Non-therapeutic Levels Research Articles

INFLUENCE OF VARIOUS FACTORS ON ANTI-XA LEVELS IN HOSPITALIZED MEDICAL PATIENTS RECEIVING PARENTERAL THROMBOPROPHYLAXIS

Objective: Venous thromboembolism (VTE) stands as a prevalent vascular disease, intimately linked to increased risk for morbidity and mortality. The aim of this study was to investigate the influence of various factors on anti-Xa levels in hospitalized medical patients receiving parenteral thromboprophylaxis. Design and method: This is a single-center cohort study encompassing patients admitted to the Internal Medicine Department of the University Hospital of Heraklion, from March to August 2023. These patients were placed on thromboprophylaxis due to a heightened risk of developing VTE. Data regarding demographics, past medical history, somatometric and laboratory findings as well as the type and dose of parenteral anticoagulant were recorded. The measurement of anti-Xa levels were conducted 4 hours subsequent to the third subcutaneous administration of anticoagulant. Results: In this study, we enrolled 150 individuals [91 women (60.7%)], with an average age of 80 years. Sixty-two (41.4%) patients exhibited non-therapeutic anti-Xa levels. The levels were subtherapeutic (<0.2units/mL) in 36 patients and supratherapeutic (>0.5units/mL) in 26 patients. Non-therapeutic anti-Xa levels were observed in all underweight patients and in 12 out of 13 obese class II and III patients. It's noteworthy that therapeutic anti-Xa levels were observed in more than half of healthy-weight and overweight patients. A univariate logistic regression analyses was conducted to explore factors (age, sex, past medical history, somatometric and laboratory findings) that had impact on anti-Xa levels. Among these, only body weight emerged as independent factor influencing anti-Xa levels. Conclusions: In our study, we demonstrated that 41.3% of medical patients who were administered parenteral thromboprophylaxis exhibited non-therapeutic anti-Xa levels. This was more profound for underweight or obese class II and III patients. Body weight was emerged as independent factor influencing anti-Xa levels. Further studies on weight-based LMWH thromboprophylaxis dosing in this population are likely to yield new insights improving decisions in daily clinical practice.

Non-therapeutic plasma levels in individuals utilizing curcumin supplements in daily life

IntroductionThe spice curcumin and its metabolites are widely used by cancer patients but have not shown proven health benefits in clinical studies, likely due to low plasma concentrations after oral intake. However, public interest in curcumin continues to grow, and companies claim enhanced absorption in their formulations. This study aims to determine if daily oral intake of curcumin leads to sufficient plasma concentrations for health effects. The study was registered in the Dutch Clinical Trial Register with ID NL5931.MethodsWe used a validated HPLC-MS/MS method to measure curcumin and its metabolites in 47 individuals using their own curcumin formulations. Questionnaires assessed other supplement and medication use. Plasma samples were collected before and 1.5 h after intake, analyzing curcumin and metabolite levels with and without β-glucuronidase pretreatment to measure conjugated and unconjugated forms.ResultsPlasma concentrations of curcumin, demethoxycurcumin, bisdemethoxycurcumin and tetrahydrocurcumin, ranged between 1.0 and 18.6 ng/mL. Adding β-glucuronidase resulted in an increase of unconjugated curcumin plasma levels to 25.4 ng/mL; however still significantly below (1000-fold) a plasma concentration that is expected to have a beneficial health effect. The use of adjuvants like piperine did not result in higher curcumin plasma concentrations.DiscussionOur study shows that using oral curcumin supplements still does not result in therapeutic plasma levels. Health care practitioners need to be critical toward the claimed beneficial systemic health effects of current curcumin supplement use by their patients.Clinical Trial Registrationhttps://onderzoekmetmensen.nl/en/trial/25480, NL5931.

Abstract A089: Antithrombin III and fibrinogen activity as surrogate markers in predicting therapeutic asparaginase activity levels in children with acute lymphoblastic leukemia

Abstract Background. The incorporation of asparaginase has played an important role in improving survival rates in pediatric patients treated for acute lymphoblastic leukemia (ALL). Measuring asparaginase levels is one method to determine the efficacy of this chemotherapy. Determination of antithrombin III (ATIII) and/or fibrinogen (FIB) activity can be clinically useful as indirect asparaginase (ASP) level assessments since serum assays of ASP levels are not widely available, can be costly, and are performed at specialized labs. Previous studies have identified ATIII and FIB as potential markers in characterizing low or undetectable asparaginase activity in pediatric patients with ALL. The objective of this study was to determine whether FIB and ATIII levels can be used as surrogate markers in predicting therapeutic ASP activity in a predominantly Hispanic ALL population. Methods. FIB and ATIII levels were collected prior and 7 days post PEG-asparaginase (PEG) infusion. ASP levels were collected 7 days post-PEG. Mean differences in levels of FIB and ATIII activity were compared using t-tests for means and Mann-Whitney tests for medians. The Spearman correlation was used to evaluate the association between asparaginase activity, FIB, and ATIII levels. Unadjusted odds ratios were calculated to assess the predictive value of differences from baseline to Day 7 in ATIII and FIB levels associated with therapeutic levels (≥ 0.1 IU/mL). Results. Twenty patients were enrolled. The cohort was predominantly Hispanic (60%) and male (68%) with a median age of 8 years [range 2-19]. The median FIB level post-PEG was 155 mg/dL [nl 212-466] and the median ATIII activity level was 61% [nl 84-125] in those with therapeutic ASP levels. A median decrease in FIB and ATIII activity levels of 52% were seen with therapeutic ASP levels. By contrast in those with non-therapeutic levels, the difference was 7% and 28%, respectively. The bivariate correlation between ATIII and 7-day asparaginase levels was significant when controlling for BMI (Spearman’s ρ=0.62, p=0.001); the 7-day association between ASP and FIB was not influenced by BMI (Spearman’s ρ=-0.46, p=0.05). FIB and ATIII were correlated (Spearman’s ρ =.47;p=0.03). Both FIB (OR=0.004[0.0003-0.44]; p=0.02) and ATIII (OR=0.004[0.0002-1.0]; p=0.04) demonstrated reduced odds of higher therapeutic levels compared to lower therapeutic levels when mediated by Hispanic ethnicity. ATIII mean changes baseline to Day 7 were significantly smaller for Hispanic ethnicity [(Hispanic =-0.45(0.18) vs. Non-Hispanic =0.52(0.05); p=0.05)]. There were no significant differences in FIB by Hispanic ethnicity. Conclusions. Decreases in ATIII levels from baseline are associated with reduced odds of therapeutic asparaginase levels while decreased FIB levels may also indicate subtherapeutic levels. Hispanic ethnicity appears to mediate the observed effects from ATIII. ATIII and FIB levels may be important indirect markers in ASP activity monitoring when serum asparaginase assays are unavailable. Citation Format: Sonia Morales, Edith Williams, Kirsten Kasper, Keri Zabokrtsky, Lois Sayrs, Diane Nugent, Van Huynh. Antithrombin III and fibrinogen activity as surrogate markers in predicting therapeutic asparaginase activity levels in children with acute lymphoblastic leukemia [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A089.

Therapies to Prevent Progression of COVID-19, Including Hydroxychloroquine, Azithromycin, Zinc, and Vitamin D3 With or Without Intravenous Vitamin C: An International, Multicenter, Randomized Trial.

BackgroundCOVID-19 is a global pandemic. Treatment with hydroxychloroquine (HCQ), zinc, and azithromycin (AZM), also known as the Zelenko protocol, and treatment with intravenous (IV) vitamin C (IVC) have shown encouraging results in a large number of trials worldwide. In addition, vitamin D levels are an important indicator of the severity of symptoms in patients with COVID-19.ObjectivesOur multicenter, randomized, open-label study aimed to assess the effectiveness of HCQ, AZM, and zinc with or without IVC in hospitalized patients with COVID-19 in reducing symptom severity and duration and preventing death.MethodsHospitalized patients with COVID-19 in seven participating hospitals in Turkey were screened for eligibility and randomly allocated to receive either HCQ, AZM, and zinc (group 1) or HCQ, AZM, zinc plus IV vitamin C treatment (group 2) for 14 days. The patients also received nontherapeutic levels of vitamin D3.The trial is registered on the Australian and New Zealand Clinical Trial Registry ACTRN12620000557932 and has been approved by the Australian Therapeutic Goods Administration (TGA).ResultsA total of 237 hospitalized patients with COVID-19 aged 22-99 years (mean: 63.3 ± 15.7 years) were enrolled in the study. Almost all patients were vitamin D deficient (97%), 55% were severely vitamin D deficient (<25 nmol/L) and 42% were vitamin D deficient (<50 nmol/L); 3% had insufficient vitamin D levels (<75 nmol/L), and none had optimal vitamin D levels.Of the patients, 73% had comorbidities, including diabetes (35%), heart disease (36%), and lung disease (34%).All but one patient (99.6%; n = 236/237) treated with HCQ, AZM, and zinc with or without high-dose IV vitamin C (IVC) fully recovered. Additional IVC therapy contributed significantly to a quicker recovery (15 days versus 45 days until discharge; p = 0.0069).Side effects such as diarrhea, nausea, and vomiting, reported by 15%-27% of the patients, were mild to moderate and transient. No cardiac side effects were observed.Low vitamin D levels were significantly correlated with a higher probability of admission to the intensive care unit (ICU) and longer hospital stay.Sadly, one 70-year-old female patient with heart and lung disease died after 17 days in ICU and 22 days in the hospital. Her vitamin D level was 6 nmol/L on admission (i.e., severely deficient).ConclusionsOur study suggests that the treatment protocol of HCQ, AZM, and zinc with or without vitamin C is safe and effective in the treatment of COVID-19, with high dose IV vitamin C leading to a significantly quicker recovery.Importantly, our study confirms vitamin D deficiency to be a high-risk factor of severe COVID-19 disease and hospitalization, with 97% of our study’s patient cohort being vitamin D deficient, 55% of these being severely vitamin D deficient, and none had optimal levels.Future trials are warranted to evaluate the treatment with a combination of high-dose vitamin D3 in addition to HCQ, AZM, and zinc and high-dose intravenous vitamin C.

Challenges in schizoaffetive disorder therapeutic – a case report of a patient with hiperprolactinemia

IntroductionThe only FDA approval therapeutic for schizoaffective disorder is paliperidone. Hiperprolactinemia is one of the most frequent side effects induced by first generation antipsychotics (FGA) or by second generation antipsychotic (SGA), such as risperidone and paliperidone. Prolactin related symptoms (PRS) include amenorrhea, galactorrhea, gynecomastia and fluctuations in psychotic symptoms.ObjectivesTo report the case of a patient with schizoaffective disorder difficult to manage due to symptom resistance and PRS, that improved symptomatology when prolactin serum levels were reduced.MethodsClinical-demographic data collected by clinical interview and clinical process consultation. Non-systematic literature review, searching “psychosis”; “prolactin”; “antipsychotic”; “schizoaffective disorder” on Pubmed database.ResultsWe report the case of 33 years-old female, admitted to our psychiatry inpatient unit for persecutory delusions, loosening of association, auditory hallucinations, and irritability with functional impairment. Symptoms began 13 years before. She was medicated with paliperidone 100mg IM monthly, lithium 800mg daily and clozapine 225mg daily. When admitted she wasn’t adhering to oral medication. On physical examination presented some PRS. The serum presented hyperprolactinemia and lithium in non-therapeutic levels. Initially was re-introduced the previous therapeutic without improval. It was made a therapeutic switch to associate aripiprazole 400mg IM monthly and clozapine 225mg daily, and lithium 800mg daily resulting in prolactine normalization and subsequent improval of psychotic symptoms previously presented.ConclusionsThis case reports challenges in management of patients diagnosed with Schizoaffetive Disorder due to therapeutic refractoriness and side effects. PRS can be ruling, therefore impacting therapeutic choices. We propose a possible role of combination of clozapine and aripiprazole in this scenario.DisclosureNo significant relationships.

Cell-Free DNA to Monitor Immunosuppression Adequacy in Lung Transplantation

<h3>Purpose</h3> Tacrolimus is a primary immunosuppressive drug used in lung transplantation (LTx). Unfortunately, significant variability in drug level monitoring and dosing makes it challenging to determine immunosuppression adequacy. Furthermore, the relationship between drug levels and allograft injury remain poorly defined. This study examines the relationship between tacrolimus blood and donor-derived cell-free DNA (ddcfDNA), a biomarker of allograft injury. <h3>Methods</h3> 96 LTx from a multicenter cohort were included. Periodic tacrolimus blood levels (n= 4,204) were obtained. Serial plasma samples (n=2,122) were assayed for %ddcfDNA by shotgun sequencing. %ddcfDNA was log-transformed to adjust for skewness. Tacrolimus trough levels were dichotomized to "therapeutic" and "non-therapeutic" based on clinically desirable trough ranges. Tacrolimus trough and %ddcfDNA trends were analyzed. Separate analysis was performed in patients with and without ACR (> Grade 1 per ISHLT criteria). <h3>Results</h3> Over a 24-month follow up period, %ddcfDNA showed an inverse relationship to tacrolimus tough levels (Figure 1a); patients showed higher %ddcfDNA with non-therapeutic tacrolimus trough levels than with therapeutic levels (p<0.0001) (Figure 1b). 27% of patients experienced at least one episode of ACR. During the study follow-up, their %ddcfDNA levels were higher (p=0.049) and their percentage of non-therapeutic trough levels was higher (p=0.006) compared to patients with no ACR. However, even when tacrolimus trough levels were therapeutic, patients with ACR showed higher %ddcfDNA levels compared to patients without ACR (p=0.020). <h3>Conclusion</h3> %ddcfDNA levels vary inversely with tacrolimus blood trough levels in LTx. Even in patients with therapeutic trough levels, those with ACR demonstrate higher %ddcfDNA levels. Further studies should examine whether sensitive biomarkers such as ddcfDNA can be used to augment immunosuppression monitoring in LTx rather than trough levels alone.

Transplantation and Adherence: Evaluating Tacrolimus Usage in Pediatric Patients With Cancer.

Researchers have estimated that about 50% of pediatric patients with chronic illness adhere to tacrolimus therapy, a medication responsible for preventing critical side effects in patients undergoing hematopoietic stem cell transplantation (HSCT). The purpose of this study was to describe patient adherence to tacrolimus by reviewing documentation from the electronic health record and therapeutic drug levels. This retrospective descriptive study examined 357 clinic visits by 57 patients undergoing HSCT. Direct (tacrolimus levels) and indirect (subjective reporting) measures were evaluated. The authors found that, in 51% of visits, adherence was not documented. The overall nontherapeutic drug level rate was 60%. Because of the small sample size, nonadherence did not statistically correlate with nontherapeutic levels. The findings highlight the need for adherence awareness, assessment, and documentation in clinical practice.

Evaluation of Fosphenytoin Therapeutic Drug Monitoring in the Neurocritical Care Unit.

ObjectiveThe aim of this study was to determine whether the current method of calculating a fosphenytoin reloading dose results in a therapeutic free phenytoin level on subsequent days.MethodsMedical records of patients receiving fosphenytoin in the neurocritical care unit between July 2017 and June 2018 were screened. Included patients were those who had received at least three doses of fosphenytoin and required reloading doses according to concentrations obtained through therapeutic drug monitoring. Free phenytoin levels were categorized based on the prespecified patient-specific target range, generally between 1.5 and 2.5 mcg/mL.ResultsOf the fosphenytoin reloading doses administered, 48% (73/152) resulted in a therapeutic free phenytoin concentration on the subsequent day, with the remaining 52% resulting in nontherapeutic levels (39% subtherapeutic, 13% supratherapeutic). Our evaluation of reloading dose calculation strategies indicated that patients were two times as likely to obtain a therapeutic level when a modified pharmacokinetic equation omitting the use of volume of distribution or salt formulation was used (58%, n = 39) than they were with doses calculated using the current pharmacokinetic model (41%, n = 20) or doses based on provider preference (39%, n = 14).ConclusionThe current method of calculating a fosphenytoin reloading dose in the critically ill population does not consistently result in therapeutic concentrations. With multiple factors affecting the pharmacokinetics of critically ill patients, the creation of a new pharmacokinetic model with less emphasis on volume of distribution may more consistently result in therapeutic concentrations.

P027 Could Fecal Calprotectin Guide the Therapeutic Regimen of Infliximab in Inflammatory Bowel Disease?

BACKGROUND: Infliximab is a monoclonal antibody against tumor necrosis factor α approved for induction and maintenance of remission in inflammatory bowel disease (IBD). Therapeutic monitoring, with determination of infliximab levels, allows to guide therapeutic decisions and helps to prevent loss of response. AIM: To identify predictive factors of non-therapeutic infliximab levels (<0.50 µg/mL) in IBD patients. METHODS: Retrospective single-center study including patients treated with infliximab with at least one determination of infliximab levels and with a minimum follow-up of six months. Clinical and demographic data obtained included disease phenotype, surgical background, duration of infliximab therapy, presence of anti-infliximab antibodies at the time of analysis, concomitant immunomodulator therapy, compliance, occurrence of an infusion reaction and biochemical assessment at the time of first induction infusion. RESULTS: 104 patients were included, 56 females (53.8%) with a mean age of 38.2 ± 13.1 years. The overall prevalence of non-therapeutic infliximab levels was 29.8%. In the majority (90.4%) of the patients, the first determination was performed during maintenance therapy. 29.0% of the patients with non-therapeutic levels had simultaneously positive antibodies, and of the remainder, 27.3% acquired antibodies in a subsequent analysis. It was found that patients with non-therapeutic levels had significantly higher fecal calprotectin values at the initiation of treatment with infliximab (1184 ± 679 vs 708 ± 621, P = 0.02). No statistically significant association was found with other analytical parameters, like haemoglobin (12.7 ± 1.7 vs 12.9 ± 1.6, P = 0.55), C-reactive protein (11.2 ± 12.2 vs 15.9 ± 20.0, P = 0.22), sedimentation rate (22.4 ± 20.7 vs 23.7 ± 19.3, P = 0.76), ferritin (138.3 ± 128.2 vs 165.5 ± 166.6, P = 0.42) or albumin (3.50 ± 0.45 vs 3.56 ± 0.47, P = 0.54). CONCLUSION(S): Patients with non-therapeutic levels of infliximab have higher values of calprotectin prior to treatment, which may be related to increased inflammatory activity. In these cases infliximab regimens with higher and/or more frequent doses may be considered.

P026 Investigating Predictors of Antibodies to Infliximab Formation in Inflammatory Bowel Disease – The Importance of Immunomodulators

BACKGROUND: Anti-tumor necrosis factor (TNF)-α have revolutionized the treatment of inflammatory bowel diseases (IBD), modifying their natural history. Loss of response to anti-TNFs is a clinical challenge and has been associated with formation of antibodies. AIM: To identify predictive factors of antibodies to infliximab (ATI) formation in IBD patients. METHODS: Retrospective single-center study including all consecutive IBD patients being treated with infliximab with at least one ATI and infliximab level determination and with a minimum follow-up of six months after the first testing. Presence of ATI was considered if at least one determination was positive during the follow-up and infliximab levels at this testing were registered. Clinical and demographic data obtained included disease phenotype, surgical background, duration of infliximab therapy, use of premedication, concomitant immunomodulator therapy at the time of testing, compliance, occurrence of an infusion reaction and biochemical assessment at the time of first induction treatment. RESULTS: 104 patients were included, 56 females (53.8%) with mean age of 38.2 ± 13.1 years. The overall prevalence of detectable ATI was 28.8% (30) and the mean time to its formation was 32.8 ± 24.3 months. Most (66.7%) patients with ATI had simultaneously nontherapeutic levels of infliximab. Patients treated with concomitant immunomodulators were less likely to develop ATI (33% versus 88%, P < 0.001). Additionally, it was found that patients with Ulcerative Colitis (UC) were more likely to have detectable ATI than those with Crohn Disease (CD) (44.4% vs 23.4%, P = 0.04). However, UC patients were less treated with concomitant immunomodulators (48.1% vs 80.5%, P = 0.001). At logistic regression analysis only lack of immunomodulator use (P < 0.001; OR 13.5, CI 95%, 4.63–40.0) was independently associated with ATI formation. CONCLUSION(S): Concomitant immunomodulator therapy was the only protective factor for the ATI formation, supporting its institution to prevent loss of response to anti-TNFs.

The Medication Level Variability Index (MLVI) as a potential predictive biomarker of graft-versus-host disease in pediatric hematopoietic stem cell transplant patients.

The purpose of this study was to examine the potential predictive value of the Medication Level Variability Index (MLVI) biomarker with graft-versus-host disease (GVHD) in the pediatric hematopoietic stem cell transplant (HSCT) patient during the acute phase post-transplant. This retrospective descriptive study evaluated a total of 406 tacrolimus levels in 64 patients over a varying number of weeks per participant (median=8, min=3, max=11). Patients were followed until Day 100 post-transplant or tacrolimus taper began. A total of 72 episodes of non-therapeutic levels occurred during the acute phase. Of those, 40 (56%) were <5, while 32 (44%) were >15. Approximately 39% (n=25 of 64) of the participants in the study developed GVHD post-discharge. Those with GVHD had a statistically significantly higher MLVI than those that did not (median=3.1, IQR=2.5-4.7 vs 2.3, IQR=1.6-3.4, respectively, P=0.024). Using a criterion of MLVI>3, there was a statistically significant increased likelihood of GVHD (OR=3.82, 95% CI=1.32=11.04, P=0.013). Area under the curve (AUC) calculation for the sensitivity and specificity of using the MLVI for GVHD was also conducted. The AUC of 0.67 was statistically significant (95% CI 0.53-0.81, P=0.024). This is the first-known study to report the use of the MLVI in HSCT patients. The MLVI is associated with a main adverse outcome related to HSCT, GVHD. These results are encouraging of a new potential biomarker to evaluate tacrolimus serum assay levels and identify patients at risk for developing GVHD.

Use of Nano- SIMS at the single cell-level to evaluate drug penetration into mycobacterial biofilms

Non-tuberculous mycobacteria (NTMs), such as Mycobacterium abscessus and chimaera, can cause high mortality and morbidity amongst patients who are immunocompromised or have chronic lung diseases, such as cystic fibrosis. Mycobacterial biofilms can form in the alveolar walls of such patients following inhalation from environmental reservoirs. Recently, pathogenic strains have been isolated from shower heads and hospital air conditioning units. Biofilms are notoriously difficult to eradicate and are associated with the development of increased antimicrobial resistance (AMR). Treatment for M. abscessus and chimaera infections often requires 2–3 antibiotics over 2 years. The question we want to address is whether the increased AMR and treatment time in NTM biofilm formation is due to lack of antibiotic penetration, resulting in non-therapeutic and AMR-generative levels, or the development of phenotypic and/or genetic resistance. In this project we will use Nano-SIMS (nano-scale secondary ion mass spectrometry) to measure penetration of the antibiotic bedaquiline (BDQ), used to treat NTM infections, into individual cells of NTM biofilms (M. abscessus and M. chimaera). Nano-SIMS maps the relative abundance of different ions down to the nano-scale and can be used to measure in profile through the biofilm. In addition, the minimum inhibitory concentration (MIC) and minimum duration for killing (MDK) of BDK will be measured to determine antibiotic susceptibility in biofilms and a planktonic growth control. Understanding the AMR generation and prolonged treatment in NTM biofilms could lead to improved mortality and morbidity. The development of novel treatment strategies could enhance treatment efficacy, reduce treatment duration and AMR development.

Impact of a Pharmacist Driven Anti-Xa Level Monitoring Protocol on Therapeutic Drug Monitoring Practice Patterns

Introduction:Low molecular weight heparin (LMWH) has a favorable pharmacokinetic profile which precludes the need for routine laboratory monitoring. However, certain patient populations, including those with extreme body weight (overweight or underweight), renal dysfunction, history of bleeding event while receiving LMWH, or previous failure of therapy, may benefit from therapeutic monitoring. Suboptimal drug monitoring of enoxaparin due to incorrect timing of anti-Xa levels, delayed blood sample draws, and/or lack of follow up once the anti-Xa level has resulted has been documented in the literature and may lead to toxicity or suboptimal efficacy (Hosp Pharm. 2017 Mar; 52(3): 214-220.). A retrospective chart review conducted at our institution in 2015 evaluated 100 adult patients who were prescribed LMWH and were ordered an anti-Xa level over a ten month period. In 36% of patients, there was no documented indication for therapeutic monitoring of the LMWH. The study also demonstrated that 35% of anti-Xa levels were drawn outside of the recommended 3 to 5 hour time frame after the previous LMWH dose, and follow up action to abnormal levels was only performed for 39% of patients. In October 2018, our institution implemented a pharmacist driven protocol for anti-Xa level monitoring, including restriction of ordering of anti-Xa levels by a pharmacist, and recommendations for dose adjustments in response to non-therapeutic levels. The purpose of this analysis was to evaluate the impact of a pharmacist driven anti-Xa level monitoring protocol on compliance with institutional guidelines for LMWH monitoring, including indication for drug monitoring, timing of levels, and follow up to abnormal anti-Xa levels.Methods:We conducted a retrospective chart review of adult patients who received therapeutic enoxaparin and were ordered for an anti-Xa level between October 17, 2017 and July 1, 2018. Pediatric patients (<18 years of age) and patients receiving prophylactic enoxaparin were excluded. Levels were assessed for each patient encounter in patients who had more than one hospital admission during the study period, however only the first anti-Xa level on each admission was evaluated. Data analyzed included patient demographics, enoxaparin dose and indication, ordering service, presence of a Hematology consult, indication for anti-Xa level monitoring, timing of the level after previous enoxaparin dose, timing of sample collection by nursing staff, appropriate number of doses prior to level, appropriateness of follow up action to abnormal levels, bleeding events, and recurrent thrombosis.Results:During the study period, a total of 109 anti-Xa levels were ordered for 102 patients who met inclusion criteria. The most common indication for enoxaparin therapy was for venous thromboembolism (81%), followed by atrial fibrillation (9%). The most common indication for assessment of anti-Xa levels were for body weight ≥150 kg and/or BMI ≥40 kg/m2 (28%), creatinine clearance <30 ml/min or renal replacement therapy (23%), and previous failure of anticoagulation (19%). Of the 109 anti-Xa levels assessed, 93% were ordered appropriately (3-5 hours post scheduled dose and after ≥3 doses of enoxaparin). Of the 97 total anti-Xa levels scheduled correctly, 87% were drawn at the appropriate time by nursing staff. Of the 57 levels that were not within the therapeutic range, 75% had a documented follow up facilitated by the pharmacist, which included a recommendation of follow up action.Conclusion:Appropriate monitoring of enoxaparin and correct timing of anti-Xa levels is crucial to facilitate proper clinical decision making and dose adjustments. Timely follow up to drug levels is also critical when the values are out of range, which may increase the risk of toxicity or decreased efficacy. The implementation of a pharmacist driven anti-Xa level protocol at our institution dramatically increased the number of correctly drawn anti-Xa levels, from 65% to 87% (p=0.00016). Follow up to non-therapeutic levels also increased significantly from 39% to 75% (p=0.0001) after implementation of the protocol. Further analysis and assessment of levels from a larger time period may be necessary to determine the clinical impact of implementation of a pharmacist driven anti-Xa monitoring protocol. DisclosuresNo relevant conflicts of interest to declare.

P460 Impact of anti-TNFα exposure during pregnancy for maternal inflammatory bowel disease on serologic response to vaccination of exposed children

Anti-TNFα therapy is increasingly used during pregnancy for women with inflammatory bowel disease (IBD). Thus, the knowledge on long-term evolution of exposed children, including response to vaccinations is crucial. A recent study demonstrated an adequate response to two non-live vaccines in 71% and 80% of exposed infants.1 Our aim was to assess the impact of anti-TNFa exposure in utero for maternal IBD on serologic response to vaccinations in exposed children. We prospectively included consecutive children (≥12 months of age) born to mothers with IBD (2007–2016) treated with anti-TNFa during pregnancy in three medical centres in Czech Republic. Data on birth, perinatal period, psychomotor development, vaccination, infections, antibiotic use and atopy were collected by treating paediatricians from children’s medical files using a predefined questionnaire. Furthermore, a subset of children had a blood sample taken for assessment of immunologic parameters including serologic response to vaccination: (A) non-live vaccines (given within the first year of live): Haemophilus influenza B-HiB, tetanus-TET, diphtheria-DIF, Streptococcus pneumoniae-PNE; (B) live vaccines (given since 15th month of life): parotitis-PAR, rubeola-RUB, morbilli-MOR. Sixty-nine exposed children were included (47.8% girls, median age 35.4 months at last follow-up). Of them, 45 (65.2%) children had a blood sample taken at a median age of 34.8 months. After completion of vaccination protocol, protective antibodies to all non-live vaccines were detected in 63.6% of children while 36.4% of them had inadequate response to at least one non-live vaccine: 23.2% to HiB, 4.5% to TET and 2.4% to PNE. Regarding live-vaccines, protective titres of antibodies were found in 71.4% of vaccinated children and 28.6% had insufficient titres: 25.7% to PAR and 2.9% to each of MOR and RUB. Anti-TNFα levels in cord blood were available for 25 children with blood samples. No significant difference in proportion of protective antibodies to non-live or live vaccines was observed comparing children with a therapeutic (≥3 μg/ml) vs. non-therapeutic cord levels of anti-TNFα (p > 0.05). Two-thirds of children exposed to anti-TNFα in utero had adequate serologic response to non-live and/or live vaccines which is in agreement with findings of a previous study.1 The highest rate of inadequate response to vaccination was observed in case of haemophilus and parotitis vaccines. A control group of unexposed children is needed to assess the vaccination response in general paediatric population. 1. Beaulieu et al. Use of biologic therapy by pregnant women with inflammatory bowel disease does not affect infant response to vaccines. CGH 2017.

Farm Animal Welfare and Human Health.

The paper examines the relationship between farm animal welfare, industrial farm animal production, and human health consequences. The data suggest that when the animal welfare of land-based farm animals is compromised, there are resulting significant negative human health consequences due to environmental degradation, the use of non-therapeutic levels of antibiotics for growth promotion, and the consequences of intensification. This paper accepts that even if meat and fish consumption is reduced, meat and fish will be part of the diet of the future. Industrial production modified from the current intensified systems will still be required to feed the world in 2050 and beyond. This paper identifies the concept of sustainable intensification and suggests that if farm animal welfare is improved, many of the human health consequences of intensified industrial production can be eliminated or reduced. In water-based farm animal production, many new systems are resulting in a product that actually protects the environment and can be done at industrial levels without the use of antibiotics.

Clinical Practice Patterns of Anti-Xa Monitoring During Low Molecular Weight Heparin Therapy

Introduction: Therapeutic low molecular weight heparin (LMWH) regimens were developed empirically based on patient weight and renal function without the need for laboratory monitoring. The role of anti-Xa monitoring for patients receiving LMWH has yet to be fully established and is routinely performed only in high risk patients. At our institution, guidelines for monitoring LMWH recommend drawing anti-Xa levels for patients with chronic kidney disease or those with obesity requiring long-term therapy. The purpose of this analysis was to evaluate compliance with institutional guidelines for monitoring anti-Xa levels for patients receiving LMWH, including indication for anti-Xa monitoring, timing of anti-Xa level in relation to drug administration, and follow up actions of providers in response to abnormal anti-Xa levels.Methods: We conducted a retrospective chart review of adult patients who received therapeutic LMWH (enoxaparin or dalteparin) and were ordered for an anti-Xa level between September 1, 2014 and July 1, 2015. Patients were excluded if they were ordered for an anti-Xa level while on a prophylactic dose of LMWH or while on a non-LMWH factor Xa inhibitor. Data collected included patient demographics, LMWH dose and indication, ordering service, presence of a Hematology consult, reason for anti-Xa monitoring, timing of the level after the previous LMWH dose, and provider response to the level.Results: One hundred patients met inclusion criteria, 99 of whom received enoxaparin. Venous thromboembolism was the most common reason for LMWH therapy (85%) followed by atrial fibrillation (11%). The most frequent doses of enoxaparin administered were 1 mg/kg every 12 hours (52%), 1 mg/kg every 24 hours (22%) and 1.5 mg/kg every 24 hours (21%). The most frequently specified indications for anti-Xa monitoring were renal dysfunction and acute kidney injury (30%), followed by abnormal body mass index (13%); no indication was specified by the prescriber or pharmacist in 36% of cases. Of the 100 anti-Xa levels in the study, 65 were drawn at the correct time (3-5 hours after the previous dose of enoxaparin); of the 35 drawn at an incorrect time, 33 had levels measured more than 5 hours after the previous enoxaparin dose. Fifty-four of the initial anti-Xa levels were not within the therapeutic range for the dosing interval of LMWH; of these, follow up action was taken for only 21 patients (39%), most frequently resulting in a dose increase or decrease.Conclusions: In clinical practice, the use of anti-Xa monitoring is inconsistent and commonly done without a documented need. The majority of anti-Xa levels at our institution are drawn at the appropriate time after the previous dose of LMWH, but action is generally not taken in response to non-therapeutic levels. Additional guidance on the use of LMWH monitoring is needed. DisclosuresNo relevant conflicts of interest to declare.

Infliximab Therapeutic Drug Monitoring in Clinical Practice: Indications and Utility

Purpose: Infliximab (IFX) is effective for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). Measurement of serum IFX levels and antibodies to infliximab (ATI) have shown utility in the management of inflammatory bowel disease (IBD) patients with inadequate/loss of response (LOR) to IFX or infusion reactions. Evolving evidence suggests additional indications for therapeutic drug monitoring using IFX and ATI concentrations in patients without specific response-related issues, and in patients restarting IFX after drug holiday, may help predict and optimize response to IFX. Here, we report the spectrum of use of IFX and ATI testing at an academic IBD Center, including novel indications such as reintroduction of IFX and therapeutic drug monitoring. Methods: We conducted a retrospective review of the electronic medical records of all IBD patients at our institution who underwent IFX/ATI testing between January 1, 2010 and December 31, 2012. The testing date, results, indication for testing, and clinical management based on test results were obtained. Results: One hundred forty two IBD patients (83 with CD, 58 with UC, one with indeterminate colitis) underwent 205 IFX/ATI tests. Sixty-one percent (87/142) of patients received concomitant immunosuppression (IS). The most common indications for testing were inadequate/LOR (50%) and therapeutic drug monitoring (19%). Of 49 patients with confirmed LOR, 50% (25/49) had non-therapeutic IFX levels, and additional 16% (8/49) had detectable ATI with undetectable IFX levels. Thirty-eight patients underwent testing for therapeutic drug monitoring: 16% (6/38) had nontherapeutic IFX levels, 3% (1/38) had detectable ATI, and 3% (1/38) had measurable IFX with detectable ATI. Of seven patients tested prior to reintroduction of IFX, 43% (3/7) were found to have detectable ATI. Of 11 patients tested after re-challenge with IFX, 55% (6/11) had nontherapeutic IFX concentrations, and 36% (4/11) had detectable ATI. Concomitant IS therapy was significantly associated with negative ATI status (p=0.0026). Non-therapeutic IFX concentration was associated with higher C-reactive protein (p<0.0001). Testing resulted in changes in therapy in 67% of patients with LOR, and 21% of patients undergoing routine therapeutic drug monitoring. Conclusion: The measurement of IFX and ATI concentrations in IBD patients receiving IFX can aid decision-making in multiple clinical scenarios and frequently results in changes in clinical care. Disclosure - Dr. Sandborn - Consultant and Grant/Research Support: Janssen Biotech, Inc, Consultant: P rometheus Laboratories, Inc.; Dr. Levesque - Consultant: Prometheus Laboratories, Inc.

Non-therapeutic anti-Xa levels in medical patients receiving anticoagulant therapy with enoxaparin

Anticoagulant activity of enoxaparin is not routinely monitored even when previous studies have shown a high pharmacological variability. The aim of this study is to determine the prevalence of non-therapeutic anti-Xa levels among medical patients using enoxaparin as anticoagulant therapy and to point out potential risk factors related to the risk of having a sub-therapeutic level. Anti-Xa levels were measured in a cohort of sixty patients with medical indication for enoxaparin. Patients were categorized according to anti-Xa levels as follows: suboptimal anticoagulation (<0.5 IU/ml), optimal anticoagulation (between 0.5 and 1.2 IU/ml) or overanticoagulated (>1.2 IU/ml). Demographic and clinical variables and the use of concomitant medications were described for each group. Univariate and multivariate analysis were performed to assess the relationship between sub-optimal anticoagulation and potential predictive variables. A linear regression analysis was done to assess the relationship between anti-Xa activity, age, weight, body mass index, administered dose/weight and creatinine clearance. The mean anti-Xa activity was 0.71±0.32 UI/ml. Thirty one percent of patients had anti-Xa levels out of the therapeutic range, most of them (twenty-eight percent of total population) with a sub-therapeutic level. None of the variables were associated with the risk of a sub-therapeutic anti-Xa level. Almost one third of patients receiving enoxaparin had anti-Xa levels out of the therapeutic range. We need more studies to determine the clinical relevance of these findings.

Do Sound Levels and Space Contribute to Agitation in Nursing Home Residents with Dementia?

Individuals with dementia living in nursing homes may be exposed to non-therapeutic levels of sound. There is insufficient research examining the relationship between sound levels, personal space, and agitation in people with dementia. Using an observational designed study, 53 participants from four southeastern Wisconsin nursing homes were observed; data on sound levels, space, and agitation levels were obtained. Sound was a significant predictor of agitation. The accumulation of sound predicted agitated behavior and explained 16% of the variance, F(5, 47) = 4.520, p < 0.002, and adjusted R(2) = 0.253. The findings suggest agitation may be a clue that sound in the environment is causing stress for residents with dementia.

Potential benefits of warfarin monitoring by a clinical pharmacist in a long term care facility

The primary objective of this study was to determine whether warfarin therapy monitoring by a pharmacist would benefit a long-term care facility, by maintaining patients within therapeutic INR range more consistently than the current practice of physician monitoring.Secondary objectives included whether adverse events resulting from non-therapeutic INR levels differed significantly between groups and whether pharmacist interventions resulted in decreased overall costs to the facility. A retrospective chart review was conducted on all patients treated with warfarin for a minimum of 14 days within a Long-Term Care (LTC) facility to compare Time within Therapeutic Range (TTR) between staff treated patients versus pharmacist treated patients. A total of 552 INRs were obtained for all patients during the study period: 499 (90.4%) under staff supervision and 53 (9.6%) under clinical pharmacist supervision. Of the 499 tests performed by the River Garden staff, 203 were within the desired range, compared with 29 of the 53 tests performed by the clinical pharmacist being in range. For the primary endpoint, a total of 1483 INRs were imputed, corresponding to the number of days between true INR measurements. INRs attributable to clinic staff management were within the therapeutic range 47.1% of the time, whereas INRs attributable to clinical pharmacist management were within the therapeutic range 58.7% of the time (P < 0.0001 for the comparison). Warfarin can be effectively monitored by a clinical pharmacist and routinely lead to appropriate INR levels in the nursing home setting, while potentially saving the facility healthcare dollars.