COVID-19 and Pregnancy: Risk, Symptoms, Diagnosis, and Treatment.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel virus responsible for causing an infection known as COVID-19. Several pulmonary and systemic manifestations of the illness have been described since the discovery of this virus. However, there have been higher-risk populations in which this infection has not been well studied nor documented. One of these populations includes the pregnant cohort. The purpose of this article is to describe the clinical manifestations of COVID-19 infection in the pregnant population and review the implications and sequelae of the infection throughout pregnancy and outcomes of live births. Also, we summarize the understanding and safety of current treatments and vaccination in pregnancy. This comprehensive review article comprises several case reports, case series, cohort studies, retrospective studies, and randomized clinical trials. Findings regarding maternal morbidity included an increased risk of acquiring severe COVID-19 infection requiring a higher level of inpatient hospital care along with an increased risk of preterm labor and cesarean delivery. Neonatal COVID-19 vertical transmission was shown to have conflicting data as there was a presence of transmission in certain retrospective studies and absence in others. There was also no evidence of teratogenicity from maternal COVID-19 infection. In conclusion, in part due to the unique physiologic state of pregnancy and part due to unknown factors, pregnant patients are at increased risk for negative outcomes of COVID-19 infection and must be classified as a high-risk population.

Hypoglycemic Confidence in the Partners of Adults with Type 1 Diabetes.

Background: Hypoglycemic confidence (HC) represents the degree to which an individual feels secure regarding his or her ability to stay safe from hypoglycemia-related problems. Self-report scales assessing HC in adults with type 1 diabetes (T1D) have found that greater HC is associated with better glycemic control and that HC rises significantly after real-time continuous glucose monitoring is introduced. To determine whether HC might be similarly meaningful in the partners of T1D adults, we developed the Hypoglycemic Confidence Scale for Partners (Partner-HCS). This article describes the construction and validation of the Partner-HCS and examines how HC in T1D partners is related to hypoglycemia-related experience and key psychosocial constructs. Methods: Items were developed from interviews with seven T1D partners, resulting in 12 self-report items. Exploratory factor analysis (EFA) was then conducted on data collected from T1D partners (n = 218). Variables to establish construct validity for the Partner-HCS included partner-reported diabetes distress, hypoglycemic fear, generalized anxiety, and confidence regarding glucagon use, as well as frequency of recent severe hypoglycemia in the T1D adult. Hierarchical regression analyses examined the unique contribution of Partner-HCS scores, independent of hypoglycemic fear, to key psychosocial constructs and hypoglycemia-related factors. Results: EFA of the 12 items yielded a single-factor solution, accounting for 51.2% of the variance. Construct validity was demonstrated by significant univariate associations with key psychosocial constructs. Importantly, Partner-HCS total score was, independent of hypoglycemic fear, significantly associated with diabetes distress (P < 0.05), overall relationship satisfaction (P = 0.004), number of severe hypoglycemic episodes in the last 6 months (P < 0.05), and confidence using glucagon (P = 0.007). In total, 38.5% of T1D partners indicated relatively low HC. Conclusions: HC is an important facet of the experiences of T1D partners. It is related to, yet distinct from, hypoglycemic fear. The Partner-HCS is a reliable, valid method for assessing HC in partners of T1D adults.

The phenylephrine concentration-response relationship for blood pressure after nasal delivery in children.

BACKGROUND: Intranasal phenylephrine is commonly used to vasoconstrict the nasal mucosa, reducing bleeding associated with nasotracheal intubation or endoscopic sinus surgery. There are few data quantifying either absorption pharmacokinetics or phenylephrine concentration effect on blood pressure in children. METHODS: Published observations of plasma concentration and blood pressure changes after phenylephrine nasal administration (0.1 mL kg-1 , 0.25% or 0.5%) in children (n = 52, 2-12 years, 10-40 kg) were pooled with those in adults (23-81 years) given phenylephrine 2.5% (n = 10) and 10% (n = 10) eyedrops. Further pharmacokinetic (PK) data were available from healthy volunteers given oral phenylephrine 10 mg alone, with blood for concentration assay taken at 5, 15, 30, 45 minutes and 1, 2, 3, 6 hours (n = 28). Intravenous time-concentration data were available from four healthy volunteers given phenylephrine 1 mg and who had blood taken for assay on 17 occasions over the subsequent 4 hours. Data were analyzed using an integrated pharmacokinetic-pharmacodynamic (PK-PD) model using nonlinear mixed-effects models. Allometry, scaled to a 70-kg person, was used for PK size standardization. Effect was described using an EMAX model. RESULTS: A two-compartment model was used to fit PK data while an additional compartment, linked by an equilibration half-time (T1/2 keo), was used to describe effect. PK parameter estimates for the nasal formulation were clearance (CL) 160 L h-1 , central volume of distribution (V1) 13.3 L, intercompartment clearance (Q) 25.3 L h-1 , peripheral volume of distribution (V2) 225 L, absorption half-time (Tabs) 6.2 minutes, absorption lag time (Tlag) 1.5 minutes, and bioavailability (F) 0.183. Bioavailability and absorption of the ophthalmic solution were concentration dependent (F 0.13, Tabs 5.5 minutes for 2.5% solution; F 0.15, Tabs 9.6 minutes for 10% solution). Absorption of the oral formulation was slow (Tabs 48 minutes) with poor bioavailability (F 0.0128). The pediatric PD interrogation revealed a baseline mean arterial pressure of 60 mm Hg, a maximum effect (EMAX ) of 25 mm Hg, and an EC50 of 10.3 µg L-1 . The effect on vasculature was immediate and T1/2 keo was not estimable. CONCLUSION: Absorption of phenylephrine through the nasal mucosa was rapid and similar to the ophthalmic formulation. Bioavailability was also similar to the ophthalmic formulation. The maximum effect (EMAX ) in children was half that in adults (EMAX 50 mm Hg).

Hemodynamic responses and plasma phenylephrine concentrations associated with intranasal phenylephrine in children.

INTRODUCTION: Intranasal phenylephrine, an alpha-1 adrenergic agonist, causes vasoconstriction of the nasal mucosa and is used to reduce bleeding associated with nasotracheal intubation or endoscopic sinus surgery. The purpose of this study was to describe the hemodynamic effects associated with plasma phenylephrine concentrations following topical intranasal administration of 0.25% and 0.5% phenylephrine in children. METHODS: After Institutional Review Board and parental approval, 77 children between the ages of 2 and 12 years were studied in a prospective, double-blind manner and randomized into three groups. Group 1 received intranasal saline, while groups 2 and 3 received 0.1 mL/kg of 0.25% or 0.5% phenylephrine, respectively. All received the same anesthetic of halothane, N2 O, O2 , and vecuronium. After inhalation induction, endtidal halothane and PaCO2 were maintained at 1.5% and 35 mm Hg, respectively. Heart rate and rhythm, systolic, diastolic, and mean, noninvasive arterial blood pressures were recorded and venous blood was obtained for measurement of plasma phenylephrine concentration by high-performance liquid chromatography at baseline and at 2, 5, 10, and 20 minutes following intranasal spray application of the study drug. Nasotracheal intubation was performed immediately following the 5-minute measurements, and the presence of bleeding was assessed. Hemodynamic data were compared by analysis of variance for repeated measures. Bleeding and arrhythmia incidence among groups were analyzed using chi-squared tests. Phenylephrine levels were correlated with hemodynamic values via regression analysis. RESULTS: Fifty-two patients received intranasal phenylephrine. Increases in blood pressure correlated with increasing plasma phenylephrine concentration. Systolic blood pressure increased 8%, and mean blood pressure increased 14%, which were statistically significant but clinically insignificant. Heart rate did not change, and the incidence of arrhythmia was low and similar among groups. Bleeding following nasotracheal intubation was less frequent in Group 3 (11/27 subjects) than in Group 1 (17/25). Peak plasma phenylephrine concentrations were observed by 14±7 minutes following intranasal administration, and were highly variable among individuals (37.8±39.7 and 49.6±93.9 ng/mL [mean±SD] in Groups 2 and 3). DISCUSSION: Administration of intranasal phenylephrine, 0.25% and 0.50%, results in rapid but highly variable systemic absorption that is associated with mild increases of blood pressure that are clinically insignificant. Bleeding associated with nasotracheal intubation was less following administration of 0.5% intranasal phenylephrine than following intranasal saline.

Budget impact modeling for a single-tablet formulation of ibuprofen and famotidine for prevention of upper gastrointestinal ulcers in patients with osteoarthritis and/or rheumatoid arthritis.

BACKGROUND: Single-tablet ibuprofen/famotidine is approved by the US Food and Drug Administration for the relief of signs and symptoms of rheumatoid arthritis and osteoarthritis and to decrease the risk of developing upper gastrointestinal (GI) ulcers in patients taking ibuprofen for those indications. Currently, little is known about the cost impact of gastroprotective therapies, and an estimate of the financial consequences of adopting these therapies will be helpful to decision makers. OBJECTIVES: The goal of this study was to review a model that evaluates the expected financial impact to US health care plans from the introduction of single-tablet ibuprofen/famotidine into the chronic NSAID user population. METHODS: A budget impact model, considering a typical health plan of 1 million enrollees, was used to compare patients receiving: (1) single-tablet ibuprofen/famotidine; (2) chronic NSAID treatment plus any GI-protective agent; and (3) chronic NSAID treatment without a GI-protective agent. RESULTS: The expected medication cost for single-tablet ibuprofen/famotidine was $734,192 ($81,577 in year 1, $244,731 in year 2, and $407,884 in year 3), corresponding to a total per-member per-month cost of $0.020 ($0.007 in year 1, $0.020 in year 2, and $0.034 in year 3). Considering anticipated decreases in the use of other NSAIDs, the use of GI-protective agents, and GI complications, the total expected 3-year drug cost for single-tablet ibuprofen/famotidine was offset by 50%, representing an estimated total budget impact of $364,396 or $0.010 per member per month. Sensitivity analyses of cost and market share variables and clinical and drug characteristics identified the most influential variables to be the cost of the drug and persistence to the ibuprofen/famotidine formulation, respectively. CONCLUSIONS: The expected decrease in treatment costs for less serious GI-related complications illustrates the benefits of single-tablet ibuprofen/famotidine as a gastroprotective therapy in patients receiving chronic NSAID treatment, with a modest financial impact on total health care costs.

Using one question to identify women at risk for an alcohol-exposed pregnancy.

CONTEXT: Consumption of 8 alcoholic drinks per week or 5 alcoholic drinks on one occasion by a pregnant woman can affect the developing fetus. However, it can be difficult to determine which patients are at risk. OBJECTIVE: To evaluate how well the answer to a single question about binge drinking could help identify women at risk of an alcohol-exposed pregnancy (AEP). METHODS: Using data from a study of methods to prevent AEPs, the authors compared the efficacy of self-reported answers to a screening question about binge drinking (5 or more standard drinks on one occasion) within the past 90 days with answers to a question about drinking quantity (weekly consumption of 8 or more standard drinks) within the past 90 days. RESULTS: The participants were 354 women of childbearing age who met screening criteria for being at risk of an AEP. The binge question was answered positively by 346 women (97.7%) at risk, while only 209 women (59.0%) reported that they drank 8 or more drinks in a week. CONCLUSION: A single question about binge drinking can effectively and quickly identify the majority of women at risk of an AEP.

Agreement between insurance claim and self-reported hospital and emergency room utilization data among persons with diabetes.

As part of a retrospective evaluation of a diabetes management program, the agreement between self-reported and insurance claim data on hospitalization and emergency room utilization was examined. Data agreement on hospitalization or emergency room visits between the two collection modes was evaluated through the use of simple agreement proportions and the kappa agreement statistic. A total of 1,230 participant responses were studied. The proportions of patients with hospitalization or emergency room visits were indistinguishable between the self-reported and medical claims data, and kappa statistics also indicated good-to-excellent agreement between data sets. The percentages of participants whose self-reported hospitalization and emergency room utilization exactly matched data derived from insurance claims were high (89.1% and 87.2%, respectively). Furthermore, the kappa statistics of agreement for the number of hospitalizations (0.6366) and emergency room visits (0.5390) indicate good agreement between self-reported and insurance claim data. The results of this study suggest either self-reported or insurance claims data can be used to evaluate the impact of health care interventions on hospital or emergency room utilization.