Although N-acetyl-cysteine (NAC) has long been used for the treatment of acetaminophen poisoning/overdose, the optimal NAC dosing regimen for varying patterns or severity of the poisoning/overdose is ...still unknown.
Relevant literature was searched for in the MEDLINE (from 1964 until August 31
, 2022), SCOPUS (from 2004 until August 31
, 2022) and GOOGLE SCHOLAR (from 2004 until August 31
, 2022) databases, without restriction in terms of publication date. The inclusion criteria were: original clinical studies reporting results, and studies investigating efficacy and safety of NAC dosing regimens in case(s) of overdose or poisoning with acetaminophen.
For a more effective treatment of acetaminophen poisoning in the future, it will be crucial to advance the technology of measuring acetaminophen, its metabolites and NAC in the serum, preferably with the point-of-care technique, so that in real time it can be continuously assessed whether it is necessary to administer NAC, and further to increase the dose of NAC and extend the duration of its administration, or not.
Serious hematological adverse drug reactions (HADRs) may lead to or prolong hospitalization and even cause death. The aim of this study was to determine the regulatory factors associated with HADRs ...caused by drugs that were authorized up to July 2023 by the European Medicines Agency (EMA) and to evaluate the frequency of HADRs. Using a cross-sectional approach, the type and frequency of HADRs were collected from the Summaries of Product Characteristics of Drugs Authorized by the EMA and analyzed within proprietary, nonproprietary, and biosimilar/biological frameworks. Multivariate statistical analysis was used to investigate the associations of generic status, biosimilar status, conditional approval, exceptional circumstances, accelerated assessment, orphan drug status, years on the market, administration route, and inclusion on the Essential Medicines List (EML) with HADRs. In total, 54.78% of proprietary drugs were associated with HADRs at any frequency, while anemia, leucopenia, and thrombocytopenia were observed in approximately 36% of the patients. The predictors of any HADR, anemia, and thrombocytopenia of any frequency are generic status, biosimilar status, and inclusion on the EML, while the only protective factor is the administration route. Biosimilars and their originator biologicals have similar frequencies of HADRs; the only exception is somatropin. Knowledge of the regulatory factors associated with HADRs could help clinicians address monitoring issues when new drugs are introduced for the treatment of patients.
GABA A receptors are ubiquitous in the central nervous system and there is a huge diversity of receptor subtypes in almost all regions of the brain. However, the expression of GABA A receptor ...subtypes is altered in both the gray and white matter of patients with focal epilepsy. Although there is a number of anticonvulsants with marketing authorization for the treatment of focal epilepsy which act through GABA A receptors, potentiating the inhibitory effects of GABA, it is necessary to develop more potent and more specific GABAergic anticonvulsants that are effective in drug-resistant patients with focal epilepsy. There are three orthosteric and at least seven allosteric agonist binding sites at the GABA A receptor. In experimental and clinical studies, full agonists of GABA A receptors showed a tendency to cause desensitization of the receptors, tolerance, and physical dependence; therefore, partial orthosteric agonists and positive allosteric modulators of GABA A receptors were further developed. Preclinical studies demonstrated the anticonvulsant efficacy of positive allosteric modulators with selective action on GABA A receptors with α
/α
subunits, but only a handful of them were further tested in clinical trials. The best results were obtained for clobazam (already marketed), ganaxolone (in phase III trials), CVL-865 (in phase II trials), and padsevonil (in phase III trials). Several compounds with more selective action on GABA A receptors, perhaps only in certain brain regions, have the potential to become effective drugs against specific subtypes of focal-onset epilepsy. However, their development needs time, and in the near future we can expect only one or two new GABA A agonists to obtain marketing authorization for focal epilepsy, an advance that would be of use for just a fraction of patients with drug-resistant epilepsy.
Abstract
Although being very effective in the treatment of diabetes and a few other conditions, metformin (MTF) cannot be tolerated by many patients due to gastrointestinal (GI) complaints. A number ...of risk factors for intolerance were identified, but many are still controversial or uninvestigated. The aim of this study was to further investigate possible risk factors for the occurrence of GI complaints in patients on MTF therapy. A cross-sectional design was used for this multicentric study on adult patients visiting 50 community pharmacies in Montenegro. The patients were surveyed by semi-structured questionnaire after a service of a pharmacist was delivered, and their drugs dispensed. Uni- and multi-variate regression methods were used for processing the data.
In total 330 patients participated in the study. A higher body mass index (OR = 1.113,
p
= 0.003), living at a higher altitude (OR = 1.725,
p
= 0.000), anaemia (OR = 4.221,
p
= 0.008), and intestinal infection in the last 3 months (OR = 2.801,
p
= 0.006) increased the risk of GI complaints in patients on MTF therapy, while the use of statins was protective (OR = 0.204,
p
= 0.016). Each case of MTF intolerance should be carefully investigated for risk and protective factors, which could be potentially eliminated or augmented, respectively, and MTF withdrawal avoided.
Background
Although the costs of treating inflammatory bowel disease (IBD) in developed countries are well established, they remain largely unknown in countries with recent histories of ...socio-economic transition including Serbia.
Objective
To estimate the costs of treatment including the resources used by patients with IBD in Serbia from a societal perspective. This includes both Crohn’s disease and ulcerative colitis.
Methods
This cost-of-illness study was conducted to identify direct, indirect and out-of-pocket costs of treating patients with IBD in Serbia. Patients with IBD (
n
= 112) completed a semi-structured questionnaire with data concerning their utilisation of heath-care resources and illness-related expenditures. All costs were calculated in Republic of Serbia dinars (RSD) at a 1-year level (2014) and subsequently converted to Euros. Median values and ranges were reported to avoid potential distortions associated with mean costs.
Results
Median total direct costs and total indirect costs per patient per year in patients with Crohn’s disease were 192,614.32RSD (€1602.97) and 28,014.00RSD (€233.13) and 142,267.15RSD (€1183.97) and 21,436.00RSD (€178.39), respectively, in patients with ulcerative colitis. In both groups, the greatest component of direct costs was hospitalisation.
Conclusions
Costs of IBD in Serbia are lower than in more developed countries for two reasons. These include the fact that expensive biological therapy is currently under-utilised in Serbia and prices of health services are largely controlled by the State at a low level. The under-utilisation of biologicals may change with the advent of biosimilars at increasingly lower prices.
► We investigated chemical composition of acetone extracts of two lichens species. ► Antioxidant, antimicrobial, and anticancer activities of extracts were tested. ► Antioxidant, antimicrobial, and ...anticancer activities of metabolites were tested. ► Tested lichen extracts and compounds demonstrated strong biological effects. ► Lichens may be used as natural antioxidant, antimicrobial and anticancer agents.
The aim of this study is to investigate chemical composition of acetone extracts of the lichens Evernia prunastri and Pseudoevernia furfuraceae and in vitro antioxidant, antimicrobial, and anticancer activities of these extracts and some their major metabolites. HPLC–UV method was used for identification of secondary metabolites. Antioxidant activity was evaluated by free radical scavenging, superoxide anion radical scavenging, reducing power and determination of total phenolic compounds. As a result of the study physodic acid had largest antioxidant activities. Total content of phenol in extracts was determined as pyrocatechol equivalent. The antimicrobial activity was estimated by determination of the minimal inhibitory concentration by the broth microdilution method. The most active was also physodic acid. Anticancer activity was tested against FemX (human melanoma) and LS174 (human colon carcinoma) cell lines using MTT method.
Refractory status epilepticus (RSE) is a diagnosis that can be made when tonic-clonic status epilepticus (SE) and focal SE cannot be stopped by at least two anti-seizure medications after 30 and 60 ...minutes, respectively, from the time of commencement. It could result in mortality, loss of functionality, neurological deficiency, and other serious short- and long-term effects.
This narrative review covers original clinical studies of any design and case series investigating long-term outcomes of RSE recorded after at least a year from the SE onset.
The future of a patient with RSE rests mostly on the long-term effects of this severe pathological condition, which may be accompanied with systemic complications like hyperthermia, hyperkalemia, acidosis, and/or stress cardiomyopathy. Younger patients with less severe RSE of shorter duration, particularly of the convulsive kind, are reported to have better long-term outcomes. Previous studies on the factors influencing the long-term outcomes of RSE, however, did not link the outcomes to treatment options for the condition. Such circumstances currently prevent making any definitive recommendations on the treatment of RSE until future research with adequate statistical power is completed.
This observational clinical study was composed of two substudies: a non-comparative one (
= 166), testing only lysozyme-based compounds (LBCs), and a comparative substudy (
= 275), testing both LBCs ...and bicarbonate-based local compounds (BBCs) on the healing of oral mucositis during radio- or chemotherapy. The density of ulcerations has decreased significantly after the treatment with lysozyme in both substudies. The density of ulcerations in the radiotherapy group was lower in patients treated with LBCs compared to patients treated with BBCs (
< 0.001). In the chemotherapy group, reduction of ulceration density was similar with both LBCs and BBCs. The LBCs reduced pain intensity during the intake of solid food and speech more than BBCs in both patient cohorts (
< 0.05). In the radiotherapy cohort, pain intensity when consuming liquid foods was reduced more with LBCs than with BBCs (
< 0.05). No adverse events were recorded. This study demonstrates the advantages of treating oral mucositis during radiotherapy or chemo-therapy with LBCs.
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