DEVELOPMENT AND VALIDATION OF AN OPTICALLY-BASED STRAIN MEASURING ORTHOPAEDIC SCREW FOR FRACTURE FIXATION IMPLANTS

In the USA over 28 million musculoskeletal injuries are treated annually, including 2 million fracture fixation surgeries (about 0.5% of the population).[1] Treatment of large osseous defects use allografts which have failure rates of up to 25%, and complication rates as high as 30-60%.[2] Fracture fixation usually involves mechanical fixation with rods, plates and/or screws which repair slowly and are susceptible to infection. Implant infection and loosening are serious concerns, but can currently only be measured through expensive instrumented implants, biopsy culture, or radiographs. However, none of these directly quantify implant loading and stability. There is therefore a need for a simple, cost effective way to quantify implant loading and stability in patients. The purpose of this study is to develop an optically-based strain measuring orthopaedic screw prototype to quantify strain variation in the implant in-vivo after surgery and monitor the load sharing between the bone and the implant. The screw developed as part of this thesis incorporates a spectral ruler into the screw head, and is based on the Moire effect which indicates strain. The prototype underwent mechanical testing (cyclic loads ranging from 500 N - 2000 N) to closely resemble in-vivo conditions in order to verify the repeatability and reproducibility of the screw to operate as a measurement system. The screw system developed was able to quantify clinically-relevant bone healing strains in the range of 10-3000 ustrains, corresponding to 0.2 -100 um change in length for a 5 mm gauge length spectral ruler. A 1500 N load resulted in 68.64% color change of a 100 micron spectral ruler with the screw able to measure load fluctuations as small as 2.17 N. It exhibited good repeatability and reproducibility but also possessed some amount of hysteresis due to the mechanism of the screw. The work presented in this research also gives a brief background on the evolution of screw prototypes leading to the development of the orthopaedic screw. The findings in this research show encouraging results which will help develop a unique portable tool for physicians to quantify bone healing, implant loosening and/or infection in vivo rather than relying on less quantitative assessments based on pain and radiography. Future research will involve the development of next generation prototypes for orthopaedic screws. It will also look more closely into bending in orthopedic screws and use of luminescent spectral rulers through layers of tissue

Hemodynamic Perspectives in Anemia

Oxygen delivery in normal physiologic states is determined by cardiac output, hemoglobin, oxygen saturation, and to a lesser extent, dissolved oxygen in the blood. Compensatory mechanisms such as an increase in stroke volume, heart rate, and re-distribution of blood flow helps in scenarios with increased oxygen demand. In cases of acute hemodynamic decompensation, this pre-existing physiologic relation between oxygen delivery and oxygen consumption is altered, resulting in tissue hypoxia and resultant anaerobic metabolism. A persistent state of sub-critical O2 delivery correlates with increased mortality. Oxygen consumption itself is usually independent of delivery unless a critical threshold is unmet. We can use various parameters such as serum lactate, oxygen extraction, and central venous oxygen saturation to determine this pathology. A basic understanding of this physiology will help better tailor therapy to improve outcomes in critically ill patients

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Bronchoscopic lung volume reduction in emphysema: a review

Purpose of review: Chronic obstructive pulmonary disease (COPD) poses a substantial burden on the healthcare system and is currently considered the sixth leading cause of death in the United States. Emphysema, as evidenced by severe air-trapping in patients with COPD, leads to significant dyspnea and morbidity. Lung volume reduction via surgery or minimally invasive endobronchial interventions are currently available, which improve lung function and quality of life. Recent findings: Newer studies have noted a survival benefit in patients post bronchoscopic lung volume reduction vs. those subjected to standard of care. The presence of collateral ventilation is one of the most common impeding factors to placing endobronchial valves, and if placed, these patients might not achieve lobar atelectasis; however, there are newer modalities that are now available for patients with collateral ventilation which we have described. Summary: Combining standard of care treatment that includes smoking cessation, bronchodilators, preventive care including vaccinations, pulmonary rehabilitation, and endobronchial treatment using various interventions in decreasing hyperinflation improves quality of life and may improve survival and hence significantly reduce the burden of COPD on healthcare

Advanced Imaging for Robotic Bronchoscopy: A Review

Recent advances in navigational platforms have led bronchoscopists to make major strides in diagnostic interventions for pulmonary parenchymal lesions. Over the last decade, multiple platforms including electromagnetic navigation and robotic bronchoscopy have allowed bronchoscopists to safely navigate farther into the lung parenchyma with increased stability and accuracy. Limitations persist, even with these newer technologies, in achieving a similar or higher diagnostic yield when compared to the transthoracic computed tomography (CT) guided needle approach. One of the major limitations to this effect is due to CT-to-body divergence. Real-time feedback that better defines the tool–lesion relationship is vital and can be obtained with additional imaging using radial endobronchial ultrasound, C-arm based tomosynthesis, cone-beam CT (fixed or mobile), and O-arm CT. Herein, we describe the role of this adjunct imaging with robotic bronchoscopy for diagnostic purposes, describe potential strategies to counteract the CT-to-body divergence phenomenon, and address the potential role of advanced imaging for lung tumor ablation

Post hypoxic myoclonus: A tale of two minds

Post hypoxic myoclonus (PHM) is considered a poor prognostic sign and may influence decisions regarding withdrawal of treatment. PHM is generally categorized in literature as either acute or chronic (also commonly referred to as Lance-Adams Syndrome) based on the onset of myoclonus. However, it may be more accurate to differentiate between the various presentations of PHM based on the clinical characteristics and electroencephalogram (EEG) findings for prognostication. Here, we describe a case of a 33-year-old female who presented after a cardiopulmonary arrest. MRI of the brain and cervical spine on admission were unremarkable. Twelve hours later, she developed generalized, stimulus-sensitive myoclonus suggestive of acute PHM. Various medications were trialed, and her symptoms eventually improved on clonazepam. On day 14, she started having resting and intention myoclonus, and dysarthria, consistent with LAS. Several adjustments were again made to her regimen, and she was eventually switched from clonazepam to baclofen which improved her resting myoclonus. This case highlights that PHM can present differently and have a markedly different outcome. It is important to develop a better understanding of the various types of PHM so as to avoid premature withdrawal of care

Luminescent spectral rulers for non-invasive strain measurement through tissue

Dynamic compression plates and orthopedic screws maintain proper bone alignment and share load with bone as a fracture heals. We are developing luminescent spectral rulers to evaluate strain on the surface of these devices to mechanically monitor fracture healing and aid in detection of hardware fatigue (e.g. load sharing, implant loosening, and non-union). The strain sensors contain two patterned surfaces: (1) an “encoder†patterned with alternating luminescent lines, and (2) a transparent “analyzer mask†patterned with opaque lines that overlay and mask a portion of the encoder below. Moving the encoder with respect to the analyzer generates a color change that is detected by spectrometer and analyzed in MATLAB. We have fabricated a bromocresol purple patterned encoder that overlays an X-ray scintillator film (Gd2O2S:Eu). The dye absorbs a portion of the Gd2O2S:Eu luminescence spectrum in a position-dependent manner. With our x-ray scintillator sensors reproducible small displacements (~13 microns) through 6 mm thick chicken breast tissue have been detected. Additionally, we have fabricated sensors that do not require ionizing radiation; a 633 nm laser is used for excitation. The sensors contain an encoder patterned with alternating spectrally distinct fluorescent materials. Both sensors provide a non-invasive method for strain analysis through tissue

Post hypoxic myoclonus: A tale of two minds

Post hypoxic myoclonus (PHM) is considered a poor prognostic sign and may influence decisions regarding withdrawal of treatment. PHM is generally categorized in literature as either acute or chronic (also commonly referred to as Lance-Adams Syndrome) based on the onset of myoclonus. However, it may be more accurate to differentiate between the various presentations of PHM based on the clinical characteristics and electroencephalogram (EEG) findings for prognostication. Here, we describe a case of a 33-year-old female who presented after a cardiopulmonary arrest. MRI of the brain and cervical spine on admission were unremarkable. Twelve hours later, she developed generalized, stimulus-sensitive myoclonus suggestive of acute PHM. Various medications were trialed, and her symptoms eventually improved on clonazepam. On day 14, she started having resting and intention myoclonus, and dysarthria, consistent with LAS. Several adjustments were again made to her regimen, and she was eventually switched from clonazepam to baclofen which improved her resting myoclonus. This case highlights that PHM can present differently and have a markedly different outcome. It is important to develop a better understanding of the various types of PHM so as to avoid premature withdrawal of care. Keywords: Lance-Adams syndrome; Myoclonus; Post hypoxic

Rapid Intensive Care Unit Onboarding in Response to a Pandemic

Background: In the wake of the coronavirus disease 2019 (COVID-19) pandemic, hospital resources have been stretched to their limits. We introduced an innovative course to rapidly on-board a group of non-intensive care unit (ICU) nurse practitioners as they begin to practice working in a critical care setting. Objective: To assess whether a brief educational course could improve non-ICU practitioners\u27 knowledge and comfort in practicing in an intensive care setting. Methods: We implemented a multi-strategy blended 12-week curriculum composed of bedside teaching, asynchronous online learning and simulation. The course content was a product of data collected from a targeted needs assessment. The cognitive learning objectives were taught through the online modules. Four simulation sessions were used to teach procedural skills. Bedside teaching simultaneously occurred from critical care faculty during daily rounds. We assessed learning through a pre and post knowledge multiple choice question (MCQ) test. Faculty assessed learners by direct observation and review of clinical documentation. We evaluated learner reaction and comfort in critical practice by comparing pre and post surveys. Results: All 7 NPs were satisfied with the course and found the format to work well with their clinical schedules. The course also improved their self-reported comfort in managing critically ill patients in a medical ICU. There was an increase in the mean group score from the pre-to the post-course MCQ (60% vs 73%). Conclusions: The COVID-19 Critical Care Course (CCCC) for NPs was implemented in our ICU to better prepare for an anticipated second surge. It focused on delivering practical knowledge and skills as learners cared for critically ill COVID-19 patients. In a short period of time, it engaged participants in active learning and allowed them to feel more confident in applying their education. Keywords: COVID-19; ICU; accelerated curriculum; blended learning; critical care; eLearning