove to be more reliable and sensitive to subtle shifts in HRV than linear methods.[iii][iv][v][vi][vii] With a decrease in the stress reponse, one would expect to see the following. Fast Fourier Transform. A Decrease in the LFR/HFR from segment a (1 minute to 6 minutes) and b (minutes 6 to 11.) Poincare Plots (SD1/SD2) are a valuable method which is a simple visualization tool, can identify ectopic beats so is less dependent on a pristine heart tracing.[viii] Would expect to see an increase in the SD1/SD2 between a and b segments.[viii] Sample Entropy, SampEn is widely accepted as a more consistent and less biased complexity measure than Approximate Entropy. You would expect to see an increase in Sample Entropy from the first to the second time window.

5 References [i] Ernst and leeErnst M, Lee M. Sympathetic effects of manual and electrical [i] acupuncture of the Tsusanli knee point: comparison with the Hoku hand point sympathetic effects. Exp Neurol. 1986;94: 1–10. [ii] Anderson S, Lundeberg T. Med Hypothesis. 1995;45:273–28 [ii] [iii] Napadow- Monitoring acupuncture effects on human brain by FMRI.Hui KK, Napadow V, Liu J, Li M, Marina O, Nixon EE, Claunch JD, LaCount L, Sporko T, Kwong KK. [iii] J Vis Exp. 2010 Apr 8;(38). pii: 1190. doi: 10.3791/1190. [iv] Sakai Autonomic Neuroscience 2007 May 30;133(2) 158-69Specific acupuncture sensation correlates with EEGs and autonomic [iv] changes in human subjects Shigekazu Sakai, Etsuro Hori, Katsurni Umeno, Nobuhide Kitabayashi, Taketoshi Ono, Hisao Nishijo * [v] Acupuncture in migraine: investigation of autonomic effects [v] Bäcker M, Grossman P, Schneider J, Michalsen A, Knoblauch N, Tan L, Niggemeyer C, Linde K, Melchart D, Dobos GJ. Clin J Pain. 2008 Feb;24(2):106-15. [vi] MEDICAL ACUPUNCTURE Volume 19, Number 1, 2007Analysis of Heart Rate Variability in Acupuncture Practice: [vi] Can It Improve Outcomes? K. Sparrow, MD [vii] Chambers AS, Allen JJ. Vagal tone as an indicator of treatment repsonse in major depression. Psychophysiology. [vii] 2002;39:861–864. [viii] Poincaré Plots:A MiniReview ReyLab, Beth Israel Deaconess Medical Center Harvard Medical SchoolDept. Psychiatry, Taipei Veterans General Hospital, Taiwan Albert C.C.Yang, MD [viii] [1] Tulppo et al. Circulation2005; 112:314-319 [1] Medicina (Kaunas) 2010;46(6):,393-400Linear and nonlinear heart rate dynamics in elderly inpatients.Relations with comorbidity and depression Cristina Blasco-Lafarga1, 2, Ignacio Martínez-Navarro1, María Elisa

6 Materials and Methods Design, Setting, and Patients: Case study of 20 patients representing 80 treatment sessions. The presenting diagnoses were varied including hypertension(3), low back pain/sciatica (3), headache/migraine(5), depression/anxiety(4), peripheral neuropathy (2), allergy (1), IBS(1), PCOS (1). When patients were in a prone or lateral position, the data was collected but not used in the study. Controls: This study did not use controls, rather compared like kind data between acupuncture sessions and between patients. Intervention: All patients received body acupuncture according Traditional Chinese Medicine principles. Electro-acupuncture was used if following a protocol (PCOS), or if manual acupuncture was not proving effective. Heart rate data was collected after needle placement for 20 minutes, and analyzed after treatment. The heart rate tracing was analyzed by pasting into the Kubios system, read out in 5 minute windows starting at 1 minute. The use of 5 minute intervals has precedent in the literature, and is seen as an appropriate time window for analysis. The specific 5 minute intervals (minute 1 to 6, and then 6 to 11) are used because of previous studies trial and error to be the most indicative. These were then saved as an Excel Spreadsheet for tabulating. The heart rate tracings had to be scanned for artifact by filtering. Tracings with too many artifacts were excluded from study. Main Outcome Measure: Patients were assessed by symptom resolution. Some conditions were easier to quantify than others. Headaches, panic attacks, insomnia, knee pain easier to quantify than IBS and PCOS for example. Their HRV data were compared for the time frames a (60 to 360 sec) and b (360 to 660 sec) using Kubios shareware for: 1. Time series: pnn50 % (not included in current results because of poor correlation) 2. Frequency Domain: FFT (LFR/HFR) ratios and HFR ms 3. Nonlinear results: Poincaré Plots (SD1/SD2) and Sample entropy

7 Results It is feasible to evaluate HRV in the acupuncture clinic both by nonlinear and linear measurements. The total calculation time is 7 minutes. Patients who responded to their acupuncture treatment tended to exhibit a decrease in their LFR/HFR ratio from segment a to segment b, an increase in their SD1/SD2, and an increase in their Samp En: all of these trends indicating a decrease in their stress response Non-responders, or patients who were aggravated by a particular treatment tended to show no change or an increase in their LFR/HFR from minute and a decrease in their SD1/SD2 from the first to second time window, and an increase in their Sample Entropy There were notable exceptions, i.e. patients who were strong responders, who did not exhibit the consistent pattern above. In these patients, Sample Entropy was the strongest predictor of successful treatment. Because of the prevalence of artifact in heart rate monitoring, the addition of nonlinear measures gives added confidence to the measurements obtained. Changing the needle placement prescription and type of stimulation changed outcomes corresponding to HRV results in some cases.

8 Discussion The goal of having a non-invasive monitoring system that can detect subtle shifts with acupuncture physiologically is the thrust of the authors research. Exploring HRV with acupuncture over the last several years revealed, somewhat counterintuitively, that there is an intra-treatment increase in HRV. This phenomenon has been corroborated in other studies[i][ii]. The Bäcker study saw only decreases in LFR, other studies have only seen changes in HF.[iii]. With more trustworthy HRV data collection and analysis, comparing of acupoints, various types of acupuncture stimulation, duration of treatment, and spacing of visits would be of interest also.[i][ii][iii] This study is far from scientific, but rather a case study in monitoring HRV in the actual acupuncture clinic, and the author felt compelled to share and tabulate the results of these recent efforts. Clinical outcomes are not graded per se in this study, but are the result of careful interviews on subsequent patient visits. HRV measurement and analysis is an exacting undertaking, but with the addition of nonlinear measurements, which are less affected by artifact, the results are more trustworthy. In this study there are noted outliers where there were strong responders who had significant and profound relief from symptoms, but their HRV did not reflect that (PeAl,GuPa,RuSu). The correlation is not perfect. Comparing patients and treatment sessions instead of control groups, can still give interesting and provocative findings. In controlled studies not available to the clinical practitioner, these trends could hopefully be verified. And finally, there is an ever increasing focus on the adverse physiological effects of stress. Recent Nobel Prize winning research[iv] shows the effects on a cellular level of stress on aging. Traditionally, in Chinese Medicine, prevention and anti-aging are pillars of practice. If acupuncture can be shown to be an effective treatment option for physiological stress, not only will the ancient practitioners be vindicated, but we will be offering real preventative treatment.[iv] [i] Acupuncture in migraine: investigation of autonomic effects Bäcker M, Clin J Pain. 2008 Feb;24(2):106-15 [i] [ii] Effect of acupuncture on heart rate variability in primary dysmenorrheic women. Kim E, Cho JH, Jung WS, Lee S, Pak SC.Am J Chin Med. 2011;39(2):243-9. [ii] [iii] Auton Neurosci. 2011 Apr 26;161(1-2):116-20. Epub 2011 Jan 7. [iii] Acupuncture to Danzhong but not to Zhongting increases the cardiac vagal component of heart rate variability. Kurono Y, Minagawa M, Ishigami T, Yamada A, Kakamu T, Hayano J [iv] Accelerated telomere shortening in response to life stress. PNAS 2004 Dec 7;101(49):17312-5 Blackburn E [iv]

9 Responders

10

11

12 Partial Responders Patients with partial resolution of Sx MoAn had less pain but still extreme constipation. For last treatment stopped electro. FlSt had less IBS. Also changed protocol for last two visits and removed electro with better results

13 Nonresponders to Responders with Change in Needle Protocol In these patients, the needle protocol was changed and lead to better results clinically, reflected partially by HRV results

14 Nonresponders to Responders with Change in Needle Protocol Needle placement changed to assymetric, smaller gauge, fewer needles.

15 Nonresponders

16 Heart Rate Variability Analysis in the Acupuncture Clinic: Correlation with Clinical Outcomes Kristen Sparrow, MD Private Practice San Francisco, California

17

18 Introduction The ultimate goal of these studies is to develop a system of 1. Reliable measurement of HRV(Heart Rate Variability) during acupuncture treatment to help guide and inform treatment. 2. To establish the utility of acupuncture as a stress reducing treatment. 3. To develop a dependable system of measurement to be used to correlate with more invasive and expensive measures of stress and health such as cortisol measurements, fMRI, EEG, and telomere evaluations. The Autonomic Nervous System and Acupuncture: Autonomic balance has been implicated in acupunctures results [i][ii]. Increased parasympathetic activity and decreased sympathetic activity can be beneficial to the patient in that increased stress and elevated cortisol levels coincide with increased sympathetic tone and have an incalculable negative impact on pain, mood, immunity, longevity, and health in general.7,8[i][ii] HRV and Autonomic Nervous System: The basic concept in HRV is that more complexity is a sign of greater health. HRV is often measured after a physiological intervention, such as postural change, a cardiac stressor, or even mental challenges. Acupuncture and HRV : Acupuncture is a subtle intervention that achieves its results by triggering multiple neurotransmitters including local and central effects, and it may be possible to detect some of those changes by subtle changes in HRV. HRV has been studied with acupuncture in the laboratory setting, on healthy volunteers, and in the clinic on specific patients. HRV has been explored in conjunction with fMRI[iii] and EEG[iv] in the acupuncture context also. There are a few studies correlating HRV with positive clinical outcomes[v][vi][vii], but in general, HRV is for the most part relegated to studies, not as a practical tool to be used in the clinic. There is good reason for this, There are multiple confounds in combining the acupuncture and HRV, including the constraints of clinical practice and the propensity to artifact in cardiac monitoring. The author hypothesized that with the newer capabilities of Kubios shareware to analyze HRV with nonlinear methods, inclusion of nonlinear parameters could prove to be more reliable and sensitive to subtle shifts in HRV than linear methods.[iii][iv][v][vi][vii] With a decrease in the stress reponse, one would expect to see the following. Fast Fourier Transform. A Decrease in the LFR/HFR from segment 1 minute to 6 minutes and minutes 6 to 11. Poincare Plots (SD1/SD2) are a valuable method which is a simple visualization tool, can identify ectopic beats so is less dependent on a pristine heart tracing.[viii] Would expect to see an increase in the SD1/SD2 between 5 minute segments.[viii] Sample Entropy, SampEn is widely accepted as a more consistent and less biased complexity measure than Approximate Entropy. You would expect to see an increase in Sample Entropy from the first to the second time window.

19 References [i] Ernst and leeErnst M, Lee M. Sympathetic effects of manual and electrical acupuncture of the Tsusanli knee point: comparison with the Hoku hand point sympathetic effects. Exp Neurol. 1986;94: 1–10. [ii] Anderson S, Lundeberg T. Med Hypothesis. 1995;45:273–28 [iii] Napadow [iv] Sakai Autonomic Neuroaciencc: Basic and Clinical xx (2007) xxx – xxx AUTONOMIC NEUROSCIENCE: Basic & CIinlcal [i][ii][iii][iv] Specific acupuncture sensation correlates with EEGs and autonomic changes in human subjects Shigekazu Sakai, Etsuro Hori, Katsurni Umeno, Nobuhide Kitabayashi, Taketoshi Ono, Hisao Nishijo * [v] Acupuncture in migraine: investigation of autonomic effects [v] Bäcker M, Grossman P, Schneider J, Michalsen A, Knoblauch N, Tan L, Niggemeyer C, Linde K, Melchart D, Dobos GJ. Clin J Pain. 2008 Feb;24(2):106-15. [vi] MEDICAL ACUPUNCTURE Volume 19, Number 1, 2007Analysis of Heart Rate Variability in Acupuncture Practice: [vi] Can It Improve Outcomes?K. Sparrow, MD [vii] Chambers AS, Allen JJ. Vagal tone as an indicator of treatment repsonse in major depression. Psychophysiology. [vii] 2002;39:861–864. [viii] Poincaré Plots:A MiniReview ReyLab, Beth Israel Deaconess Medical Center Harvard Medical SchoolDept. Psychiatry, Taipei Veterans General Hospital, Taiwan Albert C.C.Yang, MD [viii] [1] Tulppo et al. Circulation2005; 112:314-319 [1] Medicina (Kaunas) 2010;46(6):,393-400Linear and nonlinear heart rate dynamics in elderly inpatients.Relations with comorbidity and depression Cristina Blasco-Lafarga1, 2, Ignacio Martínez-Navarro1, María Elisa

20 Materials and Methods Design, Setting, and Patients: Case study of 20 patients representing 80 treatment sessions. The presenting diagnoses were varied including hypertension(3), low back pain/sciatica (3), headache/migraine(5), depression/anxiety(4), peripheral neuropathy (2), allergy (1), IBS(1), PCOS (1). When patients were in a prone or lateral position, the data was collected but not used in the study. Controls: This study did not use controls, rather compared like kind data between acupuncture sessions and between patients. Intervention: All patients received body acupuncture according Traditional Chinese Medicine principles. Electro-acupuncture was used if following a protocol (PCOS), or if manual acupuncture was not proving effective. Heart rate data was collected after needle placement for 20 minutes, and analyzed after treatment. The heart rate tracing was analyzed by pasting into the Kubios system, read out in 5 minute windows starting at 1 minute. The use of 5 minute intervals has precedent in the literature, and is seen as an appropriate time window for analysis. These were then saved as an Excel Spreadsheet for tabulating. The heart rate tracings had to be scanned for artifact by filtering. Tracings with too many artifacts were excluded from study. Main Outcome Measure: Patients were assessed by symptom resolution. Their HRV data were compared for the time framesa (60 to 360 sec) andb ( 360 to 660 sec) using Kubios shareware for: 1. Time series: pnn50 % 2. Frequency Domain: FFT (LFR/HFR) ratios and HFR ms 3. Nonlinear results: Poincaré Plots (SD1/SD2) and Sample entropy

21 Results It is feasible to evaluate HRV in the acupuncture clinic both by nonlinear and linear measurements. The total calculation time is 7 minutes. Filtering of the heart rate data to get rid of artifacts is a crucial part the HRV analysis and adds greatly to the time of calculation and uncertainty of the results. Patients who responded to their acupuncture treatment tended to exhibit a decrease in LFR/HFR in the minute 1 to 6 versus minutes 6 to 11 of a treatment session. Non-responders, or patients who were aggravated by a particular treatment tended to show no change or an increase in their LFR/HFR from minute and a decrease in their SD1/SD2 from the first to second time window.

22 Summary It Patients with positive clinical outcomes tended to showed vagal enhancement and increased complexity as shown by SampEn

23 Responders

24

25

26 Partial Responders Patients with partial resolution of Sx MoAn had less pain but still extreme constipation. For last treatment stopped electro. FlSt had less IBS. Also changed protocol for last two visits and removed electro with better results

27 Nonresponders to Responders with Change in Needle Protocol In these patients, the needle protocol was changed and lead to better results clinically, reflected partially by HRV results

28 Nonresponders to Responders with Change in Needle Protocol Needle placement changed to assymetric, smaller gauge, fewer needles.

29 Nonresponders


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