Abstract P416: Remote Ischemic Conditioning Reduces Perihematomal Edema After Intracerebral Hemorrhage: First Proof-Of-Concept Randomized Controlled Trial

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Zhao Wenbo ◽  
Fang Jiang ◽  
Sijie Li ◽  
Yuchuan Ding ◽  
Xunming Ji
Keyword(s):  
Intracerebral Hemorrhage ◽  
Controlled Trial ◽  
Neurological Deterioration ◽  
Hematoma Expansion ◽  
Control Group ◽  
Hematoma Volume ◽  
Remote Ischemic Conditioning ◽  
Ischemic Conditioning ◽  
Significant Difference ◽  
Perihematomal Edema

Introduction: The prognosis of intracerebral hemorrhage (ICH) is poor because of the mass effect arising from the hematoma and the associated perihematomal edema (PHE). Remote ischemic conditioning (RIC) has been shown to promote hematoma clearance and reduce PHE in animal models, however it remains unknown whether RIC is safe and effective in reducing PHE in ICH patients. Objective: To evaluate the safety and efficacy of RIC in reducing PHE after ICH. Methods: In this open-label, rater-blind, randomized control trial, 40 subjects with supratentorial ICH (hematoma volume:10-30 ml) diagnosed between 24 to 48 hours of onset were assigned to the RIC group or control group. All subjects received standard background medical therapy. Subjects in the RIC group underwent repeated daily RIC (4 cycles of 5 minutes inflation [200 mmHg] /deflation [0 mmHg] of cuff on one arm) for 7 consecutive days. The primary efficacy outcome was PHE volume at 7 days, and both absolute PHE volume and relative PHE volume (defined as absolute PHE volume divided by hematoma volume) were measured. Safety outcome included death, neurological deterioration, hematoma expansion, and any other severe adverse events. Results: All 40 subjects completed this study. Mean age was 59.3±11.7 years, and 57.5% were male. At baseline, the median National Institutes of Health Stroke Scale score was 9.5 (range 1-28), median Glasgow Come Score was 15 (range 10-15), and mean ICH volume was 13.9±4.5 ml. The mean relative PHE volume was 1.11±0.26 in the control group and 1.05±0.23 in the RIC group at baseline; and 1.49±0.30 vs. 1.33 ±0.32 at Day 3 (p>0.05 each) respectively. After 7 days of treatment, RIC significantly reduced the relative PHE volume as compared to the control (1.77±0.39 vs. 2.02±0.27, p=0.02). The absolute PHE volume and hematoma volume at Day 3 and Day 7 had no significant difference between groups (p>0.05 each). No subject died or suffered from neurological deterioration or hematoma expansion and no adverse event was associated with RIC. Conclusion: RIC seemed to be safe in patients with ICH and induced a significant reduction in the relative PHE volume after 7 day of treatment. These results warrant a further study with large sample to examine the effect of RIC on functional outcome after ICH.

EXPRESS: Safety and Efficacy of Remote Ischemic Conditioning for the Treatment of Intracerebral Hemorrhage: A Proof-of-Concept Randomized Controlled Trial

2021 ◽  
pp. 174749302110065
Author(s):  
Wenbo Zhao ◽  
Fang Jiang ◽  
Sijie Li ◽  
Guiyou Liu ◽  
Chuanjie Wu ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Intracerebral Hemorrhage ◽  
Functional Outcomes ◽  
Controlled Trial ◽  
Control Group ◽  
Hematoma Volume ◽  
Remote Ischemic Conditioning ◽  
Resolution Rate ◽  
Ischemic Conditioning ◽  
Randomized Controlled

Background Remote ischemic conditioning (RIC) can promote hematoma resolution, attenuate brain edema, and improve neurological recovery in animal models of intracerebral hemorrhage (ICH). Aims This study aimed to evaluate the safety and preliminary efficacy of RIC in patients with ICH. Methods In this multicenter, randomized, controlled trial, 40 subjects with supratentorial ICH presenting within 24-48 hours of onset were randomly assigned to receive medical therapy plus RIC for consecutive 7 days or medical therapy alone. The primary safety outcome was neurological deterioration within 7 days of enrollment, and the primary efficacy outcome was the changes of hematoma volume on CT images. Other outcomes included hematoma resolution rate at 7 d ([hematoma volume at 7 d − hematoma volume at baseline]/hematoma volume at baseline), perihematomal edema (PHE), and functional outcome at 90 days. Results The mean age was 59.3±11.7 years and hematoma volume was 13.9±4.5 mL. No subjects experienced neurological deterioration within 7 days of enrollment, and no subject died or experienced RIC-associated adverse events during the study period. At baseline, the hematoma volumes were 14.19±5.07 mL in the control group and 13.55±3.99 mL in the RIC group, and they were 8.54±3.99 mL and 6.95±2.71 mL at 7 days after enrollment, respectively, not a significant difference (p>0.05 each). The hematoma resolution rate in the RIC group (49.25±9.17%) was significantly higher than in the control group (41.92±9.14%; MD, 7.3%; 95% CI, 1.51% to 13.16%; p=0.015). The absolute PHE volume was 17.27±8.34 mL in the control group and 12.92±7.30 mL in the RIC group at 7 days after enrollment, not a significant between-group difference (p=0.087), but the relative PHE in the RIC group (1.77±0.39) was significantly lower than in the control group (2.02±0.27; MD, 0.25; 95% CI, 0.39-0.47; p=0.023). At 90-day follow-up, 13 subjects (65%) in the RIC group and 12 subjects (60%) in the control group achieved favorable functional outcomes (mRS score≤3), not a significant between-group difference (p=0.744). Conclusions Repeated daily RIC for consecutive 7 days was safe and well-tolerated in patients with ICH, and it may be able to improve hematoma resolution rate and reduce relative PHE. However, effects RIC on the absolute hematoma and PHE volume and functional outcomes in this patient population need further investigations. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT03930940.

Late Neurological Deterioration after Acute Intracerebral Hemorrhage: A post hoc Analysis of the ATACH-2 Trial

2020 ◽  
Vol 49 (1) ◽  
pp. 26-31 ◽  
Author(s):  
Shuhei Okazaki ◽  
Haruko Yamamoto ◽  
Lydia D. Foster ◽  
Mayumi Fukuda-Doi ◽  
Masatoshi Koga ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Intracerebral Hemorrhage ◽  
Significant Risk ◽  
Blood Pressure Level ◽  
Neurological Deterioration ◽  
Major Influence ◽  
Case Report Form ◽  
Hematoma Volume ◽  
Systolic Blood Pressure Level ◽  
Significant Difference

Background: Neurological deterioration (ND) has a major influence on the prognosis of intracerebral hemorrhage (ICH); however, factors associated with ND occurring after 24 h of ICH onset are unknown. Methods: We performed exploratory analyses of data from the Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 trial, which compared intensive and standard blood pressure lowering treatment in ICH. NDs were captured on the adverse event case report form. Logistic regression analysis was performed to examine the independent predictors of late ND. Results: Among 1,000 participants with acute ICH, 82 patients (8.2%) developed early ND (≤24 h), and 64 (6.4%) had late ND. Baseline hematoma volume (adjusted OR [aOR] per 1-cm3 increase 1.04, 95% CI 1.02–1.06, p < 0.0001), hematoma volume increase in 24 h (aOR 2.24, 95% CI 1.23–4.07, p = 0.008), and the presence of intraventricular hemorrhage (IVH; aOR 2.38, 95% CI 1.32–4.29, p = 0.004) were independent predictors of late ND (vs. no late ND). Late ND was a significant risk factor for poor 90-day outcome (OR 3.46, 95% CI 1.82–6.56). No statistically significant difference in the incidence of late ND was noted between the 2 treatment groups. Conclusions: Initial hematoma volume, early hematoma volume expansion, and IVH are independent predictors of late ND after ICH. Intensive reduction in the systolic blood pressure level does not prevent the development of late ND.

scholarly journals Early Predictors of the Increase in Perihematomal Edema Volume After Intracerebral Hemorrhage: A Retrospective Analysis From the Risa-MIS-ICH Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Gengzhao Ye ◽  
Shuna Huang ◽  
Renlong Chen ◽  
Yan Zheng ◽  
Wei Huang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Black Hole ◽  
Intracerebral Hemorrhage ◽  
Clinical Laboratory ◽  
Characteristic Curve ◽  
Hematoma Expansion ◽  
Hematoma Volume ◽  
Absolute Increase ◽  
Poor Outcome ◽  
Perihematomal Edema

Background and Purpose: Perihematomal edema (PHE) is associated with poor functional outcomes after intracerebral hemorrhage (ICH). Early identification of risk factors associated with PHE growth may allow for targeted therapeutic interventions.Methods: We used data contained in the risk stratification and minimally invasive surgery in acute intracerebral hemorrhage (Risa-MIS-ICH) patients: a prospective multicenter cohort study. Patients' clinical, laboratory, and radiological data within 24 h of admission were obtained from their medical records. The absolute increase in PHE volume from baseline to day 3 was defined as iPHE volume. Poor outcome was defined as modified Rankin Scale (mRS) of 4 to 6 at 90 days. Binary logistic regression was used to assess the relationship between iPHE volume and poor outcome. The receiver operating characteristic curve was used to find the best cutoff. Linear regression was used to identify variables associated with iPHE volume (ClinicalTrials.gov Identifier: NCT03862729).Results: One hundred ninety-seven patients were included in this study. iPHE volume was significantly associated with poor outcome [P = 0.003, odds ratio (OR) 1.049, 95% confidence interval (CI) 1.016–1.082] after adjustment for hematoma volume. The best cutoff point of iPHE volume was 7.98 mL with a specificity of 71.4% and a sensitivity of 47.5%. Diabetes mellitus (P = 0.043, β = 7.66 95% CI 0.26–15.07), black hole sign (P = 0.002, β = 18.93 95% CI 6.84–31.02), and initial ICH volume (P = 0.018, β = 0.20 95% CI 0.03–0.37) were significantly associated with iPHE volume. After adjusting for hematoma expansion, the black hole sign could still independently predict the increase of PHE (P &lt; 0.001, β = 21.62 95% CI 10.10–33.15).Conclusions: An increase of PHE volume &gt;7.98 mL from baseline to day 3 may lead to poor outcome. Patients with diabetes mellitus, black hole sign, and large initial hematoma volume result in more PHE growth, which should garner attention in the treatment.

scholarly journals Coronavirus disease 2019 (COVID-19) can predispose young to Intracerebral hemorrhage: a retrospective observational study

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Michael T. Lawton ◽  
Ehsan Alimohammadi ◽  
Seyed Reza Bagheri ◽  
Arash Bostani ◽  
Siavash Vaziri ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Glasgow Coma Scale ◽  
Intracerebral Hemorrhage ◽  
Intraventricular Hemorrhage ◽  
Length Of Hospital Stay ◽  
Control Group ◽  
Case Group ◽  
Hematoma Volume ◽  
Coma Scale ◽  
Significant Difference

Abstract Background The respiratory system involvement is the most common presentation of Coronavirus disease 2019 (COVID-19). However, other organs including the central nervous system (CNS) could be affected by the virus. Strokes, seizures, change in mental status, and encephalitis have been reported as the neurological manifestation of the disease. We hypothesized that COVID-19 could predispose younger patients to spontaneous intracerebral hemorrhage (ICH). The present study aimed to investigate whether COVID-19 has any relationship with the occurrence of spontaneous ICH in young or not. Methods We retrospectively evaluated all the patients with spontaneous ICH who were referred to our center between 20 Feb and 1 Sep 2020. The demographic, clinical, radiological, and laboratory test data were evaluated. Patients were divided into two groups. The COVID-19 positive patients and COVID-19 negative ones. All the variables including age, sex, history of hypertension, diabetes mellitus, smoking, Glasgow Coma Scale (GCS), hematoma volume and location, the presence of intraventricular hemorrhage and hydrocephalus on admission, the length of hospital stay, the lab test results and the clinical outcome at last visit or discharge as Glasgow Outcome Scale (GOS) were compared between the two groups. Results There were 22 COVID-19 positive patients (20.8%) and 84 COVID-19 negative ones (79.2%). The mean age of the patients in the case group (54.27 ± 4.67) was significantly lower than that in the control group (69.88 ± 4.47) (p < 0.05). Meanwhile, our results showed a significant difference between the two groups based on the presence of chronic arterial hypertension (p < 0.05). There were no significant differences between the two groups based on gender, diabetes mellitus, smoking, Glasgow Coma Scale (GCS), hematoma volume, need for surgery, the presence of intraventricular hemorrhage and hydrocephalus on admission, White Blood Cell (WBC) count, platelet count, Prothrombin Time (PT), and Partial Thromboplastin Time (PTT) (p > 0.05). Conclusions Our results show that COVID positive patients with ICH are younger and with less predisposing factors than COVID negative subjects with ICH.

Abstract W P326: Comparison of Spontaneous Intracerebral Hemorrhage Outcomes in Patients with Warfarin and Antiplatelet Medication Use

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Santosh Murthy ◽  
Yogesh Moradiya ◽  
Jesse Dawson ◽  
Kennedy Lees ◽  
Daniel F Hanley ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Functional Outcomes ◽  
Intraventricular Hemorrhage ◽  
Hematoma Expansion ◽  
Spontaneous Intracerebral Hemorrhage ◽  
Hematoma Volume ◽  
Computed Tomographic ◽  
Warfarin Group ◽  
Antiplatelet Medication ◽  
Perihematomal Edema

Background: Use of antiplatelet medications and warfarin has been associated with poor clinical outcomes in spontaneous intracerebral hemorrhage (ICH). However, a head to head comparison between these groups has not been performed. We compared ICH outcomes among patients on these medications. Methods: In this cohort study, we analyzed 987 patients with ICH from the Virtual International Stroke Trials Archive. Patients with ICH presented within six-hours of symptom onset had baseline clinical, radiological data, and computed tomographic scan at 72 hours. Hematoma expansion was defined as interval increase in size by >33%. Main outcome variables were 90-day mortality, and modified Rankin Score (mRS) at 90 days dichotomized into 0-3 vs 4-6. Results: Of 987 ICH patients 154 had prior antiplatelet use, 30 had warfarin, and 803 had neither of the two medications. The warfarin group had significantly higher age (p<0.001) and higher prevalence of atrial fibrillation (p<0.001). Of the ICH characteristics, comparing warfarin, antiplatelet and no warfarin/antiplatelet cohorts, the warfarin group had lower Glasgow coma scale (GCS) scores (p=0.049), higher intraventricular hemorrhage (IVH) rate (p=0.010), and more hydrocephalus (p<0.001). Hematoma expansion at 72 hours was significantly higher with warfarin use (p=0.003), while the ratio of perihematomal edema volume to hematoma volume at 72 hours was lowest with warfarin use (p<0.001). In the logistic regression model adjusted for age, sex, race, hematoma volume, perihematomal edema, GCS, IVH and hydrocephalus; warfarin patients had significantly lower odds of achieving mRS 0-3 (OR: 0.23, 95% CI: 0.06-0.83, p=0.025), while the antiplatelet group had similar functional outcomes compared to no warfarin/antiplatelet use (OR: 0.75, 95% CI: 0.46-1.23, p=0.260). The 90-day mortality outcomes were not significantly different across the three groups (18.7% to 40.3%, p=0.520). Conclusion: Warfarin use is associated with a higher incidence of hydrocephalus, intraventricular hemorrhage and hematoma expansion, but lesser perihematomal edema relative to the hematoma volume. Warfarin associated ICH appears to be independently associated with worse functional outcomes but not with 90-day mortality in ICH.

Reducing the Social Stigma Associated with Obsessive Compulsive Disorder: A Controlled Trial of an Intervention Program in a Turkish Community Sample

2020 ◽  
Vol 20 (2) ◽  
pp. 101-120
Author(s):  
Ayça Aktaç Gürbüz ◽  
Orçun YORULMAZ ◽  
Gülşah DURNA
Keyword(s):  
Obsessive Compulsive Disorder ◽  
Intervention Program ◽  
Controlled Trial ◽  
Community Sample ◽  
Case Vignette ◽  
Control Group ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Significant Difference ◽  
The Impact

Scientific research into the reduction of stigmatization, particularly related to specific problems such as Obsessive-Compulsive Disorder (OCD), is scarce. In the present study, we examine the impact of a video-based antistigma intervention program for OCD in a pretest-posttest control group research. After being randomly assigned to either an intervention (n= 101) or control group (n= 96), the participants reported their attitudes on a hypothetical case vignette before and after OCD vs. Multiple Sclerosis (MS) videos, and again six months later as a follow up assessment. The mixed design analyses for the group comparisons indicated that although there was no significant difference in the measures of the control group, the participants watching the anti-stigma OCD video, in which the focus was psychoeducation and interaction strategies, reported significantly lower scores on social distances and negative beliefs for the case vignettes they read, and this difference was maintained six months later. Then, the present results indicate the effectiveness of our anti-stigma intervention program for OCD. Interventions to reduce stigmatization can also be viewed as effective tools for changing the attitudes of people toward OCD, although further research and applications are needed related to specific disorders if a longlasting impact is to be achieved.

Breastfeeding Training through Role-Play and Effects on Mother-infant Attachment Behaviours: A Randomised Controlled Trial

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Farokh Saljughi ◽  
Mitra Savabi-Esfahani ◽  
Shahnaz Kohan ◽  
Soheila Ehsanpour
Keyword(s):  
Pregnant Women ◽  
Maternal Employment ◽  
Controlled Trial ◽  
Role Play ◽  
Intervention Group ◽  
Control Group ◽  
Maternal Behaviour ◽  
Infant Attachment ◽  
Significant Difference ◽  
History Of

Mother-infant attachment is an intimate, lasting and satisfying relationship that leads to better cognitive, emotional and social growth of the infant. The aim of this study was to determine the effects of breastfeeding training by role-play on mother-infant attachment behaviours. This research was a randomised clinical trial (parallel design). Inclusion criteria were: no history of mental disorders; ability to read and write the Persian language to complete the questionnaire; no history of drug and tobacco intake in primigravida women. The sample comprised 100 pregnant women (in 2 groups), selected through simple random sampling at healthcare centres. The researcher reviewed prenatal care registries of selected healthcare centres and extracted the names of pregnant women in their early third trimester. The data were imported into randomisation software. The control group received routine breastfeeding training, while the intervention group received routine training together with training through role-play. The data collection tool was the Maternal Behaviour Inventory Questionnaire. Consequently 75 samples were analysed in SPSS16. Independent t-tests and chi-square tests were used to examine the difference between the two groups. Results showed that the mean score of mother-infant attachment one week after delivery was significantly higher in the intervention group in comparison to that in the control group (p<0.001). No significant difference was observed between the two groups in maternal age, age of marriage, neonatal gender, maternal employment and education, number of parity, and number of abortions (P>0.05). Since breastfeeding training through role-play could affect mother-infant attachment, it is suggested that this type of training should be provided for pregnant women to promote mother-infant attachment and exclusive breastfeeding.

The Effect of Reflexology on Labor Pain and Length Among Primiparous Women: A Randomized Controlled Trial

2018 ◽  
Vol 7 ◽  
Author(s):  
Azita Kamjoo
Keyword(s):  
Controlled Trial ◽  
Intervention Group ◽  
Active Phase ◽  
Labor Pain ◽  
Control Group ◽  
Singleton Pregnancy ◽  
Group Data ◽  
Significant Difference ◽  
Labor Length ◽  
Primiparous Women

Background: Pain control is considered as the key issue in modern midwifery. Along with medical painkillers, reflexology is viewed as a non-medical and noninvasive method. Hence, we aimed to investigate the effect of reflexology on the intensity of pain and length of labor. Materials and Methods: In this clinical trial, participants included 240 Iranian primiparous women with term and singleton pregnancy. Having a 3-4 cm cervical dilatation once they visited the hospital. Through a convenient sampling method, they were selected and then randomly divided into two groups. In the intervention group, reflexology was performed, and the intensity of pain during the active phase of labor along with the length of labor in the active phase was measured by visual analog scale (VAS) and compared with the control group. Data were analyzed using descriptive statistics, t-test, and Mann-Whitney U-test. Result: Data analysis showed a statistically significant difference between the intensity of pain in the 5-7 and 8-10 cm dilatation in the two groups (P=0.01). Moreover, the labor length in the active phase was found to be significantly shorter in the intervention group (P<0.001). Conclusion: It appears that reflexology can lead to a reduction in the pain and length of labor. Therefore, through instructing this technique, a goal of midwifery, which is reducing labor pain and its length can be achieved. Keywords: Reflexology, Labor Pain, Labor Length, Primiparous Women

The effect of foot reflexology on chemotherapy-induced nausea and vomiting in digestive or lung cancer patients: a randomized controlled trial (Preprint)

2020 ◽  
Author(s):  
Audrey Murat-Ringot ◽  
Pierre Jean Souquet ◽  
Fabien Subtil ◽  
Florent Boutitie ◽  
Marie Preau ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Controlled Trial ◽  
Nausea And Vomiting ◽  
Control Group ◽  
Digestive Cancer ◽  
Complementary Medicines ◽  
Antiemetic Drugs ◽  
Platinum Based Chemotherapy ◽  
Significant Difference ◽  
Delayed Nausea

BACKGROUND Cancer is a chronic disease with an incident worldwide had been 24.5 million and 9.6 million deaths in 2017. Lung and colorectal cancer are the most common cancer for both sexes and according to national and international recommendations platinum-based chemotherapy is the reference adjuvant treatment. This chemotherapy can be moderately to highly emetogenic. Despite antiemetic therapy, chemotherapy-induced nausea and vomiting may persist. Moreover, cancer patient are increasingly interested in alternative and complementary medicines and express the desire that non-pharmacological treatments be used in hospitals. Among alternative and complementary medicines, foot reflexology decreases significantly the severity of chemotherapy-induced nausea and vomiting in breast cancer patients. OBJECTIVE The primary objective of the present study was to assess the benefits of foot reflexology as a complement to conventional treatments on severity of acute chemotherapy-induced nausea and vomiting in digestive or lung cancer patients. The secondary objectives assessed were the frequency and severity of delayed chemotherapy-induced nausea and vomiting, quality of life, anxiety, and self-esteem. METHODS The present study was conducted between April 2018 and April 2020 in French University Hospital. This is an open-label randomized controlled trial. Participants are randomized into two groups: 40 to interventional group (conventional care with foot reflexology) and 40 to control group (conventional care without foot reflexology). Foot reflexology sessions (30 minutes) are performed on an outpatient or inpatient. Eligible participants are patients with a lung or digestive cancer with indication for platinum-based chemotherapy. RESULTS The severity of acute nausea and vomiting was assessed with a visual analogue scale during the second cycle of chemotherapy. A significant increase of at least 2 points was observed for control group (20.6%, P = 0.01). Across all cycle, the foot reflexology group showed a trend towards less frequent delayed nausea (P=0.28), a significantly less frequent consumption of antiemetic drugs (P=0.04), and no significant difference for vomiting (P=0.99); there was a trend towards a perception of stronger severity for delayed nausea in the control group (P=0.39). According to quality of life and anxiety, there was no significant difference between the interventional group and the control group (P=0.32 and P=0.53 respectively). CONCLUSIONS In conclusion, the present study results indicated that foot reflexology decreased significantly the severity of acute nausea and consumption of antiemetic drugs in lung and digestive cancer patients. No side effects from foot reflexology have been noted. In order to better respond to a desire of patients for non-pharmacological treatments and CAMs to be used in hospitals to improve their care, the results of this study showed that foot reflexology seems to be a promising complement to conventional antiemetic drugs. To assess the performance of this intervention in routine practice, a larger study with several health care centers would be relevant with a cluster RCT. CLINICALTRIAL The present study registered with clinicaltrials.gov: NCT03508180 (28/06/2018) INTERNATIONAL REGISTERED REPORT RR2-10.2196/17232

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