The Brighton collaboration standardized module for vaccine benefit-risk assessment.

Vaccine Benefit-Risk (B-R) assessment consists of evaluating the benefits and risks of a vaccine and making a judgment whether the expected key benefits outweigh the potential key risks associated with its expected use. B-R supports regulatory and public health decision-making throughout the vaccine's lifecycle. In August 2021, the Brighton Collaboration's Benefit-Risk Assessment of VAccines by TechnolOgy (BRAVATO) Benefit-Risk Assessment Module working group was established to develop a standard module to support the planning, conduct and evaluation of structured B-R assessments for vaccines from different platforms, based on data from clinical trials, post-marketing studies and real-world evidence. It enables sharing of relevant information via value trees, effects tables and graphical depictions of B-R trade-offs. It is intended to support vaccine developers, funders, regulators and policy makers in high-, middle- or low-income countries to help inform decision-making and facilitate transparent communication concerning development, licensure, deployment and other lifecycle decisions.

A National Advisory Committee on Immunization (NACI) update on invasive meningococcal disease (IMD) epidemiology and program-relevant considerations for preventing IMD in individuals at high risk of exposure.

Following recent outbreaks of invasive meningococcal disease (IMD) in Canada and updates to provincial vaccination guidelines, the National Advisory Committee on Immunization (NACI) conducted a targeted review of evidence with a focus on immunization of adolescents and young adults. NACI reviewed national and international immunization recommendations for populations at high-risk of IMD, national IMD epidemiology and program-relevant considerations. Given the varied IMD epidemiology, NACI determined that recommending a pan-Canadian targeted program is currently challenging and that regional programs may be better suited to prevent IMD in population groups considered to be at high-risk of exposure. Further data is needed to ascertain contemporary risk factors for IMD (including activities and settings associated with bacterial acquisition, carriage and transmission) and estimate the true cost of meningococcal vaccine-preventable infections in Canada. To support provinces and territories in their decision-making, an outline of program-relevant elements for provincial and territorial consideration is provided.

Revaccination and Adverse Event Recurrence in Patients with Adverse Events following Immunization.

OBJECTIVES: To estimate the risk of recurrence of adverse events following immunization (AEFIs) upon revaccination and to determine among patients with suspected vaccine allergy whether allergy skin test positivity was associated with AEFI recurrence. STUDY DESIGN: This prospective observational study included patients assessed in the Canadian Special Immunization Clinic Network from 2013 to 2019 with AEFIs who required revaccination with the vaccine temporally associated with their AEFI. Participants underwent standardized assessment and data collection. Special Immunization Clinic physicians used guidelines to inform their recommendations. Participants were followed up after revaccination to capture AEFI recurrences. Data were transferred to a central database for descriptive analysis. RESULTS: Overall, 588 participants were assessed for 627 AEFIs; 570 (91%) AEFIs occurred in children <18 years of age. AEFIs included immediate hypersensitivity (130/627; 21%), large local reactions (110/627; 18%), nonurticarial rash (51/627; 8%), seizures (26/627; 4%), and thrombocytopenia (11/627; 2%). Revaccination was recommended to 513 of 588 (87%) participants. Among participants recommended and due for revaccination during the study period, 63% (299/477) were revaccinated. AEFI recurrence was 10% (31/299) overall, 31% (15/49) for large local reactions, and 7% (5/66) for immediate hypersensitivity. No recurrence was serious. Among 92 participants with suspected vaccine allergy who underwent skin testing and were revaccinated, the negative predictive value of skin testing for AEFI recurrence was 96% (95% CI 92.5%-99.5%). CONCLUSIONS: Most individuals with AEFIs were safely revaccinated. Among those with suspected vaccine allergy, skin testing may help determine the safety of revaccination.

Myocarditis and/or pericarditis risk after mRNA COVID-19 vaccination: A Canadian head to head comparison of BNT162b2 and mRNA-1273 vaccines.

BACKGROUND: Canadian and international data suggest the risk of myocarditis and/or pericarditis is elevated during the week after mRNA COVID-19 vaccination, particularly in younger age groups, in males, and after second doses. OBJECTIVES: This article examines whether there is a product-specific difference in the risk for myocarditis and/or pericarditis between the two mRNA vaccines administered in Canada: BNT162b2 (Pfizer-BioNTech Comirnaty) and mRNA-1273 (Moderna Spikevax). MATERIALS AND METHODS: Reporting rates of myocarditis and/or pericarditis were calculated from reports received by the Canadian Adverse Events Following Immunization Surveillance System from December 2020-March 2022. Excess cases and attributable incidence among individuals aged 18-39 were estimated for each vaccine in comparison with background rates from 2015 to 2019. Head-to-head comparisons used Poisson regression, conditioned on week of vaccine administration, to estimate rate ratios for the week after mRNA-1273 vaccination versus the week after BNT162b2, by age and sex as well as overall. Analyses were restricted to May 30-March 13, 2021, when heightened media awareness was unlikely to have affected reporting rates for the two products differentially. RESULTS: In 18-29 year-old males who received a second dose of mRNA COVID-19 vaccine, attributable risk of myocarditis and/or pericarditis was found to be 5.69 (95% CI: 4.07 - 7.95; p < 0.001) times higher among mRNA-1273 recipients (n = 106) as compared to BNT162b2 recipients (n = 33). In the same group, Poisson regression modelling estimated that the risk of myocarditis and/or pericarditis was 4.72 (p-value = <0.001) times higher after mRNA-1723 compared to BNT162b2 vaccination. CONCLUSIONS: The risk of myocarditis and/or pericarditis is higher after mRNA-1723 vaccination than BNT162b2 vaccination in those aged 18-39 years, especially in males aged 18-29 years, where the risk is several times higher.

Physician vaccination practices in mild to moderate inborn errors of immunity and retrospective review of vaccine completeness in IEI: results from the Canadian Immunization Research Network.

BACKGROUND AND OBJECTIVES: Safety and effectiveness concerns may preclude physicians from recommending vaccination in mild/moderate inborn errors of immunity (IEI). This study describes attitudes and practices regarding vaccination among physicians who care for patients with mild/moderate B cell or mild/moderate combined immunodeficiencies (CID) and vaccination completeness among patients diagnosed with IEIs. METHODS: Canadian physicians caring for children with IEI were surveyed about attitudes and practices regarding vaccination in mild/moderate IEI. Following informed consent, immunization records of pediatric patients with IEI evaluated before 7 years of age were reviewed. Vaccine completeness was defined at age 2 years as 4 doses of diphtheria-tetanus-pertussis (DTaP), 3 doses pneumococcal conjugate (PCV), and 1 dose measles-mumps-rubella (MMR) vaccines. At 7 years 5 doses of DTP and 2 doses MMR were required. RESULTS: Forty-five physicians from 8 provinces completed the survey. Most recommended inactivated vaccines for B cell deficiency: (84% (38/45) and CID (73% (33/45). Fewer recommended live attenuated vaccines (B cell: 53% (24/45), CID 31% (14/45)). Of 96 patients with IEI recruited across 7 centers, vaccination completeness at age 2 was 25/43 (58%) for predominantly antibody, 3/13 (23%) for CID, 7/35 (20%) for CID with syndromic features, and 4/4 (100%) for innate/phagocyte defects. Completeness at age 7 was 15%, 17%, 5%, and 33%, respectively. CONCLUSION: Most physicians surveyed recommended inactivated vaccines in children with mild to moderate IEI. Vaccine completeness for all IEI was low, particularly at age 7. Further studies should address the reasons for low vaccine uptake among children with IEI and whether those with mild-moderate IEI, where vaccination is recommended, eventually receive all indicated vaccines.

Effectiveness of palivizumab immunoprophylaxis to prevent respiratory syncytial virus hospitalizations in healthy full-term <6-month-old infants from the circumpolar region of Nunavik, Quebec, Canada.

In Quebec, Canada, eligibility for palivizumab (PVZ) immunoprophylaxis was expanded in fall 2016 to include healthy-full-term (HFT) infants residing in the circumpolar region of Nunavik and aged <3 months at the start of the RSV season or born during the season. This study assessed the effectiveness of PVZ to prevent RSV hospitalizations in these infants during the 3 seasons following its implementation. Medical and laboratory records of <1-year-old infants (375 average annual birth cohort) admitted to regional and tertiary hospitals with respiratory infection during 6 years were reviewed. Individual pharmacy data and birth registries were used to estimate adherence to PVZ and direct PVZ effectiveness in 0-5-month-old HFT infants by comparing the incidence of RSV hospitalizations 1) in protected and unprotected infants, and 2) during PVZ-protected and unprotected days. Over six seasons, the RSV hospitalization rate was 50.2/1000 (72.6/1000 adjusted for underdetection) in <1-year-old infants. PVZ was administered to 73% (469) of eligible HFT infants; 37% (237) received all recommended doses. Overall for the three RSV seasons the incidence of RSV hospitalization in PVZ-protected infants was similar to PVZ-unprotected infants, resulting in PVZ direct effectiveness of -6.7% (95% CI -174.8%, 85.6%). The incidence of RSV hospitalization during PVZ-protected and during PVZ-unprotected days was also similar, resulting in PVZ direct effectiveness of -3.8% (CI -167.6%, 64.9%). Over three RSV seasons, there was no evidence that PVZ reduced RSV hospitalizations in HFT Nunavik infants. In addition, the sub-optimal adherence to the recommended PVZ administration schedule suggests feasibility and acceptability issues.

Neuroimaging findings in headache with normal neurologic examination: Systematic review and meta-analysis.

OBJECTIVE: To determine if pooled estimates of the prevalence of unexpected findings in patients with headache and normal neurologic examination support current expert opinion-based neuroimaging guidelines. METHODS: We searched PubMed and EMBASE for studies reporting neuroimaging findings in patients with headache and normal neurologic examination up to September 30, 2017. The overall and disease-specific prevalence of unexpected findings were pooled through random-effects meta-analysis. This study is registered with PROSPERO, registration number CRD42017079714. RESULTS: In forty-one studies including 15,760 participants, the overall prevalence of unexpected findings and normal variants was 17.5% (95% CI: 13.1-22.3). The prevalence was 26.6% (95% CI: 15.5-39.4) in studies using MRI only. The prevalence of vascular, neoplastic, and non-neoplastic findings was 6.6%, 1.4%, and 9.6%. The pooled disease-specific prevalence was 2.0% for stroke, 1.8% for aneurysms, 0.8% for subdural hematoma, 0.7% for hydrocephalus, 0.2% for glioma, and 0.1% for meningioma. In secondary analysis, there was 0.4% increase in the prevalence of vascular unexpected findings with each 1% increase in the proportion of migraine with aura (p-value for meta-regression = 0.005). CONCLUSIONS: In patients with headache and normal neurologic examination, important vascular and neoplastic unexpected findings are rare and better detected with MRI. This supports current American College of Radiology and European Headache Federation recommendations to avoid systematic imaging in such patients and prefer MRI when imaging is needed.

Adverse events following immunisation with four-component meningococcal serogroup B vaccine (4CMenB): interaction with co-administration of routine infant vaccines and risk of recurrence in European randomised controlled trials.

OBJECTIVES: (1) To assess if co-administration of four-component meningococcal serogroup B vaccine (4CMenB) and other routine vaccines caused an interaction increasing the risk and/or severity of adverse events following immunisation (AEFI) compared with administration at separate visits and (2) to estimate the risk of AEFI recurrence. DESIGN: Risk-interval design SETTING: Three randomised controlled trials conducted in Europe. PARTICIPANTS: A total of 5026 healthy 2-month-old to 15-month-old infants. INTERVENTIONS: 4CMenB and routine vaccines (hexavalent combined diphtheria-tetanus-acellular pertussis-inactivated polio-Haemophilus influenzae type b-hepatitis B vaccine+seven-valent pneumococcal conjugate vaccine or measles-mumps-rubella-varicella vaccine) administered concomitantly or separately 1 month apart, in regular (2, 4, 6 and 12 months), accelerated (2, 3, 4 and 12 months) or delayed (two doses of 4CMenB at ≥12 months of age) schedules. OUTCOME MEASURES: Primary: Fever (≥38°C) during the first 48 hours post immunisation. Secondary: crying, change in eating habits, diarrhoea, irritability and tenderness at the 4CMenB injection site. RESULTS: Compared with separate administration, concomitant administration decreased the overall incidence of fever (≥38°C), 86% versus 75%, and other systemic AEFIs but increased the incidence of 4CMenB injection site tenderness, 55% versus 66%, moderate/severe fevers (≥39°C), 13% versus 18%, and long-lasting (>1 day) fevers, 23% versus 33%. Co-administration reduced AEFI risk by 4%-49% with the greatest impact among infants with prior AEFI(s). Fever recurrence risk was proportional to the number of prior fever events: 79% at dose 2 with one prior episode; 44% and 74% at dose 3 with one and two prior episodes, respectively; and 29%, 45% and 60% at dose 4 with one, two and three prior episodes, respectively. Severity was not increased at recurrence and a similar pattern of recurrence risk proportional to the number of prior events was observed for other AEFIs. CONCLUSIONS: The cumulative risk of AEFI is reduced with concomitant versus separate administration of 4CMenB and routine infant vaccines. Infants with a prior AEFI are at higher risk of the same AEFI at subsequent immunisations, but severity with recurrence is usually not increased. TRIALS REGISTRATION NUMBER: NCT00657709, NCT00847145, NCT00721396 and NCT02712177; Pre-results.

Rate of Recurrence of Adverse Events Following Immunization: Results of 19 Years of Surveillance In Quebec, Canada.

BACKGROUND: While adverse events following immunization (AEFI) are frequent, there are limited data on the safety of reimmunizing patients who had a prior AEFI. Our objective was to estimate the rate and severity of AEFI recurrences. METHODS: We analyzed data from the AEFI passive surveillance system in Quebec, Canada, that collects information on reimmunization of patients who had a prior AEFI. Patients with an initial AEFI reported to the surveillance system between 1998 and 2016 were included. Rate of AEFI recurrence was calculated as number of patients with recurrence/total number of patients reimmunized. RESULTS: Overall, 1350 patients were reimmunized, of which 59% were 2 years of age or younger. The AEFI recurred in 16% (215/1350) of patients, of whom 18% (42/215) rated the recurrence as more severe than the initial AEFI. Large local reactions extending beyond the nearest joint and lasting 4 days or more had the highest recurrence rate (67%, 6/9). Patients with hypotonic hyporesponsive episodes had the lowest rate of recurrence (2%, 1/50). Allergic-like events recurred in 12% (76/659) of patients, but none developed anaphylaxis. Of 33 patients with seizures following measles mumps rubella with/without varicella vaccine, none had a recurrence. Compared with patients with nonserious AEFIs, those with serious AEFIs were less often reimmunized (60% versus 80%; rate ratio: 0.8; 95% confidence interval: 0.66-0.86). CONCLUSIONS: Most patients with a history of mild or moderate AEFI can be safely reimmunized. Additional studies are needed in patients with serious AEFIs who are less likely to be reimmunized.

Investigation of an increase in large local reactions following vaccine schedule change to include DTaP-HB-IPV-Hib (Infanrix-hexa®) and MMRV (ProQuad®) at 18 months of age.

CONTEXT: In 2015 in Quebec, Canada, the passive vaccine adverse event reporting system detected an increase in large local reactions associated with vaccines recommended at the 18-month visit. This followed changes to the pediatric vaccine schedule to include hexavalent diphtheria-tetanus-acellular-pertusis-inactivated polio-Haemophilus influenzae type b-hepatitis B vaccine (DTaP-IPV-Hib-HB, Infanrix-hexa®, GSK) and quadrivalent measles-mumps-rubella-varicella vaccine (MMRV, ProQuad®, Merck) as 18-month booster doses. OBJECTIVES: To determine if the excess of large local reactions was caused by a specific vaccine or their co-administration in the same limb or during the same visit. METHODS: A case-control study was conducted among cases born between January 2012 and April 2015 with a large local reaction following MMR ±â€¯V or DTaP-IPV-Hib ±â€¯HB vaccines administered between 16 and 23 months of age. Controls were randomly selected from the provincial medicare database among children born during the same period. RESULTS: Our analysis included 96 cases and 494 controls vaccinated with MMRV or DTaP-IPV-Hib ±â€¯HB vaccines. Among the 96 cases, 46% had a cellulitis and 54% had an injection site reaction extending beyond the nearest joint and/or lasting ≥ 4 days. Among the 39 cases who were immunized in different limbs, 77% of the large local reactions were located at the Infanrix-hexa® site, 5% at the DTaP-IPV-Hib site and 18% at the ProQuad® site. Large local reactions were significantly more frequent with Infanrix-hexa® than with DTaP-IPV-Hib vaccine (OR 5.9 95% CI: 1.4-25.7). Administration of ProQuad® and Infanrix-hexa® in the same limb did not increase the risk of large local reactions. CONCLUSION: This investigation suggested that most large local reactions were causally associated with the Infanrix-hexa® vaccine and that the risk was not greater when ProQuad® and Infanrix-hexa® were administered in the same limb. Given the improved vaccine coverage for hepatitis B, benefit-risk analysis likely still favours ongoing use of Infanrix-hexa® with informed parental consent.

Impact of the addition of new vaccines in the early childhood schedule on vaccine coverage by 24 months of age from 2006 to 2016 in Quebec, Canada.

CONTEXT: Between 2004 and 2016, in the province of Quebec (Canada), 4 new antigens were added in the early childhood vaccine schedule from birth to 18 months, increasing the number of injections or doses needed from 7 to 12. These additions may have decreased the proportion of children who had received all recommended vaccines. OBJECTIVES: To assess the impact of the introduction of new vaccines to the childhood schedule on the 24-month vaccine coverage from 2006 to 2016 and identify factors associated with incomplete vaccination status by 24 months of age. METHODS: We used the data from six cross-sectional vaccine coverage surveys conducted every two years which included a total of 3515 children aged 2 years old and randomly selected from the Quebec public health insurance database. Factors associated with an incomplete vaccine status by 24 months were identified with multivariable logistic regression. RESULTS: Despite the addition of 4 new vaccine antigens since 2004, the vaccine coverage remained high from 2006 (82.4%) through 2016 (88.3%) for vaccines present in the schedule since 2006. In 2016, vaccine coverage was 78.2% for all vaccines included in the schedule. The vaccine coverage of new vaccines increases rapidly within 2 years of their introduction. For both new and older vaccines, incomplete vaccine status by 24 months of age is associated with a delay of 30 days or more in receiving the vaccines scheduled at 2 and 12 months of age. CONCLUSIONS: Increasing to 12 the number of doses in the recommended schedule has slightly reduced the vaccine coverage by 24 months of age and the vaccine coverage of vaccines already in the schedule remained stable over the years. Future additions to the vaccine schedule may not be similarly accepted by the population and this will require continuing the monitoring of vaccine coverage.

Cardiac complications after stroke: protocol for a systematic review and meta-analysis.

INTRODUCTION: Stroke is the second most common cause of death after ischaemic heart diseases and the third leading cause of disability worldwide. The contribution of cardiac complications to the mortality of patients with stroke is variable across studies, ranging from 12.5% to 22.7%. Many of these cardiac complications are preventable, and early recognition and adequate management guided by appropriate up-to-date knowledge of their relative incidence and fatality can help to improve patients' outcomes. This systematic review aims to summarise the available data on the burden of cardiac complications after stroke. METHODS AND ANALYSIS: This review will include all cross-sectional, case-control and cohort studies and clinical trials published between 1 January 1950 and 31 December 2017, involving adults and/or children, and reporting on the prevalence, the incidence and/or the mortality of cardiac complications after stroke. Two reviewers will independently screen titles and abstracts of records retrieved from PubMed, Excerpta Medica Database, ISI Web of Science and the Cumulative Index to Nursing and Allied Health Literature for eligibility, and then assess the risk of bias and quality of reporting to select the studies which will be included. All authors will contribute to the retrieval of full texts of eligible records and data extraction. Heterogeneity across studies will be evaluated by the χ2 test on Cochran's Q statistic. Study-specific estimates of the prevalence, incidence and mortality of cardiac complications after stroke across studies will be pooled through random-effect or fixed-effect meta-analysis depending on the source of the heterogeneity, after stabilising the variance of individual studies using the Freeman-Tukey double arcsine transformation. Visual analysis of funnel plots and Egger's test will be done to detect small-study effect. ETHICS AND DISSEMINATION: This review and meta-analysis will be based on published data and will therefore not require a specific ethical clearance. The results will be published in peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42018082551.

Neuroimaging of headaches in patients with normal neurological examination: protocol for a systematic review.

INTRODUCTION: Headache disorders (HD) are among the most frequent neurological disorders seen in neurology practice. Because secondary HD are rare, patients' examination is most often unremarkable. However, the will to relieve patients' anxiety and the fear of prosecutions lead to overuse of neuroimaging thus resulting in the discovery of incidental findings (IF) or normal variants that can lead to futile or harmful procedures. Knowing the probability of identifying a potentially clinically significant lesion in patients with isolated headache could facilitate decision-making and reduce health costs. This review aims to determine the prevalence of incidental findings and normal anatomic variants (NAV) on neuroimaging studies performed in patients presenting with headache and normal neurological examination. METHOD AND ANALYSIS: Studies reporting neuroimaging findings in patients with headache and normal neurological examination and published before the 30 September 2017 will be identified by searching PubMed, Medline and EMBASE (Excerpta Medica Database). Relevant unpublished papers and conference proceedings will also be checked. Full texts of eligible studies will then be accessed and data extracted using a standard data extraction sheet. Studies will be assessed for quality and risk of bias. Heterogeneity of studies will be evaluated by the χ2 test on Cochrane's Q statistic. The prevalence of NAV and IF across studies and in relevant subgroups will be estimated by pooling the study-specific estimates using a random-effects meta-analysis. Visual analysis of funnel plot and Egger's test will be used to detect publication bias. The report of this systematic review will be compliant with the Meta-analysis of Observational Studies in Epidemiology guidelines. ETHICS AND DISSEMINATION: The current study is based on published data; ethical approval is, therefore, not required. The final report of this systematic review will be published in a peer-reviewed journal. Furthermore, findings will be presented at conferences and submitted to relevant health authorities. TRIAL REGISTRATION NUMBER: CRD42017079714.

Risk of Recurrence of Adverse Events Following Immunization: A Systematic Review.

CONTEXT: Reimmunizing patients who had an adverse event following immunization (AEFI) is sometimes a challenge because there are limited data on the risk and severity of AEFI recurrence. OBJECTIVE: To summarize the literature on the risk of AEFI recurrence. DATA SOURCES: PubMed, Embase, and Cochrane library. STUDY SELECTION: We included articles in English or French published before September 30, 2016. Articles were selected if they estimated the risk of AEFI recurrence in at least 5 individuals. Studies with experimental vaccines were excluded. DATA EXTRACTION: Data on study design, setting, population, vaccines, and AEFI recurrence were extracted. RESULTS: Twenty-nine articles were included. Among patients with a history of hypotonic hyporesponsive episode (n = 398), anaphylaxis (n = 133), or seizures (n = 60) who were reimmunized, events recurred in 0% to 0.8%. Allergic-like events recurred in 30 of 594 reimmunized patients. Fever recurred in 0% to 84% of 836 reimmunized patients, depending on the vaccine and dose number. Among children with extensive limb swelling after the fourth dose of diphtheria-tetanus-acellular pertussis vaccine, recurrence was higher when the fifth dose was given withthe full-antigen formulation (78%) compared with the reduced-antigen formulation (53%, P = .02) LIMITATIONS: Many studies, included few patients, and those with severe AEFIs were often not reimmunized. CONCLUSIONS: Despite vaccines being administered to millions of people annually, there are few studies in which researchers evaluated AEFI recurrence. Published studies suggest that reimmunization is usually safe. However in these studies, severe cases were often not reimmunized.

Clinical Approach Used in Medical Consultations for Allergic-Like Events Following Immunization: Case Series Report in Relation to Practice Guidelines.

BACKGROUND: The Joint Task Force on Practice Parameters (JTFPP) guidelines for the investigation and reimmunization of patients who experienced allergic-like events (ALEs) after immunization are predicated on the likelihood of anaphylaxis, assessed through the time to symptom onset (≤ or >4 hours) and number of systems involved. OBJECTIVE: The objectives of this study were to compare the management of a series of patients with ALE in actual practice relative to JTFPP guidelines and to discuss key concepts and considerations in their use. METHODS: This retrospective study was based on a chart review of patients who consulted for suspected vaccine-associated ALEs at a large allergy department in Canada. RESULTS: Only 3 of the 135 patients who presented ALEs after immunization were referred for suspected anaphylaxis. There was no significant difference in the frequency of skin testing or reimmunization of patients whatever the time to symptom onset or number of systems involved in the ALE. Eight patients whose initial ALE occurred within 1 hour after immunization had a recurrence on reimmunization. Another patient whose initial ALE occurred 10 hours after influenza immunization had throat tightening and difficulty swallowing without objective signs. CONCLUSIONS: Most ALEs after immunization are not suggestive of anaphylaxis and should not be managed as such. The definition of anaphylaxis in the JTFPP guidelines is nonspecific and may need to be revisited. Restricting skin testing and graded dose reimmunization to patients whose ALE onset is ≤1 hour (compatible with IgE-mediated reaction) and to those meeting specific clinical criteria for anaphylaxis (whatever the timing) is likely a sufficiently sensitive and cautious approach.

Hypertension prevalence, incidence and risk factors among children and adolescents in Africa: a systematic review and meta-analysis protocol.

INTRODUCTION: The African adult population is facing a growing epidemic of hypertension. Establishment of accurate epidemiological data on hypertension in African children and adolescents may have important implications for hypertension preventive strategies in Africa. METHODS AND ANALYSIS: This systematic review and meta-analysis will follow the MOOSE Guidelines. Relevant abstracts published in English/French from 1 January 1985 to 31 July 2015 will be searched in PubMed, Google Scholar and Online African journals. Full texts of eligible studies will then be accessed through PubMed, Google Scholar, HINARI and the respective journals' websites. Relevant unpublished papers and conference proceedings will also be checked. Data will be analysed using R statistical software. The study-specific estimates will be pooled through a random-effects meta-analysis model to obtain an overall summary estimate of the prevalence/incidence of hypertension across studies. Also, we will assess the association between risk factors and hypertension. Heterogeneity of studies will be evaluated by the χ(2) test on Cochrane's Q statistic. Funnel plots analysis and Egger's test will be done to detect publication bias. Results will be presented by geographic region (central, eastern, northern, southern and western Africa). A p value less than 0.05 will be considered significant for factors that predicted hypertension. ETHICS AND DISSEMINATION: The current study is based on published data, and thus ethical approval is not required. This systematic review and meta-analysis is expected to serve as input for designing early life preventive and control strategies, and as a guide for future research based on existing gaps. The final report of the systematic review in the form of a scientific paper will be published in peer-reviewed journals. Findings will further be presented at conferences and submitted to relevant health authorities. TRIAL REGISTRATION NUMBER: CRD42015019029.

Effect of HIV Infection and Highly Active Antiretroviral Therapy on Hearing Function: A Prospective Case-Control Study From Cameroon.

IMPORTANCE: Human immunodeficiency virus (HIV) infection remains a major cause of morbidity and mortality worldwide. Many studies have found a higher prevalence of hearing impairment among HIV-positive individuals. OBJECTIVE: To investigate the effect of HIV and highly active antiretroviral treatment (HAART) on the hearing function in a Cameroonian population. DESIGN, SETTING, AND PARTICIPANTS: We conducted a prospective case-control study from March 1, 2012, through January 31, 2013. The study took place at the National Social Insurance Fund Hospital in Yaoundé, Cameroon, a public health facility. We included 90 HIV-positive case patients and 90 HIV-negative control patients aged 15 to 49 years without any history of hearing loss or treatment with a known ototoxic drug. The case group was further divided into 3 subgroups: 30 HAART-naive patients, 30 patients receiving first-line HAART, and 30 patients receiving second-line HAART. INTERVENTIONS: Hearing function was assessed by pure-tone audiometry and classified according to the criteria of the Bureau International d'Audio-Phonologie. MAIN OUTCOMES AND MEASURES: Hearing loss due to HIV and HAART. RESULTS: The HIV-positive patients had more otologic symptoms (hearing loss, dizziness, tinnitus, and otalgia) than HIV-negative patients (41 vs 13, P = .04). There were 49 cases (27.2%) of hearing loss in the HIV-positive group vs 10 (5.6%) in the HIV-negative group (P = .04). Compared with HIV-negative individuals, the odds of hearing loss were higher among HIV-infected HAART-naive patients (right ear: odds ratio [OR], 6.7; 95% CI, 4.3-9.7; P = .004; left ear: OR, 6.2; 95% CI, 3.5-8.3; P = .006), patients receiving first-line HAART (right ear: OR, 5.6; 95% CI, 1.9-10.5; P = .01; left ear: OR, 12.5; 95% CI, 8.5-15.4; P < .001), and patients receiving second-line HAART (right ear: OR, 6.7; 95% CI, 3.3-9.6; P = .004; left ear: OR, 3.7; 95% CI, 3.0-5.0; P = .08). CONCLUSIONS AND RELEVANCE: Hearing loss is more frequent in HIV-infected patients compared with uninfected patients. Therefore, HIV-infected patients need special audiologic care. Further studies are needed because controversy remains regarding the factors that lead to ear damage.