Abstract
Aims
Two post-authorisation studies assessed the safety and persistence of patients’ use of nalmefene.
Methods
The START study (EUPAS5678) was a non-interventional, multi-country, ...prospective, 18-month (8 follow-up visits) cohort study including outpatients initiating nalmefene for the first time. The multi-database retrospective cohort study (MDRC, EUPAS14083) included baseline and follow-up data from German, Swedish and UK healthcare databases. Both studies permitted ‘all comers’ without explicit exclusion criteria; predefined subgroups of interest included the elderly (≥65 years) as well as patients with significant psychiatric and/or somatic comorbidities.
Results
START study: Overall, the mean duration of nalmefene treatment was 10.3 ± 7.3 months (N = 1348), with 49.0% of patients treated for ≥1 year; frequent reasons for treatment discontinuation were ‘goal reached’ and ‘drug cost’. The most frequently reported adverse drug reactions (ADRs) were nausea (4.7%), dizziness (3.2%) and insomnia (2.0%). ADR rates appeared higher in the elderly subpopulation (18.6% reported ≥1 ADR vs. 12.0% in the total population) but were not higher in the other predefined subgroups.
MDRC study: The database follow-up analysis followed 2892 patients over 18 months for whom the duration of nalmefene treatment was between 2 and 3 months and <5% of patients used nalmefene for ≥1 year.
Conclusions
Despite the inclusion of a wider patient population (e.g. elderly patients and those with relevant co-morbidities), the safety and tolerability profile of nalmefene given in routine practice was consistent with previous clinical studies. The differing rates of persistence beyond 1 year likely reflect the different methodologies and highlight the relevance of psychosocial support at follow-up visits.
Short Summary: Two studies were used to evaluate the safety and persistence of nalmefene in the routine management of alcohol dependence in Europe as part of the overall risk management plan. Although adverse events appeared more common in over 65-year olds, there were no major differences in safety outcomes between the total population, and those with psychiatric and somatic comorbidities or those with a history of seizures. Findings were in line with those from previous clinical studies. The differing rates of persistence beyond 1 year (49% in the prospective study and < 5% in the multi-database retrospective cohort study) likely reflect the different study methodologies and serve to highlight the relevance of follow-up support.
Biodiesel represents a renewable alternative to conventional diesel, offering comparable potential. This paper delves into the production of biodiesel from non-edible oil seeds, emphasizing ...kernel-based feedstocks for their sustainable qualities. We discuss the critical stages of kernel separation and degumming, offering an in-depth examination of seed distribution, attributes, pretreatment, and oil extraction methodologies. Additionally, the paper considers the status of life cycle assessment (LCA) associated with biodiesel. Furthermore, it outlines the necessary steps toward sustainable biodiesel production and underscores the importance of integrating a sustainable circular bioeconomy in biodiesel synthesis.
The human gut microbiome regulates brain function through the microbiome-gut-brain axis and is implicated in several neuropsychiatric disorders. However, the relationship between the gut microbiome ...and the pathogenesis of schizophrenia (SCZ) is poorly defined, and very few studies have examined the effect of antipsychotic treatment response. We aim to study the differences in the gut microbiota among drug-naïve (DN SCZ) and risperidone-treated SCZ patients (RISP SCZ), compared to healthy controls (HCs). We recruited a total of 60 participants, from the clinical services of a large neuropsychiatric hospital, which included DN SCZ, RISP SCZ and HCs (n = 20 each). Fecal samples were analyzed using 16s rRNA sequencing in this cross-sectional study. No significant differences were found in taxa richness (alpha diversity) but microbial composition differed between SCZ patients (both DN and RISP) and HCs (PERMANOVA, p = 0.02). Linear Discriminant Analysis Effect Size (LEfSe) and Random Forest model identified the top six genera, which significantly differed in abundance between the study groups. A specific genus-level microbial panel of Ruminococcus, UCG005, Clostridium_sensu_stricto_1 and Bifidobacterium could discriminate SCZ patients from HCs with an area under the curve (AUC) of 0.79, HCs vs DN SCZ (AUC: 0.68), HCs vs RISP SCZ (AUC: 0.93) and DN SCZ vs RISP SCZ (AUC: 0.87). Our study identified distinct microbial signatures that could aid in the differentiation of DN SCZ, RISP SCZ, and HCs. Our findings contribute to a better understanding of the role of the gut microbiome in SCZ pathophysiology and suggest potential targeted interventions.
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Asian Indians have an increased susceptibility to type 2 diabetes and premature coronary artery disease. Nuts, like almonds, are rich in unsaturated fat and micronutrients with known health benefits.
...This study aimed to assess the efficacy of almonds for reduction of insulin resistance and improving lipid profile in overweight Asian Indian adults.
This parallel-arm, randomized, controlled trial was conducted in Chennai, India on 400 participants aged 25-65 years with a body mass index ≥ 23 kg/m
. The intervention group received 43 g of almonds/day for 12 weeks, while the control group was advised to consume a customary diet but to avoid nuts. Anthropometric, clinical, and dietary data were assessed at periodic intervals. Glucose tolerance, serum insulin, glycated hemoglobin, C-peptide and lipid profile were assessed at baseline and end of the study. Insulin resistance (homeostasis assessment model-HOMA IR) and oral insulin disposition index (DIo) were calculated.
A total of 352 participants completed the study. Significant improvement was seen in DIo mean (95% CI) = + 0.7 mmol/L (0.1, 1.3);
= 0.03, HOMA IR (-0.4 (-0.7, -0.04;
= 0.03) and total cholesterol (-5.4 mg/dl (-10.2, -0.6);
= 0.03) in the intervention group compared to the control group. Incremental area under the curve (IAUC) and mean amplitude of glycemic excursion (MAGE) assessed using continuous glucose monitoring systems were also significantly lower in the intervention group. Dietary 24-h recalls showed a higher significant reduction in carbohydrate and increase in mono unsaturated fatty acid (MUFA) and polyunsaturated fatty acids (PUFA) intake in the intervention group compared to the control group.
Daily consumption of almonds increased the intake of MUFA with decrease in carbohydrate calories and decreases insulin resistance, improves insulin sensitivity and lowers serum cholesterol in Asian Indians with overweight/obesity. These effects in the long run could aid in reducing the risk of diabetes and other cardiometabolic disease.
We focus on automatically finding similar documents using coherent chunks. The similarity between the documents is determined by identifying the coherent chunks present in them. We apply linguistic ...rules in identifying the coherent chunks and uses Vector Space Model (VSM) in determining the similarity among documents. We have taken patent documents from USPTO for this work. This method of using coherent chunks for identifying similar documents has shown encouraging results.
Electrochemotherapy is an effective palliative way of treating inoperable chemo-resistant cancers. It is a therapeutic technique for treating tumors with nonpermeant drugs using electroporation of ...cells. The cells are electroporated to form temporary hydrophilic pores. The various parameters which affect the electroporation efficacy are, the voltage (electric field intensity), pulse length, number of pulses, pulse interval and the electrode. The electrode provides a contact between the high voltage pulse generator and the patient, and as such it plays a vital role in the treatment outcome. In general, needle array electrodes are used in many cases, including treating of deep seated tumors. The electric field distribution varies according to the electrode design. This paper explores the effectiveness of a pentagonal array electrode with a centre electrode for obtaining uniform electric field distribution in the treated area. This model is symmetrical in which surrounding electrodes are displaced by 4 mm from the centre electrode. The diameter of the needle is 1 mm. The electric field simulations were implemented in 2D in ANSYS 13.0. The electric field considered for the analysis is 1200 V/cm, same as what is currently used in the clinics. The results indicate that the electric field distribution is uniform at a value of 1200 V/cm.
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