Patient-Centric Quality Standards.

To ensure the quality, safety and efficacy of medicinal products, it is necessary to develop and execute appropriate manufacturing process and product control strategies. Traditionally, product control strategies have focused on testing known quality attributes with limits derived from levels administered in preclinical and clinical studies with an associated statistical analysis to account for variability. However, not all quality attributes have impact to the patient and those with the potential to impact safety and efficacy may not be significant when dosed at patient-centric levels. Therefore, achieving patient-centricity is understanding patient relevance, which is defined as the level of impact that a quality attribute could have on safety and efficacy within the potential exposure range. A patient-centric quality standard (PCQS) is therefore a set of patient relevant attributes and their associated acceptance ranges to which a drug product should conform within the expected patient exposure range. This manuscript describes historical perspectives details the way to create and leverage a PCQS in a variety of pharmaceutical product modalities.

The World Neurosurgery Global Champions Program: First-Year Experience of a Model Initiative for Reducing Disparities in Global Neurosurgical Literature.

OBJECTIVE: Most surgical journals are published in English, representing a challenge for researchers from non-Anglophone countries. We describe the implementation, workflow, outcomes, and lessons learned from the WORLD NEUROSURGERY Global Champions Program (GCP), a novel journal-specific English language editing program for articles rejected because of poor English grammar or usage. METHODS: The GCP was advertised via the journal website and social media. Applicants were selected to be a reviewer for the GCP if they demonstrated English proficiency on writing samples supplied in their application. The demographics of GCP members and characteristics and outcomes of articles edited by the GCP during its first year were reviewed. Surveys of GCP members and authors who used the service were conducted. RESULTS: Twenty-one individuals became part of the GCP, representing 8 countries and 16 languages apart from English. A total of 380 manuscripts were peer reviewed by the editor-in-chief, who determined these manuscripts to have potentially worthwhile content but needed to be rejected due to poor language. The authors of these manuscripts were informed of the existence of this language assistance program. Forty-nine articles (12.9%) were edited by the GCP in 41.6 ± 22.8 days. Of 40 articles resubmitted to WORLD NEUROSURGERY, 24 (60.0%) were accepted. GCP members and authors understood the purpose and workflow of the program and recognized improvements in article quality and the probability of acceptance through their participation. CONCLUSIONS: The WORLD NEUROSURGERY Global Champions Program mitigated a critical barrier to publication in an English language journal for authors from non-Anglophone countries. This program promotes research equity by providing a free, largely medical student and trainee operated, English language editing service. This model or a similar service can be replicated by other journals.

Rapid Extraction and Qualitative Screening of 30 Drugs in Oral Fluid at Concentrations Recommended for the Investigation of DUID Cases.

A rapid, simple extraction method followed by qualitative screening using liquid chromatography-tandem mass spectrometry (LC-MS-MS) for drugs in oral fluid is presented. The decision points were selected to be at, or lower, than those recommended as Tier I compounds by the National Safety Council's Alcohol, Drugs and Impairment Division for toxicological investigation of driving under the influence of drug (DUID) cases and were also at, or lower, than those recommended by Substance Abuse and Mental Health Service Administration and the Department of Transportation for Federal workplace drug testing programs. The method included 30 drugs: delta-9-tetrahydrocannabinol, amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxyamphetamine, cocaine, benzoylecgonine, carisoprodol, meprobamate, zolpidem, alprazolam, clonazepam, 7-aminoclonazepam, diazepam, nordiazepam, lorazepam, oxazepam, temazepam, codeine, morphine, 6-acetylmorphine, buprenorphine, fentanyl, hydrocodone, hydromorphone, oxycodone, oxymorphone, methadone, tramadol and phencyclidine. Phencyclidine was included because it is in the Federal workplace program even though it is considered a Tier II drug for DUID cases. A liquid-liquid extraction method using isopropanol, hexane and ethyl acetate to extract drugs from the oral fluid-buffer mix collected in a Quantisal™ device, followed by LC-MS-MS screening, was developed and validated according to ANSI/ASB 2019 Standard Practices for Method Validation in Forensic Toxicology. Interference studies, limit of detection, precision at the decision point, ionization suppression/enhancement and processed sample stability were determined for each drug. The method was successfully applied to proficiency specimens and routine samples received in the laboratory.

Re-Envisioning Pharmaceutical Manufacturing: Increasing Agility for Global Patient Access.

The traditional paradigm for pharmaceutical manufacturing is focused primarily upon centralized facilities that enable mass production and distribution. While this system reliably maintains high product quality and reproducibility, its rigidity imposes limitations upon new manufacturing innovations that could improve efficiency and support supply chain resiliency. Agile manufacturing methodologies, which leverage flexibility through portability and decentralization, allow manufacturers to respond to patient needs on demand and present a potential solution to enable timely access to critical medicines. Agile approaches are particularly applicable to the production of small-batch, personalized therapies, which must be customized for each individual patient close to the point-of-care. However, despite significant progress in the advancement of agile-enabling technologies across several different industries, there are substantial global regulatory challenges that encumber the adoption of agile manufacturing techniques in the pharmaceutical industry. This review provides an overview of regulatory barriers as well as emerging opportunities to facilitate the use of agile manufacturing for the production of pharmaceutical products. Future-oriented approaches for incorporating agile methodologies within the global regulatory framework are also proposed. Collaboration between regulators and manufacturers to cohesively navigate the regulatory waters is ultimately needed to best serve patients in the rapidly-changing healthcare environment.

Upregulation of pERK and c-JUN by γ-tocotrienol and not α-tocopherol are essential to the differential effect on apoptosis in prostate cancer cells.

BACKGROUND: α-tocopherol (AT) and γ-tocotrienol (GT3) are vitamin E isoforms considered to have potential chemopreventive properties. AT has been widely studied in vitro and in clinical trials with mixed results. The latest clinical study (SELECT trial) tested AT in prostate cancer patients, determined that AT provided no benefit, and could promote cancer. Conversely, GT3 has shown antineoplastic properties in several in vitro studies, with no clinical studies published to date. GT3 causes apoptosis via upregulation of the JNK pathway; however, inhibition results in a partial block of cell death. We compared side by side the mechanistic differences in these cells in response to AT and GT3. METHODS: The effects of GT3 and AT were studied on androgen sensitive LNCaP and androgen independent PC-3 prostate cancer cells. Their cytotoxic effects were analyzed via MTT and confirmed by metabolic assays measuring ATP. Cellular pathways were studied by immunoblot. Quantitative analysis and the determination of relationships between cell signaling events were analyzed for both agents tested. Non-cancerous prostate RWPE-1 cells were also included as a control. RESULTS: The RAF/RAS/ERK pathway was significantly activated by GT3 in LNCaP and PC-3 cells but not by AT. This activation is essential for the apoptotic affect by GT3 as demonstrated the complete inhibition of apoptosis by MEK1 inhibitor U0126. Phospho-c-JUN was upregulated by GT3 but not AT. No changes were observed on AKT for either agent, and no release of cytochrome c into the cytoplasm was detected. Caspases 9 and 3 were efficiently activated by GT3 on both cell lines irrespective of androgen sensitivity, but not in cells dosed with AT. Cell viability of non-cancerous RWPE-1 cells was affected neither by GT3 nor AT. CONCLUSIONS: c-JUN is a recognized master regulator of apoptosis as shown previously in prostate cancer. However, the mechanism of action of GT3 in these cells also include a significant activation of ERK which is essential for the apoptotic effect of GT3. The activation of both, ERK and c-JUN, is required for apoptosis and may suggest a relevant step in ensuring circumvention of mechanisms of resistance related to the constitutive activation of MEK1.

Introduction of Group Electronic Monitoring of Hand Hygiene on Inpatient Units: A Multicenter Cluster Randomized Quality Improvement Study.

BACKGROUND: The current approach to measuring hand hygiene (HH) relies on human auditors who capture <1% of HH opportunities and rapidly become recognized by staff, resulting in inflation in performance. Group electronic monitoring is a validated method of measuring HH adherence, but data demonstrating the clinical impact of this technology are lacking. METHODS: A stepped-wedge cluster randomized quality improvement study was performed on 26 inpatient medical and surgical units across 5 acute care hospitals in Ontario, Canada. The intervention involved daily HH reporting as measured by group electronic monitoring to guide unit-led improvement strategies. The primary outcome was monthly HH adherence (percentage) between baseline and intervention. Secondary outcomes included transmission of antibiotic-resistant organisms such as methicillin-resistant Staphylococcus aureus (MRSA) and other healthcare-associated infections. RESULTS: After adjusting for the correlation within inpatient units and hospitals, there was a significant overall improvement in HH adherence associated with the intervention (incidence rate ratio [IRR], 1.73 [95% confidence interval {CI}, 1.47-1.99]; P < .0001). Monthly HH adherence relative to the intervention increased from 29% (1 395 450/4 544 144) to 37% (598 035/1 536 643) within 1 month, followed by consecutive incremental increases up to 53% (804 108/1 515 537) by 10 months (P < .0001). There was a trend toward reduced healthcare-associated transmission of MRSA (IRR, 0.74 [95% CI, .53-1.04]; P = .08). CONCLUSIONS: The introduction of a system for group electronic monitoring led to rapid, significant improvements in HH performance within a 2-year period. This method offers significant advantages over direct observation for measurement and improvement of HH.

Evaluation of a nanoscale zero-valent iron amendment as a potential tool to reduce mobility, toxicity, and bioaccumulation of arsenic and mercury from wetland sediments.

Gold mining in the 1800s has led to the contamination of wetlands with introduced mercury (Hg) and geogenic arsenic (As). In situ risk management tools to reduce mobility and toxicity of Hg and As are needed to support natural restoration of impacted ecosystems. Here, we explored whether a nanoscale zero-valent iron (nZVI) slurry injected into two different contaminated wetland sediments can reduce Hg and As mobility to the overlaying water and toxicity to two aquatic invertebrates, burrowing mayflies (Hexagenia spp.) and Chinese mystery snails (Cipangopaludina chinensis). Total water Hg and As concentrations overlying both contaminated sediments were reduced by at least 75% and 88% respectively when treated with nZVI slurry. In the first sediment, juvenile snail survival increased from 75% in the untreated sediment to 100% in all nZVI treatments. The 2% nZVI treatment level was the only one with surviving mayflies (33%) and growth of juvenile snails. No snails or mayflies survived in the second sediment, regardless of nZVI treatment level. However, snails survived longer in this sediment with 4% and 8% nZVI. To improve reactivity of nZVI without increasing nZVI dose, future studies should investigate matrix-supported nZVI for reducing mobility and toxicity of As and Hg in wetland sediments.

Frequency of hand hygiene opportunities in patients on a general surgery service.

BACKGROUND: Some electronic hand hygiene (HH) monitoring systems require a benchmark of HH opportunities. To establish a benchmark, we measured rates of HH opportunities among general surgery patients at a tertiary care hospital. METHODS: Trained observers recorded HH opportunities for newly admitted patients daily for up to 5 days. We used multivariable logistic regression to assess the relationship between patient variables and the HH opportunity rate. A subset of observed HH events was compared to event data from an electronic HH monitoring system. RESULTS: We observed 2,404 HH opportunities over 677.4 care-hours for 23 patients (median 3.25 per hour; IQR 2.2-4.7, range 0-13). Rates of HH opportunities were significantly higher on admission day 1, for sessions starting before 9 AM, and for patients without roommates. HH was performed using alcohol-based hand rub from dispensers at the door to a patient's room more often than bedside or pocket dispensers (72.7% vs 20.8% or 5.1%). Electronic dispenser event counts did not match observed event counts. CONCLUSIONS: Our results provide a benchmark HH opportunity rate for general surgery patients, and highlight the importance of validating electronic HH event counts. Further research is needed to determine which patient factors affect HH opportunity rates.

Effects of Polyethylene Glycol-20k on Coronary Perfusion Pressure and Postresuscitation Myocardial and Cerebral Function in a Rat Model of Cardiac Arrest.

Background Epinephrine increases the rate of return of spontaneous circulation. However, it increases severity of postresuscitation myocardial and cerebral dysfunction and reduces duration of survival. We investigated the effects of aortic infused polyethylene glycol, 20 000 molecular weight (PEG-20k) during cardiopulmonary resuscitation on coronary perfusion pressure, postresuscitation myocardial and cerebral function, and duration of survival in a rat model of cardiac arrest. Methods and Results Twenty-four male rats were randomized into 4 groups: (1) PEG-20k, (2) epinephrine, (3) saline control-intravenous, and (4) saline control-intra-aortic. Cardiopulmonary resuscitation was initiated after 6 minutes of untreated ventricular fibrillation. In PEG-20k and Saline-A, either PEG-20k (10% weight/volume in 10% estimated blood volume infused over 3 minutes) or saline was administered intra-aortically after 4 minutes of precordial compression. In epinephrine and placebo groups, either epinephrine (20 µg/kg) or saline placebo was administered intravenously after 4 minutes of precordial compression. Resuscitation was attempted after 8 minutes of cardiopulmonary resuscitation. Sublingual microcirculation was measured at baseline and 1, 3, and 5 hours after return of spontaneous circulation. Myocardial function was measured at baseline and 2, 4, and 6 hours after return of spontaneous circulation. Neurologic deficit scores were recorded at 24, 48, and 72 hours after return of spontaneous circulation. Aortic infusion of PEG-20k increased coronary perfusion pressure to the same extent as epinephrine. Postresuscitation sublingual microcirculation, myocardial and cerebral function, and duration of survival were improved in PEG-20k (P<0.05) compared with epinephrine (P<0.05). Conclusions Aortic infusion of PEG-20k during cardiopulmonary resuscitation increases coronary perfusion pressure to the same extent as epinephrine, improves postresuscitation myocardial and cerebral function, and increases duration of survival in a rat model of cardiac arrest.

The utility of delta 9-tetrahydrocannabinol (THC) measures obtained from oral fluid samples in traffic safety.

Objective: Blood and/or urine are typical drug detection matrices used by law enforcement. There are some concerns about using oral fluid (OF) in the identification of drivers potentially impaired by cannabis, particularly regarding their accuracy when compared to blood. The study objectives were to (1) examine the accuracy of predicting delta 9-tetrahydrocannabinol (THC) in blood from THC measured in OF and (2) examine factors influencing prediction accuracy. Methods: Using data from the 2007 and 2013-2014 National Roadside Survey (NRS) of Alcohol and Drug Use, 7,517 drivers with known laboratory results in both OF and blood were included in this study. OF samples were collected using the Quantisal® device and analyzed at the same private laboratory in both the 2007 and 2013-2014 NRS. The Quantisal device has consistently shown to collect 1 mL ±10%. Descriptive statistical analyses were used to examine and compare the distribution of THC concentrations in OF and blood. A hurdle model was applied to examine factors influencing the accuracy of the THCblood predictions based on THCOF while accounting for the decisions of cannabis consumption. We estimated the number of true positives (TPs), false positives (FPs), true negatives (TNs), false negatives (FNs), sensitivity, specificity, and positive predicted value (PPV). Results: This study found that THC measured in OF (THCOF) is a good predictor of THC measured in blood (THCblood), in particular when THCOF > 0 ng/mL is used to predict being positive for THCblood (THCblood > 0 ng/mL). However, as blood and OF concentrations depart from 0 ng/mL, the proportion of TPs (sensitivity) decreases, which might be a concern for law enforcement. The likelihood of accurately predicting THCblood from THCOF is lower for drivers who were simultaneously using cannabis and other drugs. Conclusions: The findings of this study are based on THC measures obtained in a laboratory, which may not be the same as those conducted by police using point-of-care devices. However, this study is unique due to its large sample of drivers obtained in similar roadside locations and times to actual law enforcement activities. Though a positive THCOF may assist law enforcement in probable cause for a blood draw, efforts to develop reliable methods to detect drug impairment based on OF should continue.

Correction: Evidence of transmission of Clostridium difficile in asymptomatic patients following admission screening in a tertiary care hospital.

[This corrects the article DOI: 10.1371/journal.pone.0207138.].

Author Correction: CHD3 helicase domain mutations cause a neurodevelopmental syndrome with macrocephaly and impaired speech and language.

The HTML and PDF versions of this Article were updated after publication to remove images of one individual from Figure 1.

Chemical evidence for the use of multiple psychotropic plants in a 1,000-year-old ritual bundle from South America.

Over several millennia, various native plant species in South America have been used for their healing and psychoactive properties. Chemical analysis of archaeological artifacts provides an opportunity to study the use of psychoactive plants in the past and to better understand ancient botanical knowledge systems. Liquid chromatography tandem mass spectrometry (LC-MS/MS) was used to analyze organic residues from a ritual bundle, radiocarbon dated to approximately 1,000 C.E., recovered from archaeological excavations in a rock shelter located in the Lípez Altiplano of southwestern Bolivia. The site is located at an elevation of ∼3,900 m above sea level and contains evidence of intermittent human occupations during the last 4,000 years. Chemical traces of bufotenine, dimethyltryptamine, harmine, and cocaine, including its degradation product benzoylecgonine, were identified, suggesting that at least three plants containing these compounds were part of the shamanic paraphernalia dating back 1,000 years ago, the largest number of compounds recovered from a single artifact from this area of the world, to date. This is also a documented case of a ritual bundle containing both harmine and dimethyltryptamine, the two primary ingredients of ayahuasca. The presence of multiple plants that come from disparate and distant ecological areas in South America suggests that hallucinogenic plants moved across significant distances and that an intricate botanical knowledge was intrinsic to pre-Columbian ritual practices.

Carbon dynamics, net primary productivity and human-appropriated net primary productivity across a forest-cocoa farm landscape in West Africa.

Terrestrial net primary productivity (NPP) is an important metric of ecosystem functioning; however, there are little empirical data on the NPP of human-modified ecosystems, particularly smallholder, perennial crops like cocoa (Theobroma cacao), which are extensive across the tropics. Human-appropriated NPP (HANPP) is a measure of the proportion of a natural system's NPP that has either been reduced through land-use change or harvested directly and, previously, has been calculated to estimate the scale of the human impact on the biosphere. Additionally, human modification can create shifts in NPP allocation and decomposition, with concomitant impacts on the carbon cycle. This study presents the results of 3 years of intensive monitoring of forest and smallholder cocoa farms across disturbance, management intensity, distance from forest and farm age gradients. We measured among the highest reported NPP values in tropical forest, 17.57 ± 2.1 and 17.7 ± 1.6 Mg C ha-1  year-1 for intact and logged forest, respectively; however, the average NPP of cocoa farms was still higher, 18.8 ± 2.5 Mg C ha-1  year-1 , which we found was driven by cocoa pod production. We found a dramatic shift in litterfall residence times, where cocoa leaves decomposed more slowly than forest leaves and shade tree litterfall decomposed considerably faster, indicating significant changes in rates of nutrient cycling. The average HANPP value for all cocoa farms was 2.1 ± 1.1 Mg C ha-1  year-1 ; however, depending on the density of shade trees, it ranged from -4.6 to 5.2 Mg C ha-1  year-1 . Therefore, rather than being related to cocoa yield, HANPP was reduced by maintaining higher shade levels. Across our monitored farms, 18.9% of farm NPP was harvested (i.e., whole cocoa pods) and only 1.1% (i.e., cocoa beans) was removed from the system, suggesting that the scale of HANPP in smallholder cocoa agroforestry systems is relatively small.

Evidence of transmission of Clostridium difficile in asymptomatic patients following admission screening in a tertiary care hospital.

BACKGROUND: Clostridium difficile (CD) is the leading cause of infectious health-care associated diarrhea. However, little is known regarding CD carriage and transmission amongst asymptomatic colonizers. We evaluated carriage, characterized strains and examined epidemiologic linkages in asymptomatic colonized CD patients. METHODS: Rectal swabs from asymptomatic patients admitted to the general medicine ward from April 1-June 30 2012 were collected. PCR-confirmed CD colonies were ribotyped and characterized by Modified-Multi Locus Variable Number Tandem Repeat Analysis (MMLVA). RESULTS: 1549-swabs were collected from 474-patients. Overall, 50/474(10.6%) were CD PCR-positive, 24/50 were colonized at admission, while 26/50 were first identified > = 72 hours after admission. Amongst the 50 CD PCR-positive patients, 90% were asymptomatically colonized and 80% of individuals carried toxigenic CD-strains, including ribotype-027 (5/45:11%). MMLVA revealed five-clusters involving 15-patients harboring toxigenic (4/5) and non-toxigenic CD strains (1/5). In two clusters, patients were CD positive on admission while in the other three clusters involving 10 patients, we observed CD transmission from asymptomatically colonized patients to 8 previously CD-negative patients. CONCLUSIONS: We identified increasing rates of colonization during admission to medical wards. MMLVA typing effectively discriminated between strains and suggests that 20% of patients with CD colonization acquired their strain(s) from asymptomatically colonized individuals in hospital.

Author Correction: CHD3 helicase domain mutations cause a neurodevelopmental syndrome with macrocephaly and impaired speech and language.

The original version of this Article contained an error in the spelling of the author Laurence Faivre, which was incorrectly given as Laurence Faive. This has now been corrected in both the PDF and HTML versions of the Article.

Analysis of Drugs in Oral Fluid Using LC-MS/MS.

Oral fluid analysis for drugs is increasingly used in a variety of testing areas: pain management and medication monitoring, parole and probation situations, driving under the influence of drugs (DUID), therapeutic drug monitoring, and testing for drugs in the workplace. The sample collection itself is straightforward, rapid, observable, and noninvasive, requiring no special facilities (compared to urine) or medical personnel (compared to blood). The pH of saliva is slightly acidic relative to blood; therefore, drugs which are more basic tend to be present in higher concentration in oral fluid than in blood: cocaine, amphetamines, oxycodone, tramadol, buprenorphine, methadone, and fentanyl. Conversely, acidic drugs and drugs which are strongly protein bound have lower concentrations in oral fluid than in blood: examples include benzodiazepines, barbiturates, and carisoprodol. Because of the low volume of specimen available for analysis and the drug concentrations present (generally much lower than those in urine), efficient extraction methods and sensitive confirmation procedures are necessary for routine analysis of drugs in oral fluid. In this chapter, solid-phase extraction methods are described for a variety of drugs with liquid chromatography-tandem mass spectrometry detection.

Prevalence of antibiotic-resistant organisms in Canadian Hospitals. Comparison of point-prevalence survey results from 2010, 2012, and 2016.

OBJECTIVE: Point-prevalence surveys for infection or colonization with methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae (CREs), and for Clostridium difficile infection (CDI) were conducted in Canadian hospitals in 2010 and 2012 to better understanding changes in the epidemiology of antimicrobial-resistant organisms (AROs), which is crucial for public health and care management. METHODS: A third survey of the same AROs in adult inpatients in Canadian hospitals with ≥50 beds was performed in February 2016. Data on participating hospitals and patient cases were obtained using standard criteria and case definitions. Associations between ARO prevalence and institutional characteristics were assessed using logistic regression models. RESULTS: In total, 160 hospitals from 9 of the 10 provinces with 35,018 adult inpatients participated in the survey. Median prevalence per 100 inpatients was 4.1 for MRSA, 0.8 for VRE, 1.1 for CDI, 0.8 for ESBLs, and 0 for CREs. No significant change occurred compared to 2012. CREs were reported from 24 hospitals (15%) in 2016 compared to 10 hospitals (7%) in 2012. Routine universal or targeted admission screening for VRE decreased from 94% in 2010 to 74% in 2016. Targeted screening for MRSA on admission was associated with a lower prevalence of MRSA infection. Large hospitals (>500 beds) had higher prevalences of CDI. CONCLUSION: This survey provides national prevalence rates for AROs in Canadian hospitals. Changes in infection control and prevention policies might lead to changes in the epidemiology of AROs and our capacity to detect them.

A Cryptic Cause of Cardiac Arrest.

BACKGROUND: RIPPLY2-associated spondylocostal dysostosis is a rare disorder that leads to segmentation defects of the vertebrae. These vertebral defects can result in severe instability of the cervical spine, leading to cardiac arrest after only minor whiplash injury. CASE REPORT: We present the case of a healthy 7-year-old child who experienced an out-of-hospital cardiac arrest. He was reported to have profound respiratory distress and collapsed after going down a slide, without trauma. He was resuscitated in the field, and presented to the emergency department, where return of spontaneous circulation was achieved. Imaging of his cervical spine revealed multiple abnormalities. It was determined that a whiplash injury led to hypoxia and bradycardia due to the anatomic abnormalities of his cervical spine, resulting in cardiovascular collapse. He recovered fully and was later diagnosed with SCDO6, an autosomal recessive inherited disorder caused by a mutation in the RIPPLY2 gene. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Unfamiliarity of providers with this mechanism of cardiac arrest, and the rarity of the syndrome itself, make early recognition very difficult. Late diagnosis and lack of preventative measures, including immediate cervical spine stabilization, can lead to catastrophic outcomes. In patients with cardiac arrest of unclear etiology, early consideration of cervical spine immobilization and evaluation can be lifesaving.