Patients’ experiences of cold exposure during ambulance care
© Aléx et al.; licensee BioMed Central Ltd. 2013
Received: 15 March 2013
Accepted: 1 June 2013
Published: 6 June 2013
Exposure to cold temperatures is often a neglected problem in prehospital care. Cold exposure increase thermal discomfort and, if untreated causes disturbances of vital body functions until ultimately reaching hypothermia. It may also impair cognitive function, increase pain and contribute to fear and an overall sense of dissatisfaction. The aim of this study was to investigate injured and ill patients’ experiences of cold exposure and to identify related factors.
During January to March 2011, 62 consecutively selected patients were observed when they were cared for by ambulance nursing staff in prehospital care in the north of Sweden. The field study was based on observations, questions about thermal discomfort and temperature measurements (mattress air and patients’ finger temperature). Based on the observation protocol the participants were divided into two groups, one group that stated it was cold in the patient compartment in the ambulance and another group that did not. Continuous variables were analyzed with independent sample t-test, paired sample t-test and dichotomous variables with cross tabulation.
In the ambulance 85% of the patients had a finger temperature below comfort zone and 44% experienced the ambient temperature in the patient compartment in the ambulance to be cold. There was a significant decrease in finger temperature from the first measurement indoor compared to measurement in the ambulance. The mattress temperature at the ambulance ranged from −22.3°C to 8.4°C.
Cold exposure in winter time is common in prehospital care. Sick and injured patients immediately react to cold exposure with decreasing finger temperature and experience of discomfort from cold. Keeping the patient in the comfort zone is of great importance. Further studies are needed to increase knowledge which can be a base for implications in prehospital care for patients who probably already suffer for other reasons.
It is estimated that approximately 280 million people live in the circumpolar regions . Circumpolar environmental conditions like those found in Sweden are characterized by considerable fluctuations in temperature—long, cold, and dark winters and short summers .
Thermal comfort is defined in the present study as, “a subjective response, or state of mind, where a person expresses satisfaction with the thermal environment” (, s.21). People experience a wide range of temperatures between cold and heat. Within this range, skin temperatures over about 43°C and below about 15°C trigger not only a sensation of thermal discomfort, but also feelings of pain [4–6]. When the body is in the comfort zone, skin temperature varies from 31 – 34°C . A change in skin temperature greater than ±2°C is considered large enough to elicit statements of thermal discomfort . Several studies have clearly concluded that women have a lower hand temperature than men even at thermo-neutrality [4, 9]; in cold conditions, women will therefore experience discomfort earlier than men [10, 11].
Cold exposure increases discomfort and, if untreated, causes incremental disturbances of vital body functions until ultimately reaching hypothermia . The initial reaction to cold exposure is peripheral vasoconstriction leading to peripheral blood being shunted to central body regions in order to support vital organs and to retain body heat [13, 14]. Tonus of skeletal muscle increases (“shivering”), which can effectively increase heat generation up to four times [13, 15].
Hypothermic patients (having a core body temperature <36°C)  are affected with a higher range of physiological and pathological responses and dysfunctions , like increased oxygen consumption , inhibition of drug metabolism [18, 19], disturbance of blood clotting mechanisms [20–22], changes in mental status , and a longer duration of hospital stay , compared to normothermic patients.
Cold exposure may also impair cognitive function, increase pain, aggravate thermal discomfort, and contribute to fear and an overall sense of dissatisfaction [25, 26]. Onset of rain and wind significantly increases the thermal and physical effects of the environment on already affected people .
A study by Henriksson et al.  has shown that insulation and protection from cold are important in prehospital care and also that the polyester blankets used in ambulance care are essentially worthless in windy conditions. In a study by Aléx et al.  patients injured outdoors described how they struggled, trying to move from side to side, to avoid contact with the ground and that protecting themselves from the chill that came from the ground was very important and necessary. It was described as if cold was creeping through their bodies from the ground, causing them to experience thermal discomfort from the cold.
Caring for comfort is the goal of helping patients reach well-being . In ambulance care, it is important for nursing staff to identify and prevent heat loss to avoid patients’ thermal discomfort and hypothermia. Still, exposure to cold temperatures is often a neglected problem in prehospital care . Hypothermia does not occur only for patients lying outside but can also be found in non-traumatized indoor patients . Ambulance care especially with respect to patients ‘experience of thermal discomfort is rarely described in the research literature on prehospital care. In terms of cold exposure, ambulance care may be particularly challenging in circumpolar regions with conditions like those in Sweden.
The aim of this study is to investigate injured and ill patients’ experiences of cold exposures and to identify related factors during ambulance care.
The present study is a field study in ambulance care performed in northern Sweden.
Comparison of patient data between the group who reported cold (n = 27), and those who did not (n = 35)
Experience of cold
No experience of cold
Observation time (minutes)
Thermal discomfort from cold
Conditions described by the Emergency Service Center prior to ambulance transport (n = 62)
Internal medicine, various
Based on the observation protocol, participants were initially divided into two groups, one group that reported the experience of that it was cold in the patient compartment in the ambulance and another group that did not report that it was cold in the patient compartment in the ambulance. Next, comparisons were made between those who reported the mattress to be cold with those who did not. Data collected from the observation protocol and data from measurements of O2 levels, respiratory frequency, heart rate, and blood pressure were statistically analyzed. Continuous variables were analyzed with independent sample t-test, paired sample t-test, and dichotomous variables with cross tabulation (Chi square test and Fisher’s exact test; significance level 0.05). To quantify the size of the difference between groups, standardized effect size (ES) was calculated, along with Cohen ’s d for parametric data and Phi for non-parametric data. All statistical analyses were performed with SPSS software (version 18.0, SPSS Inc., Chicago, IL, USA).
The study was approved by the Regional Ethics Committee, Umeå, Sweden (Dnr. 2010-391-31 M). The participants were provided information about the study and informed that their participation was voluntary and that they had the right to withdraw at any time without affecting their care.
Mattress, air and patient finger temperature at baseline, in the ambulance and at the emergency department (n = 62)
When the ambulance staff arrived, 21 of the patients were wearing thin clothes, like t-skirts, and nightdresses, with one patient wearing no clothes at all. Almost all patients (n = 59) were exposed to an air temperature <24°C in the ambulance. Internal ear temperature ranged from 35.5°C to 39.5°C (mean 37.1°C, ± 0.9).
A significant difference was found between the patients that reported cold and those who did not concerning the mattress (p = 0.001; ES = 0.46), shivering (p < 0.018; ES = 0.34), and thermal discomfort from cold (p < 0.001; ES = 0.62) (see Table 1).
Among the 54 indoor patients, there was a significant decrease in finger temperature from baseline measurement indoors (mean = 28.4 ± 4.47) to measurement in the ambulance (mean = 25.2, ± 5.08; Cl 2.15 to 4.15; p = 0.001; ES = 0.66).
Comparison of mattress, air and patient finger temperature between the groups who reported the mattress to be cold (n = 14) and those who did not (n = 48)
Experience of cold matt
No experience of cold matt
No significant difference was found between women and men with the respect to the report of cold ambient temperature (p = 0.789) or shivering (p = 0.557). There were no significant differences between the two groups in terms of core body temperature, including vital parameters, among those who experienced the mattress to be cold and those who did not. The measurements of O2 levels, respiratory frequency, heart rate and blood pressure showed no significant differences between groups.
The present study reveals that there is a problem of cold ambient temperature in ambulance care and also that patients have negative experiences and physiological reactions to cold exposure denote to decreased finger temperatures. From the results in this study, it is confirmed that the ambient temperature in the patient compartment is too low to be comfortable. More research is needed to confirm that this is true for other circumpolar regions as well. However, this may also be a problem for indoor patients lying on the floor for several hours  and in subtropical climates where trauma patients are at risk of developing hypothermia .
Out of 62 patients, nearly half thought it was cold in the patient compartment in the ambulance and a majority (59 patients) were exposed to an air temperature <24°C in the patient compartment in the ambulance. Elderly patients suffering from hypo-metabolic diseases may feel discomfort from cold even in air temperature of 24°C . The very old, children, and the chronically ill are at higher risk of hypothermia in cold-susceptible environments . In a study of thermal comfort, preferred room temperature for patients was 23.9°C in winter and 24.6°C in summertime . The patients in this study were exposed to cold ambient temperatures (c.f. Table 3), increasing thermal discomfort.
One fourth of the patient’s reported that the mattress was cold when lying on the stretcher in the ambulance and Phi indicated a medium effect size (0.46) between the experience of cold and the experience of a cold mattress. Body heat is lost to the environment by convection, such as with wind, radiation, and evaporation, and through conduction, when the body is in direct contact with cold surfaces [28, 34]. Conduction is an effective method of heat transfer . Cooling of the back and chest are the leading influences of the overall sensation of discomfort from cold . If an injured or ill person is lying on a cold surface, heat loss by conduction increases significantly [13, 28]. Early application of adequate insulation, in addition to immediate care for life-threatening conditions, to reduce heat loss and prevent core body temperature cooling is an important intervention in prehospital care . A study by Lundgren and Henriksson  shows that warming modalities are effective for patients and prevent further decrease of core body temperature. In this study, the patients were embedded in a polyester synthetic blanket to protect their body integrity but also to protect them from cold. It is well known that contact with metal increases heat loss but surprisingly the material on the stretcher, plastic and polyester synthetic blankets, adapted to the ambient temperature almost immediately when the patients were outside and when staff prepared for transport. The ambulance mattress appears to have been an important factor in cooling the patient. In the present study, it seems that patients were warming up the stretcher, and not the other way around.
The present study shows that those who reported the patient compartment to be cold also shivered (ES = 0.34). Shivering however can be precipitated for reasons other than from cold exposure, e.g. as a result of drugs . For each 1°C fall in core body temperature, the musculature maximal power falls by 3% and mechanical efficiency is simultaneously reduced . Shivering can increase oxygen demand up to 500% which might be detrimental for patients with cardiac dysfunction . At minor trauma events outside in wintertime, shivering has been described as the worst experience from the injury because of the lack of bodily control and as devastating for those suffering from, for example, fractures. Supplying active heat decreased shivering regardless of whether the shivering developed from fear or pain . The experience of cold is subjective and thermal discomfort can vary with the conditions people are expected to be in. It is possible that people do not report thermal discomfort even though the environment may be out of the comfort zone, if they do not expect a better condition . Following our results and those of other researchers, it is important to provide prehospital patients a warm patient compartment in the ambulance and active heat supply to minimize discomfort from cold as well as shivering.
In the present study, there was a significant decrease in finger temperature between measurements of temperature indoors compared to inside the ambulance compartment (ES = 0.66). People can only be in a comfort zone when heat production and heat loss are balanced . Candas and Dufour  clearly state that there is a relationship between skin temperature and discomfort. Even in normothermic patients, the cold stress response renders thermal discomfort, which increases the experience of anxiety and pain . The experience of thermal sensation and thermal discomfort are controllers of thermoregulation irrespective of changes in temperature . A study of whole-body cold discomfort  showed that when finger temperature was above 30°C, there was no experience of cold discomfort. But when finger temperature was below 30°C, cold discomfort was a possibility. The present study has shown that, at baseline, only one third of the patients were in the skin temperature comfort zone and in the ambulance only 15% had a finger temperature in the comfort zone, i.e. patients had a finger temperature that was below the comfort zone when the ambulance staff arrived, which then decreased even further during prehospital care. The results in the present study indicate the importance of the possibility of providing heat to patients to increase the skin temperature into the comfort zone.
Patients’ core body temperature in the present study was on average 37°C. This high mean temperature may be dependent on the fact that one fifth of the patients had a fever, which contributed to a normothermic mean temperature. The experience of cold is subjective and we considered including patients with fever as they also can report being cold. In our study, the change in core body temperature between groups was not significant, which is not surprising because the cold exposure from the ambient temperature was apparently too short. A longer cold exposure probably would have resulted in a decreased core body temperature.
In the present study, women did not report their discomfort from cold higher than men. These results differ from other studies finding that women react earlier to cold stress then men [4, 9, 10]. Further studies are needed.
In this study no significant differences between the sexes were found. This may be explained by the sample size or length of time in the ambulance. The time for the observations, i.e. wintertime, was chosen to be sure of an exposure of cold temperatures. All data was collected by the first author using the same measurement instruments for all observations. Two observations were done to test the observation protocol before the study started. The relevance of the protocol was checked and found valid, which strengthens the present study. The results are clinically significant even if there were few participants. Another limitation is that patients’ medical condition, e.g. metabolic diseases and medication such as vasoconstrictors were not assessed. These factors may contribute to the test results. It is also well known that patients in pain are influenced by sympathetic nervous reactions, which also lead to vasoconstriction. The patients participating in this study are probably comparable to typical patients in prehospital care with respect to age, proportion of men and women, and reasons for ordering an ambulance.
In wintertime, the climate is cold in the north of Sweden and cold exposure is common in prehospital care. Sick and injured patients immediately react to cold exposure with decreasing finger temperature and reporting experience of discomfort from cold. Keeping the patient in the comfort zone is of great importance. Further studies are needed to increase knowledge that can be a base for implications in prehospital care for patients who probably already suffer for other reasons.
Jonas Aléx is an RN, a PEN and a PhD student. Sig Karlsson is an RN, PhD and professor, Britt-Inger Saveman is an RNT, PhD, FEANS and professor. All are employed at the Department of Nursing, Umeå University. B-I Saveman is also the pro-Director at the National Centre of Disaster Medicine, Umeå University, Sweden.
We would like to thank the Medical Faculty and Dept. of nursing, Umeå University as well as Västerbottens County Councils for funding the study. We would also like to thank Umeå Ambulance Service who made it possible to do the field study.
- Reed H, Reedy K, Palinkas L, Van Do N, Finney N, Case H, LeMar H, Wright J, Thomas J: Impairment in cognitive and exercise performance during prolonged Antarctic residence: effect of thyroxine supplementation in the polar triiodothyronine syndrome. J Clin Endocrinol Metab. 2001, 86: 110-10.1210/jc.86.1.110.PubMedGoogle Scholar
- Bogoyavlenskiy D, Siggner A: Arctic demography. Arctic Human Development Report (AHDR). Edited by: Einarsson N, Nymand Larsen J, Nilsson A, Young OR. 2004, Akureyre: Artic Institure, 27-41.Google Scholar
- Olesen BW, Brager GS: A better way to predict comfort: The new ASHRAE standard 55-2004. ASHRAE J. 2004, 46: 20-28.Google Scholar
- Havenith G, van de Linde EJG, Heus R: Pain, thermal sensation and cooling rates of hands while touching cold materials. Eur J Appl Physiol Occup Physiol. 1992, 65: 43-51. 10.1007/BF01466273.View ArticlePubMedGoogle Scholar
- Kregel KC, Seals DR, Callister R: Sympathetic nervous system activity during skin cooling in humans: relationship to stimulus intensity and pain sensation. J Physiol. 1992, 454: 359-371.PubMed CentralView ArticlePubMedGoogle Scholar
- Tillman DB, Treede RD, Meyer RA, Campbell JN: Response of C fibre nociceptors in the anaesthetized monkey to heat stimuli: estimates of receptor depth and threshold. J Physiol. 1995, 485: 753-765.PubMed CentralView ArticlePubMedGoogle Scholar
- Auliciems A, Szokolay SV: Passive and Low Energy Archtecture International (PLEA )in association with Department of Architecture. 2007, Brisbane: University of Quensland, Designe tools and techniques, note 3, 2Google Scholar
- Pellerin N, Deschuyteneer A, Candas V: Local thermal unpleasantness and discomfort prediction in the vicinity of thermoneutrality. Eur J Appl Physiol. 2004, 92: 717-720. 10.1007/s00421-004-1127-0.View ArticlePubMedGoogle Scholar
- Jay O, Havenith G: Finger skin cooling on contact with cold materials: a comparison between male and female responses during short-term exposures. Eur J Appl Physiol. 2004, 91: 373-381. 10.1007/s00421-003-0986-0.View ArticlePubMedGoogle Scholar
- Candas V, Dufour A: Hand skin temperatures associated with local hand discomfort under whole-body cold exposure. J Hum Environ Syst. 2007, 10: 31-37. 10.1618/jhes.10.31.View ArticleGoogle Scholar
- Lan L, Lian Z, Liu W, Liu Y: Investigation of gender difference in thermal comfort for Chinese people. Eur J Appl Physiol. 2008, 102: 471-480. 10.1007/s00421-007-0609-2.View ArticlePubMedGoogle Scholar
- Lintu NS, Mattila MAK, Holopainen JA, Koivunen M, Häninen OOP: Reactions to cold exposure emphasize the need for weather protection in prehospital care: an experimental study. Prehosp Disaster Med. 2006, 21: 316-321.PubMedGoogle Scholar
- Lundgren P, Henriksson O, Widfeldt N, Wikström T: Insulated spine boards for prehospital trauma care in a cold environment. Int J Disaster Med. 2004, 2: 33-37. 10.1080/15031430410023913.View ArticleGoogle Scholar
- Stocks JM, Taylor NA, Tipton MJ, Greenleaf JE: Human physiological responses to cold exposure. Aviat Space Environ Med. 2004, 75: 444-457.PubMedGoogle Scholar
- Farley A, McLafferty E: Nursing management of the patient with hypothermia. Nurs Stand. 2008, 22: 43-46.View ArticlePubMedGoogle Scholar
- Schmied H, Kurz A, Sessler DI, Kozek S, Reiter A: Mild hypothermia increases blood loss and transfusion requirements during total hip arthroplasty. Lancet. 1996, 347: 289-292. 10.1016/S0140-6736(96)90466-3.View ArticlePubMedGoogle Scholar
- Peng RY, Bongard FS: Hypothermia in trauma patients. J Am Coll Surg. 1999, 188: 685-10.1016/S1072-7515(99)00035-6.View ArticlePubMedGoogle Scholar
- Giesbrecht GG: Emergency treatment of hypothermia. Emerg Med. 2001, 13: 9-16. 10.1046/j.1442-2026.2001.00172.x.View ArticleGoogle Scholar
- Leslie K, Sessler DI, Bjorksten AR, Moayeri A: Mild hypothermia alters propofol pharmacokinetics and increases the duration of action of atracurium. Anesth Analg. 1995, 80: 1007-1014.PubMedGoogle Scholar
- Doufas AG: Consequences of inadvertent perioperative hypothermia. Best Pract Res Clin Anaesthesiol. 2003, 17: 535-549. 10.1016/S1521-6896(03)00052-1.View ArticlePubMedGoogle Scholar
- Tsuei BJ, Kearney PA: Hypothermia in the trauma patient. Injury. 2004, 35: 7-15. 10.1016/S0020-1383(03)00309-7.View ArticlePubMedGoogle Scholar
- Valeri CR, MacGregor H, Cassidy G, Tinney R, Pompei F: Effects of temperature on bleeding time and clotting time in normal male and female volunteers. Crit Care Med. 1995, 23: 698-704. 10.1097/00003246-199504000-00019.View ArticlePubMedGoogle Scholar
- Makinen TM, Palinkas LA, Reeves DL, Paakkonen T, Rintamaki H, Leppaluoto J, Hassi J: Effect of repeated exposures to cold on cognitive performance in humans. Physiol Behav. 2006, 87: 166-176. 10.1016/j.physbeh.2005.09.015.View ArticlePubMedGoogle Scholar
- Kurz A, Sessler DI, Lenhardt R: Perioperative normothermia to reduce the incidence of surgical-wound infection and shorten hospitalization. N Engl J Med. 1996, 334: 1209-1216. 10.1056/NEJM199605093341901.View ArticlePubMedGoogle Scholar
- Kober A, Scheck T, Fulesdi B, Lieba F, Vlach W, Friedman A, Sessler DI: Effectiveness of resistive heating compared with passive warming in treating hypothermia associated with minor trauma: a randomized trial. Mayo Clin Proc. 2001, 76: 369-375.View ArticlePubMedGoogle Scholar
- Kurz A, Sessler DI, Birnbauer F, Illievich UM, Spiss CK: Thermoregulatory vasoconstriction impairs active core cooling. Anesthesiol. 1995, 82: 870-10.1097/00000542-199504000-00008.View ArticleGoogle Scholar
- Danzl DF, Pozos RS: Accidental hypothermia. N Engl J Med. 1994, 331: 1756-1760. 10.1056/NEJM199412293312607.View ArticlePubMedGoogle Scholar
- Henriksson O, Lundgren JP, Kuklane K, Holmér I, Bjornstig U: Protection against cold in prehospital care—thermal insulation properties of blankets and rescue bags in different wind conditions. wear. 2009, 27: 28-Google Scholar
- Aléx J, Lundgren P, Henriksson O, Saveman BI: Being cold when injured in a cold environment–Patients’ experiences. Int Emerg Nurs. 2013, 21: 42-49. 10.1016/j.ienj.2011.10.006.View ArticlePubMedGoogle Scholar
- Morse JM: Comfort. Clin Nurs Res. 1992, 1: 91-106. 10.1177/105477389200100110.View ArticlePubMedGoogle Scholar
- Russo S, Timmermann A, Radke O, Kerren T, Bräuer A: Accidental hypothermia in the household environment. Importance of preclinical temperature measurement. Der Anaesthesist. 2005, 54: 1209-10.1007/s00101-005-0930-2.View ArticlePubMedGoogle Scholar
- Collins K: Low indoor temperatures and morbidity in the elderly. Age and Ageing. 1986, 15: 212-220. 10.1093/ageing/15.4.212.View ArticlePubMedGoogle Scholar
- Aitken LM, Hendrikz J, Dulhunty J, Rudd M: Hypothermia and associated outcomes in seriously injured trauma patients in a predominantly sub-tropical climate. Resuscitation. 2009, 80: 217-223. 10.1016/j.resuscitation.2008.10.021.View ArticlePubMedGoogle Scholar
- Keim SM, Guisto JA, Sullivan JB: Environmental thermal stress. Ann Agric Environ Med. 2002, 9: 1-15.PubMedGoogle Scholar
- Verheyen J, Theys N, Allonsius L, Descamps F: Thermal comfort of patients: objective and subjective measurements in patient rooms of a Belgian healthcare facility. Build Environ. 2011, 46: 1195-1204. 10.1016/j.buildenv.2010.12.014.View ArticleGoogle Scholar
- Zhang H, Huizenga C, Arens E, Wang D: Thermal sensation and comfort in transient non-uniform thermal environments. Eur J Appl Physiol. 2004, 92: 728-733. 10.1007/s00421-004-1137-y.View ArticlePubMedGoogle Scholar
- Giesbrecht GG, Wilkerson JA: Hypothermia, frostbite, and other cold injuries: prevention, survival, rescue and treatment. 2006, Seattle: The Mountaineers BooksGoogle Scholar
- Lundgren JP, Henriksson O, Pretorius T, Cahill F, Bristow G, Chochinov A, Pretorius A, Bjornstig U, Giesbrecht GG: Field torso-warming modalities: a comparative study using a human model. Prehosp Emerg Care. 2009, 13: 371-378. 10.1080/10903120902935348.View ArticlePubMedGoogle Scholar
- De Witte J, Sessler DI: Perioperative shivering: physiology and pharmacology. Anesthesiol. 2002, 96: 467-484. 10.1097/00000542-200202000-00036.View ArticleGoogle Scholar
- Bergh U, Ekblom B: Influence of muscle temperature on maximal muscle strength and power output in human skeletal muscles. Acta Physiologica Scandinavica. 1979, 107: 33-37. 10.1111/j.1748-1716.1979.tb06439.x.View ArticlePubMedGoogle Scholar
- Scott E, Buckland R: A systematic review of intraoperative warming to prevent postoperative complications. AORN journal. 2006, 83: 1090-10.1016/S0001-2092(06)60120-8.View ArticlePubMedGoogle Scholar
- Ji SH: Shifting of thermal comfort zone due to outdoor temperature. Master thesis. 2006, Austin: University of Texas, Department in sustainable designGoogle Scholar
- Kingma B, Frijns A, van Marken Lichtenbelt W: The thermoneutral zone: implications for metabolic studies. Frontiers in Bioscience. 1975, 2012: 4-Google Scholar
- Robinson S, Benton G: Warmed blankets: an intervention to promote comfort for elderly hospitalized patients. Geriatr Nurs. 2002, 23: 320-323. 10.1067/mgn.2002.130273.View ArticlePubMedGoogle Scholar
- Schlader ZJ, Simmons SE, Stannard SR, Mündel T: The independent roles of temperature and thermal perception in the control of human thermoregulatory behavior. Physiol Behav. 2011, 103: 217-224. 10.1016/j.physbeh.2011.02.002.View ArticlePubMedGoogle Scholar
- Wang D, Zhang H, Arens E, Huizenga C: Observations of upper-extremity skin temperature and corresponding overall-body thermal sensations and comfort. Build Environ. 2007, 42: 3933-3943. 10.1016/j.buildenv.2006.06.035.View ArticleGoogle Scholar
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