Retrospective evaluation of Penguin Cold Caps for chemotherapy-induced alopecia.

BACKGROUND: Scalp cooling is an increasingly recognized non-pharmacologic approach to minimize chemotherapy-induced alopecia (CIA). Several commercially available machine-based and manual scalp cooling systems are available; however, literature reports of effectiveness are highly variable. The purpose of this study was to determine real-world tolerability and subjective effectiveness of a manual cold capping system in minimizing CIA across a variety of patient race and hair types. This study was a single-institution review of outcomes from manual cold capping. METHODS: We identified retrospective cohort of adult patients who presented to discuss cold capping between January 14, 2019, and March 31, 2022. Data collected from medical records included demographics, decision to pursue/continue cold capping, diagnoses, chemotherapy regimens, hair characteristics (length, thickness, coarseness, type), and subjective perception of percentage of hair retained. Those with successful vs. unsuccessful cold capping (≥ 50% vs. < 50% of hair retained) were compared based on the patient-level factors of interest. FINDINGS: A total of 100 patients initiated cold capping during the study period, and 95% of them completed cold capping. The majority of patients who started cold capping completed it. The median-reported percentage of hair maintained was 75%, and 82/89 (92.1% of patients) had favorable results, defined as ≥ 50% of hair retained. The only patient-level factor associated with favorable response was chemotherapy regimen, with fewer patients receiving doxorubicin-containing regimens having successful hair retention compared to other chemotherapy types (71.4% successful results vs. 95.7% for those receiving paclitaxel-containing regimens and 96.6% for those receiving docetaxel-containing regimens (p = 0.018). There was no difference in success based on patient race/ethnicity or hair characteristics. INTERPRETATION: The overall effectiveness (92.1%) in this study is consistent to higher than many literature reports. One possible reason for the high success in our cohort is compliance with cold capping protocols, meaning applying the cap in the appropriate manner and wearing the cap for the prescribed durations, which may impact effectiveness.

Impact of a Hyperkalemia Protocol Tailored to Glucose Concentration and Renal Function on Insulin-Induced Hypoglycemia in Patients with Low Pretreatment Glucose.

BACKGROUND: Hyperkalemia is a common electrolyte abnormality that requires urgent treatment. Insulin is an effective treatment for hyperkalemia, but risk factors for developing insulin-induced hypoglycemia exist (e.g., low pretreatment glucose or renal impairment). OBJECTIVE: This study evaluated the impact of a hyperkalemia protocol tailored to glucose concentration and renal function on insulin-induced hypoglycemia. METHODS: This was a retrospective cohort study of emergency department patients with glucose ≤ 100 mg/dL treated with insulin for hyperkalemia. The primary outcome was incidence of hypoglycemia in patients treated prior to (July 1, 2018-June 30, 2019) vs. after (January 1, 2020-December 31, 2020) the protocol update, which individualized insulin and dextrose doses by glucose concentration and renal function. Secondary outcomes included change in potassium and protocol safety. We assessed factors associated with hypoglycemia using multiple logistic regression. RESULTS: We included 202 total patients (preimplementation: 114, postimplementation: 88). Initial insulin dose was lower in the postimplementation group (p < 0.001). We found a nonsignificant reduction in hypoglycemia in the postimplementation group (42.1% vs. 30.7%, p = 0.10). Degree of potassium reduction was similar in patients who received insulin 5 units vs. 10 units (p = 0.72). Higher pretreatment glucose (log odds ratio [OR] -0.05, 95% confidence interval [CI] -0.08 to -0.02) and additional insulin administration (log OR -1.55, 95% CI -3.01 to -0.25) were associated with reduced risk of developing hypoglycemia. CONCLUSION: A hyperkalemia protocol update was not associated with a significant reduction in hypoglycemia, and the incidence of hypoglycemia remained higher than anticipated. Future studies attempting to optimize treatment in this high-risk population are warranted.

Four-factor prothrombin complex concentrate for the reversal of factor Xa inhibitors for traumatic intracranial hemorrhage.

OBJECTIVE: The objective of this study was to determine the effectiveness and safety of four-factor prothrombin complex concentrate (4F-PCC) for the reversal of factor Xa inhibitors in patients with traumatic intracranial hemorrhage (ICH). METHODS: This was a retrospective cohort study of patients taking factor Xa inhibitors with traumatic ICH between March 1, 2015 and August 31, 2017 at two trauma centers. The primary outcome was in-hospital mortality in patients who received 4F-PCC (4F-PCC group) compared to those who did not (no reversal group). Secondary outcomes included functional recovery, hospital and intensive care unit (ICU) length of stay (LOS), and thromboembolic complications. RESULTS: There were 62 patients included in the study. Injury Severity Score (ISS) was significantly higher in the 4F-PCC group (17.6 vs. 12.1, p = 0.019). The 4F-PCC group had a significantly higher mortality (22.9% vs. 3.7%, p = 0.034) and longer ICU LOS (2.5 vs. 1.4 days, p = 0.0024). The no reversal group had a significantly higher incidence of ischemic stroke/transient ischemic attack (TIA) (0% vs. 14.8%, p = 0.019). After controlling for ISS, there was no significant difference in mortality (p = 0.20), ICU LOS (p = 0.64), or ischemic stroke/TIA (p = 0.94). There was no difference in hospital LOS, discharge disposition, final Activity Measure for Post Acute Care daily activity score, VTE, or MI. CONCLUSION: Patients with a higher ISS received 4F-PCC preferentially, which led to an apparent mortality benefit the no reversal group. After adjusting for baseline differences between groups, there was no difference in mortality, functional recovery, hospital and ICU LOS, or thromboembolic complications.

Documentation of International Classification of Headache Disorders Criteria in Patient Medical Records: A Retrospective Cohort Analysis.

OBJECTIVE: To determine headache diagnosis and treatment patterns in the outpatient setting, focusing on documentation of the International Classification of Headache Disorders (ICHD) criteria. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort data were collected from electronic medical records of adults aged 18-35 who presented to resident-staffed family medicine outpatient clinics in the Midwest, USA, for a new or worsening headache between 2015 and 2016. Diagnosis codes were used to summarize the overall nature and prevalence of headaches. A random subset of 30 patients each for migraine headache (MGH) with and without aura and tension-type headache (TTH) were reviewed to determine how many of the five possible ICHD criteria were documented. Demographics/clinical characteristics, ICHD criteria, number and type of medications, and healthcare utilization (imaging, primary and emergency department care) through one year following the initial visit were summarized and compared across headache types. RESULTS: There were 716 unique patients during the study period (414 MGH, 227 unspecified headaches, 75 TTH, or others). Complete ICHD criteria were documented for two patients in total. There was partial documentation (e.g., one to four of the possible five) for 30% of TTH, 63% of MGH without aura, and 77% of MGH with aura (p<0.05). Across headache types, patients were prescribed an average of 2.3 to 3.3 medications over one year, with MGH patients generally trying more medications (up to eight for those with aura and up to 12 for those without). Abortive or rescue medications were prescribed to nearly all patients; prophylactics were prescribed for 50% of MGH with aura, 66.7% of MGH without aura, and 53.3%. Non-pharmacologic interventions were less prescribed: 33.3% of TTH patients and 3.3% of MGH types combined (p<0.05). Healthcare utilization was highest for MGH with aura (ED visits) and without aura (clinic visits) patients compared to TTH (p<0.001). CONCLUSION: Headache-related documentation is often incomplete, which may limit interpretation and associations between diagnoses, prescribing patterns, and healthcare utilization. Future studies should evaluate the use of electronic medical records (EMR)-based templates to improve documentation, and additional detailed studies are needed in the local setting to determine whether treatment, including the use of non-pharmacologic and prophylactic methods of treatment, is optimal.

Survey of Buprenorphine Low-dose Regimens Used by Healthcare Institutions.

BACKGROUND: Buprenorphine microdosing ("low-dosing") allows for initiation of buprenorphine without requiring patients to endure withdrawal. Case studies suggest its favorable utility as an alternative to conventional buprenorphine induction. However, published regimens vary in duration, dosage forms used, and timing of full opioid agonist discontinuation. METHODS: This cross-sectional survey study sought to determine how buprenorphine low-dosing is approached by medical institutions across the United States. The primary end point was characterization of inpatient buprenorphine low-dosing regimens. Situations and types of patients in which low-dosing is used and obstacles to institutional protocol development were also collected. An online survey was disseminated through professional pharmacy organizations and personal contacts. Responses were collected over 4 weeks. RESULTS: Twenty-three unique protocols were collected from 25 institutions. Most protocols used buccal (8 protocols) or transdermal (8 protocols) buprenorphine as first doses before transitioning to sublingual buprenorphine. The most common starting doses were buprenorphine 20 µg/h transdermal, 150 µg buccal, and 0.5 mg sublingual. Patients unable to tolerate conventional buprenorphine induction or those who potentially used fentanyl nonmedically were most likely to be prescribed low-dosing. The most common obstacle to developing an internal low-dosing protocol was lack of existing consensus guidelines. CONCLUSIONS: Similar to published regimens, internal protocols are variable. Buccal first doses may be used more commonly in practice based on survey results, while transdermal first doses are more commonly reported in publications. More research is needed to determine whether differences in starting formulations impact safety and efficacy of buprenorphine low-dosing in the inpatient setting.

A tranquil virtual reality experience to reduce subjective stress among COVID-19 frontline healthcare workers.

OBJECTIVE: The novel coronavirus-19 (COVID-19) has taken an immense physical, social, and emotional toll on frontline healthcare workers. Research has documented higher levels of anxiety, depression, and burnout among healthcare workers during the pandemic. Thus, creative interventions are needed now more than ever to provide brief, accessible support to frontline workers. Virtual reality is a rapidly growing technology with potential psychological applications. In this study, we piloted a three-minute Tranquil Cinematic-VR simulation of a nature scene to lower subjective stress among frontline healthcare workers in COVID-19 treatment units. We chose to film a nature scene because of the extensive empirical literature documenting the benefits of nature exposure and health. METHODS: A convenience sample of frontline healthcare workers, including direct care providers, indirect care providers, and support or administrative services, were recruited from three COVID-19 units located in the United States. Inclusion criteria for participation included adults aged 18 years and older who could read and speak in English and were currently employed by the healthcare system. Participants viewed a 360-degree video capture of a lush, green nature preserve in an Oculus Go or Pico G2 4K head-mounted display. Prior to viewing the simulation, participants completed a brief demographic questionnaire and the visual analogue scale to rate their subjective stress on a 10-point scale, with 1 = 'Not at all stressed' to 10 = 'Extremely stressed.' We conducted paired t-tests to examine pre- and post-simulation changes in subjective stress as well as Kruskal-Wallis tests and Mann-Whitney U tests to examine differences by demographic variables. All analyses were conducted in SPSS statistical software version 28.0. We defined statistical significance as a p-value less than .05. RESULTS: A total of 102 individuals consented to participate in the study. Eighty-four (82.4%) participants reported providing direct patient care, 73 (71.6%) identified as women, 49 (48.0%) were between the ages of 25-34 years old, and 35 (34.3%) had prior experience with VR. The pre-simulation mean stress score was 5.5±2.2, with a range of 1 to 10. Thirty-three (32.4%) participants met the 6.8 cutoff for high stress pre-simulation. Pre-simulation stress scores did not differ by any demographic variables. Post-simulation, we observed a significant reduction in subjective stress scores from pre- to post-simulation (mean change = -2.2±1.7, t = 12.749, p < .001), with a Cohen's d of 1.08, indicating a very large effect. Further, only four (3.9%) participants met the cutoff for high stress after the simulation. Post-simulations scores did not differ by provider type, age range, gender, or prior experience with virtual reality. CONCLUSIONS: Findings from this pilot study suggest that the application of this Tranquil Cinematic-VR simulation was effective in reducing subjective stress among frontline healthcare workers in the short-term. More research is needed to compare the Tranquil Cinematic-VR simulation to a control condition and assess subjective and objective measures of stress over time.

Safety and efficacy of thromboelastography guidance of antifibrinolytic therapy in trauma patients: An observational cohort analysis.

BACKGROUND: Tranexamic acid (TXA) is an antifibrinolytic therapy intended to decrease blood loss and improve hemostasis in traumatic hemorrhage. Viscoelastic assays, such as thromboelastography (TEG), allow for the identification of a patient's specific hemostasis. The purpose of this research study was to explore the safety and efficacy of TEG-guided antifibrinolytic therapy in trauma patients. METHODS: This study was a retrospective review of trauma patients meeting institution-specific inclusion criteria for TXA. Patients were assigned to fibrinolytic groups per TEG LY30 data. Safety outcomes (24-h mortality, overall in-hospital mortality, and thromboembolic events) were compared between patients who did or did not receive TXA and within fibrinolytic groups. Mortality outcomes were adjusted for baseline Injury Severity Score (ISS). Secondary aims included blood product utilization, length of hospital, and intensive care unit stay. RESULTS: Hypofibrinolysis was the most common fibrinolytic phenotype. Adjusting for ISS, there were no significant differences in mortality. A 30.7% thromboembolism incidence was identified in the TXA group compared to 16.6% not receiving TXA (P = 0.26), with 72.7% of these patients experiencing fibrinolytic shutdown. CONCLUSIONS: There were no differences in 24-h mortality, all-cause mortality, or secondary outcomes. The difference in thromboembolic rates between patients receiving TXA and those who did not, while not statistically significant, poses clinical concern.

Combined administration of platelet rich plasma and autologous bone marrow aspirate concentrate for spinal cord injury: a descriptive case series.

Administration of platelet rich plasma (PRP) and bone marrow aspirate concentrate (BMAC) has shown some promise in the treatment of neurological conditions; however, there is limited information on combined administration. As such, the purpose of this study was to assess safety and functional outcomes for patients administered combined autologous PRP and BMAC for spinal cord injury (SCI). This retrospective case series included seven patients who received combined treatment of autologous PRP and BMAC via intravenous and intrathecal administration as salvage therapy for SCI. Patients were reviewed for adverse reactions and clinical outcomes using the Oswestry Disability Index (ODI) for up to 1 year, as permitted by availability of follow-up data. Injury levels ranged from C3 through T11, and elapsed time between injury and salvage therapy ranged from 2.4 months to 6.2 years. Post-procedure complications were mild and rare, consisting only of self-limited headache and subjective memory impairment in one patient. Four patients experienced severe disability prior to PRP combined with BMAC injection, as evidenced by high (> 48/100) Oswestry Disability Index scores. Longitudinal Oswestry Disability Index scores for two patients with incomplete SCI at C6 and C7, both of whom had cervical spine injuries, demonstrated a decrease of 28-40% following salvage therapy, representing an improvement from severe to minimal disability. In conclusion, intrathecal/intravenous co-administration of PRP and BMAC resulted in no significant complications and may have had some clinical benefits. Larger clinical studies are needed to further test this method of treatment for patients with SCI who otherwise have limited meaningful treatment options. This study was reviewed and approved by the OhioHealth Institutional Review Board (IRB No. 1204946) on May 16, 2018.

A Comparison of Complications and Reoperations Between Open Reduction and Internal Fixation Versus Primary Arthrodesis Following Lisfranc Injury.

There is a lack of consensus in the literature regarding optimal treatment methods for Lisfranc injuries, and recent literature has emphasized the need to compare open reduction and internal fixation (ORIF) with primary arthrodesis (PA). The purpose of the current study is to compare reoperation and complication rates between ORIF and PA following Lisfranc injury in a private, outpatient, orthopaedic practice. A retrospective chart review was performed on patients undergoing operative intervention for Lisfranc injury between January 2009 and September 2015. A total of 196 patients met the inclusion criteria (130 ORIF, 66 PA), with a mean follow-up of 61.3 and 81.7 weeks, respectively. The ORIF group had a higher reoperation rate than the PA group, due to hardware removal. When hardware removals were excluded, the reoperation rate was similar. Postsurgical complications were compared between the 2 groups with no significant difference. In conclusion, ORIF and PA had similar complication rates. When hardware removals were excluded, the reoperation rates were similar, although hardware removals were more common in the ORIF group compared with the PA group.Levels of Evidence: Level III.

Enoxaparin Dosing for Venous Thromboembolism Prophylaxis in Low Body Weight Patients.

BACKGROUND: The appropriate dose of enoxaparin for venous thromboembolism (VTE) prophylaxis in low body weight patients is unknown. OBJECTIVE: The aim of this study is to evaluate the impact of enoxaparin dosing on major and minor bleeding events in low body weight patients. METHODS: This was a retrospective cohort study of patients weighing less than 45 kg receiving subcutaneous (SC) enoxaparin for VTE prevention. The primary objective was to determine whether enoxaparin dose was associated with major and minor bleeding. The secondary objective was to determine the incidence of VTE by enoxaparin dose. RESULTS: There were 173 patients included in the study, of which 37 patients received 2 different courses of enoxaparin during hospitalization, resulting in 210 enoxaparin courses. Among all enoxaparin courses, 16.2% were associated with major bleeding and 5.2% with minor bleeding. There was no difference in the incidence of major bleeding by dose (enoxaparin 30 mg SC daily, 30 mg SC twice daily, or 40 mg SC daily; P = .409). Patients who experienced major bleeding were older (54.9 ± 16.1 years) than patients who did not (48.4 ± 18.4 years) (P = .043). There was no difference in the incidence of minor bleeding by dosing schedule (P = .14). No patients experienced a VTE. CONCLUSION AND RELEVANCE: The risk of bleeding was similar by enoxaparin dose but increased with age in low body weight patients. Given the low incidence of VTE in this study, it is reasonable to consider decreasing the prophylactic enoxaparin dose in low body weight patients, especially in the elderly population.

Prenatal kynurenine exposure in rats: age-dependent changes in NMDA receptor expression and conditioned fear responding.

RATIONALE: Levels of kynurenic acid (KYNA), an endogenous negative modulator of alpha 7 nicotinic acetylcholine receptors (α7nAChRs) and antagonist at glutamatergic N-methyl-D-aspartate receptors (NMDARs), are elevated in the brain of patients with schizophrenia (SZ). In rats, dietary exposure to KYNA's immediate precursor kynurenine during the last week of gestation produces neurochemical and cognitive deficits in adulthood that resemble those seen in patients with SZ. OBJECTIVES: The present experiments examined whether prenatal kynurenine exposure results in age-dependent changes in the kynurenine pathway (KP), expression of selected receptors, and cognitive function. METHODS: Pregnant dams were fed unadulterated mash (progeny = ECON) or mash containing kynurenine (100 mg/day; progeny = EKYN) from embryonic day (ED) 15 to 22. Male offspring were assessed as juveniles, i.e., prior to puberty (postnatal day [PD] 32), or as adults (PD70) for brain KYNA levels, α7nAChR and NMDAR gene expression, and performance on a trace fear conditioning (TFC) task. RESULTS: KYNA levels were comparable between juvenile ECON and EKYN rats, whereas EKYN adults exhibited a ~3-fold increase in brain KYNA relative to ECONs. NR2A expression was persistently reduced (30-40 %) in EKYN rats at both ages. Compared to ECON adults, there was a 50 % reduction in NR1, and a trend toward decreased α7nAChR expression, in adult EKYN rats. Surprisingly, juvenile EKYN rats performed significantly better in the TFC paradigm than controls, whereas adult EKYN animals showed the predicted deficits. CONCLUSIONS: Collectively, our results provide evidence that KP changes in the fetal brain alter neuronal development and cause age-dependent effects on neurochemistry and cognitive performance.

Elevated levels of kynurenic acid during gestation produce neurochemical, morphological, and cognitive deficits in adulthood: implications for schizophrenia.

The levels of kynurenic acid (KYNA), an endogenous negative modulator of alpha7 nicotinic acetylcholine receptors (α7nAChRs), are elevated in the brains of patients with schizophrenia (SZ). We reported that increases of brain KYNA in rats, through dietary exposure to its precursor kynurenine from embryonic day (ED)15 to postnatal day (PD) 21, result in neurochemical and cognitive deficits in adulthood. The present experiments focused on the effects of prenatal exposure to elevated kynurenine on measures of prefrontal excitability known to be impaired in SZ. Pregnant dams were fed a mash containing kynurenine (100 mg/day; progeny = EKYNs) from ED15 until ED22. Controls were fed an unadulterated mash (progeny = ECONs). The dietary loading procedure elevated maternal and fetal plasma kynurenine (2223% and 693% above controls, respectively) and increased fetal KYNA (forebrain; 500% above controls) on ED21. Elevations in forebrain KYNA disappeared after termination of the loading (PD2), but KYNA levels in the prefrontal cortex (PFC) were unexpectedly increased again when measured in adults (PD56-80; 75% above controls). We also observed changes in several markers of prefrontal excitability, including expression of the α7nAChR (22% and 17% reductions at PD2 and PD56-80), expression of mGluR2 (31% and 24% reductions at ED21 and PD56-80), dendritic spine density (11-14% decrease at PD56-80), subsensitive mesolimbic stimulation of glutamate release in PFC, and reversal/extra-dimensional shift deficits in the prefrontally-mediated set-shifting task. These results highlight the deleterious impact of elevated KYNA levels during sensitive periods of early development, which model the pathophysiological and cognitive deficits seen in SZ.

Transient inactivation of the neonatal ventral hippocampus impairs attentional set-shifting behavior: reversal with an α7 nicotinic agonist.

Cognitive deficits represent a core symptom cluster in schizophrenia that are thought to reflect developmental dysregulations within a neural system involving the ventral hippocampus (VH), nucleus accumbens (NAC), and prefrontal cortex (PFC). The present experiments determined the cognitive effects of transiently inactivating VH in rats during a sensitive period of development. Neonatal (postnatal day 7, PD7) and adolescent (PD32) male rats received a single bilateral infusion of saline or tetrodotoxin (TTX) within the VH to transiently inactivate local circuitry and efferent outflow. Rats were tested as adults on an attentional set-shifting task. Performance in this task depends upon the integrity of the PFC and NAC. TTX infusions did not affect the initial acquisition or ability to learn an intra-dimensional shift. However, TTX rats required a greater number of trials than did controls to acquire the first reversal and extra-dimensional shift (ED) stages. These impairments were age and region-specific as rats infused with TTX into the VH at PD32, or into the dorsal hippocampus at PD7, exhibited performance in the task similar to that of controls. Finally, acute systemic administration of the partial α7 nicotinic acetylcholine receptor (nAChR) agonist SSR 180711 (3.0 mg/kg) eliminated the TTX-induced performance deficits. Given that patients with schizophrenia exhibit hippocampal pathophysiology and deficits in the ED stages of set-shifting tasks, our results support the significance of transient hippocampal inactivation as an animal model for studying the cognitive impairments in schizophrenia as well as the pro-cognitive therapeutic potential of α7 nAChR agonists.