vaccination

BACKGROUND:

Acute otitis media (AOM) is one of the most common childhood illnesses. While many children experience sporadic AOM episodes, an important group suffer from recurrent AOM (rAOM), defined as three or more episodes in six months, or four or more in one year. In this subset of children AOM poses a true burden through frequent episodes of ear pain, general illness, sleepless nights and time lost from nursery or school. Grommets, also called ventilation or tympanostomy tubes, can be offered for rAOM.

OBJECTIVES:

To assess the benefits and harms of bilateral grommet insertion with or without concurrent adenoidectomy in children with rAOM.

SEARCH METHODS:

The Cochrane ENT Information Specialist searched the Cochrane ENT Trials Register; CENTRAL; MEDLINE; EMBASE; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 4 December 2017.

SELECTION CRITERIA:

Randomised controlled trials (RCTs) comparing bilateral grommet insertion with or without concurrent adenoidectomy and no ear surgery in children up to age 16 years with rAOM. We planned to apply two main scenarios: grommets as a single surgical intervention and grommets as concurrent treatment with adenoidectomy (i.e. children in both the intervention and comparator groups underwent adenoidectomy). The comparators included active monitoring, antibiotic prophylaxis and placebo medication.

DATA COLLECTION AND ANALYSIS:

We used the standard methodological procedures expected by Cochrane. Primary outcomes were: proportion of children who have no AOM recurrences at three to six months follow-up (intermediate-term) and persistent tympanic membrane perforation (significant adverse event). Secondary outcomes were: proportion of children who have no AOM recurrences at six to 12 months follow-up (long-term); total number of AOM recurrences, disease-specific and generic health-related quality of life, presence of middle ear effusion and other adverse events at short-term, intermediate-term and long-term follow-up. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics.

MAIN RESULTS:

Five RCTs (805 children) with unclear or high risk of bias were included. All studies were conducted prior to the introduction of pneumococcal vaccination in the countries' national immunisation programmes. In none of the trials was adenoidectomy performed concurrently in both groups.Grommets versus active monitoringGrommets were more effective than active monitoring in terms of:- proportion of children who had no AOM recurrence at six months (one study, 95 children, 46% versus 5%; risk ratio (RR) 9.49, 95% confidence interval (CI) 2.38 to 37.80, number needed to treat to benefit (NNTB) 3; low-quality evidence);- proportion of children who had no AOM recurrence at 12 months (one study, 200 children, 48% versus 34%; RR 1.41, 95% CI 1.00 to 1.99, NNTB 8; low-quality evidence);- number of AOM recurrences at six months (one study, 95 children, mean number of AOM recurrences per child: 0.67 versus 2.17, mean difference (MD) -1.50, 95% CI -1.99 to -1.01; low-quality evidence);- number of AOM recurrences at 12 months (one study, 200 children, one-year AOM incidence rate: 1.15 versus 1.70, incidence rate difference -0.55, 95% -0.17 to -0.93; low-quality evidence).Children receiving grommets did not have better disease-specific health-related quality of life (Otitis Media-6 questionnaire) at four (one study, 85 children) or 12 months (one study, 81 children) than those managed by active monitoring (low-quality evidence).One study reported no persistent tympanic membrane perforations among 54 children receiving grommets (low-quality evidence).Grommets versus antibiotic prophylaxisIt is uncertain whether or not grommets are more effective than antibiotic prophylaxis in terms of:- proportion of children who had no AOM recurrence at six months (two studies, 96 children, 60% versus 35%; RR 1.68, 95% CI 1.07 to 2.65, I2 = 0%, fixed-effect model, NNTB 5; very low-quality evidence);- number of AOM recurrences at six months (one study, 43 children, mean number of AOM recurrences per child: 0.86 versus 1.38, MD -0.52, 95% CI -1.37 to 0.33; very low-quality evidence).Grommets versus placebo medicationGrommets were more effective than placebo medication in terms of:- proportion of children who had no AOM recurrence at six months (one study, 42 children, 55% versus 15%; RR 3.64, 95% CI 1.20 to 11.04, NNTB 3; very low-quality evidence);- number of AOM recurrences at six months (one study, 42 children, mean number of AOM recurrences per child: 0.86 versus 2.0, MD -1.14, 95% CI -2.06 to -0.22; very low-quality evidence).One study reported persistent tympanic membrane perforations in 3 of 76 children (4%) receiving grommets (low-quality evidence).Subgroup analysisThere were insufficient data to determine whether presence of middle ear effusion at randomisation, type of grommet or age modified the effectiveness of grommets.

AUTHORS' CONCLUSIONS:

Current evidence on the effectiveness of grommets in children with rAOM is limited to five RCTs with unclear or high risk of bias, which were conducted prior to the introduction of pneumococcal vaccination. Low to very low-quality evidence suggests that children receiving grommets are less likely to have AOM recurrences compared to those managed by active monitoring and placebo medication, but the magnitude of the effect is modest with around one fewer episode at six months and a less noticeable effect by 12 months. The low to very low quality of the evidence means that these numbers need to be interpreted with caution since the true effects may be substantially different. It is uncertain whether or not grommets are more effective than antibiotic prophylaxis. The risk of persistent tympanic membrane perforation after grommet insertion was low.Widespread use of pneumococcal vaccination has changed the bacteriology and epidemiology of AOM, and how this might impact the results of prior trials is unknown. New and high-quality RCTs of grommet insertion in children with rAOM are therefore needed. These trials should not only focus on the frequency of AOM recurrences, but also collect data on the severity of AOM episodes, antibiotic consumption and adverse effects of both surgery and antibiotics. This is particularly important since grommets may reduce the severity of AOM recurrences and allow for topical rather than oral antibiotic treatment.

Introduction

Healthcare personnel influenza vaccination can reduce influenza illness and patient mortality. State laws are one tool promoting healthcare personnel influenza vaccination.

Methods

A 2016 legal assessment in 50 states and Washington DC identified (1) assessment laws: mandating hospitals assess healthcare personnel influenza vaccination status; (2) offer laws: mandating hospitals offer influenza vaccination to healthcare personnel; (3) ensure laws: mandating hospitals require healthcare personnel to demonstrate proof of influenza vaccination; and (4) surgical masking laws: mandating unvaccinated healthcare personnel to wear surgical masks during influenza season. Influenza vaccination was calculated using data reported in 2016 by short-stay acute care hospitals (n=4,370) to the National Healthcare Safety Network. Hierarchical linear modeling in 2018 examined associations between reported vaccination and assessment, offer, or ensure laws at the level of facilities nested within states, among employee and non-employee healthcare personnel and among employees only.

Results

Eighteen states had one or more healthcare personnel influenza vaccination-related laws. In the absence of any state laws, facility vaccination mandates were associated with an 11–12 percentage point increase in mean vaccination coverage (p<0.0001). Facility-level mandates were estimated to increase mean influenza vaccination coverage among all healthcare personnel by 4.2 percentage points in states with assessment laws, 6.6 percentage points in states with offer laws, and 3.1 percentage points in states with ensure laws. Results were similar in analyses restricted only to employees although percentage point increases were slightly larger.

Conclusions

State laws moderate the effect of facility-level vaccination mandates and may help increase healthcare personnel influenza vaccination coverage in facilities with or without vaccination requirements.

BACKGROUND:

The consequences of influenza in adults are mainly time off work. Vaccination of pregnant women is recommended internationally. This is an update of a review published in 2014. Future updates of this review will be made only when new trials or vaccines become available. Observational data included in previous versions of the review have been retained for historical reasons but have not been updated due to their lack of influence on the review conclusions.

OBJECTIVES:

To assess the effects (efficacy, effectiveness, and harm) of vaccines against influenza in healthy adults, including pregnant women.

SEARCH METHODS:

We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 12), MEDLINE (January 1966 to 31 December 2016), Embase (1990 to 31 December 2016), the WHO International Clinical Trials Registry Platform (ICTRP; 1 July 2017), and ClinicalTrials.gov (1 July 2017), as well as checking the bibliographies of retrieved articles.

SELECTION CRITERIA:

Randomised controlled trials (RCTs) or quasi-RCTs comparing influenza vaccines with placebo or no intervention in naturally occurring influenza in healthyindividuals aged 16 to 65 years. Previous versions of this review included observational comparative studies assessing serious and rare harms cohort and case-control studies. Due to the uncertain quality of observational (i.e. non-randomised) studies and their lack of influence on the review conclusions, we decided to update only randomised evidence. The searches for observational comparative studies are no longer updated.

DATA COLLECTION AND ANALYSIS:

Two review authors independently assessed trial quality and extracted data. We rated certainty of evidence for key outcomes (influenza, influenza-like illness (ILI), hospitalisation, and adverse effects) using GRADE.

MAIN RESULTS:

We included 52 clinical trials of over 80,000 people assessing the safety and effectiveness of influenza vaccines. We have presented findings from 25 studies comparing inactivated parenteral influenza vaccine against placebo or do-nothing control groups as the most relevant to decision-making. The studies were conducted over single influenza seasons in North America, South America, and Europe between 1969 and 2009. We did not consider studies at high risk of bias to influence the results of our outcomes except for hospitalisation.Inactivated influenza vaccines probably reduce influenza in healthy adults from 2.3% without vaccination to 0.9% (risk ratio (RR) 0.41, 95% confidence interval (CI) 0.36 to 0.47; 71,221 participants; moderate-certainty evidence), and they probably reduce ILI from 21.5% to 18.1% (RR 0.84, 95% CI 0.75 to 0.95; 25,795 participants; moderate-certainty evidence; 71 healthy adults need to be vaccinated to prevent one of them experiencing influenza, and 29 healthy adults need to be vaccinated to prevent one of them experiencing an ILI). The difference between the two number needed to vaccinate (NNV) values depends on the different incidence of ILI and confirmed influenza among the study populations. Vaccination may lead to a small reduction in the risk of hospitalisation in healthy adults, from 14.7% to 14.1%, but the CI is wide and does not rule out a large benefit (RR 0.96, 95% CI 0.85 to 1.08; 11,924 participants; low-certainty evidence). Vaccines may lead to little or no small reduction in days off work (-0.04 days, 95% CI -0.14 days to 0.06; low-certainty evidence). Inactivated vaccines cause an increase in fever from 1.5% to 2.3%.We identified one RCT and one controlled clinical trial assessing the effects of vaccination in pregnant women. The efficacy of inactivated vaccine containing pH1N1 against influenza was 50% (95% CI 14% to 71%) in mothers (NNV 55), and 49% (95% CI 12% to 70%) in infants up to 24 weeks (NNV 56). No data were available on efficacy against seasonal influenza during pregnancy. Evidence from observational studies showed effectiveness of influenza vaccines against ILI in pregnant women to be 24% (95% CI 11% to 36%, NNV 94), and against influenza in newborns from vaccinated women to be 41% (95% CI 6% to 63%, NNV 27).Live aerosol vaccines have an overall effectiveness corresponding to an NNV of 46. The performance of one- or two-dose whole-virion 1968 to 1969 pandemic vaccines was higher (NNV 16) against ILI and (NNV 35) against influenza. There was limited impact on hospitalisations in the 1968 to 1969 pandemic (NNV 94). The administration of both seasonal and 2009 pandemic vaccines during pregnancy had no significant effect on abortion or neonatal death, but this was based on observational data sets.

AUTHORS' CONCLUSIONS:

Healthy adults who receive inactivated parenteral influenzavaccine rather than no vaccine probably experience less influenza, from just over 2% to just under 1% (moderate-certainty evidence). They also probably experience less ILI following vaccination, but the degree of benefit when expressed in absolute terms varied across different settings. Variation in protection against ILI may be due in part to inconsistent symptom classification. Certainty of evidence for the small reductions in hospitalisations and time off work is low. Protection against influenza and ILI in mothers and newborns was smaller than the effects seen in other populations considered in this review.Vaccines increase the risk of a number of adverse events, including a small increase in fever, but rates of nausea and vomiting are uncertain. The protective effect of vaccination in pregnant women and newborns is also very modest. We did not find any evidence of an association between influenzavaccination and serious adverse events in the comparative studies considered in this review. Fifteen included RCTs were industry funded (29%).

Update of

Vaccines for preventing influenza in healthy adults. [Cochrane Database Syst Rev. 2014]