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Chronic cough is a common disorder lasting more than 8 weeks and affecting all age groups. The evidence supporting the role of neutrophils in chronic cough pathology is based on many patients with chronic cough developing airway neutrophilia. How neutrophils influence the development of chronic cough is unknown. However, they are likely involved in multiple aspects of cough etiology, including promoting airway inflammation, airway remodeling, hyper-responsiveness, local neurogenic inflammation, and other possible mechanisms. Neutrophilic airway inflammation is also associated with refractory cough, poor control of underlying diseases (e.g., asthma), and insensitivity to cough suppressant therapy. The potential for targeting neutrophils in chronic cough needs exploration, including developing new drugs targeting one or more neutrophil-mediated pathways or altering the neutrophil phenotype to alleviate chronic cough. How the airway microbiome differs, plays a role, and interacts with neutrophils in different cough etiologies is poorly understood. Future studies should focus on understanding the relationship between the airway microbiome and neutrophils. [ABSTRACT FROM AUTHOR]

Gefapixant (MK‐7264, RO4926219, AF‐219) is a first‐in‐class P2X3 antagonists being developed to treat refractory or unexplained chronic cough. The initial single‐ and multiple‐dose safety, tolerability, and pharmacokinetics of gefapixant at doses ranging from 7.5 to 1800 mg were assessed in four clinical trials. Following single‐dose administration of 10‐450 mg, the pharmacokinetic (PK) profile of gefapixant in plasma and urine demonstrated low inter‐subject variability and a dose‐proportional exposure. Following administration of multiple doses twice daily, the plasma exposures were dose‐proportional at doses ranging from 7.5 to 50 mg and less than dose‐proportional at doses ranging from 100 to 1800 mg. The time to mean peak drug concentration ranged from 2 to 3 h post‐dose, and steady state was achieved by 7 days after dosing, with an accumulation ratio of approximately 2, comparing data from day 1 to steady state. The mean apparent terminal half‐life ranged from 8.2 to 9.6 h. Gefapixant was primarily excreted unmodified in urine. Gefapixant was well tolerated following single‐dose administration up to 1800 mg and multiple doses up to 1800 mg twice daily; there were no serious adverse events (AEs) reported. The most common AE reported was dysgeusia. The PK profile supports a twice‐daily dosing regimen. [ABSTRACT FROM AUTHOR]

Background: Community pharmacy-delivered interventions for smoking cessation are effective. The impact of behavioural interventions on short-term health benefits remains unclear. Objective: We aimed to evaluate a community pharmacy-delivered motivational interview for smoking cessation with characterization of the population that can be reached and assessment of the association between the motivation to quit smoking and short-term health benefits. Method: Demographics of smokers approached during a Flemish community pharmacy-delivered encouragement for smoking cessation in the months May-June 2021, their motivation to quit and dispensing records were retrieved from the pharmacy database. The use of pharmacotherapeutic smoking cessation aids and inhalers, cough medicines, antibiotics and oral corticosteroids (proxies for short-term health benefits) was evaluated 90 and 180 days after the interview. Data were analysed using the Mann-Whitney U test, χ² test and binary logistic regression analysis. Results: Community pharmacists provided a brief motivational interview to a broad population (n=300), including young persons and persons without chronic medication use. Two out of three were motivated to quit (67.7%) and a third (33.0%) purchased a smoking cessation aid on the index date (36.7% after 90 and 39.3% after 180 days). Smokers motivated to quit and purchasing a smoking cessation aid on the index date, had a significantly lower use of cough (OR = 0.37; p = 0.032) and inhaler medication (OR = 0.37; p = 0.009) after 90 days than those not motivated to quit. Effects were less pronounced after 180 days but still statistically significant for lower inhaler use (OR = 0.46; p = 0.031). Conclusion: By implementing a brief pharmaceutical counselling for smoking cessation in Belgian community pharmacies, a broad range of smokers can be reached, motivated to quit and triggered to start smoking cessation aids. A motivation to quit is associated with suggestive short-term health benefits. [ABSTRACT FROM AUTHOR]

Introduction: Noscapine is a commonly used cough suppressant, with ongoing research on its anti-inflammatory and anti-tumor properties. The drug has a pronounced pharmacokinetic variability. Objective: This evaluation aims to describe the pharmacokinetics of noscapine using a semi-mechanistic population pharmacokinetic model and to identify covariates that could explain inter-individual pharmacokinetic variability. Methods: Forty-eight healthy volunteers (30 men and 18 women, mean age 33 years) were enrolled in a randomized, two-period, two-stage, crossover bioequivalence study of noscapine in two different liquid formulations. Noscapine plasma concentrations following oral administration of noscapine 50 mg were evaluated by a non-compartmental analysis and by a population pharmacokinetic model separately. Results: Compared to the reference formulation, the test formulation exhibited ratios (with 94.12% confidence intervals) of 0.784 (0.662–0.929) and 0.827 (0.762–0.925) for peak plasma concentrations and area under the plasma concentration–time curve, respectively. Significant differences in p values (< 0.01) were both observed when comparing peak plasma concentrations and area under the plasma concentration–time curve between CYP2C9 genotype-predicted phenotypes. A three-compartmental model with zero-order absorption and first-order elimination process best described the plasma data. The introduction of a liver compartment was able to describe the profound first-pass effect of noscapine. Total body weight and the CYP2C9 genotype-predicted phenotype were both identified as significant covariates on apparent clearance, which was estimated as 958 ± 548 L/h for extensive metabolizers (CYP2C9*1/*1 and *1/*9), 531 ± 304 L/h for intermediate metabolizers with an activity score of 1.5 (CYP2C9*1/*2), and 343 ± 197 L/h for poor metabolizers and intermediate metabolizers with an activity score of 1.0 (CYP2C9*1/*3, *2/*3, and*3/*3). Conclusion: The current work is expected to facilitate the future pharmacokinetic/pharmacodynamic development of noscapine. This study was registered prior to starting at "Deutsches Register Klinischer Studien" under registration no. DRKS00017760. [ABSTRACT FROM AUTHOR]

Levodropropizine, a nonopioid antitussive agent, is being increasingly used in clinical practice with the development of several formulations for symptomatic relief of acute and chronic bronchitis. However, scientific and quantitative population pharmacokinetic analyses of levodropropizine are lacking. Moreover, no integrated quantitative comparison has been performed between formulations. This study quantitatively evaluated and predicted pharmacokinetic properties of formulations through population pharmacokinetic model–based comparisons of commercially available formulations. Plasma concentration profile results from bioequivalence studies of 60-mg immediate release (IR) levodropropizine tablets in 40 healthy Korean males were used as population pharmacokinetic modeling data. For interindividual variability in levodropropizine pharmacokinetics, body surface area was identified as an effective covariate that was positively correlated with peripheral compartment distribution volume. Population pharmacokinetic model for IR tablets well-described the levodropropizine syrup and capsule datasets, suggesting no significant differences in pharmacokinetics among IR tablets, syrups, and capsules of levodropropizine. In contrast, pharmacokinetic profiles differed between 90-mg controlled release (CR) and IR levodropropizine tablets; however, separate parameter estimation was possible by applying the same model structure. In terms of pharmacokinetics, twice-daily regimen of 90-mg CR tablets was equivalent to thrice-daily regimen of 60-mg IR tablets. However, at steady-state, interindividual plasma concentration variability within population was reduced by approximately 36.71–83.18%. For levodropropizine CR tablets, a high-fat diet significantly delayed gastrointestinal absorption but maintained overall plasma exposure equivalent. This study provides useful quantitative judgment data for precision medicine of levodropropizine and can be helpful in predicting the pharmacokinetics of levodropropizine based on commercialized formulation switching. [ABSTRACT FROM AUTHOR]

Cough is a common symptom of several respiratory diseases. However, frequent coughing from acute to chronic often causes great pain to patients. It may turn into cough variant asthma, which seriously affects people's quality of life. For cough treatment, it is dominated by over-the-counter antitussive drugs, such as asmeton, but most currently available antitussive drugs have serious side effects. Thus, there is a great need for the development of new drugs with potent cough suppressant. BALB/c mice were used to construct mice model with cough to investigate the pharmacological effects of pectolinarigenin (PEC). Hematoxylin-eosin and Masson staining were used to assess lung injury and airway remodeling, and ELISA was used to assess the level of inflammatory factor release. In addition, inflammatory cell counts were measured to assess airway inflammation. Airway hyperresponsiveness assay was used to assess respiratory resistance in mice. Finally, we used Western blotting to explore the potential mechanisms of PEC. We found that PEC could alleviate lung tissue injury and reduce the release of inflammatory factors, inhibit of cough frequency and airway wall collagen deposition in mice model with cough. Meanwhile, PEC inhibited the Ras/ERK/c-Fos pathway to exhibit antitussive effect. Therefore, PEC may be a potential drug for cough suppression. [ABSTRACT FROM AUTHOR]

Breast cancer is the second leading contributor to the age-standardized mortality rate, for both sexes and all ages worldwide. In Europe and the United States, it is the second leading cause of mortality, with an incidence rate of about 2.6 million cases per year. Noscapine, a well-known alkaloid used as a cough suppressant, demonstrated anti-tumor effects by triggering apoptosis in various cancer cell lines and has the potential to become another ally against breast, ovarian, colon, and gastric cancer, among other types of malignancy. Apoptosis plays a crucial role in the treatment of cancer. Noscapine affected BAX, CASP8, CASP9, NFKBIA, and RELA gene and protein expression in the MCF-7 and MDA-MB-231 cell lines. Gene expression was higher in tumor than in normal tissue, including the BAX expression levels in lung, ovary, endometrium, colon, stomach, and glioblastoma patients; BCL2L1 expression in endometrium, colon, and stomach patients; CASP8 gene expression levels in lung, endometrium, colon, stomach, and glioblastoma patients; RELA in colon, stomach, and glioblastoma patients; and NFKBIA in glioblastoma patients. It can be concluded that noscapine affected genes and proteins related to apoptosis in cancer cell lines and several types of cancer patients. [ABSTRACT FROM AUTHOR]

Background: Fritillariae Cirrhosae Bulbus is an antitussive and expectorant Chinese medicinal material derived from the dried bulbs of six Fritillaria species. In the 2015 edition of the Chinese Pharmacopoeia, the polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) is the officially listed method for their authenfication. Specifically, the ~ 300-bp ITS1 amplicon of only Fritillariae Cirrhosae Bulbus but not other Fritillaria species can be cleaved into two smaller fragments with restriction enzyme SmaI. Considering repeated reported cases of incomplete digestion of ITS1 amplicon, this study aims to investigate the possibility of heterogeneous ITS1 sequences contained in the Fritillariae Cirrhosae Bulbus. Methods: In this study, ITS1 amplicons of Fritillaria Cirrhosae Bulbus and four other Fritillaria species were sequenced on Illumina platform. We utilised high-throughout amplicon sequencing to determine ITS1 haplotypes and their frequencies in Fritillaria genomes. Results: Our results showed that all six botanical sources of Fritillariae Cirrhosae Bulbus indeed possess ITS1 haplotypes with no SmaI restriction site, and the average percentages of ITS1 reads containing SmaI restriction site ranged from 63.60% to 91.81%. Conclusion: Our findings suggest that the incomplete digestion in PCR–RFLP analysis of Fritillariae Cirrhosae Bulbus is caused by the presence of ITS1 haplotypes without SmaI restriction site due to intragenomic heterogeneity. [ABSTRACT FROM AUTHOR]

Background: We investigated the differences in the characteristics and prognoses between the sexes of patients with chronic cough who were prescribed antitussive agents, using a Korean population-based database. Methods: Claims data from South Korea's Health Insurance Review and Assessment (HIRA) service were analyzed. This retrospective observational cohort study considered chronic cough patients aged 18 years and older who were consistently prescribed antitussive agents for more than 2 months between 1 January 2017 and 30 June 2019. Results: Among the 207,989 patients treated for chronic cough, the prevalence of unexplained cough was higher in women (men: 6.2% vs. women: 9.7%) and the prevalence of persistent cough was higher in men (men: 16.8% vs. women: 14.3%). The gap in the proportion of COPD, lung cancer, ILD, GERD, and TB between women and men were largest around the age range of 60–70 years. With the exception of those in their 60s and 70s, women were more likely to have chronic cough and persistent cough than men. Women were more likely to discontinue medication after treatment completion than men. Only 53.9% of patients discontinued cough medication for more than 6 months after treatment completion. Within 12 and 18 months, respectively, 8.9% and 11.9% of them revisited the hospital for chronic cough. Via Cox regression analysis, an age in the 60s or 70s and explained cough were independently associated with a higher risk of revisit for treatment. Conclusions: Among patients treated for chronic cough, there were distinct differences in cough characteristics and prescription status between men and women. Our data highlight the need for a new personalized treatment approach to chronic cough, taking into account the gender, age, and underlying diseases of patients. Further research is needed to determine whether appropriate underlying disease control and gender-specific treatment are effective for managing chronic cough. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) pandemic occurred in Hong Kong for more than two years. This article conducted a cross-sectional study for participants to investigate the behavioral prevention, treatment, and rehabilitation of using Western medicines or herbal products for COVID-19 in Hong Kong. A questionnaire was designed and performed over 2 weeks from 1 May to 15 May 2022. It consisted of five parts with around 20 questions conducted including sociodemographic information, prevention, treatment, rehabilitation of COVID-19, and also the sources of information. The pattern usage of Chinese or Western medicines for COVID-19 was studied after data collection. 318 people participated in this survey, and only 311 were qualified. The sociodemographic information, e.g., personal educational level, and behavior for the prevention of COVID-19, which included wearing masks (98.7%), using alcohol hand sanitizer (83.0%), washing hands frequently (82.4%), avoiding crowds (53.1%), and staying home more often (50.6%). Western medicines, such as antipyretic drugs, antitussive drugs, and pain reliever drugs, whilst Chinese medicines, such as Lianhua Qingwen Jiaonang, Huoxiang Zhengqi San or Wan, and Nin Jiom Pei Pa Koa, were most commonly used in the treatment and rehabilitation periods of COVID-19. Herbal products, including lemon, honey, ginger, and herbal tea, were used as a daily diet to fight against COVID-19. Based on the result findings, Chinese medicines or herbal products were used during the COVID-19 pandemic, but most of the participants used an unknown Chinese medicine practitioner's prescription and self-administered Chinese medicine. The pattern of Chinese medicines and Western medicines' usage in the prevention, treatment, and rehabilitation of COVID-19 was also investigated; this showed a statistically significant association between the variables according to gender, age, and Chinese or Western medicines for further investigation. [ABSTRACT FROM AUTHOR]

The paper reviews herbal medicinal products used in infectious diseases of the respiratory tract. Due to the multidirectional effects of the biological action of the contained herbal active substances (anti-inflammatory, antioxidant, antimicrobial, antitussive, diuretic and others), they have the properties that alleviate the severity of symptoms, reduce their frequency and, consequently, shorten the duration of the disease, as well as reduce the risk of complications. Some of them have additional immunomodulatory properties, supporting natural immune mechanisms. [ABSTRACT FROM AUTHOR]

Amygdalin (AMY), a plant secondary metabolite containing nitrile, is a major component of the seeds of Rosaceae family plants. It is known that this compound has many pharmacological activities such as cancer prevention, antipyretic, and cough suppressant. In this study, the genotoxic and modulatory effects of amygdalin were assessed by chromosomal aberration (CA), sister chromatid exchange (SCE), and cytokinesis‐block micronucleus assay (CBMN) assays using human peripheral lymphocytes (HPLs) in the absence and presence of metabolic activator (S9 mix). Lymphocytes were exposed to various concentrations of amygdalin (0.86, 1.72, 3.43, 6.86, and 13.75 μg/mL) alone and in combination with mitomycin‐C (MMC, 0.20 μg/mL) or cyclophosphamide (CP, 12 μg/mL). The mitotic index (MI), replication index (RI), cytokinesis‐block proliferation index (CBPI), and cytostasis were also evaluated to determine cytotoxicity. Amygdalin alone did not exhibit genotoxic and cytotoxic effects at all the tested concentrations both in the absence and presence of the S9 mix. In contrast, amygdalin significantly reduced the frequencies of CA (especially at 48 h treatments), SCE, and MN (except 0.86 μg/mL in pre‐ and simultaneous treatment) induced by MMC in all the tested concentrations and treatment protocols. It has also considerably decreased CP‐induced CA and SCE frequencies at all the concentrations (except 0.86 μg/mL) in simultaneous treatment. This study demonstrated that amygdalin alone was not genotoxic, on the contrary, it has revealed modulatory effects against chemotherapy agents that induced genomic damage in human lymphocytes, suggesting its chemopreventive potential. [ABSTRACT FROM AUTHOR]

Background and Objective: Cough is invariably encountered during flexible bronchoscopy despite sedation and topical anaesthetics. The ideal cough suppressant during flexible bronchoscopy is not known. We assessed the role of dextromethorphan premedication in relieving the cough during flexible bronchoscopy in adults. Methods: In this single‐centre study, we randomized patients aged ≥18 years to receive dextromethorphan syrup 30 ml (90 mg) or an equal volume of placebo 1 h before the procedure. Patients rated their cough severity and discomfort on a visual analogue scale at the end of the procedure. Bronchoscopists also rated cough severity at the end of the procedure. Results: Out of 112 patients screened, 94 patients (median (interquartile range [IQR]) age 51 (36.25–60.75) years, male: female 2.13:1) were randomized to either the dextromethorphan (n = 47) or placebo (n = 47) groups. The patients‐rated median (IQR) cough scores at the end of the procedure were 15 (10–23) mm in dextromethorphan versus 20 (12–45.5) mm in placebo groups (p = 0.03). Patients‐rated median cough scores at 1 h (5 mm vs. 6 mm, p = 0.21), discomfort scores (12.5 mm vs. 12.5 mm, p = 0.49), and midazolam and lignocaine usage were similar between the two groups. The bronchoscopist‐rated median cough score was non‐significantly lower in the intervention compared to the placebo (26 mm vs. 35 mm, p = 0.09) groups. Conclusion: Dextromethorphan premedication 1 h before flexible bronchoscopy may have an additive effect on cough suppression under conscious sedation and topical lignocaine. Further trials are needed to reiterate our findings with certainty. [ABSTRACT FROM AUTHOR]

It has been shown that muscarinic acetylcholine receptors (mAChRs) located within the caudal nucleus tractus solitarii (cNTS) mediate a cholinergic inhibitory control mechanism of the cough reflex. Thus, identification of the involved mAChR subtypes could be of considerable interest for novel therapeutic strategies. In pentobarbital sodium-anesthetized, spontaneously breathing rabbits we investigated the contribution of different mAChR subtypes in the modulation of mechanically and chemically induced cough reflex. Bilateral microinjections of 1 mM muscarine into the cNTS increased respiratory frequency and decreased expiratory activity even to complete suppression. Interestingly, muscarine induced strong cough-suppressant effects up to the complete abolition of the reflex. Microinjections of specific mAChR subtype antagonists (M1-M5) into the cNTS were performed. Only microinjections of the M4 antagonist tropicamide (1 mM) prevented muscarine-induced changes in both respiratory activity and cough reflex. The results are discussed in light of the notion that cough involves the activation of the nociceptive system. They also suggest that M4 receptor agonists may have an important role in cough downregulation within the cNTS. [ABSTRACT FROM AUTHOR]

Background: The management of refractory chronic cough (RCC) is a great challenge. Neuromodulators have long been used for RCC with imperfect efficacy. Objectives: We summarized the outcomes of the current treatments used at our specialist cough clinic, which provides a guideline-led service and real-world experience for the future management of RCC. Design: This is a single-centre retrospective observational cohort study. Methods: Consecutive RCC patients (the first clinic visit between January 2016 and May 2021) were included into this observational cohort study. Medical records in the Chronic Cough Clinical Research Database were fully reviewed using uniform criteria. The included subjects were followed-up for at least 6 months after the final clinic visit via instant messages with the link to self-scaled cough-associated questionnaires. Results: Overall, 369 RCC patients were analysed with a median age of 46.6 years and a cough duration of 24.0 months. A total of 10 different treatments were offered. However, 96.2% of patients had been prescribed at least one neuromodulator. One-third of patients had alternative treatments prescribed given the poor response to the initial therapy and 71.3% favourably responded to at least one of the treatments. Gabapentin, deanxit, and baclofen had comparable therapeutic efficacy (56.0%, 56.0%, and 62.5% respectively; p = 0.88) and overall incidences of adverse effects (28.3%, 22.0%, and 32.3% respectively; p = 0.76). However, 19.1 (7.7–41.8) months after the last clinic visit, 65.0% reported improvement (24.9%) or control of their cough (40.1%); 3.8% reported a spontaneous remission and 31.2% still had a severe cough. Both HARQ (n = 97; p < 0.001) and LCQ (n = 58; p < 0.001) demonstrated marked improvement. Conclusion: Trying different neuromodulators is a pragmatic strategy for RCC, which helped around two-thirds of patients. Relapse is common on withdrawal or reduction of dosage. Novel medication for RCC is an urgent clinical need. Plain language summary: This is the first report that fully represented a guideline-led treatment protocol for refractory chronic cough (RCC) based on a large series of patients, which evaluated the short- and long-term effects of the currently available treatments for RCC. We found that the therapeutic trial of different neuromodulators is a pragmatic strategy, which helped around two-thirds of patients. Gabapentin, deanxit (flupentixol/melitracen), and baclofen had similar therapeutic outcomes. This study may offer real-world experience for the future management of RCC. [ABSTRACT FROM AUTHOR]

Introduction: Benzonatate is an FDA-approved antitussive agent that resembles tetracaine, procaine, and cocaine in its chemical structure. Based on structural similarities to known local anesthetics and recent findings of benzonatate exerting local anesthetic-like effects on voltage-gated sodium channels in vitro, we hypothesized that benzonatate will act as a local anesthetic to yield peripheral nerve blockade. Methods: Benzonatate was injected at the sciatic nerve of Sprague-Dawley rats. Sensory and motor blockade were assessed using a modified hot plate test and a weight-bearing test, respectively. Additionally, the effect of co-injection with tetrodotoxin and Tween 80 (a chemical permeation enhancer) was examined. Myotoxicity of benzonatate was assessed in vivo by histological analysis. Results: Benzonatate produced a concentration-dependent sensory and motor nerve blockade with no appreciable systemic effects. Co-injection with tetrodotoxin or Tween 80 produced prolongation of sensory nerve blockade. Histologic assessment showed significant inflammation and myotoxicity from benzonatate injection, even at low concentrations. Conclusion: This study demonstrates that benzonatate does act as a local anesthetic at the peripheral nerve, with sensory and motor nerve blockade. Benzonatate interacts with tetrodotoxin and Tween 80 to prolong nerve blockade. However, benzonatate causes significant myotoxicity, even at subtherapeutic concentrations. [ABSTRACT FROM AUTHOR]

Background: Despite the frequent use of symptomatic therapies in cough, evidence of their benefits is lacking.Objective: We compared the effectiveness of 3 symptomatic therapies and usual care in acute bronchitis.Methods: Multicenter, pragmatic, multiarm parallel group, open randomized trial in primary care (ClinicalTrials.gov, Identifier: NCT03738917) was conducted in Catalonia. Patients ≥18 with uncomplicated acute bronchitis, with cough<3 weeks as the main symptom, scoring ≥4 in either daytime or nocturnal cough (7-point Likert scale), were randomized to usual care, dextromethorphan 15 mg t.i.d., ipratropium bromide inhaler 20 µg 2 puffs t.i.d, or 30 mg of honey t.i.d., all taken for up to 14 days. The main outcome measure was the number of days with moderate-to-severe cough. A symptom diary was given. A second visit was scheduled at days 2-3 for assessing evolution, with 2 more visits at days 15 and 29 for clinical assessment, evaluation of adverse effects, re-attendance, and complications.Results: We failed to achieve the sample size scheduled due to the COVID-19 pandemic. We finally recruited 194 patients. The median number of days with moderate-to-severe cough (score ≥ 3) in the usual care arm was 5 (interquartile range [IQR], 4, 8.75), 5 in the ipratropium bromide arm (IQR, 3, 8), 5 in the dextromethorphan arm (IQR, 4, 9.75), and 6 in the honey arm (IQR, 3.5, 7). The same results were obtained in the Kaplan-Meier survival analysis for the median survival time of each arm with the usual care as the reference group.Conclusion: The symptomatic treatment evaluated has shown to be ineffective against cough. [ABSTRACT FROM AUTHOR]

Background: In two phase 3, global clinical trials (COUGH-1 and COUGH-2), the P2X3-receptor antagonist gefapixant significantly reduced objective 24-h cough frequency in participants with refractory or unexplained chronic cough (RCC or UCC) at a dosage of 45 mg twice daily (BID), with an acceptable safety profile. The primary objective of this phase 3, randomized, double-blind, parallel-group study was to assess the safety and tolerability of gefapixant in Japanese participants with RCC or UCC (ClinicalTrials.gov, NCT03696108; JAPIC-CTI, 184154). Methods: Participants aged ≥20 years with chronic cough lasting ≥4 months and a diagnosis of RCC or UCC despite treatment in accordance with Japanese Respiratory Society guidelines were randomized 1:1 to receive gefapixant 15 or 45 mg BID for 52 weeks. The primary objective was to evaluate the safety and tolerability of gefapixant, including adverse events (AEs) and discontinuations due to AEs. Cough-specific quality of life was assessed using the Leicester Cough Questionnaire as a secondary objective. Results: Of 169 randomized and treated participants, 63% were female and mean age was 58 years. Adverse events were reported by 79 (94%) and 82 (96%) participants in the 15- and 45-mg BID groups, respectively. Most treatment-related AEs were taste related. Discontinuations due to AEs occurred in 6 (7%) and 17 (20%) participants receiving gefapixant 15 or 45 mg BID, respectively. There were no serious treatment-related AEs or deaths. Leicester Cough Questionnaire total scores improved from baseline through Week 52. Conclusions: Gefapixant had an acceptable safety profile, with no serious treatment-related AEs in Japanese participants.

Abstract Introduction Cough is one of the most common presenting symptoms of COVID‐19, which can persist for weeks or months. Objective The goal of this study was to evaluate the effectiveness of gabapentin (GBT) alone and in combination with montelukast (MTL) for improving cough. Methods In this open‐label randomized controlled clinical trial, eligible cases were patients hospitalized with moderate to severe COVID‐19 who had cough with a Breathlessness, Cough, and Sputum Scale (BCSS) score of at least 2 based on its cough subscale. The participants were randomly assigned to three groups including two experimental groups and one control group. The first and second experimental groups received GBT and GBT/MTL, respectively, whereas the control group received dextromethorphan (DXM). Treatment duration was 5 days in all groups. Before and after the interventions, the severity of cough was evaluated using BCSS scale and Visual Analog Scale (VAS). Results A total of 180 patients were included; GPT, GPT/MTL, and DXM consisted of 76, 51, and 53 patients, respectively. There was no significant difference between the three groups in terms of age, gender, and comorbidities (P > 0.05). Regarding BCSS and VAS scores, there was significant reduction from the baseline values in all groups (P

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In this paper, we present the results of toxicological analyses of preserved brain tissue and bone samples from the remains of the seventeenth century patients of the Ospedale Maggiore, the main hospital in Milan and one of the most innovative hospitals in Europe from the Renaissance period. Beneath it, the crypt functioned as the burial place for the deceased of the hospital. In this multidisciplinary study of the remains, toxicological analyses in particular were performed with HPLC–MS/MS on different biological samples from nine individuals. Anthropological, paleopathological, histological, radiological examinations and radiocarbon dating were also carried out. As a result, archeotoxicological analyses revealed the presence of codeine, morphine, noscapine and papaverine, derived from Papaver somniferum, a plant present in the hospital pharmacopeia used as a narcotic, analgesic, astringent, coagulant, and antitussive agent. Such analyses have shed light on the pharmacological therapies administered to the patients near the time of death and have implemented our knowledge of medical treatment and drug administration in the 1600's. [ABSTRACT FROM AUTHOR]

Introduction: Refractory/unexplained chronic cough (RUCC) is a highly prevalent debilitating condition. The characteristics of RUCC suggest neuronal excitability. The biological mechanisms leading to this in humans are uncertain but are thought to involve changes in both the peripheral and central nervous system. Efficacy of P2X purinoceptor 3 (P2X3) antagonists suggests a role for extracellular adenosine triphosphate (ATP) in RUCC. In guinea pigs, ATP release occurs in response to hypotonic saline, through a transient receptor potential cation channel subfamily V member 4 (TRPV4)-ATP-P2X3 axis. Aims: In this review we discuss data from two European Respiratory Society 2022 abstracts in RUCC, as well as current insights and future directions in chronic cough. Results: We show that hypotonic saline cough challenge, measured by maximum evoked cough response, effectively discriminates RUCC from healthy volunteers. We show that low-dose morphine is efficacious in up to 75% of patients with RUCC and that side effects, experienced in around 38% of cases, can usually be managed. Further areas: We discuss treatable traits in chronic cough, existing pharmacological management options and future antitussives. [ABSTRACT FROM AUTHOR]

Electronic cigarette (e-cigarette) or vaping associated lung injury (EVALI) cases have increased with the popularity of e-cigarettes in the mostly young, healthy population. Some common symptoms associated with EVALI include shortness of breath and chest pain, and the most common diagnostic imaging findings are organizing pneumonia and diffuse alveolar damage seen on computed tomography (CT). Pneumomediastinum is a known sequela of EVALI.1 In the setting of pneumomediastinum in EVALI, EVALI is a diagnosis of exclusion, so other sources of pneumomediastinum need to be evaluated. EVALI has diverse presentations, and this case is a unique representation of a disease process that is becoming more commonplace with the increase in popularity of vaping. It is important to be aware of the clinical symptoms of EVALI, which can be nonspecific and can include gastrointestinal symptoms along with respiratory symptoms. It is equally important to recognize the diverse image findings of EVALI, which can include subcutaneous emphysema and pneumomediastinum. In this case, pneumomediastinum is seen in EVALI, and the patient was successfully treated with empiric antibiotic coverage, steroids, and conservative measures-- making sure to limit any coughing or increases in intrathoracic pressure that can cause worsening of pneumomediastinum. Topics: EVALI, vaping, pneumomediastinum, E-cigarette, ground-glass opacity. [ABSTRACT FROM AUTHOR]

Psychosis is known as a broad term of symptoms that cause serious disorganization of behavior, thinking, and perception of reality. One of the medicines that recently gained much attention in terms of its psychotic potential is dextromethorphan (DXM). DXM, a widely used antitussive drug, is a commonly abused drug because of its euphoric, hallucinogenic, and dissociative properties. To date, DXM is a legally marketed cough suppressant that is neither a controlled substance nor a regulated chemical under the Controlled Substances Act. The management of DXM-related psychosis is dependent on the type of psychotic symptoms. Atypical neuroleptics (i.e., olanzapine, risperidone, quetiapine) and typical haloperidol have been used in symptomatic treatment due to their efficacy, especially in positive symptoms (hallucinations and delusions). These agents are also recognized as the preferred option in the symptomatic treatment of DXM-related psychosis due to their better efficacy and safety profile than typical haloperidol in the short-term course. The focus of the present review concerns the current stage of knowledge about DXM psychotic potency as well as the management of DXM-related psychoses with a special emphasis on atypical antipsychotic drugs (i.e., olanzapine, risperidone, quetiapine, and haloperidol). [ABSTRACT FROM AUTHOR]

This article provides information on different types of cough preparations and their efficacy. It explains that expectorants help in coughing up mucus, while mucolytics reduce the thickness of mucus. Bronchodilators widen the airways, and cough suppressants are used for severe, dry coughs. Demulcents, such as honey and glycerine, have a soothing effect. The article advises selecting cough syrups based on the type of cough and recommends consulting a doctor if the cough persists or worsens. [Extracted from the article]

BACKGROUND AND OBJECTIVES: Adverse events (AE), including death, occur in children with benzonatate use. This study aims to understand recent trends in benzonatate exposure and clinical consequences in pediatric patients. METHODS: This retrospective analysis of data from IQVIA pharmacy drug dispensing, National Poison Data System, National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance Project, FDA Adverse Event Reporting System, and the medical literature evaluated exposure trends and medication-related AEs with benzonatate. Trends for comparator narcotic and nonnarcotic antitussive medications were analyzed where possible for context. RESULTS: During the study period, pediatric benzonatate prescription utilization increased but remained low compared with pediatric utilization of dextromethorphan-containing prescription antitussive medications. Among the 4689 pediatric benzonatate exposure cases reported to US poison control centers from 2010 to 2018, 3727 cases (80%) were for single-substance exposures. Of these, 3590 cases (77%) were unintentional exposures and most involved children 0 to 5 years old (2718 cases, 83%). Cases involving intentional benzonatate exposure increased among children 10 to 16 years old with a more pronounced increase for multiple-substance exposures. Most benzonatate cases involving misuse or abuse were for children 10 to 16 years old (59 cases, 61%). The proportion of cases with serious adverse effects was low. There were few cases annually of serious AEs with benzonatate in children. CONCLUSIONS: There were rising patterns of unintentional ingestion of benzonatate in children 0 to 5 years old and intentional benzonatate ingestion in children 10 to 16 years old. Rational prescribing and improved provider and caregiver awareness of benzonatate toxic effects may reduce risks associated with benzonatate exposure. [ABSTRACT FROM AUTHOR]

Background: Athletes are subjected to disciplinary action for even unintentional doping. This study aimed to clarify the effectiveness of prior checks on athletes' drug regimens by medical personnel with knowledge of anti-doping to prevent unintentional doping. Methods: This is a retrospective evaluation of the inquiries to the Anti-Doping Committee by the Japan Table Tennis Association national team athletes and athlete support personnel between 2011 and 2019 regarding whether the drug in question was permitted and whether it contained any prohibited substance. Discrete evaluations were performed for ethical and over-the-counter drugs, in addition to the evaluation of all drugs. Additionally, we evaluated the drugs according to therapeutic category and World Anti-Doping Agency's classification. Results: Overall, 85/1238 (6.9%) ethical drugs, 49/259 (18.9%) over-the-counter drugs and 134/1497 (9.0%) total drugs were considered as not allowed for use. The proportion of over-the-counter drugs judged as not allowed for use was higher than that of ethical drugs (p < 0.001). When tabulating the drugs not allowed for use in the therapeutic category, numerous prohibited substances were identified in adrenal hormone preparations, Kampo products, synthetic narcotics, antitussives, antihemorrhoidals, and bronchodilators among ethical drugs and in cold remedies, gastrointestinal drugs, and antitussives and expectorants among over-the-counter drugs. Conclusions: Of the ethical and over-the-counter drugs that elite athletes wanted to use, approximately 10% were not allowed because of the risk of unintentional doping. These results suggest that conducting prior checks of the athletes' drug regimens by medical personnel with anti-doping knowledge are effective measures to prevent unintentional doping. [ABSTRACT FROM AUTHOR]

Ineffective over-the-counter (OTC) drugs should be removed from the US market. Despite solid research showing that oral phenylephrine is ineffective as a decongestant, the US Food and Drug Administration has failed to respond to a 2015 citizen's petition to remove it from the OTC nasal decongestant monograph. Other examples of scientifically proven ineffective OTC medications include guaifenesin as an expectorant, dextromethorphan as a cough suppressant, and chlorpheniramine for cold symptoms. [ABSTRACT FROM AUTHOR]

Dextromethorphan or DXM is an effective and harmless cough and cold suppressant available in many cold and cough preparations. At maximum dosage, it mimics hallucinogenic and psychoactive effects in human body and hence it is appealing for abuse. In this work, a detailed study of an antitussive agent i.e. Dextromethorphan which is a semi-synthetic opioid and a replacement of codeine and pholcodine in various cough linctuses has been described extensively. This review also revolves around the structured detailing of Dextromethorphan, its physical and chemical properties as well its pharmacokinetics in human body and also its effect on human brain and its relationship with NMDA receptors. This study also focuses on the emergence of Dextromethorphan as new drug of abuse due to its easy availability and as it possesses similar effects with LSD and other hallucinogens when taken in overdose in addition with the Toxicological analysis of Dextromethorphan from biological matrices using respective analytical methods. [ABSTRACT FROM AUTHOR]

Introduction: Concerns over serious respiratory depression in children led to two European Union (EU) referral procedures (in 2013 and 2015) to review the benefit-risk balance of codeine in this population when used for pain relief, cough or cold. Consequently, codeine should no longer be used in children aged < 12 years and restrictions were introduced for treatment in children ≥ 12 years.Objective: This multinational collaborative study aimed to assess the effectiveness of these risk minimisation measures by evaluating changes in prescribing of codeine and alternative treatments.Method: Children under 12 and 12-18 years old were followed between 2010 and 2017 to analyse quarterly trends in prescribing of codeine and alternative treatments in electronic health records from France, Germany, Norway, Spain and the United Kingdom using interrupted time series analysis.Results: Overall prescribing of codeine in children decreased in all five countries, reaching near zero prevalence in children under 12 years of age. This was accompanied by an increase in use of other opioid analgesics in France (from 0.15 to 0.56 prevalence per 100 person-years immediately after the first referral), Norway (from 0.0006 to 0.0013 at the end of the study), the United Kingdom (from 0.018 to 0.05 at the end of the study), and an increase in non-opioid analgesics in Norway (from 0.045 to 0.075 at the end of the study) after the referral on pain relief indication. The referral on cough/cold indication led to a decrease in use of opioid and non-opioid antitussives in children aged < 12 years in France (from 10 to 7 and 20 to 16, respectively) and had no impact in other countries. Overall prescribing trends for codeine and alternatives were similar across both age groups within each country.Conclusion: The decrease in use of codeine shows that healthcare professionals followed the adopted measures and switched prescribing practices for pain management in children aged < 18 years towards opioid or non-opioid analgesics depending on national clinical and reimbursement settings. Whist the magnitude of the first referral on pain differed between countries, the second referral on cough/cold had only a minimal impact on the use of codeine and antitussives. [ABSTRACT FROM AUTHOR]

In two phase 3, global clinical trials (COUGH-1 and COUGH-2), the P2X3-receptor antagonist gefapixant significantly reduced objective 24-h cough frequency in participants with refractory or unexplained chronic cough (RCC or UCC) at a dosage of 45 mg twice daily (BID), with an acceptable safety profile. The primary objective of this phase 3, randomized, double-blind, parallel-group study was to assess the safety and tolerability of gefapixant in Japanese participants with RCC or UCC (ClinicalTrials.gov , NCT03696108; JAPIC-CTI, 184154). Participants aged ≥20 years with chronic cough lasting ≥4 months and a diagnosis of RCC or UCC despite treatment in accordance with Japanese Respiratory Society guidelines were randomized 1:1 to receive gefapixant 15 or 45 mg BID for 52 weeks. The primary objective was to evaluate the safety and tolerability of gefapixant, including adverse events (AEs) and discontinuations due to AEs. Cough-specific quality of life was assessed using the Leicester Cough Questionnaire as a secondary objective. Of 169 randomized and treated participants, 63% were female and mean age was 58 years. Adverse events were reported by 79 (94%) and 82 (96%) participants in the 15- and 45-mg BID groups, respectively. Most treatment-related AEs were taste related. Discontinuations due to AEs occurred in 6 (7%) and 17 (20%) participants receiving gefapixant 15 or 45 mg BID, respectively. There were no serious treatment-related AEs or deaths. Leicester Cough Questionnaire total scores improved from baseline through Week 52. Gefapixant had an acceptable safety profile, with no serious treatment-related AEs in Japanese participants. [ABSTRACT FROM AUTHOR]

Background  Students studying at a university of health sciences may have different perceptions regarding illness and treatment. Moreover, as they have access to healthcare, it may influence their health-seeking behavior. It is important to identify the health-seeking behavior of the students and to guide them accordingly. Methods  The present study was designed to assess the health-seeking behavior of undergraduate students. It was a cross-sectional descriptive study. A total of 236 students pursuing undergraduate courses in medicine, dentistry, nursing, and physiotherapy participated in the study. Checklist and perception scales were used to collect data that were then analyzed using descriptive and inferential statistics. Results  Use of the Internet to get information about illness, treatment, and medications (60.3%; 139), self-investigations (50.6%; 122) as well as self-medication practices (54.4%; 130) was commonly seen in students. Among the self-medications, antibiotics (63.7%; 152), antipyretics (45.6%; 109), analgesics (43.9%; 104), and cough syrup (48.9%; 116) were common. Regarding perception on health-seeking behavior, the majority (49.3%; 118) opined neutral for the statement that self-diagnosis is not wrong, (49.4%; 120) reported that over-the-counter medications can be taken, (66.5%; 157) agreed that keeping healthy by eating healthy can keep you away from the hospital. The barriers for health-seeking behavior, stigma, fear of confidentiality issues, fear of unwanted intervention, and unaware where to seek help were more commonly reported for mental healthcare-seeking behavior (odds ratio [OR]: 29.33, 23.18, 34.16, and 11.96, respectively), whereas issues relating to high cost, the long waiting hour in healthcare facility, and fear of side effects were reported for physical healthcare-seeking (OR: 9.80, 7.15, and 18.66, respectively) behavior. Conclusion  Self-investigation, self-medications, and use of the Internet to seek healthcare information are evident among students of university. Students exhibited different health-seeking behavior for physical and mental illnesses. Barriers to health-seeking also differed. Institutions should use this information for the effective usage of healthcare services by students. [ABSTRACT FROM AUTHOR]

Chronic cough has a significant impact on those affected and has a financial impact when not diagnosed in a timely manner. Effective therapies are currently lacking but at least one new class of medication is likely to be FDA-approved in the next year. Managed care will need to address appropriate utilization of this class. [ABSTRACT FROM AUTHOR]

Introduction: Cough is one of the most common presenting symptoms of COVID‐19, which can persist for weeks or months. Objective: The goal of this study was to evaluate the effectiveness of gabapentin (GBT) alone and in combination with montelukast (MTL) for improving cough. Methods: In this open‐label randomized controlled clinical trial, eligible cases were patients hospitalized with moderate to severe COVID‐19 who had cough with a Breathlessness, Cough, and Sputum Scale (BCSS) score of at least 2 based on its cough subscale. The participants were randomly assigned to three groups including two experimental groups and one control group. The first and second experimental groups received GBT and GBT/MTL, respectively, whereas the control group received dextromethorphan (DXM). Treatment duration was 5 days in all groups. Before and after the interventions, the severity of cough was evaluated using BCSS scale and Visual Analog Scale (VAS). Results: A total of 180 patients were included; GPT, GPT/MTL, and DXM consisted of 76, 51, and 53 patients, respectively. There was no significant difference between the three groups in terms of age, gender, and comorbidities (P > 0.05). Regarding BCSS and VAS scores, there was significant reduction from the baseline values in all groups (P < 0.0001), with the change rate being significantly higher in DXM group. The amount of reduction of BCSS in the GPT/MTL group was significantly more than the GPT group, whereas there was no significant difference between the two groups regarding VAS score. Although the duration of hospitalization differed between the groups with the GPT/MTL group having the shortest duration, the difference was statistically significant only between the GPT and GPT/MTL groups (P < 0.0001). Conclusion: GPT, both alone and in combination with MTL, improves cough frequency and severity in hospitalized patients with COVID‐19, with the combination being more efficacious. This regimen may be useful in patients who cannot tolerate opioids. [ABSTRACT FROM AUTHOR]

Background. Reineckia carnea (RC), a perennial evergreen herb which belongs to Reineckia Kunth (Liliaceae), can be used for clearing the lungs and relieving cough, reducing phlegm and anti-inflammatory effects. Moreover, chronic obstructive pulmonary disease (COPD) is characterized by airway and lung inflammation and increased secretion of airway mucus. Therefore, RC has the potential to treat COPD. Methods. NR8383 cells were cultured and treated with various concentrations of RC (100 mg/mL, 10 mg/mL, 1 mg/mL, 100 μg/mL, 10 μg/mL, 1 μg/mL, 100 ng/mL, and 10 ng/mL). Cell viability and levels of interleukin (IL)-1β, cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2) in the cell culture supernatant or rat serum were analyzed using CCK-8 and enzyme-linked immunosorbent assay (ELISA), respectively. Sprague Dawley rats were assigned to mock, COPD model, RC (0.67 g/kg, 1.35 g/kg, and 2.7 g/kg), and ambroxol (5.4 mg/kg) groups. Western blot and quantitative polymerase chain reaction (qPCR) analyses were used to evaluate the protein and mRNA expression levels of mucin 5AC (MUC5AC) and Toll-like receptor 4 (TLR4). Results. The results showed that Reineckia carnea (RC) extract (RCE) inhibited the proliferation of NR8383 cells and suppressed the production of IL-1β, PGE2, and COX-2 in NR8383 cells. Moreover, RCE decreased the levels of IL-1β, PGE2, and COX-2 in the serum of rats with COPD and alleviated the expression of TLR4 and MUC5AC induced by COPD in rat lung tissue. Conclusion. RCE alleviated COPD by inhibiting the expression of COPD-induced inflammatory cytokines and MUC5AC in rats. [ABSTRACT FROM AUTHOR]

Objective To study the rules of symptoms, patterns, and medicines of medical records of lung distention treated by Xin'an doctors through data mining methods, and to explore the characteristics of Xin'an doctors in the treatment of lung distention. Methods Medical records related to the treatment of lung distention by Xin'an doctors were collected and sorted from the medical books of Xin'an. After the standardized processing of various information, mathematical models such as frequency analysis, topology analysis, Louvain clustering, and factor analysis were used to conduct data mining research on symptoms, patterns, and prescriptions. Results We included 361 medical records and counted 272 traditional Chinese medicines in total. Among them, 35 were core medicines, including Poria, Radix Glycyrrhizae, Semen Armeniacae Amarum, Semen Coicis, Rhizoma Pinelliae, Radix Ginseng, Rhizoma Atractylodis Macrocephalae, and Fructus Schisandrae Chinensis. In the lung distention, clinical practice of Xin'an doctors, tonic medicines (30.14%) were used most, followed by expectorant cough suppressants and anti-asthmatic medicines (22.81%). The pattern of phlegm and dampness accumulating in the lung (30.19%) was the most commonly observed, and the patterns of deficiency were mainly lung qi deficiency (22.44%), spleen qi deficiency (21.05%), and kidney qi deficiency (17.45%). Semen Armeniacae Amarum, Poria, Semen Coicis, Rhizoma Pinelliae, and Exocarpium Citri Grandis were the core prescription medicines for the pattern of phlegm and dampness accumulating in the lung. Poria, Radix Glycyrrhizae, Radix Ginseng, Rhizoma Atractylodis Macrocephalae, Semen Armeniacae Amarum, and Pericarpium Citri Reticulatae were the core prescription medicines of the lung qi deficiency pattern. Poria, Radix Ginseng, Radix Glycyrrhizae, Rhizoma Atractylodis Macrocephalae, Pericarpium Citri Reticulatae, and Rhizoma Pinelliae were the core prescription medicines of the spleen qi deficiency pattern. Poria, Rhizoma Dioscoreae, Radix Rehmanniae Preparata, Fructus Corni, and Fructus Schisandrae Chinensis were the core prescription medicines of the kidney qi deficiency pattern. Furthermore, 10 common factors were extracted by factor analysis. The disease's main locations were the lung, spleen, and kidney. Water dampness, phlegm, and blood stasis were the main pathological factors. Conclusion Lung distention is a disease whose pathogenesis is the root deficiency with the branch in excess. The deficiency of the lung, spleen, and kidney are the root, while the pathological factors of phlegm, blood stasis, and heat are its branch. In Xin'an doctors' clinical practice, they preferred to use Poria, Semen Coicis, Radix Ginseng, and Rhizoma Atractylodis Macrocephalae to treat lung distention. While eliminating phlegm, clearing the lung, relieving cough, and relieving asthma were used to correct the obvious and superficial pathological factors of lung distention, these were often combined with medicines for tonifying the lung and kidney as well as strengthening the spleen to benefit the root cause. [ABSTRACT FROM AUTHOR]

Aims: The French Ministry of Health scheduled opioid cough suppressants as prescription‐only drugs on 12 July 2017. The present study assessed the impact of this regulation on the diversion modalities of the concerned drugs and the related drug pholcodine by analysing the national OSIAP (Ordonnances Suspectes Indicateur d'Abus Possible) database. Methods: Medical prescriptions with at least 1 mention of codeine, dextromethorphan, ethylmorphine, noscapine or pholcodine for cough suppression recorded in 2013–2019 were extracted from OSIAP. Annual mentioning rates were estimated by dividing numbers of mentions over those of prescriptions recorded the year considered. A descriptive analysis compared the characteristics of prescriptions before and after 12 July 2017. Results: Overall, 832 mentions of the requested drugs were retrieved on 827 prescription forms. Codeine was the most frequent (n = 809, 8.7%) with 6 additional mentions of codeine/ethylmorphine combination, followed by dextromethorphan (n = 11, 0.1%) and pholcodine (n = 6, 0.1%). There was no mention of noscapine. Annual mentioning rates varied between 0 and 0.3% for all drugs except codeine. Codeine mentioning rates ranged between 0.3% (n = 2) and 0.7% (n = 9) before 12 July 2017 and increased to 10.1% (n = 61) thereafter in 2017, 16.1% (n = 314) in 2018, and 19.8% (n = 414) in 2019. The profile of subjects evolved accordingly with an increased male/female ratio (10.0 vs. 1.5 before) and decreased age (23 vs. 40 y before, P <.001). Discussion: The sharp increase of recourse to falsified prescription forms indicates that codeine diversion continues despite restricted access, whereas the other drugs studied do not seem to have been impacted. [ABSTRACT FROM AUTHOR]

Malva parviflora L., Little mallow, has been traditionally used as an alternative food source. It acts as a medicinal herb containing a potential source of mucilage thus herein; we aimed to assess the toxicity, anti-inflammatory, antitussive and gastro-protective actions of M. parviflora mucilage extracted from its leaves (MLM) and fruit (MFM). Toxicity studies were investigated by in vitro hemolytic assay whereas acute anti-inflammatory and antitussive activities were assessed by carrageenan-induced paw edema and sulphur dioxide induced cough model in rats, respectively. Gastro-protective effects were studied using ethanol induced acute and chronic gastric ulcer rat models. Their metabolic profiles were determined using gas chromatography. The results revealed that MLM and MFM were non-toxic towards human erythrocytes and their lethal doses were found to be greater than 5 g/kg. Pretreatment with MLM (500 mg/kg) and MFM (500 mg/kg) significantly reduced the carrageenan-induced paw thickness (p < 0.001). Maximum edema inhibition (%) was observed at 4 h in diclofenac sodium (39.31%) followed by MLM (27.35%) and MFM (15.68%). Animals pretreated with MLM (500 mg/kg) significantly lower the cough frequency in SO2 gas induced cough models in contrast to control. Moreover, MLM at doses of 250 and 500 mg/kg reduced the ethanol induced gastric mucosal injuries in acute gastric ulcer models presenting ulcer inhibition of 23.04 and 38.74%, respectively. The chronic gastric ulcer model MFM (500 mg/kg) demonstrated a remarkable gastro-protective effect showing 63.52% ulcer inhibition and results were closely related to standard drug sucralfate. In both models, MLM and MFM decreased gastric juice volume and total acidity in addition to an increased gastric juice pH and gastric mucous content justifying an anti-secretary role of this mucilage that was further confirmed by histopathological examination. Meanwhile, GC analyses of the mucilage revealed their richness with natural as well as acidic monosaccharides. It is concluded that MLM and MFM can be used therapeutically for the management of inflammation, cough and gastric ulcer. [ABSTRACT FROM AUTHOR]