Is the clinical frailty scale feasible to use in an emergency department setting? A mixed methods study.

BACKGROUND: The Clinical Frailty Scale (CFS) is a frailty assessment tool used to identify frailty in older patients visiting the emergency department (ED). However, the current understanding of how it is used and accepted in ED clinical practice is limited. This study aimed to assess the feasibility of CFS in an ED setting. METHODS: This was a prospective, mixed methods study conducted in three Swedish EDs where CFS had recently been introduced. We examined the completion rate of CFS assessments in relation to patient- and organisational factors. A survey on staff experience of using CFS was also conducted. All quantitative data were analysed descriptively, while free text comments underwent a qualitative content analysis. RESULTS: A total of 4235 visits were analysed, and CFS assessments were performed in 47%. The completion rate exceeded 50% for patients over the age of 80. Patients with low triage priority were assessed to a low degree (24%). There was a diurnal variation with the highest completion rates seen for arrivals between 6 and 12 a.m. (58%). The survey response rate was 48%. The respondents rated the perceived relevance and the ease of use of the CFS with a median of 5 (IQR 2) on a scale with 7 being the highest. High workload, forgetfulness and critical illness were ranked as the top three barriers to assessment. The qualitative analysis showed that CFS assessments benefit from a clear routine and a sense of apparent relevance to emergency care. CONCLUSION: Most emergency staff perceived CFS as relevant and easy to use, yet far from all older ED patients were assessed. The most common barrier to assessment was high workload. Measures to facilitate use may include clarifying the purpose of the assessment with explicit follow-up actions, as well as formulating a clear routine for the assessment. REGISTRATION: The study was registered on ClinicalTrials.gov 2021-06-18 (identifier: NCT04931472).

Workload and sex effects in comprehensive assessment of cutaneous microcirculation.

INTRODUCTION: Workload and sex-related differences have been proposed as factors of importance when evaluating the microcirculation. Simultaneous assessments with diffuse reflectance spectroscopy (DRS) and laser Doppler flowmetry (LDF) enable a comprehensive evaluation of the microcirculation. The aim of the study was to compare the response between sexes in the microcirculatory parameters red blood cell (RBC) tissue fraction, RBC oxygen saturation, average vessel diameter, and speed-resolved perfusion during baseline, cycling, and recovery, respectively. METHODS: In 24 healthy participants (aged 20 to 30 years, 12 females), cutaneous microcirculation was assessed by LDF and DRS at baseline, during a workload generated by cycling at 75 to 80 % of maximal age-predicted heart rate, and recovery, respectively. RESULTS: Females had significantly lower RBC tissue fraction and total perfusion in forearm skin microcirculation at all phases (baseline, workload, and recovery). All microvascular parameters increased significantly during cycling, most evident in RBC oxygen saturation (34 % increase on average) and perfusion (9-fold increase in total perfusion). For perfusion, the highest speeds (>10 mm/s) increased by a factor of 31, whereas the lowest speeds (<1 mm/s) increased by a factor of 2. CONCLUSION: Compared to a resting state, all studied microcirculation measures increased during cycling. For perfusion, this was mainly due to increased speed, and only to a minor extent due to increased RBC tissue fraction. Skin microcirculatory differences between sexes were seen in RBC concentration and total perfusion.

Inter-rater reliability of the Clinical Frailty Scale by staff members in a Swedish emergency department setting.

INTRODUCTION: As frailty among the elderly is receiving increasing attention in emergency departments (EDs) around the world, the use of frailty assessment tools is growing. An often used such tool is the Clinical Frailty Scale (CFS), whose inter-rater reliability has been sparingly investigated in ED settings. No inter-rater reliability study regarding CFS has previously been performed within the Scandinavian ED context. The primary aim of this study was to evaluate the inter-rater reliability of the CFS in a Swedish ED setting. METHODS: This was a prospective observational study conducted at three Swedish EDs. Patients ≥65 years were independently assessed with CFS by their responsible physician, registered nurse, and assistant nurse. Demographic information for each assessor was collected, along with frailty status (frail/not frail) on the basis of clinical judgment. Inter-rater reliability was calculated using intraclass correlation coefficient (ICC), whereas agreement of frailty assessed by CFS (dichotomized between frail/not frail, cutoff at ≥5 points) versus solely by clinical judgment was calculated by using cross-tabulation. RESULTS: One-hundred patients were included. We found inter-rater reliability to be moderate to good (ICC 0.78, 95% confidence interval [CI] 0.72-0.84), regardless of whether the care team included an emergency physician (ICC 0.74, 95% CI 0.62-0.83) or an intern/resident from another specialty (ICC 0.83, 95% CI 0.74-0.89). The agreement of clinically judged frailty compared to frailty according to CFS was 84%. In the opposing cases, staff tended to assess patients as frail to a higher extent using clinical judgment than by applying CFS on the same patient. CONCLUSIONS: The CFS appears to have a moderate to good inter-rater reliability when used in a clinical ED setting. When guiding clinical decisions, we advise that the CFS score should be discussed within the team. Further research needs to be performed on the accuracy of clinical judgment to identify frailty in ED patients.

Local Response and Barrier Recovery in Elderly Skin Following the Application of High-Density Microarray Patches.

The high-density microneedle array patch (HD-MAP) is a promising alternative vaccine delivery system device with broad application in disease, including SARS-CoV-2. Skin reactivity to HD-MAP applications has been extensively studied in young individuals, but not in the >65 years population, a risk group often requiring higher dose vaccines to produce protective immune responses. The primary aims of the present study were to characterise local inflammatory responses and barrier recovery to HD-MAPs in elderly skin. In twelve volunteers aged 69−84 years, HD-MAPs were applied to the forearm and deltoid regions. Measurements of transepidermal water loss (TEWL), dielectric permittivity and erythema were performed before and after HD-MAP application at t = 10 min, 30 min, 48 h, and 7 days. At all sites, TEWL (barrier damage), dielectric permittivity (superficial water);, and erythema measurements rapidly increased after HD-MAP application. After 7 days, the mean measures had recovered toward pre-application values. The fact that the degree and chronology of skin reactivity and recovery after HD-MAP was similar in elderly skin to that previously reported in younger adults suggests that the reactivity basis for physical immune enhancement observed in younger adults will also be achievable in the older population.

In vivo dose-response analysis to acetylcholine: pharmacodynamic assessment by polarized reflectance spectroscopy.

Transdermal iontophoresis offers an in vivo alternative to the strain-gauge model for measurement of vascular function but is limited due to lack of technical solutions for outcome assessment. The aims of this study were to, after measurement by polarized reflectance spectroscopy (PRS), use pharmacodynamic dose-response analysis on responses to different concentrations of acetylcholine (ACh); and to examine the effect of three consecutively administered iontophoretic current pulses. The vascular responses in 15 healthy volunteers to iontophorised ACh (5 concentrations, range 0.0001% to 1%, three consecutive pulses of 0.02 mA for 10 min each) were recorded using PRS. Data were fitted to a four-parameter logistic dose response model and compared. Vascular responses were quantifiable by PRS. Similar pharmacodynamic dose response curves could be generated irrespectively of the ACh concentration. Linearly increasing maximum vasodilatory responses were registered with increasing concentration of ACh. A limited linear dose effect of the concentration of ACh was seen between pulses. Polarized reflectance spectroscopy is well suited for measuring vascular responses to iontophoretically administrated ACh. The results of this study support further development of iontophoresis as a method to study vascular function and pharmacological responses in vivo.

Pathways to the emergency department - a national, cross-sectional study in Sweden.

BACKGROUND: Swedish Emergency Departments (EDs) see 2.6 million visits annually. Sweden has a strong tradition of health care databases, but information on patients' pathways to the ED is not documented in any registry. The aim of this study was to provide a national overview of pathways, degree of medical acuteness according to triage, chief complaints, and hospital admission rates for adult patients (≥18 years) visiting Swedish EDs during 24 h. METHODS: A national cross-sectional study including all patients at 43 of Sweden's 72 EDs during 24 h on April 25th, 2018. Pathway to the ED, medical acuteness at triage, admission and basic demographics were registered by dedicated assessors present at every ED for the duration of the study. Descriptive data are reported. RESULTS: A total of 3875 adult patients (median age 59; range 18 to 107; 50% men) were included in the study. Complete data for pathway to the ED was reported for 3693 patients (98%). The most common pathway was self-referred walk-in (n = 1310; 34%), followed by ambulance (n = 920; 24%), referral from a general practitioner (n = 497; 1 3%), and telephone referral by the national medical helpline "1177" (n = 409; 10%). In patients 18 to 64 years, self-referred walk-in was most common, whereas transport by ambulance dominated in patients > 64 years. Of the 3365 patients who received a medical acuteness level at triage, 4% were classified as Red (Immediate), 18% as Orange (very urgent), 47% as Yellow (Urgent), 26% as Green (Standard), and 5% as Blue (Non-Urgent). Abdominal or chest pain were the most common chief complaints representing approximately 1/3 of all presentations. Overall, the admission rate was 27%. Arrival by ambulance was associated with the highest rate of admission (53%), whereas walk-in patients and telephone referrals were less often admitted. CONCLUSION: Self-referred walk-in was the overall most common pathway followed by ambulance. Patients arriving by ambulance were often elderly, critically ill and often admitted to in-patient care, whereas arrival by self-referred walk-in was more common in younger patients.

Hydrogels and Cubic Liquid Crystals for Non-Invasive Sampling of Low-Molecular-Weight Biomarkers-An Explorative In Vivo Study.

The molecular composition of human skin is altered due to diseases, which can be utilized for non-invasive sampling of biomarkers and disease diagnostics. For this to succeed, it is crucial to identify a sampling formulation with high extraction efficiency and reproducibility. Highly hydrated skin is expected to be optimal for increased diffusion of low-molecular-weight biomarkers, enabling efficient extraction as well as enhanced reproducibility as full hydration represents a well-defined endpoint. Here, the aim was to explore water-based formulations with high water activities, ensuring satisfactory skin hydration, for non-invasive sampling of four analytes that may serve as potential biomarkers, namely tryptophan, tyrosine, phenylalanine, and kynurenine. The included formulations consisted of two hydrogels (chitosan and agarose) and two different liquid crystalline cubic phases based on the polar lipid glycerol monooleate, which were all topically applied for 2 h on 35 healthy subjects in vivo. The skin status of all sampling sites was assessed by electrical impedance spectroscopy and transepidermal water loss, enabling explorative correlations between biophysical properties and analyte abundancies. Taken together, all formulations resulted in the successful and reproducible collection of the investigated biomarkers. Still, the cubic phases had an extraction capacity that was approximately two times higher compared to the hydrogels.

Micropuncture closure following high density microarray patch application in healthy subjects.

BACKGROUND: The high-density microarray patch (HD-MAP) promises to be a robust vaccination platform with clear advantages for future global societal demands for health care management. The method of action has its base not only in efficient delivery of vaccine but also in the reliable induction of a local innate physical inflammatory response to adjuvant the vaccination process. The application process needs to induce levels of reactivity, which are acceptable to the vaccine, and from which the skin promptly recovers. MATERIALS AND METHODS: 1 × 1 cm HD-MAP patches containing 5000, 250-µm long microprojections were applied to the skin in 12 healthy volunteers. The return of skin barrier function was assessed by transepidermal water loss (TEWL) and reaction to topical histamine challenge. RESULTS: Skin barrier recovery by 48 h was confirmed for all HD-MAP sites by recovered resistance to the effects of topical histamine application. CONCLUSIONS: Our previous observation, that the barrier disruption indicator TEWL returns to normal by 48 h, is supported by this paper's demonstration of return of skin resistance to topical histamine challenge in twelve healthy subjects.

Respiratory rate monitoring in healthy volunteers by central photoplethysmography compared to capnography.

Monitoring of respiration is a central task in clinical medicine, crucial to patient safety. Despite the uncontroversial role of altered respiratory frequency as an important sign of impending or manifest deterioration, reliable measurement methods are mostly lacking outside of intensive care units and operating theaters. Photoplethysmography targeting the central blood circulation in the sternum could offer accurate and inexpensive monitoring of respiration. Changes in blood flow related to the different parts of the respiratory cycle are used to identify the respiratory pattern. The aim of this observational study was to compare photoplethysmography at the sternum to standard capnography in healthy volunteers. Bland Altman analysis showed good agreement (bias -0.21, SD 1.6, 95% limits of agreement -3.4 to 2.9) in respiratory rate values. Photoplethysmography provided high-quality measurements of respiratory rate comparable to capnographic measurements. This suggests that photoplethysmography may become a precise, cost-effective alternative for respiratory monitoring.

Moisture sensor for exudative wounds - A pilot study.

BACKGROUND: Exudative wounds cause discomfort for patients. Introduction of a moisture sensor to dressings could facilitate change of dressings only when needed. The aim of this pilot study was to evaluate the ability of a newly developed moisture sensor to detect moisture in relation to the absorbing capacity of the dressing. MATERIALS AND METHODS: In five patients, with one leg ulcer each, three dressing changes per patient were observed. Interval of dressing change was according to clinical need and healthcare professional's decision. Sensor activation, dressing weight and complications were registered. To investigate the effect of dressing on sensor activation, half of the observations were made without an extra layer of non-woven between the dressing and sensor (Variant A), and half with (Variant B). RESULTS: The sensor indicated time for dressing change in six out of fifteen observations. Variants A and B did not differ regarding activation or the timing of the activation. CONCLUSIONS: The addition of a moisture sensor for facilitating management of exudative wounds is promising. We recommend future larger studies evaluating the potential clinical benefits and risks of the addition of a moisture sensor. We also recommend evaluation of potential home monitoring of wounds by a moisture sensor.

Microvascular effects of microneedle application.

BACKGROUND: The efficiency of transdermal drug delivery may be increased by pretreating the skin with microneedles, but distinct effects of microneedles and the microneedle-enhanced delivery of vasoactive drugs on the skin microvasculature are still not well investigated. MATERIALS AND METHODS: In eight healthy human subjects, we measured the microvascular response to microneedle-induced microtraumas in the skin microvasculature using polarized light spectroscopy imaging (Tissue Viability imaging, TiVi). The microvascular response was assessed for up to 48 hours for three microneedle sizes (300 µm, 500 µm, and 750 µm) and for different pressures and application times. RESULTS: In our results, microneedle application increased the local red blood cell (RBC) concentration for up to 24 hours dependent on the needle lengths, applied time, and force. CONCLUSION: Optimization of microneedles size, pressure, and application time should be taken into account for future protocols for drug delivery and experimental provocations.

Innate local response and tissue recovery following application of high density microarray patches to human skin.

The development of microarray patches for vaccine application has the potential to revolutionise vaccine delivery. Microarray patches (MAP) reduce risks of needle stick injury, do not require reconstitution and have the potential to enhance immune responses using a fractional vaccine dose. To date, the majority of research has focused on vaccine delivery with little characterisation of local skin response and recovery. Here we study in detail the immediate local skin response and recovery of the skin post high density MAP application in 12 individuals receiving 3 MAPs randomly assigned to the forearm and upper arm. Responses were characterised by clinical scoring, dermatoscopy, evaporimetry and tissue viability imaging (TiVi). MAP application resulted in punctures in the epidermis, a significant transepidermal water loss (TEWL), the peak TEWL being concomitant with peak erythema responses visualised by TiVi. TEWL and TiVi responses reduced over time, with TEWL returning to baseline by 48 h and erythema fading over the course of a 7 day period. As MAPs for vaccination move into larger clinical studies more variation of individual subject phenotypic or disease propensity will be encountered which will require consideration both in regard to reliability of dose delivery and degree of inherent skin response.

Prevalence of crowding, boarding and staffing levels in Swedish emergency departments - a National Cross Sectional Study.

BACKGROUND: Emergency Department (ED) crowding occurs when demand for care exceeds the available resources. Crowding has been associated with decreased quality of care and increased mortality, but the prevalence on a national level is unknown in most countries. METHOD: We performed a national, cross-sectional study on staffing levels, staff workload, occupancy rate and patients waiting for an in-hospital bed (boarding) at five time points during 24 h in Swedish EDs. RESULTS: Complete data were collected from 37 (51% of all) EDs in Sweden. High occupancy rate indicated crowding at 12 hospitals (37.5%) at 31 out of 170 (18.2%) time points. Mean workload (measured on a scale from 1, no workload to 6, very high workload) was moderate at 2.65 (±1.25). Boarding was more prevalent in academic EDs than rural EDs (median 3 vs 0). There were an average of 2.6, 4.6 and 3.2 patients per registered nurse, enrolled nurse and physician, respectively. CONCLUSION: ED crowding based on occupancy rate was prevalent on a national level in Sweden and comparable with international data. Staff workload, boarding and patient to staff ratios were generally lower than previously described.

Assessment of oxygenation with polarized light spectroscopy enables new means for detecting vascular events in the skin.

INTRODUCTION: Impaired oxygenation in the skin may occur in disease states and after reconstructive surgery. We used tissue viability imaging (TiVi) to measure changes in oxygenation and deoxygenation of haemoglobin in an in vitro model and in the dermal microcirculation of healthy individuals. MATERIALS AND METHODS: Oxygenation was measured in human whole blood with different levels of oxygenation. In healthy subjects, changes in red blood cell concentration (CRBC,TiVi), oxygenation (ΔCOH,TiVi) and deoxygenation (ΔCDOH,TiVi) of haemoglobin were measured during and after arterial and venous occlusion using TiVi and were compared with measurements from the enhanced perfusion and oxygen saturation system (EPOS). RESULTS: During arterial occlusion, CRBC,TiVi remained unchanged while ΔCOH,TiVi decreased to -44.2 (10.4) AU (p = 0.04), as compared to baseline. After release, CRBC,TiVi increased to 39.2 (18.8) AU (p < 0.001), ΔCOH,TiVi increased to 38.5. During venous occlusion, CRBC,TiVi increased to 28.9 (11.2) AU (p < 0.001), ΔCOH,TiVi decreased to -52.2 (46.1) AU (p < 0.001) compared to baseline after 5 min of venous occlusion. There was a significant correlation between the TiVi Oxygen Mapper and EPOS, for arterial (r = 0.92, p < 0.001) and venous occlusion (r = 0.87, p < 0.001), respectively. CONCLUSION: This study shows that TiVi can measure trends in oxygenation and deoxygenation of haemoglobin during arterial and venous stasis in healthy individuals.

Man versus machine: comparison of naked-eye estimation and quantified capillary refill.

BACKGROUND: Capillary refill (CR) time is traditionally assessed by 'naked-eye' inspection of the return to original colour of a tissue after blanching pressure. Few studies have addressed intra-observer reliability or used objective quantification techniques to assess time to original colour. This study compares naked-eye assessment with quantified CR (qCR) time using polarisation spectroscopy and examines intra-observer and interobserver agreements in using the naked eye. METHOD: A film of 18 CR tests (shown in a random fixed order) performed in healthy adults was assessed by a convenience sample of 14 doctors, 15 nurses and 19 secretaries (Department of Emergency Medicine, Linköping University, September to November 2017), who were asked to estimate the time to return to colour and characterise it as 'fast', 'normal' or 'slow'. The qCR times and corresponding naked-eye time assessments were compared using the Kruskal-Wallis test. Three videos were shown twice without observers' knowledge to measure intra-observer repeatability. Intra-observer categorical assessments were compared using Cohen's Kappa analysis. Interobserver repeatability was measured and depicted with multiple-observer Bland-Altman plotting. Differences in naked-eye estimation between professions were analysed using ANOVA. RESULTS: Naked-eye assessed CR time and qCR time differ substantially, and agreement for the categorical assessments (naked-eye assessment vs qCR classification) was poor (Cohen's kappa 0.27). Bland-Altman intra-observer repeatability ranged from 6% to 60%. Interobserver agreement was low as shown by the Bland-Altman plotting with a 95% limit of agreement with the mean of ±1.98 s for doctors, ±1.6 s for nurses and ±1.75 s for secretaries. The difference in CR time estimation (in seconds) between professions was not significant. CONCLUSIONS: Our study suggests that naked-eye-assessed CR time shows poor reproducibility, even by the same observers, and differs from an objective measure of CR time.

Hyaluronic Acid Accelerates Re-epithelialization and Alters Protein Expression in a Human Wound Model.

BACKGROUND: Hyaluronic acid (HA), a large glycosaminoglycan involved in proliferation, migration, and tissue repair, is suggested to be an important factor for keratinocyte activation and re-epithelialization. The experimental hypothesis of this study was that HA accelerates re-epithelialization, and we aimed to investigate the effect of exogenous intradermal HA during deep dermal, incisional wound healing in vivo in humans, the primary endpoint being re-epithelialization. METHODS: A total of 8 standardized deep dermal incisional wounds (depth 1.6 mm, width 1.8 mm) per subject were induced in 10 healthy volunteers. Two of the wound sites per subject were pretreated with injections of HA and 2 with saline solution. At 2 time points (24 hours and 14 days), 2 biopsies for each treatment group (one for histology and one for proteomics) were taken. Skin erythema was measured at 24-hour intervals for 14 days as a surrogate measurement of inflammation. RESULTS: At 24 hours, 8 of 9 wounds pretreated with HA showed complete re-epithelization, whereas none of the wounds pretreated with saline had re-epithelized. Wounds pretreated with HA also showed a 10-fold regulation of 8 identified proteins involved in wound healing compared to wounds treated with saline solution. No difference in inflammation, as measured as erythema, could be seen between any of the groups. CONCLUSIONS: We conclude that HA accelerates re-epithelialization and stimulates an altered protein expression in vivo in human deep dermal incisional skin wounds, but has no effect on the inflammation process as measured by erythema.

Cellular metabolism and pore lifetime of human skin following microprojection array mediation.

Skin-targeting microscale medical devices are becoming popular for therapeutic delivery and diagnosis. We used cryo-SEM, fluorescence lifetime imaging microscopy (FLIM), autofluorescence imaging microscopy and inflammatory response to study the puncturing and recovery of human skin ex vivo and in vivo after discretised puncturing by a microneedle array (Nanopatch®). Pores induced by the microprojections were found to close by ~25% in diameter within the first 30 min, and almost completely close by ~6 h. FLIM images of ex vivo viable epidermis showed a stable fluorescence lifetime for unpatched areas of ~1000 ps up to 24 h. Only the cells in the immediate puncture zones (in direct contact with projections) showed a reduction in the observed fluorescence lifetimes to between ~518-583 ps. The ratio of free-bound NAD(P)H (α1/α2) in unaffected areas of the viable epidermis was ~2.5-3.0, whereas the ratio at puncture holes was almost double at ~4.2-4.6. An exploratory pilot in vivo study also suggested similar closure rate with histamine administration to the forearms of human volunteers after Nanopatch® treatment, although a prolonged inflammation was observed with Tissue Viability Imaging. Overall, this work shows that the pores created by the microneedle-type medical device, Nanopatch®, are transient, with the skin recovering rapidly within 1-2 days in the epidermis after application.

Wireless vitals-Proof of concept for wireless patient monitoring in an emergency department setting.

Vital sign assessment is a common task in emergency medicine, but resources for continuous monitoring are restricted, data is often recorded manually, and entangled wires cause frustration. Therefore, we designed a small, wireless photoplethysmographic device capable of continuously assessing pulse, respiratory frequency and oxygen saturation on the sternum and tested the performance and feasibility in an emergency department setting. Fifty (56.3 ± 20.2 years), consenting emergency patients (29 male) were recruited. Heart rate, respiratory rate and oxygen saturation were recorded simultaneously using the device and standard monitoring equipment. Data was compared using Bland-Altman plotting (heart rate, respiratory rate) and mean difference (oxygen saturation). The bias for heart- and respiratory rate was 0.4 (limits of agreements -11.3, 12.2 and -6.1, 7.0). Mean difference for oxygen saturation was -0.21 ± 2.35%. This may be the first wireless device to use photoplethysmography on the sternum for vital sign assessment. We noted good agreement with standard monitors, but lack of standardization in data processing between monitoring systems may limit the generalizability of these findings. Although further improvements are needed, the feasibility of this approach provides proof of concept for a new paradigm of large scale, wireless patient monitoring.

A cool response-The influence of ambient temperature on capillary refill time.

OBJECTIVE: To describe the effect of low ambient temperature on skin temperature and capillary refill (CR) time in forehead, sternum and finger pulp. METHODS: An observational, nonrandomized experimental study on 15 healthy subjects (6 females) in a cold room (8°C). Outcome measures were skin temperature and quantified CR test after application of a standardized blanching pressure (9 N/cm2 ) using digital photographic polarization spectroscopy to generate CR times. RESULTS: The finger pulp showed marked temperature fall and prolonged CR times (>10 seconds). The CR registrations of the forehead and sternum were more comparable to curves observed in a control material at room temperature, and skin temperature falls were less marked. CR times were not prolonged in forehead measurements. At the sternum, some individuals showed CR times beyond guideline recommendations despite only a marginal reduction in skin temperature. CONCLUSIONS: Low ambient temperature is a strong independent factor for CR time at peripheral sites. Reservation about sternum as a site of measurement is warranted since cold provocation produced prolonged CR times in some individuals. We found that the forehead is the most thermostable of the 3 sites and thus the preferred site to avoid ambient temperature artifact in measuring CR time.