Detecting Visual Field Worsening From Optic Nerve Head and Macular Optical Coherence Tomography Thickness Measurements.

Purpose: Compare the use of optic disc and macular optical coherence tomography measurements to predict glaucomatous visual field (VF) worsening. Methods: Machine learning and statistical models were trained on 924 eyes (924 patients) with circumpapillary retinal nerve fiber layer (cp-RNFL) or ganglion cell inner plexiform layer (GC-IPL) thickness measurements. The probability of 24-2 VF worsening was predicted using both trend-based and event-based progression definitions of VF worsening. Additionally, the cp-RNFL and GC-IPL predictions were combined to produce a combined prediction. A held-out test set of 617 eyes was used to calculate the area under the curve (AUC) to compare cp-RNFL, GC-IPL, and combined predictions. Results: The AUCs for cp-RNFL, GC-IPL, and combined predictions with the statistical and machine learning models were 0.72, 0.69, 0.73, and 0.78, 0.75, 0.81, respectively, when using trend-based analysis as ground truth. The differences in performance between the cp-RNFL, GC-IPL, and combined predictions were not statistically significant. AUCs were highest in glaucoma suspects using cp-RNFL predictions and highest in moderate/advanced glaucoma using GC-IPL predictions. The AUCs for the statistical and machine learning models were 0.63, 0.68, 0.69, and 0.72, 0.69, 0.73, respectively, when using event-based analysis. AUCs decreased with increasing disease severity for all predictions. Conclusions: cp-RNFL and GC-IPL similarly predicted VF worsening overall, but cp-RNFL performed best in early glaucoma stages and GC-IPL in later stages. Combining both did not enhance detection significantly. Translational Relevance: cp-RNFL best predicted trend-based 24-2 VF progression in early-stage disease, while GC-IPL best predicted progression in late-stage disease. Combining both features led to minimal improvement in predicting progression.

Chiropractic management of lumbar spinal epidural lipomatosis in a U.S. Veterans Affairs clinic: a report of two cases.

Background: Spinal epidural lipomatosis (SEL) is a rare contributor of low back pain (LBP) that can present with or without radicular symptoms. Case Presentation: A 51-year-old and 65-year-old male presented with chronic LBP to the Veterans Affairs chiropractic clinic for a trial of care. One had a moderate degree of lumbar spinal stenosis with known SEL and the other had severe. The patient with moderate grade stenosis responded favorably with weeks of transient benefit after visits and the patient with severe grade did not find benefit with care. Summary: SEL is a condition that conservative care providers should be aware of as a potential cause of central canal stenosis or neuroforaminal narrowing. Chiropractic management of SEL has been scarcely reflected in the published literature, but may be a viable option for transient symptom management.

Utilizing a composite citation index for evaluating clinical ophthalmology research: insights into gender, nationality, and self-citation among top ophthalmology researchers.

OBJECTIVES: To compare the performance of a composite citation score (c-score) and its six constituent citation indices, including H-index, in predicting winners of the Weisenfeld Award in ophthalmologic research. Secondary objectives were to explore career and demographic characteristics of the most highly cited researchers in ophthalmology. METHODS: A publicly available database was accessed to compile a set of top researchers in the field of clinical ophthalmology and optometry based on Scopus data from 1996 to 2021. Each citation index was used to construct a multivariable model adjusted for author demographic characteristics. Using area under the receiver operating curve (AUC) analysis, each index's model was evaluated for its ability to predict winners of the Weisenfeld Award in Ophthalmology, a research distinction presented by the Association for Research in Vision and Ophthalmology (ARVO). Secondary analyses investigated authors' self-citation rates, career length, gender, and country affiliation over time. RESULTS: Approximately one thousand unique authors publishing primarily in clinical ophthalmology/optometry were analyzed. The c-score outperformed all other citation indices at predicting Weisenfeld Awardees, with an AUC of 0.99 (95% CI: 0.97-1.0). The H-index had an AUC of 0.89 (95% CI: 0.83-0.96). Authors with higher c-scores tended to have longer career lengths and similar self-citation rates compared to other authors. Sixteen percent of authors in the database were identified as female, and 64% were affiliated with the United States of America. CONCLUSION: The c-score is an effective metric for assessing research impact in ophthalmology, as seen through its ability to predict Weisenfeld Awardees.

The Impact of Achieving Target Intraocular Pressure on Glaucomatous Retinal Nerve Fiber Layer Thinning in a Treated Clinical Population.

PURPOSE: To estimate the effect of being below and above the clinician-set target intraocular pressure (IOP) on rates of glaucomatous retinal nerve fiber layer (RNFL) thinning in a treated real-world clinical population. DESIGN: Retrospective cohort study. METHODS: A total of 3256 eyes (1923 patients) with ≥5 reliable optical coherence tomography scans and 1 baseline visual field test were included. Linear mixed-effects modeling estimated the effects of the primary independent variables (mean target difference [measured IOP - target IOP] and mean IOP, mm Hg) on the primary dependent variable (RNFL slope, µm/y) while accounting for additional confounding variables (age, biological sex, race, baseline RNFL, baseline pachymetry, and disease severity). A spline term accounted for differential effects when above (target difference >0 mm Hg) and below (target difference ≤0 mm Hg) target pressure. RESULTS: Eyes below and above target had significantly different mean RNFL slopes (-0.44 vs -0.71 µm/y, P < .001). Each 1 mm Hg increase above target had a 0.143 µm/y faster rate of RNFL thinning (P < .001). Separating by disease severity, suspect, mild, moderate, and advanced glaucoma had 0.135 (P = .002), 0.116 (P = .009), 0.203 (P = .02), and 0.65 (P = .22) µm/y faster rates of RNFL thinning per 1 mm Hg increase, respectively. CONCLUSIONS: Being above the clinician-set target pressure is associated with more rapid RNFL thinning in suspect, mild, and moderate glaucoma. Faster rates of thinning were also present in advanced glaucoma, but statistical significance was limited by the lower sample size of eyes above target and the optical coherence tomography floor effect.

Sexually Transmitted Infections & the Heart.

Sexually transmitted infections (STIs) have substantial morbidity and mortality worldwide, with over 1 million new infections occurring daily. Similarly, cardiovascular (CV) disease is the leading global cause of death and has tremendous impact on disability as well as quality of life. Several STIs have potential CV consequences and may precipitate reoccurrence of underlying CV comorbidity. Notably, untreated STIs and associated CV complications have an increased impact on marginalized individuals and those with limited access to health resources and care. Syphilis, human immunodeficiency virus, human papillomavirus, herpes simplex virus, hepatitis B, hepatitis C, cytomegalovirus, chlamydia, gonorrhea, and trichomoniasis have been identified as having CV implications. Yet, the data linking compromised CV health and STIs have not previously been summarized. The present review encapsulates the current knowledge surrounding the impacts of STIs on CV health as well as diagnostic and treatment strategies.

Effectiveness of Netarsudil versus Brimonidine in Eyes already Being Treated with Glaucoma Medications at a Single Academic Tertiary Care Practice: A Comparative Study.

Background: Rho kinase inhibitors, such as netarsudil, are a relatively new class of medications recently introduced into the market for the treatment of glaucoma, the leading cause of irreversible blindness in the world. Previous clinical trials have studied netarsudil's efficacy when used as a first- or second-line agent but limited studies have investigated its effectiveness in the real world where it is more commonly used as a third, fourth, or fifth agent in combination with other topical medications. Equally important, prior studies have not compared its effectiveness to its peer medications in these settings. Objective: To compare intraocular pressure (IOP) lowering after initiation of netarsudil or brimonidine therapy in patients with glaucoma using >2 medications for IOP management. Methods: A chart review of 369 eyes from 279 patients followed at a single academic tertiary practice was performed with an institutional review board waiver of consent to compare IOP lowering after prescription of netarsudil (n = 176) versus brimonidine (n = 193) as a third, fourth, or fifth IOP-lowering agent. Patients were identified by querying the electronic medical record for those with a glaucoma-related diagnosis who were prescribed either medication. Five sequential IOP measurements were obtained to determine the mean change in IOP before and after treatment (ΔIOP = mean IOP4,5 - mean IOP1,2,3). A multilevel linear mixed-effects model assessed the influence of medication (independent variable) on ΔIOP (dependent variable). Additional independent variables of interest included the number of glaucoma medications at baseline, age, sex, glaucoma type and severity, race, and pretreatment IOP. Bootstrap analysis was performed to remove sampling bias and confirm mixed-effects model findings. Kaplan-Meier survival analysis evaluated the probability of requiring additional intervention within 3 years following the date of medication prescription. Results: The unadjusted mean (SD) ΔIOP for netarsudil and brimonidine was -2.20 (4.11) mm Hg and -2.21 (3.25) mm Hg, respectively (P = 0.484). The adjusted linear mixed-effects models and bootstrap analysis demonstrated that there was no statistical difference in IOP-lowering effectiveness between the medications. Netarsudil and brimonidine failed to adequately control IOP at similar rates with 42% and 47% probabilities of survival respectively by the 3-year follow-up (P = 0.520). Conclusions: When escalating pharmacologic therapy, the IOP-lowering effect of netarsudil appeared to be similar to that produced by brimonidine. (Curr Ther Res Clin Exp. 2023; 84:XXX-XXX).

Management of uncomplicated rhegmatogenous retinal detachments: a comparison of practice patterns and clinical outcomes in a real-world setting.

OBJECTIVE: To investigate practice patterns and clinical outcomes in the repair of uncomplicated rhegmatogenous retinal detachments (RRD) in a real-world setting over a 10-year period. METHODS: We compared preferences for scleral buckling (SB), pars plana vitrectomy (PPV), PPV/SB, or pneumatic retinopexy (PR) over time, and examined the 1-year single surgery anatomic success (SSAS) and best-corrected visual acuity (BCVA) at a tertiary academic institution from 2008-2018. RESULTS: Eight hundred eight eyes had RRD repair between 2008-2011 (n = 240), 2012-2014 (n = 271), and 2015-2017 (n = 297). Compared to 2008-2011, PPV was preferred over SB in 2012-2014 (OR: 2.93; 95% CI: 1.86-4.63) and 2015-2017 (OR: 5.94; 95% CI: 3.76-9.38), and over PPV/SB in 2012-2014 (OR: 2.74; 95% CI: 1.65-4.56) and 2015-2017 (OR: 3.16; 95% CI: 31.96-5.12). PR was uncommonly utilized (<10%). Younger surgeons (graduating 2010-2017) favored PPV over SB when compared to older surgeons [graduating 1984-2000 (OR: 1.77; 95% CI: 1.18-2.65) and 2001-2009 (OR 1.73; 95% CI: 1.14-2.65)], but similarly selected PPV vs. PPV/SB as their older counterparts (p > 0.05). Compared to PPV, SSAS was higher with SB (OR: 1.53; 95% CI: 1.03-2.26) and PPV/SB (OR: 2.55; 95% CI: 1.56-4.17). One-year BCVA was markedly improved compared to baseline only for eyes that achieved SSAS (p < 0.001). CONCLUSIONS: Over the past 10 years, PPV has become the favored approach to repair uncomplicated RRD and this appears to be driven by younger surgeons' preferences. Given the superior long-term SSAS in SB and PPV/SB as compared to PPV, SB and PPV/SB should be more frequently considered when determining the appropriate repair strategy for uncomplicated RRD.

Perioperative leadership in the non-operating room and ambulatory setting.

To create a successful ambulatory care center, healthcare systems need management that can understand and improve key ambulatory success factors such as quality of clinical care, clinical competence, regulatory compliance, financial management, and customer service. Effective leadership is a vital skill that can improve all these factors. This manuscript discusses successful perioperative leadership styles in the ambulatory setting and provides a framework for proven strategies that have improved patient care.

Spinal Cord Stimulation for Post Total Knee Replacement Pain: A Case Series.

It is not uncommon for orthopedic patients to experience pain following a total knee replacement (TKR). Use of oral pain medications, nerve blocks, and periarticular injections are implemented to provide multimodal analgesia and to reduce postoperative chronic pain. Spinal cord stimulation (SCS) can also be used to control pain in patients who are refractory to conservative measures. Few studies have explored this possibility for patients with chronic pain status post TKR. We present three cases that demonstrate the effectiveness of SCS in this challenging patient population.

Novel Local Anesthetics in Clinical Practice: Pharmacologic Considerations and Potential Roles for the Future.

The treatment of pain, both acute and chronic, has been a focus of medicine for generations. Physicians have tried to develop novel ways to effectively manage pain in surgical and post-surgical settings. One intervention demonstrating efficacy is nerve blocks. Single-injection peripheral nerve blocks (PNBs) are usually preferred over continuous PNBs, since they are not associated with longer lengths of stay. The challenge of single injection PNBs is their length of duration, which at present is a major limitation. Novel preparations of local anesthetics have also been studied, and these new preparations could allow for extended duration of action of anesthetics. An emerging preparation of bupivacaine, exparel, uses a multivesicular liposomal delivery system which releases medication in a steady, controlled manner. Another extended-release local anesthetic, HTX-011, consists of a combination of bupivacaine and low-dose meloxicam. Tetrodotoxin, a naturally occurring reversible site 1 sodium channel toxin derived from pufferfish and shellfish, has shown the potential to block conduction of isolated nerves. Neosaxitoxin is a more potent reversible site 1 sodium channel toxin also found in shellfish that can also block nerve conduction. These novel formulations show great promise in terms of the ability to prolong the duration of single injection PNBs. This field is still currently in development, and more researchers will need to be done to ensure the efficacy and safety of these novel formulations. These formulations could be the future of pain management if ongoing research continues to prove positive effects and low side effect profiles.

Ophthalmic trauma: the top 100 cited articles in Ophthalmology journals.

OBJECTIVES: To analyze the top 100 cited papers on ophthalmic trauma. METHODS: A literature search of Ophthalmology journals within the ISI Web of Science database for the most cited papers related to ophthalmic trauma. RESULTS: The most cited articles were published between 1943 and 2013, the greatest number being published in 2000. Ophthalmology (45), Archives of Ophthalmology (17), and the American Journal of Ophthalmology (15) published most of the articles. The institutions with the highest number of publications were Wilmer Eye Institute (10) and Massachusetts Eye and Ear Infirmary (7). Sixty-seven percent of the articles originated from the USA. The most common type of trauma studied was non-open-globe injuries and the most frequent topic studied were pathological conditions secondary to trauma (34), particularly endophthalmitis (8), and optic neuropathy (6). Articles presenting a standardized classification system for eye injury received the highest average of citations per publication. Types of research most frequently cited were observational clinical studies (62) and epidemiological studies (30); the least frequent were clinical trials (2). CONCLUSION: This bibliographic study provides a historical perspective of the literature and identifies trends within the most highly influential papers on ophthalmic trauma. Many of these articles emerged within the past three decades and came from Ophthalmology journals that remain high impact to this day. Clinical trials have been difficult to conduct and are lacking, reflecting a critical need in ophthalmic trauma research, as most of our understanding of ophthalmic trauma comes from observational and epidemiological studies.

Repair of progressive retinal detachment complicating degenerative retinoschisis: surgical management and outcomes in phakic eyes.

BACKGROUND: Degenerative retinoschisis is a common condition defined by the splitting of the neurosensory retina that may rarely be associated with progressive retinal detachment (RD). Here, we aim to describe the anatomic and functional outcomes of surgical treatment of progressive symptomatic retinal detachment complicating degenerative retinoschisis (PSRDCR) using pars plana vitrectomy (PPV), scleral buckle (SB), or combined PPV/SB procedure. METHODS: A retrospective chart review of patients with PSRDCR between Jan 1, 2008 and Dec 31, 2019 was conducted. Data regarding demographics, surgical approach, and anatomic/functional outcomes were collected. RESULTS: Of the 4973 charts with RD repair during the study period, 36 eyes (0.7%) had retinoschisis with RD. 18 eyes met inclusion criteria (0.4%). The median age was 54 years (range 18-74) and all eyes were phakic. All eyes had outer layer breaks (OLBs) and 16 eyes (89%) had identifiable inner layer breaks. All OLBs were posterior to the equator in charts where position was recorded (16 eyes). The single surgery anatomic success (SSAS) and final anatomical success rates were 66% (12/18) and 100%, respectively. Eyes treated with PPV/SB had an SSAS rate of 75% (9/12), while PPV and SB had SSAS rates of 66% (2/3) and 33% (1/3), respectively. CONCLUSIONS: PSRDCR is an exceedingly rare complication of degenerative retinoschisis associated with an SSAS rate lower than for uncomplicated rhegmatogenous RD. The majority of PSRDCR were repaired via combined PPV/SB in our study, and the rarity of this complication limits statistical support of an optimal surgical method in our and prior studies. The role of SB combined with PPV for PSRDCR requires further investigation.

Economic impact of COVID-19 pandemic on healthcare facilities and systems: International perspectives.

International hospitals and healthcare facilities are facing catastrophic financial challenges related to the COVID-19 pandemic. The American Hospital Association estimates a financial impact of $202.6 billion in lost revenue for America's hospitals and healthcare systems, or an average of $50.7 billion per month. Furthermore, it could cost low- and middle-income countries ~ US$52 billion (equivalent to US$8.60 per person) each four weeks to provide an effective healthcare response to COVID-19. In the setting of the largest daily COVID-19 new cases in the US, this burden will influence patient care, surgeries, and surgical outcomes. From a global economic standpoint, The World Bank projects that global growth is projected to shrink by almost 8% with poorer countries feeling most of the impact, and the United Nations projects that it will cost the global economy around 2 trillion dollars this year. Overall, a lack of preparedness was a major contributor to the struggles experienced by healthcare facilities around the world. Items such as personal protective equipment (PPE) for healthcare workers, hospital equipment, sanitizing supplies, toilet paper, and water were in short supply. These deficiencies were exposed by COVID-19 and have prompted healthcare organizations around the world to invent new essential plans for pandemic preparedness. In this paper, we will discuss the economic impact of COVID-19 on US and international hospitals, healthcare facilities, surgery, and surgical outcomes. In the future, the US and countries around the world will benefit from preparing a plan of action to use as a guide in the event of a disaster or pandemic.

COVID-19 impact on the renal system: Pathophysiology and clinical outcomes.

Coronavirus disease (COVID-19) causes many deleterious effects throughout the body. Prior studies show that the incidence of acute kidney injury in COVID-19 patients could be as high as 25%. There are also autopsy reports showing evidence of viral tropism to the renal system. In this regard, COVID-19 can damage the kidneys and increase a patient's risk of requiring dialysis. Available evidence suggests that renal involvement in COVID-19 infection is not uncommon, and there has been an increased incidence of chronic kidney disease related to the pandemic. In this literature analysis, we address COVID-19 and its effects on the renal system, including the pathophysiologic mechanisms. We also address current studies on the causes of injury to the renal system, the cause of kidney failure, its effect on mortality, the impact on dialysis patients, and the impact on renal transplant patients. COVID-19 disease may have unique features in individuals on chronic dialysis and kidney transplant recipients, requiring increased vigilance in limiting viral transmission in perioperative, in-patient, and dialysis center settings.

A study of 3D radial density adapted trajectories for sodium imaging.

Sodium imaging typically employs ultrashort echo time radial, density adapted and cones trajectories to capture the rapidly decaying short T2 signal. The present study considers the parameter choices involved in the use of these trajectories in terms of their impact on the resolution and signal to noise ratio. Many parameters have a strong effect on these image properties, particularly the number of spokes which impacts voxel size. The present article develops an understanding of the trade-offs involved and how to choose optimal (or at least reasonable) parameter values. This has a practical role in designing clinical protocols for imaging sodium.

Cortical morphometric correlational networks associated with cognitive deficits in first episode schizophrenia.

Schizophrenia (SCZ) is a chronic cognitive and behavioral disorder associated with abnormal cortical activity during information processing. Several brain structures associated with the seven performance domains evaluated using the MATRICS (Measurement and Treatment Research to Improve Cognition in Schizophrenia) Consensus Cognitive Battery (MCCB) have shown cortical volume loss in first episode schizophrenia (FES) patients. However, the relationship between morphological organization and MCCB performance remains unclear. Therefore, in the current observational study, high-resolution structural MRI scans were collected from 50 FES patients, and the morphometric correlation network (MCN) using cortical volume was established to characterize the cortical pattern associated with poorer MCCB performance. We also investigated topological properties, such as the modularity, the degree and the betweenness centrality. Our findings show structural volume was directly and strongly associated with the cognitive deficits of FES patients in the precuneus, anterior cingulate, and fusiform gyrus, as well as the prefrontal, parietal, and sensorimotor cortices. The medial orbitofrontal, fusiform, and superior frontal gyri were not only identified as the predominant nodes with high degree and betweenness centrality in the MCN, but they were also found to be critical in performance in several of the MCCB domains. Together, these results suggest a widespread cortical network is altered in FES patients and that performance on the MCCB domains is associated with the core pathophysiology of SCZ.

The Effect of Transitioning from SITA Standard to SITA Faster on Visual Field Performance.

PURPOSE: To determine the effect of transitioning from Swedish Interactive Thresholding Algorithm (SITA) Standard to SITA Faster on visual field (VF) performance in glaucomatous eyes with a broad spectrum of disease severity undergoing longitudinal VF testing in a real-world clinical setting. DESIGN: Retrospective, longitudinal study. PARTICIPANTS: A total of 421 patients (766 eyes) with manifest or suspect glaucoma followed at a single institution. METHODS: Each included eye received the following sequence of VF examinations during routine clinical care: (1) SITA Standard, (2) SITA Standard, and (3) SITA Faster (mean time between tests = 13.9 months). Intra-eye comparisons were made between the first 2 VFs (Standard-Standard sequence) and the last 2 VFs (Standard-Faster sequence). The primary dependent variable was the difference in mean deviation (MD) between the second and first VF of the sequence (ΔMD, calculated as MDVF2 - MDVF1). The primary independent variable was the VF sequence (Standard-Standard or Standard-Faster). Linear mixed-effects models were used to study the effect of testing sequence on ΔMD, adjusting for confounders including time between VFs and change in false-positive (FP) errors. Results were stratified to understand the effect of glaucoma severity on the relationship between testing sequence and ΔMD. MAIN OUTCOME MEASURES: The difference in ΔMD between Standard-Standard and Standard-Faster sequence by mild, moderate, and advanced disease severity. RESULTS: In eyes with mild or suspect glaucoma, there was no significant difference in ΔMD between Standard-Faster and Standard-Standard sequences (-0.23 decibels [dB]; 95% confidence interval [CI], -0.60 to 0.15 dB). However, the Standard-Faster sequence was associated with a 0.87 dB (95% CI, 0.18-1.57 dB) improvement in ΔMD compared with the Standard-Standard sequence in eyes with moderate glaucoma and a 1.49 dB (95% CI, 0.79-2.19 dB) improvement in ΔMD in eyes with advanced glaucoma. CONCLUSIONS: Converting to SITA Faster in eyes that were previously followed with SITA Standard led to similar VF performance in mild glaucoma but resulted in higher MD values in moderate and advanced glaucoma. For patients with moderate or severe glaucoma, this may conceal disease progression when transitioning testing strategies.

HTX-011 (bupivacaine and meloxicam) for the prevention of postoperative pain - clinical considerations.

HTX-011 is an extended-release, dual-acting local anesthetic consisting of bupivacaine (sodium-channel blocker) and low-dose meloxicam (non-steroidal anti-inflammatory drug [NSAID]) applied needle-free during surgery. Introducing low-dose meloxicam addresses the limited efficacy of liposomal bupivacaine in acidic inflamed tissues and allows enhanced analgesic effects over three days. It has great promise to be an extremely effective postoperative pain regimen and produce an opioid-free surgical recovery, as it has consistently significantly reduced pain scores and opioid consumption through 72 h. This manuscript provides an updated, concise narrative review of the pharmacology, clinical efficacy, safety and tolerability of this drug and its applications to prevent postoperative pain.

Lay abstract HTX-011 is a local anesthetic (a drug to induce temporary loss of sensation or awareness, usually during a medical procedure), which is made up of a combination of two drugs and applied needle-free during surgery. It has great promise to provide effective treatment for postoperative pain (pain after an operation), allowing patients to have an opioid-free option for their pain relief. This paper reviews how this drug works and the clinical trials that have taken place so far to investigate its safety and effectiveness in reducing pain after an operation.

Folic Acid Supplementation in Patients with Elevated Homocysteine Levels.

INTRODUCTION: Folic acid is the most important dietary determinant of homocysteine (Hcy). Hcy serves as a critical intermediate in methylation reactions. It is created from methionine and either converted back to methionine or transformed into cysteine. This process is aided through several enzymes and three vitamins, folic acid, B12, and B6. Daily supplementation with 0.5-5.0 mg of folic acid typically lowers plasma Hcy levels by approximately 25%. Hyperhomocysteinemia is a known risk factor for coronary artery disease. In this regard, elevated levels of Hcy have been found in a majority of patients with vascular disease. METHODS: A literature review of folic acid supplementation for various disease states including cardiovascular disease was conducted. This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors. RESULTS: In this review, we discuss the biochemistry of folic acid, Hcy biosynthesis, Hcy and hydrogen sulfide bioavailability, pathogenesis of hyperhomocysteinemia and its role as a risk factor for disease, and treatment studies with folic acid supplementation in disease states. CONCLUSION: Folic acid supplementation should be recommended to any patient who has an elevated Hcy level, and this level should be measured and treated at an early age, since folic acid is easily obtained and may likely reduce vascular disease and other deleterious pathologic processes in high-risk populations.