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Rates of acute intracerebral hemorrhage (ICH) increase in winter months but the magnitude of risk is unknown. We aimed to quantify the association of ambient temperature with the risk of ICH in the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT2) participants on an hourly timescale. INTERACT2 was an international, open, blinded endpoint, randomized controlled trial of patients with spontaneous ICH (<6h of onset) and elevated systolic blood pressure (SBP, 150-220 mmHg) assigned to intensive (target SBP <140 mmHg) or guideline-recommended (SBP <180 mmHg) BP treatment. We linked individual level hourly temperature to baseline data of 1997 participants, and performed case-crossover analyses using a distributed lag non-linear model with 24h lag period to assess the association of ambient temperature and risk of ICH. Results were presented as overall cumulative odds ratios (ORs) and 95% CI. Low ambient temperature (≤10°C) was associated with increased risks of ICH: overall cumulative OR was 1.37 (0.99-1.91) for 10°C, 1.92 (1.31-2.81) for 0°C, 3.13 (1.89-5.19) for -10°C, and 5.76 (2.30-14.42) for -20°C, as compared with a reference temperature of 20°C.There was no clear relation of low temperature beyond three hours after exposure. Results were consistent in sensitivity analyses. Exposure to low ambient temperature within several hours increases the risk of ICH. ClinicalTrials.gov NCT00716079.

Haemodialysis centres have conventionally provided maintenance haemodialysis using a standard dialysate temperature (eg, 36·5°C) for all patients. Many centres now use cooler dialysate (eg, 36·0°C or lower) for potential cardiovascular benefits. We aimed to assess whether personalised cooler dialysate, implemented as centre-wide policy, reduced the risk of cardiovascular-related death or hospital admission compared with standard temperature dialysate. MyTEMP was a pragmatic, two-arm, parallel-group, registry-based, open-label, cluster-randomised, superiority trial done at haemodialysis centres in Ontario, Canada. Eligible centres provided maintenance haemodialysis to at least 15 patients a week, and the medical director of each centre had to confirm that their centre would deliver the assigned intervention. Using covariate-constrained randomisation, we allocated 84 centres (1:1) to use either personalised cooler dialysate (nurses set the dialysate temperature 0·5–0·9°C below each patient's measured pre-dialysis body temperature, with a lowest recommended dialysate temperature of 35·5°C), or standard temperature dialysate (36·5°C for all patients and treatments). Patients and health-care providers were not masked to the group assignment; however, the primary outcome was recorded in provincial databases by medical coders who were unaware of the trial or the centres’ group assignment. The primary composite outcome was cardiovascular-related death or hospital admission with myocardial infarction, ischaemic stroke, or congestive heart failure during the 4-year trial period. Analysis was by intention to treat. The study is registered at ClinicalTrials.gov, NCT02628366. We assessed all of Ontario's 97 centres for inclusion into the study. Nine centres had less than 15 patients and one director requested that four of their seven centres not participate. 84 centres were recruited and on Feb 1, 2017, these centres were randomly assigned to administer personalised cooler dialysate (42 centres) or standard temperature dialysate (42 centres). The intervention period was from April 3, 2017, to March 31, 2021, and during this time the trial centres provided outpatient maintenance haemodialysis to 15 413 patients (about 4·3 million haemodialysis treatments). The mean dialysate temperature was 35·8°C in the cooler dialysate group and 36·4°C in the standard temperature group. The primary outcome occurred in 1711 (21·4%) of 8000 patients in the cooler dialysate group versus 1658 (22·4%) of 7413 patients in the standard temperature group (adjusted hazard ratio 1·00, 96% CI 0·89 to 1·11; p=0·93). The mean drop in intradialytic systolic blood pressure was 26·6 mm Hg in the cooler dialysate group and 27·1 mm Hg in the standard temperature group (mean difference –0·5 mm Hg, 99% CI –1·4 to 0·4; p=0·14). Centre-wide delivery of personalised cooler dialysate did not significantly reduce the risk of major cardiovascular events compared with standard temperature dialysate. The rising popularity of cooler dialysate is called into question by this study, and the risks and benefits of cooler dialysate in some patient populations should be clarified in future trials. Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Ontario Renal Network, Ontario Strategy for Patient-Oriented Research Support Unit, Dialysis Clinic, Inc., ICES (formerly known as the Institute for Clinical Evaluative Sciences), Lawson Health Research Institute, and Western University.

This study compared the effects of cold water immersion (CWI) and hot water immersion (HWI) on muscle recovery following a muscle-damaging exercise protocol in women. Thirty healthy women (23.3 ± 2.9 years) were randomly assigned to either the CWI, HWI, or control (CON) groups. Participants completed a standardised exercise protocol (5 x 20 drop-jumps), followed by a 10 min recovery intervention (CWI, HWI, or CON) immediately and 120 min post-exercise. Physiological responses, including muscle oxygen saturation (SmO 2 ), core and skin temperature, and heart rate, were assessed at baseline, immediately post-exercise, after the first recovery intervention (postInt), and during 30 min follow-up. Recovery was evaluated through maximal voluntary isometric contraction, muscle swelling, muscle soreness ratings, and serum creatine kinase at baseline, 24, 48, and 72 h post-exercise. A mixed-effects model was used to account for repeated measures over time. Results showed lower SmO 2 values in the CWI compared to the HWI group at 20 min (Δ-6.76%, CI: −0.27 to −13.25, p = 0.038) and 30 min (Δ-9.86%, CI: −3.37 to −16.35, p = 0.001), and compared to CON at 30 min (Δ-7.28%, CI: −13.77 to −0.79, p = 0.022). Core temperature was significantly higher in the HWI than the CWI group (postInt and 30 min), while it was significantly lower in the CWI group than CON (30 min). CWI caused a substantial decrease in skin temperature compared to HWI and CON between postInt and 30 min follow-up (all p < 0.001). Skin temperature was higher in the HWI group compared to CON at postInt and throughout 30 min follow-up (all p < 0.001). No significant differences in recovery markers were observed between CWI and HWI groups, although HWI led to slightly higher creatine kinase levels (24 h and 72 h) and greater muscle swelling (24 h) compared to CON. Despite distinct acute physiological responses to CWI and HWI, neither improved subjective or objective recovery outcomes during the 72 h follow-up compared to CON in women following a muscle-damaging exercise protocol.

Two research lines argue for rapid stress-induced reallocations of neural network activity involving the amygdala. One focuses on the role of norepinephrine (NE) in mediating a shift towards the salience network and improving vigilance processing, whereas the other focuses on the role of cortisol in enhancing automatic, habitual responses. It has been suggested that the mineralocorticoid receptor (MR) is critical in shifting towards habitual responses, which are supported by the dorsal striatum. However, until now it remained unclear whether these two reallocations of neural recourses might be part of the same phenomenon and develop immediately after stress onset. We combined methods used in both approaches and hypothesized specifically that stress would lead to rapidly enhanced involvement of the striatum as assessed by amygala-striatal connectivity. Furthermore, we tested the hypothesis that this shift depends on cortisol interacting with the MR, by using a randomized, placebo-controlled, full-factorial, between-subjects design with the factors stress and MR-blockade (spironolactone). We investigated 101 young, healthy men using functional magnetic resonance imaging after stress induction, which led to increased negative mood, heart rate, and cortisol levels. We confirmed our hypothesis by revealing a stress-by-MR-blockade interaction on the functional connectivity between the centromedial amygdala (CMA) and the dorsal striatum. Stress rapidly enhanced CMA-striatal connectivity and this effect was correlated with the stress-induced cortisol response, but required MR availability. This finding might suggest that the stress-induced shift described by distinct research lines might capture different aspects of the same phenomenon, ie, a reallocation of neural resources coordinated by both NE and cortisol.

Background Advanced medical procedures in prehospital settings are often performed in hostile environments, where cold temperatures may impair manual and cognitive performance. Although such procedures are essential in mountain rescue missions, the effects of cold conditions on their execution and associated workload and stress are unknown. Objective This randomized controlled simulation study evaluated differences in performance, perceived workload, and stress during the execution of three advanced emergency medical procedures under cold (− 20 °C) versus control (+ 20 °C) ambient temperatures. Additionally, the study examined the influence of operator experience on these outcomes. Methods Thirty-six members of the International Medical Commission for Alpine Rescue participated in a crossover study conducted at the terraXcube environmental simulator in Bolzano, Italy. Participants performed orotracheal intubation via videolaryngoscopy (OTI-VLS), mini-thoracostomy, and front-of-neck airway (FONA) procedures under both temperature conditions. Time to procedure completion, number of attempts, and perceived workload and stress (using the NASA Task Load Index and Visual Analogue Scale) were measured. Operators were categorized into high or low experience groups based on self-reported prior procedure frequency. Results Time to complete the procedures tended to be longer in cold conditions for all procedures, with the largest difference observed for OTI-VLS (14 s, p  = 0.076). Success rates exceeded 90% on the first attempt under both conditions. Perceived workload and stress increased significantly in cold environments across all procedures, especially for less experienced participants. Experienced operators completed OTI-VLS and mini-thoracostomy significantly faster and reported lower stress and workload levels compared to their less experienced counterparts. Conclusions While cold environments had low impact on procedural time, they significantly increased perceived workload and stress among rescue personnel. Experience mitigated these effects, emphasizing the importance of tailored training programs to enhance both technical and non-technical skills in challenging conditions. While this study has explored the impact of temperature, it would be valuable to investigate how other environmental factors, such as wind and rain, might affect clinical actions.

PurposeChanges in mean skin temperature (Tsk) have been shown to modify the maximum rate of sweat ion reabsorption. This study aims to extend this knowledge by investigating if modifications could also be caused by local Tsk.MethodsThe influence of local Tsk on the sweat gland maximum ion reabsorption rates was investigated in ten healthy volunteers (three female and seven male; 20.8 ± 1.2 years, 60.4 ± 7.7 kg, 169.4 ± 10.4 cm) during passive heating (water-perfused suit and lower leg water immersion). In two separate trials, in a randomized order, one forearm was always manipulated to 33 °C (Neutral), whilst the other was manipulated to either 30 °C (Cool) or 36 °C (Warm) using water-perfused patches. Oesophageal temperature (Tes), forearm Tsk, sweat rate (SR), galvanic skin conductance (GSC) and salivary aldosterone concentrations were measured. The sweat gland maximum ion reabsorption rates were identified using the ∆SR threshold for an increasing ∆GSC.ResultsThermal [Tes and body temperature (Tb)] and non-thermal responses (aldosterone) were similar across all conditions (p > 0.05). A temperature-dependent response for the sweat gland maximum ion reabsorption rates was evident between 30 °C (0.18 ± 0.10 mg/cm2/min) and 36 °C (0.28 ± 0.14 mg/cm2/min, d = 0.88, p < 0.05), but not for 33 °C (0.22 ± 0.12 mg/cm2/min), d = 0.44 and d = 0.36, p > 0.05.ConclusionThe data indicate that small variations in local Tsk may not affect the sweat gland maximum ion reabsorption rates but when the local Tsk increases by > 6 °C, ion reabsorption rates also increase.

The cold pressor test (CPT) is widely implemented and offers a simple, experimental acute pain model utilizing cold pain. Previous trials have frequently paired the CPT with opioids in order to investigate the mechanisms underlying pharmacological analgesia, due to their known analgesic efficacy. However, opioid side effects may lead to unblinding and raise concerns about the safety of the experimental setting. Despite the established clinical efficacy of dipyrone (metamizole), its efficacy, tolerability, and safety in cold pressor pain has not been systematically addressed to date. This pooled analysis included data of 260 healthy volunteers from three randomized, placebo‐controlled, double‐blind substudies using the CPT following a pre‐test‐post‐test‐design. These substudies allow for comparing a single dose of 800 mg dipyrone with two different doses of the opioid tilidine/naloxone (50/4 mg and 100/8 mg, respectively). Outcomes included pain intensity ratings, pain tolerance, medication‐attributed side effects, as well as changes of blood pressure and heart rate. We demonstrate that both opioid doses and dipyrone had a comparable, significant analgesic effect on cold pressor pain. However, dipyrone was associated with significantly less self‐reported adverse effects and these were not significantly different from those under placebo. These results indicate that the combination of dipyrone and the CPT provides a safe, tolerable, and effective experimental model for the study of pharmacological analgesia. In combination with a CPT, dipyrone may be useful as a positive control, or baseline medication for the study of analgesic modulation.

Indoor temperature is relevant with regard to mortality and heat-related self-perceived health problems. The aim of this study was to describe the association between indoor temperature and physical performance in older adults. Eighty-one older adults (84% women, mean age 80.9 years, standard deviation 6.53) were visited every four weeks from May to October 2015 and additionally during two heat waves in July and August 2015. Indoor temperature, habitual gait speed, chair-rise performance and balance were assessed. Baseline assessment of gait speed was used to create two subgroups (lower versus higher gait speed) based on frailty criteria. The strongest effect of increasing temperature on habitual gait speed was observed in the subgroup of adults with higher gait speed (−0.087 m/s per increase of 10 °C; 95% confidence interval (CI): −0.136; −0.038). The strongest effects on timed chair-rise and balance performance were observed in the subgroup of adults with lower gait speed (2.03 s per increase of 10 °C (95% CI: 0.79; 3.28) and −3.92 s per increase of 10 °C (95% CI: −7.31; −0.52), respectively). Comparing results of physical performance in absentia of a heat wave and during a heat wave, habitual gait speed was negatively affected by heat in the total group and subgroup of adults with higher gait speed, chair-rise performance was negatively affected in all groups and balance was not affected. The study provides arguments for exercise interventions in general for older adults, because a better physical fitness might alleviate impediments of physical capacity and might provide resources for adequate adaptation in older adults during heat stress.

Energy drink consumption has been anecdotally linked to the development of adverse cardiovascular effects in consumers, although clinical trials to support this link are lacking. The effects of Red Bull® energy drink on cardiovascular and neurologic functions were examined in college-aged students enrolled at Winona State University. In a double-blind experiment where normal calorie and low calorie Red Bull® were compared to normal and low calorie placebos, no changes in overall cardiovascular function nor blood glucose (mg/dL) were recorded in any participant (n = 68) throughout a 2-h test period. However, in the second experiment, nine male and twelve female participants subjected to a cold pressor test (CPT) before and after Red Bull® consumption showed a significant increase in blood sugar levels pre- and post Red Bull® consumption. There was a significant increase in diastolic blood pressure of the male volunteers immediately after submersion of the hand in the 5°C water for the CPT. Under the influence of Red Bull®, the increase in diastolic pressure for the male participants during the CPT was negated. There were no significant changes in the blood pressure of the female participants for the CPT with or without Red Bull®. Finally, the CPT was used to evaluate pain threshold and pain tolerance before and after Red Bull® consumption. Red Bull® consumption was associated with a significant increase in pain tolerance in all participants. These findings suggest that Red Bull® consumption ameliorates changes in blood pressure during stressful experiences and increases the participants’ pain tolerance.

Background This study aims to evaluate the safety, efficacy, and feasibility of a full randomized clinical trial of Ojeok-san in Korean female patients with cold hypersensitivity in the hands and feet. Methods This study is a multicenter, double-blinded, randomized, placebo-controlled, two-arm, parallel-group pilot clinical trial. A total of 60 participants will be enrolled and randomly assigned to the Ojeok-san treatment group or the placebo control group, in a 1:1 ratio using an Internet-based randomization system. Each group will be administered Ojeok-san or placebo three times per day for 8 weeks. The primary outcome will be the mean change in the Visual Analog Scale scores of cold hypersensitivity in the hands from baseline to week 8. Secondary outcomes will include the mean changes in the skin temperature of the extremities, recovery rate of the skin temperature of hands after cold stress test, and the score of Korean version of the WHO Quality of Life Scale abbreviated version. Discussion The findings of this study should provide meaningful information for a further large-scale, randomized controlled trial to confirm the safety and efficacy of Ojeok-san on cold hypersensitivity in the hands and feet in female patients. Trial registration ClinicalTrials.gov, ID: NCT03083522 . Registered on 20 March 2017.