The independent and combined impact of moral injury and moral distress on post-traumatic stress disorder symptoms among healthcare workers during the COVID-19 pandemic.

Background: Healthcare workers (HCWs) across the globe have reported symptoms of Post-Traumatic Stress Disorder (PTSD) during the COVID-19 pandemic. Moral Injury (MI) has been associated with PTSD in military populations, but is not well studied in healthcare contexts. Moral Distress (MD), a related concept, may enhance understandings of MI and its relation to PTSD among HCWs. This study examined the independent and combined impact of MI and MD on PTSD symptoms in Canadian HCWs during the pandemic.Methods: HCWs participated in an online survey between February and December 2021, with questions regarding sociodemographics, mental health and trauma history (e.g. MI, MD, PTSD, dissociation, depression, anxiety, stress, childhood adversity). Structural equation modelling was used to analyze the independent and combined impact of MI and MD on PTSD symptoms (including dissociation) among the sample when controlling for sex, age, depression, anxiety, stress, and childhood adversity.Results: A structural equation model independently regressing both MI and MD onto PTSD accounted for 74.4% of the variance in PTSD symptoms. Here, MI was strongly and significantly associated with PTSD symptoms (ß = .412, p < .0001) to a higher degree than MD (ß = .187, p < .0001), after controlling for age, sex, depression, anxiety, stress and childhood adversity. A model regressing a combined MD and MI construct onto PTSD predicted approximately 87% of the variance in PTSD symptoms (r2 = .87, p < .0001), with MD/MI strongly and significantly associated with PTSD (ß = .813, p < .0001), after controlling for age, sex, depression, anxiety, stress, and childhood adversity.Conclusion: Our results support a relation between MI and PTSD among HCWs and suggest that a combined MD and MI construct is most strongly associated with PTSD symptoms. Further research is needed better understand the mechanisms through which MD/MI are associated with PTSD.

MI and MD were each independently associated with PTSD symptoms (including dissociation), when controlling for sex, age, childhood adversity, depression, anxiety and stress.Combining both MI and MD constructs into a single latent variable accounted for the greatest proportion of variance explained in PTSD symptoms among HCWs during the COVID-19 pandemic.Results suggest that expanding the construct of MI to include team and systemic organisational MD may be appropriate in the healthcare context.

Canadian respiratory therapists who considered leaving their clinical position experienced elevated moral distress and adverse psychological and functional outcomes during the COVID-19 pandemic. / Détresse morale et conséquences psychologiques et fonctionnelles négatives chez les thérapeutes respiratoires canadiens ayant envisagé de quitter leur poste clinique pendant la pandémie de COVID-19.

INTRODUCTION: Respiratory therapists (RTs) faced morally distressing situations throughout the COVID-19 pandemic, including working with limited resources and facilitating video calls for families of dying patients. Moral distress is associated with a host of adverse psychological and functional outcomes (e.g. depression, anxiety, symptoms of posttraumatic stress disorder [PTSD] and functional impairment) and consideration of position departure. The purpose of this study was to understand the impact of moral distress and its associated psychological and functional outcomes on consideration to leave a clinical position among Canadian RTs during the COVID-19 pandemic. METHODS: Canadian RTs (N = 213) completed an online survey between February and June 2021. Basic demographic information (e.g. age, sex, gender) and psychometrically validated measures of moral distress, depression, anxiety, stress, PTSD, dissociation, functional impairment, resilience and adverse childhood experiences were collected. RESULTS: One in four RTs reported considering leaving their position. RTs considering leaving reported elevated levels of moral distress and adverse psychological and functional outcomes compared to RTs not considering leaving. Over half (54.5%) of those considering leaving scored above the cut-off for potential diagnosis of PTSD. Previous consideration to leave a position and having left a position in the past each significantly increased the odds of currently considering leaving, along with system-related moral distress and symptoms of PTSD, but the contribution of these latter factors was small. CONCLUSIONS: Canadian RTs considering leaving their position reported elevated levels of distress and adverse psychological and functional outcomes, yet these individual-level factors appear unlikely to be the primary factors underlying RTs' consideration to leave, because their effects were small. Further research is required to identify broader, organizational factors that may contribute to consideration of position departure among Canadian RTs.

The mental health toll of service: an examination of self-reported impacts of public safety personnel careers in a treatment-seeking population.

Introduction: Public safety personnel (PSP), including firefighters, paramedics, and police officers, are exposed to traumatic events as part of their day-to-day jobs. These traumatic events often result in significant stress and increase the likelihood of negative mental health outcomes, including post-traumatic stress disorder (PTSD). The present study sought to develop an in-depth understanding of the lived experiences of PSPs as related to the mental health toll of their service. Through a series of targeted focus groups, Canadian PSP were asked to provide their perspectives on the PTSD-related symptoms that resulted as a by-product of their occupational service. The DSM-5-TR PSTD criteria (A-E) provided a thematic lens to map the self-described symptomatic expression of PSP's lived experiences.Methods: The present study employed a phenomenological focus-group approach with a treatment-seeking inpatient population of PSP. Participants included PSP from a variety of occupational backgrounds. Using semi-structured focus groups, fifty-one participants were interviewed. These focus groups were audio recorded, with consent, and transcribed verbatim. Using an interpretive phenomenological approach, emergent themes within the data were inductively developed, examined, and connected across individual cases.Results: Utilizing the primary criteria of PTSD (Criteria A-E) outlined by the DSM-5-TR, we identified qualitative themes that included exposure to a traumatic event, intrusion symptoms, avoidance symptoms, negative alterations in mood and cognition, and marked alterations in arousal and reactivity.Conclusion: PSP are exposed to extreme stressors as a daily part of their occupation and are at elevated risk of developing mental health difficulties, including PTSD. In the present study, focus groups were conducted with PSP about the mental health toll of their occupations. Their experiences mapped onto the five primary criteria of PTSD, as outlined by the DSM-5-TR. This study provides crucial descriptive information to guide mental health research aims and treatment goals for PSTD in PSP populations.

Repeated exposure to stressful and traumatic events is often a daily occurrence for public safety personnel, actively contributing to an increased risk of development of mental health disorders, including Post-Traumatic Stress Disorder, in this population.Through a series of interviews, the present study examined the subjective experiences of traumatic events in a treatment-seeking population of public safety personnel. Participants' narrative descriptions of their experiences were examined and analysed using the criteria of Post-Traumatic Stress Disorder, as outlined by the Diagnostic and Statistical Manual of Mental Illness-Version V ­ Text Revision, as a thematic lens. Analyses yielded rich descriptive information of the symptomatic expression of criterion-specific themes.The present study offers valuable insights into how a treatment-seeking population of public safety personnel experience their trauma-related symptoms. It also offers an opportunity for both researchers and practitioners to better understand the way public safety personnel may differ from other populations in how they express and understand their experience of Post-Traumatic Stress symptoms.

Coping, Supports and Moral Injury: Spiritual Well-Being and Organizational Support Are Associated with Reduced Moral Injury in Canadian Healthcare Providers during the COVID-19 Pandemic.

Healthcare providers (HCPs) have described the onset of shame- and trust-violation-related moral injuries (MI) throughout the COVID-19 pandemic. Previous research suggests that HCPs may turn to various coping methods and supports, such as spirituality/religiosity, substance use, friends/family or organizational support, to manage workplace stress. It remains unknown, however, if similar coping methods and supports are associated with MI among this population. We explored associations between MI (including the shame and trust-violation presentations individually) and coping methods and supports. Canadian HCPs completed an online survey about their mental health and experiences during the COVID-19 pandemic, including demographic indices (e.g., sex, age, mental health history) and measures of MI, organizational support, social support, spiritual well-being, self-compassion, alcohol use, cannabis use and childhood adversity. Three hierarchical multiple linear regressions were conducted to assess the associations between coping methods/supports and (i) MI, (ii) shame-related MI and (iii) trust-violation-related MI, when controlling for age, mental health history and childhood adversity. One hundred and seventy-six (N = 176) HCPs were included in the data analysis. Spiritual well-being and organizational support were each significantly associated with reduced total MI (p's < 0.001), shame-related MI (p = 0.03 and p = 0.02, respectively) and trust-violation-related MI (p's < 0.001). Notably, comparison of the standardized beta coefficients suggests that the association between trust-violation-related MI and both spiritual well-being and organizational support was more than twice as great as the associations between these variables and shame-related MI, emphasizing the importance of these supports and the trust-violation outcomes particularly. Mental health history (p = 0.02) and self-compassion (p = 0.01) were additionally related to shame-related MI only. Our findings indicate that heightened levels of spiritual well-being and organizational support were associated with reduced MI among HCPs during the COVID-19 pandemic. Rather than placing sole responsibility for mental health outcomes on HCPs individually, organizations can instead play a significant role in mitigating MI among staff by implementing evidence-informed organizational policies and interventions and by considering how supports for spiritual well-being may be implemented into existing models of care where relevant for employees.

Characterizing the mental health and functioning of Canadian respiratory therapists during the COVID-19 pandemic.

Introduction: Healthcare professionals (HCPs) appear to be at increased risk for negative psychological outcomes [e.g. depression, anxiety, post-traumatic stress disorder (PTSD), moral distress] and associated impacts on functioning throughout the COVID-19 pandemic. HCPs working on designated COVID-19 units may be further impacted than their colleagues not on these units given added demands of patient care and risk of contracting COVID-19. Little is known, however, about the mental health and functioning of specific professional groups beyond nurses and physicians, including respiratory therapists (RTs), over the course of the pandemic. Accordingly, the purpose of the present study was to characterize the mental health and functioning of Canadian RTs and compare profiles between RTs working on and off designated COVID-19 units.Methods: Canadian RTs completed an online survey between February and June 2021, including demographic information (e.g. age, sex, gender,) and measures of depression, anxiety, stress, PTSD, moral distress and functional impairment. Descriptive statistics, correlation analyses and between-groups comparisons were conducted to characterize RTs and compare profiles between those on and off COVID-19 units.Results: Two hundred and eighteen (N = 218) RTs participated in this study. The estimated response rate was relatively low (6.2%) Approximately half of the sample endorsed clinically relevant symptoms of depression (52%), anxiety (51%) and stress (54%) and one in three (33%) screened positively for potential PTSD. All symptoms correlated positively with functional impairment (p's < .05). RTs working on COVID-19 units reported significantly greater patient-related moral distress compared to those not on these units (p < .05).Conclusion: Moral distress and symptoms of depression, anxiety, stress and PTSD were prevalent among Canadian RTs and were associated with functional impacts. These results must be interpreted with caution given a low response rate, yet raise concern regarding the long-term impacts of pandemic service among RTs.

Research on RTs' mental health prior to and during the COVID-19 pandemic is scant, especially in comparison to other HCPs.RTs in the present study reported experiencing moral distress and clinically significant symptoms of depression, anxiety and PTSD, with associated functional impairment.One in three RTs screened positive for likely PTSD on the PCL-5.There is a need to provide RTs with adequate mental health supports and to understand the long-term impacts of pandemic service among RTs.

The Hidden Crisis: Understanding Potentially Morally Injurious Events Experienced by Healthcare Providers during COVID-19 in Canada.

BACKGROUND: Healthcare providers (HCPs) may be at elevated risk for moral injury due to increased exposure to potentially morally injurious events (PMIEs) throughout the COVID-19 pandemic. Identifying PMIEs experienced during the COVID-19 pandemic is a critical first step for understanding moral injury in HCPs. Accordingly, the purpose of the present study was to gain a deeper understanding of the work-related PMIEs experienced by HCPs in Canada during the pandemic. METHODS: Canadian HCPs completed an online survey between February and December 2021 about mental health and functioning, including demographics and the Moral Injury Outcome Scale (MIOS). We conducted a qualitative thematic analysis of PMIEs described extemporaneously by HCPs in the open-text field of the MIOS. RESULTS: One-hundred and twenty-four (N = 124) HCPs were included in analysis. Eight PMIE-related themes were identified, comprising patients dying alone; provision of futile care; professional opinion being ignored; witnessing patient harm; bullying, violence and divided opinions; resources and personal protective equipment; increased workload and decreased staffing; and conflicting values. CONCLUSIONS: Understanding broad categories of PMIES experienced by Canadian HCPs during the COVID-19 pandemic provides an opportunity to enhance cultural competency surrounding their experiences which will aid the development of targeted prevention and intervention approaches.

Associations between trauma and substance use among healthcare workers and public safety personnel during the SARS-CoV-2 (COVID-19) pandemic: the mediating roles of dissociation and emotion dysregulation.

BACKGROUND: Given the highly stressful environment surrounding the SARS-CoV-2 pandemic, healthcare workers (HCW) and public safety personnel (PSP) are at an elevated risk for adverse psychological outcomes, including posttraumatic stress disorder (PTSD) and alcohol/substance use problems. As such, the study aimed to identify associations between PTSD severity, related dissociation and emotion dysregulation symptoms, and alcohol/substance use problems among HCWs and PSP. METHODS: A subset of data (N = 498; HCWs = 299; PSP = 199) was extracted from a larger study examining psychological variables among Canadian HCWs and PSP during the pandemic. Structural equation modelling assessed associations between PTSD symptoms and alcohol/substance use-related problems with dissociation and emotion dysregulation as mediators. RESULTS: Among HCWs, dissociation fully mediated the relation between PTSD and alcohol-related problems (indirect effect ß = .133, p = .03) and emotion dysregulation partially mediated the relation between PTSD and substance-related problems (indirect effect ß = .151, p = .046). In PSP, emotion dysregulation fully mediated the relation between PTSD and alcohol-related problems (indirect effects ß = .184, p = .005). For substance-related problems among PSP, neither emotion dysregulation nor dissociation (ps >.05) had any effects. CONCLUSION: To our knowledge, this is the first study examining associations between PTSD severity and alcohol/substance use-related problems via mediating impacts of emotion dysregulation and dissociation among HCWs and PSP during the SARS-CoV-2 pandemic. These findings highlight dissociation and emotion dysregulation as important therapeutic targets for structured interventions aimed at reducing the burden of PTSD and/or SUD among Canadian HCWs or PSP suffering from the adverse mental health impacts of the SARS-CoV-2 pandemic.

Among healthcare workers, dissociation mediated relation between posttraumatic stress disorder (PTSD) severity and alcohol-related problems and emotion dysregulation mediated relation between PTSD severity and substance-related problems.Among public safety personnel, emotion dysregulation mediated relation between PTSD severity and alcohol-related problems. Neither dissociation nor emotion dysregulation mediated relation between PTSD severity and substance-related problems.Results underscore dissociation and emotion dysregulation as potential key therapeutic targets for intervention for healthcare workers and public safety personnel struggling with PTSD and comorbid alcohol/substance use-related problems.

A Qualitative Approach to Understanding Canadian Healthcare Workers' Use of Coping Strategies during the COVID-19 Pandemic.

Throughout the COVID-19 pandemic, healthcare workers (HCWs) have been exposed to highly stressful situations, including increased workloads and exposure to mortality, thus posing a risk for adverse psychological outcomes, including acute stress, moral injury, and depression or anxiety symptoms. Although several reports have sought to identify the types of coping strategies used by HCWs over the course of the pandemic (e.g., physical activity, religion/spirituality, meditation, and alcohol), it remains unclear which factors may influence HCWs' choice of these coping strategies. Accordingly, using a qualitative approach, the purpose of the present study was to gain a deeper understanding of the factors influencing HCWs' choice of coping strategies during the COVID-19 pandemic in Canada. Fifty-one HCWs participated in virtual, semi-structured interviews between February and June 2021. Interview transcripts were analysed through an inductive thematic approach, yielding two primary themes. First, HCWs described an ongoing shift in their approach to coping depending on their mental "bandwidth", ranging from "quick fix" to more "intentional effort" strategies to engage in proactive strategies to improve mental health. Second, many HCWs identified various barriers to desired coping strategies during the pandemic, including the preponderance of pandemic- and other circumstantial-related barriers. The findings from this study offer a unique understanding of the factors influencing HCWs' choice of coping strategies under novel and increased stress. This knowledge will be central to developing appropriate forms of support and resources to equip HCWs throughout and after the pandemic period, and in mitigating the potential adverse mental health impacts of this period of prolonged stress and potential trauma.

Small molecule modulation of the large-conductance calcium-activated potassium channel suppresses salicylate-induced tinnitus in mice.

Tinnitus is the phantom perception of sound that has no external source. A neurological signature of tinnitus, and the frequently associated hyperacusis, is an imbalance between excitatory and inhibitory activity in the central auditory system (CAS), leading to dysregulated network excitability. The large conductance, calcium-activated potassium (BK) channel is a key player in pre- and post-synaptic excitability through its mediation of K+ currents. Changes in BK channel activity are associated with aberrant network activity in sensory regions of the CNS, raising the possibility that BK channel modulation could regulate activity associated with tinnitus and hyperacusis. To test whether BK channel openers are able to suppress biomarkers of drug-induced tinnitus and hyperacusis, the 1,3,4 oxadiazole BMS-191011 was given to young adult CBA mice that had been administered 250 mg/kg sodium salicylate (SS). Systemic treatment with BMS-191011 reduced behavioral manifestations of SS-induced tinnitus, but not hyperacusis, probed via the gap-in-noise startle response method. Systemic BMS-191011 treatment did not influence SS-induced increases in auditory brainstem response functions, but local application at the inferior colliculus did reverse SS-suppressed spontaneous activity, particularly in the frequency region of the tinnitus percept. Thus, action of BMS-191011 in the inferior colliculus may contribute to the reduction in behaviorally measured tinnitus. Together, these findings support the utility of BK channel openers in reducing central auditory processing changes associated with the formation of the tinnitus percept.

Sodium salicylate alters temporal integration measured through increasing stimulus presentation rates.

OBJECTIVE: High doses of sodium salicylate (SS) are known to induce tinnitus, general hyperexcitability in the central auditory system, and to cause mild hearing loss. We used the auditory brainstem response (ABR) to assess the effects of SS on auditory sensitivity and temporal processing in the auditory nerve and brainstem. ABRs were evoked using tone burst stimuli varying in frequency and intensity with presentation rates from 11/s to 81/s. DESIGN: ABRs were recorded and analysed prior to and after SS treatment in each animal, and peak 1 and peak 4 amplitudes and latencies were determined along with minimal response threshold. STUDY SAMPLE: Nine young adult CBA/CaJ mice were used in a longitudinal within-subject design. RESULTS: No measurable effects of presentation rate were found on ABR threshold prior to SS; however, following SS administration increasing stimulus rates lowered ABR thresholds by as much as 10 dB and compressed the peak amplitude by intensity level functions. CONCLUSIONS: These results suggest that SS alters temporal integration and compressive nonlinearity, and that varying the stimulus rate of the ABR may prove to be a useful diagnostic tool in the study of hearing disorders that involve hyperexcitability.

Construction and Evaluation of Rodent-Specific rTMS Coils.

Rodent models of transcranial magnetic stimulation (TMS) play a crucial role in aiding the understanding of the cellular and molecular mechanisms underlying TMS induced plasticity. Rodent-specific TMS have previously been used to deliver focal stimulation at the cost of stimulus intensity (12 mT). Here we describe two novel TMS coils designed to deliver repetitive TMS (rTMS) at greater stimulation intensities whilst maintaining spatial resolution. Two circular coils (8 mm outer diameter) were constructed with either an air or pure iron-core. Peak magnetic field strength for the air and iron-cores were 90 and 120 mT, respectively, with the iron-core coil exhibiting less focality. Coil temperature and magnetic field stability for the two coils undergoing rTMS, were similar at 1 Hz but varied at 10 Hz. Finite element modeling of 10 Hz rTMS with the iron-core in a simplified rat brain model suggests a peak electric field of 85 and 12.7 V/m, within the skull and the brain, respectively. Delivering 10 Hz rTMS to the motor cortex of anaesthetized rats with the iron-core coil significantly increased motor evoked potential amplitudes immediately after stimulation (n = 4). Our results suggest these novel coils generate modest magnetic and electric fields, capable of altering cortical excitability and provide an alternative method to investigate the mechanisms underlying rTMS-induced plasticity in an experimental setting.

Alterations in peripheral and central components of the auditory brainstem response: a neural assay of tinnitus.

Chronic tinnitus, or "ringing of the ears", affects upwards of 15% of the adult population. Identifying a cost-effective and objective measure of tinnitus is needed due to legal concerns and disability issues, as well as for facilitating the effort to assess neural biomarkers. We developed a modified gap-in-noise (GIN) paradigm to assess tinnitus in mice using the auditory brainstem response (ABR). We then compared the commonly used acoustic startle reflex gap-prepulse inhibition (gap-PPI) and the ABR GIN paradigm in young adult CBA/CaJ mice before and after administrating sodium salicylate (SS), which is known to reliably induce a 16 kHz tinnitus percept in rodents. Post-SS, gap-PPI was significantly reduced at 12 and 16 kHz, consistent with previous studies demonstrating a tinnitus-induced gap-PPI reduction in this frequency range. ABR audiograms indicated thresholds were significantly elevated post-SS, also consistent with previous studies. There was a significant increase in the peak 2 (P2) to peak 1 (P1) and peak 4 (P4) to P1 amplitude ratios in the mid-frequency range, along with decreased latency of P4 at higher intensities. For the ABR GIN, peak amplitudes of the response to the second noise burst were calculated as a percentage of the first noise burst response amplitudes to quantify neural gap processing. A significant decrease in this ratio (i.e. recovery) was seen only at 16 kHz for P1, indicating the presence of tinnitus near this frequency. Thus, this study demonstrates that GIN ABRs can be used as an efficient, non-invasive, and objective method of identifying the approximate pitch and presence of tinnitus in a mouse model. This technique has the potential for application in human subjects and also indicates significant, albeit different, deficits in temporal processing in peripheral and brainstem circuits following drug induced tinnitus.

Preventing texting while driving: a statement of the American College of Preventive Medicine.

The American College of Preventive Medicine (ACPM) is providing a set of recommendations designed to reduce the morbidity and mortality associated with distractions due to texting while driving. According to the National Highway Traffic Safety Administration, 12% of all fatal crashes involving at least one distracted driver are estimated to be related to cell phone use while driving. Given the combination of visual, manual, and cognitive distractions posed by texting, this is an issue of major public health concern for communities. Therefore, the ACPM feels it is timely to discuss this issue and provide the following recommendations: 1. Encourage state legislatures to develop and pass legislation banning texting while driving, while simultaneously implementing comprehensive and dedicated law enforcement strategies including penalties for these violations. Legislatures should establish a public awareness campaign regarding the dangers of texting while driving as an integral part of this legislation. 2. Promote further research into the design and evaluation of educational tools regarding texting while driving that can be incorporated into the issuance of driver's licenses. 3. Provide primary care providers with the appropriate tools to educate patients of all ages. 4. Conduct additional studies investigating the risks associated with cell phone usage while driving, particularly texting, with motor vehicle crashes.

Policies to restrict secondhand smoke exposure: American College of Preventive Medicine Position Statement.

Secondhand smoke (SHS) exposure poses serious health risks for all nonsmokers, especially children and pregnant women. SHS is estimated to contribute to heart attacks in nonsmokers and nearly 53,800 deaths in the U.S. annually. A literature review of English-language articles was performed using PubMed, organizational websites, and pertinent review articles. Over the past 25 years, smokefree policies have protected nearly half the U.S. population from the adverse health effects of SHS. Smokefree policies have been shown to improve health outcomes with no consequences to local businesses. As of April 2013, a total of 24 states and 561 municipalities and territories, including the District of Columbia, New York City, Puerto Rico, and the U.S. Virgin Islands, have established laws that require nonhospitality workplaces, restaurants, and bars to be 100% smokefree. Four other states-Florida, Indiana, Louisiana, and Nevada-have smokefree laws that cover restaurants but provide an exemption for stand-alone bars. At least 14 states have no smokefree laws. This paper describes the benefits of policies that reduce SHS and concludes with recommendations for future directions. The American College of Preventive Medicine (ACPM) recommends expanded clean indoor air policies for workplaces, stand-alone bars, restaurants, and multi-use family housing such as apartment buildings. ACPM recommends clean air policies for all university campuses, secondary school campuses, primary schools, child care centers, and city landmarks to further shift social norms and protect the health of children, adolescents, and adults. ACPM recommends closing existing gaps in clean indoor air policies.

Evaluation of the effect of two gadolinium-containing contrast-enhancing agents, gadobutrol and gadoxetate disodium, on colorimetric calcium determinations in serum and plasma.

OBJECTIVE: To determine the extent to which the gadolinium-containing contrast agents, gadobutrol (Gadovist) and gadoxetate disodium (Primovist/Eovist), interfere with the colorimetric measurement of calcium concentrations in serum and plasma. MATERIALS AND METHODS: Gadobutrol and gadoxetate disodium were added in various concentrations to serum and plasma from healthy volunteers; the calcium concentration in these samples was then measured by standard colorimetry methods and atomic absorption. RESULTS: At clinically relevant concentrations, neither gadobutrol nor gadoxetate disodium influenced the results of the calcium measurement in serum or plasma. Only at the highest concentrations tested (50 mM gadobutrol; 25 mM gadoxetate disodium), an effect was seen in some cases. Results were confirmed by atomic absorption spectroscopy as the reference method. CONCLUSIONS: At clinically relevant concentrations, gadobutrol and gadoxetate disodium did not interfere with standard colorimetric methods for calcium determination.

Impact of renal impairment on long-term retention of gadolinium in the rodent skin following the administration of gadolinium-based contrast agents.

OBJECTIVE: Several publications have suggested a possible association between Gd-based contrast agents (GBCAs) and the development of nephrogenic systemic fibrosis, a rare but serious disease. To date, nephrogenic systemic fibrosis has been observed only in patients with severe renal insufficiency.The aim of this study was to determine the impact of a prolonged circulation time of GBCAs caused by reduced renal clearance on the long-term retention of Gd in the skin of rats after administration of different GBCAs. MATERIAL AND METHODS: Renally impaired Han Wistar Rats (5/6-nephrectomized rats) were injected with Omniscan, OptiMARK, Magnevist, or Gadovist. The contrast agents were administered once daily for 5 consecutive days into the tail vein at a dose of 2.5 mmol Gd/kg b.w. Skin biopsies were taken at various time points, and the gadolinium (Gd) concentration was determined by inductive coupled plasma mass spectrometry (ICP-MS) over an observation period of 168 days post injection (p.i.). RESULTS: Differences in the skin Gd concentrations were observed between the 4 investigated GBCAs. For the nonionic linear compounds, Omniscan and OptiMARK, high Gd concentrations were maintained in the skin over the observation period of up to 168 days p.i. For the ionic linear compound, Magnevist, comparatively lower Gd retention in the skin was observed over time. For the macrocyclic compound, Gadovist, the Gd values in the skin were even lower, and significantly lower than Gd values in the skin in Omniscan and OptiMARK treated animals. CONCLUSION: The results of this preclinical study support the use of 5/6-nephrectomized rats as a model for prolonged circulation time of GBCAs as seen in patients with severe renal impairment. Surgically induced severe renal impairment resulted in delayed clearance of the administered GBCAs in the study animals. The highest amount of Gd was observed in the skin after treatment with the nonionic linear GBCAs, whereas the lowest Gd values were observed after treatment with the macrocyclic agent. This suggests that the difference in the Gd values observed in rat skin tissue after treatment with the different GBCAs is caused of a different propensity of the different GBCAs to release Gd in vivo. However, the analytical method used does not distinguish between chelated and unchelated Gd.

Interference of gadolinium-containing contrast-enhancing agents with colorimetric calcium laboratory testing.

OBJECTIVES: The purpose of this study was to evaluate the extent to which various commercially available gadolinium-containing contrast-enhancing (CE) agents can interfere with the measurement of calcium levels by currently used laboratory methods, suggesting (spurious) hypocalcemia or hypercalcemia with a potential risk for the patient. MATERIALS AND METHODS: Serum and plasma from healthy volunteers were spiked with various concentrations of 4 marketed CE agents. The calcium concentration was measured by widely used laboratory methods: the colorimetric systems Cobas Mira and Vitros 950 analyzer. RESULTS: The measurement of calcium in serum and in plasma was not affected by the presence of gadopentetate dimeglumine (Magnevist, Schering AG, Berlin, Germany) or gadobenate dimeglumine (MultiHance, Bracco-Byk Gulden, Constance, Switzerland) in clinically relevant concentrations (up to 5 mM CE agent). Gadodiamide (Omniscan, Amersham Health, Cork, Ireland) and gadoversetamide (OptiMARK, Mallinckrodt, St. Louis, MO) did produce noticeable-and therefore potentially misleading-effects at these concentrations. CONCLUSIONS: The study demonstrates that gadopentetate dimeglumine and gadobenate dimeglumine generate no interference with colorimetric methods for calcium determination, whereas strong interference was shown for gadodiamide and gadoversetamide under clinically relevant conditions.

Transcutaneous electric nerve stimulation: the effect of intensity on local and distal cutaneous blood flow and skin temperature in healthy subjects.

OBJECTIVE: To determine what effect transcutaneous electric nerve stimulation (TENS) intensity has on local and distal cutaneous blood flow and skin temperature. DESIGN: Double-blind conditions. SETTING: University research laboratory. PARTICIPANTS: Forty subjects (20 men, 20 women) randomly assigned to 1 of 4 groups (10 per group): control, above-motor-threshold TENS, below-motor-threshold TENS, or perception-threshold TENS. INTERVENTION: TENS (4Hz, 200micros) was applied over the median nerve of the right forearm for 15 minutes. MAIN OUTCOME MEASURES: Blood flow measured by laser Doppler flowmeter and skin temperature measured by skin thermistor were recorded during TENS and for 15 minutes after it. RESULTS: Significant differences occurred between groups for forearm (P <.0001; repeated-measures analysis of variance) but not fingertip cutaneous blood flow. Post hoc Fisher tests showed a significant increase in forearm blood flow during TENS application in the above-motor-threshold TENS group compared with the other 3 groups. No significant differences between groups for skin temperature data were observed. CONCLUSIONS: The effect of TENS on cutaneous blood flow depends on whether muscle activity is induced. Low-frequency TENS applied above the motor threshold significantly increases local cutaneous blood flow. There were no significant differences between groups for skin temperature.

The lack of hypoalgesic efficacy of H-wave therapy on experimental ischaemic pain.

The hypoalgesic effect of H-wave therapy (HWT) at various frequencies (2-60 Hz) was assessed using a standardised form of the submaximal effort tourniquet technique (SETT). Healthy human volunteers (n = 112; 56 men, 56 women) were required to attend on two occasions; on the first, baseline pain scores were obtained and on the second, 48 h later, subjects were randomly assigned to control, placebo or 1 of 5 H-wave treatment conditions. In the treatment groups 2 self-adhesive electrodes were attached to the ipsilateral Erb's point and just lateral to the spinous processes of C6/C7. H-wave stimulation commenced 10 min prior to pain induction and continued throughout the 12-min duration of the technique. In the placebo group electrodes were attached as normal but leads were connected to a dummy power output. Analysis of variance of the differences in visual analogue scale and McGill Pain Questionnaire scores showed no significant differences in the treatment groups compared to placebo or controls. These results do not provide convincing evidence for any hypoalgesic effects of HWT at the frequency parameters stated on the experimental model of pain used.