Using machine learning for process improvement in sepsis management.

INTRODUCTION: In the U.S., sepsis afflicts 1.7 million adults, causing 270,000 deaths each year. Early detection of sepsis could decrease the number of deaths by 92,000 annually and decrease hospital expenditures by 1.5 billion USD. Few prior studies and reviews have presented a holistic understanding of the relationship between machine learning and existing process improvement measures. This study, in addition to discussing machine learning and existing process improvements measures, elaborates on the disadvantages and the barriers to integrating machine learning into the clinic. This article synthesizes previous studies to educate healthcare professionals on effectively managing sepsis by leveraging the benefits of machine learning. METHODS: This study used the PubMed database. Search terms include sepsis antibiotics, sepsis process improvement, sepsis machine learning. Our search criteria included previous studies published between January 1, 2017, and February 1, 2022. RESULTS/DISCUSSION: Although machine learning algorithms have better predictive capabilities, their effectiveness in the clinical setting is limited as studies show mixed results because the medical staff often fails to intervene. To overcome poor interventional response, clinicians need to work with the facility's IT department to ensure integration into clinical workflow and minimize alert-fatigue. Algorithms should enhance the productivity of clinical teams, not attempt to replace them entirely. CONCLUSION: Hospitals can employ process improvement measures that effectively utilize machine learning algorithms to ensure integration into clinical workflows. Healthcare professionals can utilize workflow tools in addition to the predictive capabilities of machine learning to enhance clinical decisions in sepsis.

Association between socioeconomic factors and origin of hospital referrals among patients with oral cancer.

BACKGROUND: The Brazilian Unified Health System (SUS) is responsible for offering free assistance to more than 100 million Brazilians, including treatment of oral cancer lesions. Considering that the Brazilian public system aids the most vulnerable population, this study analyzed whether the origin of hospital referrals of patients with oral cancer is associated with socioeconomic factors. MATERIAL AND METHODS: A cross-sectional study was carried out from cancer hospital records of the National Cancer Institute (RHC-INCA), considering the primary locations (C00 to C06) diagnosed between 2016 and 2019. Data on gender, skin color (white and non-white), education (no schooling, incomplete or complete elementary education; high school; incomplete and complete higher education) and origin of referral (SUS and non-SUS) were analyzed by multiple logistic regression (p<0.05). RESULTS: Higher referral rates by the SUS were observed in 2017 (OR=1.27; 95% CI=1.098-1.480) and 2018 (OR=1.28; 95% CI=1.101-1.490); no differences were found between the years 2016 and 2019. Regarding gender, men were 40% more likely to have the SUS as the source of referral (OR=1.40; 95% CI=1.233-1.600). Non-white individuals were 34% more likely to have the SUS as the source of the referral (OR=1.34; 95% CI=1.190-1.512). Illiterate individuals or individuals who only attended elementary school were 6.38 times more likely to be referred by the SUS than individuals with higher education (OR=6.38; 95% CI=5.228-7.796). CONCLUSIONS: It is concluded that the origin of hospital referrals via SUS of patients with oral cancer is associated with socioeconomic factors.

Effects of feeding 25-hydroxyvitamin D3 with an acidogenic diet during the prepartum period in dairy cows: Mineral metabolism, energy balance, and lactation performance of Holstein dairy cows.

Our objective was to determine the effects of feeding 25-hydroxyvitamin D3 [25(OH)D3], or vitamin D3 (cholecalciferol) on plasma, mineral, and metabolite concentrations, mineral balance, mineral excretion, rumination, energy balance, and milk production of dairy cows. We hypothesized that supplementing 3 mg/d of 25(OH)D3 during the prepartum period would be more effective than supplementing vitamin D3 at the National Research Council (2001) levels to minimize calcium imbalance during the transition period and improve milk production of dairy cows. Forty multiparous, pregnant nonlactating-Holstein cows were enrolled in this study. Body weight, body condition score, parity, and milk yield in the previous lactation (mean ± standard deviation) were 661 ± 59.2, 3.46 ± 0.35, 1.79 ± 0.87, and 33.2 ± 6.43 kg/d, respectively. Cows were enrolled into the blocks (n = 20 for each treatment) at 30 d of the expected day of calving to receive an acidogenic diet (373 g/kg of neutral detergent fiber and 136 g/kg of crude protein, dry matter basis; -110 mEq/kg) associated with the treatments: (1) control (CTRL), vitamin D3 at 0.625 mg/d (equivalent to 25,000 IU of vitamin D3/d) or (2) 25(OH)D3 at 3 mg/d (equivalent to 120,000 IU of vitamin D3/d). All cows were fed with the base ration for 49 d after calving. Blood samples were taken on d 7, 0, 1, 2, 21, and 42, relative to calving. No effect of treatment was observed for prepartum dry matter intake or body condition score. A trend for increase of ionized Ca was observed for the cows fed 25(OH)D3, compared with the CTRL, but no effect of treatment was detected for total Ca or total P. Feeding 25(OH)D3 increased colostrum yield. The plasmatic concentration of 25-hydroxyvitamin D3 was increased with 25(OH)D3 supplementation. 25-Hydroxyvitamin D3 supplementation increased plasma glucose concentration at parturition. The postpartum dry matter intake was not influenced by treatments. Feeding 25(OH)D3 increases milk yield, 3.5% fat-corrected milk, and energy-corrected milk and improves milk yield components in early lactation. Overall, these findings suggest that 25(OH)D3 at 3 mg/d can improve the energy metabolism and lactation performance, compared with the current-feeding practice of supplementing vitamin D3 at 0.625 mg/d.

Using rumination and activity data for early detection of anaplasmosis disease in dairy heifer calves.

Bovine anaplasmosis causes considerable economic losses in dairy cattle production systems worldwide, ranging from $300 million to $900 million annually. It is commonly detected through rectal temperature, blood smear microscopy, and packed cell volume (PCV). Such methodologies are laborious, costly, and difficult to systematically implement in large-scale operations. The objectives of this study were to evaluate (1) rumination and activity data collected by Hr-Tag sensors (SCR Engineers Ltd.) in heifer calves exposed to anaplasmosis; and (2) the predictive ability of recurrent neural networks in early identification of anaplasmosis. Additionally, we aimed to investigate the effect of time series length before disease diagnosis (5, 7, 10, or 12 consecutive days) on the predictive performance of recurrent neural networks, and how early anaplasmosis disease can be detected in dairy calves (5, 3, and 1 d in advance). Twenty-three heifer calves aged 119 ± 15 (mean ± SD) d and weighing 148 ± 20 kg of body weight were challenged with 2 × 107 erythrocytes infected with UFMG1 strain (GenBank no. EU676176) isolated from Anaplasma marginale. After inoculation, animals were monitored daily by assessing PCV. The lowest PCV value (14 ± 1.8%) and the finding of rickettsia on blood smears were used as a criterion to classify an animal as sick (d 0). Rumination and activity data were collected continuously and automatically at 2-h intervals, using SCR Heatime Hr-Tag collars. Two time series were built including last sequence of -5, -7, -10, or -12 d preceding d 0 or a sequence of 5, 7, 10, or 12 d randomly selected in a window from -50 to -15 d before d 0 to ensure a sequence of days in which PCV was considered normal (32 ± 2.4%). Long short-term memory was used as a predictive approach, and a leave-one-animal-out cross-validation (LOAOCV) was used to assess prediction quality. Anaplasmosis disease reduced 34 and 11% of rumination and activity, respectively. The accuracy, sensitivity, and specificity of long short-term memory in detecting anaplasmosis ranged from 87 to 98%, 83 to 100%, and 83 to 100%, respectively, using rumination data. For activity data, the accuracy, sensitivity, and specificity varied from 70 to 98%, 61 to 100%, and 74 to 100%, respectively. Predictive performance did not improve when combining rumination and activity. The use of longer time-series did not improve the performance of models to predict anaplasmosis. The accuracy and sensitivity in predicting anaplasmosis up to 3 d before clinical diagnosis (d 0) were greater than 80%, confirming the possibility for early identification of anaplasmosis disease. These findings indicate the great potential of wearable sensors in early identification of anaplasmosis diseases. This could positively affect the profitability of dairy farmers and animal welfare.

A 10-s sprint performed prior to moderate-intensity exercise prevents early post-exercise fall in glycaemia in individuals with type 1 diabetes.

AIMS/HYPOTHESIS: We investigated whether a 10-s maximal sprint effort performed immediately prior to moderate-intensity exercise provides another means to counter the rapid fall in glycaemia associated with moderate-intensity exercise in individuals with type 1 diabetes. MATERIALS AND METHODS: Seven complication-free type 1 diabetic males (21.6 +/- 3.6 years; mean+/-SD) with HbA(1c) levels of 7.4 +/- 0.7% injected their normal morning insulin dose and ate their usual breakfast. When post-meal glycaemia fell to approximately 11 mmol/l, participants were asked to perform a 10-s all-out sprint (sprint trial) or to rest (control trial) immediately before cycling at 40% of peak rate of oxygen consumption for 20 min, with both trials conducted in a random counterbalanced order. RESULTS: Sprinting did not affect the rapid fall in glycaemia during the subsequent bout of moderate-intensity exercise (2.9 +/- 0.4 mmol/l in 20 min; p = 0.00; mean+/-SE). However, during the following 45 min of recovery, glycaemia in the control trial decreased by 1.23 +/- 0.60 mmol/l (p = 0.04) while remaining stable in the sprint trial, subsequently decreasing in this latter trial at a rate similar to that in the control trial. The large increase in noradrenaline (norepinephrine) (p = 0.005) and lactate levels (p = 0.0005) may have contributed to the early post-exercise stabilisation of glycaemia in the sprint trial. During recovery, adrenaline (epinephrine) and NEFA levels increased marginally in the sprint trial, but other counter-regulatory hormones did not change significantly (p < 0.05). CONCLUSIONS/INTERPRETATION: A 10-s sprint performed immediately prior to moderate-intensity exercise prevents glycaemia from falling during early recovery from moderate-intensity exercise in individuals with type 1 diabetes.

Lower prevalence of reported asthma in adolescents with symptoms of rhinitis that received neonatal BCG.

BACKGROUND: BCG is a vaccine used against tuberculosis and leprosy and is an immunostimulant that primes T(H)1 lymphocytes to produce cytokines that antagonize atopy both in animal models and in man. Considering that atopy is the main risk factor for asthma, one can hypothesize that vaccination inducing T(H)1 responses, such as BCG, can be protective against asthma. OBJECTIVE: To estimate the association between neonatal BCG vaccination and prevalence of asthma among adolescents. STUDY DESIGN: Cross-sectional study with schoolchildren aged 12-16 years. The presence of a scar compatible with BCG was used as a surrogate of neonatal vaccination. A self administered structured questionnaire was prepared based on that used by the International Study of Asthma and Allergies in Childhood. The prevalence of asthma was categorized according to the report of lifetime wheeze, lifetime asthma, lifetime asthma among those referring allergy and among those referring allergy and sneezing. RESULTS: Neonatal BCG vaccination was not associated with the overall prevalence of reported wheezing or asthma. However, in the subgroup reporting current allergy and sneezing, neonatal BCG was associated with a 37% reduction of prevalence of lifetime asthma. CONCLUSIONS: In the population we surveyed, neonatal BCG scar was associated with a reduction in the risk of asthma only in individuals with a past history suggestive of allergic rhinitis.

Glycogen resynthesis in the absence of food ingestion during recovery from moderate or high intensity physical activity: novel insights from rat and human studies.

The finding that during recovery from high intensity exercise, rats have the capacity to replenish their muscle glycogen stores even in the absence of food intake has provided us with an experimental model of choice to explore further this process. Our objective here is to share those questions arising from research carried out by others and ourselves on rats and humans that are likely to be of interest to comparative biochemists/physiologists. On the basis of our findings and those of others, it is proposed that across vertebrate species: (1). the capacity of muscles to replenish their glycogen stores from endogenous carbon sources is dependent on the type of physical activity and animal species; (2). lactate and amino acids are the major endogenous carbon sources mobilized for the resynthesis of muscle glycogen during recovery from exercise, their relative contributions depending on the duration of recovery and type of exercise; (3). the relative contributions of lactate glyconeogenesis and hepatic/renal gluconeogenesis to muscle glycogen synthesis is species- and muscle fiber-dependent; and (4). glycogen synthase and phosphorylase play an important role in the control of the rate of glycogen synthesis post-exercise, with the role of glucose transport being species-dependent.

Sciatic nerve lipoprotein lipase is reduced in streptozotocin-induced diabetes and corrected by insulin.

The metabolic abnormalities underlying the cause of diabetic neuropathy have been the subject of much debate. Lipoprotein lipase (LPL) is a 56-kDa enzyme produced by several tissues in the body and has recently been shown in vitro to be expressed in cultured Schwann cells, where it is important in phospholipid synthesis. This suggests a role for LPL in myelin biosynthesis in the peripheral nervous system. The aim of this study was to determine if acute streptozotocin (STZ)-induced diabetes reduces the expression and regulation of sciatic nerve LPL in vivo. Adult Sprague Dawley rats were rendered diabetic via an sc injection of STZ. A decrease in sciatic nerve LPL activity was observed in the STZ-treated rats after just 2 d of diabetes and remained significantly reduced for at least 35 d. The decrease in LPL activity coincided temporally with a drop in motor nerve conduction velocity. Treatment with insulin for 4 d showed a normalization of sciatic nerve LPL activity. These results show that STZ-induced diabetes causes a decrease in LPL activity in the sciatic nerve that, as in other tissues, is reversible with insulin treatment. These data may suggest a role for LPL in the pathophysiology of diabetic neuropathy.

Clinical impact of transesophageal echocardiography in patients with stroke without clinical evidence of cardiovascular sources of emboli.

OBJECTIVE: The purpose of this study is to evaluate the impact of transeophageal echocardiography on management of patients at low-risk for cardiogenic embolism to prevent new potential cardiovascular sources of emboli. METHODS: We studied 69 patients with ischemic stroke at low-risk for cardiogenic embolism. Transeophageal echocardiography was performed to access: left atrium enlargement; communication or aneurysm of the interatrial septum; patent foramen ovale; spontaneous echo contrast or intracavitary thrombi; the presence of intraaortic atherosclerotic plaques or thrombi; significant valvar morphologic alteration or dysfunction; left ventricle enlargement, hypertrophy, or contractile abnormality. Transesophageal echocardiography altered clinical management, and we adopted anticoagulant therapy or another procedure apart from the use of acetylsalicylic acid. RESULTS: Transeophageal echocardiography detected at least one abnormality in 40 cases (58%). Clinical conduct was adjusted after the performance of transesophageal echocardiography in 11 patients (15.9%); anticoagulation was added in 10 cases and surgical correction in one patient. CONCLUSION: Transeophageal echocardiography was a very useful tool in the secondary prevention for stroke in patients at low risk for cardiogenic embolism.

Overexpressing human lipoprotein lipase in mouse skeletal muscle is associated with insulin resistance.

Lipoprotein lipase (LPL) plays a rate-limiting role in triglyceride-rich lipoprotein metabolism and is expressed in most tissues. Overexpression of LPL in skeletal muscle has been linked with higher plasma glucose levels suggesting insulin resistance (Jensen et al., Am J Physiol 273:R683-R689, 1997). The aim of our study was to ascertain whether the overexpression of human LPL in skeletal muscle leads to insulin resistance and to investigate the mechanism. Respiratory quotient measurements in both transgenic (MCKhLPL) and nontransgenic mice on a high-carbohydrate diet were conducted and showed a shift in fuel usage in transgenic mice when fasting but not when actively feeding. An increase in citrate and glucose 6-phosphate levels in fasted MCKhLPL mice further supports this preferential use of lipids. When challenged with an intraperitoneal injection of glucose (1 g/kg), MCKhLPL mice had a higher plasma glycemic excursion than nontransgenic mice. No differences in insulin response were observed between the two groups. Further investigation using hyperinsulinemic-euglycemic clamps revealed insulin resistance in MCKhLPL mice. Despite signs of insulin resistance, there was no associated increase in free fatty acids, hypertriglyceridemia, or hyperinsulinemia in MCKhLPL mice. In conclusion, MCKhLPL mice are insulin resistant, presumably due to increased delivery of lipoprotein-derived fatty acids to muscle.

Effect of streptozotocin-induced diabetes on glycogen resynthesis in fasted rats post-high-intensity exercise.

It has recently been shown that food intake is not essential for the resynthesis of the stores of muscle glycogen in fasted animals recovering from high-intensity exercise. Because the effect of diabetes on this process has never been examined before, we undertook to explore this issue. To this end, groups of rats were treated with streptozotocin (60 mg/kg body mass ip) to induce mild diabetes. After 11 days, each animal was fasted for 24 h before swimming with a lead weight equivalent to 9% body mass attached to the tail. After exercise, the rate and the extent of glycogen repletion in muscles were not affected by diabetes, irrespective of muscle fiber composition. Consistent with these findings, the effect of exercise on the phosphorylation state of glycogen synthase in muscles was only minimally affected by diabetes. In contrast to its effects on nondiabetic animals, exercise in fasted diabetic rats was accompanied by a marked fall in hepatic glycogen levels, which, surprisingly, increased to preexercise levels during recovery despite the absence of food intake.

Prolonged exposure to halothane and associated changes in carbohydrate metabolism in rat muscles in vivo.

Halothane, an anesthetic presently used in animal experimentation, is reported to stimulate glycogen breakdown in isolated preparations of rat skeletal muscles, suggesting that it may not be a suitable anesthetic for the study of glycogen metabolism in rats in vivo. The purpose of this study was to establish whether prolonged exposure to halothane in rats in vivo is associated with accelerated glycogenolysis. Exposure of rats to halothane for up to 1 h was not accompanied by either any change in the levels of glycogen or increase in activity ratios of glycogen phosphorylase in muscles, irrespective of their fiber compositions. In marked contrast, the levels of lactate, inorganic phosphate, glucose 1-phosphate, glucose 6-phosphate, fructose 1,6-bisphosphate, and fructose 2, 6-bisphosphate changed progressively during anesthesia. Accordingly, the interpretation of muscle metabolite levels must be performed with caution in experiments involving prolonged exposure to halothane. Overall, our findings indicate that the reported halothane-mediated stimulation of glycogen breakdown in vitro is likely to be an artifact and that halothane is a suitable anesthetic for experiments concerned with glycogen metabolism in rats.

Regulation of glycogen synthase and phosphorylase during recovery from high-intensity exercise in the rat.

The aim of this study was to determine the role of the phosphorylation state of glycogen synthase and glycogen phosphorylase in the regulation of muscle glycogen repletion in fasted animals recovering from high-intensity exercise. Groups of rats were swum to exhaustion and allowed to recover for up to 120 min without access to food. Swimming to exhaustion caused substantial glycogen breakdown and lactate accumulation in the red, white and mixed gastrocnemius muscles, whereas the glycogen content in the soleus muscle remained stable. During the first 40 min of recovery, significant repletion of glycogen occurred in all muscles examined except the soleus muscle. At the onset of recovery, the activity ratios and fractional velocities of glycogen synthase in the red, white and mixed gastrocnemius muscles were higher than basal, but returned to pre-exercise levels within 20 min after exercise. In contrast, after exercise the activity ratios of glycogen phosphorylase in the same muscles were lower than basal, and increased to pre-exercise levels within 20 min. This pattern of changes in glycogen synthase and phosphorylase activities, never reported before, suggests that the integrated regulation of the phosphorylation state of both glycogen synthase and phosphorylase might be involved in the control of glycogen deposition after high-intensity exercise.