Cohort design is a type of research design where investigators follow subjects over time, tracking their development through a set of health-related metrics [1]. As opposed to experimental investigations where researchers intervene to alter the conditions of studied populations, cohort studies involve no such intervention [2]. Instead, studies begin with identifying subjects to place them into two groups: exposed and non-exposed populations [3]. Over time, these groups are studied to determine the incidence, prevalence, prognosis, and potential causes of the central condition [3].  

 

Depending on what investigators hope to study, cohort studies are either prospective or retrospective. In a prospective cohort study, the cohort is selected and measured for various risk factors and exposures before the outcome occurs [2]. An example of a prospective study would be one where investigators seek to measure the likelihood of psoriasis patients experiencing side-effects due to anesthesia. A group of patients with psoriasis would be identified. These people would be tested to ensure that they do not already have conditions that complicate the administration of anesthesia. Then, the researchers would return to these patients over an extended period, tracking whether they have experienced side-effects during procedures since the start of the experiment. 

 

Conversely, retrospective studies aim to analyze a cohort that has already experienced the given outcome [2]. Experimenters collect all their data from records [1]. They will begin with each patient’s initial exposure and status at baseline and continue to follow up into the future, accumulating further data [1]. One retrospective study tracked the occurrence of pneumonia following the contraction of HIV by 2,628 women [4]. Every six months, the subjects would fill out a survey and provide a blood sample [4].  

 

Although the aforementioned study was retrospective, it was combined with data from a simultaneous prospective study to create a more complete picture of pneumonia incidence in HIV-positive individuals [4]. Neither prospective nor retrospective studies are infallible, so combining them may allow researchers to sidestep individual shortcomings.  

 

Generally, prospective designs are considered more robust sources of valid evidence, but this is not always the case and can often come at a cost [5]. Prospective studies can provide researchers with accurate data collection that accounts for exposures, endpoints, and confounders [5]. But this high level of detail requires a vast investment of time and money. Follow-up periods are typically long, and investigators must follow-up with a large number of people [5]. Additionally, prospective designs run a greater risk of loss to follow-up, leading to lost data and reduced internal validity [5]. Especially in the context of rare diseases, where populations are already small, prospective studies may prove too inefficient and inappropriate for meaningful observation [5]. 

 

While retrospective methods offer a more time- and cost-efficient approach to cohort designs, the quality of available data can be a concern in these studies [5]. Because investigators have to work with existing data that may not have taken into account certain risk factors or exposures, these studies are more likely to be affected by confounding variables [2]. Information, recall, and selection biases may also reduce the validity of the results [3].  

 

Despite each approach’s shortcomings, many of these concerns can be avoided if investigators meticulously design their studies with these shortcomings in mind. Researchers believe that either form of cohort design, if designed carefully and thoroughly, can result in generalizable, accurate results with important implications for the study of medicine [5]. 

 

References 

 

[1] M. S. Setia, “Methodology Series Module 1: Cohort Studies,” Indian Journal of Methodology, vol. 61, no. 1, p. 21-25, Jan-Feb 2016. [Online]. Available: https://doi.org/10.4103/0019-5154.174011. 

 

[2] I. Oliveira, “Cohort studies: prospective and retrospective designs,” Students 4 Best Evidence via Cochrane, March 2019. [Online]. Available: https://bit.ly/3fN22jE. 

 

[3] X. Wang and M. W. Kattan, “Cohort Studies: Design, Analysis, and Reporting,” Chest Journal, vol. 158, no. 1, p. S72-S78, July 2020. [Online]. Available: https://doi.org/10.1016/j.chest.2020.03.014. 

 

[4] S. R. Cole et al., “Combined analysis of retrospective and prospective occurrences in cohort studies: HIV-1 serostatus and incident pneumonia,” International Journal of Epidemiology, vol. 35, no. 6, p. 1442-1446, Aug 2006. [Online]. Available: https://doi.org/10.1093/ije/dyl176. 

 

[5] A. M. Euser et al., “Cohort Studies: Prospective versus Retrospective,” Nephron Clinical Practice, vol. 113, no. 3, p. c214-c217, Oct 2009. [Online]. Available: https://doi.org/10.1159/000235241. 

 

Prevention and management of spinal anesthesia-induced hypotension is essential for preventing complications in the perioperative/peripartum period. In 2018, an international consensus statement was published that detailed guidelines for managing hypotension related to spinal anesthesia for cesarean sections. In summary, the publication recommended the following: vasopressors should be used routinely and preemptively, alpha-agonist drugs such as phenylephrine are preferred as first-line agent due to abundance of data on their use, left uterine displacement and colloid preloading or crystalloid co-loading should be routinely performed, and systolic blood pressure goal should be kept within 90% of baseline.

 

Researchers also recommended that a phenylephrine infusion should be started at 25-50mcg/min just after spinal injection (with a lower dosing recommended for pre-eclamptic patients who exhibit less hypotensive response), and tachycardia and bradycardia should be avoided and treated with fluids or beta-agonist respectively. Significant bradycardia with hypotension may warrant use of ephedrine or an anticholinergic, and circulatory collapse should be promptly treated with epinephrine.²

 

Of note, when compared to physician-controlled infusions, smart pumps and double-drug infusions may yield better hemodynamics. At least three studies have suggested that norepinephrine, when delivered via smart pump, may improve maternal and fetal physiology, but studies comparing phenylephrine and norepinephrine using standard pumps are lacking.^3-5 Such modalities perform optimally when combined with continuous non-invasive blood pressure monitoring, however, patient safety in the case of artifactual measurements needs more study as well. Regarding monitoring, standard ASA monitors are required and non-invasive blood pressures are ideally taken every 1-2 minutes as equipment/resources allow. Regarding resource-poor care areas, it is considered unreasonable to proceed with spinal blockade without vasopressor and anticholinergics readily available. For the novice provider, a fixed-rate vasopressor infusion with concurrent boluses as needed has been found to be an effective alternative to provider-managed titration of the infusion.

 

Patients with cardiac disease should be receive individualized care (choice of vasopressor, monitors, anesthetic technique, etc.) based on the entire clinical picture, taking into account their baseline physiology and expected changes related to surgery/labor, anesthesia, and delivery. Single-shot spinal blocks in the setting of cardiac disease pose increased risk of hemodynamic instability compared to combined low-dose combined spinal/epidural or epidural-only techniques. This is due to the quick-onset of sympathectomy seen with full-dose spinal anesthesia. Controlled titration of neuraxial blockade is recommended for the majority of these types of cases.

 

Results of a recently published survey from Ireland indicate that phenylephrine is the most widely used vasopressor currently. A concerning finding is that ~80% of the 15 reporting centers did not routinely maintain heart rate at baseline or use the rate as a surrogate for cardiac output. Following publication of the aforementioned consensus statement, two of the reporting centers changed practice to use phenylephrine primarily. Of note, a significant number of centers reported not using phenylephrine infusions due to fear of precipitating bradycardia and/or low cardiac output. Only 3 centers had a departmental protocol for management of spinal anesthesia-induced hypotension and only 2 changed practice based on the consensus statement, heralding a need for more support, resources, and assessment of the barriers to implementation. Furthermore, some aspects of the guideline can be improved when more evidence becomes available, such as the recommendations on ephedrine for bradycardia, smart infusions, or fluid pre/co-loading.¹

 

Potential advances in the management of spinal hypotension include the search for optimal vasopressors or combinations of drugs; advances in monitoring to allow rapid assessment of risk of hypotension, cardiac output, volume status, etc.; and genetic studies to predict individual responses to vasopressors.

 

References

 

1. ffrench-O’Carroll R, Tan T. National survey of vasopressor practices for management of spinal anaesthesia-induced hypotension during caesarean section. International Journal of Obstetric Anesthesia. 2020.  doi:10.1016/j.ijoa.2020.09.003

 

2. Kinsella SM, Carvalho B, Dyer RA, et al. International consensus statement on the management of hypotension with vasopressors during caesarean section under spinal anaesthesia. Anaesthesia. 2018;73(1):71-92.  doi:10.1111/anae.14080

 

3. Ngan Kee WD. Norepinephrine for maintaining blood pressure during spinal anaesthesia for caesarean section: A 12-month review of individual use. International Journal of Obstetric Anesthesia. 2017;30:73-74. doi:10.1016/j.ijoa.2017.01.004

 

4. Ngan Kee WD, Khaw KS, Tam Y, Ng FF, Lee SW. Performance of a closed-loop feedback computer-controlled infusion system for maintaining blood pressure during spinal anaesthesia for caesarean section: A randomized controlled comparison of norepinephrine versus phenylephrine. Journal of Clinical Monitoring and Computing. 2017;31(3):617-623. doi:10.1007/s10877-016-9883-z

 

5. Ngan Kee WD, Lee SWY, Ng FF, Tan PE, Khaw KS. Randomized double-blinded comparison of norepinephrine and phenylephrine for maintenance of blood pressure during spinal anesthesia for cesarean delivery. Anesthesiology. 2015;122(4):736-745. doi:10.1097/ALN.0000000000000601

The importance of vitamins for overall health has long been recognized [1]. Recent studies have found that optimization of vitamin levels prior to surgery is associated with improved surgical outcomes, leading to an increased awareness of the relationship between nutrition and recovery from surgery [1]. 

The influence of vitamin D levels on post-surgical outcomes has recently become a research topic of interest [2]. Vitamin D is a fat-soluble steroid hormone that is important for musculoskeletal health, playing a role in over 300 metabolic pathways [2]. Epidemiological studies have demonstrated that vitamin D is both cardioprotective and neuroprotective [3]. Additionally, it plays a role in innate and acquired immunity [3]. The recommended circulating vitamin D level is >75 nmol/L [4]. Vitamin D deficiency is most commonly caused by inadequate sun exposure and can lead to rickets in children and exacerbated osteopenia, osteoporosis, and fractures in adults [4]. Deficiencies are also associated with an increased risk of cancer, autoimmune diseases, hypertension, and infectious disease [4]. In cases of low vitamin D serum concentrations, vitamin D supplements are effective for maintaining healthy blood concentrations [4]. Higher vitamin D levels are associated with decreased risk of in-hospital mortality and morbidity [3]. 

A 2013 study completed by researchers at the University of Ottawa found that vitamin D deficiency contributes to secondary organ pathophysiology, prolonged stays in the ICU, and worse outcomes in critically ill patients [5]. The researchers focused on children with congenital heart disease (CHD), a high-risk pediatric population [5]. Post-operatively, patients with CHD commonly experience pronounced systemic inflammation, coagulopathy, respiratory failure, electrolyte disturbances, arrhythmia, myocardial dysfunction, kidney failure, and infection [5]. Vitamin D supplementation prior to surgery was determined to be an ideal intervention for improving post-surgical outcomes in children with CHD [5]. 

Similarly, a 2019 study led by researchers at the University of Edinburgh and Trinity College Dublin found strong evidence of an association between lower vitamin D levels and adverse colorectal cancer survival following surgical resection [6]. The results of the study also pointed to a strong genotype-specific effect of vitamin D, with a post-surgical survival association greatest in those with a single nucleotide polymorphism within the VDR gene sequence (rs11568820) [6]. 

The impact of other vitamins on surgical outcomes continues to be explored [7]. It is known that vitamin C is a key requirement for proper wound healing [7]. Sufficient levels of vitamin C are necessary for protocollogen hydroxylase enzyme activity, which produces collagen, the most abundant protein in the body [7]. Vitamin A has also been found to have significant wound-healing activity [7]. Vitamin A is important for proper functioning of the inflammatory response and synthesis of collagen and ground substances [7]. Lastly, vitamin K has been linked to decreased post-operative bleeding [8]. In patients receiving a left ventricular assist device (LVAD), bleeding more than 48 hours post-implant occurred in only 5% of pre-operative vitamin-K treated patients as opposed to 26% of patients not treated with vitamin K [8]. 

Optimization of nutritional state, including vitamin levels, prior to surgery leads to improved surgical outcomes [1]. As the body of literature showing the connection between vitamin levels and surgical outcomes grows, nutritional screening protocols should be considered in the pre-operative evaluation of patients [1]. 

 

References 

 

1. Evans, D., Martindale, R., Kiraly, L., & Jones, C. (2013). Nutrition Optimization Prior to Surgery. Nutrition in Clinical Practice, 29(1), 10-21. doi:10.1177/0884533613517006 
2. Iglar, P., & Hogan, K. (2015). Vitamin D status and surgical outcomes: a systematic review. Patient Safety in Surgery, 9(1). doi:10.1186/s13037-015-0060-y 
3. Turan, A., Hesler, B., You, J., Saager, L., Grady, M., & Komatsu, R. et al. (2014). The Association of Serum Vitamin D Concentration with Serious Complications After Noncardiac Surgery. Anesthesia & Analgesia, 119(3), 603-612. doi:10.1213/ane.0000000000000096 
4. Holick, M., & Chen, T. (2008). Vitamin D deficiency: a worldwide problem with health consequences. The American Journal of Clinical Nutrition, 87(4), 1080S-1086S. doi:10.1093/ajcn/87.4.1080s 
5. McNally, J., & Menon, K. (2013). Vitamin D deficiency in surgical congenital heart disease: Prevalence and relevance. Translational Pediatrics, 2(3), 99-111. doi:10.3978/j.issn.2224-4336.2013.07.03 
6. Vaughan-Shaw, P.G., Zgaga, L., Ooi, L. Y., et al. (2019). Low plasma vitamin D is associated with adverse colorectal cancer survival after surgical resection, independent of systemic inflammatory response. BMJ, 69(1), 103-111. doi:10.1136/gutjnl-2018-317922 
7. Rahm, D. (2004). A guide to perioperative nutrition. Aesthetic Surgery Journal, 24(4), 385-390. doi:10.1016/j.asj.2004.04.001 
8. Kaplon, R., Gillinov, A., Smedira, N., Kottke-Marchant, K., Wang, I., Goormastic, M., & McCarthy, P. (1999). Vitamin K reduces bleeding in left ventricular assist device recipients. The Journal of Heart and Lung Transplantation, 18(4), 346-350. doi:10.1016/s1053-2498(98)00066-7 

The human microbiome consists of all the microbes – bacteria, archaea, fungi, and even viruses – that live in and on human bodies and interact with human cells [1]. The term “microbiome” was first coined in 2001 [2] and it was discovered in subsequent years that this endogenous microbial population outnumbers human cells 10 to 1 and consists of 10,000 different microbial species [3]. This diversity helps account for the vast array of symbiotic human-microbial relationships scientists are only now beginning to uncover [4]. The absence of these beneficial microbes may heighten the risk for many diseases.  

 

While microbial communities exist in the oral cavity, respiratory tract, and on the skin, microbes in the gastrointestinal tract have thus far been found to impact human health and physiology to the greatest extent [5]. Gut microbiota carry out important metabolic functions. For example, the digestion of xyloglucans, a type of cell wall polysaccharide found in lettuce and tomatoes, is performed by a mutant from the Bacteroides ovuatus species that inhabits the human gut [6]. Gut microbes also produce metabolites that signal endocrine cells to produce various hormones, some of which regulate insulin sensitivity, glucose tolerance, and fat storage [7]. 

 

Dysbiosis, the imbalance of natural microflora, can result from exposure to various environmental factors and has been implicated in several diseases [8]. Crohn’s disease and ulcerative colitis have been associated with an increase of Enterobacteriaceae and a loss of other symbiotic taxa [9]. Beyond gastrointestinal diseases, microbes responsible for the production of short-chain fatty acids such as butyrate can help lower the risk of heart disease [10]. Clostridium difficile infection, perhaps the most well-known example of dysbiosis, can occur when antibiotics wipe out colon bacteria that normally restrict C. difficile growth [11]. 

 

Characteristic of all these examples of dysbiosis is the reduction of microbial diversity. While it is difficult, perhaps impossible, to quantify the exact benefits generated by the various microbes that compose the microbiome, it is clear that an increase in diversity better prepares an organism to effectively respond to its environment. Reese and Dunn suggest implementing experiments whereby a population is “diluted” to produce individuals with reduced diversity, which can then be compared against normal individuals [12]. Mosca et al. implicate features of the Western lifestyle – eating behaviors, disruption of the circadian clock, and antibiotic consumption – in the loss of global microbial diversity and the resulting increase of allergies and inflammatory bowel diseases in the modern world. They explore reintroducing bacterial predators into the microbiota system to restabilize the microbial ecosystem [13]. 

 

The effort to preserve and restore microbial diversity is far from simple. Bello et al. suggest several measures that can be implemented immediately – curtailing antibiotic use, limiting caesarean sections, promoting breastfeeding – but they acknowledge that ultimately, a more ambitious strategy to systematically identify and reintroduce symbiotic bacteria is needed [14]. Part of the problem stems from the difficulty of sampling and identifying the thousands of microbes inhabiting humans from different populations. A recently developed technology called Cell Alive System uses magnetic fields and mechanical vibrations to uniformly cool microbial samples, which gives them the best chance of survival in vitro. The decrease in microbial diversity is an urgent public health problem that demands our attention. As Dr. Martin Blaser, chair of the Human Microbiome at Rutgers University puts it, “The first point is to stop the damage, then rebuild” [15].

  

References 

1. “The Microbiome.” The Nutrition Source, 1 May 2020, www.hsph.harvard.edu/nutritionsource/microbiome/.  
2. Prescott, Susan L. “History of Medicine: Origin of the Term Microbiome and Why It Matters.” Human Microbiome Journal, vol. 4, 2017, pp. 24–25., doi:10.1016/j.humic.2017.05.004.  
3. “NIH Human Microbiome Project Defines Normal Bacterial Makeup of the Body.” National Institutes of Health, U.S. Department of Health and Human Services, 31 Aug. 2015, www.nih.gov/news-events/news-releases/nih-human-microbiome-project-defines-normal-bacterial-makeup-body.  
4. Ogunrinola, Grace A., et al. “The Human Microbiome and Its Impacts on Health.” International Journal of Microbiology, vol. 2020, 2020, pp. 1–7., doi:10.1155/2020/8045646. 
5. Barton, Wiley, et al. “Metabolic Phenotyping of the Human Microbiome.” F1000Research, vol. 8, 2019, p. 1956., doi:10.12688/f1000research.19481.1.  
6. Larsbrink, Johan, et al. “A Discrete Genetic Locus Confers Xyloglucan Metabolism in Select Human Gut Bacteroidetes.” Nature, vol. 506, no. 7489, 2014, pp. 498–502., doi:10.1038/nature12907.  
7. Martin, Alyce M., et al. “The Influence of the Gut Microbiome on Host Metabolism Through the Regulation of Gut Hormone Release.” Frontiers in Physiology, vol. 10, 2019, doi:10.3389/fphys.2019.00428.  
8. Carding, Simon, et al. “Dysbiosis of the Gut Microbiota in Disease.” Microbial Ecology in Health & Disease, vol. 26, 2015, doi:10.3402/mehd.v26.26191.  
9. Durack, Juliana, and Susan V. Lynch. “The Gut Microbiome: Relationships with Disease and Opportunities for Therapy.” Journal of Experimental Medicine, vol. 216, no. 1, 2018, pp. 20–40., doi:10.1084/jem.20180448.  
10. Baxter, Nielson T., et al. “Dynamics of Human Gut Microbiota and Short-Chain Fatty Acids in Response to Dietary Interventions with Three Fermentable Fibers.” MBio, vol. 10, no. 1, 2019, doi:10.1128/mbio.02566-18.  
11. “C. Difficile Infection.” American College of Gastroenterology, 6 Feb. 2020, gi.org/topics/c-difficile-infection/.  
12. Reese, Aspen T., and Robert R. Dunn. “Drivers of Microbiome Biodiversity: A Review of General Rules, Feces, and Ignorance.” MBio, vol. 9, no. 4, 2018, doi:10.1128/mbio.01294-18.  
13. Mosca, Alexis, et al. “Gut Microbiota Diversity and Human Diseases: Should We Reintroduce Key Predators in Our Ecosystem?” Frontiers in Microbiology, vol. 7, 2016, doi:10.3389/fmicb.2016.00455.  
14. Bello, Maria G. Dominguez, et al. “Preserving Microbial Diversity.” Science, vol. 362, no. 6410, 2018, pp. 33–34., doi:10.1126/science.aau8816.  
15. “Disappearance of the Human Microbiota: How We May Be Losing Our Oldest Allies.” ASM.org, asm.org/Articles/2019/November/Disappearance-of-the-Gut-Microbiota-How-We-May-Be.