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Supporting information | PMC9974128 | |||
Table 1 medicare benefits schedule categories. | (DOCX)Click here for additional data file. | PMC9974128 | ||
Fig 1 proportion of the study sample who utilised government funded medical services as classified by the 2020 medicare benefits schedule. | (DOCX)Click here for additional data file. | PMC9974128 | ||
Fig 2 proportion of the study sample who were supplied with government-subsidised medicines categorised according to the World Health Organisation Anatomical Therapeutic Chemical (ATC) classification system. | (DOCX)Click here for additional data file. | PMC9974128 | ||
Table 6 association between clinico-demographics and mean total healthcare costs. | (DOCX)Click here for additional data file. | PMC9974128 | ||
Table 7 association between clinico-demographics and mean total MBS and PBS costs. | Cancer | CANCER | (DOCX)Click here for additional data file.The authors are indebted to the people who participated in this research. We acknowledge members of the trial’s Executive Committee responsible for overseeing the project, including: Prof Melanie Lovell (Chair), Prof Meera Agar, Dr. Tim Luckett and Prof Jane Phillips. We acknowledge project team members at the coordinating centre (University of Technology Sydney) responsible for recruiting participants and collecting and managing data, including: Annmarie Hosie, Tim Luckett, Alison Read (project managers), Molly Cao, Sally Fielding, Layla Hall, Renee Xu (research assistants), Seong Cheah, Kaniz Fatema (data managers). Finally, we acknowledge members of the Stop Cancer PAIN Advisory Group for their ongoing support and advice to the project, including: Prof Sanchia Aranda, Prof Phyllis Butow, Dr. Ben Forster, A/Prof Michael Izard, Ms. Niamh O’Neill, Dr. Nathan Taylor, Dr. Ian Thong, Ms. Noelene Trotter, Ms. Jutta von Dincklage and Prof Patsy Yates. | PMC9974128 |
References | PMC9974128 | |||
Subject terms | IDA | IRON DEFICIENCY ANEMIA, EVENTS, SECONDARY, ADVERSE EVENTS | In patients on chronic hemodialysis, there is no standard protocol for maintenance iron supplementation. This study aimed to compare two fixed-dose intravenous (IV) iron protocols to reduce erythropoiesis-stimulating agents (ESA). We conducted a double-blinded, randomized controlled study on hemodialysis patients having ferritin levels between 200 and 700 ng/dl and transferrin saturation values between 20 and 40%. Patients were assigned to receive either 100 or 200 mg of IV iron each month. ESA was adjusted every month to keep Hb between 10 and 12 g/dl. ESA dose at 12 months was the primary outcome. The secondary outcomes were all-cause mortality, cardiovascular events, absolute iron deficiency anemia (IDA), blood transfusion, adverse events, and iron withholding rate. Of the 79 eligible patients, 40 received 100 mg of IV iron, while 39 received 200 mg. At month 12, the mean monthly ESA dose in the 100-mg IV iron group was 35,706 ± 21,637 IU, compared to 26,382 ± 14,983 IU in the 200-mg group (Thai Clinical Trials Registry number, TCTR20190707001. | PMC9870895 |
Introduction | death, IDA | ADVERSE EFFECTS, IRON DEFICIENCY ANEMIA | Iron deficiency anemia (IDA) remains a major problem in chronic hemodialysis patientsThe PIVOTAL trialOur aim was to find appropriate doses of maintenance iron therapy. Therefore, we conducted a randomized controlled trial to compare the efficacy of 100 mg IV iron with 200 mg IV iron per month regimens to minimize monthly ESA doses. We also explored the incidence of death, absolute IDA, blood transfusion, quality of life, changes in hemoglobin (Hb), ferritin levels, TSAT, and other adverse effects. | PMC9870895 |
Methods | PMC9870895 | |||
Trial design | infection, death | RENAL, INFECTION, KIDNEY, ADVERSE EVENTS | A single-center, double-blinded, post-hoc superiority, randomized controlled trial was conducted at Thammasat University Hospital from July 2019 to February 2021. The trial protocol was approved by the Human Research Ethics Committee of Thammasat University No 1 (Faculty of Medicine): MTU-EC-OO-4-055/62 and followed the principles of the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines. Written informed consent was obtained from all eligible participants, and the protocol was registered in the Thai Clinical Trials Registry with study number TCTR20190707001 (Date of registration 07/07/2019). This trial was funded by the Kidney Foundation of Thailand and the Research Group in Nephrology and Renal Replacement Therapy, Faculty of Medicine, Thammasat University. Study data were collected and managed using REDCap electronic data capture tools hosted at the Faculty of Medicine, Thammasat University, ThailandRandom allocation was done by computer-generated permuted blocks of varying sizes (blocks of 2 and 4). Randomization was stratified by the level of baseline Hb: < 10, 10–12 and > 12 g/dl. The investigators generated a random allocation sequence, enrolled participants, and assigned treatments. The patients were randomly assigned in a 1:1 to receive either a single, monthly dose of 100 mg or 200 mg IV iron sucrose. Since iron sucrose was mixed with 100-ml saline bags and dripped in 30 min during hemodialysis sessions, patients and care physicians cannot distinguish between both regimens (double-blinded).After randomization, trial visits were conducted every month up until 12 months. Hb levels were measured monthly; if levels were below or above target levels of 10–12 g/dl, ESA doses were adjusted to either increase or decrease ~ 25% of previous amounts. A blood transfusion would be given if Hb levels were extremely low (usually < 8 g/dl) or anemic symptoms were presented. Ferritin levels and TSAT were measured every three months and maintained in the safety ranges: ferritin 200–700 ng/dl and TSAT 20–40%. Suppose ferritin levels > 700 ng/dl or TSAT > 40%, IV iron was withheld for one month or longer until levels declined below those safety margins. Iron therapy was temporarily withheld if patients had a systemic or severe infection. In patients with absolute IDA, defined as ferritin levels < 200 ng/dl or TSAT < 20%, the treatment was unblinded, and IV iron sucrose was prescribed to be 100 mg weekly for a total of 10 doses (rescue regimen). After this, these patients would receive 200 mg IV iron monthly until the end of the study. Quality of life, measured by the EQ-5D questionnaire, was evaluated every six months. The incidence of death, hospitalizations, and adverse events were recorded throughout the study. | PMC9870895 |
Participants | infection, malignancy, HIV or hepatitis B or C infection, heart failure | HYPERSENSITIVITY REACTION, HEMATOLOGIC MALIGNANCY, INFECTION, END-STAGE RENAL DISEASE, HEART FAILURE, CHRONIC LIVER DISEASE | Adults ≥ 18 years old with end-stage renal disease, undergoing chronic hemodialysis > 90 days were enrolled in this study. Other eligibility criteria were those with a ferritin level of 200–700 ng/dl, TSAT of 20–40%, Hb > 9 g/dl, and received ESA regularly. Exclusion criteria were life expectancy < 6 months, those planning to receive a kidney transplant or switch to peritoneal dialysis in the next 6 months, active infection, active malignancy, known HIV or hepatitis B or C infection, chronic liver disease, advanced heart failure (NYHA IV), pregnancy or breastfeeding, hematologic malignancy, and previous hypersensitivity reaction to IV iron sucrose. | PMC9870895 |
Outcomes | thrombosis, death, IDA | THROMBOSIS, MYOCARDIAL INFARCTION, STROKE | The primary efficacy endpoint was to compare mean monthly doses of ESA at month 12 between the two groups. Secondary efficacy endpoints were the incidence of death, myocardial infarction, stroke, IDA, blood transfusion, quality of life, and changes in Hb, ferritin levels, TSAT, and ESA doses.Safety parameters were evaluated throughout the study, including the incidence of vascular thrombosis, hospitalization, and iron withholding rate. | PMC9870895 |
Statistical analyses | According to the PIVOTAL trialContinuous variables were expressed as mean ± standard deviation (SD) or median and IQR and compared using unpaired We presented time to withholding IV iron and time to iron rescue therapy between groups using the Kaplan–Meier curve and compared it with Cox proportional hazard models. Mean cumulative doses of IV iron between groups were compared with linear random-intercept model. The patterns of protocol compliance were presented and compared with exact probability test. Moreover, we performed post-hoc subgroup analyses to assess whether sub-populations (defined using median values of baseline Hb, ferritin, and TSAT) may have affected the IV iron therapy withholding rate. And we also test whether certain clinical features may influence the difference in ESA doses.All | PMC9870895 | ||
Results | PMC9870895 | |||
Discussion | thrombosis | THROMBOSIS, HAND INFECTION, CHRONIC BLOOD LOSS, ADVERSE EVENTS, EVENT, ADVERSE EFFECTS, EVENTS, OXIDATIVE STRESS | Our study shows that maintenance IV iron at higher doses (200 mg vs. 100 mg) was more effective in reducing ESA doses at month 12. However, the incidence of absolute IDA was significantly higher in the 100-mg IV iron group. Nevertheless, iron therapy was withheld significantly more often in the 200-mg IV iron group. There were more adverse effects in access thrombosis, hospitalization, and infection in the 200-mg IV iron group, without statistical significance.Maintenance IV iron in incident hemodialysis patients has been previously studied. As mentioned, the PIVOTAL trialSusantitaphong et al.Theoretically, the appropriate dose of iron supplementation should be equivalent to iron loss. In hemodialysis patients, losing residual blood in the circuit and chronic blood loss in the gastrointestinal tract are the significant causes of iron loss, approximately 1–3 g per year and equivalent to 83–250 mg per monthAnother observational study, using 58,058 hemodialysis patients from DaVita dialysis clinics, showed that IV iron > 400 mg per month was associated with higher all-cause and cardiovascular mortality ratesSafety is always an essential consideration in prescribing iron. IV iron may increase oxidative stress and lead to cardiovascular and infectious complicationsAdditionally, the withholding rates in our study were up to 25% and 64% in 100-mg and 200-mg IV iron. After performing subgroup analysis, baseline ferritin ≥ 364 ng/dl was significantly associated with withholding event. Therefore, in patients with high baseline ferritin levels, we suggest trying 100-mg IV iron first and promptly increasing the dose if the ferritin level does not increase appropriately. This may be less risky than starting with a fixed dose of 200 mg.To our knowledge, this is the first clinical trial of fixed-dose protocol maintenance IV iron. The strength of our study was a randomized, double-blinded, controlled trial, which minimized confounding and other bias relatively well. Secondly, our iron protocol was simple and easy to comply with. However, there were many limitations. First, this study was conducted at a single center, affecting generalizability. Second, the study population was relatively small, and our follow-up period was limited to 12 months. We cannot conclude the impact of the protocol on cardiovascular outcomes and critical adverse events, such as thrombosis and infection. Third, the actual monthly doses (174 and 116 mg) were different from the protocol because of the high withholding rate in the 200-mg group and the high rate of IDA in the 100-mg group, representing that fixed-dose is not fit for all patients. Fourth, clinicians could recognize when rescue iron therapy or withholding events occurred so that ESA dose adjustment may be affected.A maintenance IV iron regimen of 200 mg per month was more effective than the 100-mg dose to minimize ESA doses in hemodialysis patients. Nonetheless, the iron withholding rate was higher. The stepping-up protocol may be an appropriate option in patients with high baseline ferritin if within safety parameters. | PMC9870895 |
Supplementary Information | The online version contains supplementary material available at 10.1038/s41598-023-28440-3. | PMC9870895 | ||
Acknowledgements | RENAL, KIDNEY | This study is supported by the Kidney Foundation of Thailand and the Research Group in Nephrology and Renal Replacement Therapy from the Faculty of Medicine, Thammasat University. One of the ESA supplies, Hypercrit®, was partially supported by Comsa Medical Company Limited and Biosidus S.A. We would like to thank all patients for participating and Thammasat University Hospital for permitting us to conduct this study. The study could not have been completed without the help of the nurses and officers in the 60th Anniversary HRH Princess Maha Chakri Sirindhorn Dialysis Center. Finally, thank you, Ms. Debra Kim Liwiski, for being our English editor. | PMC9870895 | |
Author contributions | S.A. and P.T. designed the study. S.A. and A.C. collected data. P.T. performed the analyses and made the figures. All the authors interpreted and gave suggestions for additional analyses. S.A. and P.T. wrote the manuscript. All the authors reviewed and approved the final version of the manuscript. | PMC9870895 | ||
Funding | RENAL, KIDNEY | The Kidney Foundation of Thailand; Research Group in Nephrology and Renal Replacement Therapy, Faculty of Medicine, Thammasat University. | PMC9870895 | |
Data availability | The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request. | PMC9870895 | ||
Competing interests | The authors declare no competing interests. | PMC9870895 | ||
References | PMC9870895 | |||
Subject terms | COLD | The Wim Hof method (WHM) is a multi-disciplinary approach to physical and mental well-being combining cold exposure, breathing exercises, and meditation. This study evaluated the effects of a 15 days WHM intervention on cardiovascular parameters at rest and during a cold pressor test (CPT), as well as on various psychological parameters. Forty two participants were randomized into an intervention (IG) and a control group. Throughout the 15 days intervention, the IG performed the WHM daily. Before and after the intervention, systolic (SBP) and diastolic blood pressure (DBP), pulse wave velocity (PWV), heart rate (HR), root mean sum of squared distance (RMSSD), and standard deviation of RR-intervals (SDNN) were assessed at rest and during a CPT. Furthermore, perceived stress (PSS), positive affect (PANAS+), negative affect (PANAS−), and subjective vitality (trait (SVSt) and state (SVSs)) was determined. No significant time × group interactions could be detected in HR ( | PMC10579249 | |
Introduction | CVDs, Cardiovascular diseases, anxiety, inflammation, , reduced stress | CARDIOVASCULAR DISEASE, CARDIOVASCULAR DISEASE, INFLAMMATION, CARDIOVASCULAR MORBIDITY, COLD | Cardiovascular diseases (CVDs) are a major cause of morbidity and mortality worldwideMindfulness-based interventions aim to reduce blood pressure (BP) by employing stress-reduction techniques, including meditation, which are designed to foster a state of inner awareness and calmnessCold water immersion is hypothesized to result in increased body sturdiness, inter alia, through long-term antioxidative adaptationBreathing exercises have garnered considerable attention as promising approaches for both the treatment and prevention of cardiovascular disease. Research has demonstrated that these techniques can contribute to stress reductionThe Wim Hof Method (WHM), a multi-disciplinary approach to physical and mental well-being, has recently gained tremendous popularity. Developed by Dutch extreme athlete and multiple world record holder Wim Hof, the WHM combines cold exposure, breathing exercises, and mindfulness meditation. The cold exposure component involves exposing the body to colder temperatures through activities such as ice baths, cold showers, and cold-water immersion. The breathing exercises involve a specific pattern of deep breaths, retention, and exhalation designed to relieve tension, and activate the autonomic nervous system. The mindfulness component involves meditation and visualization techniques aimed at improving focus and reducing stressThe WHM has been claimed to have a range of benefits, including improved mood, reduced stress and anxiety, enhanced immune function, improved cardiovascular function, and increased energy and vitality, which should be evident after only 10 daysPreliminary research suggests that the WHM may have benefits in areas such as inflammation and mood regulation. Petraskova et al.Further research is necessary to understand the effects of the method and its underlying mechanisms. Currently, the effects of the WHM on cardiovascular risk factors have not been assessed.Beyond BP, which is arguably one of the most robust predictors of future cardiovascular health, other risk markers like pulse wave velocity (PWV) have gained significant attentionConsequently, the present study aimed to assess the effects of the WHM on BP, PWV, and HRV. Moreover, the possible effects of the WHM on cardiovascular response to a stressor have yet to be assessed. Literature shows that cardiovascular reactivity can predict future cardiovascular morbidity and mortality and is thus regarded as an important risk factor for developing future CVDsResearch on possible positive effects of the three components (cold exposure, breathing exercise, meditation) of the WHM supports the assumption that this method may induce positive effects on cardiovascular risk factorsIn this study, we aim to evaluate the effects of a 15 days WHM intervention on different cardiovascular parameters at rest and during a standardized stress test, as well as on various psychological parameters to better understand its potential benefits and limitations. | PMC10579249 |
Methods | PMC10579249 | |||
Study design and participants | pain | MAY, COLD | This study was designed as a randomized controlled trial with parallel arms. Participants were recruited between May and July 2022 through social media and personal contacts. Eligibility criteria included (1) being male, (2) having no underlying health conditions, (3) not using antihypertensive or other cardiovascular medications, (4) not engaging in regular exercise training, (5) and not having prior experience with any of the components of the intervention (breathing, meditation, or cold exposure). A total of 42 participants (aged 26.7 ± 5.7 years; body mass index 22.8 ± 2.0 kg/mFlow-chart.All measurements were performed in a controlled environment at the Physiology Lab of the Institute of Sports Science at the University of Bern. The measurements were carried out by trained study staff under controlled conditions using the same equipment and procedure. The participants visited the lab on two occasions for baseline and follow-up measurements, with both sessions taking place at similar times of the day to rule out circadian influences on outcomes. The participants were instructed to visit the lab at least 4 h postprandial and to avoid consuming caffeinated or alcoholic beverages and nicotine for 4 h prior to the measurements. They were further advised to abstain from vigorous physical activity for at least 24 h before each test day.The study protocol included the administration of questionnaires to obtain information on the participants’ demographics, medical history, habitual physical activity, perceived stress, affect, and vitality. Subsequently, heart rate (HR), HRV and BP readings were conducted. Finally, a cold pressor test was performed to assess HR, BP responses, and perceived pain.After baseline assessments, the participants were randomly allocated to either the intervention group (IG) or the control group (CG) by the principal investigator using a computer-generated random number table. The IG participated in the WHM daily for 15 days while the CG continued with their normal daily activities. During the intervention period, participants were asked to maintain their usual diet and physical activity patterns. | PMC10579249 |
Measurements | PMC10579249 | |||
Anthropometrics | CREST | Height and body mass were assessed using a stadiometer and scale (BC-545 Innerscan, Tanita, Netherlands). Waist circumference was measured to the nearest 0.1 cm at the midpoint between the iliac crest and the lowest ribs. Body Mass Index (BMI) was calculated as body mass in kilograms divided by height in meters squared (kg/m | PMC10579249 | |
Physical activity | Self-reported physical activity was assessed using a modified version of the Godin-Shephard Leisure-Time Physical Activity Questionnaire,a valid and reliable tool for assessing physical activity | PMC10579249 | ||
Heart rate variability | HRV was measured using a Polar RS800 CX | PMC10579249 | ||
Blood pressure | Systolic BP, diastolic BP, and PWV were obtained non-invasively using the Mobil-O-Graph | PMC10579249 | ||
Cold pressor test | pain | COLD | The cold pressor test is a common and extensively validated test for assessing cardiovascular reactivity. Trained study staff performed the cold pressor test before and after the intervention using a standardized protocol. Before the test, the participants rested in a supine position and had their BP, PWV, and HR measured. Subsequently, they immersed their right hand in cold water (5.0 °C) for two minutes while BP, PWV, and HR were monitored using the Mobil-O-Graph device. Cardiovascular reactivity was determined as the changes (Δ) in the respective parameters between the rest measurement and the subsequent cold pressor test. A numerical rating scale was used to assess participant’s level of pain on a scale ranging from 0 to 10, with 0 indicating no experience of pain and 10 indicating the most intense experience of pain possible. | PMC10579249 |
Perceived stress | The Perceived Stress Scale (PSS) by Cohen et al. | PMC10579249 | ||
Affect | POSITIVE | The Positive and Negative Affect Schedule (PANAS) | PMC10579249 | |
Vitality | The Subjective Vitality Scale (SVS) | PMC10579249 | ||
Intervention | PMC10579249 | |||
Wim Hof method | The intervention followed the guidelines provided by Wim HofAt the end of the baseline assessments, the participants received oral step-by-step instructions from the study staff, who were experienced in the WHM, on how to perform the various intervention components. They also received written instructions providing a step-by-step overview of the procedure, along with an audio file for the shower and meditation, and a video file for the breathing exercise. | PMC10579249 | ||
Breathing-method | The breathing exercises consisted of a specific sequence of deep breaths in, holds, and breaths out, performed in a cyclic manner. The participants were provided with guided audio instructions. Participants were instructed to sit or lay in a comfortable position and perform 30 to 40 conscious breaths, inhaling deeply into their abdomen and chest and then exhaling without effort. After the last exhalation, they were instructed to hold their breath as long as they felt comfortable, then inhale deeply and hold their breath for 10 to 15 s. Thereafter, they exhaled again and relaxed. This was repeated two to three times. | PMC10579249 | ||
Meditation | The meditation component of the WHM is a mindfulness-based technique that aims to regulate emotions and thoughts. Participants were instructed to find a quiet place, sit, or lie down in a comfortable position and focus their attention on their breathing and their body sensations. They were encouraged to pay attention to their thoughts, emotions, and bodily sensations and to bring their focus back to their breath if they become distracted. The meditation lasted 5 min or until the participant felt calm and centered. The goal was to cultivate a sense of inner peace, reduce stress and increase overall well-being. | PMC10579249 | ||
Cold-water exposure | COLD | The cold-water exposure component involved exposure to cold water in the form of cold showers. Participants were instructed to take shower in cold water for a set period of time, starting with 30 s, and increase the time each day by 5 s as they become acclimated. The participants received an MP3 file that emitted a sound every ten seconds to keep track of the time. Furthermore, clear instructions were provided to the participants regarding the duration and specific body parts to be exposed to the cold. They began by showering their feet and legs (front and back) for 10 s, then their torso (front and back) for 10 s, and finally their entire body, including their head, for 10 s or the remaining time. The water temperature should be adjusted to the coldest possible setting. | PMC10579249 | |
Statistics | Data analysis was conducted using IBM SPSS Statistics for Windows, Version 27.0 (IBM Corp., Armonk, NY, USA). The normal distribution of the data was checked using the Kolmogorov–Smirnov test. Independent samples t-test was applied to examine differences in baseline measures between the groups. To analyze the effect of time and group on the outcomes, a mixed-design analysis of variance (ANOVA) was employed. Post-hoc analyses, as appropriate, were performed using one-way ANOVA with Bonferroni correction. A significance level of | PMC10579249 | ||
Results | illness, hypertensive | ADVERSE EVENTS | One participant in the IG dropped out due to illness. In total, 21 participants in the IG and 20 participants in the CG were included in the final analysis. The age range was between 18 and 39 years. No adverse events occurred during the intervention period in any of the participants. The subject’s characteristics are displayed in Table Participant’s characteristics at baseline.Data expressed as means ± standard deviations. Based on the BP, eight participants were classified as having a high-normal BP (IG = 5, CG = 3) and two as hypertensive (IG = 1, CG = 1). According to the intervention logs the participants performed 13 ± 2 cold shower sessions, 12 ± 3 meditation sessions, and 12 ± 2 breathing exercise sessions throughout the 15-day intervention period. There were no significant time × group interactions (F(1,39) = 0.048, | PMC10579249 |
Cardiovascular parameters | pain | No significant time × group interactions could be detected in HR (F(1,39) = 0.14, Changes in cardiovascular outcomes, perceived pain, and MET hours from before to after intervention for the intervention group (IG) and control group (CG).Data expressed as means ± standard deviations. No main effects for time could be detected in HR (F(1,39) = 0.36, Similarly, no main effects for group could be detected for HR (F(1,39) = 0.05, | PMC10579249 | |
Cold pressor test | COLD | No significant time × group interactions could be detected in the stress response to the cold pressor test in ΔHR (F(1,39) = 0.29, Again no main effect for time could be detected in ΔHR (F(1,39) = 0.002, | PMC10579249 | |
Psychological parameters | There were no significant time × group interactions for PANAS+ (F(1,38) = 0.65, Changes in psychological outcomes from before to after intervention for the intervention group (IG) and control group (CG).Data expressed as means ± standard deviations. Only the PSS revealed a significant main effect for time (F(1,38) = 10.94, Furthermore, no significant group effects could be revealed for PANAS+ (F(1,38) = 0.07, | PMC10579249 | ||
Discussion | The present study aimed to determine the effectiveness of the WHM on various psychological and physiological parameters. No significant time × group interaction could be detected for any of the outcomes. Thus, contrary to the claim by Wim Hof | PMC10579249 | ||
Cardiovascular parameters | COLD | Unfortunately, there are no comparable studies assessing the effects of the WHM on cardiovascular parameters. However, previous studies on the different components of the WHM can inform the interpretation of the results.It has been often proposed that regular cold exposure may possibly comprise a healthier cardiovascular risk profile, as cold exposure triggers a cascade of physiological reactions, eventually leading to an increased parasympathetic and a blunted sympathetic activationIn contrast to our study, the hydrotherapeutic program included not only cold applications but also peripheral warm water baths, such as arm baths and foot baths. Mäkinen and colleaguesThe discrepancies may be attributed to differences in study design, such as the form of exposure (cryotherapy, whole-body cold-water immersion, cold shower), the exposure duration, the body area exposed to cold, the temperature, and the sessions’ frequency | PMC10579249 | |
Cardiovascular reactivity | pain | COLD | Previous research has demonstrated that cold water immersion stimulates positive adaptive changes in the human body, resulting in increased readiness to handle stress factorsWe postulated that regular cold exposure could mitigate the vasoconstrictive effects of acute cold exposure, thereby reducing the cardiovascular response to the cold pressor test. This would be of relevance as the magnitude of an individual’s hemodynamic responses to a stressor can be a marker for cardiovascular riskPrevious research has shown that repeated exposure to cold environments decreases sympathetic responses to acute cold exposure, as evidenced by reduced changes in HRV, BP, and plasma norepinephrineHowever, in the present study, no significant changes in HR, BP, PWV, and perceived pain could be reported after the WHM. As mentioned earlier, the study by Mäkinen et al. | PMC10579249 |
Meditation | Besides cold-water immersion, also meditation techniques have been reported to lower BP and improve HRV in older or at-risk patientsIn the present study, the WHM, which includes a meditation component, could not induce changes in HR, HRV, BP, and PWV. It's worth noting that the intervention period in the present study was relatively short compared to that in other studies, many of which had durations exceeding 2 months | PMC10579249 | ||
Breathing | COLD | Slow deep breathing, commonly practiced in meditation, yoga, and several relaxation techniques, has been shown to positively affect BPRecent studies by Zwaag et al.Unfortunately, there are no studies on the long-term effects of this breathing technique on HR, HRV, BP, and PWV. According to the results of the present study, regularly performing the breathing exercises in combination with cold water exposure and meditation did not alter HRV and hemodynamic parameters. | PMC10579249 | |
Psychological parameters | The present study did not detect any significant changes in affect (positive and negative), vitality, and perceived stress after regularly performing the WHM.To the best of our knowledge, no previous studies have addressed the effects of regularly performing the WHM on these psychological outcomes. Only, Petraskova et al.In the study by Huttunen et al.Meditation has also demonstrated promising results in reducing psychological distress across different populations and settings and can be effective in enhancing vitalityIt is unclear why the present intervention did not induce positive psychological effects. However, it is possible that the considerable differences in interventions applied, and participants included may account for the differences. Furthermore, the intervention period of previous studies was considerably longer. It can be speculated that longer interventions may be necessary to produce more substantial changes in psychological parameters. Moreover, it cannot be ruled out that the combination of the different components of the WHM may have blunted the effects of each other. Further research is needed to determine the effects of regularly performing the WHM on psychological outcomes. | PMC10579249 | ||
Limitations | hyperventilation | COLD | Several limitations of this study must be addressed. First, the study only included healthy young male adults, which may limit the generalizability of the results to other populations, such as individuals with a higher risk profile or female participants. Second, the home-based intervention did not allow for standardization of water temperature. Even though the participants were instructed to set the water temperature as low as possible, there were considerable differences in the water temperature throughout the intervention period and in the different regions where the participants lived. According to the local water provider (Wasserverbund Region Bern AG), the mean water temperature throughout the intervention period was 14.1 ± 3.2 °C.Third, although participants received clear instructions on the duration and the body parts to be exposed to the cold water, compliance with these instructions was only documented using a daily log. Fourth, the intervention duration was relatively short. Even though Wim Hof claims that changes will occur after 10 days, it is expected that more extended intervention periods lead to more pronounced effects. Fifth, it would be interesting to investigate the individual effects of different combinations of the intervention components (hyperventilation, meditation, cold exposure) before exploring their combined effects. Sixth, we only included individuals with no prior experience with the various components of the intervention. It could be argued that, especially for the meditation component, some prior experience and a specific mindset might be beneficial.Finally, it is unclear whether it is necessary to be trained by the creator of the intervention or a trained instructor with regard to the so-called guru effect | PMC10579249 |
Conclusion | mood, reduced stress | The WHM has gained popularity for its potential health and performance benefits, including performance enhancement, improved mood, reduced stress, enhanced immune function, improved cardiovascular function, and increased vitalityFurther studies should address the effects of a longer and more intense intervention, and should include additional parameters, especially non-linear HRV parameters, which can aid in a better interpretation of the physiological behavior of HRV. Furthermore, studies should consider a dismantling design in which the different components are compared to the full protocol. This could help determine possible opposing effects on physiological and psychological parameters. | PMC10579249 | |
Acknowledgements | We would like to thank all participants for taking part in this study. | PMC10579249 | ||
Author contributions | S.K. conceived the original idea, designed the study, processed the experimental data, performed the analysis, and drafted the manuscript. C.R.N. supervised the project, aided in interpreting the results, and worked on the manuscript. D.Q., X.B., X.M., E.B. performed the measurements, processed the experimental data, and performed the analysis. All authors provided critical feedback and helped shape the research, analysis, and manuscript. | PMC10579249 | ||
Data availability | All raw data are available on request to the corresponding author. | PMC10579249 | ||
Competing interests | The authors declare no competing interests. | PMC10579249 | ||
References | PMC10579249 | |||
1. Introduction | critically ill, dyspnea, ARDS, infection, pulmonary and cardiovascular adverse | VIRUS, CRITICALLY ILL, ARDS, INFECTION, CORONAVIRUS, SEVERE ACUTE RESPIRATORY SYNDROME, ACUTE RESPIRATORY DISTRESS SYNDROME, COMPLICATIONS | Administering N-acetylcysteine (NAC) could counteract the effect of free radicals, improving the clinical evolution of patients admitted to the Intensive Care Unit (ICU). This study aimed to investigate the clinical and biochemical effects of administering NAC to critically ill patients with COVID-19. A randomized controlled clinical trial was conducted on ICU patients (Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause dyspnea that can lead to acute respiratory distress syndrome (ARDS) leading to the production of a set of immune mediators against the invading virus [Glutathione plays a fundamental role in many biological processes essential for the homeostasis of the organism [N-acetylcysteine (NAC) might be beneficial for treating patients with COVID-19 because it helps restore glutathione levels, intervening in its synthesis. In addition, NAC has an antioxidant and anti-inflammatory effect and regulates the immune response. A high dose of intravenous NAC can be expected to play an adjunctive role in treating severe cases of COVID-19 and managing its lethal complications, including pulmonary and cardiovascular adverse events [Several studies showed that the increase in neutrophils and neutrophil extracellular traps (NETs) in COVID-19 patients contribute to increasing severity and mortality. Therefore, they can be used as therapeutic targets [The intervention with NAC was used successfully in patients with invasive mechanical ventilation, observing a decrease in ferritin and C-reactive protein (CRP) [Based on the information mentioned above, the present study proposes that the administration of NAC could counteract the effect of these free radicals, improving the antioxidant status and inflammatory situation and, therefore, the clinical evolution of the COVID-19 patient in the ICU. The main objective of our study was to investigate the clinical and biochemical effects of administering NAC to critically ill patients with COVID-19. | PMC10181318 |
2. Materials and Methods | PMC10181318 | |||
2.1. Patients and Study Design | critically ill | CRITICALLY ILL | A randomized, controlled clinical trial was conducted on critically ill patients with COVID-19. The design was a prospective, analytical, follow-up study of cases and controls. The sample of patients studied was made up of 140 consecutive patients over 18 years of age (women, 23.6%) admitted to the ICU with COVID-19. The groups’ distribution comprised a total of 72 patients treated with NAC (treated patients), and 68 patients not treated with NAC (control group patients). The sample size we used in our study is similar to the sample size of other studies similar to ours [ | PMC10181318 |
2.2. Treatment and Nutritional Support | Patients received treatment that included medications (antivirals, antibacterial, corticosteroids, etc.), respiratory support, and nutritional support (enteral, parenteral, and/or mixed enteral/parenteral) during the hospital stay. The latter was according to the Clinical Nutrition Units Guidelines of the hospitals, based on the American Society for Parenteral and Enteral Nutrition (ASPEN) and the European Society of Parenteral and Enteral Nutrition (ESPEN) guidelines [ | PMC10181318 | ||
2.3. NAC Intervention | The intravenous dosage schedule was based on that used in acute paracetamol poisoning. The NAC administration protocol was based on the Prescott et al. protocol [ | PMC10181318 | ||
2.4. Data Collection | On the day of ICU admission and on the third day, the following data were recorded: patient age, sex, Acute Physiology and Chronic Health Assessment II (APACHE II) score [ | PMC10181318 | ||
2.5. Biochemical Parameters | Initial and final plasma and erythrocyte samples were collected under fasting conditions, followed by centrifugation (4 °C for 15 min at 3500 rpm) to separate plasma and serum. The samples were stored at −80 °C before biochemical analysis for subsequent tests. Plasma and erythrocyte samples were obtained from the NAC-treated and control group patients. The following initial and final data were recorded: biochemical blood profile acid-base balance: pH; renal function: creatinine, urea, and ions; liver function: glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT); haematometric parameters: leukocytes, neutrophils, lymphocytes, and rate neutrophils/lymphocytes; inflammatory parameters: lactate dehydrogenase (LDH), PCR, lactate, ferritin, D-dimer, and procalcitonin. | PMC10181318 | ||
2.6. Assessment of GSH and GSSG | COLD | A colorimetric detection kit (Invitrogen by Thermofisher Scientific, ref: EIAGSHC, Madrid, Spain) was used to perform the GSH and GSSG determination assay. The erythrocyte samples were treated with sulfosalicylic acid to precipitate the proteins. Thereafter, 0.050 mL of the sample was placed in an Eppendorf tube and 0.150 mL of 5% sulfosalicylic acid was added. Preparation of sulfosalicylic acid: 1 g of sulfosalicylic acid was placed in a beaker and made up to 20 mL with distilled water. Samples were shaken and then incubated at room temperature for 10 min, then centrifuged at 14,000 rpm for 10 min at 4 °C. The supernatant was diluted with 1% sulfosalicylic acid. Then, 0.05 mL of the diluted sample was transferred to the test well together with a colorimetric detection reagent, glutathione reductase, and NADPH. The absorbance was measured at 405 nm in a microplate reader (Biostack neo. BiotTek. By Izasa Scientific, Madrid, Spain). An assay curve was also constructed and measured, which was then used to extrapolate the absorbance and obtain the concentration of the samples. To measure oxidized glutathione, the same procedure was followed by adding 2-vinylpyridine to the sample. Two quality controls from two known concentrations of the calibration curve were used. Samples from a temperature of −80 °C were kept cold and under the same conditions throughout the determination process by a researcher specialized in clinical analysis. | PMC10181318 | |
2.7. Assessment of Erythrocyte Glutathione Peroxidase Activity (GPx1 Activity) | The GPx1 activity of red blood cell hemolysate was assessed with a colorimetric assay using the Bioxytech | PMC10181318 | ||
2.8. Statistical Analysis | Statistical analysis was performed with SPSS version 21.0 for Windows (SPSS Inc., Chicago, IL, USA). Qualitative variables were presented as frequencies and percentages of patients, and quantitative variables as mean ± standard deviation (SD). For continuous variables, the assumption of normality was tested using the Shapiro–Wilk test. The differences in biochemical parameters and clinical outcomes between treated and control group patients were evaluated by Student’s | PMC10181318 | ||
3. Results | PMC10181318 | |||
4. Discussion | DISEASE, COVID-19 PNEUMONIA, OXIDATIVE STRESS | The main results of the present study revealed that in NAC-treated patients, PaOIn our study, both the NAC-treated and control group patients had an altered clinical outcome on the first day of the study. Moreover, a decrease in the positive end-expiratory pressure (PEEP) and an increase in PaOThe CRP, D-dimer, and LDH responses to IV NAC were favorable in our patients. It should be noted that the decrease in D-dimer should be interpreted with caution since D-dimer levels on the initial day were significantly higher in the treated patients than in the control group. In particular, it can be seen that the D-dimer results showed high intragroup variability, therefore, quantitative difference between the first and the third day was calculated, observing statistically significant differences in the evolution in ICU (The antiviral [In our study, both groups of patients showed a decrease in total glutathione levels on the third day. This decrease could have been due to glutathione consumption because of elevated oxidative stress during the ICU stay, as previously described in the literature [Our study found a larger association between glutathione levels and clinical outcomes such as SOFA and inflammatory parameters in NAC-treated patients and none in the control group patients on the first and third days of ICU stay. It has been suggested that NAC is not an antioxidant molecule itself but that its actual role lies in the specific replenishment of GSH in deficient cells, and NAC is likely to be ineffective in GSH-replete cells [Concerning clinical outcomes, previous studies in NAC-treated patients infected by SARS-CoV-2 showed no decreased intubation rate, no improvement in oxygenation index, no shortening of ICU stay, nor reduction in mortality [However, oral administration of NAC (1200 mg/day) in patients with COVID-19 pneumonia decreases the risk of mechanical ventilation and mortality [Despite the results of the present study, this work is not without limitations. Firstly, data on patients with mild symptoms were not available because the samples were collected during the highest peak of the pandemic. Secondly, the recruited patients were from a single hospital and some potential confounding factors (sociodemographic and socioeconomic status) were not evaluated. Thus, these outcomes cannot be generalized to other populations, especially considering the wide range of COVID-19 prevalence. Thirdly, the methodology used in the determination of the glutathione molecule, despite a validated colorimetric method, may not achieve sufficient sensitivity to determine this molecule, and a chromatographic method such as HPLC may be more appropriate. Finally, the overall results may be related to the heterogeneity of the subjects and their underlying disease conditions or severity. | PMC10181318 | |
5. Conclusions | critically ill, ill | CRITICALLY ILL | The administration of NAC manages to improve the clinical and analytical response of seriously ill patients with COVID-19 compared to the control group. NAC is able to stop the decrease in glutathione concentrations. Therefore, the administration of NAC in critically ill patients with COVID-19 could be assessed based on the need for quick and agile intervention through monitoring and follow-up in the ICU from the beginning of the stay to prevent and correct possible alterations and improve prognosis. | PMC10181318 |
Author Contributions | Conceptualization, Y.G.-M., J.C.-P. and E.P.; Methodology, Y.G.-M., J.F.M.-C., J.C.-P., J.M.P.-V. and E.P.; Software, Y.G.-M., L.H.-Q., J.F.M.-C. and H.V.-L.; Validation, Y.G.-M., J.M.-L. and E.P.; Formal analysis, Y.G.-M.; Investigation, L.H.-Q., H.V.-L., J.F.M.-C., J.C.-P. and J.M.P.-V.; Resources, E.P. and J.M.-L.; Data curation, Y.G.-M., J.M.-L., J.F.M.-C. and E.P.; Writing–original draft preparation, Y.G.-M.; Writing–review and editing, Y.G.-M., J.M.-L. and E.P.; Visualization, Y.G.-M., L.H.-Q., J.M.-L., H.V.-L., J.F.M.-C., J.C.-P., J.M.P.-V. and E.P.; Supervision, J.M.-L. and E.P.; Project administration, E.P.; Funding acquisition, E.P. All authors have read and agreed to the published version of the manuscript. | PMC10181318 | ||
Institutional Review Board Statement | The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of the University of Granada (protocol code 149/CEIH/2016). | PMC10181318 | ||
Informed Consent Statement | Informed consent was obtained from all subjects involved in the study. | PMC10181318 | ||
Data Availability Statement | Data will be shared upon reasonable request by the corresponding author: Yenifer Gamarra-Morales. | PMC10181318 | ||
Conflicts of Interest | The authors declare no conflict of interest. | PMC10181318 | ||
1. Introduction | oxaliplatin-induced, breast cancer, CIPN, neurotoxic, Cancer | SIDE EFFECT, BREAST CANCER, ADVERSE EVENT, CHEMOTHERAPY-INDUCED PERIPHERAL NEUROPATHY, CANCER | Chemotherapy-induced peripheral neuropathy (CIPN) is a serious side effect of weekly paclitaxel-based chemotherapy for breast cancer, that can persist for years. Cryotherapy therapy is effective for preventing early CIPN, but its protective effect on persistent CIPN is uncertain. This is a cross-sectional study conducted as an ancillary analysis of a randomized trial investigating the preventive effect of cryotherapy on CIPN in breast cancer patients receiving weekly paclitaxel-based chemotherapy (UMIN000034966). Eligible patients were evaluated for CIPN at more than a year after completion of the chemotherapy (persistent CIPN). CIPN was defined as a 6 or more points reduction from baseline in the Functional Assessment of Cancer Therapy-Neurotoxicity (FACT-NTX) score. The incidence of early and persistent CIPN was compared between cryotherapy and control groups. Thirty-eight patients were examined for both early and persistent CIPN. The median time from completion of the weekly paclitaxel-based chemotherapy to the questionnaire for persistent CIPN was 2.3 (1.3–3.1) years. In all 38 patients, persistent CIPN was demonstrated in 10 (26.3%), respectively. There was a numerical, however not significant, reduction in the incidence of persistent CIPN (15.8% vs 36.8%, Chemotherapy-induced peripheral neuropathy (CIPN) is a serious adverse event that significantly deteriorates the quality of life and survivorship.For patients with paclitaxel-induced persistent CIPN, there is weak evidence for treatment to relieve the symptoms. Duloxetine is the only recommended treatment for symptomatic CIPN, however, duloxetine may be less effective for taxane-induced than oxaliplatin-induced CIPN.Compared with the treatment of persistent CIPN, physical therapy, prevention of CIPN with cryotherapy, compression therapy and exercise may be more effective modalities in patients receiving neurotoxic chemotherapy. Cryotherapy and compression therapy are thought to prevent acute CIPN by reducing paclitaxel exposure in fingertip and toes through their analogous mechanism of compression or vasoconstriction.The study aims to assess the preventive effect of cryotherapy on persistent CIPN at more than 1 year after completing weekly paclitaxel-based chemotherapy. We conducted a cross-sectional study as an ancillary analysis of the previous trial that assessed the preventive effect of cryotherapy on paclitaxel-induced early CIPN in breast cancer patients (UMIN000034966). | PMC10118320 |
2. Materials and Methods | PMC10118320 | |||
2.1. Study design and participants | CIPN, breast cancer | BREAST CANCER | This cross-sectional study was conducted performed as adjunct to a randomized trial evaluating the preventive effect of cryotherapy on weekly paclitaxel-induced CIPN in breast cancer patients (UMIN000034966). The original randomized trial detailed information and results are described in a previous report. | PMC10118320 |
2.2. Evaluation of CIPN | CIPN, Cancer | PERIPHERAL NEUROPATHY, CANCER | Eligible patients were assessed for early and persistent CIPN using a questionnaire survey for Functional Assessment of Cancer Therapy-Neurotoxicity (FACT-NTX) score at treatment completion (evaluated as early CIPN) and more than 1 year after treatment completion (evaluated as persistent CIPN). Briefly, FACT-NTX has 11 items assessing CIPN-related symptoms with a total score range from 0 to 44. A lower FACT-NTX score indicates worse peripheral neuropathy. | PMC10118320 |
2.3. Statistical analysis | Groups assessed patient characteristics using a Fisher exact test for categorical variables and a | PMC10118320 | ||
3. Results | PMC10118320 | |||
3.1. Patient characteristics | TNBC, neurotoxic, cancer therapy-neurotoxicity | TRIPLE NEGATIVE BREAST CANCER, RECURRENT BREAST CANCER | Of the 44 patients enrolled in the previous randomized trial, 38 patients met the eligibility criteria. Six patients were exempted from this survey due to the following reasons: having neurotoxic therapy for advanced or recurrent breast cancer,Clinicopathological factors.FACT-NTx = functional assessment of cancer therapy-neurotoxicity, SD = standard deviation, TNBC = triple negative breast cancer.Factors were compared by treatment groups using Fisher exact test for categorical variables and Consort diagram for this survey. | PMC10118320 |
3.2. Effect of cryotherapy on the incidence of persistent CIPN | cancer, CIPN | REGRESSION, CANCER | In all 38 patients, persistent CIPN was demonstrated in 10 (26.3%). The incidence of persistent CIPN was 15.8% and 36.8% in the cryotherapy and control group, respectively, indicating a numerically but not significantly lower incidence of persistent CIPN in the cryotherapy group compared with the control group (A multivariate logistic regression analysis to evaluate the association between clinicopathological factors and the incidence of persistent CIPNCI = confidence interval, CIPN = chemotherapy induced peripheral neuropathy, HR = hazard ratio. A multivariate logistic regression analysis was used to evaluate predictive factor for acute and persistent CIPN.A 6-point or more decrease in the total of FACT-NTX score from baseline is regarded as occurrence of CIPN.The individual FACT-NTX scores at baseline, completion of weekly paclitaxel-based chemotherapy (early CIPN), and more than 1 year after the treatment completion (persistent CIPN) in the (A) control group and (B) cryotherapy groups. CIPN = chemotherapy-induced peripheral neuropathy, FACT-NTX = functional assessment of cancer therapy-neurotoxicity.The other clinicopathological factors were not significant predictors of persistent CIPN. Regarding compliance to cryotherapy, persistent CIPN was recognized in 3 (50%) of 6 patients with incomplete compliance and 3 (23%) of 13 patients with complete compliance, respectively. | PMC10118320 |
4. Discussion | SWOG, breast cancer, Taxane-induced CIPN, neuropathy, CIPN, taxane-induced CIPN, neurotoxic, diabetes | NEUROPATHY, BREAST CANCER, ADVERSE EVENT, REGRESSION, DIABETES | In this ancillary analysis of a previous randomized trial investigating the preventive effect of cryotherapy on weekly paclitaxel-induced CIPN in breast cancer patients, cryotherapy resulted in substantially lower incidence of early CIPN and a numerical decrease in the incidence of persistent CIPN at more than 1 year after treatment completion when compared to control. Age ≥ 65 year was a substantial predictive factor for persistent CIPN in multivariate logistic regression analysis.In early breast cancer patients administered with adjuvant taxane-based chemotherapy, CIPN is a common and prolonged adverse event that can complicate quality of life and increase the risk of falls or functional impairment. Taxane-induced CIPN is commonly recognized during chemotherapy, however, recent studies have reported the presence of persistent CIPN after treatment completion. In a randomized trial of acetyl-L-carnitine for the prevention of taxane-induced CIPN (SWOG S0715), FACT-NTX scores on the placebo and experimental arm stayed decreased during weeks 12, 24, 36, 52, and 104.Risk factors of CIPN occurrence include chemotherapy regimen, age, comorbidities, and preexisting neuropathy. Taxane-containing regimen is well established neurotoxic chemotherapy and paclitaxel is more neurotoxic than docetaxel. Regarding patient factors, age and history of diabetes are risk factors for CIPN.Previous clinical trials assessed the preventive effects of cryotherapy, compression therapy and exercise on CIPN during chemotherapy, but few reported the prevention effect of persistent CIPN with long-term follow-up. In our study, cryotherapy resulted in not only statistically lower incidence of early CIPN but also a numerically lower incidence of persistent CIPN when compared with the control group. It is possible that preventing CIPN during chemotherapy is linked to a lower incidence of persistent CIPN. A retrospective study found that having severe CIPN was a significant risk factor for CIPN duration. | PMC10118320 |
4.1. Study limitations | CIPN | First, the small sample size and unplanned nature of the ancillary analysis without statistical power limit the strength and clinical impact of our findings. Second, the study assessment of persistent CIPN was based on a subjective patient questionnaire. Objective evaluation, such as the Semmes-Weinstein monofilament test, should be integrated to the robustness of our finding. Finally, while the degree of persistent CIPN appears to be fixed over time, additional serial assessments of CIPN on individual cases may strengthen our study findings. | PMC10118320 | |
5. Conclusion | CIPN, breast cancer | BREAST CANCER | In conclusion, we demonstrated that cryotherapy reduced the incidence of persistent CIPN numerically and ≥ age 66 was a risk factor for persistent CIPN in breast cancer patients receiving weekly paclitaxel-based chemotherapy. A prospective randomized trial with a long-term period is needed to confirm the preventive effect of cryotherapy on persistent CIPN. | PMC10118320 |
Abbreviations: | breast cancer, cancer, peripheral neuropathy, Cancer | BREAST CANCER, CANCER, PERIPHERAL NEUROPATHY, CANCER | chemotherapy-induced peripheral neuropathyfunctional assessment of cancer therapy-neurotoxicityThe authors have no funding and conflicts of interest to disclose.This study was endorsed by the Ethics Committee of the National Hospital Organization of Kure Medical Center and Chugoku Cancer Center (Approval number 28–70) and adhered to the Helsinki Declaration and the ethical values for clinical research. All patients received a clarified explanation of the study from the primary physician and informed consent was obtained before enrollment.Informed consent to having de-identified data published was obtained from all individual participants included in the study.The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.All patients received a detailed explanation of the study from the primary physician and informed consent was obtained before enrollment.Trial registration: UMIN000034966.How to cite this article: Shigematsu H, Kimura Y, Itagaki T, Yasui D. Persistent weekly paclitaxel-induced peripheral neuropathy in early breast cancer patients enrolled in a randomized trial of cryotherapy. Medicine 2023;102:16(e33580). | PMC10118320 |
References | PMC10118320 | |||
Background | pectoralis nerve block II, bleeding | BLEEDING | Classic neuraxial techniques, such as thoracic epidural anesthesia, or alternative approaches like the paravertebral block, are not indicated in cardiac surgery due to increased bleeding risk. To provide satisfactory analgesia without the need for excessive opioid use, novel ultrasound techniques gained popularity and are of growing interest. The pectoralis nerve block II (PECS II) has been shown to provide good postoperative analgesia in modified radical mastectomy and might also be suitable for minimally invasive cardiac surgery. | PMC10476350 |
Methods | In a single center, prospective, triple-blinded, two-group randomized trial, 60 patients undergoing elective, unilateral minimal invasive cardiac surgery will be randomized to receive a PECS II with 30 ml of ropivacaine 0.5% (intervention group) or sodium chloride 0.9% (placebo group). The primary outcome parameter is the overall opioid demand given as intravenous morphine milligram equivalents (MME) during the first 24 h after extubation. Secondary endpoints are the visual analog scale (VAS) 2, 4, 6, 8, 12, and 24 h after extubation, the Overall Benefit of Analgesia Score (OBAS) after 24 h, the interval until extubation, and intensive care unit (ICU) discharge within 24 h, as well as the length of hospital stay (LOS). | PMC10476350 | ||
Discussion | postoperative pain | This prospective randomized, controlled, and triple-blinded trial aims to assess if a PECS II with ropivacaine 0.5% helps to decrease the opioid demand in the first 24 h and increases postoperative pain control after minimally invasive cardiac surgery. | PMC10476350 | |
Keywords | PMC10476350 | |||
Administrative information | InnsbruckInnrain, AustriaJohannes |
Elisabeth HoernerDepartment of Anaesthesiology and Intensive Care Medicine, Medical University of Innsbruck, Anichstrasse 35, 6020 AustriaOttokar StundnerDepartment of Anaesthesiology and Intensive Care Medicine, Medical University of Innsbruck, Anichstrasse 35, 6020 AustriaFelix Naegele (corresponding author)Department of Cardiac Surgery, Medical University of Innsbruck, Anichstrasse 35, 6020 AustriaAnna FialaDepartment of Anaesthesiology and Intensive Care Medicine, Medical University of Innsbruck, Anichstrasse 35, 6020 AustriaNikolaos BonarosDepartment of Cardiac Surgery, Medical University of Innsbruck, Anichstrasse 35, 6020 AustriaJohannes HolfeldDepartment of Cardiac Surgery, Medical University of Innsbruck, Anichstrasse 35, 6020 AustriaPeter MairDepartment of Anaesthesiology and Intensive Care Medicine, Medical University of Innsbruck, Anichstrasse 35, 6020 AustriaLukas GasteigerDepartment of Anaesthesiology and Intensive Care Medicine, Medical University of Innsbruck, Anichstrasse 35, 6020 AustriaMedical University of InnsbruckInnrain 52, Christoph-Probst-Platz 1,6020 Innsbruck, AustriaContact: mui-sponsor@i-med.ac | PMC10476350 | |
Introduction | PMC10476350 | |||
Background and rationale {6a} | pain | MINOR, COMPLICATION | A multidisciplinary approach in perioperative care is crucial for improving patient recovery after major surgery. The so-called Enhanced Recovery After Surgery (ERAS) is an evidence-based protocol ranging from preoperative patient optimization to intra- and postoperative strategies aiming to improve clinical outcomes and reduce hospital stays. With the introduction of minimally invasive cardiac surgery (MICS) through two or three small thoracotomies, ERAS strategies gained popularity, and recently, ERAS guidelines for cardiac surgery have been presented, emphasizing that critical factors that keep patients hospitalized after major cardiac surgery are among others, perioperative pain, prolonged mechanical ventilation, and immobilization [Apart from less invasive surgical techniques, implementing a multimodal concept for pain therapy, including regional anesthesia, is an essential element of ERAS pathways [Ultrasound-guided, interfacial plane blocks represent a relatively new route of transmitting local anesthetics to the space between two fascial layers to provide the blockade of nerves traveling within this plane, leading to analgesia of the chest or abdominal wall. These blocks have already been shown to be relatively easy to perform and to have low complication risks [The pectoral nerves (PECS) II block was initially introduced in 2012 as an extension of the PECS I block (injection of local anesthetic between the pectoralis major and pectoralis minor muscles), involving a second injection in the fascial plane between pectoralis minor and serratus anterior muscles [Therefore, this prospective, triple-blinded, randomized trial aims to evaluate the efficacy of the PECS II block in patients undergoing unilateral MICS. | PMC10476350 |
Objectives {7} | SECONDARY | The primary objective of this trial is to evaluate the efficacy of the PECS II block in patients undergoing unilateral MICS expressed as the reduction in the overall opioid demand given as intravenous MME during the first 24 h after extubation.The secondary objective of this trial is to evaluate the effect of the PECS II block in patients undergoing unilateral MICS on the interval until extubation, ICU discharge, data on ICU, length of hospital stay (LOS), the visual analog scale (VAS) at 2, 4, 6, 12, and 24 h after extubation, and the Overall Benefit of Analgesia Score (OBAS) at 24 h after extubation [ | PMC10476350 | |
Trial design {8} | This is an investigator-initiated single-center prospective, triple-blinded, two-group, randomized trial with two treatment groups. | PMC10476350 | ||
Methods: participants, interventions, and outcomes | PMC10476350 |
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