Risk Stratification for Supratherapeutic Peak Anti-Xa Levels in Adult Patients on Therapeutic Enoxaparin.

BACKGROUND: The American Society of Hematology Guidelines for the management of venous thromboembolism recommend against the use of anti-Xa monitoring for assessing enoxaparin dosing based on a low level of evidence associating supratherapeutic levels with an increased risk of bleeding. However, institutions still utilize anti-Xa levels in select patient populations with altered volume of distribution and/or excretion to monitor and adjust therapy. OBJECTIVE: The primary objective of this study was to identify risk factors associated with supratherapeutic peak anti-Xa levels (≥1.10 IU/mL) for patients receiving therapeutic enoxaparin. METHODS: This was a retrospective single-center study performed at an academic tertiary care hospital. Patients who received enoxaparin at 1 mg/kg twice daily and peak anti-Xa monitoring were separated into supratherapeutic and therapeutic/subtherapeutic cohorts. RESULTS: A total of 436 patients were screened, and 215 were included, with a mean age of 62 years. There were 108 in the therapeutic/subtherapeutic cohort and 107 in the supratherapeutic cohort. Acute kidney injury (AKI), body mass index (BMI), weight, female sex, intensive care unit (ICU) service, Sequential Organ Failure Assessment (SOFA) score ≥4, and creatinine clearance at the time of peak anti-Xa level collection were associated with supratherapeutic anti-Xa levels in univariate models. Adjusted logistic regression models were created and identified BMI in the 30 to 34.9 kg/m2 (odds ratio [OR] 4.35; 95% confidence interval [CI] 1.70-11.13, P < 0.005) and ≥35 kg/m2 (OR 6.75; 95% CI 3.05-14.94, P < 0.005) and AKI (OR 2.62; 95% CI 1.04-6.62, P = 0.042) as significant risk factors for supratherapeutic anti-Xa levels. CONCLUSION AND RELEVANCE: Our study identified BMI ≥ 30 kg/m2, AKI, female sex, ICU service, SOFA score ≥4, and creatinine clearance as risk factors for supratherapeutic anti-Xa levels in patients receiving 1 mg/kg twice daily dosing of enoxaparin. Further research should be done to provide evidence for the association between anti-Xa levels and bleeding risk.

Anticoagulation Considerations in Liver Disease.

Coagulopathy of liver disease is a complex pathology that may result in thrombosis and/or bleeding complications. Routine laboratory values are not always reflective of the degree of these risks. Additionally, prophylaxis and treatment of venous thromboembolism in patients with cirrhosis require careful evaluation when selecting and monitoring drug therapy for these indications. Therefore, this article aims to provide insight regarding coagulopathy of liver disease, influence on laboratory values, and anticoagulant therapy considerations for critical care nurses assuming care for patients with cirrhosis.

Insulin NPH for steroid-induced hyperglycemia: Predictors for success.

STUDY OBJECTIVE: This study aimed to evaluate the efficacy of insulin neutral protamine Hagedorn (NPH) for steroid-induced hyperglycemia and identify factors associated with achievement of euglycemia. DESIGN: Retrospective, single center, cohort analysis. SETTING: Quaternary care academic medical center. PATIENTS: Adult patients with steroid-induced hyperglycemia on combination therapy of an intermediate-acting steroid and once daily NPH. INTERVENTION: The primary outcome was the percentage of patients who achieved euglycemia on day 3 of combination therapy. Patients were divided into euglycemic and dysglycemic cohorts based on the primary outcome. Univariate analysis on baseline characteristics, NPH dose, and steroid dose based on prednisone equivalent dose (PED) was conducted to identify differences between the cohorts. Safety analysis was conducted to detect differences between the two cohorts. MEASUREMENTS AND MAIN RESULTS: Of 142 patients included in the primary analysis, 50 (35.2%) achieved euglycemia on day 3 of combination therapy. In univariate analysis, patients who achieved euglycemia had significantly higher median NPH dose standardized to steroid dose on day 1 (0.5 units/mg PED [25%-75% interquartile range (IQR) 0.4-0.8] vs 0.4 units/mg PED [0.2-0.8]; p = 0.046), lower median blood glucose prior to combination therapy on day 3 (111 mg/dl [96-160] vs 136 mg/dl [113-198]; p = 0.008), and lower median blood glucose 4 hours after administration of combination therapy on day 3 (147 mg/dl [116-197] vs 190 mg/dl [153-245]; p = 0.003) compared to patients who did not achieve euglycemia, respectively. Hypoglycemia and life-threatening hypoglycemia occurred at similar rates between the two cohorts. CONCLUSIONS: Neutral protamine Hagedorn is a safe and efficacious option for acute care hospitalized patients experiencing steroid-induced hyperglycemia. More aggressive dosing initiation of NPH based on steroid dose may allow for earlier achievement of euglycemia without a difference in hypoglycemia.

The impact of Grindr advertising on attendance and HIV testing by men who have sex with men at a sexual health clinic in northern Sydney.

Grindr is a geolocation smartphone application popular among men who have sex with men (MSM) to find sexual partners. We conducted a study to assess if attendance and HIV testing amongst MSM increased due to advertisements on Grindr that promoted our service. We measured clinic website hits by users clicking through from Grindr; we counted self-reported registrations that nominated referral from Grindr; and we compared new patient attendances and HIV tests in MSM with heterosexual men, for the 18 months preceding the intervention and the 18 months of the intervention. During the intervention the clinic's website received 11,799 unique hits from Grindr users. The average monthly rate of attendances by new MSM increased 70.3% from 19.0 to 32.3, compared with a 5.5% increase among new heterosexual men from 45.6 to 48.1. The average monthly rate of HIV tests among MSM increased 43.6% from 47.0 to 67.6, compared with a 3.9% increase amongst heterosexual men from 40.0 to 41.6. The MSM:heterosexual men rate ratio for new patient attendances changed from 0.42 to 0.67 (p < 0.001, adjusted for possible underlying time trends in each period), and for HIV tests this rate ratio changed from 1.18 to 1.63 (p < 0.001, adjusted for possible underlying time trends in each period). The effects of the intervention did not significantly change over the course of the 18-month intervention. This study suggests that advertising on Grindr was effective and durable as a means of increasing attendance and HIV testing rates among MSM in northern Sydney.

One year of methadone maintenance treatment in a fentanyl endemic area: Safety, repeated exposure, retention, and remission.

INTRODUCTION: Fentanyl is a potent synthetic opioid that has contributed to increasing overdose deaths in the United States in recent years. Concern over safety and efficacy of agonist treatment for fentanyl use may limit access to treatment. This study sought to address these potential concerns in a naturalistic setting. OBJECTIVES: Measure 12-month treatment outcomes for methadone maintenance treatment (MMT) in a fentanyl endemic area. OUTCOMES: Primary: 1) Treatment retention; 2) sustained remission (defined as 3 consecutive negative screens); 3) return to use; 4) methadone dosage required; and 5) number of days to achieve remission. Secondary: Mortality. METHODS: A naturalistic follow-up study and retrospective review of consecutive patients newly admitted to a single methadone maintenance treatment program in Rhode Island. RESULTS: We observed 154 unique intake events (representing 151 patients). Eighty percent (n = 121) tested positive for fentanyl at intake. Seventy-five percent of patients achieved remission within the 12-month study period. One-year retention was 53% for fentanyl-exposed individuals and 47% for those not exposed. The majority (99%) of patients who remained in treatment at 12 months achieved remission. We saw prolonged, sustained remission in 44% of patients exposed to fentanyl at intake and 47% of those who were not. Dose and time to remission were similar. Unfortunately, 4 patients died after leaving MMT prematurely. CONCLUSIONS: This study suggests MMT is safe despite repeated exposure to fentanyl while taking methadone. Remission is achievable, and MMT is protective against death among fentanyl-exposed patients while in treatment.

Methadone maintenance treatment among patients exposed to illicit fentanyl in Rhode Island: Safety, dose, retention, and relapse at 6 months.

INTRODUCTION: Illicitly manufactured fentanyl (IMF) is a potent synthetic opioid that has been contributing to overdose deaths in the United States. This study examined intake toxicology and six-month treatment outcomes for patients newly admitted to a single methadone maintenance treatment program (MMTP) in Rhode Island with a high prevalence of illicit fentanyl. METHODS: We conducted a retrospective chart review of patients admitted to a single MMTP between November 1st, 2016 and August 31st, 2017 followed for six months. Outcomes measured included: 1) retention in treatment at 6 months; 2) evidence of sustained abstinence; 3) relapse; 4) methadone dosage required to achieve sustained abstinence; and 5) the number of days required to achieve abstinence. RESULTS: We observed 154 unique intake events (representing 147 patients). 80% (n = 123) tested positive for fentanyl at intake. During the six-month follow up period, 32% (n = 49) left treatment before six months, two individuals died within five weeks of discontinuation. No deaths were seen among those remaining in treatment. The majority (89%) who remained in treatment at six months achieved abstinence. No significant difference was seen for dose or time to achieve abstinence. Relapse was common (57%). Repeated exposure to fentanyl was seen frequently (71%) while in MMT before and after achieving abstinence. CONCLUSION: While there is concern that the potency of IMF may reduce the effectiveness of MAT, this study suggests that MMT is safe, abstinence achievable, and MMT is protective against death among fentanyl-exposed patients.

Echocardiographic evidence of pulmonary hypertension is associated with increased 1-year mortality in patients admitted with chronic obstructive pulmonary disease.

Pulmonary hypertension (PH) is associated with decreased overall survival in patients with chronic lung disease. The purpose of this study was to determine the effect of echocardiographic evidence of PH on 1-year survival in patients hospitalized with acute exacerbations of chronic obstructive pulmonary disease (COPD). This is a retrospective study of patients admitted to a respiratory intermediate care unit with COPD exacerbation between October 1, 2002 and September 30, 2004. All patients who had 2D echocardiograms and pulmonary function tests done within 12 months prior to hospital admission or during the admission were examined. Charts were reviewed for the following outcomes: length of hospital stay, need for mechanical ventilation, survival at discharge, and mortality over the next year. Data were analyzed using multiple logistic regression and p values calculated using Fisher's exact test. Forty-three patients met study entry criteria, and PH, defined as systolic right ventricular pressure greater than 45 mmHg, was found in 23 (53%). Sixteen of the 23 patients (70%) with PH died during the 1-year follow-up period compared to 5 of 20 (25%) patients with no PH (p = 0.0058). The effect of PH on survival was independent of age, forced expiratory volume in 1 s (FEV(1)), arterial pH, pCO(2), or pO(2) (p < 0.01). Echocardiographic evidence of PH is associated with increased 1-year mortality in patients admitted with COPD exacerbation. Further studies are needed to determine if PH is a cause of increased mortality in this population or an indicator of other cardiovascular disease.

Other systemic manifestations of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) no longer is regarded simply as a disease of the lungs and airways. There is growing awareness of the multisystemic nature of this disease. Research has shown increased levels of systemic inflammation and cardiovascular, neurologic, psychiatric, and endocrine system dysfunction associated with COPD. Skeletal muscle dysfunction associated with COPD is discussed in the article by Schols in this issue of Clinics in Chest Medicine. In this article, other systemic manifestations of COPD are discussed. Although this field is expanding rapidly, this article focuses on recent advances and reviews.

A novel form of manually assisted ventilation.

We report an individual with limb-girdle muscular dystrophy who has devised a way to assist her respiration by using her hands braced against the tray of her wheelchair. Utilizing this method, she was able to increase her tidal volume (VT) and lower her respiratory rate compared to unassisted spontaneous breathing, thereby maintaining a stable minute volume. The manually assisted VT measurements were comparable to those achieved using an intermittent abdominal pressure respirator (pneumatic belt). We believe that others with neuromuscular syndromes could use this technique, possibly decreasing their dependence on mechanical ventilatory assist devices.