Medication-related Adverse Effects Research Articles

P-446. Outcomes of Hospitalization due to Cryptococcal Meningitis in a High-Resource Setting, 2015-2022

Abstract Background There is a paucity of outcome data in high-resource settings for cryptococcal meningitis (CM) in persons living with HIV (PWH). Novel induction regimens, such as the first-line recommended regimen from the World Health Organization, may reduce the duration of hospitalization and drug-associated adverse events with similar treatment outcomes. However, these regimens were not compared to the standard of care used in high-resource countries, leading to a reluctance to change current practice. Randomized controlled trials to compare these strategies would be cost-prohibitive in high-resource settings. To work towards quality observational data on this subject, we sought to describe medication-related adverse effects (AE) and mortality of PWH hospitalized with CM at our institution.Table 1:Patient Characteristics Methods We retrospectively obtained all electronic medical records associated with inpatient encounters and an HIV diagnosis occurring between 2015-2022 at Harbor-UCLA Medical Center in Los Angeles County, California. We screened for discharge diagnoses of CM or the immune reconstitution inflammatory syndrome due to CM (CM-IRIS). We abstracted demographic, diagnostic, therapeutic, and outcome data from these patient records.Table 2:Diagnostics and Patient Outcomes Results Thirty-one PWH were hospitalized with CM and/or CM-IRIS for a total of 51 admissions. Of these, 26 (83.9%) were cisgender men, 3 (9.7%) were cisgender women, and 2 (6.5%) were transgender women. The median age was 36 years old (IQR 30-46), and 21 (67.7%) were of self-identified Hispanic ethnicity. The median time since diagnosis of HIV was < 1 year (IQR 0-5.5). All patients were prescribed liposomal amphotericin B at 3-4mg/kg/day and flucytosine (5-FU) 100mg/kg/day for initial treatment. Fifteen (48.4%) patients failed to complete the 2-week induction, 10 (32.3%) due to AE. In-hospital mortality occurred in 4 (12.9%) patients, and 1-year mortality was documented for 7 patients (22.6%). Five patients (16.1%) had unknown status at 1 year. Conclusion We report a 1-year mortality of 22% in PWH hospitalized for CM in a high-resource setting compared to about 30-40% reported globally. However, 48% of patients were unable to complete induction, 32% due to adverse drug effects, emphasizing the importance of investigating the effectiveness of novel approaches to therapy. Disclosures All Authors: No reported disclosures

Comparison of enteral prucalopride versus intravenous metoclopramide for feeding intolerance in patients with critical illness: a randomized double-blinded study.

Feeding intolerance is commonly experienced during enteral feeding, necessitating cessation. Metoclopramide may be given to assist gastric emptying, but patients experience adverse effects and gradual loss of efficacy. Prucalopride, a safer prokinetic, may play a role in gastric emptying. Therefore, the current study aimed to assess its effectiveness and safety in feeding intolerance developed in critically ill patients. In this prospective randomized double-blinded study, patients with feeding intolerance were randomized to receive 2mg prucalopride enterally once daily or 10mg metoclopramide intravenously every 6-8h for 7days. Patients were monitored for treatment failure, successful feeding, gastric residual volume (GRV), and the development of medication-related adverse effects. A total of 70 patients (35 in the metoclopramide group and 35 in the prucalopride group) completed the study. The average daily GRV in the prucalopride group was significantly lower compared to the metoclopramide group (p=<0.001) on day 7. Additionally, the percentage change in GRV from day 1 to day 7 showed a greater significant change in the prucalopride arm versus the metoclopramide arm (p=<0.001). The treatment groups were comparable in terms of ICU length of stay (p = 0.094). Moreover, there was a significantly higher successful caloric intake in the prucalopride group compared to the metoclopramide group on day 7 (p = 0.039). Prucalopride administration in enterally fed patients with feeding intolerance may reduce GRV and improve feeding success rates compared to metoclopramide treatment. The use of prucalopride was found to be tolerable and safe in critically ill patients. clinicaltrials.gov, identifier NCT05496179.

Retrospective Review of Treatment Outcomes in Epilepsy Patients: Seizure Control and Medication Side Effects

ABSTRACT Background: Epilepsy management requires balancing seizure control with minimizing medication side effects. This retrospective review examines treatment outcomes in epilepsy patients, focusing on seizure control and medication-related adverse effects. Methods: Medical records of epilepsy subjects treated tertiary care center between 2017 and 2022 were retrospectively reviewed. Data on demographic characteristics, seizure control, medication regimen, and side effects were collected and analyzed. Results: A total of 200 subjects were included. Sixty percent of subjects achieved total seizure independence, 30% reduced seizure frequency, and 10% did not improve or deteriorate. The kind of antiepileptic medicine provided substantially affects prescription side effects (P &lt; 0.05), with drug X causing more dizziness than drug Y (P = 0.02). Elderly individuals were more likely to suffer weariness than younger ones (P = 0.03). Conclusion: This review provides valuable insights into epilepsy treatment outcomes, emphasizing the need for personalized management strategies to optimize seizure control while minimizing medication-related adverse effects.

Neuropsychiatric manifestations of Wilson’s disease – A therapeutic challenge

Abstract: Wilson’s disease (WD) occurs due to abnormal copper metabolism and often presents with various neurological, cognitive, and psychiatric symptoms. Variable symptoms and a high propensity for medication-related adverse effects frequently make their management difficult. Here, we discussed two cases of WD presented to psychiatric OPD with variable neuropsychiatric symptoms managed conservatively but frequently complicated by newer symptoms, and medication-related side effects, which lead to multiple consultations and frequent changes in drug schedule. Therefore, we found it a great therapeutic challenge, and more discussion and research are warranted for such a condition.

Comparison of Efficacy and Safety Profile of Conservative Versus Surgical Management of Meniscal Injuries

Background: Surgical management of meniscal tear carries financial implications in resource limited settings like ours. Conservative management could address this issue, if its safety and efficacy profile is better understood. Objectives: The objective of this study was to compare the efficacy and safety of conservative and surgical management of patients with meniscal tear with conservative management.Material and Methods: Descriptive comparative study of 80 patients with meniscal tear, recruited through non-probability convenient sampling technique, was carried out at Orthopedic unit MMC MTI Mardan, during 1st August 2022 and 31st July 2023. Patients were assigned to surgical and conservative group. International Knee Documentation Committee (IKDC) score at baseline and 3 months after treatment were compared for efficacy. Treatment related complications were noted.Results: A total of 80 patients were enrolled with 40 patients in each group (surgical versus conservative). The mean baseline and IKDC score at week 12 in surgical versus conservative group were 45.069±13.301 versus 51.873±17.90 and 79.52±7.40 versus 73.92±11.67 respectively. Surgical group showed treatment response in 37 patients (92.5%) versus 31 (77.5%) in conservative approach (p value 0.060). Surgical site infection was observed in 5 patients (12.5%) in surgical group. Medication related adverse effects were observed in 3 patients (7.5%) in conservative group.Conclusion: No appreciable differences in the clinical results, such as pain reduction or better knee function, between patients who received meniscal surgery and those who underwent conservative treatment for meniscal tears.Keywords: Conservative Approach, Meniscal Injury, Surgical Approach, Treatment Outcomes

P646 Clinical decision support in the prevention of adverse effects associated with immunosuppressive drugs in patients with Inflammatory Bowel Disease

Abstract Background With the goal of effective and early prevention and detection of medication-related adverse effects, an explosion of technological advances is taking place. However, none of these systems are currently intelligent enough to ensure safe prescribing of treatments on their own. Purpose To design and integrate clinical decision rules (CDR) to increase the safety of immunosuppressive treatments in patients with inflammatory bowel disease (IBD) into an electronic prescribing assistance software (HIGEA). Methods This is a descriptive study conducted in a tertiary university hospital in Madrid (Spain). 1. We reviewed the technical product information sheet of the immunomodulatory drugs used in the treatment of patients with IBD and the current recommendations and clinical practice guidelines on the management of IBD. 2. The CDR were developed within a multidisciplinary team of physicians and pharmacists by integrating data from pharmacogenetics, microbiology, biochemistry, immunology and haematology laboratories, the electronic medical record and the electronic prescribing programme. 3. Integration was performed using a standard language (HL7). Results The technical product information sheet of 33 immunomodulatory drugs (19 biological therapies, 6 small molecules and 8 traditional disease-modifying drugs) and the clinical practice guidelines for the treatment of IBD of the European Crohn's and Colitis organisation (ECCO) and the Spanish working group on Crohn's disease and ulcerative colitis (GETECCU) were reviewed. A total of 169 CDR were developed: 2 related to pharmacogenetics laboratory values, 26 to microbiology, 38 to biochemistry, 24 to immunology, 42 to haematology, 28 to clinical history and 9 related to concomitant use of other drugs. Of the 169 CDR, 50 (29.58 %) were related to screening prior to initiation of immunosuppressive treatment, 10 (5.92%) to drug interactions and 109 (64.5%) related to clinical conditions requiring adjustment or discontinuation of immunosuppressive treatment. Conclusion The incorporation of personalised clinical rules into the medical prescription and pharmaceutical validation process will allow the selection of patients in whom there could be a safety problem with immunosuppressive treatment, increasing the percentage of early detected and avoided adverse events. Future steps will be to evaluate the impact of the implementation of the CDR tool on increasing safety, reducing healthcare costs and improving patient health outcomes.

The tolerability and efficacy of antifibrotic therapy in patients with idiopathic pulmonary fibrosis: Results from a real-world study

BackgroundIdiopathic pulmonary fibrosis is a progressive and fatal lung disease lacking effective therapeutics. Treatment with pirfenidone or nintedanib is recommended for patients to delay the progression of their disease. Adverse reactions caused by anti-fibrosis drugs can sometimes interrupt treatment and even change the progression of the disease. ObjectiveThis study aimed to investigate the clinical use, adverse reactions, tolerability of pirfenidone and nintedanib in patients with idiopathic pulmonary fibrosis and the efficacy of antifibrotic therapy in a real world. MethodsWe recruited patients with idiopathic pulmonary fibrosis treated with pirfenidone or nintedanib at China-Japan Friendship Hospital from February 2017 to February 2022. We investigated the medication situation, adverse reactions, tolerability and survival of patients taking medications. ResultsA total of 303 patients with idiopathic pulmonary fibrosis were enrolled in the study. Treatment was divided between 205 patients receiving pirfenidone and 98 patients receiving nintedanib. Baseline data between the two groups were not significantly different. Patients treated with nintedanib had a higher overall discontinuation rate than those treated with pirfenidone (61.22 vs. 32.68 %, p < 0.001). Across all patient groups, the most common reason for discontinuing treatment was medication-related adverse effects. Compared to pirfenidone, nintedanib had a significantly higher discontinuation rate due to adverse events (48.98 % vs 27.80 %, p < 0.001). The most common side effect of both drugs was diarrhea. Pirfenidone was associated with a higher rate of extra-digestive adverse effects than nintedanib. Survival was not significantly different between the two drugs and using pirfenidone above 1200 mg/day did not confer significant survival benefits. The survival rate of patients who adhere to anti-fibrosis therapy for more than 6 months can be significantly improved (HR = 0.323, p = 0.0015). ConclusionGastrointestinal adverse effects were the most common adverse effects and the main reason of discontinuation of antifibrotic therapy, especially nintedanib. Consistent adherence to antifibrotic therapy may make the patients benefit from adjusting their antifibrotic medications, dosage, and active management of side effects.

Patient-reported pain, satisfaction, adverse effects, and deviations from ambulatory surgery pain medication.

Addressing the challenges of ambulatory surgery involves balancing effective pain relief with minimizing the side effects of pain medication. Due to the heightened risk of opioid abuse, Helsinki University Hospital (Finland) has had a stringent oxycodone prescription policy. This policy prompts an exploration into whether ambulatory surgery patients experience severe post-surgical pain and whether an increase in prescribed opioids would cause elevation in adverse effects. This prospective cohort study, with a 1-week follow-up, included 111 adult ambulatory surgery patients (orthopaedics, urology). The patients documented their pain levels within the first postoperative week (using a numerical rating scale [NRS] of 0-10) and pain medication intake up to two days postoperatively. Furthermore, they completed a questionnaire assessing their satisfaction with pain relief, medication-related adverse effects, and adherence to instructions. Medication intake was cross-referenced with the provided instructions and prescriptions. A notable 56% of patients reported experiencing intense pain (NRS ≥5) within a week following surgery. Of these, 52% received a single dose of slow-release oxycodone (5-20 mg) at discharge for use on the night of surgery. Predominantly prescribed pain medications included a combination of paracetamol and codeine (64%) or ibuprofen (62%). Satisfaction rates were high, with 87% expressing satisfaction with pain medication given at hospital discharge and 90% expressing contentment with the prescribed medication. The most common adverse effects were tiredness/grogginess (45%), sleep disturbances (38%), nausea (37%), and constipation (27%). Also, 24% of patients self-reported deviations from medication instructions. A comparison of self-reported and instructed medications revealed that 14% exceeded prescribed dosages, and 28% opted for preparations different from those prescribed. Notably, patients who self-reported deviations from instructions differed from those objectively deviating from instructions. Although 56% of patients had intense pain, the majority expressed satisfaction with the provided pain relief. Instances of non-adherence to medication instructions were prevalent, often going unnoticed by the patients themselves.

Perception of the general population on Epilepsy and Antiepileptic drugs: A questionnaire-based study

The impact of epilepsy is multidimensional, ranging from socioeconomic to medical to psychological problems. The additional burden on quality of life is not only due to disease but also to the antiepileptic medication-related adverse effects. Though the majority of epileptics dwell in developing countries, studies have found a lack of knowledge, attitude, and practice towards epilepsy and its management, leading to a large treatment gap. This study aimed to assess the knowledge, attitude, and practice of epilepsy and antiepileptic medication among the general population, including epileptics or caregivers. A 6 month (August 2022 to February 2023) prospective, cross-sectional online questionnaire-based study utilizing Google Forms as a data collection tool was conducted among the general population at a tertiary care hospital in Coimbatore employing convenient sampling. Descriptive and inferential statistics (paired t-test, chi-square test) were used. The results were presented as numbers and percentages. The data obtained was analyzed using Statistical Package for the Social Sciences, version 27. We received 123 responses. 87.8% and 85.4% linked epilepsy to insanity and spiritual possession/trance, respectively. More than 90% opined that epilepsy was contagious, due to patient or ancestral sins, and treatable by faith healers. The mean knowledge, attitude, and practice scores (%) were found to be 78.04 ± 1.32, 71.23 ± 1.23, and 53.15 ± 1.38, respectively. Even though the urban population had satisfactory knowledge, the same was not translated into attitude and practice. There was a wide gap between knowledge, attitude, and practice. Considering the significant disparities in awareness, attitude, and practice even after decades in urban regions, policymakers and public health professionals must incorporate health education programs and healthcare services for the masses to bring about changes in a country like India. Keywords Knowledge, Attitude, Practice, Stigma, Quality of life, People living with epilepsy

A Rare Presentation of Pancytopenia - Amiodarone-Induced Bone Marrow Granuloma

Introduction: Amiodarone is a widely used antiarrhythmic medication associated with a various range of side effects, such as thyroiditis, pneumonitis, and hepatitis. Additionally, although extremely rare, amiodarone has been reported to induce bone marrow granuloma, leading to hematologic disorders. This abstract illustrates the case of amiodarone-induced bone marrow granuloma resulting from unopposed intake of the medication. Case presentation: A 67-year-old male with a known history of iron deficiency and Vitamin B12 deficiency was referred to the hematology/oncology clinic from his primary care clinic due to persistent pancytopenia despite receiving iron and vitamin supplements. Three months before this presentation, the patient underwent EGD and colonoscopy, which did not reveal any gastrointestinal neoplasm. He denied experiencing other symptoms, such as fever, chill, nausea, or vomiting. Both his vital signs and physical examinations were unremarkable. Routine lab results showed pancytopenia, with a hemoglobin level of 11.2, MCV of 71, WBC of 2.6, and platelet of 128. The peripheral blood smear did not demonstrate any blasts or atypical leukocytes. Flow cytometry was negative for abnormal cellular populations. However, the bone marrow biopsy revealed a hypercellular marrow with numerous scattered non-necrotizing granulomas without blasts or atypical cells. A broad range of diagnoses was considered encompassing sarcoidosis, malignancy, infective diseases, and drug reactions. Chest, abdomen, and pelvis CT showed no evidence of malignancy or sarcoidosis. The patient was referred to the infectious disease department to exclude undiagnosed infectious causes. An extensive work-up ensued, including tick-borne diseases, fungal infections, tuberculosis, hepatitis, CMV, and HIV, all of which yielded negative results. The patient's medication list was reviewed to evaluate any potential medication-related adverse effects. Notably, it revealed that the patient had been self-administering amiodarone 200mg once daily for the past 18 months without appropriate cardiology supervision, which was prescribed to manage frequent premature ventricular complexes (PVCs). This situation occurred as a result of the cardiologist leaving the area, which led to a disruption in the follow-up care. Consequently, the patient was presumably diagnosed with amiodarone-induced bone marrow granuloma and was referred to cardiology for further management of amiodarone and PVC. Management: Amiodarone was discontinued and was switched to sotalol by cardiology. Simultaneously, the patient continued to follow hematology/oncology for regular follow-up of CBC. Following the cessation of amiodarone, the patient's pancytopenia gradually improved over time. Discussion: Amiodarone-induced bone marrow granuloma is an extremely rare adverse effect, and its incidence remains unknown due to limited information. However, several case reports documented a similar side effect associated with amiodarone. Typically, bone marrow biopsy reveals noncaseating granuloma, and patients may exhibit various forms of cytopenia. Patients with this condition have shown improvement in cytopenia after the discontinuation of amiodarone. Also, it was observed that granuloma of the bone marrow partially or completely resolves following the discontinuation. However, considering the wide array of potential causes of bone marrow granuloma, including infectious diseases, malignancy, or inflammatory diseases, physicians must thoroughly investigate and exclude other plausible causes before making the diagnosis. Nevertheless, it is crucial for physicians to include amiodarone as the differential diagnosis of pancytopenia as it can be easily reversed by the discontinuation of amiodarone.

Avacopan for the Treatment of Anti-Neutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis.

To review the safety and efficacy of avacopan for the treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. A systematic review of the literature was performed using the terms avacopan OR tavneos OR CCX168 OR ANCA-associated vasculitis in PubMed and Google Scholar. Articles between January 2016 and January 2023 were considered for inclusion. Bibliographies and ClinicalTrials.gov were also searched for completion. Relative English language and human studies related to pharmacology, clinical trials, and safety were included. The 52-week ADVOCATE and 12-week CLEAR clinical trials evaluated the safety and efficacy of avacopan. The remission rate was 65.7% and 54.9% in the avacopan and placebo group, respectively, in the ADVOCATE trial. The Birmingham Vasculitis Activity Score improved by ≥50% in 86.4% of avacopan treated patients and 70% of prednisone treated patients in the CLEAR trial. Glucocorticoids in combination with cyclophosphamide, azathioprine, and/or rituximab have been a mainstay of ANCA-associated vasculitis treatment. However, short- and long-term medication-related adverse effects risk negative outcomes for patients. Avacopan may provide equivalent to better treatment with fewer side effects due to a reduction, if not elimination, of glucocorticoids. Avacopan used in isolation or combination is safe and effective for ANCA-associated vasculitis.

EFFICACY AND SAFETY OF VEDOLIZUMAB AND TUMOR NECROSIS FACTOR INHIBITORS IN THE TREATMENT OF STEROID-REFRACTORY MICROSCOPIC COLITIS: A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract BACKGROUND Tumor necrosis factor (TNF-α) inhibitors and the α4β7 integrin antagonist, vedolizumab have been investigated as a treatment option for patients with steroid-refractory microscopic colitis (MC) with controversial findings. AIMS To perform a systematic review and meta-analysis to evaluate the benefit of vedolizumab and TNF-α inhibitors in patients with steroid-refractory MC. METHODS Retrospective cohort studies and case series involving adult patients with steroid-refractory MC who either received vedolizumab, adalimumab, or infliximab were eligible for inclusion. Outcomes of interest included the rate of clinical remission at induction, clinical response, maintenance of remission, histologic remission, and overall medication related adverse effects. Pooled proportional meta-analyses were used to calculate the overall rates of the primary and secondary endpoints. Heterogeneity was assessed using the I2 statistic. Publication bias was assessed via visual inspection of the funnel plots and using Egger’s regression. All statistical analysis was performed in R using the metafor and meta packages. RESULTS A total of 14 retrospective case series/studies involving 164 patients were included. Pooled analysis showed a clinical remission rate of 63.5% (95% CI [0.483; 0.776], I2=43% P=0.08), 57.8% (95% CI [0.3895; 0.7571], I2=0%, P=0.7541), and 39.3% (95% CI [0.0814; 0.7492, I2=66%, P=0.02) for vedolizumab, infliximab, and adalimumab, respectively. The maintenance of remission rate was 60.5% (95% CI [0.2772; 0.8953], I2=67%, P=0.03), 45.3% (95% CI [0.1479; 0.7747], I2=0%, P=0.36) and 32.5% (95% CI [0.000; 0.8508], I2=53%, P=0.14) in patients who received vedolizumab, infliximab, and adalimumab, respectively. Rate of biologic-related adverse events warranting discontinuation of therapy was 12.2%, 32.9%, and 23.0% for the vedolizumab, infliximab, and adalimumab groups, respectively. CONCLUSION Vedolizumab and anti-TNF-α agents demonstrated a clinical benefit in the treatment of steroid-refractory MC and with a tolerable safety profile. Given the nature of included studies, superiority of either therapy could not be elucidated. Future randomized controlled trials are needed to standardize study protocols, compare vedolizumab with TNF-α inhibitors, and further examine data on patients’ quality of life. Forest plot showing the pooled clinical remission rate at induction in patients with steroid-refractory microscopic colitis receiving (A) vedolizumab or TNF inhibitors (B) Data summary of the meta-analyses of the studies investigating secondary endpoints in patients with refractory MC receiving either (A) vedolizumab or (B) TNF inhibitors ABBREVIATIONS MR, maintenance remission; CR, clinical response; HR, histologic remission; OAE, overall adverse effects.

Effect of a Postoperative Multimodal Opioid-Sparing Protocol vs Standard Opioid Prescribing on Postoperative Opioid Consumption After Knee or Shoulder Arthroscopy

In arthroscopic knee and shoulder surgery, there is growing evidence that opioid-sparing protocols may reduce postoperative opioid consumption while adequately addressing patients' pain. However, there are a lack of prospective, comparative trials evaluating their effectiveness. To evaluate the effect of a multimodal, opioid-sparing approach to postoperative pain management compared with the current standard of care in patients undergoing arthroscopic shoulder or knee surgery. This randomized clinical trial was performed at 3 clinical sites in Ontario, Canada, and enrolled 200 patients from March 2021 to March 2022 with final follow-up completed in April 2022. Adult patients undergoing outpatient arthroscopic shoulder or knee surgery were followed up for 6 weeks postoperatively. The opioid-sparing group (100 participants randomized) received a prescription of naproxen, acetaminophen (paracetamol), and pantoprazole; a limited rescue prescription of hydromorphone; and a patient educational infographic. The control group (100 participants randomized) received the current standard of care determined by the treating surgeon, which consisted of an opioid analgesic. The primary outcome was postoperative oral morphine equivalent (OME) consumption at 6 weeks after surgery. There were 5 secondary outcomes, including pain, patient satisfaction, opioid refills, quantity of OMEs prescribed at the time of hospital discharge, and adverse events at 6 weeks all reported at 6 weeks after surgery. Among the 200 patients who were randomized (mean age, 43 years; 73 women [38%]), 193 patients (97%) completed the trial; 98 of whom were randomized to receive standard care and 95 the opioid-sparing protocol. Patients in the opioid-sparing protocol consumed significantly fewer opioids (median, 0 mg; IQR, 0-8.0 mg) than patients in the control group (median, 40.0 mg; IQR, 7.5-105.0; z = -6.55; P < .001). Of the 5 prespecified secondary end points, 4 showed no significant difference. The mean amount of OMEs prescribed was 341.2 mg (95% CI, 310.2-372.2) in the standard care group and 40.4 mg (95% CI, 39.6-41.2) in the opioid-sparing group (mean difference, 300.8 mg; 95% CI, 269.4-332.3; P < .001). There was no significant difference in adverse events at 6 weeks (2 events [2.1%] in the standard care group vs 3 events [3.2%] in the opioid-sparing group), but more patients reported medication-related adverse effects in the standard care group (32% vs 19%, P = .048). Among patients who underwent arthroscopic knee or shoulder surgery, a multimodal opioid-sparing postoperative pain management protocol, compared with standard opioid prescribing, significantly reduced postoperative opioid consumption over 6 weeks. ClinicalTrials.gov Identifier: NCT04566250.

Comparing Prescribing Practices of Statin Therapy in Atherosclerotic Cardiovascular Disease Patients with Varying Levels of Chronic Kidney Disease

Lead Author's Financial Disclosures Nothing to disclose. Study Funding None. Background/Synopsis Evidence supporting high-intensity statin therapy in patients with atherosclerotic cardiovascular disease (ASCVD) and advanced chronic kidney disease (CKD), not on dialysis, is not robust. Cardiovascular risk reduction from statin therapy within this population is predominantly derived from post-hoc subgroup analysis of larger trials. This subset of ASCVD patients is often at higher risk for medication-related adverse effects, secondary to reduced renal clearance, polypharmacy, and high prevalence of co-morbidities. This increased risk may result in provider hesitation and under prescribing of high-intensity statin therapy among ASCVD patients. Of the available high-intensity statins atorvastatin does not require renal dose adjustments although rosuvastatin does. On a population level, prescribing of statins among patients with ASCVD and CKD has improved in recent years but remains sub-optimal. Results from this study can provide insight into whether providers are following guideline recommendations and package labeled dosing when prescribing statin therapy in a real-world setting. Objective/Purpose This study aims to evaluate real-world prescribing patterns of statin-therapy among ASCVD patients with non-dialysis dependent Stage 4-5 CKD and Stage 3a and 3b CKD. Methods This study is a retrospective, cross-sectional observational study and has been reviewed by the Colorado Multiple Institutional Review Board as exempt. Patients with a diagnosis of clinical ASCVD, non-dialysis dependent CKD stage 3a-5, and prescribed a statin between 1/1/2020-9/30/2021 were identified. The primary outcome will be prescribing ahigh-intensityy statin among patients with eGFR <30 mL/min compared to patients with eGFR 30-<60 mL/min. Secondary outcomes will include differences in mean LDL-C between the two groups and proportion of patients on FDA approved dosing of rosuvastatin. A chi-square test will be used for qualitative data and a student t-test for quantitative data. Results A total of 6000 patients have been identified and will be evaluated for inclusion into this study. Results are currently in progress. Conclusions Will be presented. Nothing to disclose.

Systemic Steroids for Otolaryngology-Head and Neck Surgery Disorders: An Evidence-Based Primer for Clinicians.

To offer pragmatic, evidence-informed guidance on the use of systemic corticosteroids (SCS) for common otolaryngologic disorders. PubMed, Cochrane Library, and American Academy of Otolaryngology-Head and Neck Surgery Foundation clinical practice guidelines. A comprehensive search of published literature through November 2021 was conducted on the efficacy of SCS, alone or in combination with other treatments, for managing disorders in otolaryngology and the subdisciplines. Clinical practice guidelines, systematic reviews, and randomized controlled trials, when available, were preferentially retrieved. Interventions and outcomes of SCS use were compiled to generate summary tables and narrative synthesis of findings. Evidence on the effectiveness of SCS varies widely across otolaryngology disorders. High-level evidence supports SCS use for Bell's palsy, sinonasal polyposis, and lower airway disease. Conversely, evidence is weak or absent for upper respiratory tract infection, eustachian tube dysfunction, benign paroxysmal positional vertigo, adenotonsillar hypertrophy, or nonallergic rhinitis. Evidence is indeterminate for acute laryngitis, acute pharyngitis, acute sinusitis, angioedema, chronic rhinosinusitis without polyps, Ménière's disease, postviral olfactory loss, postoperative nerve paresis/paralysis, facial pain, and sudden sensorineural hearing loss. Clinicians should bring an evidence-informed lens to SCS prescribing to best counsel patients regarding the risks, anticipated benefits, and limited data on long-term effects. Alternate routes of corticosteroid administration-such as sprays, drops, inhalers, and intralesional injections-may be preferable for many disorders, particularly those that are self-limited or require a prolonged duration of therapy. Prudent use of SCS reduces the risk of medication-related adverse effects. Clinicians who are conversant with high-level evidence can achieve optimal outcomes and stewardship when prescribing SCS.

Development of a Web-Based System to Report Medication-Related Adverse Effects: Design and Usability Study.

BackgroundMedicine use is the most common intervention in health care. The frequency with which medicines are used means medication-related problems are very common. One common type of medication-related problems is adverse drug events, which are unintended and harmful effects associated with use of medicines. Reporting of adverse drug events to regulatory authorities is important for evaluation of safety of medicines; however, these adverse effects are frequently unreported due to various factors, including lack of consumer-friendly reporting tools.ObjectiveThe aim of this study was to develop a user-friendly digital tool for consumers to report medication-related adverse effects.MethodsThe project consisted of 3 parts: (1) content development, including a systematic literature search; (2) iterative system development; and (3) usability testing. The project was guided by participatory design principles, which suggest involving key stakeholders throughout the design process. The first 2 versions were developed as a mobile app and were tested with end users in 2 workshops. The third version was developed as a web application and was tested with consumers who were taking regular medicines. Consumers were asked to complete a modified version of the mHealth app usability questionnaire (MAUQ), an 18-item questionnaire with each item scored using a 7-point Likert scale ranging from 0 (strongly disagree) to 7 (strongly agree). The MAUQ assessed 3 subscales including ease of use (5 items), interface and satisfaction (7 items), and usefulness (6 items). Continuous variables were reported as mean (SD) values, whereas categorical variables were presented as frequencies (percentages). Data analysis was conducted in Microsoft Excel.ResultsThe content for the system was based on a systematic literature search and short-listing of questions, followed by feedback from project team members and consumers. Feedback from consumers in the 2 workshops were incorporated to improve the functionality, visual design, and stability of the third (current) version. The third version of the system was tested with 26 consumers. A total of 79% (N=307/390) of all responses on the MAUQ were scored 6 or 7, indicating that users generally strongly agree with the usability of the system. When looking at the individual domains, the system had an average score of 6.3 (SD 0.9) for “ease of use,” 6.3 (SD 0.8) for “interface and satisfaction,” and 5.2 (SD 1.4) for “usefulness.”ConclusionsThe web-based system for medicine adverse effects reporting is a user-friendly tool developed using an iterative participatory design approach. Future research includes further improving the system, particularly the usefulness of the system, as well as testing the scalability and performance of the system in practice.

Real-world experience of using combinatorial pharmacogenomic test in children and adolescents with depression and anxiety

ObjectiveTo evaluate the real-world impact of using a commercially available combinatorial pharmacogenomic (CPGx) test on medication management and clinical outcomes in children and adolescents treated at a tertiary care psychiatry practice. MethodsA retrospective cohort study using our prospectively maintained database of patients undergoing CPGx testing was performed. Only patients with clinical data at the time of ordering CPGx test (pre-baseline), potential medication change visit (baseline) and 8-weeks follow-up (post-baseline) visit were included. Clinical Global Impression (CGI) scores for each visit were calculated. Appropriate statistical analysis, including one-sample t-test, paired t-test and Chi-square test was performed. ResultsBased on the inclusion criteria, 281 (75.9%) of the 370 patients with CPGx testing were included. Their mean age was 15.8 ± 4.5 years (111 females; 39.5%). The average number of medications significantly increased to 2.4 ± 1.2 on the post-baseline visit [t(280) = 8.34, p < 0.001). Medications were added in 123 (43.7%), replaced in 92 (32.7%) patients and remained unchanged in rest. There was no significant association between medication-related adverse effects and psychotropic medication change group (p = 0.27). The study population showed a significant improvement (p < 0.001) in the CGI severity, efficacy, and global improvement indices. ConclusionIn our experience of using CPGx test in a large cohort of children and adolescents during routine clinical practice, three-quarter of them underwent medication change. Additionally, we noted an improvement in clinical outcomes without impacting adverse effects. While the role of clinical judgement in medication changes in our cohort is likely, CPGx may supplement clinical decision making. However, the best use and benefit of CPGx in routine clinical practice needs further investigation.

The Tennessee Medicaid medication therapy management program: early stage contextual factors and implementation outcomes

BackgroundFirst investigated in the 1990s, medication therapy management (MTM) is an evidence-based practice offered by pharmacists to ensure a patient’s medication regimen is individualized to include the safest and most effective medications. MTM has been shown to a) improve quality of patient care, b) reduces health care costs, and c) lead to fewer medication-related adverse effects. However, there has been limited testing of evidence-based, a-priori implementation strategies that support MTM implementation on a large scale.MethodsThe study has two objectives assessed at the organizational and individual level: 1) to determine the adoption, feasibility, acceptability and appropriateness of a multi-faceted implementation strategy to support the MTM pilot program in Tennessee; and 2) to report on the contextual factors associated with program implementation based on the Consolidated Framework for Implementation Research (CFIR). The overall design of the study was a hybrid type 2 effectiveness-implementation study reporting outcomes of Tennessee state Medicaid’s (TennCare) MTM Pilot program. This paper presents early stage implementation outcomes (e.g., adoption, feasibility, acceptability, appropriateness) and explores implementation barriers and facilitators using the CFIR. The study was assessed at the (a) organizational and (b) individual level. A mixed-methods approach was used including surveys, claims data, and semi-structured interviews. Interview data underwent initial, rapid qualitative analysis to provide real time feedback to TennCare leadership on project barriers and facilitators.ResultsThe total reach of the program from July 2018 through June 2020 was 2033 MTM sessions provided by 17 Medicaid credentialed pharmacists. Preliminary findings suggest participants agreed that MTM was acceptable (μ = 16.22, SD = 0.28), appropriate (μ = 15.33, SD = 0.03), and feasible (μ = 14.72, SD = 0.46). Each of the scales had an excellent level of internal (> 0.70) consistency (feasibility, α = 0.91; acceptability, α = 0.96; appropriateness, α = 0.98;). Eight program participants were interviewed and were mapped to the following CFIR constructs: Process, Characteristics of Individuals, Intervention Characteristics, and Inner Setting. Rapid data analysis of the contextual inquiry allowed TennCare to alter initial implementation strategies during project rollout.ConclusionThe early stage implementation of a multi-faceted implementation strategy to support delivery of Tennessee Medicaid’s MTM program was found to be well accepted and appropriate across multiple stakeholders including providers, administrators, and pharmacists. However, as the early stage of implementation progressed, barriers related to relative priority, characteristics of the intervention (e.g., complexity), and workflow impeded adoption. Programmatic changes to the MTM Pilot based on early stage contextual analysis and implementation outcomes had a positive impact on adoption.

Intestinal Microbiota in Common Chronic Inflammatory Disorders Affecting Children.

The incidence and prevalence rate of chronic inflammatory disorders is on the rise in the pediatric population. Recent research indicates the crucial role of interactions between the altered intestinal microbiome and the immune system in the pathogenesis of several chronic inflammatory disorders in children, such as inflammatory bowel disease (IBD) and autoimmune diseases, such as type 1 diabetes mellitus (T1DM) and celiac disease (CeD). Here, we review recent knowledge concerning the pathogenic mechanisms underlying these disorders, and summarize the facts suggesting that the initiation and progression of IBD, T1DM, and CeD can be partially attributed to disturbances in the patterns of composition and abundance of the gut microbiota. The standard available therapies for chronic inflammatory disorders in children largely aim to treat symptoms. Although constant efforts are being made to maximize the quality of life for children in the long-term, sustained improvements are still difficult to achieve. Additional challenges are the changing physiology associated with growth and development of children, a population that is particularly susceptible to medication-related adverse effects. In this review, we explore new promising therapeutic approaches aimed at modulation of either gut microbiota or the activity of the immune system to induce a long-lasting remission of chronic inflammatory disorders. Recent preclinical studies and clinical trials have evaluated new approaches, for instance the adoptive transfer of immune cells, with genetically engineered regulatory T cells expressing antigen-specific chimeric antigen receptors. These approaches have revolutionized cancer treatments and have the potential for the protection of high-risk children from developing autoimmune diseases and effective management of inflammatory disorders. The review also focuses on the findings of studies that indicate that the responses to a variety of immunotherapies can be enhanced by strategic manipulation of gut microbiota, thus emphasizing on the importance of proper interaction between the gut microbiota and immune system for sustained health benefits and improvement of the quality of life of pediatric patients.

P01.12 Brain Necrosis in Patients With Metastatic Lung and Breast Cancer Successfully Treated With Bevacizumab

Patients (pts) develop brain radionecrosis (BRN) as a result of radiation therapy for brain tumors or metastatic brain lesions. This is seen more often now with the use of stereotactic radiosurgery (SRS). BRN is characterized by an increase in permeability and disruption of the blood brain barrier (BBB). The mechanism of BRN is currently unknown, however it is hypothesized that there is an inflammatory reaction of the local tissue to radiation which results in a continuous process involving endothelial cell dysfunction. This leads to tissue hypoxia and increased vascular endothelial growth factor (VEGF) which in turn causes capillary leakage, progressive BBB dysfunction, and cerebral edema. There are currently no standard treatment options for BRN. Bevacizumab (BEV), a humanized monoclonal antibody with action against VEGF, has recently been used in some reports for the treatment of BRN. BEV essentially blocks VEGF from reaching its targets on the endothelium, thus making it an interesting treatment modality for BRN. We identified BRN in 15 pts with brain metastasis treated with SRS at our institution (14 diagnosed with lung cancer and one with breast cancer). We assessed the efficacy and safety of BEV for the treatment of BRN. A demographic review was conducted, analyzing pts’s age, sex, ethnicity, etc. We evaluated the BEV dose, dosing frequency, number of treatments received, medication-related adverse effects (AE), and clinical benefit. Brain imaging, mainly MRI and PET scan, were completed pre-treatment and after four cycles of therapy to evaluate the efficacy of BEV. Pts who exhibited clinical benefit, defined as complete response (CR), partial response (PR), or stable disease (SD), received an additional four cycles of treatment. The median age was 65y (range 49-78y) and 9/14 (64%) pts were female. Clinical benefit was achieved in 13/15 (87%) pts. Pts experienced improvement of cognitive function, headaches, weakness and other symptoms. MRIs showed improvement in edema and a reduction or stabilization of the brain lesions. The most frequent dosing regimen administered was 10 mg/kg of BEV every two weeks and the median number of cycles given was eight cycles (1-12). Treatment with BEV was well tolerated with eight pts (53%) experiencing BEV-related grade two or less AE including hypertension (21%), proteinuria (14%), thrombocytopenia (7%) and mild nose bleeds (7%). There were no Grade 3-5 AE. This study demonstrates that there is a clinical benefit when administering BEV for the treatment of BRN in lung cancer pts with metastatic brain lesions. BEV was well tolerated and had an acceptable safety profile.