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MSTPublications: October 2020

Posted by on Thursday, October 29, 2020 in New Publications .

Association between measured teamwork and medical errors: an observational study of prehospital care in the USA.
Herzberg S, Hansen M, Schoonover A, Skarica B, McNulty J, Harrod T, Snowden JM, Lambert W, Guise JM.
BMJ Open. 2019 Oct 31;9(10):e025314. doi: 10.1136/bmjopen-2018-025314.

Objectives: The goal of this study was to examine the relationship between measured teamwork and adverse safety events in the prehospital emergency care of children using high-fidelity simulation. We posit that non-technical skills such as leadership, teamwork, situation awareness and decision-making are associated with the clinical success of teams.
Design: Observational study.
Setting: Emergency medical services (EMS) responders were recruited from public fire and private transport agencies in Oregon State to participate in four simulations of pediatric emergencies using high-fidelity patient simulators, scene design, and professional actors playing parents and bystanders.
Participants: Forty-four fire/transport teams consisting of 259 EMS professionals consented to participate and completed simulations.
Primary and secondary outcome measures: Teams were assessed using the Clinical Teamwork Scale (CTS), a validated instrument that measures overall teamwork and 15 specific elements in five overarching domains: communication, decision-making, role responsibility (leadership and followership), situational awareness/resource management and patient-friendliness. We used generalised estimating equations to estimate the odds of error with increasing overall CTS teamwork score while adjusting for clinical scenario and potential clustering by team.
Results: Across 176 simulations, the mean overall score on the CTS was 6.04 (SD 2.10; range 1=poor to 10=perfect) and was normally distributed. The distribution of scores was similar across the four clinical scenarios. At least one error was observed in 82% of the simulations. In simulations with at least one observed error, the mean CTS score was 5.76 (SD 2.04) compared with 7.16 (SD 1.95) in scenarios with no observed error. Logistic regression analysis accounting for clustering at the team level revealed that the odds of an error decreased 28% with each unit increase in CTS (OR 0.72, 95% CI 0.59 to 0.88).
Conclusions: This study found that overall teamwork among care delivery teams was strongly associated with the risk of serious adverse events in simulated scenarios of caring for critically ill and injured children.


Histamine H3 Receptor Function Biases Excitatory Gain in the Nucleus Accumbens.
Manz KM, Becker JC, Grueter CA, Grueter BA.
Biol Psychiatry. 2020 Aug 6:S0006-3223(20)31810-2. doi: 10.1016/j.biopsych.2020.07.023. Online ahead of print.

Background: Histamine (HA), a wake-promoting monoamine implicated in stress-related arousal states, is synthesized in histidine decarboxylase-expressing hypothalamic neurons of the tuberomammillary nucleus. Histidine decarboxylase-containing varicosities diffusely innervate striatal and mesolimbic networks, including the nucleus accumbens (NAc). The NAc integrates diverse monoaminergic inputs to coordinate motivated behavior. While the NAc expresses various HA receptor subtypes, mechanisms by which HA modulates NAc circuit dynamics are undefined.
Methods: Using male D1tdTomato transgenic reporter mice, whole-cell patch-clamp electrophysiology, and input-specific optogenetics, we employed a targeted pharmacological approach to interrogate synaptic mechanisms recruited by HA signaling at glutamatergic synapses in the NAc. We incorporated an immobilization stress protocol to assess whether acute stress engages these mechanisms at glutamatergic synapses onto D1 receptor-expressing [D1(+)] medium spiny neurons (MSNs) in the NAc core.
Results: HA negatively regulates excitatory gain onto D1(+)-MSNs via presynaptic H3 receptor-dependent long-term depression that requires Gβγ-directed Akt-GSK3β signaling. Furthermore, HA asymmetrically regulates glutamatergic transmission from the prefrontal cortex and mediodorsal thalamus, with inputs from the prefrontal cortex undergoing robust HA-induced long-term depression. Finally, we report that acute immobilization stress attenuates this long-term depression by recruiting endogenous H3 receptor signaling in the NAc at glutamatergic synapses onto D1(+)-MSNs.
Conclusions: Stress-evoked HA signaling in the NAc recruits H3 heteroreceptor signaling to shift thalamocortical input onto D1(+)-MSNs in the NAc. Our findings provide novel insight into an understudied neuromodulatory system within the NAc and implicate HA in stress-associated physiological states.


Lower cardiac output is associated with neurodegeneration among older adults with normal cognition but not mild cognitive impairment.
Moore EE, Liu D, Bown CW, Kresge HA, Gupta DK, Pechman KR, Mendes LA, Davis LT, Gifford KA, Anderson AW, Wang TJ, Landman BA, Hohman TJ, Jefferson AL.
Brain Imaging Behav. 2020 Oct 10. doi: 10.1007/s11682-020-00398-0. Online ahead of print.
PMID: 33040257

Subclinical cardiac dysfunction is associated with smaller total brain volume on magnetic resonance imaging (MRI). To study whether cardiac output relates to regional measurements of grey and white matter structure, older adults (n = 326) underwent echocardiogram to quantify cardiac output (L/min) and brain MRI. Linear regressions related cardiac output to grey matter volumes measured on T1 and white matter hyperintensities assessed on T2-FLAIR. Voxelwise analyses related cardiac output to diffusion tensor imaging adjusting for demographic, genetic, and vascular risk factors. Follow-up models assessed a cardiac output x diagnosis interaction with stratification (normal cognition, mild cognitive impairment). Cardiac output interacted with diagnosis, such that lower cardiac output related to smaller total grey matter (p = 0.01), frontal lobe (p = 0.01), and occipital lobe volumes (p = 0.01) among participants with normal cognition. When excluding participants with cardiovascular disease and atrial fibrillation, associations emerged with smaller parietal lobe (p = 0.005) and hippocampal volume (p = 0.05). Subtle age-related cardiac changes may disrupt neuronal homeostasis and impact grey matter integrity prior to cognitive impairment.

Hydroxychloroquine as pre-exposure prophylaxis for COVID-19 in healthcare workers: a randomized trial.
Rajasingham R, Bangdiwala AS, Nicol MR, Skipper CP, Pastick KA, Axelrod ML, Pullen MF, Nascene AA, Williams DA, Engen NW, Okafor EC, Rini BI, Mayer IA, McDonald EG, Lee TC, Li P, MacKenzie LJ, Balko JM, Dunlop SJ, Hullsiek KH, Boulware DR, Lofgren SM.
Clin Infect Dis. 2020 Oct 17:ciaa1571. doi: 10.1093/cid/ciaa1571. Online ahead of print.

MEK inhibition activates STAT signaling to increase breast cancer immunogenicity via MHC-I expression.
Franklin DA, James JL, Axelrod ML, Balko JM.
Cancer Drug Resist. 2020;3:603-612. doi: 10.20517/cdr.2019.109. Epub 2020 Apr 25.

A Basis to Be Here: Stories from International Graduate Students in the United States.
Lemieux M, Colazo JM, Kienka T, Zhakyp A.
Cell Rep Med. 2020 Sep 22;1(6):100100. doi: 10.1016/j.xcrm.2020.100100.

Characterization of Physical, Functional, and Cognitive Performance in 15 Adults with Hypophosphatasia.
Durrough C, Colazo JM, Simmons J, Hudson M, Hu JR, Black M, de Riesthal M, Dahir K.
Bone. 2020 Oct 15:115695. doi: 10.1016/j.bone.2020.115695. Online ahead of print.

An algorithmic approach to preoperative studies and patient selection for hemispheric disconnection surgery: a literature review.
Tomycz L, Hale AT, Abdulrazeq HF, Naftel RP, Englot DJ, Segal E.
Epileptic Disord. 2020 Oct 23. doi: 10.1684/epd.2020.1205. Online ahead of print.

Predicting susceptibility to SARS-CoV-2 infection based on structural differences in ACE2 across species.
Alexander MR, Schoeder CT, Brown JA, Smart CD, Moth C, Wikswo JP, Capra JA, Meiler J, Chen W, Madhur MS.
FASEB J. 2020 Oct 4. doi: 10.1096/fj.202001808R. Online ahead of print.

Radioembolization with 90Y Resin Microspheres of Neuroendocrine Liver Metastases After Initial Peptide Receptor Radionuclide Therapy.
Braat AJAT, Ahmadzadehfar H, Kappadath SC, Stothers CL, Frilling A, Deroose CM, Flamen P, Brown DB, Sze DY, Mahvash A, Lam MGEH.
Cardiovasc Intervent Radiol. 2020 Feb;43(2):246-253. doi: 10.1007/s00270-019-02350-2. Epub 2019 Oct 23.