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Täiskasvanute astma käsitlus esmatasandil
Tõendusmaterjali kokkuvõte
Kliiniline küsimus nr 18
Kliinilise küsimuse tekst:
Kas kõigil astma diagnoosiga patsientidel kasutada või mitte kasutada
gripi vaktsineerimist vs mittevaktsineerimist?
Kokkuvõte, sh kriitiliste tulemusnäitajate kaupa
Gripivaktsiini tõhusust ja ohutust astmahaigetel on analüüsitud kahes süstemaatilises
ülevaates: Cochrane’i andmebaasi süstemaatilises ülevaates (Cates ja Rowe 2013) ja WHO
gripivaktsiini alusdokumendi soovituste aluseks olevas vastava tõendusmaterjali ülevaates.
Gripivaktsiini tõhusust astmahaigete hulgas on uuritud ainult lastel ning olulisi erinevusi
astma ägenemiste tekkimisel gripihooaja vältel vaktsineeritutel võrreldes platseeborühmaga ei
ilmnenud. Gripivaktsiini ohutust astmahaigetel on uuritud nii lastel kui ka täiskasvanutel ning
tulemusnäitajad olid väga sarnased nii vaktsineeritute kui ka platseeborühma patsientide
hulgas.
Seega võib hinnata gripivaktsiini astma patsientidele üldiselt ohutuks, kuid tõhususe kohta
astma ägenemiste ennetamisel täiskasvanute hulgas andmed puuduvad.
Tulemusnäitajad (2 nädala jooksul peale vaktsineerimist, andmed toodud trivalentse
inaktiveeritud gripivaktsiini vs platseebo kohta):
Elukvaliteet: NA
Astma ägenemine: WHO: riski erinevus (risk difference) 0.00 (95% CI -0,02 kuni 0,02); Cochrane: riski
erinevus 0,01 (-0,01 kuni 0,04), astma ägenemisi 100 patsiendi kohta platseeborühmas 25 ja vaktsiinirühmas 27
(95% CI 24-29)
Suremus (nii astmast tingitud või olenemata põhjusest e all-cause mortality): NA
Päevaste sümptomite esinemine: keskmine erinevus 0,0 (95%CI -0,3 kuni 0,3)
Öösümptomid/unehäired: NA
Hooravi vajadus keskmine erinevus 0.0 (95%CI -0,02 kuni 0,01)
Hospitaliseerimine (olenemata põhjusest): 0,0
Ravi katkestamine kõrvaltoime tõttu: NA
Füüsilise aktiivsuse piiratus: NA
Ravikulu: NA
Üldist gripivaktsineerimise tõhusust täiskasvanutel grippi haigestumise ja gripitüsistuse
ennetamiseks on analüüsitud mitmetes süstemaatilistes ülevaadetes (DiazGranados 2012,
Osterholm 2012; Jefferson 2010a , Jefferson 2010b; Villari 2004) ning omakorda
süstemaatiliste ülevaadete ülevaates (Manzoli 2012). Kokkuvõtlikult võib öelda, et
trivalentsed inaktiveeritud gripivaktsiinid (ehk meil kasutuselolevad hooajalise gripi
vaktsiinid) on täiskasvanutel mõõdukalt tõhusad ennetamaks grippi haigestumist, kusjuures
erinevate süstemaatiliste uuringute hinnangud gripivaktsiini tõhususele on sarnased (vt selle
lõigu allosas olevat väljavõtet Manzoli 2012 ülevaate tabelist – selles lõigus on toodud
inaktiveeritud trivalentsete gripivaktsiinide tõhusus laboratoorselt kinnitatud gripijuhtude
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ennetamisel). Gripivaktsiini tõhusus eakatel ei ole piisavalt tõendatud ning gripivaktsiini
tõhusust gripitüsistuste ennetamisel on vähe uuritud.
Ravijuhendid
Astma ravijuhendites soovitatakse gripivastast vaktsineerimist (EPR-2007; GINA, SIGN,
VaDoD; ISCI-2012), mõned juhendid toovad eraldi välja, et vajalik selgitada, et
gripivaktsineerimine ei pruugi ära hoida astma ägenemisi gripihooajal ning et
vaktsineerimise eesmärgiks on gripi ja gripitüsistuste ennetamine (EPR-2007 ja VaDoD)
Süstemaatilised ülevaated
Kokkuvõte
Viide kirjandusallikale
Vt allolev GRADE
tabel
Cochrane Database Syst Rev. 2013
28;2:CD000364.
10.1002/14651858.CD000364.pub4.
Vaccines for preventing influenza
people with asthma.
Cates CJ1, Rowe BH.
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Wkly Epidemiol Rec. 2012 Nov 23;87(47):461-76. Vaccines against influenza WHO position
paper – November 2012. (tabel:
http://www.who.int/immunization/position_papers/influenza_grad_efficacy_asthma.pdf
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Ravijuhendite soovitused:
EPR-2007: Consider inactivated influenza vaccination for patients who have asthma. It is safe for
administration to children more than 6 months of age and adults (Evidence A). The
Advisory Committee on Immunization Practices of the CDC recommends vaccination for
persons who have asthma, because they are considered to be at risk for complications from
influenza. However, the vaccine should not be given with the expectation that it will reduce
either the frequency or severity of asthma exacerbations during the influenza season
(Evidence B).
GINA: Patients with moderaate or severe asthma should be advised to receive an influenza
vaccination every year, or at least when vaccination of the general population is advised. Inactivated
influenza vaccines are safe for adults and children over age 3.
ISCI-2012: Clinicians should order annual influenza vaccination for patients with persistent asthma.
SIGN: There has been concern that influenza vaccination might aggravate respiratory symptoms,
though any such effect would be outweighed by the benefits of the vaccination.247 Studies in
children have suggested that immunisation with the vaccine does not exacerbate asthma248 but
has a small beneficial effect on quality of life in children with asthma.249 The immune response
to the immunisation may be adversely affected by high-dose inhaled corticosteroid therapy and
this requires further investigation.250 Recommendation (B): Immunisations should be administered
independent of any considerations related to asthma. Responses to vaccines may be attenuated by
high-dose inhaled steroids.
VaDoD 2009: All patients with asthma who are older than 6 months of age should receive inactivated
flu vaccine to decrease the risk of complications from infection with influenza. Patient or parents
should be counseled that the vaccination will not decrease the frequency or severity of exacerbations
during the flu season. [A]
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Otsistrateegia 27.02.2014 ("Influenza, Human"[Mesh] AND ("Vaccines"[Mesh] OR
"Immunization"[Mesh]) OR "Vaccination"[Mesh]) AND "Asthma"[Mesh] AND (MetaAnalysis[ptyp] OR systematic[sb] OR Randomized Controlled Trial[ptyp]) n=33, nendest
asjakohased 8 (sh välja jäetud vanemad Cochrane ülevaated):
Items 1 -8 of 8 (Display the 8 citations in PubMed)
1. Vaccines for preventing influenza in people with asthma.
Cates CJ, Rowe BH.
Cochrane Database Syst Rev. 2013 Feb 28;2:CD000364. doi:
10.1002/14651858.CD000364.pub4. Review.
PROTECTIVE EFFECTS OF INACTIVATED INFLUENZA VACCINE DURING THE INFLUENZA
SEASON: A single parallel-group trial, involving 696 children, was able to assess the protective effects of
influenza vaccination. There was no significant reduction in the number, duration or severity of influenzarelated asthma exacerbations. There was no difference in the forced expiratory volume in one second (FEV)
although children who had been vaccinated had better symptom scores during influenza-positive weeks. Two
parallel-group trials in adults did not contribute data to these outcomes due to very low levels of confirmed
influenza infection. ADVERSE EFFECTS OF INACTIVATED INFLUENZA VACCINE IN THE FIRST
TWO WEEKS FOLLOWING VACCINATION: Two cross-over trials involving 1526 adults and 712
children (over three years old) with asthma compared inactivated trivalent split-virus influenza vaccine with a
placebo injection. These trials excluded any clinically important increase in asthma exacerbations in the two
weeks following influenza vaccination (risk difference 0.014; 95% confidence interval -0.010 to 0.037).
However, there was significant heterogeneity between the findings of two trials involving 1104 adults in
terms of asthma exacerbations in the first three days after vaccination with split-virus or surface-antigen
inactivated vaccines. There was no significant difference in measures of healthcare utilisation, days off
school/symptom-free days, mean lung function or medication usage.
2. Vaccination of patients with mild and severe asthma with a 2009 pandemic H1N1 influenza
virus vaccine.
Busse WW, Peters SP, Fenton MJ, Mitchell H, Bleecker ER, Castro M, Wenzel S, Erzurum
SC, Fitzpatrick AM, Teague WG, Jarjour N, Moore WC, Sumino K, Simeone S,
Ratanamaneechat S, Penugonda M, Gaston B, Ross TM, Sigelman S, Schiepan JR, Zaccaro
DJ, Crevar CJ, Carter DM, Togias A.
J Allergy Clin Immunol. 2011 Jan;127(1):130-7, 137.e1-3. doi: 10.1016/j.jaci.2010.11.014.
Epub 2010 Dec 9.
We conducted an open-label study involving 390 participants (age, 12-79 years) enrolled in OctoberNovember 2009. Severe asthma was defined as need for 880 μg/d or more of inhaled fluticasone equivalent,
systemic corticosteroids, or both. Within each severity group, participants were randomized to receive
intramuscularly 15 or 30 μg of 2009 H1N1 vaccine twice 21 days apart. Immunogenicity end points were
seroprotection (hemagglutination inhibition assay titer ≥40) and seroconversion (4-fold or greater titer
increase). Safety was assessed through local and systemic reactogenicity, asthma exacerbations, and
pulmonary function.
RESULTS: In patients with mild-to-moderate asthma (n = 217), the 2009 H1N1 vaccine provided equal
seroprotection 21 days after the first immunization at the 15-μg (90.6%; 95% CI, 83.5% to 95.4%) and 30-μg
(95.3%; 95% CI, 89.4% to 98.5%) doses. In patients with severe asthma (n = 173), seroprotection 21 days
after the first immunization was 77.9% (95% CI, 67.7% to 86.1%) and 94.1% (95% CI, 86.8% to 98.1%) at
the 15- and 30-μg doses, respectively (P = .004). The second vaccination did not provide further increases in
seroprotection. Participants with severe asthma who are older than 60 years showed the lowest seroprotection
(44.4% at day 21) with the 15-μg dose but had adequate seroprotection with 30 μg. The 2 dose groups did not
differ in seroconversion rates. There were no safety concerns.
3. Influenza vaccination in asthmatic children: effects on quality of life and symptoms.
[Type text]
Bueving HJ, van der Wouden JC, Raat H, Bernsen RM, de Jongste JC, van Suijlekom-Smit
LW, Osterhaus AD, Rimmelzwaan GF, Mölken MR, Thomas S.
Eur Respir J. 2004 Dec;24(6):925-31.
4. Does influenza vaccination exacerbate asthma in children?
Bueving HJ, Bernsen RM, de Jongste JC, van Suijlekom-Smit LW, Rimmelzwaan GF,
Osterhaus AD, Rutten-van Mölken MP, Thomas S, van der Wouden JC.
Vaccine. 2004 Nov 15;23(1):91-6.
5. Influenza vaccination in patients with asthma: effect on the frequency of upper respiratory
tract infections and exacerbations.
Abadoğlu O, Mungan D, Paşaoglu G, Celík G, Misirligil Z.
J Asthma. 2004;41(3):279-83.
Between September 15 and November 7, 2001, a total of 128 patients with asthma were randomly assigned to
receive (n = 86) and not to receive vaccine (n = 42). The primary outcome measures were frequency of upper
respiratory tract infections and exacerbations of asthma during the winter following vaccination. Study
subjects were asked to record the presence and duration of symptoms suggestive of an upper respiratory tract
infection and call their physician in the presence of conditions suggestive of an exacerbation until March
2002. Among the vaccinated group, 48% of the patients reported that they had no upper respiratory tract
infection during the winter following injection, whereas 57% of nonvaccinated participants were upper
respiratory symptom free during the same period (p > 0.05). The frequency of upper respiratory tract infection
was also not different between the two groups in all severity forms of asthma (p > 0.05). There was no
significant difference in the frequency of exacerbations of asthma between the two groups during the study
period (p > 0.05). None of the vaccinated group was hospitalized due to an asthma attack; however, two
patients (4.8%) in the nonvaccinated group had to be hospitalized following an exacerbation (p > 0.05). In
summary, our findings do not support the protective effect of influenza vaccination for patients with asthma.
However, no firm conclusions on this effect of the vaccine can be made without the data on the rate of
influenza epidemic in that season and without the knowledge of the cause of upper respiratory tract infections
in those patients. Therefore, we believe randomized, double-blind, placebo-controlled studies, including
larger subgroups of severe asthmatics, are needed to evaluate the protective effect of influenza vaccination in
asthma.
6. Is there any evidence for influenza vaccination in children with asthma?
Carroll W, Burkimsher R.
Arch Dis Child. 2007 Jul;92(7):644-5. Review. No abstract available.
7. Influenza vaccination in children with asthma: randomized double-blind placebo-controlled
trial.
Bueving HJ, Bernsen RM, de Jongste JC, van Suijlekom-Smit LW, Rimmelzwaan GF,
Osterhaus AD, Rutten-van Mölken MP, Thomas S, van der Wouden JC.
Am J Respir Crit Care Med. 2004 Feb 15;169(4):488-93. Epub 2003 Dec 4.
8. The safety of inactivated influenza vaccine in adults and children with asthma.
[No authors listed]
N Engl J Med. 2001 Nov 22;345(21):1529-36.
multicenter, randomized, double-blind, placebo-controlled, cross-over trial in 2032 patients with asthma (age
range, 3 to 64 years). The order of injection of vaccine and placebo was assigned randomly, with a mean of
22 days between the injections. Each day during the two weeks after each injection, the patients recorded
peak expiratory flow rates, symptoms thought to be related to the injection, use of asthma medications,
unscheduled health care visits for asthma, and asthma-related absences from school or work. The primary
outcome measure was an exacerbation of asthma in the two weeks after the injections.
RESULTS: The frequency of exacerbations of asthma was similar in the two weeks after the influenza
vaccination and after placebo injection (28.8 percent and 27.7 percent, respectively; absolute difference, 1.1
percent; 95 percent confidence interval, -1.4 percent to 3.6 percent). The exacerbation rates were similar in
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subgroups defined according to age, severity of asthma, and other factors. Among symptoms thought to be
associated with the injection, only body aches were more frequent after the vaccine injection than after
placebo injection (25.1 percent vs. 20.8 percent, P<0.001).
CONCLUSIONS: The inactivated influenza vaccine is safe to administer to adults and children with asthma,
including those with severe asthma. Given the morbidity of influenza, all those with asthma should receive
the vaccine annually.
Lisaotsing gripivaktsiini kohta üldisemalt (ainult süstemaatilised ülevaated viimase 5 a
jooksul):
27.02.2014 ("Influenza, Human"[Mesh] AND ("Vaccines"[Mesh] OR
"Immunization"[Mesh]) OR "Vaccination"[Mesh]) AND (Meta-Analysis[ptyp] OR
systematic[sb]) AND ("2009/03/02"[PDat] : "2014/02/27"[PDat]) n=373
Items 1 -20 of 20
(Display the 20 citations in PubMed)
1. Association between influenza vaccination and cardiovascular outcomes in high-risk
patients: a meta-analysis.
Udell JA, Zawi R, Bhatt DL, Keshtkar-Jahromi M, Gaughran F, Phrommintikul A,
Ciszewski A, Vakili H, Hoffman EB, Farkouh ME, Cannon CP.
JAMA. 2013 Oct 23;310(16):1711-20. doi: 10.1001/jama.2013.279206.
Five published and 1 unpublished randomized clinical trials of 6735 patients (mean age, 67 years; 51.3% women; 36.2%
with a cardiac history; mean follow-up time, 7.9 months) were included. Influenza vaccine was associated with a lower
risk of composite cardiovascular events (2.9% vs 4.7%; RR, 0.64 [95% CI, 0.48-0.86], P = .003) in published trials. A
treatment interaction was detected between patients with (RR, 0.45 [95% CI, 0.32-0.63]) and without (RR, 0.94 [95% CI,
0.55-1.61]) recent ACS (P for interaction = .02). Results were similar with the addition of unpublished data.
2. Populations at risk for severe or complicated influenza illness: systematic review and metaanalysis.
Mertz D, Kim TH, Johnstone J, Lam PP, Science M, Kuster SP, Fadel SA, Tran D,
Fernandez E, Bhatnagar N, Loeb M.
BMJ. 2013 Aug 23;347:f5061. doi: 10.1136/bmj.f5061. Review.
63 537 articles were identified of which 234 with a total of 610 782 participants met the inclusion criteria. The evidence
supporting risk factors for severe outcomes of influenza ranged from being limited to absent. Lisaks tekstis: Seasonal
influenza: The presence of chronic lung disease was associated with a higher risk for admission to hospital and to an
intensive care unit, and the need for ventilator support. Asthma was only associated with a higher risk of developing
pneumonia, whereas chronic obstructive pulmonary disease was associated with a higher likelihood of needing ventilator
support.
3. Comparing influenza vaccine efficacy against mismatched and matched strains: a
systematic review and meta-analysis.
Tricco AC, Chit A, Soobiah C, Hallett D, Meier G, Chen MH, Tashkandi M, Bauch CT,
Loeb M.
BMC Med. 2013 Jun 25;11:153. doi: 10.1186/1741-7015-11-153. Review.
We included 34 RCTs, providing data on 47 influenza seasons and 94,821 participants. /:::/The trivalent inactivated
vaccine (TIV) also afforded significant protection against mismatched (nine RCTs, VE 52%, 95% CI 37% to 63%) and
matched (eight RCTs, VE 65%, 95% CI 54% to 73%) influenza strains among adults. Numerical differences were
observed between the point estimates for mismatched influenza A (five RCTs, VE 64%, 95% CI 23% to 82%) and
mismatched influenza B (eight RCTs, VE 52%, 95% CI 19% to 72%) estimates among adults.
4. Effectiveness of seasonal influenza vaccines in children -- a systematic review and metaanalysis. – ainult laste kohta ja seetõttu jäetud välja
[Type text]
5. Vaccines for preventing influenza in people with asthma.
Cates CJ, Rowe BH.
Cochrane Database Syst Rev. 2013 Feb 28;2:CD000364. doi:
10.1002/14651858.CD000364.pub4. Review.
Uncertainty remains about the degree of protection that vaccination affords against asthma exacerbations that are related
to influenza infection. Evidence from more recently published randomised trials of inactivated split-virus influenza
vaccination indicates that there is no significant increase in asthma exacerbations immediately after vaccination in adults
or children over three years of age.
6. Vaccines against influenza WHO position paper – November 2012.
[No authors listed]
Wkly Epidemiol Rec. 2012 Nov 23;87(47):461-76. English, French. No abstract available.
PMID: 23210147 [PubMed - indexed for MEDLINE] Free Article
Vt eespool
7. Seasonal influenza vaccine efficacy and its determinants in children and non-elderly adults:
a systematic review with meta-analyses of controlled trials.
DiazGranados CA, Denis M, Plotkin S.
Vaccine. 2012 Dec 17;31(1):49-57. doi: 10.1016/j.vaccine.2012.10.084. Epub 2012 Nov 7.
Review.
PMID: 23142300 [PubMed - indexed for MEDLINE]
Thirty studies were included in one or more of a total of 101 analyses, comprising 88.468 study participants. There was
evidence of heterogeneity in 49% of the analyses. Summary vaccine efficacy was 65% against any strain, 78% against
matched strains and 55% against not-matched strains. Both live-attenuated and inactivated vaccines showed similar levels
of protection against not-matched strains (60% and 55%, respectively). Live-attenuated vaccines performed better than
inactivated vaccines in children (80% versus 48%), whereas inactivated vaccines performed better than live-attenuated
vaccines in adults (59% versus 39%)./…/ Influenza vaccines are efficacious, but efficacy estimates depend on many
variables including type of vaccine and age of vaccinees, degree of matching of the circulating strains to the vaccine,
influenza type, and methods of case ascertainment.
8. Influenza vaccination for immunocompromised patients: systematic review and metaanalysis by etiology. – jäetud välja, hõlmab HIV, pahaloomuliste kasvajatega ja siirdatud
patsiendid.
9. Vaccines for preventing influenza in healthy children.
Jefferson T, Rivetti A, Di Pietrantonj C, Demicheli V, Ferroni E.
Cochrane Database Syst Rev. 2012 Aug 15;8:CD004879. doi:
10.1002/14651858.CD004879.pub4. Review.
Inactivated vaccines in children aged two years or younger are not significantly more efficacious than placebo. Twentyeight children over the age of six need to be vaccinated to prevent one case of influenza (infection and symptoms). Eight
need to be vaccinated to prevent one case of influenza-like-illness (ILI).
10. Effectiveness and harms of seasonal and pandemic influenza vaccines in children, adults and
elderly: a critical review and re-analysis of 15 meta-analyses.
Manzoli L, Ioannidis JP, Flacco ME, De Vito C, Villari P.
Hum Vaccin Immunother. 2012 Jul;8(7):851-62. doi: 10.4161/hv.19917. Epub 2012 Jul 1.
Review.
Although we identified several discrepancies among the meta-analyses on seasonal vaccines for children and
elderly, overall most seasonal influenza vaccines showed statistically significant efficacy/effectiveness, which
was acceptable or high for laboratory-confirmed cases and of modest magnitude for clinically-confirmed cases.
/…/ Data on harms are overall reassuring, but their value is diminished by inconsistent reporting.
[Type text]
Vt ka allolevat tabelit (Villari, Jefferson, Osterholm)
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11. Effectiveness of influenza vaccine in aging and older adults: comprehensive analysis of
the evidence.
Lang PO, Mendes A, Socquet J, Assir N, Govind S, Aspinall R.
Clin Interv Aging. 2012;7:55-64. doi: 10.2147/CIA.S25215. Epub 2012 Feb 24. Review.
PMID: 22393283 [PubMed - indexed for MEDLINE] Free PMC Article
Ei ole uurimuslik artikkel, vaid kirjeldav
12. Impacts on influenza A(H1N1)pdm09 infection from cross-protection of seasonal trivalent
influenza vaccines and A(H1N1)pdm09 vaccines: systematic review and meta-analyses.
Yin JK, Chow MY, Khandaker G, King C, Richmond P, Heron L, Booy R.
Vaccine. 2012 May 2;30(21):3209-22. doi: 10.1016/j.vaccine.2012.02.048. Epub 2012
Mar 2. Review.
Although cross-protection was less than the direct effect of strain-specific vaccination against A(H1N1)pdm09, trivalent
inactivated vaccine was generally beneficial before A(H1N1)pdm09 vaccine was available.
13. Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis.
Osterholm MT, Kelley NS, Sommer A, Belongia EA.
Lancet Infect Dis. 2012 Jan;12(1):36-44. doi: 10.1016/S1473-3099(11)70295-X. Epub
2011 Oct 25. Review. Erratum in: Lancet Infect Dis. 2012 Sep;12(9):655.
Efficacy of TIV was shown in eight (67%) of the 12 seasons analysed in ten randomised controlled trials (pooled
efficacy 59% [95% CI 51-67] in adults aged 18-65 years). No such trials met inclusion criteria for children aged 2-17
years or adults aged 65 years or older.
Vt ka Manzoli ja Ioannidis tabel
14. A systematic review of the evidence on the effectiveness and risks of inactivated influenza
vaccines in different target groups.
Michiels B, Govaerts F, Remmen R, Vermeire E, Coenen S.
Vaccine. 2011 Nov 15;29(49):9159-70. doi: 10.1016/j.vaccine.2011.08.008. Epub 2011
Aug 12. Review.
The inactivated influenza vaccine has been proven effective in preventing laboratory-confirmed influenza among
healthy adults (16-65 years) and children (≥6 years) (GRADE A evidence). However, there is strikingly limited goodquality evidence (all GRADE B, C or not existing) of the effectiveness of influenza vaccination on complications such
as pneumonia, hospitalisation and influenza-specific and overall mortality.
15. Immunogenicity and safety of inactivated influenza vaccines in primed populations: a
systematic literature review and meta-analysis.
Beyer WE, Nauta JJ, Palache AM, Giezeman KM, Osterhaus AD.
[Type text]
Vaccine. 2011 Aug 5;29(34):5785-92. doi: 10.1016/j.vaccine.2011.05.040. Epub 2011
May 30. Review.
Vaid immunogeensus (suurogaatmarkerid), ei ole POEM tulemusnäitajaid
16. Vaccines for preventing influenza in healthy adults.
Jefferson T, Di Pietrantonj C, Rivetti A, Bawazeer GA, Al-Ansary LA, Ferroni E.
Cochrane Database Syst Rev. 2010 Jul 7;(7):CD001269. doi:
10.1002/14651858.CD001269.pub4. Review.
PMID: 20614424 [PubMed - indexed for MEDLINE]
Influenza vaccines have a modest effect in reducing influenza symptoms and working days lost. There is no evidence
that they affect complications, such as pneumonia, or transmission
Vt ka Manzoli ja Ioannidis tabel
17. Vaccines for preventing influenza in the elderly.
Jefferson T, Di Pietrantonj C, Al-Ansary LA, Ferroni E, Thorning S, Thomas RE.
Cochrane Database Syst Rev. 2010 Feb 17;(2):CD004876. doi:
10.1002/14651858.CD004876.pub3. Review.
The available evidence is of poor quality and provides no guidance regarding the safety, efficacy or effectiveness of
influenza vaccines for people aged 65 years or older
18. Influenza as a trigger for acute myocardial infarction or death from cardiovascular
disease: a systematic review.
Warren-Gash C, Smeeth L, Hayward AC.
Lancet Infect Dis. 2009 Oct;9(10):601-10. doi: 10.1016/S1473-3099(09)70233-6. Review.
Two small randomised trials assessed the protection provided by influenza vaccine against cardiac events in people with
existing cardiovascular disease. Whereas one trial found that influenza vaccination gave significant protection against
cardiovascular death, the other trial was inconclusive. A pooled estimate from a random-effects model suggests a
protective, though non-significant, effect (relative risk 0.51, 95% CI 0.15-1.76).