scholarly journals A new polymorphic form of Otilonium Bromide

2014 ◽  
Vol 70 (a1) ◽  
pp. C1576-C1576
Author(s):  
Daniel Vega ◽  
Ricardo Baggio

"Otilonium bromide (C29H43 N2 O4+.Br-) is a quaternary ammonium derivative which has been proven a potent spasmolytic drug with a good tolerability profile, used in the treatment of irritable bowel syndrome. We present herein the structural analysis of an unreported polymorphic form (I), comparing with the only one known so far and already reported [1] polymorphic form of the compound (II). The data set for I was obtained from a twinned specimen. The poor quality of the data thus available did not pose any problem in the structure resolution, but it did instead in refinement: the alkyloxy chains and ethyl branches in the quaternary ammonium groups needed some continuity restraints in their anisotropic displacement factors. In form II this effect appeared enhanced, ending up in unusually large anisotropic displacement parameters for most atoms in the chain. The main points of molecular disagreement reside in the torsion angles where the alkyloxy chains and quaternary ammonium groups leave the planar mainframe. The only notorious intermolecular contacts in both structures appear to be a number of rather weak C–H···Br ones involving the quaternary ammonium groups somehow ""wrapping"" the bromide counterion. There are a few C–H···O contacts interlinking molecules to each other. The phase transformation occurs at 124(2)°C and can be followed by DSC and XRPD. A detailed analysis shows some features in common, viz., in both structures packing stability is mainly due to the ionic interaction between the N+ and the Br-, with the latter ion being evenly surrounded by a number of ammonium groups in a way that they define regular 2D arrays "sandwiching" the neutral part of the molecules, which thus act as spacers. These similarities allow giving a plausibility argument about the way in which the transition may take place."

Ból ◽  
2020 ◽  
Vol 20 (4) ◽  
pp. 1-4
Author(s):  
Marcin Kopka

The aim of preventive treatment of episodic and chronic migraine is to reduce the frequency and severity of attacks and thereby improve patient’s quality of life. It is suggested that calcitonin gene related peptide (CGRP) plays a critical role in migraine patophysiology. In last few decades a new class of drugs was developed – monoclonal antibodies against CGRP. One of them is erenumab, which has been available in Poland since November 2018. The aim of this study was to assess the efficacy and tolerability of erenumab in migraine prophylaxis in polish patients with episodic and chronic migraine. Adult patients diagnosed with migraine (according to ICHD 3) with at least 4 migraine headache days in month were included in this study. The primary endpoint was the proportion of patients with more than 50% reduction in number of migraine headache days after the first month of treatment. From December 2018 to April 2019 9 women (24–66 years; average 43.8 years) were included. The average migraine headache days in this study group was 9 (5–20). The participants were treated with subcutaneously delivered erenumab in daily dose of 70 mg. After the first month of treatment in 7 from 9 women (77.5 %) primary endpoint was reached. In 3 of 9 (30%) patients itch was noted. The results of this study suggest efficacy and good tolerability profile of erenumab in polish patients with episodic and chronic migraine. The future study are needed with larger groups of participants.


2013 ◽  
Vol 11 (7) ◽  
pp. 2779-2786
Author(s):  
Rahul Singhai

One relevant problem in data preprocessing is the presence of missing data that leads the poor quality of patterns, extracted after mining. Imputation is one of the widely used procedures that replace the missing values in a data set by some probable values. The advantage of this approach is that the missing data treatment is independent of the learning algorithm used. This allows the user to select the most suitable imputation method for each situation. This paper analyzes the various imputation methods proposed in the field of statistics with respect to data mining. A comparative analysis of three different imputation approaches which can be used to impute missing attribute values in data mining are given that shows the most promising method. An artificial input data (of numeric type) file of 1000 records is used to investigate the performance of these methods. For testing the significance of these methods Z-test approach were used.


2002 ◽  
Vol 34 ◽  
pp. A102
Author(s):  
P. Portincasa ◽  
A. Moschetta ◽  
V. Causarano ◽  
G. Baldassarre ◽  
D.F. Altomare ◽  
...  

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Alireza Khalilian ◽  
Davoud Ahmadimoghaddam ◽  
Shiva Saki ◽  
Younes Mohammadi ◽  
Maryam Mehrpooya

Abstract Background Ample evidence indicates the efficacy of serotonin type 3 (5-HT3) receptor antagonists in the treatment of patients with diarrhea-predominant irritable bowel syndrome (IBS-D). Mirtazapine is an atypical antidepressant with a well-known 5-HT3 receptor antagonist property. This study, therefore, was undertaken to investigate whether compared to placebo, mirtazapine would be efficacious and safe in the treatment of patients with IBS-D. Methods From November 2019 until July 2020, 67 patients meeting Rome IV criteria for IBS-D were randomized in a double-blind fashion into either the mirtazapine treatment group (n = 34) or the placebo treatment group (n = 33). Patients started with mirtazapine 15 mg/day at bedtime for one-week; after which the dose was increased to 30 mg/day for an additional 7-week. Outcomes included changes in the total IBS symptom severity score (IBS-SSS), Hospital anxiety and depression scale score (HADS), and IBS Quality of Life. Additionally, changes in the diary-based symptoms scores including pain, urgency of defecation, bloating, stool frequency, and stool consistency based on the 7-point Bristol Stool Form Scale (BSFS), and a number of days per week with pain, urgency, diarrhea, or bloating, once during the 1-week run-in period, and once during the last week of treatment were recorded. Results All analyses were performed on an Intention-to-Treat (ITT) analysis data set. The results showed compared to placebo, mirtazapine is more efficacious in decreasing the severity of IBS symptoms (P-value = 0.002). Further, at the end of the treatment period, all diary-derived symptoms except bloating showed significantly more improvement in the mirtazapine-treated subjects compared to the placebo-treated subjects. While was well-tolerated, mirtazapine also significantly improved the patients’ quality of life (P-value = 0.04) and anxiety symptoms (P-value = 0.005). Conclusions Overall, mirtazapine seems to have a potential benefit in the treatment of patients with IBS-D, particularly those with concomitant psychological symptoms. However, further studies are warranted to determine whether these findings are replicated. Trial registration Trial registration: Registration number at Iranian Registry of Clinical Trials: IRCT20120215009014N311. Registration date: 2019-10-21.


SLEEP ◽  
2019 ◽  
Vol 42 (8) ◽  
Author(s):  
Xiaowen Ji ◽  
Hans Ivers ◽  
Josée Savard ◽  
Mélanie LeBlanc ◽  
Charles M Morin

Abstract Study Objectives Chronic insomnia tends to “wax and wane” over lifetime. The presence of residual insomnia symptoms is common, especially among naturally remitted individuals. This study aims to examine the features of these residual symptoms and their potential association with future relapse. Methods A population-based data set on the natural history of insomnia was used for this secondary analysis. Residual insomnia symptoms were investigated in those who had insomnia symptoms/syndrome at baseline and achieved full remission (according to predetermined diagnostic algorithm) within the following 1 year. Cox regressions were used to determine the hazard ratio (HR) of each residual symptom for predicting relapse in the next 4 years. The nature and severity of residual symptoms were examined with an extended version of the Insomnia Severity Index (ISI), which incorporates additional items on sleep quality and specific sleep-related daytime impairments (on daytime fatigue, cognitive functioning, mood, interpersonal relationship, and daily activities). In addition, the presence of depressive symptoms and medical conditions were controlled for in investigating risks of insomnia relapse. Results A total of 434 participants were included in this study (age ranges from 18 to 94; 65.9% female); 248 of them had relapsed within 4 years. The response rate ranged from 78% to 83%. The most frequently reported residual symptoms with at least moderate severity (ISI items ≥2 on 0–4 ISI item scale) were poor “Quality of sleep” (39.2 %), followed by “difficulty maintaining sleep” (DMS; 27%). The most common residual daytime impairments related to insomnia were fatigue (24.7 %), mood disturbances (23%) and cognitive disturbances (22.6%). After controlling for baseline insomnia and depression severity and concurrent physical diseases, impairments of cognition (HR = 1.46), poor quality of sleep (HR = 1.43), disturbed mood (HR = 1.39), being female (HR = 1.36), DMS (HR = 1.35), and fatigue (HR = 1.24) were significantly associated with insomnia relapse in the next 4 years. Moreover, residual poor sleep quality and daytime insomnia symptoms were independent of DMS in predicting relapse. Subgroup regressions according to sex showed that for male participants, residual cognition impairments (HR = 1.98) was the most significant predictors of future relapse, whereas residual DMS (HR = 1.46) significantly predicted relapse for women only. Conclusion A wide range of residual symptoms exists in individuals with naturally remitted insomnia. Notably, residual DMS is the most common residual nighttime symptom and the only nighttime symptom associated with insomnia relapse. Additionally, perceived poor sleep quality and cognitive, mood, and somatic impairments attributed to sleep disturbances are also related to future relapse. Attention to these residual symptoms when initiating insomnia treatment is warranted to minimize future relapse.


2021 ◽  
Vol 28 ◽  
Author(s):  
Flavia di Michele

: Irritable bowel syndrome (IBS) is a chronic functional bowel disorder, often stress-related, identified by many abdominal symptoms, the most important of which is the chronic visceral abdominal pain. Therefore, IBS commonly impairs the quality of life of patients, moreover it is frequently linked to depressive and anxiety symptoms. The treatment of IBS primarily focuses on symptoms relief. Unfortunately, up to now, no efficacious therapies have been found. Therefore, it would be important to develop new anti-IBS interventions. The aim of this brief review is to summarize the current evidence of nutraceutical supplementation in IBS treatment, with probiotics, prebiotics, synbiotics, butyrate, palmitoylethanolamide and colostrum. Since nutraceutics are over the counter products, the review has the purpose to better inform the medicinal chemist and the practitioner about the possible benefit mechanisms and the many advantages that these therapies offer. All of these compounds present multiple mechanisms of action, such as restoring the physiological microbiota, potentiating gastrointestinal barrier’s function, immunomodulatory, anti-inflammatory and antinociceptive activities. From the literature data it results that these compounds are not only capable to improve IBS symptomatology, but mainly display an optimal safety and tolerability profile. Although extensive studies must be carried out to reinforce the evidences from the so far limited clinical trials, the supplementation with these compounds may be useful considering the warnings of prescription medicines for special populations of patients, such as elders, youngsters, or patients who need a combination therapy. Finally, the nutraceutical approach may improve adherence to treatment, given its better acceptance by the patients compared to pharmacological therapy.


2001 ◽  
Vol 120 (5) ◽  
pp. A634-A634 ◽  
Author(s):  
K OLDEN ◽  
W CHEY ◽  
J BOYLE ◽  
E CARTER ◽  
L CHANG

2020 ◽  
pp. 34-36
Author(s):  
M. A. Pokhaznikova ◽  
E. A. Andreeva ◽  
O. Yu. Kuznetsova

The article discusses the experience of teaching and conducting spirometry of general practitioners as part of the RESPECT study (RESearch on the PrEvalence and the diagnosis of COPD and its Tobacco-related aetiology). A total of 33 trained in spirometry general practitioners performed a study of 3119 patients. Quality criteria met 84.1% of spirometric studies. The analysis of the most common mistakes made by doctors during the forced expiratory maneuver is included. The most frequent errors were expiration exhalation of less than 6s (54%), non-maximal effort throughout the test and lack of reproducibility (11.3%). Independent predictors of poor spirogram quality were male gender, obstruction (FEV1 /FVC<0.7), and the center where the study was performed. The number of good-quality spirograms ranged from 96.1% (95% CI 83.2–110.4) to 59.8% (95% CI 49.6–71.4) depending on the center. Subsequently, an analysis of the reasons behind the poor quality of research in individual centers was conducted and the identified shortcomings were eliminated. The poor quality of the spirograms was associated either with the errors of the doctors who undertook the study or with the technical malfunctions of the spirometer.


2013 ◽  
Vol 154 (8) ◽  
pp. 294-304 ◽  
Author(s):  
György Miklós Buzás

After a short overview of the history of probiotics, the author presents the development of human intestinal microflora based on the newest genetic data and the microbiological features of main probiotics. The indications of probiotic administration have been defined and extended in recent years. The author reviews significant results of probiotic treatment in some gastrointestinal diseases based on meta-analytical data. Probiotics are useful in preventing and treating diarrhoea caused by antibiotics and Clostridium difficile caused diarrhoea. In the treatment of Helicobacter pylori infection, preparations containing certain Lactobacillus,Bifidobacterium strains or Saccaromyces boulardii could enhance by 5–10% the rate of successful eradication and reduce the incidence and severity of the side effects. Some symptoms of irritable bowel syndrome and thus the quality of life can be improved by probiotics. Their beneficial effect in ulcerative colitis was proven, while in Crohn’s disease has not yet been defined. The use of probiotics is not included in guidelines, with the exception of the Maastricht IV/Florence consensus. For each disease it is advisable to use probiotics containing strains only with proven beneficial effect. The efficiency of preparations containing mixed strains has not yet been properly investigated. The author reviews the rare but potentially serious side effects of probiotics. In Hungary, there are many probiotic preparations available which can be purchased in pharmacies without prescription: their use is more empirical than evidence-based. The European Food Safety Authority has recently rejected claims for probiotics to be classed as medicines given the lack of convincing evidence on the effects of probiotics on human health and well-being. Clearly, further research is needed to collect evidence which could be incorporated into the international guidelines. Orv. Hetil., 2013, 154, 294–304.


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