A real-world evidence study evaluating consumer experience of Supradyn Recharge or Supradyn Magnesium and Potassium during demanding periods.

Background: Challenging periods and/or mild micronutrient deficiencies may result in a lack of energy and general fatigue, frequently occurring in the general population. Supradyn Recharge and Supradyn Magnesium and Potassium (Mg/K) are multimineral/vitamin supplements formulated to ensure adequate daily intake of micronutrients. We conducted an observational study addressing consumption behaviour, reasons for intake, frequency of intake, and consumer experiences, satisfaction and characteristics under real-life conditions. Methods: This was a retrospective, observational study carried out with two computer-aided web quantitative interviews. Results: A total of 606 respondents (almost equally split between men and women; median age 40 years) completed the questionnaires. The majority indicated having a family, a job and a good level of education; they stated to be long-time and daily users, reporting an average daily intake of 6 days a week. More than 90% of consumers claimed they were satisfied, would use the products again and recommend them; over two-thirds felt the value for money was good. Supradyn Recharge has been mainly used to support lifestyle change and mental resilience, seasonal changes, and post-illness recovery. Supradyn Mg/K has been used to sustain or regain energy levels during hot weather or physical activity and as a support against stress. Users claimed a positive impact on quality of life. Conclusion: Overall, the perception of benefit by consumers was extremely positive as reflected in their consumption behaviour, the majority of whom stated to be long-time users and daily consumers, with an average daily intake of 6 days for both products. These data complement and add up to the results of Supradyn clinical trials.

Evaluation of a 5% dexpanthenol-containing ointment for the treatment of infant irritant diaper dermatitis through the lens of the caregiver-A real-world data observational study.

Background and Aims: Irritant diaper dermatitis (IDD) is very common in infants and usually managed by the caregiver. Dexpanthenol-containing ointment (DCO) is a decades-long established product that has demonstrated efficacy and tolerability in the treatment and prevention of infant IDD in controlled clinical settings. The aim of this study was to evaluate the effectiveness of DCO in the treatment of infant IDD from the perspective of the caregiver by collecting data not explored in clinical trials, such as infant quality of life and the speed of action. Methods: A retrospective observational real-world data (RWD) study was conducted with French adult caregivers who had used a DCO to treat IDD in their infants within the past 6 months and consented to participate to the study completed a web-based survey answering questions regarding the severity of their infants' symptoms (intensity/extent of redness and discomfort, rated using Likert scales) before and after DCO application. The speed of onset of symptom relief and product acceptability were also collected. Results: A total of 500 caregivers of 564 infants completed the survey. Of these, 80% reported that DCO visibly treats IDD. In terms of speed of action, 83% declared that the first signs of symptom relief appeared after 1 day of application and 78% reported full symptom resolution within 2 days of application. Additionally, ≥77% of caregivers agreed that DCO provided overnight relief from the discomfort caused by IDD and reduced sleep disturbance in their children. Finally, 85% of caregivers declared being satisfied with the product overall and considered the product pleasant to use. Conclusion: This evidence from caregivers' experience confirms that DCO can be considered an adequate medication to self-manage IDD episode as it provides rapid relief of the signs and symptoms of inflammation, while by being pleasant to be use.

Vulvovaginal candidiasis: A real-world evidence study of the perceived benefits of Canesten®.

Objectives: Vulvovaginal candidiasis is common in women, causing discomfort and negatively impacting quality of life. Canesten® is an established over-the-counter brand. Its clotrimazole/fluconazole-based products, available in a variety of different formulations, have demonstrated efficacy and safety in the treatment of women with thrush/vaginal yeast infection in randomized trials. This real-world evidence study, conducted in the United Kingdom and Canada, aimed to provide consumer-important information on the benefits of Canesten, collecting retrospective information from consumers about their recent experience with the product. Methods: Eligible participants were female, aged 18-60 years, and had experienced at least one episode of vaginal thrush (United Kingdom)/vaginal yeast infection (Canada) during the previous 6 months for which they had used at least one of the six Canesten products. Participants completed an online questionnaire eliciting information on the speed of onset of symptom relief, impact on quality of life, and product attributes/satisfaction. Results: Over 90% of respondents reported improvements in symptoms and quality of life after starting treatment with a Canesten product. Improvements in symptoms within 4 h of the first time of use were perceived by 42% of consumers; 76%-88% reported symptomatic relief within 1 day. The perceived general speed of onset of symptomatic relief with a Canesten oral product (1-2 days) was slightly longer than that with a Canesten topical/intra-vaginal product (⩽1 day). Most users of Canesten single (90%) and dual product treatments (95%) reported that the products started to work from the first application. Women experiencing both internal and external symptoms of thrush/vaginal yeast infection reported Canesten dual product formulations to provide faster symptomatic relief than single product treatments. Over 90% of respondents were satisfied with their use of a Canesten product. Conclusion: Canesten was found by consumers to offer rapid relief of the symptoms of thrush/vaginal yeast infection with improvements in quality of life. Consumer satisfaction was high.

A real-world evidence study evaluating Geffer effervescent granules for the symptomatic relief of digestive symptoms.

Objectives: Geffer effervescent granules (active ingredients: metoclopramide, dimethicone, and sodium bicarbonate) is an established over-the-counter medication available in Italy for the symptomatic treatment of hyperacidity (pain and/or heartburn) when accompanied by slowing of gastric transit, nausea, aerophagia, and bloating, all symptoms that can occur in functional dyspepsia and can negatively impact individuals' quality of life. The aim of this observational study was to explore the perceived benefits of, and consumer experience with, Geffer effervescent granules used for the symptomatic treatment of digestive disorders suggestive of functional dyspepsia under real-life conditions in Italy. Methods: Adults (aged 35-65 years) experiencing symptoms suggestive of functional dyspepsia/indigestion at least once a month and who had used Geffer effervescent granules within the previous 6 months completed an online questionnaire eliciting information on symptom relief (speed of onset and duration) and quality of life. Results: Geffer effervescent granules provided rapid onset of symptom relief, with 21% of respondents perceiving an effect within 10 min and 88% reporting an improvement in overall symptoms within 30 min. A similarly rapid onset of complete resolution of gastric pain/cramps, acidity, bloating, nausea, and bothersome fullness symptoms was reported by 65%-83% of respondents; 50%-59% of respondents were free from such symptoms for more than 3 h or until the next meal. Most participants (92%) reported that their quality of life improved when taking Geffer effervescent granules to treat hyperacidity symptoms. Overall, 95% of the respondents were satisfied with the effectiveness of Geffer effervescent granules on overall symptom relief. Conclusions: In Italian consumers with digestive disorders likely due to functional dyspepsia, Geffer effervescent granules was associated with rapid, complete, and durable relief of symptoms of gastric pain/cramps, acidity, bloating, nausea, and bothersome fullness; an improvement in quality of life; and a high level of consumer satisfaction.

Inhibitory potency of choline esterase inhibitors on acetylcholine release and choline esterase activity in fresh specimens of human and rat neocortex.

Fresh specimens of human and rat neocortex were used to determine direct and indirect inhibitory potencies of choline esterase inhibitors (ChEIs) on ChE and the release of acetylcholine (ACh), respectively. Km values of ChE in homogenates of rat and human neocortex did not differ significantly, whereas the specific activity of ChE was > times higher in the rat. Butyryl ChE exhibited a higher Km and a lower specific activity than ACh esterase in human neocortex. Inhibition of ChE in rat and human tissue was similar [IC50 (nM; human): donepezil: 14, physostigmine: 22, tacrine: 95, galanthamine: 575, rivastigmine: 9120]. In neocortex slices preincubated with [3H]choline, the electrically evoked release of [3H]ACh was inhibited up to 60% by ChEIs (IC50 (nM, rat): donepezil: 30, physostigmine: 39, tacrine: 302, galanthamine: 646, rivastigmine: >10000). Similar IC50-values were also estimated for ACh release in human neocortex, although the maximal inhibitory effects were much smaller ( approximately 20%). We conclude that in comparison to rats: 1) neocortical ChE concentrations are lower and 2) that ChEIs have weaker indirect (muscarine receptor-mediated) presynaptic inhibitory effects in the human brain. We further suggest that a combination of ChEIs with brain-selective muscarine autoreceptor antagonists might help to improve their clinical efficacy.

Agonist-mediated regulation of presynaptic receptor function during development of rat septal neurons in culture.

Presynaptic receptors modulating the release of acetylcholine (ACh) were studied in fetal septal neurons cultured in a growth medium to which various drugs were added from day 3 in vitro (DIV 3) to DIV 14. The influence of these drugs on the function of the presynaptic muscarinic (M-) autoreceptor was determined at DIV 14 by measuring the inhibitory effect of the M-agonist oxotremorine on the electrically-evoked release of [(3)H]ACh from cultures pre-incubated with [(3)H]choline. The presence of the M-agonists oxotremorine (100 micromol/L) or carbachol (100 micromol/L) from DIV 3 to DIV 14, or from DIV 13 to DIV 14, abolished M-autoreceptor function at DIV 14, whereas the presence of the M-antagonist atropine (10 micromol/L from DIV 3 to DIV 14) during growth left M-autoreceptor function unaltered. Inhibition of ACh esterase by donepezil (1 micromol/L from DIV 3 to DIV 14) weakly decreased M-autoreceptor function at DIV 14; inhibition of neuronal firing by 0.1 tetrodotoxin (0.1 micromol/L from DIV 3 to DIV 14) did not tend to affect M-autoreceptor function at DIV 14. Co-cultivation of fetal septal and raphe neurons for 2 weeks yielded cell cultures containing both vesicular ACh transporter- and tryptophan hydroxylase-immunopositive cells. From these cultures, the release of both [(3)H]ACh and [(3)H]5-HT could be induced by electrical field stimulation. In co-cultured neurons versus septal-only ones the inhibitory effect of oxotremorine on the evoked release of [(3)H]ACh appeared almost normal, whereas that of the selective 5-HT(1B) agonist 3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrollo[3,2-b]pyrid-5-one (CP-93,129) was completely abolished. The effects of CP-93,129 were also absent on DIV 14 in septal mono-cultures grown in the presence of CP-93,129 (10 micromol/L) from DIV 3 to DIV 14. It is therefore concluded that the regulation of presynaptic receptor function strongly depends on the concentrations of endogenous transmitters in the neuronal environment.

Modulation of electrically evoked serotonin release in cultured rat raphe neurons.

Electrically evoked release of serotonin (5-HT) and its modulation via 5-HT autoreceptors and alpha(2)-heteroreceptors was studied in primary cell cultures prepared from the embryonic (ED 15) rat mesencephalic brain region comprising the raphe nuclei. Cultures were grown for up to 3 weeks on circular glass coverslips. They developed a dense network of non-neuronal and neuronal cells, some of which were positive for tryptophan hydroxylase. To measure 5-HT release, the cultures were pre-incubated with [(3)H]5-HT (in the presence of the selective noradrenaline reuptake inhibitor oxaprotiline [1 micromol/L]), superfused with modified Krebs-Henseleit medium containing 6-nitroqipazine [1 micromol/L] and electrically stimulated using two conditions. Condition A: 360 pulses, 3 Hz, 0.5 ms, 90 mA, or condition B: 4 pulses 100 Hz, 0.5 ms, 90 mA (a condition which diminishes interactions with endogenously released transmitters during ongoing stimulation). After only 1 week in culture, the electrically evoked overflow of [(3)H] was Ca(2+) dependent and tetrodotoxin sensitive, suggesting an action-potential-induced exocytotic release of 5-HT. Using stimulation condition A in cultures grown for 2 weeks, both basal and evoked 5-HT release were strongly enhanced by methiotepine (1 micromol/L) but unaffected by the 5-HT(1B) autoreceptor agonist CP-93, 129 (1 micromol/L) and the alpha(2)-adrenoceptor agonist UK-14, 304 (1 micromol/L). Conversely, using stimulation condition B, not only CP-93, 129 (IC(50) 8.1 +/- 1.4 nmol/L) and UK-14, 304 (IC(50) 14.9 +/- 1.6 nmol/L) had inhibitory effects on cells grown for 2 weeks, but also the 5-HT(1A) agonist 8-hydroxy-2-(di-n-propylamino)tetralin. In conclusion, we describe for the first time electrically evoked release of 5-HT from primary cultures of fetal raphe cells and its modulation via 5-HT(1B) and 5-HT(1A) auto- and alpha(2)-heteroreceptors. Such cultured raphe cells may represent a suitable model to study expression and development of presynaptic receptors on serotonergic neurons in-vitro.