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Non-steroidal anti-inflammatory drugs (NSAIDs) are some of the most widely used medications globally, frequently administered to patients experiencing acute, chronic, and inflammatory forms of pain. However, both traditional nonselective NSAIDs, which inhibit the molecular cyclooxygenase pathway, and second-generation NSAIDs, which block cyclooxygenase-2, may cause adverse events, especially at prescription-level doses ¹. 

First, NSAIDs can result in gastrointestinal complications. Studies since 2012 have consistently demonstrated that both traditional NSAIDs and cyclooxygenase-2 inhibitors increase the dose-dependent risk of upper gastrointestinal complications, in the form of upper gastrointestinal bleeding or perforation and peptic ulcers ². A prior history of peptic ulcer, an older age, and concomitant aspirin use predispose individuals to such gastrointestinal complications ³.

Second, NSAIDs may yield cardiovascular complications, including in the form of myocardial infarction and stroke. A 2009 study demonstrated an increased risk of heart disease-associated hospitalization and death linked to all NSAIDs, including rofecoxib, celecoxib, ibuprofen, diclofenac, and naproxen, among others ⁴. This was confirmed by a landmark study in 2013 revealing that the administration of prescription NSAIDs dose-dependently increased an individual’s risk of heart failure, major vascular events, and mortality ⁵.

Finally, renal adverse events may result from the use of prescription-level NSAIDs. A 2006 study found that NSAID compared to non-NSAID use incurred a 3-fold greater risk of acute renal failure after adjusting for age, sex, body mass index, and several comorbidities ⁶. This risk was dose-dependent and increased with long-term use of NSAIDs, as confirmed since by various recent studies.

Various strategies have been put into place to help mitigate the risk of prescription-level NSAID-associated gastrointestinal, cardiovascular, and renal complications. First, cyclooxygenase-2 inhibitors, despite their slightly improved gastrointestinal safety as compared to traditional NSAIDs, have been particularly linked to an increased risk of developing cardiovascular-related events – either selective or nonselective NSAIDs should thus be selected depending on context and patient background. Second, an enteric coating may be used to protect the gastrointestinal tract of at-risk patients. This is often used with aspirin and ibuprofen to help alleviate stomach irritation. A number of different gastroprotectants have been proven effective to this end ³. Finally, some clinicians may choose to add a gastroprotective agent to a patient’s medication regimen. Gastroprotective agents have been found to result in an overall reduction in gastrointestinal complications ⁷. This said, additional strategies need to be developed to specifically target a reduction in cardiovascular and renal complications.

Understanding the factors predisposing individuals to adverse events from prescription-level NSAIDs is key to curbing them through heightened clinician awareness and education. For example, patients with a high gastrointestinal or cardiovascular risk should be considered for alternative therapies. In the future, additional research should seek to further specify the factors that increase a patient’s risk for adverse events in order to ensure the best patient-centric preventive medicine steps are taken. The most effective way to minimize the risk of complications is to use the minimal effective dose of NSAIDs: in 2005, the US Food and Drug Administration issued a public health advisory establishing that “NSAIDs should be administered at the lowest effective dose for the shortest duration consistent with individual patient treatment goals,” corroborated in 2007 by an additional detailed NSAID administration guide. 

References

1.        Fine, M. Quantifying the impact of NSAID-associated adverse events. American Journal of Managed Care (2013).

2.        Castellsague, J. et al. Individual NSAIDs and upper gastrointestinal complications: A systematic review and meta-analysis of observational studies (the SOS Project). Drug Safety (2012). doi:10.2165/11633470-000000000-00000

3.        Sostres, C., Gargallo, C. J., Arroyo, M. T. & Lanas, A. Adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs, aspirin and coxibs) on upper gastrointestinal tract. Best Pract. Res. Clin. Gastroenterol. (2010). doi:10.1016/j.bpg.2009.11.005

4.        Gislason, G. H. et al. Increased mortality and cardiovascular morbidity associated with use of nonsteroidal anti-inflammatory drugs in chronic heart failure. Arch. Intern. Med. (2009). doi:10.1001/archinternmed.2008.525

5.        Baigent, C. et al. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: Meta-analyses of individual participant data from randomised trials. Lancet (2013). doi:10.1016/S0140-6736(13)60900-9

6.        Schneider, V., Lévesque, L. E., Zhang, B., Hutchinson, T. & Brophy, J. M. Association of selective and conventional nonsteroidal antiinflammatory drugs with acute renal failure: A population-based, nested case-control analysis. Am. J. Epidemiol. (2006). doi:10.1093/aje/kwj331

7.        Rahme, E. et al. Gastrointestinal-related healthcare resource usage associated with a fixed combination of diclofenac and misoprostol versus other NSAIDs. Pharmacoeconomics (2001). doi:10.2165/00019053-200119050-00011

            Almost two years into the Covid-19 pandemic, the question still remains: When will the pandemic end? Some believe the answer to this question lies in herd immunity. With a highly infectious disease such as Covid-19, many have argued that eradication of the virus will occur naturally once it has spread throughout the entire community, generating antibody-mediated immunity in those that recover from the disease. The reasoning is that Covid-19 will simply fade away when there are no remaining vulnerable hosts to infect. Individuals who have argued from the herd immunity perspective often advocate for the continued opening of businesses as well as loosened restrictions for mask-wearing, social distancing, and other preventative measures. These practices, they argue, serve to simply prolong the amount of time it takes to reach herd immunity. Countries like Sweden, which have remained fairly open throughout the pandemic and now reportedly have the virus “under control,”¹ have been used to substantiate this argument. The availability of Covid-19 vaccines also raises the question of whether immunity gained from the shots differs from that gained from prior infection.

            Covid-19 vaccines are readily available in many high-income countries, including the United States. Many are asking: Is complete vaccine compliance necessary when, at the end of 2020, approximately 31 percent of the U.S. population had already been infected with Covid-19?² Ostensibly, this would mean that roughly a third of Americans already had some sort of antibody-mediated immunity to the disease, and certainly more have been infected since the publication of the aforementioned study.

            Authors Bozio et al. sought to answer this exact question in a study published in November of 2021.³ They examined a number of hospitalized individuals over the age of 18 who had either previously tested positive for Covid-19 infection (via a rapid assay test or reverse PCR testing) or been fully vaccinated with an mRNA vaccine (two doses, given within the recommended timeframe) in the past 90-179 days. The primary outcome was the result of a Covid-19 test taken at the time of hospitalization. When the results were adjusted for pertinent sociodemographic and health factors, the authors found that individuals who had received the Covid-19 vaccine were less likely to test positive for Covid-19 than those who had been previously infected. Interestingly, further analysis revealed that recipients of the Moderna vaccine appeared to have improved immunity when compared to recipients of the Pfizer-BioNTech vaccine. This was consistent with a previous study published in September of 2021 which reported similar findings.⁴

            These accumulative results would suggest that vaccines confers greater immunity when compared to a prior history of Covid-19 infection. While there are some limits to this study – for example, children were excluded, as the U.S. only recently gave full approval for administration of the Pfizer vaccine to individuals aged five and up⁵ – the results were fairly conclusive. These findings support the CDC recommendation that all Americans eligible to receive the vaccine should do so, for the benefit of both personal and public health.

References

[1] Carlsson, M., & Söderberg-Nauclér, C. (2021). Indications that Stockholm has reached herd immunity, given limited restrictions, against several variants of SARS-COV-2. (preprint). https://doi.org/10.1101/2021.07.07.21260167.

2 One in three Americans Already Had COVID-19 by the End of 2020. Columbia Public Health. (2021, August 26). Retrieved from https://www.publichealth.columbia.edu/public-health-now/news/one-three-americans-already-had-covid-19-end-2020.

3 Centers for Disease Control and Prevention. (2021, November 4). Laboratory-Confirmed COVID-19 Among Adults Hospitalized with COVID-19–Like Illness with Infection-Induced or mRNA Vaccine-Induced SARS-COV-2 Immunity – Nine States, January–September 2021. Centers for Disease Control and Prevention. Retrieved from https://www.cdc.gov/mmwr/volumes/70/wr/mm7044e1.htm?s_cid=mm7044e1_w.

4 Self WH; Tenforde MW; Rhoads JP; Gaglani M; Ginde AA; Douin DJ; Olson SM; Talbot HK; Casey JD; Mohr NM; Zepeski A; McNeal T; Ghamande S; Gibbs KW; Files DC; Hager DN; Shehu A; Prekker ME; Erickson HL; Gong MN; Mohamed A; Henning DJ; Steingrub JS; Peltan ID; Brown SM; Martin ET; Mo. (2021). Comparative effectiveness of Moderna, Pfizer-BioNTech, and Janssen (Johnson & Johnson) Vaccines in Preventing COVID-19 Hospitalizations Among Adults Without Immunocompromising Conditions – United States, March-August 2021. MMWR. Morbidity and mortality weekly report. Retrieved from https://pubmed.ncbi.nlm.nih.gov/34555004/.

5 Centers for Disease Control and Prevention. (n.d.). Covid-19 Vaccines for Children and Teens. Centers for Disease Control and Prevention. Retrieved from https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations/children-teens.html

Atelectasis occurs when air is not able to fully expand the alveoli of the lungs. 90% of patients undergoing general anesthesia experience atelectasis (Randtke et al, 2015). This is because general anesthesia decreases muscle tone and thus functional residual capacity (FRC) — the amount of air that is left in the lungs after exhaling. Atelectasis increases the risk for hypoxemia and pneumonia and can continue into the postoperative period. Preventing and reversing atelectasis can improve patient outcomes for surgeries that require general anesthesia (Randtke et al, 2015).

There are three explanations of the physiological cause of atelectasis that are generally agreed upon. The absorption mechanism is based on oxygen balance. Often, patients undergoing anesthesia will be placed on 100% oxygen, which pushes nitrogen gas out of the lungs (nitrogen is a component of normal atmospheric air) (Randtke et al, 2015). Oxygen is absorbed by the capillary bed, leaving the alveoli with too little gas remaining inside. Since the alveoli are not supported by cartilage, only the pressure of gases against their walls, they then collapse (Randtke et al, 2015). This can also occur with a low ventilation to perfusion ratio — when the capillary beds absorb oxygen faster than the person’s breathing can provide more air. The decreased FRC with general anesthesia exacerbates this problem. It is a challenge to get the appropriate oxygen balance, as not providing enough oxygen can also lead to hypoxemia during the procedure (Randtke et al, 2015).

The compression mechanism for atelectasis occurs when the pleural pressure in the chest cavity is greater than the intrapulmonary pressure. With the reduced muscle tone that occurs under anesthesia, the weight of the chest and the patient’s organs against the diaphragm are significant contributing factors in this mechanism (Randtke et al, 2015). Inflammation and buildup of fluid in the pleural space can also contribute. The pressure can push residual air out of the lungs, further decreasing the FRC and leading to alveolar collapse (Randtke et al, 2015).

The third mechanism is related to abnormalities in surfactant. Surfactant is produced by specific cells in the alveoli and reduces surface tension, making it easier for the lungs to expand (Randtke et al, 2015). Reduced surfactant makes it more difficult for alveoli to stay open in the first place,  re-inflate once collapsed and stabilized once reopened. General anesthesia may have some impact on surfactant abnormalities but more research is needed to clarify its role in atelectasis in this context (Randtke et al, 2015).

As shown in a recent meta-analysis regarding prevention and treatment pathways of postoperative pulmonary complications, there is not a lot of high-quality data currently available (Odor et al, 2020). With the lower quality data that is available, interventions found to have a significant effect include postoperative continuous positive airway pressure (CPAP), mucolytic medications (specifically ambroxol) and respiratory physiotherapy (a series of muscle training and breathing exercises practiced before and after the surgery). There is moderate quality data for intraoperative lung protective ventilation, defined as using reduced tidal volumes (<8 mL/kg), positive end expiratory pressure of at least 5 cm H2O and intermittent recruitment maneuvers (high pressure applied for a short period of time to inflate the lungs more fully) (Odor et al, 2020). It is also important to look at prevention in specific patient populations, such as in pediatric patients. One newer study suggests that use of CPAP during induction and emergence in children decreases the risk of intraoperative atelectasis, as well as the risk of residual atelectasis in the postoperative period (Acosta et al, 2021). Another recent study suggests that high-flow nasal cannula oxygen in the postoperative period reduces residual atelectasis (Lee et al, 2021). Overall, more high-quality comparative research on the effectiveness of different prevention methods is needed for all patient populations.

References

Acosta CM, Lopez Vargas MP, Oropel F, et al. Prevention of atelectasis by continuous positive airway pressure in anaesthetised children: A randomised controlled study. Eur J Anaesthesiol. 2021;38(1):41-48. doi:10.1097/EJA.0000000000001351

Lee J-H, Ji S-H, Jang Y-E, Kim E-H, Kim J-T, Kim H-S. Application of a High-Flow Nasal Cannula for Prevention of Postextubation Atelectasis in Children Undergoing Surgery: A Randomized Controlled Trial. Anesthesia & Analgesia. 2020;133(2):474-482. doi:10.1213/ane.0000000000005285

Odor PM, Bampoe S, Gilhooly D, Creagh-Brown B, Moonesinghe SR. Perioperative interventions for prevention of postoperative pulmonary complications: systematic review and meta-analysis. BMJ. 2020;368:m540. doi:10.1136/bmj.m540

Randtke MA, Andrews BP, Mach WJ. Pathophysiology and Prevention of Intraoperative Atelectasis: A Review of the Literature. J Perianesth Nurs. 2015;30(6):516-527. doi:10.1016/j.jopan.2014.03.012

Across the United States in 2019, over 1 in 10 households were defined as being food-insecure. Food-insecure households are, according to U.S. Department of Agriculture (USDA), “uncertain of having, or unable to acquire, at some time during the year, enough food to meet the needs of all their members because they had insufficient money or other resources for food.” These food-insecure households include 5.3 million U.S. households with “very low food security,” which disrupts eating patterns and leads to food intake levels below those considered adequate.¹

While rates of food insecurity have significantly declined since they spiked to nearly 15 percent of households following the 2008 stock market crash,¹ preliminary data shows that the COVID-19 pandemic has dramatically worsened food insecurity, which was already considered one of “the nation’s leading health and nutrition issues.”² Feeding America, a national anti-hunger nonprofit, estimates that 1 in 8 people may experience food insecurity in 2021, with those most impacted by the pandemic at greater risk. Notably, racial disparities in food security that existed before the COVID-19 pandemic remain severe, with 1 in 5 Black individuals in the U.S. projected to experience food insecurity in 2021 (nearly double the rate among white individuals).³

The health complications associated with food insecurity are well-documented. Among children, these include anemia, key nutrient deficiencies, behavioral problems such as aggression, and mental health challenges such as depression and suicidal ideation.² Many of these issues persist for adults, who are also more likely to develop chronic conditions, like diabetes, chronic heart disease, chronic obstructive pulmonary disease (COPD), hypertension, and hyperlipidemia.^2,4 A study from the USDA on working-age U.S. adults found that food security status is more strongly correlated with chronic disease than income, which was only associated with hepatitis, arthritis, and COPD out of 10 chronic diseases significantly associated with food insecurity.⁵

How food insecurity may cause many chronic conditions remains under-researched. One exception is type 2 diabetes, which is reportedly twice as common in food-insecure individuals than others. Food scarcity may trigger peripheral insulin resistance, increases in cortisol, and accumulation of central adiposity (belly fat), which are all conditions associated with diabetes. Obesity, which some studies have found to be associated with food insecurity, may also play a role in making individuals vulnerable to diabetes and other chronic conditions.²

These findings are indicative of the essential tie between food insecurity and an inability to access nutritious food, which together impact overall health. In general, the cost of a diet rich in healthy foods — including fruits and vegetables, fish, and nuts — is greater than one reliant on highly processed foods, including meats and refined grains, according to a Harvard School of Public Health meta-analysis of 27 studies.⁶ A USDA study likewise found that foods high in saturated fat and/or added sugars are overall less expensive, per calorie.⁷ The authors of the Harvard study estimate that a “healthy” diet costs on average $1.50 more per day, which amounts to $550 per year and is an appreciable investment for low-income individuals.⁶

Making healthier foods more accessible, the authors write, would require a reversal of many decades of policies that have created “a complex network of farming, storage, transportation, processing, manufacturing and marketing capabilities” that have generated an economy for highly processed, low-priced foods.⁶ While the federal government has historically invested in food initiatives for low-income people, notably the Supplemental Nutrition Assistance Program (SNAP), there has been little innovation in these programs over the past four decades, in spite of a dramatic increase in diet-related illnesses such as obesity and type 2 diabetes.⁸ SNAP benefits are based on a 1970s metric that represents the minimal amount of money needed to purchase a nutritious diet, and therefore do not align with modern dietary recommendations and economic circumstances. Before the pandemic, SNAP benefits averaged less than $1.40 per meal.⁹

The need for improving nutritional health and equity across the country is clear. Greater government coordination across federal agencies and programs, especially within the National Institutes of Health, can strengthen government research and programs.⁸ Beyond taxation of less healthy foods and subsidies for more nutritious options, greater governmental coordination can fuel projects to revolutionize the production, transportation and marketing of healthier foods, increasing their availability while reducing their prices.⁶

References 

1. Coleman-Jensen A, Rabbitt MP, Gregory CA, Singh A. Household Food Security in the United States in 2019. U.S. Department of Agriculture. Published 2020. https://www.ers.usda.gov/publications/pub-details/?pubid=99281 

2. Gundersen C, Ziliak JP. Food insecurity and health outcomes. Health Aff (Millwood). 2015;34(11):1830-1839. 

3. Hake M, Dewey A, Engelhard E, et al. The Impact of the Coronavirus on Food Insecurity. Feeding America. Published 2021. https://www.feedingamerica.org/sites/default/files/2021-03/National%20Projections%20Brief_3.9.2021_0.pdf 

4. Sun Y, Liu B, Rong S, et al. Food insecurity is associated with cardiovascular and all-cause mortality among adults in the United States. J Am Heart Assoc. 2020;9(19):e014629. 

5. Gregory CA, Coleman-Jensen A. Food Insecurity, Chronic Disease, and Health Among Working-Age Adults. U.S. Department of Agriculture. Published 2017. https://www.ers.usda.gov/publications/pub-details/?pubid=84466 

6. Rao M, Afshin A, Singh G, Mozaffarian D. Do healthier foods and diet patterns cost more than less healthy options? A systematic review and meta-analysis. BMJ Open. 2013;3(12):e004277. 

7. Carlson A, Frazao E. Are healthy foods really more expensive? It depends on how you measure the price. SSRN Electron J. Published online 2012. doi:10.2139/ssrn.2199553 

8. Fleischhacker SE, Woteki CE, Coates PM, et al. Strengthening national nutrition research: rationale and options for a new coordinated federal research effort and authority. Am J Clin Nutr. 2020;112(3):721-769. 

9. Carlson S, Keith-Jennings B, Llobrera J. Modernizing SNAP Benefits Would Help Millions Better Afford Healthy Food. Center on Budget and Policy Priorities. Published 2021. https://www.cbpp.org/research/food-assistance/modernizing-snap-benefits-would-help-millions-better-afford-healthy-food 

Sleep allows the body and mind to recharge; without it, the human brain cannot function properly, and the body becomes more susceptible to disease. Sleep apnea involves brief stoppages in breathing that cause a person to wake repeatedly, which over time can increase risk of cardiovascular disease, depression, high blood pressure, and type 2 diabetes (O’Connor, 2019). For those with the condition, nightly sleep becomes a noisy struggle to breathe rather than a period of restoration. The most common type of sleep apnea is known as obstructive sleep apnea (OSA), which increases the risk of complications during surgery, and despite decades of research, there are no approved medications to treat the condition (Brody, 2019). However, in June of 2021, a team of researchers at Flinders University in Australia found promising results for a potential treatment. Their research, first published in the Journal of Physiology, found that a two-drug combination can reduce sleep apnea by at least 30% (Lim et al., 2021).

There are currently only a few therapies for sleep apnea patients. Continuous positive airway pressure (CPAP) therapy works to prevent a person’s airway from collapsing during sleep (Schein, 2014). CPAP machines, which are comprised of a mask, tube, and motor, use mild air pressure to keep the mask wearer’s airways open. While the CPAP therapy approach works for many, the most common side effects include nasal congestion or runny nose, feelings of claustrophobia, and difficulty falling asleep (Bakalar, 2021). Variable and bi-level positive airway pressure (VPAP and BPAP) therapies work similarly.

An alternative approach is a mandibular repositioning device; these are oral appliances designed to keep the airway open by bringing the wearer’s jaw forward or holding their tongue in place (Marques et al., 2019). However, these devices can be expensive, cause jaw pain, and are less reliable than PAP machines (Bakalar, 2021). Surgery is the last resort for sleep apnea: in the most common of these procedures, surgeons remove obstructive tissues that block the airway (Brody, 2019). Cheaper, over-the-counter approaches like nasal decongestant and breathing strips rarely work for diagnosed sleep apnea.

Researchers at Flinders University found that a combination of two medications – butylbromide and reboxetine – kept pharyngeal muscles active during sleep in people with sleep apnea, allowing for improvement in airway collapsibility and more regular and steady breathing (Lim et al., 2021). Butylbromide is an antispasmodic drug, while reboxetine is most often used to treat depression. While the medications had previously been shown to improve upper airway function during sleep for healthy individuals, its effect on sleep apnea severity was unknown until the Flinders researchers completed their study (Flinders Newsdesk, 2021). Out of fifteen original volunteers, twelve otherwise healthy individuals with OSA completed a double-blind, randomized, placebo-controlled trial (Lim et al., 2021). The research team observed participants for two nights. Each participant received either the two-drug combination or placebo immediately prior to sleep; using nasal masks, pneumotachographs (devices that record the rate of airflow), epiglottic pressure sensors, and more, researchers captured data to create estimates of OSA severity between the two groups. “Almost everyone we studied had some improvement in sleep apnea,” said Professor Danny Eckert, lead researcher and Director of Adelaide Institute for Sleep Health at Flinders (Flinders Newsdesk, 2021). “People’s oxygen intake improved. Their number of breathing stoppages was a third or more less.”

The research team will next look at the long-term effects of this drug combination and similar medications. For now, the findings of the recent study bode well for future developments in pharmacological treatment for OSA.

References 

Bakalar, Nicholas. (2021, May 31). For Sleep Apnea, a Mouth Guard May be a Good Alternative to CPAP. The New York Times. https://www.nytimes.com/2021/05/31/well/mind/sleep-apnea-treatment-mouth-guard.html 

Brody, Jane E. (2019, May 27). Sleep Apnea Can Have Deadly Consequences. The New York Times. https://www.nytimes.com/2019/05/27/well/mind/sleep-apnea-can-have-deadly-consequences.html 

Flinders Newsdesk. (2021, July 7). Drug combo cuts severity of sleep apnoea. Flinders University. https://news.flinders.edu.au/blog/2021/07/07/drug-combo-cuts-severity-of-sleep-apnoea/ 

Lim, R., Messineo, L., Grunstein, R.R., Carberry, J.C. and Eckert, D.J. (2021), The noradrenergic agent reboxetine plus the antimuscarinic hyoscine butylbromide reduces sleep apnoea severity: a double-blind, placebo-controlled, randomised crossover trial. J Physiol. https://doi.org/10.1113/JP281912 

Marques, M., Genta, P.R., Azarbarzin, A., Taranto-Montemurro, L., Messineo, L., Hess, L.B., Demko, G., White, D.P., Sands, S.A. and Wellman, A. (2019), Structure and severity of pharyngeal obstruction determine oral appliance efficacy in sleep apnoea. J Physiol, 597: 5399-5410. https://doi.org/10.1113/JP278164 

O’Connor, Anahad. (2019, April 10). A Guide to Sleep Apnea. The New York Times. https://www.nytimes.com/guides/well/sleep-apnea-guide 

Schein, A. S., Kerkhoff, A. C., Coronel, C. C., Plentz, R. D., & Sbruzzi, G. (2014). Continuous positive airway pressure reduces blood pressure in patients with obstructive sleep apnea; a systematic review and meta-analysis with 1000 patients. Journal of Hypertension, 32(9), 1762–1773. https://doi.org/10.1097/HJH.0000000000000250 

An accurate estimation of the timing of labor is important for several clinical decisions, including determination of preterm birth and necessary treatment regimens [1]. Currently, gestational age and due date is approximated based on information about the last menstrual cycle and assumes a gestational length of 40 weeks [1,2]. Ultrasound imaging in early pregnancy can also be used to determine gestational age and estimated date of delivery [1]. Although these approaches are useful in managing pregnancy, neither method is an accurate predictor of when labor will begin, since most pregnancies deviate from the standard of 40 weeks of gestational duration [2]. To advance clinical decision-making, efforts have been made to better predict the actual onset of labor using predictive biomarkers measured by blood tests [2].

During pregnancy, the maternal circulatory system connects with the fetal circulatory system through the placenta, carrying a variety of compounds such a steroid hormones, micronutrients, and nucleic acids [1]. The maintenance of pregnancy relies on finely tuned adaptions to the concentrations of these biomarkers, which can be easily detected in maternal blood using high-content metabolomic, proteomic, and single-cell cytometric technologies [2].

A 2019 study funded by the University Hospitals of Leicester yielded results that support the idea that it may be possible to predict the onset of labor from a single blood test [3]. The researchers monitored the plasma concentrations of N-arachidonylethanolamine (AEA), N-acylethanolamines (NAE), N-oleoylethanolamide (OEA), and N-palmitoylethanolamide (PEA) in 217 pregnant patients [3]. In line with previous studies that had shown that plasma AEA concentrations increase in the third trimester and peak in labor, they found that women at risk for pre-term labor also had an elevated plasma AEA concentration [3]. The data suggested that a single AEA measurement taken from a blood sample can predict the gestational age of delivery and the remaining duration of pregnancy with better accuracy compared to conventional methods [3].

Similarly, a 2021 study by Stanford University sought to determine the dynamic changes in the maternal metabolome, proteome, and immunome preceding the day of labor [2]. The analysis of the results revealed a marked transition from pregnancy maintenance to pre-labor physiology starting 2 to 4 weeks before labor onset [2]. Endocrine and inflammatory changes were pronounced during late pregnancy, with steroid hormone metabolites being among the most informative biomarkers [2]. A decline in progesterone levels was linked to the progression to labor [2]. Moreover, the surge in steroid hormone metabolites weeks before labor coincided with changes in plasma protein concentrations and immune cell responses [2]. A sharp increase in the concentration of IL-4, an IL-33 antagonist, was found to play a prominent regulatory role during the pre-labor phase [2]. In mice, IL-33 has been shown to have a role in pregnancy maintenance [2].

The non-invasive nature of maternal blood tests offers great promise as a way to predict labor onset [3]. Research continues to determine the best biomarkers for estimating the timing of labor and has the potential to transform the management of pregnancy, especially in relation to pre-term birth [1-3].

References

1. Liang, L., Rasmussen, M., Piening, B. etc. (2020). Metabolic dynamics and prediction of gestational age and time to delivery in pregnant women. Cell, 181(7), 1680-1692. doi:10.1016/j.cell.2020.05.002
2. Stelzer, I., Ghaemi, M., Han, X. etc. (2021). Integrated trajectories of the maternal metabolome, proteome, and immunome predict labor onset. Science Translational Medicine, 13(592). doi:10.1126/scitranslmed.abd9898
3. Bachkangi, P., Taylor, A., Bari, M. etc. (2019). Prediction of preterm labour from a single blood test: The role of the endocannabinoid system in predicting preterm birth in high-risk women. European Journal of Obstetrics & Gynecology and Reproductive Biology, 243, 1-6. doi:10.1016/j.ejogrb.2019.09.029

Distal radius fractures, or breaks in the radius bone of the arm close to the wrist, are among the most common types of bone fractures. Many of these fractures, particularly if they are displaced (i.e., if the bone fragments on either side of the break are not aligned), require surgery, known as distal radius repair, to ensure proper setting and healing of the radius.¹ There are several options for anesthesia during radius repair—most notably general anesthesia, local anesthesia, and peripheral nerve blocking (a specific type of local anesthesia)—and recent studies have begun to evaluate the benefits and drawbacks of each approach, particularly with regard to pain control, postoperative functional outcomes, and length of stay.

Some studies have identified better clinical outcomes for distal radius repair with local, rather than general, anesthesia. For instance, Egol et al. collected data from 187 patients and found that patients who received local anesthesia had improved wrist and finger range of motion compared with patients who received general anesthesia and also showed higher functional scores (as measured by Disabilities of the Arm, Shoulder and Hand) at 3- and 6-month follow-ups.² In contrast, Rundgren et al. found using a single-center randomized clinical trial of 88 patients that, while local anesthesia appeared to significantly reduce early patterns of postoperative pain and opioid consumption after radius repair, neither total opioid consumption nor longer-term functional outcomes differed significantly between the local and general anesthesia groups.³

Peripheral nerve blocking, a type of local anesthesia, has also recently been employed in comparison studies with general anesthesia to examine its effects on outcomes following distal radius repair. For example, Galos et al. conducted a randomized controlled study of 36 patients to answer four questions: (1) whether patients receiving general anesthesia or brachial plexus blockade (a type of peripheral nerve blockade administered through a single infraclavicular shot) had worse pain scores at various time points, (2) whether there was a difference in operating suite time and recovery room time between the two groups, (3) whether either group experienced higher postoperative narcotic use, and (4) whether either group displayed higher functional assessment scores 6 and 12 weeks after surgery. The researchers found that patients who received general anesthesia had worse pain 2 hours postoperatively, while patients who received a brachial plexus blockade reported worse pain 12 hours postoperatively, suggesting that “rebound pain” ought to be taken into consideration when employing peripheral nerve blocking. Both time in the recovery room and overall amount of narcotics consumed was higher for patients who received general anesthesia, but functional scores did not differ between the two groups.⁴

In addition, Johnson et al. found this past year, based on a review of 80 patients, that patients who were treated with peripheral nerve blocking reported a significant decrease in postoperative pain at discharge as well as decreased length of stay. These researchers reported one minor complication with peripheral nerve blocking: a short-lived skin irritation at the site of injection.⁵

References 

(1)  Distal Radius Fracture (Wrist Fracture) | Johns Hopkins Medicine https://www.hopkinsmedicine.org/health/conditions-and-diseases/distal-radius-fracture-wrist-fracture. 

(2)  Egol, K. A.; Soojian, M. G.; Walsh, M.; Katz, J.; Rosenberg, A. D.; Paksima, N. Regional Anesthesia Improves Outcome After Distal Radius Fracture Fixation Over General Anesthesia. Journal of Orthopaedic Trauma 2012, 26 (9), 545–549. https://doi.org/10.1097/BOT.0b013e318238becb. 

(3)  Rundgren, J.; Mellstrand Navarro, C.; Ponzer, S.; Regberg, A.; Serenius, S.; Enocson, A. Regional or General Anesthesia in the Surgical Treatment of Distal Radial Fractures: A Randomized Clinical Trial. The Journal of Bone and Joint Surgery 2019, 101 (13), 1168–1176. https://doi.org/10.2106/JBJS.18.00984. 

(4)  Galos, D. K.; Taormina, D. P.; Crespo, A.; Ding, D. Y.; Sapienza, A.; Jain, S.; Tejwani, N. C. Does Brachial Plexus Blockade Result in Improved Pain Scores After Distal Radius Fracture Fixation? A Randomized Trial. Clinical Orthopaedics & Related Research 2016, 474 (5), 1247–1254. https://doi.org/10.1007/s11999-016-4735-1. 

(5)  Johnson, P.; Hustedt, J.; Matiski, T.; Childers, R.; Lederman, E. Improvement in Postoperative Pain Control and Length of Stay With Peripheral Nerve Block Prior to Distal Radius Repair. Orthopedics 2020, 43 (6). https://doi.org/10.3928/01477447-20200721-14. 

COVID-19, like many viral diseases, continues to impact patients’ health even after they have resolved their initial infections. Symptoms manifest across different organ systems with varying levels of severity. A literature review published March 22, 2021 in Nature Medicine by Nalbandian et al. surveyed the current research on post-acute COVID-19 disease. Across different studies of post-acute sequelae of SARS-CoV-2 infection (PASC), researchers observed pulmonary, cardiovascular, neuropsychiatric, hematologic, renal, endocrine, gastrointestinal, and dermatologic conditions, underscoring the complex, heterogeneous nature of the syndrome.¹

In a prospective cohort study of 1,733 Chinese patients observed at six months from the onset of COVID-19 symptoms, Huang et al. found that a majority of the patients (76 percent) reported at least one PASC symptom. Fatigue or muscular weakness were the most commonly reported symptom (63 percent), in line with other studies.² Chronic fatigue has been observed after numerous other acute infections, like SARS coronavirus.³ In one analysis, nearly all (97 percent) of a cohort of 29 patients admitted to a rehabilitation center after overcoming severe COVID-19 still experienced gait speed deficits at discharge from the rehabilitation center.⁴

Pulmonary complications are notably prevalent as well, with over one-fifth (23 percent) of participants in the study by Huang et al. experiencing dyspnea.² In smaller studies conducted over shorter follow-up periods, this number was as high as 40 percent. Other observed symptoms include cough and persistent oxygen requirements. Those who had more severe acute COVID-19, including patients who required a high-flow nasal cannula or mechanical ventilation, may be at risk for serious long-term complications like pulmonary fibrosis and pneumonia.¹

Neuropsychiatric complications continue to impact the quality of life and daily activities of a significant number of COVID-19 survivors. In the study by Huang et al., 23 percent of individuals experienced anxiety or depression and 26 percent had sleep difficulties.² In a small United Kingdom study, 30 percent of hospitalized COVID-19 patients had symptoms of PTSD. In all of the studies summarized by Nalbandian et al., loss of taste and smell was experienced by over 10 percent of study participants. Cognitive impairment has widely been noted as well, with many suffering from “brain fog” (difficulties with concentration, memory, executive function and more).¹

Beyond impacting individuals’ wellbeing, cognitive and physical fatigue associated with post-acute COVID-19 will alter productivity and the economy. Chronic fatigue symptoms bear resemblance to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), which currently poses an estimated financial burden of between $17 and $24 billion in the U.S. each year. Experts propose that even if only 25 million Americans contract COVID-19 by the end of 2021 and only 10 percent subsequently suffer from an illness meeting the ME/CFS definition, the number of Americans suffering from ME/CFS would at least double over one year. Globally, they estimate that the number of people suffering from ME/CFS would increase to 110 million during 2021.³

Pulmonary complications will also pose economic consequences. While only one year of data is available thus far on the healthcare costs associated with COVID-19, the Kaiser Family Foundation studied these figures to estimate that the annual cost of treating COVID-19 cases only for uninsured Americans might range from $13.9 billion to $41.8 billion.⁵ It is also necessary to consider healthcare costs for managing conditions that can be exacerbated by lasting damage from a previous COVID-19 infection, such as pneumonia. Before the pandemic, roughly 1.5 million people were hospitalized for pneumonia each year in the U.S., at an average cost of $20,000 per stay.

The novelty of COVID-19 and the limited opportunities to observe its ongoing impacts mean that much is unknown about the prevalence and characteristics of post-acute conditions. Hypotheses about their causes abound: the effects of hospitalization, acute respiratory distress syndrome, and the impact of the hyperinflammatory response associated with COVID-19 may all play roles. Other important factors are confounding health disparities, social determinants of health, and the psychosocial impact of the pandemic.⁶

In December, Congress promised $1.15 billion over four years for the National Institutes of Health to fund research on the prolonged health consequences of COVID-19.⁷ Moreover, over 30 U.S. hospitals and health systems have already established clinics solely devoted to post-COVID-19 research and care.⁸ The long-term effects of COVID-19 remain unclear, and health systems, researchers, and clinicians are still in the initial stages of learning about how to best care for patients.

References 

1. Nalbandian A, Sehgal K, Gupta A, et al. Post-acute COVID-19 syndrome. Nat Med. 2021;27(4):601-615. 

2. Huang C, Huang L, Wang Y, et al. 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. Lancet. 2021;397(10270):220-232. 

3. Komaroff AL, Bateman L. Will COVID-19 lead to myalgic encephalomyelitis/chronic fatigue syndrome? Front Med (Lausanne). 2020;7:606824. 

4. Olezene CS, Hansen E, Steere HK, et al. Functional outcomes in the inpatient rehabilitation setting following severe COVID-19 infection. PLoS One. 2021;16(3):e0248824. 

5. Dovere E-I. Vaccine refusal will come at a cost—for all of us. Atl Mon. Published online April 10, 2021. https://www.theatlantic.com/politics/archive/2021/04/vaccine-refusal-hesitancy-economic-costs/618528/ 

6. Bhadelia, N. “Post Acute Sequelae of SARS-CoV-2 (PAS-C)” Lecture presented at MassCPR Scientific Symposium: COVID-19 Diagnostic Testing and Clinical Management; March 30, 2021; https://www.youtube.com/watch?v=5RX2IM4Srgc.  

7. NIH launches new initiative to study “Long COVID.” NIH. Published February 23, 2021. https://www.nih.gov/about-nih/who-we-are/nih-director/statements/nih-launches-new-initiative-study-long-covid 

8. Carbajal E. 30 hospitals, health systems that have launched post-COVID-19 clinics. Beckers Hospital Review. https://www.beckershospitalreview.com/patient-safety-outcomes/13-hospitals-health-systems-that-have-launched-post-covid-19-clinics.html

The field of outpatient services has grown rapidly over the last several years, spurred by changes to reimbursements for inpatient procedures from health plan providers. One result of this is an increasing number of hybrid surgery centers — facilities that operate as both an office-based laboratory (OBL) and an ambulatory surgical center (ASC). Usually, a hybrid suite contains the imaging equipment typical of an OBL, as well as the equipment and sterilization standards necessary for surgical and non-surgical interventions [1]. While hybrid surgery centers can offer advantages to both patients and healthcare providers that a traditional hospital setting cannot, the transition to this structure may prove difficult. OBL-ASC facilities are complex structures that have many financial, legal, and practical hurdles.  

The flexibility of hybrid suites is advantageous to medical organizations and patients alike. The ability to transition from office to OR can improve patient outcomes in the event of an emergency during a routine procedure [2]. It also allows for non-surgical and surgical procedures to be performed consecutively or simultaneously, thus reducing the number of hospital admissions and shortening the length of stay for patients, which saves money and increases efficiency [3]. Hybrid centers have the potential to guide the standard for medical treatment toward a more integrated approach [4]. Improving patient outcomes and satisfaction is also beneficial for medical providers as the industry shifts toward value-based care [5]. Structurally, the hybrid center is less bureaucratic than the traditional hospital and allows physicians to increase their income through equity ownership [6].  

Despite these prospective benefits, there are many logistical obstacles to instituting a hybrid surgery center. Legal regulations can make it difficult to build a hybrid suite or convert existing offices. Under federal law, in order for an OBL and ASC to operate within the same facility, they must maintain different hours of operation and keep medical records separate. Certain states also restrict the proliferation of outpatient clinics based on need and access [7]. The performance of hybrid procedures must be accommodated not only by new facilities but by new, interdisciplinary working dynamics. Optimizing the design of hybrid centers will require repeated study of the workflow in these environments, and improved collaboration between medical professionals [7].  

Despite the difficulties of establishing hybrid surgery centers, these facilities are growing rapidly and encompass a large share of healthcare services in the country. This trend is the result of a confluence of factors. Many insurance providers no longer cover routine procedures when performed in a hospital because of the higher costs associated with inpatient procedures [8]. Patients, too, object to high costs and have demanded alternatives, pressuring the industry to embrace hybrid centers [5]. The most recent development accelerating the shift, however, is more urgent than market forces. In order to minimize exposure and free up hospital resources for COVID-19 patients, pressure for outpatient centers to increase their caseload has grown. While the pandemic is ongoing, outpatient facilities, including hybrid centers, are easing the strain on hospitals by providing care that would otherwise have been delayed [9].       

References 

[1] Bazzi, May, et al. “The Drama in the Hybrid OR: Video Observations of Work Processes and Staff Collaboration During Endovascular Aortic Repair.” Journal of Multidisciplinary Healthcare, vol. 12, 2019, pp. 453-464, doi: 10.2147/JMDH.S197727.   

[2] “Hybrid Surgical Procedures.” Hybrid Operating Rooms & Hybrid Cath Labs, J.M. Keckler Medical Co., hybridoperatingroom.com/hybrid-surgical-procedures/. 

[3] Bazzi, May, et al. “Team Composition and Staff Roles in a Hybrid Operating Room: A Prospective Study Using Video Observations.” Nursing Open, 2019, doi: 10.1002/nop2.327.   

[4] Davidson, Michael J. and Tsuyoshi Kaneko. “Use of the Hybrid Operating Room in Cardiovascular Medicine.” Circulation, vol. 130, no. 11, 2014, pp. 910-917, doi: 10.1161/CIRCULATIONAHA.114.006510. 

[5] Derek Long, David McMillan, et al.| CPA, ASA | Apr 1, 2019. “HOPDs vs. ASC: Understanding Payment Differences.” 1 Apr. 2019, https://www.hfma.org/topics/hfm/2019/ april/hopds-vs–asc–understanding-payment-differences.html. 

[6] Tim van Biesen and Todd Johnson | Healthcare Private Equity Advisers | Sept 23, 2019. “Ambulatory Surgery Center Growth Accelerates: Is Medtech Ready?” Bain & Company, 23 Sept. 2019, https://www.bain.com/insights/ambulatory-surgery-center-growth-accelerates-is- medtech-ready/. 

[7] Cilek, Jacob A. and Jason S. Greis. 12 Business and Legal Considerations for Developing a ‘Hybrid’ Office-Based Laboratory–Ambulatory Surgery Center. McGuire Woods, Sept. 2019, https://media.mcguirewoods.com/publications/2019/OBL-ASC-Hybrid-Article-12-Considerations.pdf. 

[8] Karen Blum | Office of Johns Hopkins Physicians | Apr 25, 2018. “Shifting Low-Risk Procedures to Ambulatory Surgery Centers.” BestPractice News, 25 Apr. 2018, https://www. hopkinsmedicine.org/office-of-johns-hopkins-physicians/best-practice-news/shifting-low-risk-procedures-to-ambulatory-surgery-centers. 

[9] Jacqueline LaPointe | Revcycle Intelligence | Mar 17, 2020. “Hospitals Delay, Shift Surgeries to Outpatient Due to COVID-19.” Revcycle Intelligence, 17 Mar. 2020, https://revcycleintelligen ce.com/news/hospitals-delay-shift-surgeries-to-outpatient-due-to-covid-19.

Anemia is a condition that results in low red blood cell count and hemoglobin deficiency, decreasing the blood’s capacity to carry oxygen [1]. The World Health Organization specifies that hemoglobin concentrations of less than 12.0g/dl in non-pregnant women and 13.0g/dl in men could be considered anemic [2]. There are a number of potentially serious consequences of anemia, including increased cardiac output, which can lead to damage to the heart’s muscular tissue [3]. Perioperative anemia is not uncommon and can make surgery and recovery significantly more complicated. Furthermore, anemia in surgical patients is associated with higher morbidity and mortality rates [4].  

In order to improve the survival and recovery outcomes for anemic surgical patients, the condition must first be diagnosed and treated appropriately. Unfortunately, perioperative anemia often does not receive the attention it warrants until hemoglobin levels become low enough for blood transfusion [5]. A study by Beattie et al. found that transfusion rates were three times higher for anemic patients than their non-anemic counterparts. [2]. When transfusions are required, the risk of complications such as ischemic stroke and myocardial infarction rises significantly, and transfusions are associated with higher morbidity rates among surgical patients [6].  

As anemia has gained attention in the medical community, a number of recommendations and strategies for preventing morbidities associated with anemia in surgical patients have been released. In 2005, an interdisciplinary panel of medical professionals advised that elective surgery patients have their hemoglobin levels tested at least thirty days before surgery and that unexplained anemia should always be considered as an effect of a condition that requires pre-surgical attention [7]. The American Society of Anesthesiology advises that the necessity for blood transfusion is usually indicated at a hemoglobin level of <6g/dl, but that ischemia, bleeding, and other risks should be weighed alongside it [6]. More recently, researchers created an automated system for iron-deficiency anemia screening, which they found to improve diagnosis over clinical procedures [4].  

Concerns regarding morbidity rates for anemic patients extend to all members of the surgical team, including anesthesia providers. The anesthesia provider should review vital signs and patient data and evaluate whether red blood cell transfusion is worth the risk to the patient. Because anemia is associated with poorer outcomes, care providers must carefully weigh the decision to administer a transfusion [1]. Several medical associations have issued guidelines for evaluating the necessity of transfusion. These guidelines include considerations of hemoglobin levels as well as various health factors. Current trends indicate that physicians’ ability to identify and treat anemia is developing rapidly, improving outcomes for surgical patients with anemia. 

References 

[1] Klick, John C., and Edwin G. Avery. “Anesthetic Considerations for the Patient With Anemia and Coagulation Disorders.” Anesthesiology, edited by David E. Longnecker et al, McGraw-Hill, 2012, pp. 196-216.   

[2] Beattie, Scott W., et al. “Risk Associated With Preoperative Anemia in Noncardiac Surgery: A Single-Center Cohort Study.” Anesthesiology, vol. 110, 2009, doi: 10.1097/ALN.0b013e318 19878d3. 

[3] “Anemia Compensation.” Open Anesthesia, 26 Feb., https://www.openanesthesia.org/anemia _compensation/. 

[4] Okocha, Obianuju, et al. “An Effective and Efficient Testing Protocol for Diagnosing Iron-Deficiency Anemia Preoperatively.” Anesthesiology, vol. 133, 2020, 109-118, doi: 10.1097/ALN.0000000000003263. 

[5] Warner, Matthew A., et al. “Perioperative Anemia: Prevention, Diagnosis, and Management Throughout the Spectrum of Perioperative Care.” Anesthesia & Analgesia, vol. 130, no. 5, 2020, 1364-1380, doi: 10.1213/ANE.0000000000004727. 

[6] Shander, Aryeh et al., “Anesthesia for Patients With Anemia.” Anesthesiology Clinics, vol. 34, no. 4, 2016, 711-730, doi: 10.1016/j.anclin.2016.06.007. 

[7] Goodnough, Laurence T., et al. “Detection, Evaluation, and Management of Anemia in the Elective Surgical Patient.” Anesthesia & Analgesia, vol. 101, no. 6, 2005, 1858-1861, doi: 10.1213/01.ANE.0000184124.29397.EB.