RESUMO
BACKGROUND: The common cold is an acute, self-limiting viral respiratory illness. Symptoms include nasal congestion and mucus discharge, sneezing, sore throat, cough, and general malaise. Given the frequency of colds, they are a public health burden and a significant cause of lost work productivity and school absenteeism. There are no established interventions to prevent colds or shorten their duration. However, zinc supplements are commonly recommended and taken for this purpose. OBJECTIVES: To assess the effectiveness and safety of zinc for the prevention and treatment of the common cold. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, and LILACS to 22 May 2023, and searched Web of Science Core Collection and two trials registries to 14 June 2023. We also used reference checking, citation searching, and contact with study authors to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in children or adults that tested any form of zinc against placebo to prevent or treat the common cold or upper respiratory infection (URTI). We excluded zinc interventions in which zinc was combined with other minerals, vitamins, or herbs (e.g. a multivitamin, or mineral supplement containing zinc). DATA COLLECTION AND ANALYSIS: We used the Cochrane risk of bias tool to assess risks of bias, and GRADE to assess the certainty of the evidence. We independently extracted data. When necessary, we contacted study authors for additional information. We assessed zinc (type and route) with placebo in the prevention and treatment of the common cold. Primary outcomes included the proportion of participants developing colds (for analyses of prevention trials only), duration of cold (measured in days from start to resolution of the cold), adverse events potentially due to zinc supplements (e.g. unpleasant taste, loss of smell, vomiting, stomach cramps, and diarrhoea), and adverse events considered to be potential complications of the common cold (e.g. respiratory bacterial infections). MAIN RESULTS: We included 34 studies (15 prevention, 19 treatment) involving 8526 participants. Twenty-two studies were conducted on adults and 12 studies were conducted on children. Most trials were conducted in the USA (n = 18), followed by India, Indonesia, Iran, and Turkey (two studies each), and Australia, Burkina Faso, Colombia, Denmark, Finland, Tanzania, Thailand, and the UK (one study each). The 15 prevention studies identified the condition as either common cold (n = 8) or URTI (n = 7). However, almost all therapeutic studies (17/19) focused on the common cold. Most studies (17/34) evaluated the effectiveness of zinc administered as lozenges (3 prevention; 14 treatment) in acetate, gluconate, and orotate forms; gluconate lozenges were the most common (9/17). Zinc gluconate was given at doses between 45 and 276 mg/day for between 4.5 and 21 days. Five (5/17) lozenge studies gave acetate lozenges and two (2/17) gave both acetate and gluconate lozenges. One (1/17) lozenge study administered intranasal (gluconate) and lozenge (orotate) zinc in tandem for cold treatment. Of the 17/34 studies that did not use lozenges, 1/17 gave capsules, 3/17 administered dissolved powders, 5/17 gave tablets, 4/17 used syrups, and 4/17 used intranasal administration. Most studies were at unclear or high risk of bias in at least one domain. There may be little or no reduction in the risk of developing a cold with zinc compared to placebo (risk ratio (RR) 0.93, 95% CI 0.85 to 1.01; I2 = 20%; 9 studies, 1449 participants; low-certainty evidence). There may be little or no reduction in the mean number of colds that occur over five to 18 months of follow-up (mean difference (MD) -0.90, 95% CI -1.93 to 0.12; I2 = 96%; 2 studies, 1284 participants; low-certainty evidence). When colds occur, there is probably little or no difference in the duration of colds in days (MD -0.63, 95% CI -1.29 to 0.04; I² = 77%; 3 studies, 740 participants; moderate-certainty evidence), and there may be little or no difference in global symptom severity (standardised mean difference (SMD) 0.04, 95% CI -0.35 to 0.43; I² = 0%; 2 studies, 101 participants; low-certainty evidence). When zinc is used for cold treatment, there may be a reduction in the mean duration of the cold in days (MD -2.37, 95% CI -4.21 to -0.53; I² = 97%; 8 studies, 972 participants; low-certainty evidence), although it is uncertain whether there is a reduction in the risk of having an ongoing cold at the end of follow-up (RR 0.52, 95% CI 0.21 to 1.27; I² = 65%; 5 studies, 357 participants; very low-certainty evidence), or global symptom severity (SMD -0.03, 95% CI -0.56 to 0.50; I² = 78%; 2 studies, 261 participants; very low-certainty evidence), and there may be little or no difference in the risk of a change in global symptom severity (RR 1.02, 95% CI 0.85 to 1.23; 1 study, 114 participants; low-certainty evidence). Thirty-one studies reported non-serious adverse events (2422 participants). It is uncertain whether there is a difference in the risk of adverse events with zinc used for cold prevention (RR 1.11, 95% CI 0.84 to 1.47; I2 = 0%; 7 studies, 1517 participants; very low-certainty evidence) or an increase in the risk of serious adverse events (RR 1.67, 95% CI 0.78 to 3.57; I2 = 0%; 3 studies, 1563 participants; low-certainty evidence). There is probably an increase in the risk of non-serious adverse events when zinc is used for cold treatment (RR 1.34, 95% CI 1.15 to 1.55; I2 = 44%; 2084 participants, 16 studies; moderate-certainty evidence); no treatment study provided information on serious adverse events. No study provided clear information about adverse events considered to be potential complications of the common cold. AUTHORS' CONCLUSIONS: The findings suggest that zinc supplementation may have little or no effect on the prevention of colds but may reduce the duration of ongoing colds, with an increase in non-serious adverse events. Overall, there was wide variation in interventions (including concomitant therapy) and outcomes across the studies, as well as incomplete reporting of several domains, which should be considered when making conclusions about the efficacy of zinc for the common cold.
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Resfriado Comum , Ensaios Clínicos Controlados Aleatórios como Assunto , Zinco , Adulto , Criança , Humanos , Viés , Resfriado Comum/prevenção & controle , Resfriado Comum/tratamento farmacológico , Suplementos Nutricionais , Gluconatos/uso terapêutico , Infecções Respiratórias/prevenção & controle , Infecções Respiratórias/tratamento farmacológico , Zinco/uso terapêutico , Zinco/administração & dosagemRESUMO
BACKGROUND: Human rhinovirus 3C protease (HRV-3Cpro) plays a crucial role in viral proliferation, establishing it as a prime target for antiviral therapy. However, research on identifying HRV-3Cpro inhibitors is still limited. OBJECTIVE: This study had two primary objectives: first, to validate the efficacy of an end-point colorimetric assay, previously developed by our team, for identifying potential inhibitors of HRV-3Cpro; and second, to discover phytochemicals in medicinal plants that inhibit the enzyme's activity. METHODS: Rupintrivir, a well-known inhibitor of HRV-3Cpro, was used to validate the colorimetric assay. Following this, we conducted a two-step in silico screening of 2532 phytochemicals, which led to the identification of eight active compounds: apigenin, carnosol, chlorogenic acid, kaempferol, luteolin, quercetin, rosmarinic acid, and rutin. We subsequently evaluated these candidates in vitro. To further investigate the inhibitory potential of the most promising candidates, namely, carnosol and rosmarinic acid, molecular docking studies were performed to analyze their binding interactions with HRV-3Cpro. RESULTS: The colorimetric assay we previously developed is effective in identifying compounds that selectively inhibit HRV-3Cpro. Carnosol and rosmarinic acid emerged as potent inhibitors, inhibiting HRV-3Cpro activity in vitro by over 55%. Our analysis indicated that carnosol and rosmarinic acid exert their inhibitory effects through a competitive mechanism. Molecular docking confirmed their competitive binding to the enzyme's active site. CONCLUSION: Carnosol and rosmarinic acid warrant additional investigation for their potential in the development of common cold treatment. By highlighting these compounds as effective HRV-3Cpro inhibitors, our study presents a promising approach for discovering phytochemical inhibitors against proteases from similar pathogens.
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Proteases Virais 3C , Antivirais , Resfriado Comum , Simulação de Acoplamento Molecular , Compostos Fitoquímicos , Rhinovirus , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Proteases Virais 3C/antagonistas & inibidores , Rhinovirus/enzimologia , Rhinovirus/efeitos dos fármacos , Humanos , Antivirais/farmacologia , Antivirais/química , Resfriado Comum/tratamento farmacológico , Resfriado Comum/virologia , Proteínas Virais/antagonistas & inibidores , Proteínas Virais/metabolismo , Estrutura Molecular , Relação Estrutura-Atividade , Inibidores de Proteases/farmacologia , Inibidores de Proteases/químicaRESUMO
BACKGROUND: Some studies have reported that community pharmacies in developing countries, including Indonesia, provided sub-optimal advice when handling patient's self-medication request for cough. The reasons behind such advice, therefore, need to be investigated. OBJECTIVES: To describe Indonesian pharmacists' clinical decision making when handling self-medication cases for a cough. METHODS: An open-ended questionnaire consisting of two cough clinical vignettes (case 1: cough due to asthma worsening and case 2: cough as a symptom of common cold) were developed. Pharmacists were interviewed to provide recommendations and reasons for their recommendations for these scenarios. Content analysis was used to analyse participants' statements for the two scenarios. The number of participants who provided appropriate recommendations and reasons were then counted. RESULTS: A total of 245 community pharmacists participated in the study. In the case of cough due to asthma worsening, recommending a product because the product was indicated to help with the symptoms was the most common recommendation and stated reason (40%). Appropriate recommendation (direct medical referral) with appropriate reasoning (indicating warning symptoms and/or making a symptom diagnosis) was provided by 25% participants. In the case of cough as a symptom of common cold, recommending products to help with the symptoms was also the most common recommendation and stated reason (53%). Appropriate recommendations (recommending product) with appropriate reasoning (providing product to treat the symptoms and/or indicating no warning symptoms and/or making a symptom diagnosis) was provided by 81% participants. CONCLUSION: The ability of Indonesian community pharmacists to provide appropriate recommendations for cough self-medication requests is dependent on whether triage is required. The inability of most community pharmacists to differentiate between major and minor conditions may lead to serious health implications for patients and therefore educational interventions should be undertaken to improve community pharmacists' differential diagnostic skills for triage.
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Asma , Tomada de Decisão Clínica , Serviços Comunitários de Farmácia , Tosse , Países em Desenvolvimento , Farmacêuticos , Automedicação , Humanos , Tosse/tratamento farmacológico , Indonésia , Masculino , Feminino , Adulto , Serviços Comunitários de Farmácia/organização & administração , Pessoa de Meia-Idade , Asma/tratamento farmacológico , Inquéritos e Questionários , Papel Profissional , Adulto Jovem , Resfriado Comum/tratamento farmacológicoRESUMO
Although the United States Food & Drug Administration (FDA) has provided guidance on the control of drug degradants for prescription drugs, there is less guidance on how to set degradant specifications for FDA OTC monograph drugs. Given that extensive impurity testing was not part of the safety paradigm in original OTC monographs, a weight of evidence (WOE) approach to qualify OTC degradants is proposed. This approach relies on in silico tools and read-across approaches alongside standard toxicity testing to determine safety. Using several drugs marketed under 21 CFR 341 as case studies, this research demonstrates the utility of a WOE approach across data-rich and data-poor degradants. Based on degradant levels ranging from 1 to 4% of the maximum daily doses of each case study drug and 10th percentile body weight data for each patient group, children were recognized as having the highest potential exposure relative to adults per body mass. Depending on data availability and relationship to the parent API, margins of safety (MOS) or exposure margins were calculated for each degradant. The findings supported safe use, and indicated that this contemporary WOE approach could be utilized to assess OTC degradants. This approach is valuable to establish specifications for degradants in OTCs.
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Antitussígenos , Medicamentos sem Prescrição , United States Food and Drug Administration , Medicamentos sem Prescrição/efeitos adversos , Humanos , Estados Unidos , Antitussígenos/efeitos adversos , Tosse/tratamento farmacológico , Medição de Risco , Criança , Contaminação de Medicamentos , Adulto , Testes de Toxicidade/métodos , Resfriado Comum/tratamento farmacológicoRESUMO
BACKGROUND: The common cold is one of the most frequently occurring illnesses worldwide. The aim of this study was to determine which OTC anti-common cold medications were most often recommended by pharmacists and if the COVID-19 pandemic affected such recommendations. METHODS: Non-interventional, observational research trial using a self-developed questionnaire to collect data on pharmacists' recommendations for anti-common cold OTC treatment. The data were collected during the COVID-19 pandemic (December 2021-February 2022) in four large community network pharmacies in Lodz (Poland) and then compared with an analogue period of time before the pandemic (December 2019-February 2020). RESULTS: During COVID-19 pandemic there was a significant (p < 0.05) reduction in paracetamol, acetylsalicylic acid, metamizole magnesium, inosines, alpha-mimetics, mucolytics, homeopathics, and sore throat products and an increase in other tablets/capsules and add-on product recommendations. There was a significant relationship (p < 0.05, OR > 1) between the recommended frequency of paracetamol, inosines, sore throat products (each symptom), metamizole magnesium (headache, fever), acetylsalicylic acid (headache, fever, fatigue), NSAIDs, alpha-mimetics (headache, rhinorrhea), pseudoephedrine (rhinorrhea), homeopathics (headache), herbal products (fatigue), antihistamines (rhinorrhea, cough), and mucolytics (headache, fever, cough). CONCLUSIONS: Favorable prices (before COVID-19 pandemic) and reports on common NSAIDs side effects (beginning of the pandemic) led to high sale of paracetamol. Increased awareness of clinical effectiveness of some medications or their reduced availability influenced their limited recommendations.
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COVID-19 , Resfriado Comum , Faringite , Humanos , Acetaminofen/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/uso terapêutico , Resfriado Comum/tratamento farmacológico , Resfriado Comum/induzido quimicamente , Tosse , Expectorantes/uso terapêutico , Cefaleia/induzido quimicamente , Cefaleia/tratamento farmacológico , Medicamentos sem Prescrição/uso terapêutico , Pandemias , Farmacêuticos , Faringite/induzido quimicamente , Faringite/tratamento farmacológico , RinorreiaRESUMO
BACKGROUND: The common cold is a frequent, acute, and mild upper respiratory human disease. Nasal congestion has been considered the most bothersome symptom in the common cold, impacting quality of life (QoL). Topical decongestants containing steroids benefit QoL in allergic rhinitis, but no published research has assessed the impact of topical decongestants on QoL in the common cold. OBJECTIVE: To evaluate the effects of xylometazoline hydrochloride 0.1% (Otrivin, GSK Consumer Healthcare SARL, Switzerland) for up to 7 days on QoL in participants with nasal congestion associated with the common cold. DESIGN: This was a decentralized, longitudinal, open-label study. METHODS: The study enrolled 136 participants (⩾18 years) with early symptoms of the common cold, of which 102 were included in the modified intention-to-treat (mITT) population. Within 24 h of study product receipt, participants confirmed a 'plugged nose' and ⩾1 other common cold symptom. Primary endpoints were Wisconsin Upper Respiratory Symptom Survey-21 (WURSS-21) total score, total and individual symptom scores, and total QoL score. Secondary endpoints were additional QoL scores. Exploratory and post hoc analyses included median days to resolution for each QoL factor and analyses of five QoL categories. RESULTS: Consistent improvements in symptoms and QoL were seen in the mITT population. From day 1, improvements were seen in the 'plugged nose' symptom (p = 0.0023), WURSS-21 total QoL score, and all individual QoL scores (p < 0.0001 for all). After the last dose needed, significant improvements were seen in sleep quality (73%), vitality (76%), physical activity (71%), social activity (80%), and sensation (81%). No serious or unexpected adverse events were reported. CONCLUSION: This study is the first to demonstrate in a real-life setting that treating nasal congestion in adults with xylometazoline hydrochloride 0.1% during the common cold positively impacts QoL factors relevant to daily living [Otrivin: Quality of Life (QoL) Impact in a Real-World Setting; https://clinicaltrials.gov/study/NCT05556148].
Impact of xylometazoline hydrochloride 0.1% on quality of life in people with blocked nose associated with the common coldThe common cold is a widespread, mild respiratory illness for which a hallmark symptom is a blocked or stuffy nose, which makes breathing and sleeping difficult. This study focused on how a nasal spray called Otrivin (containing xylometazoline hydrochloride 0.1%) impacts the quality of life (QoL) of people suffering from nasal congestion due to the common cold.Participants answered a questionnaire called the Wisconsin Upper Respiratory Symptom Survey-21 (WURSS-21), which helped understand how people experience respiratory symptoms and how different aspects of QoL were impacted. Participants also responded to eight additional QoL questions not covered in the WURSS-21.The results showed that from the first day of using the nasal spray, participants experienced significant relief from the blocked nose symptom and reported an overall improvement in their QoL and well-being, such as in sleep quality, energy levels, senses, and physical and social activities.In conclusion, this real-world study demonstrated that using xylometazoline hydrochloride 0.1% nasal spray during the common cold can significantly improve nasal congestion and various aspects of a person's daily life. These findings provide valuable evidence for using this nasal spray to relieve symptoms and enhance the overall well-being of individuals with the common cold.
Assuntos
Resfriado Comum , Imidazóis , Adulto , Humanos , Resfriado Comum/diagnóstico , Resfriado Comum/tratamento farmacológico , Resfriado Comum/induzido quimicamente , Descongestionantes Nasais/efeitos adversos , Qualidade de Vida , Administração IntranasalRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Ferns form an important part of the human diet. Young fern fiddleheads are mostly consumed as vegetables, while the rhizomes are often extracted for starch. These edible ferns are also often employed in traditional medicine, where all parts of the plant are used, mostly to prepare extracts. These extracts are applied either externally as lotions and baths or internally as potions, decoctions and teas. Ailments traditionally treated with ferns include coughs, colds, fevers, pain, burns and wounds, asthma, rheumatism, diarrhoea, or skin diseases (eczema, rashes, itching, leprosy). AIM OF THE REVIEW: This review aims to compile the worldwide knowledge on the traditional medicinal uses of edible fern species correlating to reported biological activities and isolated bioactive compounds. MATERIALS AND METHODS: The articles and books published on edible fern species were searched through the online databases Web of Science, Pubmed and Google Scholar, with critical evaluation of the hits. The time period up to the end of 2022 was included. RESULTS: First, the edible fern species were identified based on the literature data. A total of 90 fern species were identified that are eaten around the world and are also used in traditional medicine. Ailments treated are often associated with inflammation or bacterial infection. However, only the most common and well-known fern species, were investigated for their biological activity. The most studied species are Blechnum orientale L., Cibotium barometz (L.) J. Sm., Diplazium esculentum (Retz.) Sw., Marsilea minuta L., Osmunda japonica Thunb., Polypodium vulgare L., and Stenochlaena palustris (Burm.) Bedd. Most of the fern extracts have been studied for their antioxidant, anti-inflammatory and antimicrobial activities. Not surprisingly, antioxidant capacity has been the most studied, with results reported for 28 edible fern species. Ferns have been found to be very rich sources of flavonoids, polyphenols, polyunsaturated fatty acids, carotenoids, terpenoids and steroids and most of these compounds are remarkable free radical scavengers responsible for the outstanding antioxidant capacity of fern extracts. As far as clinical trials are concerned, extracts from only three edible fern species have been evaluated. CONCLUSIONS: The extracts of edible fern species exert antioxidant anti-inflammatory and related biological activities, which is consistent with their traditional medicinal use in the treatment of wounds, burns, colds, coughs, skin diseases and intestinal diseases. However, studies to prove pharmacological activities are scarce, and require chemical-biological standardization. Furthermore, correct botanical classification needs to be included in publications to simplify data acquisition. Finally, more in-depth phytochemical studies, allowing the linking of traditional use to pharmacological relevance are needed to be done in a standardized way.
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Queimaduras , Resfriado Comum , Gleiquênias , Dermatopatias , Humanos , Etnofarmacologia , Fitoterapia , Antioxidantes , Resfriado Comum/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Queimaduras/tratamento farmacológico , Tosse/tratamento farmacológico , Dermatopatias/tratamento farmacológicoRESUMO
INTRODUCTION: Common cold (CC) symptoms arise from an inflammatory response treatable with cineole and generally peak within two days, which complicates research implementation. We therefore explored the benefits of early cineole administration with enrolment of participants prior to CC onset. METHODS: Out of 522 adults enrolled in our phase IV, open-label, non-randomized, exploratory clinical trial (EudraCT No. 2020-000860-51), 329 developed a CC and used 200 mg cineole (Soledum®, CNL-1976) t.i.d. for max. 15 (± 2) days. Primary endpoint was burden of disease based on the Wisconsin Upper Respiratory Symptom Survey (WURSS-11). RESULTS: Comparing three strata based on time to treatment (≤ 12 h, > 12 to ≤ 24 h and > 24 h), earliest treatment resulted in lowest AUC-WURSS (Spearman correlation coefficient of 0.36) and reduced the overall burden of disease by 38% (p < 0.0001). Earlier and lower symptom severity peak resulted, with shorter time to remission (average 8.9 vs. 10.7 days with latest treatment initiation, p < 0.05), and higher and faster recovering quality of life (p < 0.05). Tolerability was mostly rated as "very good", with adverse events of suspected causal relationship reported in 4.3% of participants. CONCLUSIONS: Early intervention shows clinical benefits relevant for the effective treatment of CC with cineole.
Assuntos
Resfriado Comum , Adulto , Humanos , Resfriado Comum/tratamento farmacológico , Resfriado Comum/complicações , Eucaliptol , Qualidade de Vida , Índice de Gravidade de Doença , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Informal and unregulated rural medical practitioners (RMPs) provide healthcare services to about two-thirds of people in Bangladesh, although their service is assumed to be substandard by qualified providers. As the RMPs are embedded in the local community and provide low-cost services, their practice pattern demands investigation to identify the shortfalls and design effective strategies to ameliorate the service. METHODS: We conducted a cross-sectional study in 2015-16 using a convenient sample from all 64 districts of Bangladesh. Personnel practising modern medicine, without any recognized training, or with recognized training but practising outside their defined roles, and without any regulatory oversight were invited to take part in the study. Appropriateness of the diagnosis and the rationality of antibiotic and other drug use were measured as per the Integrated Management of Childhood Illness guideline. RESULTS: We invited 1004 RMPs, of whom 877 consented. Among them, 656 (74.8%) RMPs owned a drugstore, 706 (78.2%) had formal education below higher secondary level, and 844 (96.2%) had informal training outside regulatory oversight during or after induction into the profession. The most common diseases encountered by them were common cold, pneumonia, and diarrhoea. 583 (66.5%) RMPs did not dispense any antibiotic for common cold symptoms. 59 (6.7%) and 64 (7.3%) of them could identify all main symptoms of pneumonia and diarrhoea, respectively. In pneumonia, 28 (3.2%) RMPs dispensed amoxicillin as first-line treatment, 819 (93.4%) dispensed different antibiotics including ceftriaxone, 721 (82.2%) dispensed salbutamol, and 278 (31.7%) dispensed steroid. In diarrhoea, 824 (94.0%) RMPs dispensed antibiotic, 937 (95.4%) dispensed ORS, 709 (80.8%) dispensed antiprotozoal, and 15 (1.7%) refrained from dispensing antibiotic and antiprotozoal together. CONCLUSIONS: Inappropriate diagnoses, irrational use of antibiotics and other drugs, and polypharmacy were observed in the practising pattern of RMPs. The government and other stakeholders should acknowledge them as crucial partners in the healthcare sector and consider ways to incorporate them into curative and preventive care.
Assuntos
Resfriado Comum , Pneumonia , Humanos , Bangladesh/epidemiologia , Estudos Transversais , Resfriado Comum/tratamento farmacológico , Radar , Antibacterianos/uso terapêutico , Diarreia/tratamento farmacológico , Pneumonia/tratamento farmacológicoRESUMO
BACKGROUND: Randomized trials have shown that vitamin C shortens the duration of common colds. Some trials reported greater effects on severe cold symptoms compared with mild symptoms. This review systematically compares the effects of vitamin C on severe and mild common cold symptoms. METHODS: We included all placebo-controlled trials of orally administered vitamin C in doses of at least 1 g/day for the common cold for people in good health at baseline. The analysis was restricted to trials which reported both the total duration of the common cold, and the severity of the common cold measured using severity scales, the duration of more severe stages of the cold, or proxies for severe colds such as days indoors. Findings were pooled using the inverse variance, fixed effect options of the metacont function of the R package meta to calculate the ratio of means estimate. RESULTS: Fifteen comparisons from 10 trials which reported both mild and severe symptoms were identified. All trials were randomized and double-blind. Compared to placebo, vitamin C significantly decreased the severity of the common cold by 15% (95% CI 9-21%). The direct comparison of the effect of vitamin C on mild and severe symptoms was limited to five comparisons which found that vitamin C had a significant benefit on the duration of severe symptoms. In this subset, there was a significant difference in the size of the effect of vitamin C on the overall duration of colds versus the duration of severe colds (P = 0.002), and vitamin C had no significant effect on the duration of mild symptoms. CONCLUSIONS: The common cold is the leading cause of acute morbidity and a major cause of absenteeism from work and school. However, absenteeism is dependent on the severity of symptoms. The finding that vitamin C may have a greater effect on more severe measures of the common cold is therefore important. Further research on the therapeutic effects of vitamin C on the common cold should measure outcomes of differing levels of severity.
Assuntos
Resfriado Comum , Humanos , Resfriado Comum/tratamento farmacológico , Ácido Ascórbico/uso terapêutico , Vitaminas/uso terapêutico , Método Duplo-Cego , Absenteísmo , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Forsythin, an active compound from Forsythiae Fructus, has the potential to treat the common cold and influenza through its antipyretic-analgesic, anti-inflammatory and antiviral effects. The safety, tolerability and pharmacokinetic (PK) profile of forsythin were evaluated in healthy Chinese subjects. METHODS: This phase 1a study included three parts: double-blind, randomized, placebo-controlled single-ascending-dose (SAD) (50, 100, 200, 400, 600 or 800 mg), food effect investigation (100 mg) and multiple-ascending-dose (MAD) (50, 100 or 200 mg TID for 5 days). RESULTS: Forsythin is safe and tolerable in healthy Chinese subjects. The rates of adverse events (AEs) in the forsythin cohort were similar to those in the placebo cohort. Forsythin is well-absorbed after single or multiple doses and is extensively metabolized. The primary metabolites were aglycone M1, M1 sulphate (M2) and M1 glucuronide (M7). Exposure to forsythin (100 mg) was higher after food intake by approximately 1.4-fold, whereas M2 and M7 did not change. The steady state was reached around three days in the MAD study. Forsythin, M2 and M7 accumulation on day 5 was 1, 3 and 2, respectively. CONCLUSIONS: The safety and PK profiles of forsythin support further evaluation of its efficacy in individuals with the common cold or influenza.
Assuntos
Resfriado Comum , Influenza Humana , Humanos , Voluntários Saudáveis , Resfriado Comum/tratamento farmacológico , Área Sob a Curva , Método Duplo-Cego , Relação Dose-Resposta a DrogaRESUMO
BACKGROUND: Concerns exist regarding antibiotic prescribing for respiratory tract infections (RTIs) owing to adverse reactions, cost and antibacterial resistance. One proposed strategy to reduce antibiotic prescribing is to provide prescriptions, but to advise delay in antibiotic use with the expectation that symptoms will resolve first. This is an update of a Cochrane Review originally published in 2007, and updated in 2010, 2013 and 2017. OBJECTIVES: To evaluate the effects on duration and/or severity of clinical outcomes (pain, malaise, fever, cough and rhinorrhoea), antibiotic use, antibiotic resistance and patient satisfaction of advising a delayed prescription of antibiotics in respiratory tract infections. SEARCH METHODS: From May 2017 until 20 August 2022, this was a living systematic review with monthly searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL and Web of Science. We also searched the WHO International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov on 20 August 2022. Due to the abundance of evidence supporting the review's key findings, it ceased being a living systematic review on 21 August 2022. SELECTION CRITERIA: Randomised controlled trials involving participants of all ages with an RTI, where delayed antibiotics were compared to immediate or no antibiotics. We defined a delayed antibiotic as advice to delay the filling of an antibiotic prescription by at least 48 hours. We considered all RTIs regardless of whether antibiotics were recommended or not. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. MAIN RESULTS: For this 2022 update, we added one new trial enrolling 448 children (436 analysed) with uncomplicated acute RTIs. Overall, this review includes 12 studies with a total of 3968 participants, of which data from 3750 are available for analysis. These 12 studies involved acute RTIs including acute otitis media (three studies), streptococcal pharyngitis (three studies), cough (two studies), sore throat (one study), common cold (one study) and a variety of RTIs (two studies). Six studies involved only children, two only adults and four included both adults and children. Six studies were conducted in primary care, four in paediatric clinics and two in emergency departments. Studies were well reported and appeared to provide moderate-certainty evidence. Randomisation was not adequately described in two trials. Four trials blinded the outcome assessor, and three included blinding of participants and doctors. We conducted meta-analyses for pain, malaise, fever, adverse effects, antibiotic use and patient satisfaction. Cough (four studies): we found no differences amongst delayed, immediate and no prescribed antibiotics for clinical outcomes in any of the four studies. Sore throat (six studies): for the outcome of fever with sore throat, four of the six studies favoured immediate antibiotics, and two found no difference. For the outcome of pain related to sore throat, two studies favoured immediate antibiotics, and four found no difference. Two studies compared delayed antibiotics with no antibiotic for sore throat, and found no difference in clinical outcomes. Acute otitis media (four studies): two studies compared immediate with delayed antibiotics - one found no difference for fever, and the other favoured immediate antibiotics for pain and malaise severity on Day 3. Two studies compared delayed with no antibiotics: one found no difference for pain and fever severity on Day 3, and the other found no difference for the number of children with fever on Day 3. Common cold (two studies): neither study found differences for clinical outcomes between delayed and immediate antibiotic groups. One study found delayed antibiotics were probably favoured over no antibiotics for pain, fever and cough duration (moderate-certainty evidence). ADVERSE EFFECTS: there were either no differences for adverse effects or results may have favoured delayed over immediate antibiotics with no significant differences in complication rates (low-certainty evidence). Antibiotic use: delayed antibiotics probably resulted in a reduction in antibiotic use compared to immediate antibiotics (odds ratio (OR) 0.03, 95% confidence interval (CI) 0.01 to 0.07; 8 studies, 2257 participants; moderate-certainty evidence). However, a delayed antibiotic was probably more likely to result in reported antibiotic use than no antibiotics (OR 2.52, 95% CI 1.69 to 3.75; 5 studies, 1529 participants; moderate-certainty evidence). Patient satisfaction: patient satisfaction probably favoured delayed over no antibiotics (OR 1.45, 1.08 to 1.96; 5 studies, 1523 participants; moderate-certainty evidence). There was probably no difference in patient satisfaction between delayed and immediate antibiotics (OR 0.77, 95% CI 0.45 to 1.29; 7 studies, 1927 participants; moderate-certainty evidence). No studies evaluated antibiotic resistance. Reconsultation rates and use of alternative medicines were similar for delayed, immediate and no antibiotic strategies. In one of the four studies reporting use of alternative medicines, less paracetamol was used in the immediate group compared to the delayed group. AUTHORS' CONCLUSIONS: For many clinical outcomes, there were no differences between prescribing strategies. Symptoms for acute otitis media and sore throat were modestly improved by immediate antibiotics compared with delayed antibiotics. There were no differences in complication rates. Delaying prescribing did not result in significantly different levels of patient satisfaction compared with immediate provision of antibiotics (86% versus 91%; moderate-certainty evidence). However, delay was favoured over no antibiotics (87% versus 82%). Delayed antibiotics achieved lower rates of antibiotic use compared to immediate antibiotics (30% versus 93%). The strategy of no antibiotics further reduced antibiotic use compared to delaying prescription for antibiotics (13% versus 27%). Delayed antibiotics for people with acute respiratory infection reduced antibiotic use compared to immediate antibiotics, but was not shown to be different to no antibiotics in terms of symptom control and disease complications. Where clinicians feel it is safe not to prescribe antibiotics immediately for people with RTIs, no antibiotics with advice to return if symptoms do not resolve is likely to result in the least antibiotic use while maintaining similar patient satisfaction and clinical outcomes to delayed antibiotics. Where clinicians are not confident in not prescribing antibiotics, delayed antibiotics may be an acceptable compromise in place of immediate prescribing to significantly reduce unnecessary antibiotic use for RTIs, while maintaining patient safety and satisfaction levels. Further research into antibiotic prescribing strategies for RTIs may best be focused on identifying patient groups at high risk of disease complications, enhancing doctors' communication with patients to maintain satisfaction, ways of increasing doctors' confidence to not prescribe antibiotics for RTIs, and policy measures to reduce unnecessary antibiotic prescribing for RTIs.
Assuntos
Resfriado Comum , Otite Média , Faringite , Infecções Respiratórias , Criança , Adulto , Humanos , Resfriado Comum/tratamento farmacológico , Resfriado Comum/complicações , Antibacterianos/efeitos adversos , Tosse/tratamento farmacológico , Infecções Respiratórias/tratamento farmacológico , Faringite/tratamento farmacológico , Otite Média/tratamento farmacológico , Febre/tratamento farmacológico , Febre/etiologia , Dor/tratamento farmacológicoRESUMO
Four endemic seasonal human coronaviruses causing common colds circulate worldwide: HKU1, 229E, NL63 and OC43 (ref. 1). After binding to cellular receptors, coronavirus spike proteins are primed for fusion by transmembrane serine protease 2 (TMPRSS2) or endosomal cathepsins2-9. NL63 uses angiotensin-converting enzyme 2 as a receptor10, whereas 229E uses human aminopeptidase-N11. HKU1 and OC43 spikes bind cells through 9-O-acetylated sialic acid, but their protein receptors remain unknown12. Here we show that TMPRSS2 is a functional receptor for HKU1. TMPRSS2 triggers HKU1 spike-mediated cell-cell fusion and pseudovirus infection. Catalytically inactive TMPRSS2 mutants do not cleave HKU1 spike but allow pseudovirus infection. Furthermore, TMPRSS2 binds with high affinity to the HKU1 receptor binding domain (Kd 334 and 137 nM for HKU1A and HKU1B genotypes) but not to SARS-CoV-2. Conserved amino acids in the HKU1 receptor binding domain are essential for binding to TMPRSS2 and pseudovirus infection. Newly designed anti-TMPRSS2 nanobodies potently inhibit HKU1 spike attachment to TMPRSS2, fusion and pseudovirus infection. The nanobodies also reduce infection of primary human bronchial cells by an authentic HKU1 virus. Our findings illustrate the various evolution strategies of coronaviruses, which use TMPRSS2 to either directly bind to target cells or prime their spike for membrane fusion and entry.
Assuntos
Betacoronavirus , Receptores Virais , Serina Endopeptidases , Glicoproteína da Espícula de Coronavírus , Humanos , Betacoronavirus/metabolismo , Brônquios/citologia , Brônquios/virologia , Resfriado Comum/tratamento farmacológico , Resfriado Comum/virologia , Fusão de Membrana , Receptores Virais/metabolismo , SARS-CoV-2 , Serina Endopeptidases/metabolismo , Anticorpos de Domínio Único/farmacologia , Anticorpos de Domínio Único/uso terapêutico , Especificidade da Espécie , Glicoproteína da Espícula de Coronavírus/metabolismo , Internalização do VírusRESUMO
WHAT IS THIS SUMMARY ABOUT?: This is a summary of the results of 2 clinical studies that looked at a medicine called tezepelumab. Tezepelumab is approved in the United States of America (USA), the European Union (EU) and several other countries for the treatment of severe, uncontrolled asthma in people aged 12 and above. The results of these 2 studies, called PATHWAY and NAVIGATOR, formed the basis for tezepelumab's approval for use. Tezepelumab is a type of biologic treatment called an antibody. Biologics are treatments that target certain cells or proteins in the body and often in the immune system - the body's natural defence system against infections and diseases - to reduce patients' disease. It works by blocking a key first step in the body's chain reaction leading to inflammation in the airways of people with severe asthma. The clinical studies were done to learn if tezepelumab can be used to treat people with severe, uncontrolled asthma and to find out about its safety. In both studies, tezepelumab was compared to placebo. A placebo is a dummy treatment that looked like tezepelumab but did not have any medicine in it. WHAT WERE THE MAIN CONCLUSIONS REPORTED BY THE RESEARCHERS?: In both studies, tezepelumab reduced the number of severe asthma attacks that the participants had per year compared with placebo. It also increased the volume of air that the participants could breathe out in 1 second compared with placebo. Tezepelumab was well-tolerated, and a similar number of participants had health issues in the tezepelumab and placebo treatment groups. The most common health issues that the participants had during the PATHWAY study were: Worsening of asthma, common cold, headache, and inflammation of the airways. The most common health issues that the participants had during the NAVIGATOR study were: Common cold, infection of the sinuses, throat and airways, headache, worsening of asthma, and inflammation of the airways. WHAT ARE THE KEY TAKEAWAYS?: The results showed that participants who had monthly doses of tezepelumab had fewer severe asthma attacks and better lung function than those who had placebo. In both studies, the health issues that the participants had were similar between the tezepelumab and placebo treatment groups. Overall, the studies showed that tezepelumab worked in a broad population of people with severe asthma and that the study participants had an acceptable level of health issues during the studies. These results led to the approval of tezepelumab for people with severe asthma aged 12 and above in the USA, EU and other countries. Clinical Trial Registration: PATHWAY study: NCT02054130; NAVIGATOR study: NCT03347279 (ClinicalTrials.gov).
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Antiasmáticos , Asma , Resfriado Comum , Humanos , Antiasmáticos/uso terapêutico , Resfriado Comum/tratamento farmacológico , Método Duplo-Cego , Cefaleia , Inflamação/tratamento farmacológico , Estudos Clínicos como AssuntoRESUMO
BACKGROUND: This study aims to explore the impacts of knowledge and attitude on the behavior of antibiotic use during the treatment of the common cold based on the expanding KAP model, and then identify the critical behavioral stage. METHODS: A cross-sectional study was conducted on 815 public from 21 community health centers (CHCs) in Chongqing, China. Based on the expanding KAP model, a self-administered questionnaire was designed to measure knowledge, attitude, multi-stage behavior, and perceived threat, in which multi-stage behavior was divided into pre-use antibiotic behavior, during-use antibiotic behavior, and post-use antibiotic behavior. A structural equation model was used to examine the model fit and the direct, indirect, mediating effects, and moderating effect of the variables. RESULTS: The expanding KAP showed good model fit indices with χ²/df = 0.537, RMSEA = 0.033, CFI = 0.973, GFI = 0.971, NFI = 0.934, TLI = 0.979. Knowledge had a positive effect on attitude (ß = 0.503, p < 0.05), pre-use antibiotic behavior (ß = 0.348, p < 0.05), during-use antibiotic behavior (ß = 0.461, p < 0.001), and post-use antibiotic behavior (ß = 0.547, p < 0.001). Attitude had a positive effect on during-use antibiotic behavior (ß = 0.296, p < 0.001), and post-use antibiotic behavior (ß = 0.747, p < 0.001). The mediating effect of attitude was positive among knowledge, during-use antibiotic behavior (ß = 0.149, p < 0.05), and post-use antibiotic behavior (ß = 0.376, p < 0.001). Perceived threat also had a positive moderating effect between knowledge and post-use antibiotic behavior (ß = 0.021, p < 0.001). CONCLUSIONS: Knowledge, attitude and perceived threat had different effects on different stages of antibiotic behavior. The critical behavioral stage prioritized the post-use antibiotic behavior and during-use antibiotic behavior over pre-use antibiotic behavior.
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Resfriado Comum , Humanos , Resfriado Comum/tratamento farmacológico , Estudos Transversais , Conhecimento , Antibacterianos/uso terapêutico , ChinaRESUMO
BACKGROUND: Most childhood infections are of viral origin making antibiotics unnecessary. They are, however, the most frequently prescribed drugs dispensed to children, resulting in inappropriate antibiotic prescriptions, which are one of the main drivers of antibiotic resistance. AIM: The study aimed to determine the prevalence of antibiotic prescriptions and identify its associated factors among children below 5 years with common cold who attend the outpatient department in Tororo General Hospital. SETTING: The study was carried out in Tororo General Hospital, Eastern Uganda. METHODS: A cross-sectional survey using consecutive sampling was performed among children below 5 years with common cold attending the outpatient department. Data were collected using an interviewer-administered, structured questionnaire and analysed using STATA version 14.0. Prevalence of antibiotic prescriptions was calculated. Bivariate analysis using chi-square test and multivariate analysis using logistic regression was performed to establish factors associated with antibiotic prescription. RESULTS: The prevalence of antibiotic prescriptions for common cold among children below 5 years was 23.3%. Factors associated with antibiotic prescription for common cold were duration of symptoms of more than 5 days (OR, 95% CI: 4.49; 1.16-17.23, p = 0.029) and being attended to by a clinical officer (OR, 95% CI: 0.19; 0.04-0.91, p = 0.038). CONCLUSION: There is inappropriate antibiotic prescription among children with common cold in Tororo General Hospital. There is need for antibiotic stewardship programmes to promote optimal antibiotic use in primary care facilities.Contribution: The study's findings can be used to develop context-specific antibiotic stewardship programmes tailored to promote judicious use of antibiotics in primary care.
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Resfriado Comum , Infecções Respiratórias , Criança , Humanos , Resfriado Comum/tratamento farmacológico , Antibacterianos/uso terapêutico , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/tratamento farmacológico , Estudos Transversais , Hospitais de Distrito , Uganda , Prescrições de MedicamentosRESUMO
Macrolide usage in Japan exceeds that in Europe and the United States. Investigating the actual conditions in which macrolides are used is important for identifying further interventions for appropriate antimicrobial use; however, this situation has not been evaluated in Japan. Therefore, we aimed to clarify the number of macrolide prescriptions and their changes before and after implementation of the Antimicrobial Resistance (AMR) Action Plan. In addition, we also investigated the names of diseases for which macrolides have been prescribed and the number of days of prescription. A retrospective observational study was conducted using JMDC claims data from January 2013 to December 2018. The proportion of all oral antimicrobials and macrolides used during this period and the diseases for which macrolides were used in the 3 years before and after the AMR Action Plan were determined separately for acute (< 14 prescription days) and chronic (> 14 prescription days) diseases. The number of prescriptions for macrolides constituted approximately 30% of those for all oral antimicrobials; of these, clarithromycin accounted for approximately 60%. Most prescriptions for acute diseases were for common cold, whereas allergic and dermatological diseases were included among chronic diseases. The names of these illnesses did not change before and after the AMR Action Plan. Overall, these results indicate that appropriate macrolide use involves a review of their use for common cold along with appropriate evaluation of their long-term use for skin and allergic diseases. They also indicate the need for further fact-finding studies and ongoing AMR measures.
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Anti-Infecciosos , Resfriado Comum , Hipersensibilidade , Humanos , Macrolídeos/uso terapêutico , Resfriado Comum/tratamento farmacológico , Estudos Retrospectivos , Japão , Antibacterianos/uso terapêutico , Prescrições , Hipersensibilidade/tratamento farmacológico , Estudos Observacionais como AssuntoRESUMO
Regan Syrup has the effect of clearing heat, releasing exterior, benefiting pharynx and relieving cough, and previous phase â ¡ clinical trial showed that the efficacy of Regan Syrup high-dose and low-dose groups was better than that of the placebo group, and there was no statistically significant difference in the safety between the three groups. The present study was conducted to further investigate the efficacy and safety of the recommended dose(20 mL) of Regan Syrup in the treatment of common cold(wind-heat syndrome). Patients who met the inclusion and exclusion criteria were selected and divided into the test group(Regan Syrup+Shufeng Jiedu Capsules placebo), positive drug group(Regan Syrup placebo+Shufeng Jiedu Capsules) and placebo group(Regan Syrup placebo+Shufeng Jiedu Capsules placebo) at a 1â¶1â¶1 using a block randomization method. The course of treatment was 3 days. A total of 119 subjects were included from six study centers, 39 in the test group, 40 in the positive drug group and 40 in the placebo group. The onset time of antipyretic effect was shorter in the test group than in the placebo group(P≤0.01) and the positive drug group, but the difference between the test group and the positive drug group was not significant. The test group was superior to the positive drug group in terms of fever resolution(P<0.05), and had a shorter onset time of fever resolution than the placebo group, but without obvious difference between the two groups. Compared to the positive drug group, the test group had shortened disappearance time of all symptoms(P≤0.000 1). In addition, the test group was better than the positive drug group and the placebo group in relieving symptoms of sore throat and fever(P<0.05), and in terms of clinical efficacy, the recovery rate of common cold(wind-heat syndrome) was improved in the test group compared to that in the placebo group(P<0.05). On the fourth day after treatment, the total TCM syndrome score in both test group and positive drug group was lower than that in the placebo group(P<0.05). There was no significant difference in the incidence of adverse events between three groups and none of them experienced any serious adverse events related to the study drug. The results indicated that Regan Syrup could shorten the onset time of antipyretic effect, reduce the time of fever resolution, alleviate the symptoms such as sore throat and fever caused by wind-heat cold, reduce the total score of Chinese medicine symptoms, and improve the clinical recovery rate with good safety.
Assuntos
Antipiréticos , Resfriado Comum , Faringite , Humanos , Antipiréticos/efeitos adversos , Antipiréticos/uso terapêutico , Cápsulas , Resfriado Comum/tratamento farmacológico , Resfriado Comum/diagnóstico , Método Duplo-Cego , Febre/tratamento farmacológico , Temperatura Alta , Resultado do TratamentoRESUMO
OBJECTIVE: To determine objective and subjective endpoints most suitable for evaluating antitussive efficacy of dextromethorphan hydrobromide (DXM) in children. Spontaneous resolution of acute cough and large placebo effects are impediments to evaluating antitussive efficacy. Another impediment is paucity of age-appropriate, validated cough assessment tools. METHODS: This was a multiple-dose, double-blind, placebo-controlled, randomized, pilot clinical study in children, aged 6-11 years, with cough due to the common cold. Eligible subjects met entry criteria and qualified by completing a run-in period where coughs were recorded with a cough monitor after they were dosed with sweet syrup. They were subsequently randomized to receive DXM or placebo over 4 days. Coughs were recorded during the initial 24 h; subjective assessments of cough severity and frequency were self-reported daily during treatment. RESULTS: Data from 128 evaluable subjects (67 DXM; 61 placebo) were analyzed. Total coughs over 24-hours (primary endpoint) and cough frequency during daytime were reduced by 21.0% and 25.5%, respectively, with DXM relative to placebo. Also, greater reductions in cough severity and frequency were self-reported with DXM. These findings were statistically significant and medically relevant. No effects were detected between treatments for nighttime cough rates or impact of cough on sleep. Multiple doses of DXM and placebo were generally well-tolerated. CONCLUSION: Evidence of DXM antitussive efficacy was shown in children using objective and subjective assessment tools validated in pediatric populations. Diurnal variation of cough frequency over 24 h reduced the assay sensitivity needed to detect treatment differences at nighttime, as coughs/hour decreased during sleep for both groups.