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In medicine, pneumococcal vaccines are "[[vaccines]] or candidate vaccines used to prevent infections with [[streptococcus pneumoniae]]."<ref>{{MeSH}}</ref>
{{Infobox_Disease |
Name          = Pneumococcal vaccine |
MeshID        = D022242 |
MedlinePlus    = 007332 |
}}
 
In [[medicine]], pneumococcal vaccines are "[[vaccine]]s or candidate vaccines used to prevent infections with [[streptococcus pneumoniae]]."<ref>{{MeSH}}</ref> These infections include [[pneumonia]], [[meningitis]], [[otitis media]], and [[septic shock|sepsis]].
 
==History==
The polyvalent 14 type vaccine was licensed to Merck Sharp & Dohme in 1977.<ref name="urlwww.fda.gov">{{cite web |url=http://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM131665.pdf |title=Summary for Basis of Approval |author=Bacterial Polysaccharides Branch, DBP |authorlink= |coauthors= |date=June 30, 1983 |format= |work= |publisher= |pages= |language= |archiveurl= |archivedate= |quote=Merck Sharp & Dohme was licensed for Pneumococcal Vaccine, Polyvalent (14 types) in 1977. |accessdate=2009-08-25}}</ref>The polyvalent 23 type vaccine was licensed to Merck Sharp & Dohme in 1983.<ref name="urlwww.fda.gov">{{cite web |url=http://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM131665.pdf |title=Summary for Basis of Approval |author=Bacterial Polysaccharides Branch, DBP |authorlink= |coauthors= |date=June 30, 1983 |format= |work= |publisher= |pages= |language= |archiveurl= |archivedate= |quote=Merck Sharp & Dohme was licensed for Pneumococcal Vaccine, Polyvalent (14 types) in 1977. |accessdate=2009-08-25}}</ref> Robert Austrian contributed to the development of the vaccines.<ref>Altman, Lawrence. (March 30, 2007) [http://www.nytimes.com/2007/03/30/health/30austrian.html Robert Austrian, 90, Dies; Developed Major Vaccine] The New York Times</ref><ref name="pmid234994">Austrian, R.: Random gleanings from a life with the pneumococcus, J. Infect. Dis. 131: 474-484, 1975. PMID 234994</ref><ref name="isbn052162620X">{{Cite book | author=Galambos, Louis; Sewell, Jane Eliot | authorlink= | coauthors= | title=Networks of Innovation : Vaccine Development at Merck, Sharp and Dohme, and Mulford, 1895-1995 | date= | publisher=Cambridge University Press | location= | isbn=052162620X | pages=}}</ref>
 
==Vaccine types==
===Pneumococcal polysaccharide vaccine(PPV)===
 
===Pneumococcal conjugate vaccine (PCV)===
The conjugated pneumonia vaccine (PCV) may have better immunogenicity in children than the PPV due to this age groups lack of immune response to polysaccharides.  A [[randomized controlled trial]] compared the immunogenicity in elderly patients with recent pneumococcal pneumonia and found that PCV stimulates a more prolonged response than PPV.  <ref name="pmid18710324">{{cite journal |author=Musher DM, Rueda AM, Nahm MH, Graviss EA, Rodriguez-Barradas MC |title=Initial and subsequent response to pneumococcal polysaccharide and protein-conjugate vaccines administered sequentially to adults who have recovered from pneumococcal pneumonia |journal=J. Infect. Dis. |volume=198 |issue=7 |pages=1019–27 |year=2008 |month=October |pmid=18710324 |doi=10.1086/591629 |url=http://www.journals.uchicago.edu/doi/abs/10.1086/591629?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&fr_dat=cr_pub%3dncbi.nlm.nih.gov |issn=}}</ref>  Musher et. al. concluded that protein vaccines may be needed in the high risk elderly. 
 
==Efficacy==
Ideally, pneumococcal vaccine would protect against [[pneumonia]], invasive [[streptococcus pneumoniae|pneumococcal]] disease ([[bacteremia]] and [[bacterial meningitis|meningitis]]), [[hospitalization]]s and [[death]].
 
===Randomized controlled trials===
<!--A [[meta-analysis]] by the [[Cochrane Collaboration]] found that the pneumococcal vaccine reduced the risk of invasive [[streptococcus pneumoniae|pneumococcal]] disease among adults and the immunocompetent elderly (55 years and above) with an [[odds ratio]] 0.47 corresponding to an efficacy of 53%.  Efficacy of 50% in developed countries with an incidence of 0.01% then results in a [[number needed to treat]] (NNT) of 20,000 vaccinations per infection avoided, and perhaps 50,000 per death avoided. <ref name="pmid14583920">{{cite journal |author=Dear K, Holden J, Andrews R, Tatham D |title=Vaccines for preventing pneumococcal infection in adults |journal=Cochrane Database Syst Rev |volume= |issue=4 |pages=CD000422 |year=2003 |pmid=14583920 |doi=10.1002/14651858.CD000422 |url=http://dx.doi.org/10.1002/14651858.CD000422 |issn=}}</ref>-->
 
An updated [[Cochrane Collaboration|Cochrane]] [[meta-analysis]] of [[randomized controlled trial]]s in 2008 found:<ref name="pmid18253977">{{cite journal |author=Moberley SA, Holden J, Tatham DP, Andrews RM |title=Vaccines for preventing pneumococcal infection in adults |journal=Cochrane Database Syst Rev |volume= |issue=1 |pages=CD000422 |year=2008 |pmid=18253977 |doi=10.1002/14651858.CD000422.pub2 |url=http://dx.doi.org/10.1002/14651858.CD000422.pub2 |issn=}}</ref>
* [[Randomized controlled trial]]s provided strong evidence of vaccine efficacy against invasive pneumococcal disease (IPD) with no statistical heterogeneity (OR 0.26).  Observational studies provided evidence for protection against IPD in populations for whom the vaccine is currently utilized ([[odds ratio]] = 0.48).
* Efficacy against all cause [[pneumonia]] was inconclusive with substantial statistical heterogeneity
* Pneumococcal vaccine was not associated with substantial reductions in all-cause mortality.
* Vaccine efficacy against primary outcomes appeared poorer in adults with chronic illness but the difference was not statistically significant.
 
The authors concluded that evidence supports the recommendation for vaccination to prevent IPD in adults, but does not support vaccination to prevent all-cause pneumonia or mortality. <ref name="pmid18253977">{{cite journal |author=Moberley SA, Holden J, Tatham DP, Andrews RM |title=Vaccines for preventing pneumococcal infection in adults |journal=Cochrane Database Syst Rev |volume= |issue=1 |pages=CD000422 |year=2008 |pmid=18253977 |doi=10.1002/14651858.CD000422.pub2 |url=http://dx.doi.org/10.1002/14651858.CD000422.pub2 |issn=}}</ref> This is consistent with an earlier meta-analysis<ref name="pmid7993150">Fine MJ, Smith MA, Carson CA, Meffe F, Sankey SS, Weissfeld LA, Detsky AS, Kapoor WN. Efficacy of pneumococcal vaccination in adults. A meta-analysis of randomized controlled trials. Arch Intern Med. 1994 Dec 12-26;154(23):2666-77. PMID 7993150</ref>  and also a subsequent meta-analysis.<ref name="pmid19124790">{{cite journal |author=Huss A, Scott P, Stuck AE, Trotter C, Egger M |title=Efficacy of pneumococcal vaccination in adults: a meta-analysis |journal=CMAJ |volume=180 |issue=1 |pages=48–58 |year=2009 |month=January |url=http://www.cmaj.ca/cgi/content/full/180/1/48|pmid=19124790 |pmc=2612051 |doi=10.1503/cmaj.080734 |url= |issn=}}</ref> Although the most recent meta-analysis did not find benefit in preventing invasive disease<ref name="pmid19124790"/>, this analysis was weighted by a Ugandan study of HIV patients that showed not benefit. The Cochrane meta-analysis did not include this study and concluded that the vaccine prevents invasive disease.<ref name="pmid18253977"/>
 
===Observational studies===
Among patients hospitalized for community acquired [[pneumonia]], prior pneumococcal vaccination improved all cause mortality, respiratory failure, and reduced length of stay after adjustment for other factors in a [[cohort study]] of over 62,000 patients. <ref name="pmid16575726">{{cite journal |author=Fisman DN, Abrutyn E, Spaude KA, Kim A, Kirchner C, Daley J |title=Prior pneumococcal vaccination is associated with reduced death, complications, and length of stay among hospitalized adults with community-acquired pneumonia |journal=Clin. Infect. Dis. |volume=42 |issue=8 |pages=1093–101 |year=2006 |month=April |pmid=16575726 |doi=10.1086/501354 |url=http://www.journals.uchicago.edu/doi/abs/10.1086/501354?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dncbi.nlm.nih.gov |issn=}}</ref>
 
First, in regards to which people are at risk of invasive pneumococcal disease (IPD), a recent Finnish study found that this diagnosis carried a 12% mortality at one month for patients 65 and over.  46% of those patients that died within 1 month of having IPD did not have an indication for receipt of the vaccination prior to hospitalization, with the age group of 50-64 having proportionally higher mortality.  The authors concluded that policy makers should consider lowering the age criteria to 50.  <ref name="pmid18647385">{{cite journal |author=Klemets P, Lyytikäinen O, Ruutu P, Ollgren J, Pekka Nuorti J |title=Invasive pneumococcal infections among persons with and without underlying medical conditions: implications for prevention strategies |journal=BMC Infect. Dis. |volume=8 |issue= |pages=96 |year=2008 |pmid=18647385 |pmc=2507715 |doi=10.1186/1471-2334-8-96 |url=http://www.biomedcentral.com/1471-2334/8/96 |issn=}}</ref>
 
===Cost-benefit analyses===
A [[cost-benefit analysis]], assuming that PPV is only effective at preventing ''invasive'' pneumococcal disease, found vaccination to be cost saving for general populations of adults 50–64 years of age <ref name="pmid12809452">{{cite journal |author=Sisk JE, Whang W, Butler JC, Sneller VP, Whitney CG |title=Cost-effectiveness of vaccination against invasive pneumococcal disease among people 50 through 64 years of age: role of comorbid conditions and race |journal=Ann. Intern. Med. |volume=138 |issue=12 |pages=960–8 |year=2003 |month=June |pmid=12809452 |doi= |url=http://www.annals.org/cgi/pmidlookup?view=long&pmid=12809452 |issn=}}</ref> and 65 years of age and older<ref name="pmid9343464">{{cite journal |author=Sisk JE, Moskowitz AJ, Whang W, et al |title=Cost-effectiveness of vaccination against pneumococcal bacteremia among elderly people |journal=JAMA |volume=278 |issue=16 |pages=1333–9 |year=1997 |pmid=9343464 |doi= |url= |issn=}}</ref>.
 
==Indications==
In the [[United States of America]], the [[Centers for Disease Control and Prevention]]<ref name="pmid19124819">{{Cite journal | volume = 150 | issue = 1 | pages = 40-44 | last = Advisory Committee on Immunization Practices | title = Recommended Adult Immunization Schedule: United States, 2009* | journal = Ann Intern Med | accessdate = 2009-01-06 | date = 2009-01-06 | pmid=19124819 | url = http://www.annals.org/cgi/content/full/150/1/40 }}</ref><ref name="pmid9132580">{{cite journal |author= |title=Prevention of pneumococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP) |journal=MMWR Recomm Rep |volume=46 |issue=RR-8 |pages=1–24 |year=1997 |month=April |pmid=9132580 |doi= |url=http://www.cdc.gov/mmwr/preview/mmwrhtml/00047135.htm |issn=}}</ref><ref>Centers for Disease Control and Prevention. [http://www.cdc.gov/mmwr/pdf/wk/mm5641-Immunization.pdf Recommended Adult Immunization Schedule—United States, October 2007–September 2008]. MMWR 2007;56:Q1–Q4.:</ref> and the  Joint Commission on Accreditation of Healthcare Organizations<ref name="urlSpecification Manual | Joint Commission">{{cite web |url=http://www.jointcommission.org/PerformanceMeasurement/PerformanceMeasurement/Current+NHQM+Manual.htm |title=Specifications Manual for National Hospital Inpatient Quality Measures |author=Anonymous |authorlink= |coauthors= |date=September 19, 2008 |format=pdf |work= |publisher=Joint Commission |pages= |language= |archiveurl= |archivedate= |quote= |accessdate=}}</ref> have created recommendations for vaccination. In 2009, the [[Centers for Disease Control and Prevention]] added [[asthma]] and smoking to the indications for vaccination.<ref name="pmid20814406">{{cite journal| author=Centers for Disease Control and Prevention (CDC)| title=Updated Recommendations for Prevention of Invasive Pneumococcal Disease Among Adults Using the 23-Valent Pneumococcal Polysaccharide Vaccine (PPSV23). | journal=MMWR Morb Mortal Wkly Rep | year= 2010 | volume= 59 | issue= 34 | pages= 1102-6 | pmid=20814406 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20814406 }} </ref><ref name="pmid19124819">{{Cite journal | volume = 150 | issue = 1 | pages = 40-44 | last = Advisory Committee on Immunization Practices | title = Recommended Adult Immunization Schedule: United States, 2009* | journal = Ann Intern Med | accessdate = 2009-01-06 | date = 2009-01-06 | pmid=19124819 | url = http://www.annals.org/cgi/content/full/150/1/40 }}</ref>
 
The older [[clinical practice guideline]]s by the [[Infectious Disease Society of America]] and the [[American Thoracic Society]] recommend:
* Adults <u>></u>65 years of age
* Persons <u>></u>2 years with
** chronic illness
** anatomic or functional asplenia
** immunocompromised (disease, chemotherapy, [[steroid]]s)
** [[Human Immunodeficiency Virus]] infection
** environments or settings with increased risk
 
===Vaccination of hospitalized patients===
Although vaccination is viewed as purview of [[primary care physician]]s, vaccinating inpatients during hospitalizations may improve vaccination rates<ref name="pmid12418949">{{cite journal |author=Bratzler DW, Houck PM, Jiang H, ''et al'' |title=Failure to vaccinate Medicare inpatients: a missed opportunity |journal=Arch. Intern. Med. |volume=162 |issue=20 |pages=2349–56 |year=2002 |month=November |pmid=12418949 |doi= |url=http://archinte.ama-assn.org/cgi/pmidlookup?view=long&pmid=12418949 |issn=}}</ref>; however, inpatient vaccination may be difficult to implement<ref name="pmid16533904">{{cite journal |author=Winston CA, Lindley MC, Wortley PM |title=Lessons learned from inpatient vaccination in Michigan |journal=Am J Med Qual |volume=21 |issue=2 |pages=125–33 |year=2006 |pmid=16533904 |doi=10.1177/1062860605284361 |url=http://ajm.sagepub.com/cgi/pmidlookup?view=long&pmid=16533904 |issn=}}</ref>. Paradoxically, inpatient strategies may be less successful in hospitals that have a high volume of pneumonia cases.<ref name="pmid16490912">{{cite journal |author=Lindenauer PK, Behal R, Murray CK, Nsa W, Houck PM, Bratzler DW |title=Volume, quality of care, and outcome in pneumonia |journal=Ann. Intern. Med. |volume=144 |issue=4 |pages=262–9 |year=2006 |month=February |pmid=16490912 |doi= |url=http://www.annals.org/cgi/content/full/144/4/262 |issn=}}</ref>


==References==
==References==
<references/>
<references/>[[Category:Suggestion Bot Tag]]

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Pneumococcal vaccine
MedlinePlus 007332
MeSH D022242

In medicine, pneumococcal vaccines are "vaccines or candidate vaccines used to prevent infections with streptococcus pneumoniae."[1] These infections include pneumonia, meningitis, otitis media, and sepsis.

History

The polyvalent 14 type vaccine was licensed to Merck Sharp & Dohme in 1977.[2]The polyvalent 23 type vaccine was licensed to Merck Sharp & Dohme in 1983.[2] Robert Austrian contributed to the development of the vaccines.[3][4][5]

Vaccine types

Pneumococcal polysaccharide vaccine(PPV)

Pneumococcal conjugate vaccine (PCV)

The conjugated pneumonia vaccine (PCV) may have better immunogenicity in children than the PPV due to this age groups lack of immune response to polysaccharides. A randomized controlled trial compared the immunogenicity in elderly patients with recent pneumococcal pneumonia and found that PCV stimulates a more prolonged response than PPV. [6] Musher et. al. concluded that protein vaccines may be needed in the high risk elderly.

Efficacy

Ideally, pneumococcal vaccine would protect against pneumonia, invasive pneumococcal disease (bacteremia and meningitis), hospitalizations and death.

Randomized controlled trials

An updated Cochrane meta-analysis of randomized controlled trials in 2008 found:[7]

  • Randomized controlled trials provided strong evidence of vaccine efficacy against invasive pneumococcal disease (IPD) with no statistical heterogeneity (OR 0.26). Observational studies provided evidence for protection against IPD in populations for whom the vaccine is currently utilized (odds ratio = 0.48).
  • Efficacy against all cause pneumonia was inconclusive with substantial statistical heterogeneity
  • Pneumococcal vaccine was not associated with substantial reductions in all-cause mortality.
  • Vaccine efficacy against primary outcomes appeared poorer in adults with chronic illness but the difference was not statistically significant.

The authors concluded that evidence supports the recommendation for vaccination to prevent IPD in adults, but does not support vaccination to prevent all-cause pneumonia or mortality. [7] This is consistent with an earlier meta-analysis[8] and also a subsequent meta-analysis.[9] Although the most recent meta-analysis did not find benefit in preventing invasive disease[9], this analysis was weighted by a Ugandan study of HIV patients that showed not benefit. The Cochrane meta-analysis did not include this study and concluded that the vaccine prevents invasive disease.[7]

Observational studies

Among patients hospitalized for community acquired pneumonia, prior pneumococcal vaccination improved all cause mortality, respiratory failure, and reduced length of stay after adjustment for other factors in a cohort study of over 62,000 patients. [10]

First, in regards to which people are at risk of invasive pneumococcal disease (IPD), a recent Finnish study found that this diagnosis carried a 12% mortality at one month for patients 65 and over. 46% of those patients that died within 1 month of having IPD did not have an indication for receipt of the vaccination prior to hospitalization, with the age group of 50-64 having proportionally higher mortality. The authors concluded that policy makers should consider lowering the age criteria to 50. [11]

Cost-benefit analyses

A cost-benefit analysis, assuming that PPV is only effective at preventing invasive pneumococcal disease, found vaccination to be cost saving for general populations of adults 50–64 years of age [12] and 65 years of age and older[13].

Indications

In the United States of America, the Centers for Disease Control and Prevention[14][15][16] and the Joint Commission on Accreditation of Healthcare Organizations[17] have created recommendations for vaccination. In 2009, the Centers for Disease Control and Prevention added asthma and smoking to the indications for vaccination.[18][14]

The older clinical practice guidelines by the Infectious Disease Society of America and the American Thoracic Society recommend:

  • Adults >65 years of age
  • Persons >2 years with
    • chronic illness
    • anatomic or functional asplenia
    • immunocompromised (disease, chemotherapy, steroids)
    • Human Immunodeficiency Virus infection
    • environments or settings with increased risk

Vaccination of hospitalized patients

Although vaccination is viewed as purview of primary care physicians, vaccinating inpatients during hospitalizations may improve vaccination rates[19]; however, inpatient vaccination may be difficult to implement[20]. Paradoxically, inpatient strategies may be less successful in hospitals that have a high volume of pneumonia cases.[21]

References

  1. ↑ Anonymous (2024), Pneumococcal vaccine (English). Medical Subject Headings. U.S. National Library of Medicine.
  2. ↑ 2.0 2.1 Bacterial Polysaccharides Branch, DBP (June 30, 1983). Summary for Basis of Approval. Retrieved on 2009-08-25. “Merck Sharp & Dohme was licensed for Pneumococcal Vaccine, Polyvalent (14 types) in 1977.”
  3. ↑ Altman, Lawrence. (March 30, 2007) Robert Austrian, 90, Dies; Developed Major Vaccine The New York Times
  4. ↑ Austrian, R.: Random gleanings from a life with the pneumococcus, J. Infect. Dis. 131: 474-484, 1975. PMID 234994
  5. ↑ Galambos, Louis; Sewell, Jane Eliot. Networks of Innovation : Vaccine Development at Merck, Sharp and Dohme, and Mulford, 1895-1995. Cambridge University Press. ISBN 052162620X. 
  6. ↑ Musher DM, Rueda AM, Nahm MH, Graviss EA, Rodriguez-Barradas MC (October 2008). "Initial and subsequent response to pneumococcal polysaccharide and protein-conjugate vaccines administered sequentially to adults who have recovered from pneumococcal pneumonia". J. Infect. Dis. 198 (7): 1019–27. DOI:10.1086/591629. PMID 18710324. Research Blogging.
  7. ↑ 7.0 7.1 7.2 Moberley SA, Holden J, Tatham DP, Andrews RM (2008). "Vaccines for preventing pneumococcal infection in adults". Cochrane Database Syst Rev (1): CD000422. DOI:10.1002/14651858.CD000422.pub2. PMID 18253977. Research Blogging.
  8. ↑ Fine MJ, Smith MA, Carson CA, Meffe F, Sankey SS, Weissfeld LA, Detsky AS, Kapoor WN. Efficacy of pneumococcal vaccination in adults. A meta-analysis of randomized controlled trials. Arch Intern Med. 1994 Dec 12-26;154(23):2666-77. PMID 7993150
  9. ↑ 9.0 9.1 Huss A, Scott P, Stuck AE, Trotter C, Egger M (January 2009). "Efficacy of pneumococcal vaccination in adults: a meta-analysis". CMAJ 180 (1): 48–58. DOI:10.1503/cmaj.080734. PMID 19124790. PMC 2612051. Research Blogging.
  10. ↑ Fisman DN, Abrutyn E, Spaude KA, Kim A, Kirchner C, Daley J (April 2006). "Prior pneumococcal vaccination is associated with reduced death, complications, and length of stay among hospitalized adults with community-acquired pneumonia". Clin. Infect. Dis. 42 (8): 1093–101. DOI:10.1086/501354. PMID 16575726. Research Blogging.
  11. ↑ Klemets P, Lyytikäinen O, Ruutu P, Ollgren J, Pekka Nuorti J (2008). "Invasive pneumococcal infections among persons with and without underlying medical conditions: implications for prevention strategies". BMC Infect. Dis. 8: 96. DOI:10.1186/1471-2334-8-96. PMID 18647385. PMC 2507715. Research Blogging.
  12. ↑ Sisk JE, Whang W, Butler JC, Sneller VP, Whitney CG (June 2003). "Cost-effectiveness of vaccination against invasive pneumococcal disease among people 50 through 64 years of age: role of comorbid conditions and race". Ann. Intern. Med. 138 (12): 960–8. PMID 12809452. [e]
  13. ↑ Sisk JE, Moskowitz AJ, Whang W, et al (1997). "Cost-effectiveness of vaccination against pneumococcal bacteremia among elderly people". JAMA 278 (16): 1333–9. PMID 9343464. [e]
  14. ↑ 14.0 14.1 Advisory Committee on Immunization Practices (2009-01-06). "Recommended Adult Immunization Schedule: United States, 2009*". Ann Intern Med 150 (1): 40-44. PMID 19124819. Retrieved on 2009-01-06.
  15. ↑ (April 1997) "Prevention of pneumococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP)". MMWR Recomm Rep 46 (RR-8): 1–24. PMID 9132580. [e]
  16. ↑ Centers for Disease Control and Prevention. Recommended Adult Immunization Schedule—United States, October 2007–September 2008. MMWR 2007;56:Q1–Q4.:
  17. ↑ Anonymous (September 19, 2008). Specifications Manual for National Hospital Inpatient Quality Measures (pdf). Joint Commission.
  18. ↑ Centers for Disease Control and Prevention (CDC) (2010). "Updated Recommendations for Prevention of Invasive Pneumococcal Disease Among Adults Using the 23-Valent Pneumococcal Polysaccharide Vaccine (PPSV23).". MMWR Morb Mortal Wkly Rep 59 (34): 1102-6. PMID 20814406.
  19. ↑ Bratzler DW, Houck PM, Jiang H, et al (November 2002). "Failure to vaccinate Medicare inpatients: a missed opportunity". Arch. Intern. Med. 162 (20): 2349–56. PMID 12418949. [e]
  20. ↑ Winston CA, Lindley MC, Wortley PM (2006). "Lessons learned from inpatient vaccination in Michigan". Am J Med Qual 21 (2): 125–33. DOI:10.1177/1062860605284361. PMID 16533904. Research Blogging.
  21. ↑ Lindenauer PK, Behal R, Murray CK, Nsa W, Houck PM, Bratzler DW (February 2006). "Volume, quality of care, and outcome in pneumonia". Ann. Intern. Med. 144 (4): 262–9. PMID 16490912. [e]
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