Retrospective Observational Study of Daytime Add-On Administration of Zopiclone to Difficult-to-Treat Psychiatric Inpatients With Unpredictable Aggressive Behavior, With or Without EEG Dysrhythmia

Managing violent behavior is a particularly challenging aspect of hospital psychiatric care. Available pharmacological interventions are often unsatisfactory.Aim: To assess the effectiveness and safety of daytime zopiclone add-on administration in violent and difficult-to-treat psychiatric inpatients.Methods: Chart review of inpatients treated with daytime zopiclone, between 2014 and 2018, with up to 12 weeks follow-up. Effectiveness was retrospectively assessed with the Clinical Global Impression rating scale (CGI) and the frequency and severity of aggressive incidents recorded with the Staff Observation Aggression Scale-Revised (SOAS-R).Results: Forty-five (30 male, 15 female) cases, 18–69 years age range, average (SD) baseline CGI-S score of 5.4 (1.0), and a variety of diagnoses. Sixty-nine percent showed CGI-S improvement of any degree. For patients with at least one aggressive incident within 7 days prior to initiation of zopiclone (N = 22), average (SD) SOAS-R-Severity LOCF to baseline change was −3.5 (2.7) P < 0.0001. Most patients reported no side effects; 24% reported one or more side effects, and 11% discontinued zopiclone due to sedation (4), insomnia (1) or slurred speech (1). No SAEs were recorded. Zopiclone maximum daily dose correlated with CGI-S baseline-to-LOCF change (rho = −0.5, P = 0.0003). The ROC AUC of zopiclone maximum daily dose and improvement on CGI-S was 0.84 (95% CI 0.70–0.93, P < 0.0001). The ROC AUC of zopiclone maximum daily dose and SOAS-R-N improvement was 0.80 (95% CI 0.58–0.92; P = 0.0008) and maximum Youden's index value was achieved at a dose of >30 mg.Conclusions: Zopiclone doses >30 mg daily achieved the best anti-aggressive effect.

Trends in actual medication use for child-onset systemic lupus erythematosus using the Japanese health insurance database 2009–18

ABSTRACT Objectives Immunosuppressive therapy is the mainstay of treatment for child-onset systemic lupus erythematosus (cSLE). Since epidemiological data on Japanese cSLE patients are not available, we evaluated the trends in how treatment choices have changed over time in Japan. Methods Using the Japanese health insurance database provided by Medical Data Vision Co., Ltd, we identified cSLE patients and evaluated changes in the use of corticosteroids and immunosuppressive medications and maximum daily doses of prednisolone from 2009 to 2018. Results Of 182 cSLE patients, 86% were female, and the median age was 14 years. Oral prednisolone was used in more than 97% of cSLE patients during the study period, and the median of the maximum daily dose in each patient decreased over time. Intravenous cyclophosphamide was used less frequently after 2016, while mycophenolate mofetil and hydroxychloroquine were used frequently after 2016. The use of mizoribine reduced after 2014, whereas the other immunosuppressive medications showed no significant change over time; the use of biological agents was very limited. Conclusions Oral prednisolone was the mainstay of treatment for cSLE, and the maximum daily dose has reduced over the past decade. The most frequently prescribed immunosuppressive therapy has shifted to mycophenolate mofetil over time.

Heterogenous use of misoprostol for induction of labour: results of an online survey among midwives in German-speaking countries

Purpose This online survey looked at the experiences and general perceptions of midwives concerning induction of labour and the specific use of misoprostol. Methods We published an online questionnaire with 24 questions in German on midwives’ experiences and perceptions of different methods of induction of labour. Results The online survey was answered by 412 midwives between February 2016 and February 2017. At least 20% of the 24 questions were answered in 333 questionnaires, which were included in this analysis. Oral misoprostol was the most common induction method for primipara and for women with a previous vaginal birth and an unfavourable cervix. Apart from alternative methods for induction of labour like castor oil and complementary/alternative methods, oral misoprostol was the preferred method of induction of labour by midwives. Midwives described a wide range of dosage schedules concerning application intervals, starting doses, and the maximum daily dose of misoprostol. Approximately 50% of the participants of this study described prescriptions of more than 200 µg misoprostol daily for induction of labour. Conclusion Misoprostol is widely used in Germany and was one of the three preferred methods of induction of labour among midwives in our study next to castor oil and complementary/alternative methods. The preparation and dosage of misoprostol vary significantly among hospitals and do not adhere to international guidelines. Midwives voiced their concerns about inconsistent indications and heterogenous use of different methods and dosages of induction. They wished for more patience with late-term pregnancies and individualized shared decision-making between pregnant women and obstetricians.

P650 A trend to higher adoption of mesalazine suppository use for UC patients in 15 European countries

Background In a previous abstract (ECCO 2014), we showed geographical differences between European countries in the use of 5ASA suppositories. The updated ECCO guidelines published in 2016 reiterated the importance of mesalazine suppositories in patients with ulcerative colitis: A mesalamine 1-g suppository once daily is the preferred initial treatment for mild or moderately active proctitis, mesalamine foam or enemas are an alternative, but suppositories deliver the drug more effectively to the rectum and are better tolerated [Statement 11A]. We wanted to look at the changes in mesalazine suppositories use and compare it to 2012. Methods We collected the data of suppositories consumption from April 2019 until March 2020 from IMS, the prevalence of UC in 2019 from the Global Health Data Exchange and the estimation of the population for 15 European countries (Czech Republic, Denmark, Estonia, Finland, France, Greece, Germany, Ireland, Latvia, Lithuania, Norway, Portugal, Spain, Sweden and the United Kingdom) from the Eurostat database. For comparison purposes, we assumed that all the patients could receive a 1000 mg daily dose of mesalazine suppository. Results The aggregate sales data from IMS show that 26979 kg of mesalazine suppository were consumed during the full year in 15 European countries. If we exclude Spain from the analysis, 23096 kg were consumed by 14 countries and this is a 1.6-fold increase in comparison to 2012. Assuming a cut-off of 33% of UC patients receiving the maximum daily dose of 1000 mg, 4 countries showed high use of mesalazine suppositories above that cut off: Greece, Ireland, Spain and Portugal. Except for Ireland, those 3 other countries are from Southern Europe. In addition when we compare the data from 2019 to 2012, we see a clear increase in the use of mesalazine suppository in the 14 countries. All countries showed an increase in suppository use that is above 50% except for Czech Republic, Denmark, France and Sweden. The increase in those countries was less pronounced. Sweden and Norway had the lowest rate of suppository use compared to the other countries. Conclusion Despite all the uncertainty around the UC prevalence and parallel import (due to price difference between the different European countries), there is a clear trend toward a higher use of suppositories in all the European countries. A full analysis of the topical use of mesalazine (suppository, foam and enema) would be interesting to evaluate more accurately the adherence to the ECCO guidelines in clinical practice.

Effects of Polymyxin B Hemoperfusion on Septic Shock Patients Requiring Noradrenaline: Analysis of a Nationwide Administrative Database in Japan

<b><i>Introduction:</i></b> Polymyxin B hemoperfusion (PMX) reduces endotoxin in septic shock patients’ blood and can improve hemodynamics and organ functions. However, its effects on the reduction of septic shock mortality are controversial. <b><i>Methods:</i></b> Using the Japanese diagnosis procedure combination database from April 2016 to March 2019, we identified adult septic shock patients treated with noradrenaline. This study used propensity score matching to compare the outcome between PMX-treated and non-treated patients. The primary endpoint was 28-day mortality, counting from the day of noradrenaline initiation. The secondary endpoints were noradrenaline-, ventilator-, and continuous hemodiafiltration (CHDF)-free days at day 28. <b><i>Results:</i></b> Of 30,731 eligible patients, 4,766 received PMX. Propensity score matching produced a matched cohort of 4,141 pairs with well-balanced patient backgrounds. The 28-day survival rate was 77.9% in the PMX group and 71.1% in the control group (<i>p</i> &#x3c; 0.0001). Median days of noradrenalin-, CHDF-, and ventilator-free days were 2 days (<i>p</i> &#x3c; 0.0001), 2 days (<i>p</i> &#x3c; 0.0001), and 6 days (<i>p</i> &#x3c; 0.0001) longer in the PMX group than in the control group, respectively. When stratified with the maximum daily dose of noradrenaline, the PMX group showed a statistically significant survival benefit in the groups with noradrenaline dose &#x3c;20 mg/day but not in the noradrenaline group dose ≥20 mg/day. <b><i>Conclusion:</i></b> Analysis of large Japanese databases showed that septic shock patients who received noradrenaline might benefit from PMX treatment.

The influence of obesity on hydroxychloroquine blood levels in lupus nephritis patients

Introduction In 2016 the American Academy of Ophthalmology(2016-AAO) recommended a maximum daily HCQ use of 5.0 mg/kg real body weight(RBW) taking into consideration minimizing eye toxicity. Retinopathy in systemic lupus erythematosus(SLE) patients was recently associated with obesity and this condition is progressively more common in these patients. However, the impact of obesity in HCQ blood levels remains controversial. Objective To determine if the 2016-AAO recommendation based on RBW with and without maximum daily dose restriction results in adequate and safe blood levels in obese lupus nephritis(LN) patients. Methods A cross-sectional study was performed with 108 LN patients under the prescribed 2016-AAO dose for at least 3 months. LN patients were assessed for demographic characteristics, body mass index(BMI), disease parameters, HCQ dose, concomitant treatment and HCQ blood levels measured by liquid chromatography-tandem mass spectrometry. Obesity was defined as BMI ≥30kg/m2. Results Obesity was identified in 35/108(32%) LN patients. The calculation of HCQ daily dosage revealed that obese patients were under a lower prescribed daily dose according to the real body weight (RBW) [4.4(2.9-5.4) vs. 4.9(4-5.5)mg/Kg/day, p < 0.001] due to the maximum limit used. Regardless of that the median of HCQ blood levels was significantly higher in obese compared to non-obese patients (1562 ± 548.6 vs. 1208 ± 448.9 ng/mL, p = 0.002). Further analysis of patients under the 20016-AAO recommendation by RBW without the restriction of maximum daily dose confirmed that in spite of comparable daily dose in 14 obese patients and 61 non-obese patients [4.8 (4.5-5.4) vs. 5.0(4.5-5.5) mg/kg, p = 0.312], the median of HCQ blood levels was significantly higher in obese patients than in non-obese (1734 ± 457.3 vs. 1189 ± 449.4 ng/mL, p < 0.001). Conclusion Obese patients under the 2016-AAO prescribed dose of HCQ based on RBW with and without maximum daily dose restriction have a very high HCQ blood levels compared to non-obese patients, with a potential increased risk of ocular toxicity. The use of 2016-AAO dose of HCQ according to the ideal body weight for this group of patients should be considered.Clinicaltrials.gov #NCT0312243.

Worsening Restless Leg Syndrome Symptoms as a Presentation of Colon Cancer: A Reminder to Work Up the Anemia

Restless leg syndrome (RLS) is a common neurological disorder with an estimated prevalence of 10–35% in people over 65 years of age. Current clinical practice guidelines include the recommendation to check serum ferritin levels and provide iron supplementation if the ferritin level is ≤75 μg/L. We present a case of an 84-year-old man who developed worsening RLS symptoms over the past year despite up-titration of oral ropinirole to maximum daily dose. As part of his workup for RLS, his serum ferritin level was found to be severely low. He was also previously noted to be anemic, so we recommended that he be worked up for iron deficiency anemia. He later received a colonoscopy, which revealed a cecal polyp with high grade dysplasia, and then underwent right hemicolectomy. The patient reported significant improvement in RLS symptoms following the surgery. This case demonstrates the importance of working up iron deficiency anemia in the setting of worsening RLS symptoms, particularly in the geriatric population.

A rational approach to opioid dose reduction in the treatment of bone pain. Clinical discussion

Narcotic drugs have become more available for use, but it is obvious that monotherapy of pain syndrome with narcotic drugs is not always effective. Patients sometimes change prescribed opiates to NSAIDs on their own, because it is more effective despite the high risk of complications. In this case patient has a grade 2 pain syndrome associated with bone metastases despite taking the maximum daily dose of tramadol complicated by nausea. Treatment was successfully changed with medium doses of tramadol and dexketoprophen. We consider the combination of narcotic drugs and NSAIDs as opiate-sparing and suggest that dexketoprophen is effective for treatment of pain associated with bone metastases because of the effect on neuropathiс and central components of pain syndrome. We have analyzed the main mechanisms and options for systemic pharmacotherapy of pain syndrome in bone metastases. Some NSAIDs are known to have central analgesic effects. For example, the analgesic effect of ketorolac after an injury of sciatic nerve is explained by its ability to inhibit the synthesis of algogenic peptides in the posterior horns of the spinal cord and the decrease in astrocyte activation. However, it is the dexketoprofen/tramadol combination that is recognized as the most effective in the world.

Effect of renin angiotensin system blockade following transcatheter aortic valve replacement is dose dependent

Background There is growing body of evidence from retrospective studies that inhibition of the renin angiotensin system (RAS) improves outcome after transcatheter aortic valve replacement (TAVR). However, it remains unknown whether the effect of RAS blockade treatment on survival and left ventricular (LV) remodeling after TAVR is dose dependent. Purpose To assess clinical outcome and remodeling dependent on different RAS doses after TAVR. Methods Patients who were enrolled into our observational TAVR study at our institution were retrospectively assessed according to different dosed of RAS blockade: Group1 (no RAS blockade), group 2 (25% of the maximum daily dose), group 3 (50% of the maximum daily dose) and group 4 (100% of the maximum daily dose). Results A total of 323 patients between January 2015 and September 2019 were included. Patients with higher doses of RAS blockade showed a trend towards lower all-cause mortality at 3-year follow-up (56% with no RAS blockade vs. 66% with the 25% dose vs. 79% with the 50% dose vs. 78% with the full dose; p=0.063). After adjustment for baseline characteristics the difference in survival was significant (p=0.042). Besides NYHA class ≥ III and left ventricular ejection fraction (LV-EF) RAS blockade dose was identified as independent predictor for all-cause mortality (HR 0.72 [95% CI 0.54–0.97]; p=0.03). With respect to regression of LV mass index after TAVR the only significant change was observed in patients receiving the full dose. Conclusion The present study showed for the first time that the impact of RAS blockade treatment on clinical outcome and LV remodeling after TAVR is dose dependent. Survival dependent on RAS dosis Funding Acknowledgement Type of funding source: None

Pharmacoepidemiology of Furosemide in the Neonatal Intensive Care Unit

<b><i>Background:</i></b> Furosemide is commonly used off-label in the neonatal intensive care unit (NICU), but current dosing practices vary widely. <b><i>Objectives:</i></b> To describe dosing practices including route, dose, and duration of exposure to furosemide in a large number of community and tertiary NICUs across North America. <b><i>Method:</i></b> Using the Pediatrix Medical Group Clinical Data Warehouse, we identified infants who received ≥1 dose of furosemide between 1997 and 2016. We excluded infants with incomplete dosing data. We calculated average daily furosemide dose, cumulative dose, total days of exposure, and maximum daily dose. We compared dosing between infants born at &#x3c;32 weeks gestational age (GA) and ≥32 weeks GA. <b><i>Results:</i></b> A total of 18,572 infants had complete dosing data. The median (interquartile value) postnatal age at first exposure was 11 days (4, 26), the median maximum daily dose was 1.0 mg/kg (0.97, 1.6), the median average daily dose was 1.0 mg/kg (0.88, 1.1), and the median cumulative dose was 2.0 mg/kg (1.0, 4.5). The median total duration of exposure was 2 days (1, 4). A total of 177 (1%) infants received <i>≥</i>4 mg/kg/day of furosemide. Infants born &#x3c;32 weeks GA were an older age at initial furosemide exposure compared to those born ≥32 weeks GA: 19 versus 4 days, <i>p</i> &#x3c; 0.001. <b><i>Conclusions:</i></b> Most infants received short courses of furosemide within the labeled dosing parameters. Further studies are needed to assess the safety and efficacy of furosemide in the NICU.