[Results of a multicentre double-blind randomised placebo-controlled clinical trial evaluating the efficacy and safety of Mexidol in the treatment of Attention Deficit Hyperactivity Disorder in Children (MEGA)]. / Rezul'taty mnogotsentrovogo dvoinogo slepogo randomizirovannogo platsebo-kontroliruemogo klinicheskogo issledovaniya po otsenke effektivnosti i bezopasnosti preparata Meksidol v lechenii sindroma defitsita vnimaniya s giperaktivnost'yu u detei (MEGA).

OBJECTIVES: To evaluate the efficacy and safety of two dosing regimens of Mexidol film-coated tablets, 125 mg («RPC «PHARMASOFT¼ LLC Russia), compared with placebo in children with attention deficit hyperactivity disorder (ADHD) aged 6 to 12 years. MATERIAL AND METHODS: A multicenter randomized, double-blind, placebo-controlled study in 3 parallel groups was conducted in 14 clinical centres of the Russian Federation to assess efficacy and safety of Mexidol film-coated tablets, 125 mg («RPC «PHARMASOFT¼ LLC Russia) in the treatment of attention deficit hyperactivity disorder (ADHD) in children 6-12 years old with different dosing regimens. The study involved 333 boys and girls aged 6 to 12 years with a confirmed diagnosis of ADHD established in accordance with ICD-10 and DSM-5 criteria. After screening (up to 14 days) the patients were randomised into 3 treatment groups in a 1:1:1: Mexidol 125 mg 2 times daily, Mexidol 125 mg daily+placebo and the placebo group. The duration of treatment in all groups was 42 days. 332 children completed the study. ADHD and comorbid disorders assessment scales were used. RESULTS: There were statistically significant changes in the sum of the total scores on the SNAP-IV inattention and hyperactivity/impulsivity subscales after 6 weeks of therapy in all three study groups (p<0.05). There were statistically significant differences between the Mexidol 125 mg and placebo groups and between the Mexidol 125 mg 2 times daily and placebo groups (for the PP population: p=0.000308 and p=0.000024, respectively; for the FAS population: p=0.000198 and p=0.000024, respectively), indicating that Mexidol therapy is superior to placebo. Statistically significant differences (p<0.05) were also obtained for most of the secondary efficacy criteria (average change in SNAP-IV inattention subscale score, average change in SNAP-IV hyperactivity/impulsivity subscale score, average change in SNAP-IV subscale score - Conners index, average change in ADHD-RS-IV score, change in CGI-ADHD-S scores, change in CGI-I score - the Clinical Global Impressions Scale - Improvement) when comparing Mexidol therapy with placebo. The results of statistical analysis of the incidence of adverse events, laboratory values, physical examination show no significant differences between the compared groups in the main safety parameters. CONCLUSIONS: The regimen of Mexidol, 125 mg film-coated tablets twice daily has been shown to be superior to the regimen of Mexidol, 125 mg film-coated tablets once daily and placebo. The safety profiles of the studied dosing regimens of Mexidol and placebo were comparable.

[Study of the efficacy and safety of sequential use of the drugs Mexidol and Mexidol FORTE 250 in the treatment of stroke]. / Issledovanie effektivnosti i bezopasnosti posledovatel'nogo primeneniya preparatov Meksidol i Meksidol Forte 250 pri lechenii bol'nykh s ostrym ishemicheskim insul'tom.

OBJECTIVE: To evaluate the effect of Mexidol on the recovery of cognitive functions in patients after ischemic stroke (IS). MATERIAL AND METHODS: We examined 70 patients with acute IS, who were randomized into 2 groups by random sampling; The 1st group consisted of patients who, against the background of the main standard therapy for 14 days, received Mexidol intravenously, 500 mg 1 time per day, followed by oral administration of Mexidol FORTE 250, 750 mg per day for 60 days (40 patients; 28 men, 12 women). Group 2 consisted of 30 patients (21 men, 9 women) who received only standard therapy. RESULTS: Baseline scores on the MoCA and MMSE scales did not differ between the two groups. Retesting showed that the improvement on these scales was statistically more significant in the 1st group. The analysis of indicators of the evoked potential P300 confirmed a more pronounced positive trend in the 1st group (p<0.01). CONCLUSION: The use of sequential therapy with Mexidol is accompanied by a more complete recovery of cognitive functions in patients who have undergone IS.

Comparison Between Same-Day and Split-Dose Preparations with Sodium Picosulfate/Magnesium Citrate: A Randomized Noninferiority Study.

BACKGROUND: Sodium picosulfate/magnesium citrate (SPMC) is a small-volume bowel cleansing agent with similar efficacy to and better tolerability than polyethylene glycol. However, we found no data on which SPMC preparation (same-day vs. split-dose) provides better bowel cleansing efficacy for afternoon colonoscopy. AIMS: To compare bowel cleansing efficacy of different timing of the regimen. METHODS: This randomized, single-center, endoscopist-blinded, noninferior study compared same-day and split-dose SPMC preparations for afternoon colonoscopy in 101 and 96 patients, respectively. We also included a prospective observation group of 100 patients receiving morning colonoscopy to compare bowel preparation between morning and afternoon colonoscopies. Bowel cleansing efficacy was then evaluated by the Aronchick Scale, Ottawa Bowel Preparation Scale (OBPS), Boston Bowel Preparation Scale (BBPS), and the Bubble Scale. RESULTS: Same-day and split-dose preparations were similar in efficacy in all four scales. In the Aronchick Scale, the success rate (excellent and good cleanliness) was higher in same-day preparation than in split-dose preparation (100% vs. 92.8%). The same-day preparation also obtained a better OBPS score (1.4 vs. 2.1), but BBPS showed no difference between such groups (7.7 vs. 7.4). CONCLUSION: Same-day preparation with SPMC is not inferior to split-dose preparation for afternoon colonoscopy.

[Results of an international multicenter, randomized, double-blind, placebo-controlled study assessing the efficacy and safety of sequential therapy with Mexidol and Mexidol FORTE 250 in patients with chronic brain ischemia (MEMO)]. / Rezul'taty mezhdunarodnogo mnogotsentrovogo randomizirovannogo dvoinogo slepogo platsebo-kontroliruemogo issledovaniya otsenki effektivnosti i bezopasnosti posledovatel'noi terapii patsientov s khronicheskoi ishemiei mozga preparatami Meksidol i Meksidol FORTE 250 (issledovanie MEMO).

OBJECTIVE: To assess the efficacy and safety of sequential therapy with Mexidol solution for intravenous and intramuscular administration, 50 mg/ml and Mexidol FORTE 250 film-coated tablets, 250 mg in patients with chronic brain ischemia (CBI). MATERIAL AND METHODS: An international multicenter, randomized, double-blind, placebo-controlled trial, conducted in 15 clinical centers located in Russian Federation and Republic of Uzbekistan, included 318 patients with CBI aged 40 to 90 years. The patients were randomized into 2 groups, the patients of the 1-st group received Mexidol intravenously 500 mg once daily for 14 days, followed by Mexidol FORTE 250 - 250 mg 3 times a day orally for 60 days; patients of the 2-nd group received a placebo in a similar mode. The primary endpoint was the mean value of difference by MoCA scale at the point of completing the therapy comparing to initial value. RESULTS: According to the results of the assessment of the primary endpoint, statistically significant changes in the MoCA scores at the stage of completion of study were revealed when comparing the dynamics between the 1-st and 2-nd groups (p<0.000001). The lower limit of the 95% confidence interval for the difference in the average of the main efficacy endpoint between the 1-st and 2-nd groups was 1.51, which allows to state a higher efficacy of the use of Mexidol. According to the estimates of secondary endpoints, a statistically significant advantage over placebo at the last visit achieved while evaluation by the following scales and tests: digit symbol substitution test, MFI-20 asthenia assessment scale, Beck anxiety scale, Vane questionnaire, Tinetti scale, SF-36 questionnaire (mental component of health), CGI scale. The comparable nature of the safety profile of Mexidol and Placebo was established. CONCLUSION: The validity and expediency of the use of Mexidol and Mexidol FORTE 250 in the treatment of patients with CBI has been demonstrated.

[The efficacy and safety study of Mexidol and Mexidol FORTE 250 in patients with chronic cerebral ischemia]. / Effektivnost' i bezopasnost' terapii lekarstvennymi preparatami Meksidol i Meksidol FORTE 250 u patsientov s khronicheskoi ishemiei golovnogo mozga.

OBJECTIVE: To study the efficacy and safety of sequential MexidoL therapy, administered intravenously (500 mg once a day) for 14 days, followed by taking the oral form Mexidol FORTE 250 at a dose of 250 mg (1 tablet) 3 times a day for 60 days in elderly patients with chronic cerebral ischemia (CCI) on the background of arterial hypertension and atherosclerosis. MATERIAL AND METHODS: An open prospective observational study included 60 patients with an established diagnosis (CCI), confirmed by the results of neuroimaging. All patients were examined with an assessment of neuropsychological status (MoCA test), severity of asthenia (scale MFI-20), emotional state (Hamilton anxiety and depression scale), motor functions (formalized clinical scale for assessing motor activity of elderly Tinetti). The effectiveness of the therapy was evaluated according to the quality of life questionnaire (SF-36). RESULTS: The results of the study showed the high efficiency and safety of sequential therapy with Mexidol in relation to the relief of asthenic and emotional disorders, improving the state of cognitive functions, improving the quality of life of patients. The maximum effect occurred after the end of the full course of therapy. High adherence of patients to the therapy, low frequency of adverse events are shown. CONCLUSION: Sequential use of intravenous administration of Mexidol followed by oral administration of Mexidol FORTE 250 is an effective and safe way to treat patients with CCI.

Efficacy, tolerability and safety of a split-dose bowel cleansing regimen of magnesium citrate with sodium picosulfate - a phase IV clinical observational study.

BACKGROUND: There are contradictory results about the effect of magnesium citrate plus sodium picosulfate bowel cleansing agents on the fluid and electrolyte balance. Therefore, this study aimed to determine the efficacy, tolerability and safety of this medication in colonoscopy preparation. METHODS: 233 patients were enrolled in this phase IV prospective observational study. The effectiveness of bowel cleansing was assessed using the Boston Bowel Preparation Scale (BBPS). Adequate cleansing was defined as BBPS ≥ 6 and excellent cleansing as BBPS > 7. Tolerability was examined using a standardized questionnaire. In the safety analysis, the change of serum electrolytes levels and renal function during bowel cleansing was assessed. RESULTS: Adequate and excellent bowel cleansing were achieved 94.85% and 72.96% of cases, respectively. None or very mild symptoms were reported in 47.21% of cases. Statistically significant changes occurred in serum potassium (4.38±0.43 vs. 4.25±0.43 mmol/L, p<0.0001), urea (4.86±1.37 vs. 3.84±1.43 mmol/L, p<0.0001) and creatinine (male: 81.07±16.02 vs. 84.54±15.11 µmol/L; female: 69.32±12.22 vs. 72.96±12.11 µmol/L, p<0.0001) levels during the colonoscopy preparation. However, the number of patients with values outside of the normal range increased significantly only in the case of serum urea (3.95% vs. 26.97%, p<0.0001). CONCLUSION: Magnesium citrate with sodium picosulfate is outstandingly effective, well tolerated and a safe agent in colonoscopy preparation. It caused significant, but non-clinically relevant changes in serum electrolytes levels and renal function.

[Effectiveness and safety of mexidol forte 250 in the sequential therapy in patients with chronic ischemia]. / Effektivnost' i bezopasnost' preparata Meksidol FORTE 250 pri posledovatel'noi terapii patsientov s khronicheskoi ishemiei mozga.

OBJECTIVE: To study of efficacy and safety of mexidol used as intravenous infusion for 14 days, followed by per os treatment with mexidol FORTE 250 for 60 days in patients with chronic brain ischemia (CHM) complicated with arterial hypertension and atherosclerosis. MATERIAL AND METHODS: The mexidol group included 27 patients (24 women and 3 men) with CHM I-II gr and the combination of arterial hypertension and atherosclerosis who received intravenous infusions of mexidol (500 mg once daily) within 14 days, with the subsequent per os treatment with mexidol FORTE 250 in a daily dose of 750 mg (1 tablet 3 times a day) for 60 days. The comparison group consisted of 30 patients (22 women and 8 men) with CHM I-II gr, comparable in age, nature of risk factors and expression of neurological manifestations. Patients in both groups received basic medications to treat their risk factors. Motor activity (Tinetti test), cognitive functions (MoCa test), anxiety and depression (Hamilton anxiety and depression scale), clinical condition (General Clinical Impression scale) were assessed. RESULTS AND CONCLUSION: Inclusion of mexidol (500 mg iv infusion once a day within 14 days with the subsequent oral administration of 750 mg (1 tablet 3 times a day) for 60 days) in standard therapy of arterial hypertension with atherosclerosis and chronic brain ischemia is expedient. The results show greater clinical efficacy and sufficient safety of such combination therapy. By the end of therapy (day 74), patients in the mexidol group have a reliable improvement in motor activity, cognitive function and psychoemotional sphere, as well as a decrease in fatigue and neurological manifestations compared with the comparison group.

[Efficacy and safety of mexidol across age groups in the acute and early recovery stages of hemispheric ischemic stroke (results of additional sub-analysis of a randomized double blind multicenter placebo-controlled study, in parallel groups trial EPICA)]. / Effektivnost' i bezopasnost' Meksidola u patsientov raznykh vozrastnykh grupp v ostrom i rannem vosstanovitel'nom periodakh polusharnogo ishemicheskogo insul'ta (rezul'taty subanaliza randomizirovannogo dvoinogo slepogo mul'titsentrovogo platsebo-kontroliruemogo v parallel'nykh gruppakh issledovaniya EPIKA).

AIM: To evaluate the efficacy and safety of prolonged sequential therapy with mexidol in the acute and early recovery stages of hemispheric ischemic stroke (IS) across age groups according to the World Health Organization classification. MATERIAL AND METHODS: The study is an additional analysis across age groups among patients participated in the randomized double blind multicenter placebo-controlled, in parallel groups trial EPICA. All subjects (62 men and 88 women) were subdivided into age groups: younger than 60 years, 60-65 years, 76-90 years. Additionally, all participants were divided into 2 populations: ITT (Intent to treat population, patients who received at least one treatment/placebo dose) and PP (Per protocol population, patients who received treatment per study protocol). Results of Modified Rankin scale (mRs) at the end of treatment period, Barthel index, Beck depression inventory, European Quality of Life Questionnaire were assessed. RESULTS: The efficacy of mexidol assessed with all the scales did not differ depending on the age group. By the end of treatment, the mean mRS score was lower in the 76-90 years subgroup (in both populations), compared to placebo (p<0.001). The decrease in mean mRS score (Visit 1-5) was more prominent in patients aged 60-65 years (p=0.025), including patients with diabetes mellitus (DM). Patients aged 76-90 years and patients with DM, compared to placebo, had a decrease of the severity of cognitive-affective depression symptoms (p=0.049 and p=0.02) and an increase in patients without problems with everyday activities (p=0.007 and p=0.02). Patients with DM, compared to placebo, also had the higher levels of everyday activity (p=0.023) and quality of life (p=0.045). There were no statistically significant differences in the frequency of side-effects in patients of all groups. CONCLUSION: It is recommended to include mexidol in therapy of patients with IS in the acute and early rehabilitation stages in all age groups, including patients with DM.

[The efficacy and safety of Mexidol Forte 250 as part of long-term sequential therapy in patients with carotid stroke]. / Éffektivnost' i bezopasnost' preparata Meksidol Forte 250 v ramkakh dlitel'noi posledovatel'noi terapii u bol'nykh s ishemicheskim insul'tom v karotidnoi sisteme.

AIM: To evaluate an effect of long-term sequential therapy with mexidol and mexidol forte on the functional outcome of patients with carotid ischemic stroke. MATERIAL AND METHODS: The study included 50 patients with newly developed carotid stroke, hospitalized in the stroke unit on the first day from the onset of the disease. Patients of the main group (n=25) received mexidol in a dose of 500 mg intravenously once a day for 14 days, then mexidol forte 250 in tabs 250 mg 3 times a day for 60 days. Patients of the comparison group (n=25) received standard basic therapy. The significance of intergroup differences was assessed using the Mann-Whitney test, Fisher's exact test, and relative risk (OR) calculation. Differences were considered significant at a level of p<0,05. RESULTS: After 14 days of therapy, both groups of patients showed a positive trend compared to baseline. At the same time, patients of the mexidol group had a higher MoCA score (U=173,5, p=0,006), a lower score when performing tasks on dynamic praxis (U=214,0, p=0,028) and optical spatial disturbances (U=170,5, p=0,003), better memorization strength (181,5, p = 0,006) and better performance on abstraction MOCA subtest (U=200,5, p=0,014). By the 74th day, the absence of moderate cognitive impairment (MoCA> 26 points) was diagnosed in 17 patients (68%) of the main group and 14 patients (56%) of the comparison group. No significant differences were found. Moreover, patients of the main group had a significantly lower NIHSS score (U=124,0, p<0,001) and a lower degree of disability: a total mRS score 0-2 was achieved in 19 (76%) patients of the main group and only in 12 (48%) patients of the comparison group (OR=3,34, F=0,07, p<0,05). Also, patients receiving long-term sequential therapy with mexidol and mexidol forte 250 had milder spatial disorders than patients of the comparison group. CONCLUSION: Consecutive treatment with mexidol and mexidol forte 250 in the acute and early recovery periods of ischemic stroke positively affects the regression of local neurological symptoms, increases the likelihood of achieving independence in everyday life by 3,34 times, and reduces the severity of optical-spatial, neurodynamic and memory impairments.

[Results of the sequential use of Mexidol and Mexidol Forte 250 in patients with chronic cerebral ischemia]. / Rezul'taty posledovatel'nogo primeneniia preparatov Meksidol i Meksidol Forte 250 u bol'nykh s khronicheskoi ishemiei golovnogo mozga.

AIM: To study the efficacy and safety of mexidol's intravenous injections (500 mg once a day) for 14 days, followed by oral administration of mexidol FORTE 250 at a dose of 250 mg (1 tablet) 3 times a day for 60 days, in treatment of chronic cerebral ischemia (CCI) in patients with hypertension and atherosclerosis of the brachiocephalic arteries. MATERIAL AND METHODS: The observation program included 60 patients with an established diagnosis of CCI confirmed by neuroimaging methods. Patients of the main group (n=26) received mexidol along with basic therapy, patients of the comparison group (n=26) received only basic therapy. RESULTS AND CONCLUSION: The results of the experience show the high efficacy and safety of sequential therapy (parenteral therapy followed by tablets of mexidol FORTE 250). The treatment improves emotional and cognitive status, decreases static-motor disorders and severity of subjective neurological symptoms. High adherence of patients to the therapy is shown.

Bowel preparation agent inducing profound shock precolonoscopy.

A 73-year-old woman was admitted to the intensive care unit following vomiting and diarrhoea onset after completing oral bowel preparation prior to colonoscopy to investigate haematochezia. She had a history of severe chronic obstructive pulmonary disease, Crohn's disease, diverticular disease, hypertension and dyslipidaemia. She was resuscitated with intravenous fluids, antibiotics and required epinephrine, norepinephrine and vasopressin infusions. She improved over her 4-day intensive care admission and was discharged to the general medical ward, but ultimately died 19 days after presentation.

[Optimal Laxatives for Oral Colonoscopy Bowel Preparation: from High-volume to Novel Low-volume Solutions].

Optimal bowel preparation is essential for a more accurate, comfortable, and safe colonoscopy. The majority of postcolonoscopy colorectal cancers can be explained by procedural factors, mainly missed polyps or inadequate examination. Therefore the most important goal of optimal bowel preparation is to reduce the incidence of colorectal cancer. Although adequate preparation should be achieved in 85-90% or more of all colonoscopy as a quality indicator, unfortunately 20-30% shows inadequate preparation. Laxatives for oral colonoscopy bowel preparation can be classified into polyethylene glycol (PEG)-electrolyte lavage solution, osmotic laxatives, stimulant laxatives, and divided into high-volume solution (≥3 L) and low-volume solution (<3 L). The updated 2019 European Society of Gastrointestinal Endoscopy (ESGE) guideline is broadly similar to the 2014 American Society for Gastrointestinal Endoscopy (ASGE) recommendations and reaffirms the importance of split-dosing. However, new ESGE guideline, unlike the 2014 ASGE recommendation, suggests the use of high volume or low volume PEG-based regimens as well as that of non-PEG based agents that have been clinically validated for most outpatient scenarios. For effective, safe, and highly adherent bowel preparation, physicians who prescribe and implement colonoscopy should properly know the advantages and limitations, the dosing, and the timing of regimens. Recently many studies have attempted to find the most ideal regimens, and more convenient, effective, and safe regimens have been developed by reducing the dosing volume and improving the taste. The high tolerability and acceptability of the new low-volume regimens suggest us how we should use it to increase the participation of the national colorectal cancer screening program.

[Efficacy and safety of the drug mexidol FORTE 250 as part of sequential therapy in patients with chronic ischemia of the brain]. / Éffektivnost' i bezopasnost' preparata Meksidol FORTE 250 v ramkakh posledovatel'noi terapii u patsientov s khronicheskoi ishemiei mozga.

AIM: To study the efficacy and safety of mexidol dripped intravenously (500 mg once a day) in the form of infusions for 14 days, followed by oral administration of mexidol FORTE 250 at a dose of 250 mg (1 tablet) 3 times a day for 60 days, in treatment of chronic brain ischemia in patients with hypertension and atherosclerosis. MATERIAL AND METHODS: The open observation program included 60 patients with an established diagnosis of chronic brain ischemia confirmed by neuroimaging methods. RESULTS AND CONCLUSION: The results of the study show the high efficacy and safety of sequential therapy (injections followed by tablets of mexidol FORTE 250). The treatment improves emotional and cognitive status, decreases motor disorders and severity of subjective manifestations. High adherence of patients to the therapy is shown.

Efficacy, Tolerability, and Safety of Low-Volume Bowel Preparations for Patients with Inflammatory Bowel Diseases: The French Multicentre CLEAN Study.

BACKGROUND: Standard high-volume polyethylene glycol [PEG] bowel preparations [PEG-4L] are recommended for patients with inflammatory bowel disease [IBD] undergoing colonoscopy. However, low-volume preparations [≤2 L of active volume] are often used in clinical practice. The aim of this study was to evaluate the efficacy, tolerability, and safety of the various bowel preparations for patients with IBD, including low-volume preparations. METHODS: We conducted a French prospective multicentre observational study over a period of 1 month. Patients aged 18-75 years with IBD with an indication of colonoscopy independent of the study were enrolled. The choice of the preparation was left to the investigators, as per their usual protocol. The patients' characteristics, disease, and colonoscopy characteristics were recorded, and they were given self-reported questionnaires. RESULTS: Twenty-five public and private hospitals enrolled 278 patients. Among them, 46 had a disease flare and 41 had bowel stenoses. Bowel preparations for colonoscopy were as follows: 42% received PEG-2L, 29% received sodium picosulfate [Pico], 15% received PEG-4L, and 14% had other preparations. The preparation did not reach the Boston's score efficacy outcome in the PEG-4L group in 51.2% of the patients [p = 0.0011]. The preparation intake was complete for 59.5% in the PEG-4L group, compared with 82.9% in the PEG-2L group and 93.8% in the Pico group [p < 0.0001]. Tolerability, as assessed by the patients' VAS, was significantly better for both Pico and PEG-2L compared with PEG-4L, and better for Pico compared with PEG-2L [p = 0.008; p = 0.0003]. In multivariate analyses, low-volume preparations were independent factors of efficacy and tolerability. Adverse events occurred in 4.3% of the patients. CONCLUSIONS: Preparations with PEG-2L and Pico were equally safe, with better efficacy and tolerability outcomes compared with PEG-4L preparations. The best efficacy/tolerance/safety profile was achieved with the Pico preparation.

Long term treatment with stimulant laxatives - clinical evidence for effectiveness and safety?

OBJECTIVES: Bisacodyl and sodium picosulfate are classified both as stimulant laxatives, approved for short-term treatment of constipation and sold without prescription (OTC). Stimulant laxatives are associated with harmful long-term colonic effects and possible carcinogenic risk - and evidence support that these agents are used for longer periods. We aimed to compile and review the clinical trial evidence describing the effectiveness and safety of long-term treatment (>14 continuous days) with stimulant laxatives. METHODS: The PubMed database was searched for all randomised clinical trials (RCTs) examining the effect of bisacodyl or sodium picosulfate in adult patients diagnosed with constipation. RESULTS: Five RCTs (one open-label and four double-blinded) with intervention periods of four weeks duration were eligible. These included 1008 patients, whereof 26% dropped out. A positive global assessment of efficacy was obtained in 78-99% of the patients treated with bisacodyl or sodium picosulfate. Notably, the same global assessment was obtained in 46-54% of the placebo-treated patients. Compared to placebo, an improvement in stool consistency and a significant increase in number of bowel movements peer week were seen in favor of bisacodyl and sodium picosulfate. However, for pyridostigmine, a significant difference was seen compared to bisacodyl. AEs were generally mild, but frequent (up to 72%) mostly diarrhea and abdominal pain. CONCLUSION: The evidence base does not support use of stimulant laxatives for more than four weeks. Due to the substantial use of stimulant laxatives including sold OTC, longer term RCTs and epidemiological studies investigating effects and safety on the longer term are warranted.

Severe hyponatremia secondary to preparation for colonoscopy with sodium picosulfate/magnesium citrate.

The number of colonoscopies performed in Spain has been progressively increasing in recent years with the program of early detection of colon cancer. The preparation for this test is the key to greater profitability and the choice of the solution to be administered, decisive. The adverse effects that we can observe; usually are mild, but they can entail other more serious ones, like electrolytic imbalances as we present in this case.

[The study of the efficacy and safety of Mexidol and Mexidol Forte 250 in patients with chronic cerebral ischemia]. / Issledovanie éffektivnosti i bezopasnosti primeneniia Meksidola i Meksidola Forte 250 u bol'nykh s khronicheskoi ishemiei mozga.

AIM: To study the efficacy and safety of Mexidol used intravenously (500 mg 1 time per day) for 14 days, followed by the oral administration of Mexidol Forte 250 in a dose of 250 mg 3 times a day for 60 days, in patients with chronic cerebral ischemia (CCI). MATERIAL AND METHODS: The study included 56 patients with CCI due to a combination of hypertension and atherosclerosis. The results of physical examinations (control of blood pressure, heart rate etc.), dynamics of complaints, scores on CGI, MoCa, MFI-20, HRSD, HARS and the Tinetti test were evaluated. RESULTS AND CONCLUSION: The high level of efficacy and safety of intravenous injections of Mexidol followed by the oral administration of Mexidol Forte 250 are demonstrated. This scheme of therapy contributes to a significant decrease in the objective and subjective symptoms of CCI, leads to improvements in the emotional, cognitive and motor spheres.

Comparative safety of bowel cleansers: protocol for a systematic review and network meta-analysis.

INTRODUCTION: The US Food and Drug Administration has withdrawn the bowel cleansing kit HalfLytely (PEG 3500) with 10 mg bisacodyl tablets due to an increased risk of ischaemic colitis compared with the same kit with only 5 mg bisacodyl. This is of interest in Canada given that the bowel cleansing kit Bi-Peglyte (PEG 3500) with 15 mg bisacodyl is currently approved for use. The objective is to assess the comparative safety of various bowel cleansers with or without bisacodyl, with a primary interest inpolyethylene glycol (PEG)-based and sodium-picosulfate-based products. METHODS AND ANALYSIS: Given the existing volume of the literature, the review will be conducted in two stages. Stage 1 will consist of a scoping exercise by searching MEDLINE, Embase and the Cochrane Library (up to 21 November 2017) to identify randomised controlled trials, quasirandomised studies and non-randomised studies in which any bowel cleanser regimens were compared among persons undergoing colonoscopy. The outcomes will be mapped to establish a listing of the studies and their comparisons and outcomes currently available in the literature. From this, a data synthesis plan will be determined. In stage 2, a systematic review with meta-analyses will be pursued, focused on the bowel cleanser comparisons and outcomes of interest identified in stage 1. Two reviewers will screen, extract and quality assess the articles. Outcomes of interest include ischaemic colitis, electrolyte imbalances and their consequences, seizures, bowel perforation and patient tolerability. If sufficient data exist and studies are of sufficient homogeneity, network meta-analyses (NMAs) will be performed. ETHICS AND DISSEMINATION: Ethics approval was not necessary due to study design. Updating the safety profile of bowel cleansers among the generally healthy population undergoing colonoscopy is pertinent given recent approval changes. This will be the first NMA within this population. Policy considerations may be reconsidered to minimise risk during bowel cleanser use. PROSPERO REGISTRATION NUMBER: CRD42018084720.

Split-dose bowel cleansing with picosulphate is safe and better tolerated than 2-l polyethylene glycol solution.

BACKGROUND: In physically less fit patients and patients requiring repeated exams, adequate bowel preparation for colonoscopy remains problematic, particularly because patients need to drink large volumes of unpleasant-tasting fluids. A further concern is potential unwarranted fluid shifts. AIMS: This study aimed to compare the safety and burden of a small-volume sodium picosulphate/magnesium citrate preparation (SPS-MC) with a 2-l ascorbic-acid-enriched polyethylene glycol solution plus bisacodyl pretreatment (PEG-Asc+B). PATIENTS AND METHODS: Patients referred for colonoscopy were randomized to SPS-MC or PEG-Asc+B administered as a split-dose regimen. Patients received advice on the recommended 4-l SPS-MC and 2-l PEG-Asc+B fluid intake. Safety was assessed by blood sampling before and after the preparation and during a 30-day follow-up period. A questionnaire assessed tolerability and perceived burden of the preparation. RESULTS: A total of 341 patients underwent colonoscopy. Blood sampling showed a slight but significant decrease in sodium, chloride and osmolality and increase in magnesium in the SPS-MC group and a decrease in bicarbonate in the PEG-Asc+B group. Hyponatraemia and hypermagnesaemia without clinical signs were observed in 16 (14 SPS-MC) and 13 SPS-MC patients, respectively. Patients reported significantly fewer physical complaints and a significantly higher completion rate with SPS-MC. Patients receiving SPS-MC rated the intake as being easier and better tasting. In the event of a repeat colonoscopy, 59.7% of patients in the PEG-Asc+B and 93.6% of patients in the SPS-MC group would opt for the same preparation again. CONCLUSION: Despite electrolyte shifts, both SPS-MC and PEG-Asc+B appeared clinically safe. From a patient's perspective, a small-volume preparation formula such as SPS-MC is preferred, resulting in fewer physical complaints and greater ease of intake.