Neonatal Abstinence Syndrome in North Carolina: Incidence and Characteristics among Infants and Mothers.

BACKGROUND Neonatal abstinence syndrome (NAS) is a complex disorder characterized by withdrawal symptoms secondary to in utero exposure to drugs capable of producing physical dependence. The objective of this study was to determine the incidence of NAS, as well as infant and maternal characteristics associated with NAS in North Carolina (NC).METHODS This retrospective, cross-sectional, observational study used the State Inpatient Database (SID) to compare the incidence rates of NAS for NC for the year 2016 to historical data (years 2000 to 2013). A multivariable logistic regression model including available covariates of interest was constructed.RESULTS Overall NAS incidence rate (IR) for NC was found to be 9.7 per 1,000 live births, a 32.3-fold increase since 2000 (IR=0.3 in 2000). The multivariable logistic regression model suggested race group (both black [OR 0.11; 95% CI: 0.08, 0.16] and 'other' [OR 0.43; 95% CI: 0.31, 0.61] vs white), ethnicity [OR 0.43; 95% CI: 0.31, 0.61], insurance group (both 'other/self-pay' [OR 0.35; 95% CI: 0.24, 0.52] and 'private insurance' [OR 0.07; 95% CI: 0.05, 0.10] vs Medicaid/Medicare), region (Piedmont [OR 0.62; 95% CI: 0.50, 0.79] vs Mountain), income quartile (both 4th [OR 0.45; 95% CI: 0.26, 0.79] and 3rd [OR 0.70; 95% CI: 0.50, 0.96] vs 1st), county population size (50k-249k [OR 0.54; 95% CI: 0.34, 0.86] vs ≥1 million), birth weight [OR 0.87; 95% CI: 0.78, 0.98], and length of stay [OR 1.23; 95% CI: 1.20, 1.26] as potentially important predictors of NAS.LIMITATIONS Only hospitals providing data to the SID for 2016 were included and ICD-9 codes, in use at the time of data collection, were used.CONCLUSIONS The incidence of NAS has increased in NC in 2016 compared to prior years spanning back to 2000. Specific infant and maternal characteristics including race, ethnicity, payer type, geographic region, county population, parental income status, birth weight, and length appear to be associated with an infant bearing the diagnosis of NAS.

An Update on the Status of Vaccine Development for SARS-CoV-2 Including Variants. Practical Considerations for COVID-19 Special Populations.

The progress in the development of various vaccine platforms against SARS-CoV-2 have been rather remarkable owing to advancement in molecular and biologic sciences. Most of the current vaccines and those in development focus on targeting the viral spike proteins by generating antibodies of varying spectrum. These vaccines represent a variety of platforms including whole virus vaccines, viral vector vaccines, nucleic acid vaccines representing RNA, DNA, and their hybrid forms.The therapeutic efficacy of these vaccines varies owing to their pharmacodynamic individualities. COVID-19 variants are capable of inducing different pathologic responses and some of which may be resistant to antibodies generated by current vaccines. The current clinical use of these vaccines has been through emergency use authorization until recently. Moreover, the efficacy and safety of these vaccines have been tested in substantial numbers of individuals but studies in special populations that better reflect the global population are pending results. These specialized populations include young children, immunocompromised patients, pregnant individuals, and other specialized groups. Combination approaches, molecularly modified vaccination approaches, and vaccines conferring longer periods of immunity are being currently being investigated, as well as pharmacovigilance studies.The continual transformation of SARS-CoV-2 and its variants are of concern along with the breakthrough infections. These considerations pose new challenges for the development of vaccination platforms. For this purpose, booster doses, combination vaccine approaches, and other modalities are being discussed. This review provides an updated account of currently available vaccines and those in advanced development with reference to their composition and mechanisms of action.A discussion on the use of vaccines in special populations including immunocompromised patients, pregnant women and other specialized populations are also included.

Public Perceptions of Current COVID-19 Vaccinations. Results of a Pilot Survey.

INTRODUCTION: We conducted a cross-sectional survey as a part of an educational program in collaboration with the Global Thrombosis Forum (GTF), an affiliate of North American Thrombosis Forum (NATF), and Loyola University about public perceptions of COVID-19 and COVID-19 vaccinations in the US. In this study, we are reporting the results of this survey. MATERIALS AND METHODS: The survey, in the form of a questionnaire, has been developed by GTF and faculty members. A prepared questionnaire was sent to the members of the Georgia and Illinois communities. RESULTS: In our current study, the COVID-19 vaccine willingness rate was 94.5% and vaccination rate was 90.9%. In multivariate analysis believing to have enough information about the safety and efficacy of COVID-19 vaccines (OR: 3.730, 95% CI: 1.199-11.603, p: 0.023) and gender (OR: 0.123, 95% CI: 0.016-0.967, p: 0.046) were significant predictors for vaccine willingness. Previous COVID-19 infection (OR: 0.215, 95% CI: 0.061-0.758, p: 0.017), moderate and severe effects of COVID-19 pandemic on participant's life (OR: 4.631, 95% CI 1.681-12.760, p: 0.003) and believing to have enough information about the safety and efficacy of COVID-19 vaccines (OR: 4.119, 95% CI: 1.508-11.253, p: 0.006) were significant predictors for final vaccination status. CONCLUSION: In conclusion, currently vaccination remains one of the most effective tools in the fight against the COVID-19 pandemic. The vaccine hesitancy is a complex phenomenon that is driven by individuals' perceptions of safety, and efficiency of the vaccines. We must continue to educate the public and communities that vaccines are safe, that they are effective and that they are still required even after a COVID-19 infection.

An Update on the Pathogenesis of COVID-19 and the Reportedly Rare Thrombotic Events Following Vaccination.

Today the coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become a global health problem. After more than a year with the pandemic, although our knowledge has progressed on COVID-19, there are still many unknowns in virological, pathophysiological and immunological aspects. It is obvious that the most efficient solution to end this pandemic are safe and efficient vaccines. This manuscript summarizes the pathophysiological and thrombotic features of COVID-19 and the safety and efficacy of currently approved COVID-19 vaccines with an aim to clarify the recent concerns of thromboembolic events after COVID-19 vaccination. The influx of newer information is rapid, requiring periodic updates and objective assessment of the data on the pathogenesis of COVID-19 variants and the safety and efficacy of currently available vaccines.

Comparative Studies on the Anticoagulant Profile of Branded Enoxaparin and a New Biosimilar Version.

Low molecular weight heparins (LMWH) represent depolymerized heparin prepared by various methods that exhibit differential, biochemical and pharmacological profiles. Enoxaparin is prepared by benzylation followed by alkaline depolymerization of porcine heparin. Upon the expiration of its patent, several biosimilar versions of enoxaparin have become available. Heparinox (Sodic enoxaparine; Cristália Produtos Químicos Farmacêuticos LTDA, Sao Paulo, Brazil) is a new biosimilar form of enoxaparin. We assessed the molecular weight and the biochemical profile of Heparinox and compared its properties to the original branded enoxaparin (Lovenox; Sanofi, Paris, France). Clotting profiles compared included activated clotting time, activated partial thromboplastin time (aPTT), and thrombin time (TT). Anti-protease assays included anti-factor Xa and anti-factor IIa activities. Thrombin generation was measured using a calibrated automated thrombogram and thrombokinetic profile included peak thrombin, lag time and area under the curve. USP potency was determined using commercially available assay kits. Molecular weight profiling was determined using high performance liquid chromatography. We determined that Heparinox and Lovenox were comparable in their molecular weight profile. Th anticoagulant profile of the branded and biosimilar version were also similar in the clot based aPTT and TT. Similarly, the anti-Xa and anti-IIa activities were comparable in the products. No differences were noted in the thrombin generation inhibitory profile of the branded and biosimilar versions of enoxaparin. Our studies suggest that Heparinox is bioequivalent to the original branded enoxaparin based upon in vitro tests however will require further in vivo studies in animal models and humans to determine their clinical bioequivalence.

Viral Coagulopathy in Patients With COVID-19: Treatment and Care.

COVID-19 has proven to be particularly challenging given the complex pathogenesis of SARS-CoV-2. Early data have demonstrated how the host response to this novel coronavirus leads to the proliferation of pro-inflammatory cytokines, massive endothelial damage, and generalized vascular manifestations. While SARS-CoV-2 primarily targets the upper and lower respiratory tract, other organ systems are also affected. SARS-CoV-2 relies on 2 host cell receptors for successful attachment: angiotensin-converting enzyme 2 and transmembrane protease serine 2. Clinicopathologic reports have demonstrated associations between severe COVID-19 and viral coagulopathy, resulting in pulmonary embolism; venous, arterial, and microvascular thrombosis; lung endothelial injury; and associated thrombotic complications leading to acute respiratory distress syndrome. Viral coagulopathy is not novel given similar observations with SARS classic, including the consumption of platelets, generation of thrombin, and increased fibrin degradation product exhibiting overt disseminated intravascular coagulation-like syndrome. The specific mechanism(s) behind the thrombotic complications in COVID-19 patients has yet to be fully understood. Parenteral anticoagulants, such as heparin and low-molecular-weights heparins, are widely used in the management of COVID-19 patients. Beyond the primary (anticoagulant) effects of these agents, they may exhibit antiviral, anti-inflammatory, and cytoprotective effects. Direct oral anticoagulants and antiplatelet agents are also useful in the management of these patients. Tissue plasminogen activator and other fibrinolytic modalities may also be helpful in the overall management. Catheter-directed thrombolysis can be used in patients developing pulmonary embolism. Further investigations are required to understand the molecular and cellular mechanisms involved in the pathogenesis of COVID-19-associated thrombotic complications.

Evidence-Based Practical Guidance for the Antithrombotic Management in Patients With Coronavirus Disease (COVID-19) in 2020.

This practical guidance, endorsed by the Brazilian Society of Thrombosis and Hemostasis and The Brazilian Society of Angiology and Vascular Surgery, the International Union of Angiology and the European Venous Forum, aims to provide physicians with clear guidance, based on current best evidence-based data, on clinical strategies to manage antithrombotic strategies in patients with coronavirus disease 2019.

Stability and consistency of compounded oral liquid levothyroxine formulations.

OBJECTIVE: With consideration of the narrow therapeutic index of levothyroxine (LT4), the objective of this study was to investigate the stability and consistency of compounded oral liquid formulations of LT4. METHODS: Six pharmacies and 6 student pharmacists provided compounded oral liquid formulations of LT4. Pharmacies used their standard compounding best practice including addition of excipients, labeling, and storage instructions. The student pharmacists were required to have completed all academic compounding training and were provided instructions and materials. All analyses were performed at the Pharmaceutical Education and Research Center, a Food and Drug Administration-registered pharmaceutical sciences laboratory. The compounded products were assayed for percent of labeled strength (%LS) of LT4 on days 3, 6, 13, 20, 27, and 34. Each compounding pharmacy and student pharmacist subsequently prepared a second compounded product sample approximately 30 days later to simulate a refill prescription. RESULTS: Individual product assays on days 3, 6, 13, 20, 27, and 34 demonstrated a range in variation of %LS from 12% to 47% (mean 26.5%). Wide variations of %LS of LT4 were observed between compounding sources. The assays for all products on day 3 demonstrated a range for %LS of LT4 from 77% to 113%, and those on day 34 ranged from 30% to 97%. Assay comparison of the original compounded product (month 1) to the refill compounded product (month 2) varied from 1% to 58%. Variations in excipients and flavorings were also present. One sample contained liothyronine and was not used for evaluation. These variations may be secondary to aliquot sampling of a suspension or product degradation. CONCLUSION: Compounded oral liquid LT4 products are unlikely to deliver the precise prescribed dosage and reliable product performance when administered to patients.

Gender disparities in patient education provided during patient visits with a diagnosis of coronary heart disease.

BACKGROUND: Cardiovascular disease is the leading cause of death in females in the United States. Prior studies have reported that females receive less patient education and preventive counseling for cardiovascular disease as compared with males. The American Heart Association and others have embarked on several initiatives over the last 20 years to narrow this disparity of care. The primary objective of this study was to determine whether a gender disparity remains in the provision of patient education among patients diagnosed with coronary heart disease, a form of cardiovascular disease. The secondary objective was to determine whether there is an association between the provision of patient education and sociodemographic variables and risk factors. METHODS: This was a retrospective, cross-sectional, observational study of adults (⩾18 years) diagnosed with coronary heart disease who participated in National Ambulatory Medical Care Survey between the years 2005 and 2014, inclusive. Chi-square tests of independence were performed to address the primary objective. A multivariable logistic regression model was constructed to assess the association between gender and provision of patient education while adjusting for sociodemographic variables and risk factors of interest. RESULTS: A total raw survey sample size of 17,332 patient visits meeting the study inclusion/exclusion criteria was utilized. Patients were predominately white, male, non-Hispanic, and ⩾75 years of age. Females had 0.86 times the odds of receiving patient education compared with males (95% confidence interval = 0.78-0.95, p = 0.0024). After adjusting for covariates of interest, gender remained statistically significant in the multivariable logistic model. In addition, the variables "other payer" (vs private insurance), tobacco use, primary care physician type, obesity, hyperlipidemia, and hypertension were found to be statistically significantly associated with the provision of patient education (p < 0.05) in the multivariable analysis. CONCLUSION: In the data analyzed, gender disparities exist, as evidenced by a greater proportion of males receiving patient education than females, among coronary heart disease patients during visits seeking medical care. The acceptability of these findings in terms of overall patient management and treatment goals requires further evaluation.

Integration of Biomedical and Psychosocial Treatments in Pediatrics Functional Gastrointestinal Disorders.

Pediatric functional gastrointestinal disorders (FGIDs) are disorders of the brain-gut axis. Pathophysiological factors include alterations in gut motility, microbiota, immune system, central nervous system, and psychosocial factors. Given the complex pathophysiology of FGIDs, many patients are in need of integrative treatment approaches that may include a combination of biomedical, nutritional, and psychological approaches. In this article, we examine goals of treatment; give a brief overview of biomedical, nutritional, and psychological approaches; and finally discuss the integrative management of pediatric FGIDs.

C-H bond activation by unsymmetrical 2-(N-arylimino)pyrrolide Pt complexes: geometric effects on reactivity.

Reactions of chloroplatinum methyl complexes with N-(arylimino)pyrrolide anions afford cis and trans neutral platinum methyl complexes. Isomers with methyl trans to the pyrrolide nitrogen activate benzene C-H bonds at 85 degrees C more than 80 times faster than the corresponding cis isomer. In addition, reactions of platinum dimethyl complexes with N-(arylimino)pyrroles (Ar = 4-substituted phenyl) in C6D6 at ambient temperature give unlabeled methane and cis methyl complex containing heavily deuterated Pt-Me. In contrast, bulky aryl substituents give methane isotopomers and trans-Pt-Ph product. The origins of these observations are discussed.