Public health infection prevention: An analysis of existing training during the COVID-19 pandemic.

OBJECTIVES: In response to the COVID-19 pandemic, agencies and organizations required trainings to support the needs of the public health workforce. To better understand the training resources available, this study identified, organized, and classified infection prevention and control (IPC) training and educational opportunities. STUDY DESIGN: Environmental scan. METHODS: A total of 306 IPC training resources were compiled between January and April 2021. Key themes and topics were identified and compared to the Healthcare Infection Control Practices Advisory Committee's (HICPAC) core IPC practices. RESULTS: Three hundred and six training resources, including webinars, fact sheets, module-based learning activities, infographics, and professional practice guidance materials, were identified. Common themes included proper use of personal protective equipment (e.g., masks, gloves), community reopening guidance, and mass vaccination resources. A large proportion (74.9%) of trainings were under 60 min. Using the HICPAC framework, the most frequently addressed content included standard precautions (40%), leadership support (31.6%), and transmission-based precautions (25.8%). Few trainings addressed performance monitoring and feedback (17.1%). CONCLUSIONS: A wide range of organizations developed IPC-specific content during the pandemic. However, these resources did not address the breadth of knowledge required to implement IPC concepts effectively. The creation of universally applicable IPC core competencies and the development of high-quality IPC education and trainings for public health and the overall responder workforces should be prioritized. Accessible high-quality online and just-in-time trainings are critical for future pandemic and disaster preparedness.

Filtered Diffusion-Weighted MRI of the Human Cervical Spinal Cord: Feasibility and Application to Traumatic Spinal Cord Injury.

BACKGROUND AND PURPOSE: In traumatic spinal cord injury, DTI is sensitive to injury but is unable to differentiate multiple pathologies. Axonal damage is a central feature of the underlying cord injury, but prominent edema confounds its detection. The purpose of this study was to examine a filtered DWI technique in patients with acute spinal cord injury. MATERIALS AND METHODS: The MR imaging protocol was first evaluated in a cohort of healthy subjects at 3T (n = 3). Subsequently, patients with acute cervical spinal cord injury (n = 8) underwent filtered DWI concurrent with their acute clinical MR imaging examination <24 hours postinjury at 1.5T. DTI was obtained with 25 directions at a b-value of 800 s/mm2. Filtered DWI used spinal cord-optimized diffusion-weighting along 26 directions with a "filter" b-value of 2000 s/mm2 and a "probe" maximum b-value of 1000 s/mm2. Parallel diffusivity metrics obtained from DTI and filtered DWI were compared. RESULTS: The high-strength diffusion-weighting perpendicular to the cord suppressed signals from tissues outside of the spinal cord, including muscle and CSF. The parallel ADC acquired from filtered DWI at the level of injury relative to the most cranial region showed a greater decrease (38.71%) compared with the decrease in axial diffusivity acquired by DTI (17.68%). CONCLUSIONS: The results demonstrated that filtered DWI is feasible in the acute setting of spinal cord injury and reveals spinal cord diffusion characteristics not evident with conventional DTI.

Edoxaban vs. warfarin in patients with atrial fibrillation on amiodarone: a subgroup analysis of the ENGAGE AF-TIMI 48 trial.

BACKGROUND: In the ENGAGE AF-TIMI 48 trial, the higher-dose edoxaban (HDE) regimen had a similar incidence of ischaemic stroke compared with warfarin, whereas a higher incidence was observed with the lower-dose regimen (LDE). Amiodarone increases edoxaban plasma levels via P-glycoprotein inhibition. The current pre-specified exploratory analysis was performed to determine the effect of amiodarone on the relative efficacy and safety profile of edoxaban. METHODS AND RESULTS: At randomization, 2492 patients (11.8%) were receiving amiodarone. The primary efficacy endpoint of stroke or systemic embolic event was significantly lower with LDE compared with warfarin in amiodarone treated patients vs. patients not on amiodarone (hazard ratio [HR] 0.60, 95% confidence intervals [CIs] 0.36-0.99 and HR 1.20, 95% CI 1.03-1.40, respectively; P interaction <0.01). In patients randomized to HDE, no such interaction for efficacy was observed (HR 0.73, 95% CI 0.46-1.17 vs. HR 0.89, 95% CI 0.75-1.05, P interaction = 0.446). Major bleeding was similar in patients on LDE (HR 0.35, 95% CI 0.21-0.59 vs. HR 0.53, 95% CI 0.46-0.61, P interaction = 0.131) and HDE (HR 0.94, 95% CI 0.65-1.38 vs. HR 0.79, 95% CI 0.69-0.90, P interaction = 0.392) when compared with warfarin, independent of amiodarone use. CONCLUSIONS: Patients randomized to the LDE treated with amiodarone at the time of randomization demonstrated a significant reduction in ischaemic events vs. warfarin when compared with those not on amiodarone, while preserving a favourable bleeding profile. In contrast, amiodarone had no effect on the relative efficacy and safety of HDE.

A "SMART" design for building individualized treatment sequences.

Interventions often involve a sequence of decisions. For example, clinicians frequently adapt the intervention to an individual's outcomes. Altering the intensity and type of intervention over time is crucial for many reasons, such as to obtain improvement if the individual is not responding or to reduce costs and burden when intensive treatment is no longer necessary. Adaptive interventions utilize individual variables (severity, preferences) to adapt the intervention and then dynamically utilize individual outcomes (response to treatment, adherence) to readapt the intervention. The Sequential Multiple Assignment Randomized Trial (SMART) provides high-quality data that can be used to construct adaptive interventions. We review the SMART and highlight its advantages in constructing and revising adaptive interventions as compared to alternative experimental designs. Selected examples of SMART studies are described and compared. A data analysis method is provided and illustrated using data from the Extending Treatment Effectiveness of Naltrexone SMART study.

Variable Selection for Qualitative Interactions.

In this article we discuss variable selection for decision making with focus on decisions regarding when to provide treatment and which treatment to provide. Current variable selection techniques were developed for use in a supervised learning setting where the goal is prediction of the response. These techniques often downplay the importance of interaction variables that have small predictive ability but that are critical when the ultimate goal is decision making rather than prediction. We propose two new techniques designed specifically to find variables that aid in decision making. Simulation results are given along with an application of the methods on data from a randomized controlled trial for the treatment of depression.

Screening Experiments for Developing Dynamic Treatment Regimes.

Dynamic treatment regimes are time-varying treatments that individualize sequences of treatments to the patient. The construction of dynamic treatment regimes is challenging because a patient will be eligible for some treatment components only if he has not responded (or has responded) to other treatment components. In addition there are usually a number of potentially useful treatment components and combinations thereof. In this article, we propose new methodology for identifying promising components and screening out negligible ones. First, we define causal factorial effects for treatment components that may be applied sequentially to a patient. Second we propose experimental designs that can be used to study the treatment components. Surprisingly, modifications can be made to (fractional) factorial designs - more commonly found in the engineering statistics literature -for screening in this setting. Furthermore we provide an analysis model that can be used to screen the factorial effects. We demonstrate the proposed methodology using examples motivated in the literature and also via a simulation study.

Hand dominance and performance in a laparoscopic skills curriculum.

BACKGROUND: This study evaluated the influence of hand dominance on skill acquisition during a basic laparoscopic skills curriculum. METHODS: A total of 27 surgical residents (5 postgraduate year 3 [PGY-3] and 22 PGY-2 residents) participated in a 4-week laparoscopic skills curriculum. The residents were pre- and posttested on six laparoscopic tasks during weeks 1 and 4. During weeks 2 and 3, the residents attended a proctored practice session. The results were compared using analysis of variance (ANOVA), (with significance determined by a p value less than 0.05. RESULTS: The posttest scores were significantly higher than the pretest scores. On the pretest, lefthand-dominant (LHD) surgeons (n = 4) performed significantly better than righthand-dominant (RHD) surgeons (n = 23). In the analysis of individual task pretest scores, LHD surgeons performed significantly better on pattern cutting and vessel loop application. Posttest analysis of overall performance did not show significant differences between the RHD and LHD surgeons. CONCLUSIONS: Participation in a laparoscopic skills curriculum improved overall performance. The LHD surgeons demonstrated better initial performance, but posttest comparison showed no difference between the two groups.

An experimental design for the development of adaptive treatment strategies.

In adaptive treatment strategies, the treatment level and type is repeatedly adjusted according to ongoing individual response. Since past treatment may have delayed effects, the development of these treatment strategies is challenging. This paper advocates the use of sequential multiple assignment randomized trials in the development of adaptive treatment strategies. Both a simple ad hoc method for ascertaining sample sizes and simple analysis methods are provided.

Malignant mesothelioma presenting as stroke--a case report.

A case of a 64-year-old man with metastatic malignant mesothelioma is described in detail. When he presented to us he gave a history suggestive of transient ischaemic attack (TIA) 2 weeks before and 3 days after admission he developed weakness of the left upper limb. Computed tomographic scan of the brain revealed a solitary metastasis in the right cerebrum. A few days later, he developed subcutaneous metastasis in the chin. Malignant mesothelioma is considered to metastasize rarely and to spread locally. We suggest that distant metastasis in malignant mesothelioma is not uncommon and may be considered to behave like other forms of lung cancer. Treatment modalities should be studied in such patients.

Enoxaparin is superior to unfractionated heparin for preventing clinical events at 1-year follow-up of TIMI 11B and ESSENCE.

BACKGROUND: Enoxaparin treatment is associated with a 20% reduction in clinical events during the acute phase of management of patients with unstable angina/non ST elevation myocardial infarction. Interest in the use of enoxaparin would be enhanced further if evidence of a durable treatment benefit over the long term could be provided. METHODS: Event rates at 1 year for the composite end-point of death/non-fatal myocardial infarction/urgent revascularization and its individual components were ascertained from the TIMI 11B and ESSENCE databases. RESULTS: There was no evidence of heterogeneity between TIMI 11B and ESSENCE in tests for interactions between treatment and trial. A significant treatment benefit of enoxaparin on the rate of death/non-fatal myocardial infarction/urgent revascularization was observed at 1 year (hazard ratio 0.88;P=0.008). The event rate was 25.8% in the unfractionated heparin group and 23.3% in the enoxaparin group, an absolute difference of 2.5%. A progressively greater treatment benefit of enoxaparin was observed as the level of patient risk at baseline increased. Treatment effects for the individual end-point elements ranged from 9-14%, favouring enoxaparin. CONCLUSIONS: The stable absolute difference in event rates of 2.5% seen at 8 days and again at 1 year favouring enoxaparin may be due to more effective control of the thrombotic process surrounding the index event. Once the pharmacological effect of enoxaparin had dissipated there was no rebound increase in events. Thus, those patients who had received enoxaparin acutely were protected from experiencing a deterioration of the original therapeutic benefit. These findings regarding enoxaparin add to the data to be considered by clinicians when selecting an antithrombin for the acute phase of management of unstable angina/non-ST elevation myocardial infarction.

A simple risk index for rapid initial triage of patients with ST-elevation myocardial infarction: an InTIME II substudy.

BACKGROUND: Rapid, effective triage is integral to emergency cardiac care of patients with ST-elevation myocardial infarction (STEMI). Available models for predicting mortality in STEMI include up to 45 variables, but have consistently shown advanced age, increased heart rate, and decreased blood pressure to be among the strongest predictors. METHODS: On the basis of observed risk relations among 13,253 patients with STEMI from the InTIME II trial, we developed and assessed a simple risk index using age, heart rate, and systolic blood pressure (SBP) for predicting mortality over 30 days: (heart rate x [age/10](2))/SBP. FINDINGS: The risk index was a strong (c statistic=0.78) and independent predictor of mortality risk (p<0.0001). When the risk index was categorised into quintiles for convenient clinical use, it revealed a more than 20-fold gradient of increasing mortality from 0.8 to 17.4%, p<0.0001. The risk index was also a robust predictor of very early events, including death by 24 h (c statistic=0.81). External validation in patients with STEMI from the TIMI 9 trials (n=3659) showed both a high discriminatory capacity (c statistic=0.79), and excellent concordance between the observed 30-day mortality in each of the five risk groups and the predictions based on InTIME II (goodness-of-fit, p=0.7). INTERPRETATION: A simple risk index based on characteristics easily assessed by any paramedical or clinical personnel captures most of the information from more complex tools, and is likely to be useful in the rapid triage of patients with STEMI outside hospital or on first arrival in the hospital.

Early coronary intervention following pharmacologic therapy for acute myocardial infarction (the combined TIMI 10B-TIMI 14 experience).

Earlier studies have suggested that immediate percutaneous coronary intervention (PCI) following thrombolytic therapy for acute myocardial infarction (AMI) is associated with an increase in adverse events and that routine PCI in this setting has offered no advantage over a conservative strategy. To reassess this issue in a more recent era, we evaluated 1,938 patients from the Thrombolysis in Myocardial Infarction (TIMI) 10B and 14 trials of AMI. Patients in TIMI 10B were randomized to receive tissue plasminogen activator or TNK tissue plasminogen activator, whereas patients in TIMI 14B trial were randomized to receive thrombolytic therapy with or without abciximab. All patients underwent angiography 90 minutes after receiving pharmacologic therapy. Patients who underwent PCI were classified as having undergone a rescue procedure (TIMI 0 or 1 flow at 90 minutes), an adjunctive procedure (TIMI 2 or 3 flow at 90 minutes), or a delayed procedure (performed >150 minutes after symptom onset, median of 2.75 days). Among patients with TIMI 0 or 1 flow, there was a trend for lower 30-day mortality among patients who underwent rescue PCI than among those who did not (6% vs 17%, p = 0.01, adjusted p = 0.28). Patients who underwent adjunctive PCI had similar 30-day mortality and/or reinfarction as those who underwent delayed PCI. In a multivariate model both had lower 30-day mortality and/or reinfarction than patients with "successful thrombolysis" (i.e., TIMI 3 flow at 90 minutes) who did not undergo revascularization (p = 0.02). Thus, early PCI following AMI is associated with excellent outcomes. Randomized trials of an early invasive strategy following thrombolysis are warranted.

Early noninvasive detection of failed epicardial reperfusion after fibrinolytic therapy.

Available noninvasive techniques for identifying patients with failed epicardial reperfusion after fibrinolytic therapy are limited by poor accuracy. It is unknown whether combining multiple noninvasive predictors would improve diagnostic accuracy and facilitate identification of candidates for rescue percutaneous coronary intervention. In the Thrombolysis In Myocardial Infarction (TIMI) 14 trial, we evaluated the ability of ST-segment resolution (n = 606), chest pain resolution (n = 859), and the ratio of 60-minute/baseline serum myoglobin (n = 308) to identify patients with angiographic evidence of failed reperfusion 90 minutes after fibrinolysis. Three criteria were prospectively defined: <50% ST resolution at 90 minutes, presence of chest pain at the time of angiography, and myoglobin ratio <4. Patients who met any individual criterion were more likely to have less than TIMI 3 flow and an occluded infarct-related artery (TIMI 0/1 flow) than those who did not meet the criterion (p <0.005 for each). When the 3 criteria were used together (n = 169), patients who satisfied 0 (n = 29), 1 (n = 68), 2 (n = 51), or 3 (n = 21) of the criteria had a 17%, 24%, 35%, and 76% probability of failing to achieve TIMI 3 flow (p <0.0001 for trend), a 0%, 6%, 18%, and 57% probability of an occluded infarct-related artery (p <0.0001 for trend), and a 0%, 1.5%, 2.0%, and 9.5% rate of 30-day mortality (p = 0.05 for trend), respectively. Use of the criteria in combination increased positive predictive values without decreasing negative predictive values. In conclusion, ST-segment resolution, chest pain resolution, and early washout of serum myoglobin can be used in combination to aid in the early noninvasive identification of candidates for rescue percutaneous coronary intervention.

Impact of contrast agent type (ionic versus nonionic) used for coronary angiography on angiographic, electrocardiographic, and clinical outcomes following thrombolytic administration in acute myocardial infarction.

The goal of this study was to examine the relationship between contrast agent type (ionic vs. nonionic) and angiographic, electrocardiographic, and clinical outcomes after thrombolytic administration. Ionic or nonionic contrast agents were selected in a nonrandomized fashion for 90-min angiography and percutaneous coronary intervention (PCI) following thrombolytic administration in the TIMI 14 trial [tissue plasminogen activator (tPA) or reteplase (rPA) vs. low-dose lytic + abciximab]. There was no relationship between contrast agent type and overall patency, rate of TIMI grade 3 flow, or corrected TIMI frame counts (CTFCs) in open culprit arteries and in post-PCI patency rates or post-PCI CTFCs. In patients treated with ionic contrast, ejection fractions at 90 min were slightly but significantly lower (56.2 +/- 16.5, n = 122, vs. 59.8 +/- 14.4, n = 322; P = 0.02), chest pain duration was longer (2.8 +/- 4.1 hr, n = 255, vs. 1.7 +/- 3.6, n = 550; P = 0.0003), and complete ST segment resolution was less frequent (41.5% vs. 50.8%; P = 0.04). While there was no difference in epicardial blood flow, ionic contrast agent use was associated with poorer ST segment resolution, longer chest pain duration, and poorer ejection fractions, perhaps as a result of microvascular dysfunction.

Combination therapy with abciximab reduces angiographically evident thrombus in acute myocardial infarction: a TIMI 14 substudy.

BACKGROUND: Use of abciximab in combination with administration of thrombolytics has been shown to improve epicardial and microvascular coronary blood flow in acute myocardial infarction (AMI). As a potential mechanism, we hypothesized that combination therapy would reduce angiographically evident thrombus (AET) and would increase lumen diameter compared with thrombolytic monotherapy. METHODS AND RESULTS: Patients who received combination therapy in TIMI 14 (low-dose thrombolytic plus abciximab, n=732) were compared with patients who received thrombolytic monotherapy without abciximab in the TIMI 4, 10A, 10B, and 14 trials (n=1662). Thrombus burden was assessed 90 minutes after treatment, and quantitative angiography was performed in an angiographic core laboratory by investigators blinded to treatment assignment. The frequency of AET was reduced in patients who received abciximab combination therapy compared with thrombolytic monotherapy (26.6% versus 35.4%, P<0.001). Similar findings were observed when the analysis was restricted to patients with patent arteries (14.7% versus 20.8%, P=0.001). Residual percent diameter stenosis at 90 minutes was also improved in the abciximab therapy group both in patent arteries (64.6+/-16.6 versus 68.3+/-14.8, P<0.001) and between patent and occluded arteries (69.3+/-19.5 versus 73.8+/-17.9, P<0.001). The absence of AET was associated with an increased frequency of >70% ST-segment resolution by 90 minutes (37.2%, 110/296 versus 18.9%, 54/286, P<0.001). CONCLUSIONS: Compared with thrombolytic monotherapy, combination therapy with abciximab reduces AET, which in turn is associated with reduced residual stenosis and improved ST-segment resolution in AMI. These data provide a pathophysiological link between platelet inhibition, reduced thrombus, and improvements in both epicardial and microvascular perfusion in AMI.

Abciximab and early adjunctive percutaneous coronary intervention are associated with improved ST-segment resolution after thrombolysis: Observations from the TIMI 14 Trial.

BACKGROUND: Percutaneous coronary intervention (PCI) improves clinical outcomes in selected patients with failed thrombolysis but has not been proven to benefit patients who achieve a patent infarct-related artery. Even after successful epicardial reperfusion, myocardial perfusion may be inadequate. We sought to evaluate whether a strategy that uses a reperfusion regimen containing abciximab and a reduced-dose thrombolytic agent (combination therapy), followed by early adjunctive PCI, would result in improved myocardial perfusion, as assessed by ST-segment resolution. METHODS: ST resolution from 90 to 180 minutes after therapy was calculated for all 410 patients from the TIMI 14 trial who had evaluable electrocardiograms at both time points and who were treated with alteplase or reteplase. Patients were grouped according to whether they were treated with combination therapy or full-dose thrombolytic agent alone and whether they underwent PCI between the 90- and 180-minute electrocardiographic measurements. RESULTS: Among 105 patients who underwent adjunctive PCI between 90 and 180 minutes, mean ST resolution from 90 to 180 minutes was significantly greater in those who had received combination therapy versus those who had received full-dose thrombolytic alone (54% vs 8%; P =.002). Among 241 patients with TIMI grade 3 flow in the infarct-related artery at 90 minutes, adjunctive PCI significantly improved mean ST resolution in patients who had been treated with combination therapy (57% [PCI] vs 24% [no PCI]; P =.006), but PCI did not have this effect in patients who had received thrombolytic therapy alone (1% [PCI] vs 10% [no PCI]; P =.70). In a multivariate model controlling for factors that would be expected to independently influence 90- to 180-minute ST resolution, abciximab treatment remained significantly associated with greater ST resolution (P =.008). CONCLUSIONS: A strategy that uses a combination reperfusion regimen that includes abciximab, followed by early adjunctive PCI, is associated with greater ST-segment resolution, which may reflect enhanced tissue level and microvascular perfusion. Future studies should evaluate prospectively the clinical efficacy of this strategy.

Can we replace the 90-minute thrombolysis in myocardial infarction (TIMI) flow grades with those at 60 minutes as a primary end point in thrombolytic trials? TIMI Study Group.

The establishment of patency (Thrombolysis In Myocardial Infarction [TIMI] grade 2 or 3 flow) and/or TIMI grade 3 flow at 60 minutes after thrombolytic administration is both a univariate and multivariate predictor of in-hospital and 30-day mortality, and the odds ratios for mortality are nearly identical for TIMI grade 3 flow at 60 and 90 minutes. Thus, the 60-minute angiographic end point appears to be a valid alternative to that at 90 minutes and may permit earlier decisions regarding post-thrombolytic intervention.

Marginal Mean Models for Dynamic Regimes.

A dynamic treatment regime is a list of rules for how the level of treatment will be tailored through time to an individual's changing severity. In general, individuals who receive the highest level of treatment are the individuals with the greatest severity and need for treatment. Thus there is planned selection of the treatment dose. In addition to the planned selection mandated by the treatment rules, the use of staff judgment results in unplanned selection of the treatment level. Given observational longitudinal data or data in which there is unplanned selection, of the treatment level, the methodology proposed here allows the estimation of a mean response to a dynamic treatment regime under the assumption of sequential randomization.

Global impairment of coronary blood flow in the setting of acute coronary syndromes (a RESTORE substudy). Randomized Efficacy Study of Tirofiban for Outcomes and Restenosis.

Acute coronary syndromes result in a global impairment of coronary blood flow with nonculprit artery blood flow being associated with culprit artery flow and vice versa. Improvements in nonculprit artery flow are related to improvements in culprit artery flow after percutaneous intervention; nonculprit arteries with abnormal flow sustain greater improvements in their flow after culprit artery intervention.