Improving Neuromuscular Monitoring Through Education-Based Interventions and Studying Its Association With Adverse Postoperative Outcomes: A Retrospective Observational Study.

BACKGROUND: We assessed the association between education-based interventions, the frequency of train-of-four (TOF) monitoring, and postoperative outcomes. METHODS: We studied adults undergoing noncardiac surgery from February 1, 2020 through October 31, 2021. Our education-based interventions consisted of 3 phases. An interrupted time-series analysis, adjusting for patient- and procedure-related characteristics and secular trends over time, was used to assess the associations between education-based interventions and the frequency of TOF monitoring, postoperative pulmonary complications (PPCs), 90-day mortality, and sugammadex dosage. For each outcome and intervention phase, we tested whether the intervention at that phase was associated with an immediate change in the outcome or its trend (weekly rate of change) over time. In a sensitivity analysis, the association between education-based interventions and postoperative outcomes was adjusted for TOF monitoring. RESULTS: Of 19,422 cases, 11,636 (59.9%) had documented TOF monitoring. Monitoring frequency increased from 44.2% in the first week of preintervention stage to 83.4% in the final week of the postintervention phase. During the preintervention phase, the odds of TOF monitoring trended upward by 0.5% per week (odds ratio [OR], 1.005; 95% confidence interval [CI], 1.002-1.007). Phase 1 saw an immediate 54% increase (OR, 1.54; 95% CI, 1.33-1.79) in the odds, and the trend OR increased by 3% (OR, 1.03; 95% CI, 1.01-1.05) to 1.035, or 3.5% per week (joint Wald test, P < .001). Phase 2 was associated with a further immediate 29% increase (OR, 1.29; 95% CI, 1.02-1.64) but no significant association with trend (OR, 0.96; 95% CI, 0.93-1.01) of TOF monitoring (joint test, P = .04). Phase 3 and postintervention phase were not significantly associated with the frequency of TOF monitoring (joint test, P = .16 and P = .61). The study phases were not significantly associated with PPCs or sugammadex administration. The trend OR for 90-day mortality was larger by 24% (OR, 1.24; 95% CI, 1.06-1.45; joint test, P = .03) in phase 2 versus phase 1, from a weekly decrease of 8% to a weekly increase of 14%. However, this trend reversed again at the transition from phase 3 to the postintervention phase (OR, 0.82; 95% CI, 0.68-0.99; joint test, P = .05), from a 14% weekly increase to a 6.2% weekly decrease in the odds of 90-day mortality. In sensitivity analyses, adjusting for TOF monitoring, we found similar associations between study initiatives and postoperative outcomes. TOF monitoring was associated with lower odds of PPCs (OR, 0.69; 95% CI, 0.55-0.86) and 90-day mortality (OR, 0.79; 95% CI, 0.63-0.98), but not sugammadex dosing (mean difference, -0.02; 95% CI, -0.04 to 0.01). CONCLUSIONS: Our education-based interventions were associated with both TOF utilization and 90-day mortality but were not associated with either the odds of PPCs or sugammadex dosing. TOF monitoring was associated with reduced odds of PPCs and 90-day mortality.

Automated Emails to Improve Evening Staffing for Anesthesiologists.

Scheduling flexibility and predictability to the end of a clinical workday are strategies aimed at addressing physician burnout. A voluntary relief shift was created to increase the pool of anesthesiologists providing end of the day relief. We hypothesized that an automated email reminder would improve the number of evening relief shifts filled and increase the number of anesthesiologists participating in the program. An automated email reminder was implemented, which selectively emailed anesthesiologists without a clinical assignment one day in advance when the voluntary relief shifts were not filled, and anticipated case volume past 4:00 PM was expected to exceed the capacity of the on-call team. After implementation of the automated email reminder, the median number of providers who worked the relief shift on a typical day was 2.6, compared to 1.75 prior to the intervention. After the initial increase in the number of volunteers post-intervention, the trend in the weekly average number of volunteers tended to decrease but remained higher than before the intervention. A total of 22 unique anesthesiologists chose to participate in this program after the intervention. An automated email reminder increased the number of anesthesiologists volunteering for a relief shift. Leveraging automation to match staffing needs with case volume allows for recruitment of additional personnel on the days when volunteers are most needed. Increasing the pool of anesthesiologists available to provide relief is one strategy to improve end of the day predictability and work-life balance.

Gadolinium theranostics for the diagnosis and treatment of cancer.

According to the World Health Organization (WHO), there were 18.1 million new cancer cases and 9.6 million cancer deaths reported worldwide in 2018. These numbers are expected to rise over the next decade, and the development of new and effective cancer treatments and diagnostic tools is urgently required, particularly for aggressive and intractable malignant cancers such as those of the brain. An exciting field of cancer research involves combining therapeutic and diagnostic tools into a single 'theranostic' platform. The role of theranostics in the personalized management of oncology patients is increasing, as is the demand for new types of theranostic agents. Some of the most promising cancer theranostics exploit the lanthanoid metal gadolinium, an element possessing favourable therapeutic and imaging properties.

Evaluating the Rapid Emergence of Daptomycin Resistance in Corynebacterium: a Multicenter Study.

Members of the genus Corynebacterium are increasingly recognized as pathobionts and can be very resistant to antimicrobial agents. Previous studies have demonstrated that Corynebacterium striatum can rapidly develop high-level daptomycin resistance (HLDR) (MIC, ≥256 µg/ml). Here, we conducted a multicenter study to assay for this in vitro phenotype in diverse Corynebacterium species. Corynebacterium clinical isolates (n = 157) from four medical centers were evaluated. MIC values to daptomycin, vancomycin, and telavancin were determined before and after overnight exposure to daptomycin to identify isolates able to rapidly develop daptomycin nonsusceptibility. To investigate assay reproducibility, 18 isolates were evaluated at three study sites. In addition, the stability of daptomycin nonsusceptibility was tested using repeated subculture without selective pressure. The impact of different medium brands was also investigated. Daptomycin nonsusceptibility emerged in 12 of 23 species evaluated in this study (C. afermentans, C. amycolatum, C. aurimucosum, C. bovis, C. jeikeium, C. macginleyi, C. pseudodiphtheriticum, C. resistens, C. simulans, C. striatum, C. tuberculostearicum, and C. ulcerans) and was detected in 50 of 157 (31.8%) isolates tested. All isolates displayed low (susceptible) MIC values to vancomycin and telavancin before and after daptomycin exposure. Repeated subculture demonstrated that 2 of 9 isolates (22.2%) exhibiting HLDR reverted to a susceptible phenotype. Of 30 isolates tested on three medium brands, 13 (43.3%) had differences in daptomycin MIC values between brands. Multiple Corynebacterium species can rapidly develop daptomycin nonsusceptibility, including HLDR, after a short daptomycin exposure period.

Gut microbiota profiles and fecal beta-glucuronidase activity in kidney transplant recipients with and without post-transplant diarrhea.

Post-transplant diarrhea is a common complication after solid organ transplantation and is frequently attributed to the widely prescribed immunosuppressant mycophenolate mofetil (MMF). Given recent work identifying the relationship between MMF toxicity and gut bacterial ß-glucuronidase activity, we evaluated the relationship between gut microbiota composition, fecal ß-glucuronidase activity, and post-transplant diarrhea. We recruited 97 kidney transplant recipients and profiled the gut microbiota in 273 fecal specimens using 16S rRNA gene sequencing. We further characterized fecal ß-glucuronidase activity in a subset of this cohort. Kidney transplant recipients with post-transplant diarrhea had decreased gut microbial diversity and decreased relative gut abundances of 12 genera when compared to those without post-transplant diarrhea (adjusted p value < .15, Wilcoxon rank sum test). Among the kidney transplant recipients with post-transplant diarrhea, those with higher fecal ß-glucuronidase activity had a more prolonged course of diarrhea (≥7 days) compared to patients with lower fecal ß-glucuronidase activity (91% vs 40%, p = .02, Fisher's exact test). Our data reveal post-transplant diarrhea as a complex phenomenon with decreased gut microbial diversity and commensal gut organisms. This study further links commensal bacterial metabolism with an important clinical outcome measure, suggesting fecal ß-glucuronidase activity could be a novel biomarker for gastrointestinal-related MMF toxicity.

Efficacy of an Online Curriculum for Perioperative Goals of Care and Code Status Discussions: A Randomized Controlled Trial.

BACKGROUND: Preoperative goals of care (GOC) and code status (CS) discussions are important in achieving an in-depth understanding of the patient's care goals in the setting of a serious illness, enabling the clinician to ensure patient autonomy and shared decision making. Past studies have shown that anesthesiologists are not formally trained in leading these discussions and may lack the necessary skill set. We created an innovative online video curriculum designed to teach these skills. This curriculum was compared to a traditional method of learning from reading the medical literature. METHODS: In this bi-institutional randomized controlled trial at 2 major academic medical centers, 60 anesthesiology trainees were randomized to receive the educational content in 1 of 2 formats: (1) the novel video curriculum (video group) or (2) journal articles (reading group). Thirty residents were assigned to the experimental video curriculum group, and 30 were assigned to the reading group. The content incorporated into the 2 formats focused on general preoperative evaluation of patients and communication strategies pertaining to GOC and CS discussions. Residents in both groups underwent a pre- and postintervention objective structured clinical examination (OSCE) with standardized patients. Both OSCEs were scored using the same 24-point rubric. Score changes between the 2 OSCEs were examined using linear regression, and interrater reliability was assessed using weighted Cohen's kappa. RESULTS: Residents receiving the video curriculum performed significantly better overall on the OSCE encounter, with a mean score of 4.19 compared to 3.79 in the reading group. The video curriculum group also demonstrated statistically significant increased scores on 8 of 24 rubric categories when compared to the reading group. CONCLUSIONS: Our novel video curriculum led to significant increases in resident performance during simulated GOC discussions and modest increases during CS discussions. Further development and refinement of this curriculum are warranted.

Evaluation of NG-Test Carba 5 for Rapid Phenotypic Detection and Differentiation of Five Common Carbapenemase Families: Results of a Multicenter Clinical Evaluation.

NG-Test Carba 5 is a rapid in vitro multiplex immunoassay for the phenotypic detection and differentiation of five common carbapenemase families (KPC, OXA-48-like, VIM, IMP, and NDM) directly from bacterial colonies. The assay is simple to perform and has recently received U.S. Food and Drug Administration clearance. A method comparison study was performed at geographically diverse medical centers (n = 3) in the United States, where 309 Enterobacterales and Pseudomonas aeruginosa isolates were evaluated by NG-Test Carba 5 (NG Biotech, Guipry, France), the Xpert Carba-R assay (Cepheid, Inc., Sunnyvale, CA), the modified carbapenem inactivation method (mCIM), the EDTA-modified carbapenem inactivation method, and disk diffusion with carbapenems. Colonies from tryptic soy agar with 5% sheep blood (blood agar) and MacConkey agar were tested, and the results were compared to those obtained by a composite reference method. Additionally, a fourth medical center performed a medium comparison study by evaluating the performance characteristics of NG-Test Carba 5 from blood, MacConkey, and Mueller-Hinton agars with 110 isolates of Enterobacterales and P. aeruginosa These results were compared to the expected genotypic and mCIM results. For the multicenter method comparison study, the overall positive percent agreement (PPA) and the overall negative percent agreement (NPA) of NG-Test Carba 5 with the composite reference method were 100% for both blood and MacConkey agars. The medium comparison study at the fourth site showed that the PPA ranged from 98.9% to 100% and that the NPA ranged from 95.2% to 100% for blood, MacConkey, and Mueller-Hinton agars. NG-Test Carba 5 accurately detected and differentiated five common carbapenemase families from Enterobacterales and P. aeruginosa colonies on commonly used agar media. The results of this test will support a streamlined laboratory work flow and will expedite therapeutic and infection control decisions.

Comparison of Two High-Throughput Reverse Transcription-PCR Systems for the Detection of Severe Acute Respiratory Syndrome Coronavirus 2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as the cause of a worldwide pandemic. Many commercial SARS-CoV-2 reverse transcription-PCR (RT-PCR) assays have received Emergency Use Authorization from the U.S. Food and Drug Administration. However, there are limited data describing their performance, in particular the performance of high-throughput SARS-CoV-2 RT-PCR systems. We analyzed the diagnostic performance of two high-throughput systems: cobas 6800 and Panther Fusion, and their associated RT-PCR assays, with a collection of 389 nasopharyngeal specimens. The overall agreement between the platforms was 96.4% (375/389). Cohen's kappa analysis rated the strength of agreement between the two platforms as "almost perfect" (κ = 0.922; standard error, 0.051). Furthermore, there was no significant difference between corresponding cycle threshold values generated on the two systems (P value = 0.88; Student's t test). Taken together, these data imply that the two platforms can be considered comparable in terms of their clinical performance. We believe that this information will be useful for those who have already adopted these platforms or are seeking to implement high-throughput RT-PCR testing to stem the SARS-CoV-2 pandemic.

Limitations of exome sequencing in detecting rare and undiagnosed diseases.

While exome sequencing (ES) is commonly the final diagnostic step in clinical genetics, it may miss diagnoses. To clarify the limitations of ES, we investigated the diagnostic yield of genetic tests beyond ES in our Undiagnosed Diseases Network (UDN) participants. We reviewed the yield of additional genetic testing including genome sequencing (GS), copy number variant (CNV), noncoding variant (NCV), repeat expansion (RE), or methylation testing in UDN cases with nondiagnostic ES results. Overall, 36/54 (67%) of total diagnoses were based on clinical findings and coding variants found by ES and 3/54 (6%) were based on clinical findings only. The remaining 15/54 (28%) required testing beyond ES. Of these, 7/15 (47%) had NCV, 6/15 (40%) CNV, and 2/15 (13%) had a RE or a DNA methylation disorder. Thus 18/54 (33%) of diagnoses were not solved exclusively by ES. Several methods were needed to detect and/or confirm the functional effects of the variants missed by ES, and in some cases by GS. These results indicate that tests to detect elusive variants should be considered after nondiagnostic preliminary steps. Further studies are needed to determine the cost-effectiveness of tests beyond ES that provide diagnoses and insights to possible treatment.

Gut microbiota dysbiosis and diarrhea in kidney transplant recipients.

Posttransplant diarrhea is associated with kidney allograft failure and death, but its etiology remains unknown in the majority of cases. Because altered gut microbial ecology is a potential basis for diarrhea, we investigated whether posttransplant diarrhea is associated with gut dysbiosis. We enrolled 71 kidney allograft recipients for serial fecal specimen collections in the first 3 months of transplantation and profiled the gut microbiota using 16S ribosomal RNA (rRNA) gene V4-V5 deep sequencing. The Shannon diversity index was significantly lower in 28 diarrheal fecal specimens from 25 recipients with posttransplant diarrhea than in 112 fecal specimens from 46 recipients without posttransplant diarrhea. We found a lower relative abundance of 13 commensal genera (Benjamini-Hochberg adjusted P ≤ .15) in the diarrheal fecal specimens including the same 4 genera identified in our prior study. The 28 diarrheal fecal specimens were also evaluated by a multiplexed polymerase chain reaction (PCR) assay for 22 bacterial, viral, and protozoan gastrointestinal pathogens, and 26 specimens were negative for infectious etiologies. Using PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) to predict metagenomic functions, we found that diarrheal fecal specimens had a lower abundance of metabolic genes. Our findings suggest that posttransplant diarrhea is not associated with common infectious diarrheal pathogens but with a gut dysbiosis.

Activity of Imipenem-Relebactam and Comparator Agents against Genetically Characterized Isolates of Carbapenem-Resistant Enterobacteriaceae.

Carbapenem-resistant Enterobacteriaceae (CRE) strains are an urgent public health threat. We evaluated the in vitro activities of 19 antimicrobial agents, including imipenem-relebactam, against (i) 106 CRE bloodstream isolates that primarily expressed Klebsiella pneumoniae carbapenemase (KPC) and (ii) 20 OXA-48-like-expressing CRE isolates. Ninety-five percent of CRE bloodstream isolates were susceptible to imipenem-relebactam. In contrast to their comparable activities against KPC-producing CRE strains, ceftazidime-avibactam was more active in vitro against OXA-48-like CRE strains than was imipenem-relebactam (90% susceptible versus 15% susceptible).

Gastrointestinal pathogen colonization and the microbiome in asymptomatic kidney transplant recipients.

BACKGROUND: In kidney transplant recipients, gastrointestinal (GI) pathogens in feces are only evaluated during diarrheal episodes. Little is known about the prevalence of GI pathogens in asymptomatic individuals in this population. METHODS: We recruited 142 kidney transplant recipients who provided a non-diarrheal fecal sample within the first 10 days after transplantation. The specimens were evaluated for GI pathogens using the BioFire® FilmArray® GI Panel (BioFire Diagnostics, LLC), which tests for 22 pathogens. The fecal microbiome was also characterized using 16S rRNA gene sequencing of the V4-V5 hypervariable region. We evaluated whether detection of Clostridioides difficile and other GI pathogens was associated with post-transplant diarrhea within the first 3 months after transplantation. RESULTS: Among the 142 subjects, a potential pathogen was detected in 43 (30%) using the GI Panel. The most common organisms detected were C difficile (n = 24, 17%), enteropathogenic Escherichia coli (n = 8, 6%), and norovirus (n = 5, 4%). Detection of a pathogen on the GI panel or detection of C difficile alone was not associated with future post-transplant diarrhea (P > .05). The estimated number of gut bacterial species was significantly lower in subjects colonized with C difficile than those not colonized with a GI pathogen (P = .01). CONCLUSION: Colonization with GI pathogens, particularly C difficile, is common at the time of kidney transplantation but does not predict subsequent diarrhea. Detection of C difficile carriage was associated with decreased microbial diversity and may be a biomarker of gut dysbiosis.

The Effects of Contingent Lullaby Music on Parent-Infant Interaction and Amount of Infant Crying in the First Six Weeks of Life.

PURPOSE: The purpose of this study was to examine the effect of a live music intervention provided by the mother on full term infants' amount of crying and parent-infant interaction in the first six weeks of life. DESIGN AND METHODS: A randomized posttest-only experimental/no-contact control group design was used for this study. A sample of 66 mothers with healthy, newborn infants were recruited. The researcher wrote an original lullaby with each mother in the experimental group and gave instructions as to how to use the lullaby as reinforcement for infant quiet, non-crying behavior. Mother-infant dyads were assessed over a six-week period for infant crying amounts and parent-infant interaction behaviors. Demographic variables, postpartum depression, and value of music were assessed as well to detect associations between variables and groups. RESULTS: Results indicated that there were significant differences between groups for mean crying time per week and mother-infant interaction behaviors. Analysis by demographic variables such as mother parity, socioeconomic status, and marital status showed no significant group differences on infant crying or interaction scores. Mothers who used the contingent music intervention were more motivated to sing and valued the use of music with their infants more than mothers in the control group. CONCLUSIONS: The outcomes of this study demonstrate importance of parental singing for mother-infant bonding. PRACTICE IMPLICATIONS: Implementing early intervention services, such as music therapy in the postpartum unit, can provide new mothers useful music applications that can enhance mother-infant interaction, especially mothers living in high stress or negative environments.

Phenotypic heterogeneity of ZMPSTE24 deficiency.

A 4-year-old girl was referred to the Undiagnosed Diseases Network with a history of short stature, thin and translucent skin, macrocephaly, small hands, and camptodactyly. She had been diagnosed with possible Hallerman-Streiff syndrome. Her evaluation showed that she was mosaic for uniparental isodisomy of chromosome 1, which harbored a pathogenic c.1077dupT variant in ZMPSTE24 which predicts p.(Leu362fsX18). ZMPSTE24 is a zinc metalloproteinase that is involved in processing farnesylated proteins and pathogenic ZMPSTE24 variants cause accumulation of abnormal farnesylated forms of prelamin A. This, in turn, causes a spectrum of disease severity which is based on enzyme activity. The current patient has an intermediate form, which is a genocopy of severe Progeria.

Clinical heterogeneity of mitochondrial NAD kinase deficiency caused by a NADK2 start loss variant.

Mitochondrial NAD kinase deficiency (NADK2D, OMIM #615787) is a rare autosomal recessive disorder of NADPH biosynthesis that can cause hyperlysinemia and dienoyl-CoA reductase deficiency (DECRD, OMIM #616034). NADK2 deficiency has been reported in only three unrelated patients. Two had severe, unremitting disease; one died at 4 months and the other at 5 years of age. The third was a 10 year old female with CNS anomalies, ataxia, and incoordination. In two cases mutations in NADK2 have been demonstrated. Here, we report the fourth known case, a 15 year old female with normal intelligence and a mild clinical and biochemical phenotype presumably without DECRD. Her clinical symptoms, which are now stable, became evident at the age of 9 with the onset of decreased visual acuity, bilateral optic atrophy, nystagmus, episodic lower extremity weakness, peripheral neuropathy, and gait abnormalities. Plasma amino acid levels were within normal limits except for mean lysine and proline levels that were 3.7 and 2.5 times the upper limits of normal. Whole exome sequencing (WES) revealed homozygosity for a g.36241900 A>G p. Met1Val start loss mutation in the primary NADK2 transcript (NM_001085411.1) encoding the 442 amino acid isoform. This presumed hypomorphic mutation has not been previously reported and is absent from the v1000GP, EVS, and ExAC databases. Our patient's normal intelligence and stable disease expands the clinical heterogeneity and the prognosis associated with NADK2 deficiency. Our findings also clarify the mechanism underlying NADK2 deficiency and suggest that this disease should be ruled out in cases of hyperlysinemia, especially those with visual loss, and neurological phenotypes.

Evaluation of Pyrrolidonyl Arylamidase Activity in Staphylococcus delphini.

Clinical reference textbooks lack data for pyrrolidonyl arylamidase (PYR) activity in Staphylococcus delphini This study evaluated PYR activities of 21 S. delphini strains by reference broth, rapid disc, and rapid slide methods. Species and subgroup identifications were confirmed by nucleic acid-based methods and included nine group A and 12 group B strains. Testing by rapid PYR methods with products from four manufacturers was performed at two testing locations, and, with the exception of one strain tested at one location using reagents from one manufacturer, each S. delphini strain tested positive for PYR activity. Therefore, PYR may be a useful single-test adjunct for distinguishing Staphylococcus aureus from S. delphini and other members of the Staphylococcus intermedius group.

In Vitro Antimicrobial Susceptibility of Staphylococcus pseudintermedius Isolates of Human and Animal Origin.

MIC results for 115 Staphylococcus intermedius group isolates are presented. Of these, 33% were methicillin resistant, among which 51.4% were susceptible to doxycycline, 29.7% to clindamycin, and 21.6% to trimethoprim-sulfamethoxazole. All of the isolates were susceptible to ceftaroline, daptomycin, linezolid, nitrofurantoin, quinupristin-dalfopristin, rifampin, tigecycline, and vancomycin. Of all the isolates, 82.6%, 67.8%, and 23.5% were susceptible to ciprofloxacin, erythromycin, and penicillin, respectively. No isolates harbored mupA or qacA/B genes, which suggested a lack of resistance to mupirocin or chlorhexidine.