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1.
Front Pain Res (Lausanne) ; 5: 1328495, 2024.
Article in English | MEDLINE | ID: mdl-39091382

ABSTRACT

Chronic pain syndromes affect over one-third of the US adult population and often lead to significant disability and a reduced quality of life. Despite their high prevalence, causal links between chronic pain syndromes and anatomic abnormalities are often not apparent. Most current chronic pain treatments provide modest, if any, relief. Thus, there is a pressing need to understand the causal mechanisms implicated in chronic pain as a means to develop more targeted interventions for improvement in clinical outcomes and reduction in morbidity and financial burden. In the present manuscript, we summarize the current literature on treatment for chronic pain, and hypothesize that non-specific chronic back pain (without a clear organic etiology, such as tumors, infections or fractures) is of psychophysiologic origin. Based on this hypothesis, we developed Psychophysiologic Symptom Relief Therapy (PSRT), a novel pain reduction intervention for understanding and treating chronic pain. In this manuscript, we provide the rationale for PSRT, which we have tested in a pilot trial with a subsequent larger randomized trial underway. In the proposed trial, we will evaluate whether non-specific chronic back pain can be treated by addressing the underlying stressors and psychological underpinnings without specific physical interventions.

2.
Resusc Plus ; 19: 100667, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38827271

ABSTRACT

Aim: Whether changes in oxygen metabolism, as measured by oxygen consumption (VO2), carbon dioxide production (VCO2) and the respiratory exchange ratio (RER), are associated with survival after cardiac arrest is poorly understood. In this prospective observational study, we investigated the association between VO2, VCO2, and RER in the initial 12 and 24 h after return of spontaneous circulation (ROSC) and survival to hospital discharge. Methods: Adults with ROSC after cardiac arrest, admitted to the intensive care unit, requiring mechanical ventilation and treated with targeted temperature management were included. VO2 and VCO2 were measured continuously for 24 h after ROSC, using a noninvasive anesthesia monitor. Area under the curve for VO2, VCO2 & RER was calculated using all available values over 12 and 24 h after ROSC. Using logistic regression, we evaluated the relationship between these metabolic variables and survival to hospital discharge. Analyses were adjusted for temperature, vasopressors, and neuromuscular blockade. Results: Sixty four patients were included. Mean age was 64 ± 16 years, and 59% were women. There was no significant association between the area under the curve of VO2 or VCO2 and survival. A higher RER in the initial 12 h was associated with better survival (aOR = 3.97, 95% CI [1.01,15.6], p = 0.048). Survival was lower in those with median RER < 0.7 in the initial 12 h compared with those with a median RER ≥ 0.7 (25% vs 67%, p = 0.011). Conclusion: Higher RER in the initial 12 h was associated with survival after cardiac arrest. The etiology of unusually low RERs in this patient population remains unclear.

3.
Resuscitation ; 198: 110158, 2024 May.
Article in English | MEDLINE | ID: mdl-38428720

ABSTRACT

INTRODUCTION: Thiamine is a key cofactor for aerobic metabolism, previously shown to improve mortality and neurological outcomes in a mouse model of cardiac arrest. We hypothesized that thiamine would decrease lactate and improve outcomes in post-arrest patients. METHODS: Single center, randomized, blinded, placebo-controlled, Phase II trial of thiamine in adults within 4.5 hours of return of spontaneous circulation after out-of-hospital cardiac arrest (OHCA), with coma and lactate ≥ 3 mmol/L. Participants received 500 mg IV thiamine or placebo twice daily for 2 days. Randomization was stratified by lactate > 5 or ≤ 5 mmol/L. The primary outcome of lactate was checked at baseline, 6, 12, and 24 hours, and compared using a linear mixed model to account for repeated measures. Secondary outcomes included SOFA score, pyruvate dehydrogenase, renal injury, neurological outcome, and mortality. RESULTS: Of 93 randomized patients, 76 were enrolled and included in the analysis. There was no difference in lactate over 24 hours (mean difference 0.34 mmol/L (95% CI: -1.82, 2.50), p = 0.43). There was a significant interaction between randomization lactate subgroup and the effect of the intervention on mortality (p = 0.01) such that mortality was higher with thiamine in the lactate > 5 mmol/L group and lower with thiamine in the < 5 mmol/L group. This subgroup difference prompted the Data and Safety Monitoring Board to recommend the study be terminated early. PDH activity increased over 72 hours in the thiamine group. There were no differences in other secondary outcomes. CONCLUSION: In this single-center randomized trial, thiamine did not affect lactate over 24 hours after OHCA.


Subject(s)
Lactic Acid , Out-of-Hospital Cardiac Arrest , Thiamine , Out-of-Hospital Cardiac Arrest/mortality , Out-of-Hospital Cardiac Arrest/therapy , Humans , Thiamine/therapeutic use , Thiamine/administration & dosage , Male , Female , Middle Aged , Aged , Lactic Acid/blood , Cardiopulmonary Resuscitation/methods , Vitamin B Complex/therapeutic use , Vitamin B Complex/administration & dosage , Double-Blind Method
4.
Resuscitation ; 198: 110160, 2024 May.
Article in English | MEDLINE | ID: mdl-38428722

ABSTRACT

INTRODUCTION: Elevated lactate is associated with mortality after cardiac arrest. Thiamine, a cofactor of pyruvate dehydrogenase, is necessary for aerobic metabolism. In a mouse model of cardiac arrest, thiamine improved pyruvate dehydrogenase activity, survival and neurologic outcome. AIM: To determine if thiamine would decrease lactate and increase oxygen consumption after in-hospital cardiac arrest. METHODS: Randomized, double-blind, placebo-controlled phase II trial. Adult patients with arrest within 12 hours, mechanically ventilated, with lactate ≥ 3 mmol/L were included. Randomization was stratified by lactate > 5 or ≤ 5 mmol/L. Thiamine 500 mg or placebo was administered every 12 hours for 3 days. The primary outcome of lactate was checked at baseline, 6, 12, 24, and 48 hours, and compared using a linear mixed model, accounting for repeated measures. Secondary outcomes included oxygen consumption, pyruvate dehydrogenase, and mortality. RESULTS: Enrollments stopped after 36 patients due Data Safety and Monitoring Board concern about potential harm in an unplanned subgroup analysis. There was no overall difference in lactate (mean difference at 48 hours 1.5 mmol/L [95% CI -3.1-6.1], global p = 0.88) or any secondary outcomes. In those with randomization lactate > 5 mmol/L, mortality was 92% (11/12) with thiamine and 67% (8/12) with placebo (p = 0.32). In those with randomization lactate ≤ 5 mmol/L mortality was 17% (1/6) with thiamine and 67% (4/6) with placebo (p = 0.24). There was a significant interaction between randomization lactate and the effect of thiamine on survival (p = 0.03). CONCLUSIONS: In this single center trial thiamine had no overall effect on lactate after in-hospital cardiac arrest.


Subject(s)
Heart Arrest , Thiamine , Humans , Thiamine/therapeutic use , Thiamine/administration & dosage , Male , Double-Blind Method , Female , Middle Aged , Heart Arrest/therapy , Heart Arrest/mortality , Aged , Lactic Acid/blood , Oxygen Consumption/drug effects , Cardiopulmonary Resuscitation/methods , Vitamin B Complex/therapeutic use , Vitamin B Complex/administration & dosage , Pyruvate Dehydrogenase Complex/metabolism
5.
Contemp Clin Trials ; 139: 107486, 2024 04.
Article in English | MEDLINE | ID: mdl-38431131

ABSTRACT

INTRODUCTION: Acute pancreatitis is a common disease which, in its severe form, is associated with significant morbidity and mortality. Currently, there is no specific therapy known to attenuate organ failure in severe pancreatitis and treatment consists primarily of supportive care. Corticosteroids have been shown to be beneficial in disease processes associated with systemic inflammation and could potentially improve outcomes in severe acute pancreatitis. METHODS: The Corticosteroids to Reduce Inflammation in Severe Pancreatitis (CRISP) trial is a multi-centre, double-blind, randomized, placebo-controlled clinical trial that aims to determine the impact of corticosteroids versus placebo on organ injury in patients with severe acute pancreatitis. Patients are randomized to receive 100 mg of hydrocortisone parenterally versus matching placebo every 8 h for 3 days. Clinical and laboratory data are collected at the time of study enrollment, at 24, 48 and 72 h. The primary end-point for the trial is the difference in 72-h change in the Sequential Organ Failure Assessment (SOFA) score between hydrocortisone and placebo groups. Additional key secondary outcomes include ventilator free days and 28-day mortality. DISCUSSION: This study will add to the evidence base in the treatment of severe acute pancreatitis. The results will inform clinical practice and future studies in the field. Trial registration number The trial is registered on clinicaltrials.gov (NCT05160506). It was posted on December 16th, 2021. The study protocol was approved by the Beth Israel Deaconess Medical Center Committee on Clinical Investigation (CCI) (protocol 2021 P-000803).


Subject(s)
COVID-19 , Pancreatitis , Humans , SARS-CoV-2 , Hydrocortisone/therapeutic use , Acute Disease , Prospective Studies , Pancreatitis/drug therapy , Inflammation , Treatment Outcome , Double-Blind Method , Randomized Controlled Trials as Topic , Multicenter Studies as Topic
6.
Crit Care ; 28(1): 41, 2024 02 06.
Article in English | MEDLINE | ID: mdl-38321529

ABSTRACT

BACKGROUND: This is a post hoc analysis of combined cohorts from two previous Phase II clinical trials to assess the effect of thiamine administration on kidney protection and mortality in patients with septic shock. METHODS: Patient-level data from the Thiamine in Septic Shock Trial (NCT01070810) and the Thiamine for Renal Protection in Septic Shock Trial (NCT03550794) were combined in this analysis. The primary outcome for the current study was survival without the receipt of renal replacement therapy (RRT). Analyses were performed on the overall cohort and the thiamine-deficient cohort (thiamine < 8 nmol/L). RESULTS: Totally, 158 patients were included. Overall, thiamine administration was associated with higher odds of being alive and RRT-free (adjusted odds ratio [aOR]: 2.05 [95% confidence interval (CI) 1.08-3.90]) and not needing RRT (aOR: 2.59 [95% CI 1.01-6.62]). In the thiamine-deficient group, thiamine administration was associated with higher odds of being alive and RRT-free (aOR: 8.17 [95% CI 1.79-37.22]) and surviving to hospital discharge (aOR: 6.84 [95% CI 1.54-30.36]). There was a significant effect modification by baseline thiamine deficiency for alive and RRT-free (interaction, p = 0.016) and surviving to hospital discharge (p = 0.019). CONCLUSION: In the combined analysis of two previous randomized trials, thiamine administration was associated with higher odds of being alive and RRT-free at hospital discharge in patients with septic shock. This signal was stronger in patients with thiamine deficiency.


Subject(s)
Sepsis , Shock, Septic , Thiamine Deficiency , Humans , Kidney , Randomized Controlled Trials as Topic , Sepsis/complications , Shock, Septic/drug therapy , Thiamine/therapeutic use , Thiamine Deficiency/complications , Thiamine Deficiency/drug therapy
7.
BMJ Open ; 14(2): e077586, 2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38423765

ABSTRACT

INTRODUCTION: Diabetic ketoacidosis (DKA) is a potentially life-threatening diabetic complication. Despite the high prevalence of DKA and the substantial associated healthcare burden, limited research on strategies to improve outcomes currently exists.Thiamine (vitamin B1) is a cofactor of pyruvate dehydrogenase, which plays a key role in aerobic glucose metabolism. Thiamine deficiency is common in patients with DKA, resulting in a shift to anaerobic metabolism and hyperlactatemia, which can prolong and complicate recovery. Therefore, we hypothesise that thiamine administration will improve aerobic metabolism and lead to faster resolution of acidemia in patients with DKA. METHODS AND ANALYSIS: In this single centre, double-blind, randomised, placebo-controlled, parallel group interventional trial, 100 patients admitted to the hospital with DKA will be randomised to receive either intravenous thiamine (200 mg in 50 mL 0.9% saline) or placebo (0.9% saline identical in appearance and volume) two times per day for 2 days. The primary outcome will be the change in bicarbonate level over 24 hours as compared between the two treatment groups. Additional secondary outcomes include the change over time in anion gap, lactate levels, oxygen consumption by circulating mononuclear cells, intensive care unit and hospital length-of-stay and hospital resource usage when comparing the two study arms. ETHICS AND DISSEMINATION: This trial was approved by the Committee on Clinical Investigations, the institutional review board of Beth Israel Deaconess Medical Center (protocol number 2018P000475). Findings will be disseminated through peer-reviewed publications and professional conference presentations. TRIAL REGISTRATION NUMBER: NCT03717896; clinicaltrials.gov.


Subject(s)
Diabetes Mellitus , Diabetic Ketoacidosis , Humans , Administration, Intravenous , Diabetes Mellitus/drug therapy , Diabetic Ketoacidosis/drug therapy , Double-Blind Method , Prospective Studies , Randomized Controlled Trials as Topic , Saline Solution , Thiamine/therapeutic use , Treatment Outcome
8.
Clin Exp Emerg Med ; 11(2): 205-212, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38286499

ABSTRACT

OBJECTIVE: We hypothesized that the administration of amantadine would increase awakening of comatose patients resuscitated from cardiac arrest. METHODS: We performed a prospective, randomized, controlled pilot trial, randomizing subjects to amantadine 100 mg twice daily or placebo for up to 7 days. The study drug was administered between 72 and 120 hours after resuscitation and patients with absent N20 cortical responses, early cerebral edema, or ongoing malignant electroencephalography patterns were excluded. Our primary outcome was awakening, defined as following two-step commands, within 28 days of cardiac arrest. Secondary outcomes included length of stay, awakening, time to awakening, and neurologic outcome measured by Cerebral Performance Category at hospital discharge. We compared the proportion of subjects awakening and hospital survival using Fisher exact tests and time to awakening and hospital length of stay using Wilcoxon rank sum tests. RESULTS: After 2 years, we stopped the study due to slow enrollment and lapse of funding. We enrolled 14 subjects (12% of goal enrollment), seven in the amantadine group and seven in the placebo group. The proportion of patients who awakened within 28 days after cardiac arrest did not differ between amantadine (n=2, 28.6%) and placebo groups (n=3, 42.9%; P>0.99). There were no differences in secondary outcomes. Study medication was stopped in three subjects (21.4%). Adverse events included a recurrence of seizures (n=2; 14.3%), both of which occurred in the placebo group. CONCLUSION: We could not determine the effect of amantadine on awakening in comatose survivors of cardiac arrest due to small sample size.

9.
Article in English | MEDLINE | ID: mdl-37987121

ABSTRACT

OBJECTIVE: To determine the normal reference interval (RI) for thiamine concentrations in healthy dogs and investigate the prevalence of thiamine deficiency in critically ill dogs with and without sepsis. DESIGN: Prospective, observational, multicenter study, conducted between 2019 and 2021. SETTING: Two veterinary university teaching hospitals. ANIMALS: A total of 109 dogs were enrolled into 3 groups: 40 healthy dogs, 33 dogs with suspected or confirmed sepsis and evidence of tissue hypoperfusion (Doppler blood pressure ≤90 mm Hg or plasma lactate ≥3 mmol/L), and 36 dogs with other critical illnesses and evidence of tissue hypoperfusion. INTERVENTIONS: For each dog, CBC, serum biochemistry, plasma lactate concentration, whole-blood thiamine concentration, blood pressure, vital parameters, Acute Patient Physiologic and Laboratory Evaluation (APPLE)fast score, and clinical outcomes were recorded, alongside basic patient parameters and dietary history. Whole-blood thiamine pyrophosphate (TPP) concentrations were measured using high-performance liquid chromatography. MEASUREMENTS AND MAIN RESULTS: The RI for whole-blood TPP in healthy dogs was 70.9-135.3 µg/L. Median TPP concentrations were significantly lower in septic dogs compared to healthy controls (P = 0.036). No significant difference in median TPP concentrations was found between septic dogs and nonseptic critically ill dogs, or between healthy dogs and nonseptic critically ill dogs. TPP concentrations were below the normal RI in 27.3% of septic dogs, compared to 19.4% of nonseptic critically ill dogs (P = 0.57). No correlations were found between TPP concentrations and lactate concentrations, age, body condition scores, time since last meal, RBC count, serum alanine aminotransferase, APPLEfast scores, or patient outcomes. CONCLUSIONS: TPP concentrations were significantly lower in septic dogs compared to healthy controls, with an absolute thiamine deficiency found in 27.3% of septic dogs. The established TPP RI allows for further investigation of thiamine deficiency in critically ill dogs.


Subject(s)
Dog Diseases , Sepsis , Thiamine Deficiency , Humans , Dogs , Animals , Thiamine , Prospective Studies , Critical Illness , Chromatography, High Pressure Liquid/veterinary , Prevalence , Thiamine Deficiency/epidemiology , Thiamine Deficiency/veterinary , Sepsis/epidemiology , Sepsis/veterinary , Thiamine Pyrophosphate , Lactates , Dog Diseases/epidemiology
12.
Resusc Plus ; 17: 100512, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38076388

ABSTRACT

Guidelines for the management of in-hospital cardiac arrest resuscitation are often drawn from evidence generated in out-of-hospital cardiac arrest populations and applied to the in-hospital setting. Approach to airway management during resuscitation is one example of this phenomenon, with the recommendation to place either a supraglottic airway or endotracheal tube when performing advanced airway management during in-hospital cardiac arrest based mainly in clinical trials conducted in the out-of-hospital setting. The Hospital Airway Resuscitation Trial (HART) is a pragmatic cluster-randomized superiority trial comparing a strategy of first choice supraglottic airway to a strategy of first choice endotracheal intubation during resuscitation from in-hospital cardiac arrest. The design includes a number of innovative elements such as a highly pragmatic design drawing from electronic health records and a novel primary outcome measure for cardiac arrest trials-alive-and-ventilator free days. Many of the topics explored in the design of HART have wide relevance to other trials in in-hospital cardiac arrest populations.

13.
J Pain Res ; 16: 3871-3880, 2023.
Article in English | MEDLINE | ID: mdl-38026456

ABSTRACT

Purpose: Widely used therapeutic approaches, such as cognitive-behavioral and mindfulness-based therapies, can improve pain and functioning in people with chronic back pain, but the magnitude and duration of their effects are limited. Our team developed a novel 12-week program, psychophysiologic symptom relief therapy (PSRT), to substantially reduce or eliminate pain and disability. This study examined whether PSRT helped more patients achieve large-magnitude (≥30%, ≥50%, ≥75%) reductions in back pain-related disability compared to mindfulness-based stress reduction (MBSR) and usual care (UC), and if the beneficial effects of PSRT were explained by reductions in pain-related anxiety following treatment. Patients and Methods: Data from a three-armed randomized controlled trial were used (N=35 adults with chronic back pain). Change scores (baseline to 4-, 8-, 13-, and 26-weeks post-enrollment) were computed for back pain disability (RDQ) and pain-related anxiety (PASS-20). Fisher's exact tests and mediation analyses were conducted. Results: Compared to MBSR and UC, PSRT helped significantly more patients achieve ≥75% reductions in back pain disability at all timepoints and in pain anxiety at all timepoints except 13-weeks. Change in pain anxiety significantly mediated the relationship between treatment group and change in back pain disability from baseline to 26-weeks. Conclusion: PSRT helped more patients achieve substantial reductions in disability than an established treatment (MBSR) and usual care. Findings indicate reduced pain anxiety may be a mechanism by which PSRT confers long-term benefits on disability. Importantly, this work aims to move the field toward more precise and effective treatment for chronic back pain.

14.
Shock ; 60(4): 539-544, 2023 10 01.
Article in English | MEDLINE | ID: mdl-37752082

ABSTRACT

ABSTRACT: Introduction: In this study, we assessed whether changes in oxygen consumption (VO 2 ) and other metabolic parameters could be used as an early warning system for detecting clinical deterioration in mechanically ventilated patients. Methods: This was a prospective cohort study of adult patients requiring mechanical ventilation between February 2016 and March 2019. We looked for changes in VO 2 , carbon dioxide production (VCO 2 ), respiratory quotient (RQ), and end-tidal carbon dioxide (EtCO 2 ), occurring prior to clinical deterioration. Clinical deterioration was predefined as a requirement of vasopressor, an increase in serum lactate by 20% where at least one value was above 3 mmol/L, or a decrease in hemoglobin by 20% in the 4 hours prior to clinical deterioration. Results A total of 141 patients were included. There were no detectable changes in VO 2 , VCO 2 , and EtCO 2 within the 4 hours prior to any clinical deterioration. RQ increased significantly within the 4 hours prior to an increase in lactate as compared with no increase in lactate, but there were no detectable changes prior to other clinical deteriorations. Conclusions RQ has the potential to be an early marker of tissue hypoperfusion or mitochondrial dysfunction. However, future studies are necessary to evaluate the use of RQ as a bedside monitor in critical care settings.


Subject(s)
Clinical Deterioration , Critical Illness , Adult , Humans , Carbon Dioxide/metabolism , Prospective Studies , Respiration, Artificial/methods , Oxygen Consumption , Lactates
15.
Circulation ; 148(12): 982-988, 2023 09 19.
Article in English | MEDLINE | ID: mdl-37584195

ABSTRACT

Targeted temperature management has been a cornerstone of post-cardiac arrest care for patients remaining unresponsive after return of spontaneous circulation since the initial trials in 2002 found that mild therapeutic hypothermia improves neurological outcome. The suggested temperature range expanded in 2015 in response to a large trial finding that outcomes were not better with treatment at 33° C compared with 36° C. In 2021, another large trial was published in which outcomes with temperature control at 33° C were not better than those of patients treated with a strategy of strict normothermia. On the basis of these new data, the International Liaison Committee on Resuscitation and other organizations have altered their treatment recommendations for temperature management after cardiac arrest. The new American Heart Association guidelines on this topic will be introduced in a 2023 focused update. To provide guidance to clinicians while this focused update is forthcoming, the American Heart Association's Emergency Cardiovascular Care Committee convened a writing group to review the TTM2 trial (Hypothermia Versus Normothermia After Out-of-Hospital Cardiac Arrest) in the context of other recent evidence and to present an opinion on how this trial may influence clinical practice. This science advisory was informed by review of the TTM2 trial, consideration of other recent influential studies, and discussion between cardiac arrest experts in the fields of cardiology, critical care, emergency medicine, and neurology. Conclusions presented in this advisory statement do not replace current guidelines but are intended to provide an expert opinion on novel literature that will be incorporated into future guidelines and suggest the opportunity for reassessment of current clinical practice.


Subject(s)
Cardiopulmonary Resuscitation , Hypothermia, Induced , Out-of-Hospital Cardiac Arrest , Humans , Adult , Temperature , American Heart Association , Coma/therapy , Out-of-Hospital Cardiac Arrest/therapy , Survivors
16.
Resuscitation ; 190: 109911, 2023 09.
Article in English | MEDLINE | ID: mdl-37499974

ABSTRACT

AIM: To evaluate the performance of kidney-specific biomarkers (neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and cystatin-C) in early detection of acute kidney injury (AKI) following cardiac arrest (CA) when compared to serum creatinine. METHODS: Adult CA patients who had kidney-specific biomarkers of AKI collected within 12 h of return of spontaneous circulation (ROSC) were included. The association between renal biomarker levels post-ROSC and the development of KDIGO stage III AKI within 7 days of enrollment were assessed as well as their predictive value of future AKI development, neurological outcomes, and survival to discharge. RESULTS: Of 153 patients, 54 (35%) developed stage III AKI within 7 days, and 98 (64%) died prior to hospital discharge. Patients who developed stage III AKI, compared to those who did not, had higher median levels of creatinine, NGAL, and cystatin-C (p < 0.001 for all). There was no statistically significant difference in KIM-1 between groups. No biomarker outperformed creatinine in the ability to predict stage III AKI, neurological outcomes, or survival outcomes (p > 0.05 for all). However, NGAL, cystatin-C, and creatinine all performed better than KIM-1 in their ability to predict AKI development (p < 0.01 for all). CONCLUSION: In post-CA patients, creatinine, NGAL, and cystatin-C (but not KIM-1) measured shortly after ROSC were higher in patients who subsequently developed AKI. No biomarker was statistically superior to creatinine on its own for predicting the development of post-arrest AKI.


Subject(s)
Acute Kidney Injury , Heart Arrest , Adult , Humans , Lipocalin-2 , Creatinine , Kidney , Biomarkers , Acute Kidney Injury/diagnosis , Acute Kidney Injury/etiology , Heart Arrest/complications , Heart Arrest/diagnosis
17.
Am J Respir Crit Care Med ; 208(5): 570-578, 2023 09 01.
Article in English | MEDLINE | ID: mdl-37364280

ABSTRACT

Rationale: Kidney injury is common and associated with worse outcomes in patients with septic shock. Mitochondrial resuscitation with thiamine (vitamin B1) may attenuate septic kidney injury. Objectives: To assess whether thiamine supplementation attenuates kidney injury in septic shock. Methods: The TRPSS (Thiamine for Renal Protection in Septic Shock) trial was a multicenter, randomized, placebo-controlled trial of thiamine versus placebo in septic shock. The primary outcome was change in serum creatinine between enrollment and 72 hours after enrollment. Measurements and Main Results: Eighty-eight patients were enrolled (42 patients received the intervention, and 46 received placebo). There was no significant between-groups difference in creatinine at 72 hours (mean difference, -0.57 mg/dl; 95% confidence interval, -1.18, 0.04; P = 0.07). There was no difference in receipt of kidney replacement therapy (14.3% vs. 21.7%, P = 0.34), acute kidney injury (as defined by stage 3 of the Kidney Disease: Improving Global Outcomes acute kidney injury scale; 54.7% vs. 73.9%, P = 0.07), or mortality (35.7% vs. 54.3%, P = 0.14) between the thiamine and placebo groups. Patients who received thiamine had more ICU-free days (median [interquartile range]: 22.5 [0.0-25.0] vs. 0.0 [0.0-23.0], P < 0.01). In the thiamine-deficient cohort (27.4% of patients), there was no difference in rates of kidney failure (57.1% thiamine vs. 81.5% placebo) or in-hospital mortality (28.6% vs. 68.8%) between groups. Conclusions: In the TRPSS trial, there was no statistically significant difference in the primary outcome of change in creatinine over time. Patients who received thiamine had more ICU-free days, but there was no difference in other secondary outcomes. Clinical trial registered with www.clinicaltrials.gov (NCT03550794).


Subject(s)
Acute Kidney Injury , Shock, Septic , Humans , Thiamine/therapeutic use , Shock, Septic/complications , Shock, Septic/drug therapy , Creatinine , Kidney , Acute Kidney Injury/prevention & control , Acute Kidney Injury/complications
18.
Article in English | MEDLINE | ID: mdl-37361483

ABSTRACT

Objective: To determine if psychophysiologic symptom relief therapy (PSRT) will reduce symptom burden in patients suffering from post-acute sequelae of COVID-19 (PASC) who had mild/moderate acute COVID-19 disease without objective evidence of organ injury. Patients and Methods: Twenty-three adults under the age of 60 with PASC for at least 12 weeks following COVID-19 infection were enrolled in an interventional cohort study conducted via virtual platform between May 18, 2021 and August 7, 2022. Participants received PSRT during a 13 week (approximately 44 hour) course. Participants were administered validated questionnaires at baseline and at 4, 8, and 13 weeks. The primary outcome was change in somatic symptoms from baseline, measured using the Somatic Symptom Scale-8 (SSS-8), at 13 weeks. Results: The median duration of symptoms prior to joining the study was 267 days (IQR: 144, 460). The mean SSS-8 score of the cohort decreased from baseline by 8.5 (95% CI: 5.7-11.4), 9.4 (95% CI: 6.9-11.9), and 10.9 (95% CI: 8.3-13.5) at 4, 8, and 13 weeks respectively (all p<.001). Participants also experienced statistically significant improvements across other secondary outcomes including changes in dyspnea, fatigue, and pain (all p<.001). Conclusion: PSRT may effectively decrease symptom burden in patients suffering from PASC without evidence of organ injury. The study was registered on clinicaltrials.gov (NCT04854772).

19.
J Behav Med ; 46(5): 890-896, 2023 10.
Article in English | MEDLINE | ID: mdl-36892781

ABSTRACT

BACKGROUND: Cardiac arrest (CA) survivors experience continuous exposures to potential traumas though chronic cognitive, physical and emotional sequelae and enduring somatic threats (ESTs) (i.e., recurring somatic traumatic reminders of the event). Sources of ESTs can include the daily sensation of an implantable cardioverter defibrillator (ICD), ICD-delivered shocks, pain from rescue compressions, fatigue, weakness, and changes in physical function. Mindfulness, defined as non-judgmental present-moment awareness, is a teachable skill that might help CA survivors cope with ESTs. Here we describe the severity of ESTs in a sample of long-term CA survivors and explore the cross-sectional relationship between mindfulness and severity of ESTs. METHODS: We analyzed survey data of long-term CA survivors who were members of the Sudden Cardiac Arrest Foundation (collected 10-11/2020). We assessed ESTs using 4 cardiac threat items from the Anxiety Sensitivity Index-revised (items range from 0 "very little" to 4 "very much") which we summed to create a score reflecting total EST burden (range 0-16). We assessed mindfulness using the Cognitive and Affective Mindfulness Scale-Revised. First, we summarized the distribution of EST scores. Second, we used linear regression to describe the relationship between mindfulness and EST severity adjusting for age, gender, time since arrest, COVID-19-related stress, and loss of income due to COVID. RESULTS: We included 145 CA survivors (mean age: 51 years, 52% male, 93.8% white, mean time since arrest: 6 years, 24.1% scored in the upper quarter of EST severity). Greater mindfulness (ß: -30, p = 0.002), older age (ß: -0.30, p = 0.01) and longer time since CA (ß: -0.23, p = 0.005) were associated with lower EST severity. Male sex was also associated with greater EST severity (ß: 0.21, p = 0.009). CONCLUSION: ESTs are common among CA survivors. Mindfulness may be a protective skill that CA survivors use to cope with ESTs. Future psychosocial interventions for the CA population should consider using mindfulness as a core skill to reduce ESTs.


Subject(s)
COVID-19 , Heart Arrest , Mindfulness , Humans , Male , Middle Aged , Female , Heart Arrest/complications , Heart Arrest/therapy , Heart Arrest/psychology , Anxiety/epidemiology , Survivors/psychology
20.
J Am Heart Assoc ; 12(7): e028558, 2023 04 04.
Article in English | MEDLINE | ID: mdl-36942758

ABSTRACT

Background Thiamine supplementation has demonstrated protective effects in a mouse model of cardiac arrest. The aim of this study was to investigate the neuroprotective effects of thiamine in a clinically relevant large animal cardiac arrest model. The hypothesis was that thiamine reduces neurological injury evaluated by neuron-specific enolase levels. Methods and Results Pigs underwent myocardial infarction and subsequently 9 minutes of untreated cardiac arrest. Twenty minutes after successful resuscitation, the pigs were randomized to treatment with either thiamine or placebo. All pigs underwent 40 hours of intensive care and were awakened for assessment of functional neurological outcome up until 9 days after cardiac arrest. Nine pigs were included in both groups, with 8 in each group surviving the entire intensive care phase. Mean area under the curve for neuron-specific enolase was similar between groups, with 81.5 µg/L per hour (SD, 20.4) in the thiamine group and 80.5 µg/L per hour (SD, 18.3) in the placebo group, with an absolute difference of 1.0 (95% CI, -57.8 to 59.8; P=0.97). Likewise, there were no absolute difference in neurological deficit score at the end of the protocol (2 [95% CI, -38 to 42]; P=0.93). There was no absolute mean group difference in lactate during the intensive care period (1.1 mmol/L [95% CI, -0.5 to 2.7]; P=0.16). Conclusions In this randomized, blinded, placebo-controlled trial using a pig cardiac arrest model with myocardial infarction and long intensive care and observation for 9 days, thiamine showed no effect in changes to functional neurological outcome or serum levels of neuron-specific enolase. Thiamine treatment had no effect on lactate levels after successful resuscitation.


Subject(s)
Cardiopulmonary Resuscitation , Heart Arrest , Myocardial Infarction , Animals , Cardiopulmonary Resuscitation/methods , Disease Models, Animal , Heart Arrest/drug therapy , Heart Arrest/etiology , Lactic Acid , Myocardial Infarction/complications , Myocardial Infarction/drug therapy , Phosphopyruvate Hydratase , Swine , Thiamine/pharmacology , Thiamine/therapeutic use
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