Use Of Adjunctive Medications Research Articles

Phenobarbital Dosing for the Treatment of Alcohol Withdrawal Syndrome: A Review of the Literature

Objective: To determine the most appropriate phenobarbital dosing regimen by evaluating the safety and efficacy of the drug when specifically used in alcohol withdrawal syndrome (AWS). Data sources: A comprehensive literary search was conducted using PubMed and bibliographic mining in October 2023. Study selection and data extraction: An established monotherapy phenobarbital regimen needed to be established within the article to be included in analysis. Location of implementation was not a deterrent to evaluation, nor was the route of phenobarbital administration. Data synthesis: Six publications were evaluated in this review, and two main phenobarbital dosing regimens emerged. While fix-based dosing strategies and weight-based dosing strategies resulted, the dosing within the regimens resulted in the same or relatively similar doses employed, respectively. Each of the studies had a statistically significant decrease in their primary outcome being studied, and the use of phenobarbital as monotherapy was proven to improve AWS symptoms, significantly decrease intensive care unit and hospital length of stay, decrease the use of adjunctive medications, decrease the use of a ventilator, and prevent seizures. Conclusions: Despite benzodiazepines having been the clinical first-line therapy for AWS, research shows that the pharmacokinetic stability and clinical benefits of phenobarbital are in support creation of phenobarbital protocols, as monotherapy, in hospitals or institutions for patients with AWS.

Effect of Phenobarbital-Based Alcohol Withdrawal Protocol on Provider Practice and Patient Outcomes—A Quality Improvement Study

Introduction: Alcohol is the most common substance use disorder in the United States. Despite this prevalence, there remains significant heterogeneity in medical management of alcohol withdrawal syndrome (AWS). While the 2020 American Society of Addition Medicine continues to recommend the use of benzodiazepines as first-line therapy for AWS, there is increasing use of phenobarbital in patients at high risk of severe AWS. Despite phenobarbital’s favorable pharmacologic profile, historically, clinical utilization on general medicine services has been low and often restricted. In this project, we have examined practice patterns and associated clinical outcomes in adult patients experiencing AWS on the general medicine service pre and post implementation of a phenobarbital-based protocol for the treatment of severe AWS at our institution. Methods: This quality improvement study evaluated changes in management of AWS on general medicine units associated with implementation of a phenobarbital-based protocol and order set in the electronic medical record (EMR). Our primary outcome measures were receipt of a phenobarbital loading dose, concomitant benzodiazepine administration, and total benzodiazepine dose. Safety outcomes were also explored to assess clinical impacts of this protocol implementation. The project was determined “not research” by our Institutional Review Board. Results: Phenobarbital-protocol implementation was associated with increased frequency of receiving a phenobarbital loading dose (49.5% vs 9.4%; P < .001), decreased use of concomitant benzodiazepine/phenobarbital (4.3% vs 28.9%; P < .001), and decreased total benzodiazepine dose (7.8 vs 15.5 mg; P < .001). Regarding safety, there was no significant pre/post difference in the rate of ICU transfer, but among those transferred there was a trend toward decreased mechanical ventilation rate (100% vs 28.6%; P = .051), and a significantly reduced ICU length of stay (median 11 vs 3 days; P = .04). There were no pre/post differences in seizures, delirium or use of adjunct medications. Conclusions: This quality improvement study demonstrates a marked change in provider prescribing practices for treating AWS after implementation of an institutional phenobarbital-based protocol. We observed no difference in overall clinical outcomes after protocol implementation, although a larger follow-up study is needed to confirm this and to further explore the shorter ICU length of stay for patients with AWS postimplementation.

"Should We Phenobarb-it-All?" A Phenobarbital-Based Protocol for Non-Intensive Care Unit Trauma Patients at High Risk of or Experiencing Alcohol Withdrawal.

Alcohol use is frequent in trauma patients and alcohol withdrawal syndrome (AWS) is associated with significant morbidity. Benzodiazepines are commonly used for AWS, but may cause neurologic and respiratory adverse events (AEs). The objective was to evaluate the effectiveness and safety of a phenobarbital-based protocol for the treatment of AWS in non-intensive care unit (ICU) trauma patients. Adult non-ICU trauma patients at high risk of or experiencing AWS PRE and POST implementation of a phenobarbital-based protocol were included. Outcomes were AWS-related complications (AWS-RC), benzodiazepine use, adjunctive medication use, hospital length of stay (HLOS), and medication-related AEs. Subgroup analyses were performed on patients with traumatic brain injury (TBI), rib fractures, and at high risk of severe AWS. Overall, 110 patients were included (51 PRE, 59 POST). AWS-RC developed in 17 PRE patients compared to 10 POST patients (33% vs 17%; P = .05). PRE patients were more likely to receive benzodiazepines (88% vs 42%, P < .0001) and higher total dose (11 vs 4mg lorazepam equivalent; P = .001). No difference noted in HLOS (8 vs 8 days, P = .27), adjunctive medication use (49% vs 54%, P = .60), or AEs (57% vs 39%, P = .06). There was no difference in AWS-RC in the TBI subgroup (P = .19), less AEs in the rib fracture POST subgroup (P = .04), and less AWS-RC in the high risk of severe AWS POST subgroup (P = .03). A phenobarbital-based protocol in trauma patients is effective in preventing AWS-RC and decreasing benzodiazepine use without increasing AEs.

Managing Opioid Withdrawal Symptoms During the Fentanyl Crisis: A Review.

Illicitly manufactured fentanyl (IMF) is a significant contributor to the increasing rates of overdose-related deaths. Its high potency and lipophilicity can complicate opioid withdrawal syndromes (OWS) and the subsequent management of opioid use disorder (OUD). This scoping review aimed to collate the current OWS management of study populations seeking treatment for OWS and/or OUD directly from an unregulated opioid supply, such as IMF. Therefore, the focus was on therapeutic interventions published between January 2010 and November 2023, overlapping with the period of increasing IMF exposure. A health science librarian conducted a systematic search on November 13, 2023. A total of 426 studies were screened, and 173 studies were reviewed at the full-text level. Forty-nine studies met the inclusion criteria. Buprenorphine and naltrexone were included in most studies with the goal of transitioning to a long-acting injectable version. Various augmenting agents were tested (buspirone, memantine, suvorexant, gabapentin, and pregabalin); however, the liberal use of adjunctive medication and shortened timelines to initiation had the most consistently positive results. Outside of FDA-approved medications for OUD, lofexidine, gabapentin, and suvorexant have limited evidence for augmenting opioid agonist initiation. Trials often have low retention rates, particularly when opioid agonist washout is required. Neurostimulation strategies were promising; however, they were developed and studied early. Precipitated withdrawal is a concern; however, the rates were low and adequately mitigated or managed with low- or high-dose buprenorphine induction. Maintenance treatment continues to be superior to detoxification without continued management. Shorter induction protocols allow patients to initiate evidence-based treatment more quickly, reducing the use of illicit or non-prescribed substances.

Opioid Utilization After Scoliosis Surgery is Greater in Marfan Syndrome Than Adolescent Idiopathic Scoliosis.

Retrospective matched case cohort. Compare postoperative opioid utilization and prescribing behaviors between patients with Marfan syndrome (MFS) and adolescent idiopathic scoliosis (AIS) after posterior spinal fusion (PSF). Opioids are an essential component of pain management after PSF. However, due to the potential for opioid use disorder and dependence, current analgesic strategies aim to minimize their use, especially in younger patients. Limited information exists on opioid utilization after PSF for syndromic scoliosis. Twenty adolescents undergoing PSF with MFS were matched with patients with AIS (ratio, 1:2) by age, sex, degree of spinal deformity, and the number of vertebral levels fused. Inpatient and outpatient pharmaceutical data were reviewed for the quantity and duration of opioid and adjunct medications. Prescriptions were converted to morphine milligram equivalents (MMEs) using CDC's standard conversion factor. Compared with patients with AIS, patients with MFS had significantly greater total inpatient MME use (4.9 vs . 2.1 mg/kg, P ≤ 0.001) and longer duration of intravenous patient-controlled anesthesia (3.4 vs . 2.5 d, P = 0.001). Within the first 2 postop days, MFS patients had more patient-controlled anesthesia boluses (91 vs . 52 boluses, P = 0.01) despite similar pain scores and greater use of adjunct medications. After accounting for prior opioid use, MFS was the only significant predictor of requesting an opioid prescription after discharge (odds ratio: 4.1, 95% CI: 1.1-14.9, P = 0.03). Patients with MFS were also more likely to be discharged with a more potent prescription (1.0 vs . 0.72 MME per day/kg, P ≤ 0.001) and to receive a longer-duration prescription (13 vs . 8 d, P = 0.005) with a greater MME/kg (11.6 vs . 5.6 mg/kg, P ≤ 0.001) as outpatients. Despite a similar intervention, patients with MFS and AIS seem to differ in their postoperative opioid usage after PSF, presenting an opportunity for further research to assist clinicians in better anticipating the analgesic needs of individual patients, particularly in light of the ongoing opioid epidemic.

Real-world treatment patterns and use of adjunctive pain and anti-inflammatory medications among patients with psoriatic arthritis treated with IL-17A inhibitors in the United States.

BACKGROUND: Much of the current research on treatment patterns and use of adjunctive pain and anti-inflammatory medications among patients living with psoriatic arthritis (PsA) predates the approval and uptake of IL (interleukin)-17A inhibitors. OBJECTIVE: To compare real-world treatment patterns and use of adjunctive pain and antiinflammatory medications between patients with PsA initiating the IL-17A inhibitors, ixekizumab and secukinumab, in a US-managed care population. METHODS: We conducted a retrospective cohort study using the HealthCore Integrated Research Database. Patients with a PsA diagnosis who initiated ixekizumab or secukinumab treatment between December 1, 2017, and November 30, 2019, were identified. Two cohorts were created based on which of the 2 medications was initiated (index date), and patients with prior use of either drug were excluded, as were patients with ankylosing spondylitis. Patients had to be continuously enrolled in the health plan for 6 months prior to (baseline) and 12 months after the index date (post-index). Inverse probability of treatment weighting was used to minimize confounding from baseline demographic and clinical differences between cohorts. Treatment patterns (dosing, persistence, discontinuation, and switching) and use of adjunctive pain/anti-inflammatory medications were assessed and compared between weighted cohorts using chi-square and t-tests. RESULTS: In total, 407 patients were identified in the ixekizumab cohort (mean age 51.6 years; 54% female) and 1,508 patients were identified in the secukinumab cohort (mean age 50.1 years; 59% female). Prior to weighting, presence of a psoriasis diagnosis code (ixekizumab: 60% vs secukinumab: 45%; standardized difference [std diff] = -0.30), specialty of the index prescriber (std diff = 0.38), and mean number of prior advanced therapies (2.0 vs 1.5; std diff = -0.33) were different between cohorts. Cohorts were well balanced after weighting. The majority of secukinumab patients (71%) received an index dose of 300 mg. Rates of persistence (ixekizumab: 40% vs secukinumab: 43%; P = 0.411) and switching (25% vs 20%; P = 0.072) were not statistically different between cohorts. Use of new adjunctive pain and anti-inflammatory medications was not statistically different between cohorts either (ixekizumab: 63% vs secukinumab: 58%; P = 0.187). CONCLUSIONS: Real-world treatment patterns and use of adjunctive pain and anti-inflammatory medications were similar in patients with PsA initiating ixekizumab and secukinumab in this US-managed care population. Further research examining reasons for discontinuation, switching, and use of adjunctive medications may help inform treatment decisions for patients living with PsA. DISCLOSURES: Ms Pizzicato, Ms Ketkar, and Dr Grabner are employees of HealthCore, Inc, which received funding from Eli Lilly and Company for the conduct of the study on which this manuscript is based. Ms Pepe was an employee of HealthCore, Inc., during the time the study was conducted. Dr Grabner is a shareholder of Elevance Health (legacy Anthem, Inc.). Dr Vadhariya, Dr Birt, and Ms Bolce are employees of Eli Lilly and Company, the manufacturer of ixekizumab (Taltz). Dr Birt and Ms Bolce are shareholders of Eli Lilly and Company. Dr Walsh is a paid consultant to Eli Lilly and Company and Novartis, the manufacturers of ixekizumab (Taltz) and secukinumab (Cosentyx), respectively. Additionally, Dr Walsh is a paid consultant for Pfizer, Janssen, AbbVie, and UCB and has contracts with Pfizer, AbbVie, and Merck.

1105: PHENOBARBITAL VERSUS LORAZEPAM FOR THE MANAGEMENT OF ALCOHOL WITHDRAWAL IN HOSPITALIZED PATIENTS

Introduction: Alcohol withdrawal syndrome (AWS) is a potentially life-threatening medical condition and even though benzodiazepines (BZDs) are the standard of care in the treatment of AWS, therapy-associated complications like respiratory depression requiring ventilatory support and the use of adjunctive pharmacotherapy persist. Studies have shown promising results with phenobarbital (PB), but have been limited to use in the emergency department or as an agent of choice for refractory AWS in the intensive care unit (ICU). Our study aims to compare the ICU admissions rate between lorazepam versus PB in treating AWS in hospitalized patients. Methods: We conducted a retrospective cohort study on patients hospitalized for AWS from 2019 to 2022. Patients were categorized into those who received lorazepam using the revised Clinical Institute Withdrawal Assessment of alcohol scale (CIWA-Ar) and those who received PB based on the Richmond Agitation- Sedation scale (RASS). The primary outcome was the rate of admission to the ICU. Secondary outcomes included total length of hospital and ICU stay, mechanical ventilation rate, use of adjunctive medications and mortality. Results: 300 patients met the inclusion criteria, of whom 148 received lorazepam and 152 received PB. The mean patient age was 56 years and 51 years in the PB and lorazepam groups, respectively (p=0.001). There were significant differences between lorazepam and PB in terms of ICU admission (13.5% vs 5.3%, p=0.014), mechanical ventilation rate (9.5% vs 0.7%, p=0.0004), need for adjunctive dexmedetomidine (9.5% vs 1.3%, p=0.0016) and mean length of hospital days (6.16 vs 4.89 days, p value =0.004), and ICU days (1.07 vs 0.21 days, respectively, p value=0.003). Conclusions: AWS patients treated with PB per protocol were found to have a significantly decreased rate of ICU admission, need for invasive ventilation and adjunctive dexmedetomidine treatment, along with reduced ICU and total length of hospital stay as compared to those treated with lorazepam. We conclude that our results support the growing evidence of efficacy of PB over lorazepam as the primary treatment for AWS patients, due to its mechanism of action that better targets AWS pathophysiology. Prospective, randomized controlled studies that compare PB vs BDZs for AWS are needed.

Effect of Enteral Guanfacine on Dexmedetomidine Use in the ICU.

Retrospective descriptive analysis. Six hundred thirteen-bed academic medical center from October 2020 to October 2021. All Adult patients on IV dexmedetomidine who received at least one dose of guanfacine for sedation or agitation were included. Enteral guanfacine. The primary outcome was discontinuation of dexmedetomidine therapy within 48 hours after guanfacine initiation. Secondary outcomes assessed included adjunctive medication use, rate of dexmedetomidine reinitiation, and safety outcomes. One hundred five patients were included in the analysis. Median age was 59 years old, 66% were male, and median daily dose of guanfacine was 1.5 mg. Dexmedetomidine was discontinued within 48 hours in 58% of patients (n = 61) and within 72 hours in 71% of patients (n = 75). Fifty-five percent of patients (n = 58) required rescue medications for poorly controlled agitation, sedation, or pain while on guanfacine. Dexmedetomidine withdrawal occurred in 2% of patients (n = 2) while on guanfacine. Adverse effects attributed to guanfacine occurred in 8% of patients (n = 8), all experiencing hypotension leading to medication discontinuation. Dexmedetomidine was successfully weaned within 48 hours of guanfacine initiation in 58% of patients with minimal withdrawal or adverse effects. Guanfacine may be an effective and safe enteral option for dexmedetomidine weaning in critically ill patients.

Periosteal block versus intravenous regional anesthesia for reduction of distal radius fractures: A randomized controlled trial.

We compare periosteal block and intravenous regional anesthesia (IVRA) as anesthetic techniques for reduction of distal radius fractures when performed by emergency department (ED) clinicians following brief training. This was a single-center, nonblinded randomized controlled trial of a convenience sample of patients presenting with distal radius fractures requiring closed reduction. Primary outcome measure was patient reported fracture reduction pain score, rated on a 100-mm visual analog scale. Secondary outcomes included adjunct pain medication use, ED length of stay, remanipulation rates, participant satisfaction, clinician assessed efficacy, and clinician-assessed ease of the procedure. Eighty-one patients were randomized to receive IVRA (n= 41) or periosteal block (N= 40). Reduction pain scores were not normally distributed. Median (25th-75th percentile) pain scores in participants assigned to IVRA and periosteal block were 5 (1-27.5) and 26 (8.5-63)mm, respectively, (p= 0.007). Use of adjunct medications during reduction was higher for the periosteal block group compared with IVRA (57.5% vs. 22.5%, p= 0.003). Remanipulation rates were 17.5% for periosteal block versus 7.5% for IVRA (p= 0.31). There was no difference in length of stay, patient satisfaction, or clinician's assessed ease of the anesthetic technique. There was a difference in clinician's assessment of efficacy between groups, with IVRA described as "extremely effective" by 65% and periosteal block described as "extremely effective" by 25% (p= 0.003). When performed by a diverse group of ED clinicians periosteal block provided inferior analgesia to IVRA but may provide an alternative when IVRA cannot be performed.

Prescription Patterns of Adjuvant Pain Medications Following an Opioid Supply Restriction Law: An Interrupted Time Series Analysis.

Florida House Bill 21 (HB21) was implemented in July 2018 to limit prescriptions of Schedule II opioids for acute pain patients, but it is unclear whether such restrictions have a collateral influence on the utilization of commonly prescribed adjuvant pain medications. The objective of this study was to assess whether this law was associated with a change in use patterns of gabapentinoids, benzodiazepines, and muscle relaxants. We obtained prescription claims for medications dispensed from January 1, 2015, to June 31, 2019, from a health plan serving a large Florida employer. Interrupted time series analyses were conducted to compare pre-HB21 and post-HB21 implementation changes in the mean monthly number of users and prescriptions for gabapentinoids, benzodiazepines, and muscle relaxants. There was a 6% immediate increase (relative risk: 1.06; 95% confidence interval: 1.02, 1.11) in the monthly proportion of gabapentinoid users, and an 11% immediate increase in the monthly proportion of gabapentinoids prescriptions (relative risk: 1.11; 95% confidence interval: 1.04, 1.18) per 1000 patients following law implementation. However, after the law, we observed a significant reduction in trend for the monthly proportion of muscle relaxants and benzodiazepine users. An increased number of patients and prescriptions were observed for gabapentinoids, while fewer patients received benzodiazepines and muscle relaxants after HB21. In previous studies, opioid prescription restriction laws are shown to reduce opioids, but this work suggests that these laws may also have unintended consequences for the use of adjunctive medications that were not intended to be affected.

Outcomes After Implementation of a Benzodiazepine-Sparing Alcohol Withdrawal Order Set in an Integrated Health Care System

Alcohol withdrawal syndrome (AWS) is a common inpatient diagnosis managed primarily with benzodiazepines. Concerns about the adverse effects associated with benzodiazepines have spurred interest in using benzodiazepine-sparing treatments. To evaluate changes in outcomes after implementation of a benzodiazepine-sparing AWS inpatient order set that included adjunctive therapies (eg, gabapentin, valproic acid, clonidine, and dexmedetomidine). This difference-in-differences quality improvement study was conducted among 22 899 AWS adult hospitalizations from October 1, 2014, to September 30, 2019, in the Kaiser Permanente Northern California integrated health care delivery system. Data were analyzed from September 2020 through November 2021. Implementation of the benzodiazepine-sparing AWS order set on October 1, 2018. Adjusted rate ratios for medication use, inpatient mortality, length of stay, intensive care unit admission, and nonelective readmission within 30 days were calculated comparing postimplementation and preimplementation periods among hospitals with and without order set use. Among 904 540 hospitalizations in the integrated health care delivery system during the study period, AWS was present in 22 899 hospitalizations (2.5%), occurring among 16 323 unique patients (mean [SD] age, 57.1 [14.8] years; 15 764 [68.8%] men). Of these hospitalizations, 12 889 (56.3%) used an order set for alcohol withdrawal. Among hospitalizations with order set use, any benzodiazepine use decreased after implementation from 6431 hospitalizations (78.1%) to 2823 hospitalizations (60.7%) (P < .001), with concomitant decreases in the mean (SD) total dosage of lorazepam before vs after implementation (19.7 [38.3] mg vs 6.0 [9.1] mg; P < .001). There were also significant changes from before to after implementation in the use of adjunctive medications, including gabapentin (2413 hospitalizations [29.3%] vs 2814 hospitalizations [60.5%]; P < .001), clonidine (1476 hospitalizations [17.9%] vs 2208 hospitalizations [47.5%]; P < .001), thiamine (6298 hospitalizations [76.5%] vs 4047 hospitalizations [87.0%]; P < .001), valproic acid (109 hospitalizations [1.3%] vs 256 hospitalizations [5.5%]; P < .001), and phenobarbital (412 hospitalizations [5.0%] vs 292 hospitalizations [6.3%]; P = .003). Compared with AWS hospitalizations without order set use, use of the benzodiazepine-sparing order set was associated with decreases in intensive care unit use (adjusted rate ratio [ARR], 0.71; 95% CI, 0.56-0.89; P = .003) and hospital length of stay (ARR, 0.71; 95% CI, 0.58-0.86; P < .001). This study found that implementation of a benzodiazepine-sparing AWS order set was associated with decreased use of benzodiazepines and favorable trends in outcomes. These findings suggest that further prospective research is needed to identify the most effective treatments regimens for patients hospitalized with alcohol withdrawal.

Prevention and Management of Common Adverse Effects of Ketamine and Esketaminein Patients with Mood Disorders.

The emerging roles of ketamine and esketamine as effective rapid-acting antidepressants hold promise for patients suffering from treatment-resistant depression and/or major depressive disorder with suicidality. Practitioner familiarity with common tolerability/safety concerns along with pragmatic prevention and management strategies are needed to reduce patient burden and improve the acceptability and accessibility of these treatments. The most common treatment-emergent adverse events associated with ketamine/esketamine are dissociation, anxiety, nausea, increased blood pressure, and headache. The majority of side effects are mild, transient, dose dependent, and attenuate with subsequent treatments. Patient selection, baseline physical and psychiatric assessments, and an appropriate setting are critical first steps in the prevention and mitigation of adverse events. Patient education and supportive interventions play central roles in the prevention and management of select adverse events. Severe and/or clinically significant adverse effects may necessitate the judicious use of adjunctive medications. Moreover, practitioners must remain vigilant to the potential for abuse liability and long-term adverse events, for which there are insufficient data. This article succinctly reviews common treatment-emergent adverse events of ketamine and esketamine within the context of mood disorders, and provides practical suggestions for prevention and management at point-of-care.

Non-infectious uveitis affecting the posterior segment treated with fluocinolone acetonide intravitreal implant: 3-year fellow eye analysis

BackgroundPrevention of non-infectious uveitis of the posterior segment (NIU-PS) recurrence using 0.2 μg/day fluocinolone acetonide implant (FAi) was assessed over 3 years (NCT01694186). Outcomes for FAi-treated and fellow eyes with NIU-PS were compared, to evaluate FAi versus conventional treatment strategies.MethodsEligible subjects had >1-year recurrent NIU-PS history and either ≥2 separate recurrences requiring treatment, or corticosteroid therapy (systemic or ocular) in the 12 months preceding study entry. Bilateral disease was present and analysed in 59/87 FAi-treated participants. Recurrence rates, best-corrected visual acuity (BCVA) changes, cataract surgery, intraocular pressure (IOP) events and adjunctive medication use were compared for FAi-treated and fellow eyes.ResultsOver 36 months, more FAi-treated than fellow eyes remained recurrence-free (28.8% vs. 5.1%, P = 0.001; mean 1.9 vs. 4.7 recurrences, respectively, P < 0.0001). FAi-treated eyes gained +9.6 letters BCVA, versus a loss of −4.4 in fellow eyes (P < 0.0001). Systemic medications were given to 42.4% of subjects. Intra/periocular adjunctive injections were lower in FAi-treated than fellow eyes (20.3% vs. 66.1%, P < 0.0001); topical corticosteroid use was also lower in FAi-treated than fellow eyes (27.1% vs 52.5%, P = 0.0041). IOP-related events occurred at similar rates in both FAi-treated and fellow eyes, excepting IOP-lowering surgery (5.1% vs. 15.3%, respectively; P = 0.1251). Cataract surgery occurred in 72.0% of FAi-treated and 37.0% of fellow eyes.ConclusionsIn subjects with bilateral NIU-PS, continuous, low-dose corticosteroid with 0.2 μg/day FAi reduced recurrence and adjunctive medication requirements, and improved vision over 36 months, providing greater protection against ocular inflammation than a reactive approach using standard of care.

Control of Hemodynamic Responses and Perioperative Outcomes in Transsphenoidal Pituitary Surgery: A Qualitative Systematic Review of the Available Evidence.

Transnasal transsphenoidal (TNTS) pituitary surgery is associated with short-lived but intense nociceptive stimuli which cause substantial hemodynamic perturbations that may increase blood loss and impair visualization of the surgical field. This systematic review aimed to critically appraise the clinical evidence for the efficacy and safety of various anesthetic techniques, other pharmacological modalities, and supplementary interventions by assessing intraoperative systemic hemodynamics, use of adjunct medications, quality of the surgical field, intraoperative blood loss, and recovery profiles in patients undergoing TNTS pituitary surgery. Relevant randomized clinical trials and observational studies were identified in a systematic literature search; 16 studies (13 randomized clinical trials, 3 observational studies) enrolling a total of 907 patients were identified for inclusion in this review. Propofol provided more potent hemodynamic control compared with volatile anesthetics with a sparing effect on the need for additional drugs to blunt hemodynamic responses. Recovery profiles between propofol and sevoflurane were either equivalent or favored sevoflurane, but both agents were superior to isoflurane. Regarding intraoperative analgesia, remifentanil was associated with superior hemodynamic control and recovery profiles than fentanyl. Dexmedetomidine had beneficial effects on hemodynamics, surgical field quality, recovery characteristics, and nociceptive properties compared with placebo. Although there was no clear-cut superiority of other adjunct pharmacological modalities on hemodynamic responses during surgery, regional blocks were associated with beneficial impacts on both primary and secondary outcomes. In summary, short-acting anesthetics, analgesics and dexmedetomidine seem to improve intraoperative hemodynamics, blood loss, and recovery qualities during TNTS pituitary surgery. However, definitive conclusions cannot be drawn because of methodological heterogeneity in the identified studies.

Patterns of opioid prescription post ureteroscopy among members of the Endourological Society.

BackgroundPostoperative opioid prescribing has been linked with persistent opioid use. Ureteroscopy (URS) is a common urologic procedure and a potential area to focus on opioid reduction. We aim to characterize international practice patterns of opioid prescribing post URS and what measures may decrease the need for opioid prescription.MethodsWe developed a survey directed to members of the Endourological Society. The survey queried the frequency of opioid prescribing post URS, challenges when opioids are not prescribed, and measures thought to reduce the need for opioids.ResultsWe received 159 responses with the majority reported practicing urology for >20 years (37.1%), and performing 10–20 ureteroscopies/month (45.3%). Forty-one percent were from the United States (US) and Canada. Sixty-six percent completed a fellowship, 84% in endourology. Twenty-six percent prescribe opioids more than half the time and the majority do so less than 10% of the time (61.6%). Thirty-eight percent had no challenges when opioids were omitted. Measures felt to decrease the need for opioids were preoperative counseling, nonsteroidal anti-inflammatory drugs use, and use of adjunct medications. After adjusting for location and type of practice, endourology fellowship completion, years of practice, and number of ureteroscopies/month, we found that respondents from the US and Canada were more likely to prescribe opioids more than half the time post URS compared to respondents from the rest of the world [odds ratio (OR): 87.5, P<0.001, 95% confidence interval (CI): 17.3–443.5].ConclusionsDespite proven feasibility of non-opioid pathway, nearly one-quarter of participants in our survey prescribe opioids >50% of the time post URS. Most important factors felt to reduce opioid prescription post URS were preoperative counseling, nonsteroidal anti-inflammatory drugs use. US and Canadian urologists were more likely to prescribe opioids >50% of the time post URS compared to the rest of the world. We believe best practice guidelines should be considered by the American and Canadian Urological Associations to address post URS opioid prescribing.

Do Newer Antidepressant Drugs Really Have Reduced Side Effects? Examining a Random “Real World” Sample of 300+ Receivers of Medications

Newer antidepressant drugs are frequently cited as having reduced side effect profiles to that of their older counterparts. However, recent studies have begun to dispute this claim, citing selective sampling, short clinical trials, and clinical trial environments as influencing reported outcomes. At present, little research on antidepressant side effects draws on RWD (Real-World Data). Despite this, interest in examining RWD samples for antidepressant drug side effects is increasing as of 2020. The reported study asked a random sample of 300+ individuals taking a variety of different antidepressant medications to complete online drug side effect self-report scales with previously high validity. Newer antidepressants belonging to the atypical antidepressant drug class were reported as having only slightly reduced side effects of weight gain compared with older SSRI-class medications. No reduced side effects of increased depression, anxiety, sexual dysfunction (SD), sleepiness, or suicidal ideation (SI) were found for the newer atypical-class medications vs older SSRI-class agents. Medication adherence did not differ significantly between SSRI and atypical classes. No evidence for reduced side effects was found for newer SSRI and atypical antidepressants vs older same-class drugs when comparing six new and old medications drawn from atypical and SSRI classes. However, atypical antidepressants were associated with increased use of adjunct medications to bolster primary treatment.

Opioid Analgesia for Medical Abortion: A Randomized Controlled Trial.

To estimate the effect of oral opioids on patient pain during first-trimester medical abortion. We conducted a randomized, double-blind, placebo-controlled trial where patients up to 10 0/7 weeks of gestation undergoing a medical abortion with mifepristone and misoprostol took 10 mg oral oxycodone or placebo at onset of painful cramping. Additionally, all patients received 800-mg ibuprofen tablets, 4-mg ondansetron oral dissolving tablets, and a written prescription for adjunctive pain medication (six tablets oxycodone 5 mg). Participants used a text-messaging service to report pain scores on a numerical rating scale from 0 to 10 (0 being no pain, 10 being worst pain) for 24 hours at start of misoprostol dosing. The primary outcome was maximum pain experienced within 24 hours postmisoprostol. Our secondary outcomes were maximum pain stratified by gestational age (less than 7 weeks of gestation, 7-10 weeks of gestation), duration of maximum pain, use of adjunctive medication, presence of nausea or vomiting, and satisfaction. We needed at least 76 participants per group to differentiate a clinically important pain difference of 2 points on the numerical rating scale. From May 2017 to May 2018, we randomized 172 participants (placebo group with 86, oxycodone group with 86). The study groups had comparable baseline characteristics. We found no difference between groups in median maximum pain scores (placebo 8 [range 1-10], oxycodone 8 [range 2-10], P=.92) and the median duration of maximum pain (placebo 0.75 hours range 0.01-15 vs oxycodone 1 hour range 0.02-10, P=.39). Groups were also similar in the proportion obtaining (placebo 62%, oxycodone 49%, P=.09) and using (placebo 48%, oxycodone 40%, P=.28) adjunctive medication, experiencing nausea or vomiting (placebo 59%, oxycodone 65%, P=.43) and reported satisfaction with pain medications (placebo 62%, oxycodone 65%, P=.63). Oxycodone does not reduce the maximum level of pain experienced by women undergoing medical abortion up to 10 0/7 weeks of gestation or improve satisfaction. ClinicalTrials.gov, NCT03139240.

Update on childhood/adolescent obesity and its sequela.

We aim to describe current concepts on childhood and adolescent obesity with a strong focus on its sequela. Childhood obesity is a national epidemic with increasing prevalence over the past three decades placing children at increased risk for many serious comorbidities, previously felt to be only adult-specific diseases, making this topic both timely and relevant for general pediatricians as well as for subspecialists. Childhood obesity develops through an interplay of genetics, environment, and behavior. Treatment includes lifestyle modification, and now metabolic and bariatric surgery is more commonly considered in carefully selected adolescents. The off-label use of adjunct medications for weight loss in childhood and adolescent obesity is still in its infancy, but will likely become the next logical step in those with lifestyle modification refractory obesity. Obesity can lead to several comorbidities, which can persist into adulthood potentially shortening the child's lifespan. Efforts should be focused primarily on reducing childhood and adolescent obesity, and when indicated treating its sequela in effort to reduce future morbidity and mortality in this precious population. VIDEO ABSTRACT: http://links.lww.com/MOP/A36.

Utilization of COMT inhibitors, dopamine agonists, and MAO-B inhibitors with levodopa-carbidopa instestinal gel in advanced Parkinson's disease patients: Summary of phase 3 and real-world studies

Levodopa remains the most effective treatment for Parkinson's disease (PD); however, as disease evolves, uncontrolled motor and non-motor symptoms with chronic oral therapy may necessitate the use of advanced therapies. Continuous levodopa delivery with levodopa-carbidopa intestinal gel (LCIG) improves motor fluctuations and may reduce the need for concomitant dopamine replacement therapies (DRT). This analysis summarizes add-on medication use in advanced PD patients before and after LCIG treatment from a phase 3 study and real-world observations. Add-on PD medication use including catechol-O-methyl transferase (COMT) inhibitors, dopamine agonists (DAs), and monoamine oxidase (MAO)-B inhibitors was determined at baseline (recent use before LCIG) and after approximately 1 year of LCIG treatment from a phase 3 study (NCT00335153), UK-based retrospective chart review (IRAS ID: 135453), and GLORIA observational registry. The phase 3 trial required LCIG monotherapy (no concomitant PD medications) from LCIG initiation to treatment week 4, after which adjunctive medication use was permitted. In the phase 3 study, patients using COMT inhibitors decreased from 28% to 1%, representing a 96% reduction. Under real-world conditions, patients using COMT inhibitors decreased from 23% to 2% in the retrospective chart review and from 57% to 9% in the GLORIA registry, representing 91% and 84% reductions, respectively. Decreased DA and MAO-B inhibitor use after LCIG therapy were observed in all three studies (Fig. 1). This summary of 840 advanced PD patients treated in a controlled clinical trial setting or during routine clinical care highlights reductions in add-on DRT use following 12 months of LCIG treatment.

Effect of Mobile Device-Assisted N-of-1 Trial Participation on Analgesic Prescribing for Chronic Pain: Randomized Controlled Trial

Opioids and non-steroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed for chronic musculoskeletal pain, despite limited evidence of effectiveness and well-documented adverse effects. We assessed the effects of participating in a structured, personalized self-experiment ("N-of-1 trial") on analgesic prescribing in patients with chronic musculoskeletal pain. We randomized 215 patients with chronic pain to participate in an N-of-1 trial facilitated by a mobile health app or to receive usual care. Medical records of participating patients were reviewed at enrollment and 6months later to assess analgesic prescribing. We established thresholds of ≥ 50, ≥ 20, and > 0 morphine milligram equivalents (MMEs) per day to capture patients taking relatively high doses only, patients taking low-moderate as well as relatively high doses, and patients taking any dose of opioids, respectively. There was no significant difference between the N-of-1 and control groups in the percentage of patients prescribed any opioids (relative odds ratio (ROR) = 1.05; 95% confidence interval [CI] = 0.61 to 1.80, p = 0.87). There was a clinically substantial but statistically not significant reduction of the percentage of patients receiving ≥ 20 MME (ROR = 0.58; 95% CI = 0.33 to 1.04, p = 0.07) and also in the percentage receiving ≥ 50 MME (ROR = 0.50; 95% CI = 0.19 to 1.34, p = 0.17). There was a significant reduction in the proportion of patients in the N-of-1 group prescribed NSAIDs compared with control (relative odds ratio = 0.53; 95% CI = 0.29 to 0.96, p = 0.04), with no concomitant increase in average pain intensity. There was no significant change in use of adjunctive medications (acetaminophen, gabapentenoids, or topicals). These exploratory results suggest that participation in N-of-1 trials may reduce long-term use of NSAIDs; there is also a weak signal for an effect on use of opioids. Additional research is needed to confirm these results and elucidate possible mechanisms. ClinicalTrials.gov Identifier: NCT02116621.