Husten Wann Zum Arzt Kind

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Du schaust: Husten wann zum arzt kind


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Background

Cough in children zu sein a frequently experienced symptom that is damit verbundenen with raised health leistungen utilisation und burden to parents. Ns presence von chronic (equal zu or an ext than 4 weeks) cough in children may show a significant underlying condition such as inhaled international body or bronchiectasis. Codeine (and derivative)‐based drugs are occasionally used to treat cough due to their antitussive properties. However, there are innate risks associated with ns use of these medicines such together respiratory journey suppression, anaesthetic‐induced anaphylaxis, und addiction. Metabolic response and dosage variability ar children weist increased risk von experiencing together side effects. A systematic evaluation evaluating the quality von the accessible literature would be useful kommen sie inform administration practices.

Objectives

To evaluate the safety and efficacy of codeine (and derivatives) in the treatment von chronic cough bei children.

Search methods

We searched ns Cochrane Airways group Register of Trials, Cochrane central Register of Controlled Trials (CENTRAL), MEDLINE (1946 kommen sie 8 June 2016), EMBASE (1974 to 8 June 2016), the online trials registries of the world Health Organization und ClinicalTrials.gov, und the bibliographic references von publications. We imposed no language restrictions.

Selection criteria

We considered studien eligible zum analysis when: die participant population included children aged less than 18 years v chronic cough (duration equal kommen sie or an ext than four weeks at the time des intervention); und the study design evaluated codeine or codeine‐based derivatives versus placebo v a randomised managed trial.

Data collection und analysis

Two evaluation authors individually screened die search results kommen sie determine eligibility against a standardised criteria, und we had actually a pre‐planned method weil das analysis.

Main results

We established a total des 556 records, von which 486 documents were exclude, on the basis of title and abstract. We retrieved the remaining 70 references in full kommen sie determine eligibility. No forschung fulfilled ns inclusion criteria des this review, and thus we discovered no evidence zu support or oppose ns use von codeine or derivatives as antitussive agents zum chronic cough bei children.

While chronic cough ist not die same together acute cough, systematic reviews on ns use of codeine efficacy for acute cough in children conclude bei overall lack of evidence zu support or oppose the use von over‐the‐counter cough and cold drugs containing codeine (or derivatives) for treatment of acute cough bei children. Ns lack des sufficient evidence to support ns use of these medications has actually been consistently reaffirmed von medical experts in international chronic sneeze guidelines and by administrate medical and pharmaceutical authorities bei the USA, Europe, Canada, neu Zealand, und Australia. early to ns lack von sufficient evidence to support efficacy, and the known risks damit verbundenen with usage ‐ in particular ns increased risks zum children ‐ these medicines are now notfall recommended for children less than 12 years von age and children betwee 12 kommen sie 18 years with respiratory conditions.

Authors"https://miyvue.com/husten-wann-zum-arzt-kind/imager_2_2996_700.jpg conclusions

This review has highlighted die absence von any randomised regulated trials examining codeine‐based medications an the treatment von childhood chronic cough. Given die potential disadvantage events des respiratory suppression und opioid toxicity, national therapeutic regulatory authorities recommend die contraindication of access zu codeine in children less than 12 years of age. We imply that clinical practice adhere kommen sie clinical practice guidelines und thus aufhören from making use of codeine or its derivatives to treat cough an children. Aetiological‐based management practices continue kommen sie be advocated zum children v chronic cough.


Codein weil das die behandlung von chronischem Husten an Kindern

Fragestellung

Wir gingen das Frage nach, wenn die behandlung mit Codein (oder mit Arzneimitteln, die ende Codein ist hergestellt werden) an Kindern mit chronischem Husten (vier Wochen heu länger) verträglich und effizienz ist.

Hintergrund

Husten ist einer sehr häufige erkrankung und einer ns häufigsten ursache einen arzt oder einen anderen Gesundheitsdienstleister aufzusuchen. Chronischer Husten (vier Wochen oder länger) an Kindern tun können ein Anzeichen für einer ernstzunehmende Grunderkrankung sein. Codein (oder Arzneimittel, die das ende Codein hergestellt werden) ist an einigen freiverkäuflichen ebenso auch an einigen verschreibungspflichtigen Hustensäften enthalten. Dies Arzneimittel genutzt man, ca den Husten zu lindern, duf mit der antrag bekannte Risiken relevant sind, unter Atemschwierigkeiten, allergische reaktion und Sucht. Uns wollten das Sicherheit und ns Nutzen dieser Arzneimittel zum die behandelt von chronischem Husten in Kindern untersuchen.

Suchdatum

Wir suchten nach allen Studien, die bis um zum 8. Juni 2016 bereits veröffentlicht waren hagen kurz vor standen.

Studienmerkmale

Wir gesucht nach allen randomisierten kontrollierten Studien, in denen die behandelt von chronischem Husten (vier Wochen hagen länger) in Kindern bis zu 18 jahr mit entweder Codein (oder Arzneimittel, die ende Codein ist hergestellt werden) oder einer Scheinmedikament (Placebo) vergleichen wurde.

Hauptergebnisse

Die suchen ergab 556 Treffer. Uns überprüften und bewerteten alle nach vor festgelegten Einschluss‐ und Ausschlusskriterien. Wir gründen keine Studien, die geeignet waren, um sie in dies Review aufzunehmen. Jedoch gründen wir in unserer finden suchen Studien in denen die behandelt von kindern mit akutem Husten (zwei Wochen hagen weniger) mit Codein (oder Arzneimitteln, die aus Codein ist hergestellt werden) sondiert wurde. Bei einem ist anders Cochrane‐Review besonders für kinder mit akutem Husten wurden dies Studien bereits bewertet und es wurde sind nicht Evidenz weil das oder gegen das Verwendung by Codein (oder Arzneimitteln, die aus Codein hergestellt werden) gefunden. Dieser Mangel in Evidenz steht im Einklang mit internationalen Leitlinien zum chronischen Husten, das empfehlen die Ursache ns Hustens kommen sie behandeln. Aufgrund der bekannten Risiken, die mit der antrag verbunden sind, und insbesondere der erhöhten Risiken für Kinder vorstellen Dachverbände aus den USA, Europa, Kanada, Neuseeland und australien diese medizin für Kinder darunter 12 Jahren nicht und ebensowenig zum Kinder mit Atemproblemen mitte 12 und 18 Jahren. Weil befürwortende forschung fehlen, weil der Ergebnisse by Studien kommen sie akutem Husten bei Kindern und da der bekannten schädlichen Nebenwirkungen daraus schließen wir, dass Codein‐basierte arzneimittel für die behandelt von kindern mit chronischem Husten nicht beraten werden können.

Qualität ns Evidenz

Wir gründen keine Studien, daher gibt das keine Bewertung der Qualität ns Evidenz.


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Implications zum practice

There zu sein currently no published RCT and hence no proof on die efficacy des codeine (or codeine derivatives)‐based medicines as antitussives an improving clinical outcomes zum chronic cough bei children. Over there are, however, recorded risks verbunden with ns use des these medications, und children room particularly hinweisen risk. There is a high degree of variability an codeine‐morphine metabolism in children, with ns potential adverse events von respiratory suppression and opioid‐toxicity being an especially concerning. Furthermore, in the management of chronic cough an children, die underlying aetiology have to be defined, fairly than die cough empirically treated, together recommended bei national cough guidelines und systematic evaluate (Chang 2006b; Chang 2016; Gibson 2010; Shields 2008). Thus, together recommended bei many national guidelines, it is currently advocated that codeine und its derivatives are notfall used zum cough bei children less than 12 years von age.

Implications zum research

Childhood chronic cough is a comprehensive burden zum families and the healthcare system alike. This review has highlighted a lack des high‐quality RCTs assessing codeine‐based medications an the treatment von childhood chronic cough. However, given the damit verbundenen risks an children and that aetiological‐based administration practices space advocated in the management von chronic cough in children (Chang 2006b; Chang 2016), it zu sein highly unlikely that RCTs making use of currently obtainable preparations von codeine or/and that derivatives will be undertaken bei children. If future derivatives that carry out not schutz the next effects associated with codeine (and derivatives) come to be available, such studien should it is in parallel, double‐blinded RCTs using validated cough outcome actions that incorporate patient‐relevant und objective outcomes (Boulet 2015),


Description von the condition

Cough is a typically experienced symptom within ns community (Chang 2015), und was established as die leading reason zum acute consultations kommen sie general practitioners bei Australia betwee 2009 and 2010 (Britt 2010). Cough in children kann sein be extensively categorised right into acute (coughing lasting much less than two weeks) or chronic (coughing duration longer than 4 weeks) (Chang 2006a; dach Jongste 2003; Gibson 2010). Ns latter was the subject of this review.

Unlike acute cough (which regularly results from a famous infection), die aetiology von chronic cough is diverse and may indicate a significant underlying an illness such as an airway abnormality or bronchiectasis. Irrespective of the type von cough or that aetiology, parents und carers regularly seek relief zum their child"https://miyvue.com/husten-wann-zum-arzt-kind/imager_2_2996_700.jpgs sneeze (Vernacchio 2008). This zu sein not surprising as the burden des cough ist multidimensional and can negatively affect individuals and their family members (Anderson‐James 2014; Marchant 2008).

Description of the intervention

Codeine is derived from ns Papaver somniferum, or minus poppy plant, and was erste extracted bei 1830 by a French chemist, Pierre‐Jean Robiquet (Kane 2007). Codeine is in alkaloid opiate compound und is predominantly offered as in analgesic and antitussive (cough suppressant) agent in health care. Since the discovery von codeine, numerous opiates and semi‐synthetic derivatives have been developed and utilised zum many reasons, consisting of their antitussive nature (Kane 2007). If preparations may be prescription controlled, many des these drugs are readily available und easily accessible bei combination therapies with antihistamines, antipyretics, decongestants, or expectorants as over‐the‐counter, non‐prescription sneeze syrups or lozenges. Ns ease of accessibility of such treatments has actually likely contributed zu a perception von their safety and efficacy und has contributed zu widespread usage within ns community (Lokker 2009).

How the beteiligung might work

Codeine (and derivatives) schutz been provided as an antitussive for centuries. Die medication acts mostly through opioid receptors von the central nervous system, although ns exact mechanisms of action space unknown (Takahama 2007). In alternative mechanism of action zu sein through sedation (Dickinson 2014). The pharmacodynamic properties von codeine in children are poorly understood, although over there are recognized inherent und undesirable side effects associated with this class of antitussives.

Side effects may include respiratory depression, pruritis, rash, facial swelling, vomiting, and ataxia (Fleming 2014). Codeine ist metabolised von several enzyme such together CYP3A4 und CYP2D6. Ns latter switch codeine zu morphine, the active metabolite. There are genetic variants des CYP2D6, und rapid metabolism rates increase ns risk des respiratory drive suppression und adverse results (Committee on medicine 1997). Separation, personal, instance responsiveness zu codeine‐based combination therapies is unpredictable, with age, hereditary make‐up, ethnicity, und disease aetiology influencing the outcome (Fleming 2014; Gadomski 1992).

There is growing international concern regarding the availability und safety of codeine, with the consequences of hyper‐metabolism, drug abuse, and the risk des anaesthetic‐induced anaphylaxis at die forefront of reform agendas (European Medicines agency 2015; Florvaag 2012; Mattoo 1997).

Why it zu sein important zu do this review

Codeine (and derivatives)‐based against agents room widely used bei the paediatric population, although the mechanism of action ist poorly understood. Ns safety und efficacy von exposure ist highly variable, with children weist increased risk des experiencing far-ranging adverse effects (Gadomski 1992). Die burden von cough ist multifaceted, resulting notfall only an parental stress und worry, but also on a child"https://miyvue.com/husten-wann-zum-arzt-kind/imager_2_2996_700.jpgs ability kommen sie participate completely within die gesellschaft due zu school and work time ns (Marchant 2008). Rigorously evaluating the efficacy von various therapy options, including codeine and its derivatives as antitussive agents, will thus assist in clinical management and allow informed burden‐reduction therapy strategies an children.


Criteria zum considering studies weil das this review

Types of studies

We planned kommen sie include randomised regulated trials (RCTs), quasi‐RCTs, und stratified RCTs that contrasted codeine (or derivatives) versus placebo. We planned zu include lernen reported as full text, those released as abstract only, and unpublished data.

Types of participants

Due to ns differing definitions und aetiology des chronic cough betwee children und adults, us sought zu include studies von children age 18 year or younger v a diagnosis of chronic cough (cough lasting 4 or an ext weeks). We excluded participants with acute cough.

Types of interventions

We sought to include lernen comparing medicines that contained codeine or codeine derivatives matches placebo.

We included ns following derivative agents in the search strategy: dihydrocodeine, nalodeine, azidocodeine, acetylcodeine, dextromethorphan, nicocodine, pholcodine, alpha‐codeimethine, 6‐succinylcodeine, 6‐codeinone, 14‐hydroxycodeine, n‐methylcodinium iodine, codeine‐7,8‐oxide, codeine‐6‐glucronide, and O(6)‐codeine methyl ether.

We planned kommen sie include ns following comparisons.

sneeze mixture include codeine or codeine derivative just as ns active ingredient versus placebo.

Cough mixture comprise codeine or codeine derivative add to other active ingredient/s versus cough mixture containing placebo plus die same other energetic ingredient/s.

Types von outcome steps major outcomes

Primary outcomes were those that reflected target measures of treatment superiority, non‐inferiority, or inferiority, and included:

number of children notfall cured punkt follow‐up;

serious adverse events (a reaction to die study medicine that results in hospital join or loss des life, or both).

an additional outcomes

The following an additional outcome measures add to the strength des primary result analysis:

symptoms und burden of cough as reported bei cough indices such as cough quality des life scores, diary card, und cough severity table of contents scores;

adverse events/side effects (any occasion that zu sein not taken into consideration life‐threatening and does not result in a hospital admission and would otherwise not occur there is no exposure to die study medication).

Reporting one or more von the outcomes detailed above in the trial was not an inclusion criterion zum the review.

Search methods for identification of studies

digital searches

We searched die following databases.

Cochrane Airways group Register of Trials (via die Cochrane Register von Studies): all years zu 8 June 2016

Cochrane central Register of Controlled Trials (CENTRAL) via die Cochrane Register des Studies Online: every years zu 8 June 2016

MEDLINE (Ovid): 1946 to June woche 1 2016

EMBASE (Ovid): 1974 zu week 23 2016

Trials registries (ClinicalTrials.gov und the welt Health Organization international Clinical Trials Registry communication (WHO ICTRP))

The MEDLINE strategy ist listed bei Appendix 1. We adapted this strategy weil das use in the other databases. Us searched all databases from their inception to die 8 June 2016. Us searched ns trials registries des ClinicalTrials.gov und WHO ICTRP every years zu 9 June 2016 (Appendix 2). We inserted no restrictions on the language of publication.

Searching other resources

We checked the reference lists des all verwandt, angemessen articles weil das additional references.

Data collection und analysis

Selection von studies

We uploaded digital search outcomes to the Covidence software application platform (Covidence 2015), and summarised results using die PRISMA flow diagram (Figure 1). Us identified und excluded duplicates und collated multiple reports von the same study. Tworeview writer (SG, HP) separately screened ns titles and abstracts des all lernen identified zum inclusion. We excluded documents on the basis of the title und abstract alone wie study design was clearly defined with no ambiguity. We retrieved ns full‐text publications of records that compelled further clarification, consisting of those published an a language other than English. We sought translation zum non‐English publications utilizing a standardised inclusion/exclusion criteria sheet. Testimonial authors separately recorded the reason zum exclusion. Whereby there to be discrepancies, a third personen (AC) adjudicated.


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säule extraction und management

It was planned the two review authors (SG, HP) were kommen sie extract the following study features from had studies.

Methods: examine design, gesamt duration des study, einzelheiten of any kind of "https://miyvue.com/husten-wann-zum-arzt-kind/imager_2_2996_700.jpgrun in"https://miyvue.com/husten-wann-zum-arzt-kind/imager_2_2996_700.jpg period, number of study centres and location, study setting, withdrawals, und date des study.

Participants: N, median age, period range, gender, severity of condition, diagnostic criteria, baseline lung function, smoking cigarettes history, consist of criteria, und exclusion criteria.

Interventions: intervention, comparison, concomitant medications, und excluded medications.

Outcomes: primary und secondary outcomes specified and collected, and time points reported.

Notes: funding for trial, und notable conflicts of interest of trial authors.

However, together no forschung fulfilled ns inclusion criteria, dünn extraction was notfall possible.

Assessment of risk des bias in included studies

It was planned the two evaluation authors (SG, HP) would separately assess risk of bias for each contained study using die criteria outlined in theCochrane Handbook zum Systematic Reviews von Interventions(Higgins 2011). Us would oase resolve any disagreements von discussion or über involving one more review writer (AC). Us planned zu assess die risk des bias according to the following domains.

random sequence generation.

Allocation concealment.

Blinding of participants and personnel.

Blinding von outcome assessment.

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Incomplete outcome data.

Selective outcome reporting.

Other bias.

We planned zu grade each potential source von bias together high, low, or unclear and provide a quote from die study report along with a justification for our judgement an the "https://miyvue.com/husten-wann-zum-arzt-kind/imager_2_2996_700.jpgRisk von bias"https://miyvue.com/husten-wann-zum-arzt-kind/imager_2_2996_700.jpg table. We planned kommen sie summarise die "https://miyvue.com/husten-wann-zum-arzt-kind/imager_2_2996_700.jpgRisk of bias"https://miyvue.com/husten-wann-zum-arzt-kind/imager_2_2996_700.jpg judgements across different studies zum each von the domain names listed. Had we determined sufficient studies, us would schutz considered blinding separately zum different vital outcomes where crucial (for example weil das unblinded outcome assessment, risk of bias zum all‐cause mortality may be very different than zum a patient‐reported pain scale). Where die info on risk des bias related to unpublished säule or correspondence v a trialist, us would have noted this in the "https://miyvue.com/husten-wann-zum-arzt-kind/imager_2_2996_700.jpgRisk von bias"https://miyvue.com/husten-wann-zum-arzt-kind/imager_2_2996_700.jpg table.

When considering treatment effects, we planned zu take into account the risk von bias for the lernen that contributed zu that outcome.

Assessment of bias in conducting the systematic testimonial

We conducted ns review follow to die published protocol and reported any kind of deviations native it in the Differences bolzen protocol und review section of this methodical review.

Measures of treatment impact

We to plan to analyse dichotomous säule as odds ratios and continuous data as mean distinction or standardised median difference. We planned zu enter dünn presented together a scale with a continuous direction von effect.

We planned zu undertake meta‐analyses only where this was meaningful, that ist if ns treatments, participants, und underlying clinical concerns were comparable enough for pooling kommen sie make sense.

We would oase narratively described skewed dünn reported as medians und interquartile ranges.

If multiple trial arms had been reported bei a single trial, we would schutz included only the verwandt, angemessen arms. Where two comparisons (for instance drug A versus placebo and drug b versus placebo) to be combined bei the very same meta‐analysis, we would have halved the control gruppe to protect against double‐counting.

Unit of analysis concerns

For dichotomous data, we planned kommen sie report ns proportion of participants contributing to each outcome in comparison with ns total number randomised. Zum rate ratios of common events whereby one participant may have more than one event, us would oase used generic inverse variance. We would oase taken the rate ratios from ns published papers and calculated die standard errors native confidence intervals (CI) or P values published in the papers. Zum cross‐over studies, median treatment differences would oase been calculation from raw data, extract or imputed and entered as fixed‐effect share inverse variance outcome, to provide an introduction weighted differences und 95% CIs.

managing missing dünn

We planned to contact investigators or examine sponsors in order kommen sie verify an essential study characteristics and obtain missing numerical outcome charme where feasible (for example wie man a study was identified as abstract only). Whereby this was not possible, and the missing dünn were thought kommen sie introduce major bias, us would oase explored the impact des including such studies in the all at once assessment von results über a sensitivity analysis.

Assessment des heterogeneity

We planned kommen sie describe und test any heterogeneity bolzen the study outcomes to lakers if it got to statistical significance using a Chi2 test. Us would oase included the 95% CI estimated using a random‐effects modell whenever there were concerns about statistical heterogeneity. We would oase considered heterogeneity far-reaching when ns P value was less than 0.10 (Higgins 2011). We would oase used die I2 statistic zu measure heterogeneity among the trials in each analysis. Had actually we identified an extensive heterogeneity, us would schutz reported this und explored feasible causes von prespecified subgroup analysis.

Assessment von reporting biases

Had us been able to pool more 보다 10 trials, we would schutz created and examined a funnel plot zu explore possible small‐study und publication biases and would oase consulted a statistician zu ensure proper analysis was conducted.

data synthesis

We planned zu use a random‐effects model and perform a sensitivity analysis with a fixed‐effect model.

"https://miyvue.com/husten-wann-zum-arzt-kind/imager_2_2996_700.jpgSummary des findings"https://miyvue.com/husten-wann-zum-arzt-kind/imager_2_2996_700.jpg table

We planned to create a "https://miyvue.com/husten-wann-zum-arzt-kind/imager_2_2996_700.jpgSummary von findings"https://miyvue.com/husten-wann-zum-arzt-kind/imager_2_2996_700.jpg table reporting the following outcomes: number of children not cured punkt follow‐up; number des children who competent a reduction in cough severity; serious adverse events; und symptoms und burden des cough as reported bei cough exponentiation tools. Us planned to use die five class considerations (study limitations, consistency of effect, imprecision, indirectness, und publication bias) kommen sie assess the quality des a body des evidence as it relates zu the forschung that contribute dünn to the meta‐analyses zum the prespecified outcomes. Us planned zu use methods and recommendations described in Section 8.5 and Chapter 12 von the Cochrane Handbook zum Systematic Reviews of Interventions (Higgins 2011), utilizing GRADEpro software program (GRADEpro GDT). We planned zu justify all decisions kommen sie down‐ or up‐grade ns quality von studies using footnotes and make comments to aid the reader"https://miyvue.com/husten-wann-zum-arzt-kind/imager_2_2996_700.jpgs understanding von the evaluation where necessary.

Subgroup analysis und investigation von heterogeneity

We planned kommen sie carry out die following subgroup analyses.

kids aged much less than seven years and seven year or older.

Children v diagnosed respiratory conditions (e.g. Cystic fibrosis (CF), non‐CF bronchiectasis) versus children with no diagnosed respiratory tract condition.

Active ingredient various other than codeine (e.g. Expectorants, antihistamines, decongestants, antipyretics, building material that may soften sneeze such as honey or syrup).

We planned zu use die following outcomes in subgroup analyses.

Number of children not cured hinweisen follow‐up.

Number des children who knowledgeable a reduction an cough severity based upon objective symptom measures of sputum production, runny nose, fevers, and air entry; as well as subjective measures von cough burden.

Serious adverse events.

We planned to use die formal test zum subgroup interactions an Review direktors 5 (RevMan 2014).

Sensitivity evaluation

We planned zu carry out die following sensitivity analyses.

A comparison based upon "https://miyvue.com/husten-wann-zum-arzt-kind/imager_2_2996_700.jpgRisk des bias"https://miyvue.com/husten-wann-zum-arzt-kind/imager_2_2996_700.jpg assessments.

A comparison of available‐case analyses matches true intention‐to‐treat (ITT) analyses, when die ITT analyses to be imputed with best‐case and worse‐case result data.

A comparison von results native fixed‐effect modell versus results from random‐effects models.


Description von studies

We figured out 903 records through database looking and in additional 25 records through other sources. After ~ removing duplicates, we screened 556 records and excluded 486 records. We retrieved full‐text articles for the continuing to be 70 records, von which 23 were excluded due kommen sie irrelevance und 47 to be excluded through reasons. We uncovered no studies that to be eligible zum inclusion in this review. Seen Figure 1 zum PRISMA diagram und the Characteristics of excluded lernen table for specific details on to exclude, records.

Results des the search

We originally performed the Cochrane Airways group Register of Trials literary works search top top 27 in march 2015, and subsequently re‐ran die search on ns 11 september 2015 und then again on ns 8 June 2016, which gave in a total von 903 recommendations (Figure 1). A search des ClinicalTrials.gov and the who ICTRP yielded bei additional 25 results. ~ de‐duplication, we taken into consideration 556 abstracts weil das inclusion against die predetermined criteria.

We exclude, a total von 486 lernen on the base of the abstract alone. Us retrieved full‐text publications for the remaining 70 references bei order zu further identify inclusion eligibility. Of these, 16 posts were published an a language various other than English (German, Italian, Czech, Spanish, und French). Translation was provided versus a standardised inclusion/exclusion template. We considered a total des 23 records irrelevant. Die remaining 47 publication did not fulfil die inclusion criteria; reasons zum exclusion space provided in the Characteristics von excluded studien table.

Included studies

There to be no contained studies.

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Excluded forschung

Reasons zum exclusion of the abovementioned full‐text articles were one of two people solely, or a combination of, the following: non‐RCT publication (n = 15); non‐placebo‐controlled study entwurf (n = 6); studies evaluating acute sneeze (n = 6); und studies with bei adult‐only participant population (n = 20). Us excluded NCT02651116 because it go not fit our consists criteria (acute cough), but this study is ongoing. We have provided full einzelheiten of reasons weil das exclusion in the Characteristics of excluded studies table.

Risk von bias an included studies

No studien met the inclusion criteria.

Effects von interventions

Due kommen sie a lack des included studies, us were unable to evaluate ns effects of codeine (and derivatives)‐based medications weil das the treatment von chronic cough in children.


Summary of hauptsächlich results

We established no forschung eligible for inclusion in this review, and thus found no evidence kommen sie support or oppose ns use des codeine or derivatives together antitussive agents weil das chronic cough an children. Ours review process identified paediatric studien that evaluated acute cough, an Bhattacharya 2013, paul 2004, Shadkam 2010, taylor 1993, and Yoder 2006, and adult‐specific chronic cough trials (Barroso 1973; Dierckx 1981; Edwards 1977; Matthys 1983, Matthys 1985; Thackray 1978).

Of die paediatric‐specific RCTs the evaluated acute cough (Bhattacharya 2013; paul 2004; Shadkam 2010; taylor 1993; Yoder 2006), nobody reported any type of statistically far-ranging difference an cough severity betwee treatment arm and placebo. As die evaluation des safety was in objective von this review, und the authors reported side effects, we oase provided a summary von these result below.

A single‐dose, double‐blind, placebo‐controlled RCT evaluate dextromethorphan, diphenhydramine (an antihistamine) versus placebo zum the treatment des nocturnal cough due zu upper respiratory tract infections an 37 youngsters aged 6 kommen sie 18 year (Yoder 2006). The mean sneeze duration des each treatment arm was 4.17, 3.92, and 4.23 days, respectively. This study found no difference betwee treatment arms and reported no adverse effects. A similar single‐dose RCT des dextromethorphan, diphenhydramine, and placebo ~ above acute (seven job or less) nocturnal cough an children found that neither drug was superior zu placebo in regards zu reducing ns frequency, severity, and bothersome nature of cough (Paul 2004). More notably, however, this study did report an increased adverse reaction des insomnia in the dextromethorphan arm, yet this was notfall significant (P = 0.07). The entwurf of this study was limited von the inclusion of concurrent antibiotic treatments, typical analgesics such together acetaminophen und ibuprofen, administration of a einzel dose, und the possibility of placebo effect. This findings are consistent with in earlier study von Taylor 1993, that conducted in RCT von 49 kids with acute cough (duration von less than 12 days) und found the codeine or dextromethorphan compared kommen sie placebo was notfall more efficacious bei reducing cough score und symptom score.

Bhattacharya 2013 conducted a double‐blind RCT des dextromethorphan, promethazine, und placebo in 120 youngsters with acute cough. Ns study uncovered that wie compared zu placebo ns treatment eight did not confer any greater benefit with respect zu symptom scores. Ns authors so noted that bei the whole cohort there was a propensity zum the cough to resolve, irrespective des the beteiligung type (Bhattacharya 2013). Ns cohort was evenly divided between groups, v 40 children bei each arm. Adverse events were higher bei children treated through dextromethorphan (32.5%) contrasted to ns placebo kopieren, gruppe (5%). Adverse events included ab pain, nausea, vomiting, drowsiness, und irritability.

In a non‐blind RCT bolzen dextromethorphan, diphenhydramine, honey, und a control gruppe involving 139 youngsters (mean period 37.75 months) v acute cough von 5 days, Shadkam 2010 found honey kommen sie be more effective in improving cough frequency, cough severity, and sleep quality wie man comparing honey v each group separately. However, after ~ each beteiligung (that zu sein honey, dextromethorphan, und diphenhydramine), die mean difference from baseline was statistically significant. No side effects were reported in the dextromethorphan arm, and in spite of the relative superiority des honey, nervousness was a reported adverse reaction in two children, and the authors more acknowledged die risk relevant with honey with regards zu botulism an children aged less than 1 year.

The evidence pertaining to acute‐cough monitoring practices was previously evaluated über Smith 2014, who conducted a methodical review des evidence evaluating ns antitussive efficacy von over‐the‐counter (OTC) medications in the treatment of acute cough bei both adults and children. This review similarly found in overall lack des well‐designed studies and no evidence zum or against the efficacy des OTC against medications. Die lack of evidence kommen sie support codeine und OTC medications for cough an children ist further reflected in their lack from fließend position statements und international sneeze guidelines (Berlin 1997; Chang 2006b; Gibson 2010; Gibson 2016; Shields 2008).

An boosted awareness von risks relevant with codeine has prompted many governmental bodies to review legislation and moderate availability von these drugs, and bei recent year there has actually been in increasing international trend toward greater regulatory framework surrounding die availability und use des codeine bei children. Following ns American College des Chest Physician"https://miyvue.com/husten-wann-zum-arzt-kind/imager_2_2996_700.jpgs chronic sneeze guidelines, i m sorry recommended versus using codeine und OTC medications for cough bei children (Chang 2006b), and a citizen petition on the safety und efficacy of OTC cough and cold medications, the US Food and Drug management convened in expert advisory committee kommen sie evaluate the dispensing practices and accessibility of OTC medications to children (US Food and Drug administration 2015). Much more recently, an April 2015 the Pharmacovigilance risk Assessment Committee (PRAC) of the european Medicines company conducted in investigation into ns use von codeine‐based medicines as against agents. The investigation concluded the there zu sein a lack of sufficient evidence to support die use von codeine as in effective antitussive agent and that there space continued and varied safety concerns verbunden with this drug. Together a result, the PRAC uncovered codeine to be contraindicated bei children much less than 12 years von age and recommended it not be used. Ns report more recommended together medications notfall be used von children aged 12 kommen sie 18 year with der atem difficulties; any personen known to be in ultra‐rapid metaboliser; or breastfeeding mother (European Medicines agency 2015). Major justification zum reform zu sein the unpredictability von codeine zu morphine conversion in children und the increased vulnerabilities of children predisposed kommen sie airway insufficiency (European Medicines agency 2015). Similar conclusions pertaining kommen sie codeine use were made following investigations by Health Canada (Health Canada 2015), the new Zealand drugs Adverse reactions Committee (Medsafe 2015), und the Therapeutic Goods kombination of Australia (Therapeutic Goods administration 2015). Reviews into the continued risks, drug availability, und scheduling share are currently under way an the united States, united state Food and Drug administration 2016, and bei Australia, whereby these medicines continue to be made available OTC zum children age 6 zu 11 years.

Overall completeness and applicability von evidence

This review has actually highlighted a substantial gap bei evidence evaluating codeine (and derivatives) antitussive agents bei childhood chronic cough. Established studies of relevance focused on paediatric populations with acute sneeze or ~ above adult populations. The pathophysiological differences bolzen adults und children, bei addition to the different aetiologies between acute und chronic cough, limit ns overall generalisability von these findings.

Quality des the evidence

We discovered no evidence kommen sie support or oppose ns use von codeine (or derivatives) for the management des chronic cough in children.

Potential biases an the review process

There to be no protocol deviations in ~ this testimonial process, and two review authors individually reviewed ns searches utilizing a standardised inclusion/exclusion criteria. We thus believe that there were no potential biases bei the determination of studies eligible for inclusion in this review.

Agreements und disagreements v other studien or reviews

Our findings von the absence of any RCTs on the efficacy von codeine und its derivatives zum chronic cough, along with its potential significant adverse occasions including death, are consistent with other prior organized reviews undertaken an the writing von national und international cough guidelines zum children (Chang 2006b; Gibson 2010; Shields 2008). Bei acute cough, a organized review found "https://miyvue.com/husten-wann-zum-arzt-kind/imager_2_2996_700.jpgcodeine to be no much more effective than placebo"https://miyvue.com/husten-wann-zum-arzt-kind/imager_2_2996_700.jpg (Smith 2014). This Cochrane evaluation on OTC medications zum children and adults concluded that "https://miyvue.com/husten-wann-zum-arzt-kind/imager_2_2996_700.jpgthere zu sein no great evidence zum or against ns effectiveness des over‐the‐counter sneeze medicine"https://miyvue.com/husten-wann-zum-arzt-kind/imager_2_2996_700.jpg (Smith 2014). In adults through chronic cough, a organized review found codeine and dextromethorphan more beneficial bei reducing cough frequency and severity 보다 placebo but, due zu a limited number des studies and study entwurf flaws, the authors concluded that "https://miyvue.com/husten-wann-zum-arzt-kind/imager_2_2996_700.jpgthere to be insufficient säule to draw conclusions around their family member efficacy"https://miyvue.com/husten-wann-zum-arzt-kind/imager_2_2996_700.jpg (Yancy 2013).