Unexpected spotlight on two unusual substances

Acute liver failure (ALF) is a rare and unexpected condition, which is commonly related to drug ingestion and viral infections. Here, two ALF fatalities are presented, which showed a rapid progression between the onset of symptoms and death. Both cases gained attention as unusual substances were suspected to be the reason for the fatal ALF, namely the prescription-free natural remedy Iberogast® (Bayer Vital GmbH, Leverkusen, Germany) and freely available energy drinks. Autopsy findings revealed that the fatal ALFs were unrelated to the ingestion of these two substances.

Endoscopic removal of slow release oxycodone tablets in a case of voluntary acute poisoning

We describe a case of 83-years-old women admitted to the Emergency Department after massive ingestion of slow release Oxycodone pills for suicidal purpose. After gastric lavage only few tablets has been retrieved and Naloxone infusion was necessary. After 2 hours from drug ingestion Esophagogastroduodenoscopy (EGDS) was performed and a number of tablets have been removed. Intoxication symptoms completely resolved and Naloxone infusion has been stopped. The clinical courses of this intoxication suggest that the utility of EGDS to remove tablets should be considered in selected cases of drug poisoning.

Pharyngeal Pumping and Tissue-Specific Transgenic P-Glycoprotein Expression Influence Macrocyclic Lactone Susceptibility in Caenorhabditis elegans

Macrocyclic lactones (MLs) are widely used drugs to treat and prevent parasitic nematode infections. In many nematode species including a major pathogen of foals, Parascaris univalens, resistance against MLs is widespread, but the underlying resistance mechanisms and ML penetration routes into nematodes remain unknown. Here, we examined how the P-glycoprotein efflux pumps, candidate genes for ML resistance, can modulate drug susceptibility and investigated the role of active drug ingestion for ML susceptibility in the model nematode Caenorhabditis elegans. Wildtype or transgenic worms, modified to overexpress P. univalens PGP-9 (Pun-PGP-9) at the intestine or epidermis, were incubated with ivermectin or moxidectin in the presence (bacteria or serotonin) or absence (no specific stimulus) of pharyngeal pumping (PP). Active drug ingestion by PP was identified as an important factor for ivermectin susceptibility, while moxidectin susceptibility was only moderately affected. Intestinal Pun-PGP-9 expression elicited a protective effect against ivermectin and moxidectin only in the presence of PP stimulation. Conversely, epidermal Pun-PGP-9 expression protected against moxidectin regardless of PP and against ivermectin only in the absence of active drug ingestion. Our results demonstrate the role of active drug ingestion by nematodes for susceptibility and provide functional evidence for the contribution of P-glycoproteins to ML resistance in a tissue-specific manner.

KAMI-PMO TB (EDUKASI DAN PENDAMPINGAN PENGAWAS MENELAN OBAT TB) DALAM PENGENDALIAN MDR TB

Tuberculosis control in Indonesia is still not optimal. The problem of MDR TB (Multidrug-Resistant Tuberculosis) is an obstacle to controlling TB in Indonesia. MDR TB is caused by no response from TB germs to treatment isoniazid and rifampicin, anti-tuberculosis drugs. TB incidence rate in Serang district ranks second in Banten Province after Tangerang. The number of pulmonary TB cases is due to the lack of public knowledge and awareness about pulmonary TB disease. To reduce the adverse effects of MDR TB requires the involvement of cadres or family members who controlling drug ingestion (PMO). The form of activities carried out through the formation of cadres to care for TB through the KAMI-PMO TB (Education and Assistance for TB Medication Supervisors) in Desa Baros, Kabupaten Serang. The purpose is to increase the commitment, ability, and knowledge of cadres as coordinator of PMO (Drug Swallow Supervisor) to control MDR TB. The method of implementing activities is counseling, demonstrations, and assistance to cadres. The media used were PPT, WE-PMO TB Booklet, and educational videos. The result of the training was an increase in the ability of cadres in providing PMO counseling by 87%. The Paired T-Test analysis results showed a p-value of 0.000, which means that the training conducted affected cadres' knowledge of PMO TB. In conclusion, education and assistance to cadres have a good influence in increasing knowledge and abilities. The expected result is TB care cadres can provide aid and become the coordinator of TB PMO (Drug Ingestion Supervisor). ABSTRAK:Pengendalian Tuberculosi di Indonesia masih belum optimal.Permasalahan MDR TB (Multidrug Resistant Tuberculosis) merupakan hambatan pengendalian TB di Indonesia. MDR TB disebabkan tidak ada respon kuman TB terhadap pengobatan isoniazid dan rifampizin yang merupakan obat anti tuberculosis. Angka kejadian TB di kabupaten Serang menempati urutan kedua di Provinsi Banten setelah Tangerang, dan banyaknya kasus TB Paru dikarenakan pengetahuan dan kesadaran masyarakat tentang penyakit TB Paru masih kurang. Untuk mengurangi dampak buruk MDR TB dibutuhkan keterlibatan peran serta kader peduli TB atau anggota keluarga yang berperan dalam pengawasan menelan obat (PMO). Bentuk kegiatan yang dilakukan sebagai bentuk pemberdayaan masyarakat melalui pembentukan kader peduli TB melalui KAMI-PMO TB (Edukasi dan Pendampinga Pengawas Menelan Obat TB) di Desa Baros Kabupaten Serang. Tujuan dari pengabdian masyarakat adalah meningkatkan komitmen, kemampuan dan pengetahuan kader sebagai koordinator PMO (Pengawas Menelan Obat) dalam upaya pengendalian MDR TB. Metode pelaksanaan kegiatan adalah penyuluhan, demontrasi, dan pendampingan kader. Media yang digunakan yaitu PPT, Booklet KAMI-PMO TB , dan video edukasi. Hasil dari kegiatan adalah meningkatnya kemampuan kader dalam memberikan penyuluhan PMO cukup tinggi sebesar 87%. Hasil analisis uji Paired T- Test didapatkan nilai p value 0,000 yang artinya ada pengaruh pelatihan yang dilakukan terhadap pengetahuan kader tentang PMO TB. Kesimpulannya edukasi dan pendampingan kepada kader memiliki pengaruh yang baik dalam meningkatkan pengetahuan dan kemampuan, sehingga hasil yang diharapkan kader peduli TB dapat melakukan pendampingan pada pasien TB dan menjadi koordinator PMO (Pengawas Menelan Obat) TB dalam upaya pengendalian MDR TB

Pharyngeal pumping and tissue-specific transgenic P-glycoprotein expression influence macrocyclic lactone susceptibility in Caenorhabditis elegans

Macrocyclic lactone (ML) resistance has emerged in many parasitic nematodes including the pathogenic horse roundworm Parascaris univalens. The underlying mechanism of ML resistance and the drug penetration routes into the nematodes remain to be elucidated. Drug efflux by P-glycoproteins is considered a potential resistance mechanism but conclusive functional evidence is lacking. To this end, we used a motility assay modified to stimulate pharyngeal pumping (PP) by bacteria or serotonin and tissue-specific expression of Pun- PGP-9 in the free-living model nematode Caenorhabditis elegans. Here, stimulation of PP was identified as an important factor for C. elegans ML susceptibility, increasing the EC50 values of ivermectin by up to 11.1-fold and of moxidectin by 1.2-fold. In this context, intestinal Pun-PGP-9 expression elicited a protective effect against ivermectin and moxidectin only in the presence of PP stimulation, increasing the EC50 values by approximately 3- to 4-fold (ivermectin) or by < 1.3-fold (moxidectin). Conversely, epidermal Pun-PGP-9 expression protected against moxidectin regardless of PP with EC50 fold changes below 1.5 but against ivermectin with a considerable 2.9-fold EC50 increase only when the drug is not actively ingested. Our results highlight the role of active drug ingestion by nematodes for susceptibility and provide conclusive functional evidence for a contribution of P-glycoproteins to ML resistance.Author SummaryParasitic nematode infections pose a serious threat to animal health, in particular in light of the widespread anthelmintic resistance in different nematode species. In equines, the roundworm Parascaris univalens is a major pathogen of foals, exhibiting widespread resistance against macrocyclic lactones (MLs). This represents a particular challenge to animal health, but the underlying mechanisms and drug penetration routes remain mostly unknown. P-glycoprotein ABC-transporters have been linked to ML resistance in several parasitic nematodes. Here we demonstrate by tissue-specific overexpression of Pun-PGP-9 in the free-living model nematode Caenorhabditis elegans their ability to reduce the susceptibility to two commonly used MLs, ivermectin and moxidectin. At the same time, active drug ingestion by pharyngeal pumping (PP) strongly enhanced ivermectin and moderately effects moxidectin susceptibility. In more detail, the effect of intestinal or epidermal Pun-PGP-9 was dependent on active drug ingestion. These observations indicate differences in the drug penetration routes between ML derivatives and allow novel insight into the functional role of P-glycoproteins.

P431Flecainide or propafenone oral bolus to facilitate electrical cardioversion of persistent atrial fibrillation

Background electrical cardioversion (ECV) of atrial fibrillation (AF) is a pivotal component of the rhythm control approach. Although ECV is safe and effective in the majority of patients, approximately one patient out of ten experiences an early or very early recurrence. In order to improve ECV’s success rate, oral or intravenous amiodarone pre-treatment is commonly prescribed and followed by a second ECV attempt. However, due to the long time needed to achieve therapeutic levels and the high risk of phlebitis, faster and safer strategies to facilitate ECV are highly needed. Purpose to evaluate whether the administration of a flecainide or propafenone oral bolus followed by ECV would prove effective and safe in facilitating conversion to sinus rhythm in patients with persistent AF and a prior ECV failure. Methods we conducted a prospective, open-label, single center observational study. The case group was formed by patients with persistent AF and a prior ECV failure receiving flecainide or propafenone oral bolus (at the same doses used for the "pill-in-the-pocket" approach) followed by a second ECV attempt 3 hours after drug ingestion. For comparison, we selected patients with a prior ECV failure that underwent amiodarone-facilitated ECV. Before ECV, amiodarone was either administered orally for at least 1 month or intravenously for 24 hours. The primary outcome was conversion to sinus rhythm, defined as sinus rhythm persisting for at least 12 hours after ECV. Results patient’s characteristics were well balanced in the 3 groups, apart from slightly lower left ventricular ejection fraction values in the amiodarone groups. The day after ECV failure, 29 patients received oral flecainide at a 200 mg (n = 15) or at a 300 mg (n = 14) dose and one patient received oral propafenone at a 600 mg dose before undergoing a second ECV attempt. In nine patients, amiodarone was given intravenously for 24 hours. Amiodarone was prescribed orally to 22 patients for a median of seven weeks at an average daily dose of 241.4 mg. In the flecainide/propafenone group, one patient converted to sinus rhythm one hour after drug ingestion; among the other 29 subjects, the second ECV was effective in 23 (cumulative effectiveness: 80.0%). In the intravenous amiodarone group, 2 patients converted to sinus rhythm during drug infusion; among the other 7, the second ECV proved effective in 4 (cumulative effectiveness: 66.7%). In the oral amiodarone group, ECV was successful in 17 patients (77.3%). When comparing the three groups, the primary outcome occurred in a similar proportion of patients (Chi-squared test: p = 0.34; Fisher’s exact test: p = 0.24). Serious adverse events were not reported. Conclusions flecainide or propafenone oral bolus quickly facilitated conversion to sinus rhythm in the vast majority of patients with persistent AF and a prior ECV failure with a low inherent risk of adverse events. Flecainide effectiveness proved similar to intravenous or oral amiodarone.

0094 The Effect of Zolpidem on Sleep-Dependent Declarative Memory Consolidation

Introduction Sleep plays a critical role in memory consolidation. At the same time, about 20% of population in the U.S. suffer from sleep disorders or deprivation, and about 16% of them reported using sleep aids (CDC, 2015). However, the effect of sleep aids on sleep-dependent memory consolidation remains unclear. Previous studies have observed an improvement in sleep-dependent declarative memory consolidation with zolpidem over a daytime nap (Mednick et al., 2013). The current study investigates the effect of zolpidem on declarative memory consolidation over a night of sleep and over 24 hours. Methods This study employed a double-blind, placebo-controlled, within-subject design, in which every subject (N=26, 12 females) experienced both zolpidem and placebo. All subjects were healthy, college-aged adults without sleep disorder. A 32-channel electroencephalogram cap was used to record brain activity during sleep. Word paired-associates task was used to evaluate memory performance. Participants reported to the laboratory in the evening, performed word paired-associates task (test1), then ingested either zolpidem or placebo before sleep. They were tested on the task in the following morning (test2) as well as in the following evening (test3). Paired-sample t-tests for retrieval difference scores between placebo and zolpidem conditions were conducted. Results Participants showed similar baseline performance on the word paired-associates task (test 1, p=0.45). Zolpidem condition showed higher memory retention compared to placebo 24hr after drug ingestion (test3-test1, t₂ 5=2.09, p&lt;0.05). The improvement in performance for zolpidem condition occurred across the following day (test3-test2, t₂ 5=2.22, p&lt;0.05), as no difference was observed between conditions after sleep (test2-test1, t₂ 5=0.34, p=0.74) Conclusion Consistent with previous studies, participants showed better memory performance after taking zolpidem compared to placebo. However, the current study showed that the improvement in memory occurred across a day of wakefulness after nighttime drug ingestion, while other studies observed improvements shortly after sleep, indicating a potential delayed benefit of zolpidem on memory consolidation. Support This work was supported by the Office of Naval Research grant N00014-14-1-0513