Quote: (09-27-2012 11:23 PM)BIGINJAPAN Wrote:
I know what it is. And vioxx. The point is they are fabricating studies and in this case they didn't even have any patients
So your argument is that one (or a few) researchers fabricated data, therefore all evidence-based medicine is worthless. Sounds convincing.
This is the last thing I'm going to post about flu vaccines because I know that I will never convince you since beliefs like yours are not based on evidence. For the benefit of anyone else reading, here is the section on efficacy from the article "Seasonal Influenza Vaccination in Adults" on UpToDate, an evidence-based medicine database for physicians. The evidence is clear that if you want to avoid getting the flu, getting vaccinated is a good idea, especially if you are a child or elderly. But hey, apparently it's all fabricated by evil drug companies who just want to make money by making your kids autistic so believe whatever you want.
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EFFICACY — Because inactivated vaccines take approximately nine months to manufacture, they necessarily contain antigens from strains that circulated during the previous year. The protective efficacy of the vaccine is largely determined by the relationship (closeness of "fit" or "match") between the strains in the vaccine and viruses that circulate in the outbreak. If this "fit" is close, rates of protection of 50 to 80 percent against clinical influenza would be expected [21-24].
A study that compared the effectiveness of the inactivated influenza vaccine during influenza seasons with differing degrees of vaccine match illustrates the importance of the fit between circulating influenza virus strains and the vaccine [21]. During the 2004 to 2005 influenza season, the antigenic match was only 5 percent compared with 91 percent during the 2006 to 2007 season, which resulted in a vaccine effectiveness of 10 versus 52 percent, respectively.
A repeated finding in the studies described below is that vaccination produces a greater reduction in serologically confirmed influenza than in clinical influenza. Universal influenza vaccination in Ontario, Canada has also been shown to reduce the number of antibiotic prescriptions during periods of peak influenza activity [25].
Healthy adults — A number of studies have examined influenza vaccine efficacy in different populations. As illustrated by the following observations in healthy adults, vaccination produces marked reductions in serologically confirmed influenza and smaller reductions in clinical influenza.
Efficacy of inactivated vaccine — A randomized trial evaluated the effectiveness of the intramuscular inactivated influenza vaccine in 264 healthcare workers (mean age 28 years) without chronic medical conditions over three consecutive influenza seasons in Baltimore [26]. Vaccinees had a substantially reduced probability of influenza A or B infection based upon careful serologic testing compared with controls (1.7 versus 13.4 percent); overall vaccine efficacy was 88 percent for influenza A (95% CI 47-97 percent) and 89 percent (95% CI 14-99 percent) for influenza B. Cumulative days of febrile respiratory illness or absence from work were reduced in vaccine recipients but did not achieve statistical significance. This highlights the much greater protection against serologic compared with clinical influenza.
The importance of the match between the circulating strains of virus and the strains in the vaccine was illustrated in a report of more than 1100 full-time employees (mean age 44 years) of a United States manufacturing company during two consecutive influenza seasons [27]. In the first year, the vaccine did not match circulating viruses well; the efficacy of vaccination against serologically confirmed influenza was 50 percent, but there were no differences in influenza-like illnesses, physician visits, and lost workdays between those who were vaccinated and controls. In the second season, when circulating viruses were better covered in the vaccine, efficacy against serologically confirmed influenza was 86 percent, and vaccinated employees had fewer influenza-like illnesses, physician visits, and lost workdays compared with placebo recipients.
A subsequent systematic review of published reports through 2006 that evaluated 15 trials of the inactivated influenza vaccine found that the vaccine was 80 percent effective (95% CI 56-91 percent) against laboratory-confirmed influenza when the vaccine matched the circulating strain(s) compared with 50 percent (95% CI 27-65 percent) when it did not [28].
A case-control study in adults 40 years or older found that influenza vaccination was associated with a reduction in the rate of first acute myocardial infarction (adjusted odds ratio 0.81, 95% CI 0.77-0.85) [29].
Efficacy of live-attenuated vaccine — A randomized, double-blind trial compared the live-attenuated influenza vaccine (LAIV) preparation with placebo in 4561 healthy, employed adults followed through an influenza season [30]. Vaccination was associated with significant reductions in severe febrile illnesses (19 percent), febrile upper respiratory tract illnesses (24 percent), and days of work lost for febrile upper respiratory tract illnesses (28 percent). The vaccine was well tolerated and appeared to protect against the prevailing strain of influenza A that season, despite the virus showing considerable drift from the vaccine strain.
The 2006 systematic review cited above evaluated six trials of the LAIV [28]. The vaccine was 62 percent effective (95% CI 45-73 percent) at preventing laboratory-confirmed influenza. The authors noted that it was not possible to make conclusions about the utility of the LAIV because the assessment of effectiveness was based upon a limited number of studies that had conflicting results.
Comparisons of inactivated and live-attenuated vaccines — Although in children the LAIV may be more effective than the inactivated vaccine, studies in adults have shown that the inactivated vaccine is either equivalent to or more effective than the live-attenuated vaccine. (See "Seasonal influenza vaccination in children", section on 'LAIV compared with TIV'.)
Comparisons of inactivated and live-attenuated vaccines have shown the following:
A randomized trial compared the intramuscular inactivated and intranasal live-attenuated influenza vaccines in 5210 normal subjects over five years of age [31]. In terms of preventing culture-positive influenza A, the inactivated and live-attenuated vaccines were 76 and 85 percent effective against H1N1 disease and 74 and 58 percent effective against H3N2 disease, respectively. The differences between the two vaccines were not statistically significant.
A subsequent randomized trial was performed in 1247 healthy adults in Michigan during the 2004 to 2005 influenza season [32]. Both vaccines had similar efficacy against culture-proven influenza A infection (74 percent), despite the fact that most circulating viruses were dissimilar to those included in the vaccines. In contrast, the inactivated vaccine was superior to the live-attenuated vaccine against culture-confirmed type B influenza infections (80 versus 40 percent efficacy).
In another randomized trial that included 1952 adults in Michigan vaccinated during the 2007 to 2008 influenza season, the inactivated vaccine was superior to the live-attenuated vaccine against influenza infection as detected by viral culture, real-time polymerase chain reaction, or both (68 versus 36 percent absolute efficacy, respectively) [33]. During the same influenza season, 90 percent of isolates were influenza A H3N2 and 9 percent of isolates were influenza B. The absolute efficacy against the influenza A strain was 72 percent for the inactivated vaccine compared with 29 percent for the live-attenuated vaccine.
In a large surveillance study of US military personnel during three influenza seasons between 2004 and 2007, immunization with the inactivated vaccine was associated with lower rates of health care visits for pneumonia and influenza compared with the live-attenuated vaccine (8.6 versus 19.4 per 1000 person-years in 2004 to 2005; 7.8 versus 10.9 per 1000 person-years in 2005 to 2006; and 8.0 versus 11.7 per 1000 person-years in 2006 to 2007) [34]. However, among individuals who had not been immunized the previous year, the effect of the live-attenuated vaccine was comparable to the inactivated vaccine during the 2005 to 2006 and 2006 to 2007 seasons. Whether these results can be generalized to other populations is uncertain.
The relative performance of the vaccines may vary according to the age of the recipient, the level of pre-existing immunity, and the specific circulating virus [35].
Elderly patients — More than 90 percent of influenza-related deaths occur among people over 60 years of age [36] and elderly patients have increased morbidity from the disease.
Until recently, the CDC’s ACIP cautioned that influenza-specific antibodies wane more rapidly in elderly adults than in younger individuals. However, a 2008 literature review that included studies of individuals >60 years old found that seroprotection was maintained for at least 4 months after influenza vaccination in all eight studies that assessed antibody responses to the H3N2 component and in five of seven studies that assessed responses to the H1N1 and B components [37]. Seroprotection rates were maintained for up to or longer than 6 months for the H3N2 and H1N1 components.
Regardless of the influenza-specific antibody levels achieved and maintained in the immunized elderly individual, the main question is whether the vaccine reduces influenza-related morbidity and mortality. The efficacy of the inactivated influenza vaccine in elderly patients (in whom the live vaccine is not recommended) has been evaluated in a few randomized trials [38,39] and multiple large observational studies, both in the community and in long term care facilities [40-47], as well as in sicker patients such as those with chronic lung disease [48-50] with conflicting results.
A 2005 systematic review summarized the available data [38]. Among residents of long term care facilities, vaccines well-matched for the circulating influenza viruses were not effective against influenza, but were associated with 54 to 58 percent reductions in pneumonia, hospital admission, and death from influenza or pneumonia. A similar conclusion was reached for elderly patients living in the community, except that the vaccine did not reduce the rate of pneumonia in this population.
A 2008 case-control study evaluated 1173 cases and 2346 controls among community-dwelling elderly individuals during three pre-influenza periods and influenza seasons, also during a period when there was good antigenic match between the influenza vaccine and circulating viruses [46]. This study also found that influenza vaccination did not reduce the risk of pneumonia (including those who did not require hospitalization), after adjusting for the presence and severity of comorbidities. In contrast, in a 2012 cohort study of community-dwelling elderly individuals that evaluated 12.6 million person-influenza seasons, vaccination was associated with a reduction in the composite endpoint of hospitalization (for pneumonia and influenza) and death during influenza season (adjusted odds ratio 0.86, 95% CI 0.79-0.92) [51].
Since protection against influenza is suboptimal in the elderly, it is not surprising that the outbreaks of influenza have occurred in nursing homes where 80 to 98 percent of residents were vaccinated [45]. (See 'Healthcare workers' below.)
Effect on mortality — It has been difficult to demonstrate an improvement in survival after influenza vaccination in elderly patients in randomized controlled trials because mortality is a rare end-point. The systematic review cited above found a significant reduction in death from influenza or pneumonia [38], but some have suggested that frailty selection bias in cohort studies has led to an overestimation of any mortality benefit of influenza vaccination in elderly adults [52].
A pooled cohort study published after the systematic review demonstrated a small but significant reduction in mortality in vaccinated elderly individuals (1.0 versus 1.6 percent in unvaccinated individuals) [41]. A sensitivity analysis was performed to detect unmeasured confounders. Even when a higher rate of confounders was assumed, there was still a significant reduction in mortality. Other studies have supported this finding [53]. Any mortality benefit in elderly patients is increased with annual vaccination [44]. (See 'Need for annual vaccination' below.)
The difficulty of using observational data to evaluate the effect of influenza vaccine on mortality is further illustrated by a prospective case-control study of patients (mostly over the age of 65) with community-acquired pneumonia (CAP). The study assessed the impact of influenza vaccination on in-hospital mortality in patients admitted during the off-season for influenza [54]. A significant mortality reduction was observed in vaccinated patients (OR 0.49; 95% CI 0.30-0.79). However, when adjustments were made to address confounding factors (eg, functional and socioeconomic status), the mortality benefit became nonsignificant (adjusted OR 0.81; 95% CI 0.35-1.85). This study shows that the presence of bias may overestimate the mortality benefit of influenza vaccination [55].
In contrast to the studies described above, a large cohort study of community-dwelling elderly individuals did not detect a mortality benefit from influenza vaccination [51]. An important limitation of this study was the likely underreporting of vaccination status, which could have contributed to the vaccine appearing ineffective [56].
Dual influenza and pneumococcal vaccination — A cohort study has suggested that dual influenza and pneumococcal vaccination is superior to either vaccine alone for preventing complications in elderly adults with chronic illnesses [57]. In adults ≥65 years of age with chronic illnesses, dual vaccination with the inactivated influenza vaccine and the pneumococcal polysaccharide vaccine resulted in lower rates of death (hazard ratio
0.65, 95% CI 0.55-0.77), pneumonia (HR 0.57, 95% CI 0.51-0.64), ischemic stroke (HR 0.67, 95% CI 0.54-0.83), and acute myocardial infarction (HR 0.52, 95% CI 0.38-0.71) compared with unvaccinated individuals. Dual vaccination also resulted in fewer coronary (HR 0.59, 95%CI, 0.44-0.79) and intensive care unit admissions (HR 0.45, 95% CI 0.22-0.94) compared with unvaccinated individuals. Since this was not a randomized trial, it is possible that the results might be biased, particularly since individuals who received both vaccines may also have other behaviors that result in better health.
In contrast to influenza vaccination, which should be given annually to all adults, only one or two doses of the pneumococcal polysaccharide vaccine are recommended for adults ≥65 years of age and in younger patients with a number of conditions that increase the risk of invasive pneumococcal disease (table 3). Pneumococcal vaccination is discussed in detail separately. (See "Pneumococcal vaccination in adults", section on 'Indications'.)
