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1.  Anaphylaxis-related deaths in Ontario: a retrospective review of cases from 1986 to 2011 
Background
Examining deaths caused by anaphylaxis may help identify factors that may decrease the risk of these unfortunate events. However, information on fatal anaphylaxis is limited. The objectives of our study were to examine all cases of fatal anaphylaxis in Ontario to determine cause of death, associated features, co factors and trends in mortality. The identification of these factors is important for developing effective strategies to overcome gaps in monitoring and treatment of patients with food allergies and risk for anaphylaxis.
Methods
This was a retrospective case-series analysis of all causes of anaphylaxis-related deaths using data from the Ontario Coroner’s database between 1986 and 2011. Quantitative data (e.g. demographic) were analyzed using descriptive statistics and frequency analysis using SPSS. Qualitative data were analyzed using content analysis of grounded theory methodology.
Results
We found 92 deaths in the last 26 years related to anaphylaxis. Causes of death, in order of decreasing frequency, included food (40 cases), insect venom (30 cases), iatrogenic (16 cases), and idiopathic (6 cases). Overall, there appears to be a decline in the frequency of food related deaths, but an increase in iatrogenic causes of fatalities. We found factors associated with fatal anaphylaxis included: delayed epinephrine administration, asthma, allergy to peanut, food ingestion outside the home, and teenagers with food allergies.
Conclusions
Our findings indicate the need to improve epinephrine auto-injector use in acute reactions, particularly for teens and asthmatics with food allergies. In addition, education can be improved among food service workers and food industry in order to help food allergic patients avoid potentially fatal allergens. The increasing trend in iatrogenic related anaphylaxis is concerning, and requires monitoring and more investigation.
doi:10.1186/1710-1492-10-38
PMCID: PMC4322510  PMID: 25670935
Anaphylaxis; Severe allergic reaction; Anaphylaxis mortality; Food allergy; Medication allergy; Adverse drug reaction; Venom allergy; Insect sting allergy; Iatrogenic anaphylaxis
2.  Anaphylaxis: incidence, presentation, causes and outcome in patients in a tertiary-care hospital in Karachi, Pakistan 
Background: Anaphylaxis is a potentially fatal condition requiring immediate resuscitation. Data regarding the epidemiology of anaphylaxis are limited and inconsistent. A reason for the variability was unavailability of a universally acceptable case definition till 2005. We reviewed cases using this new definition
Aim: To review the incidence, clinical presentation, cause and outcome of anaphylaxis at a tertiary-care centre in a low-income country.
Design: Retrospective, case series
Methods: Chart review of all patients discharged from Aga Khan University Hospital between January 1988 and December 2012 (24 years) with anaphylaxis definition as per second National Institute of Allergy and Infection disease/Food Allergy and Anaphylaxis Network Symposium
Results: Total of 129 cases were found with mean age of 41.6 years (SD 18.8). Majority of patients had cutaneous features (76.7%), followed by respiratory (68.9%), cardiac (64.3%) and gastrointestinal (20.9%) symptoms, respectively. About 22.4% of patients had positive history for allergens out of which 31% (n = 9) were exposed to the same allergens. The common causes identified for anaphylaxis were drugs (60.5%), food (16.3%) and intravenous contrast (10.9%), respectively. Only 22.5% of cases received epinephrine as a part of their initial management. In four patients (3.1%) the cause of death was attributed to anaphylaxis.
Conclusion: Anaphylaxis is a rare but life-threatening condition. Though cutaneous features are most common, their absence does not exclude the diagnosis. Drugs were the most common cause and epinephrine was not commonly used as first-line agent for its management.
doi:10.1093/qjmed/hct179
PMCID: PMC3840329  PMID: 24082151
3.  38 Drug Induced Anaphylaxis in a University Hospital in Sao Paulo, Brazil 
Background
Adverse drug reactions (ADRs) are common in clinical practice, most of them presented only with mucocutaneous symptoms. Drug induced anaphylaxis is rare, but it is responsible for most deaths due to ADRs. The aim of this study was to evaluate drug induced anaphylaxis treated in an Allergy Outpatient Clinic of a University Hospital.
Methods
Retrospective analysis of medical records from patients who seek assistance because of ADR. We looked for clinical criteria for diagnosing anaphylaxis, as recommended in WAO Guidelines. Criteria were classified in numbers 1 to 3:1) Acute onset of an illness (minutes to several hours) with involvement of the skin-mucosal tissue and respiratory and/or cardiovascular compromise; 2) Two or more of the following that occur rapidly after exposure to a likely allergen: involvement of skin-mucosal tissue, respiratory, cardiovascular and/or gastrointestinal compromise; 3) Reduced blood pressure after exposure to known allergen for that patient. We analyzed patients gender and age, drugs involved in reactions and administration of epinephrin.
Results
We studied 806 patients with history of ADR, of whom 123 (15.3%) presented clinical criteria of anaphylaxis (mean age 39.0 year old, female 101). The first clinical criteria was found in 60.2% and the second one in 38.2%. Epinephrin was injected in only 42 patients (34.1%). Non-steroidal anti-inflammatory drugs (NSAIDs) were most commonly suspected culprit drugs involved in anaphylactic reactions, with 59 patients (47.9%), followed by 40 patients with perioperative anaphylaxis (32.5%), 6 cases due to local anesthetics (4.9%) and 4 to antibiotics (3.2%). Between perioperative anaphylaxis, latex was involved in 10 reactions and neuromuscular blocking agents in 3.
Conclusions
We found a high prevalence of anaphylaxis, probably because patients with severe ADRs tend to be followed in university hospitals. Nevertheless, anaphylaxis is underdiagnosed in emergency departments, as we observed less than 35% of patients with drug induced anaphylaxis were treated with epinephrin. NSAIDs are still the most common drugs involved in ADRs in Brazil, including severe reactions, as anaphylaxis. In our country, latex still is an important agent incriminated in perioperative anaphylaxis, but anaphylaxis due to antibiotics are less common than in other countries.
doi:10.1097/01.WOX.0000411783.13086.83
PMCID: PMC3512976
4.  Predictors of the Severity and Serious Outcomes of Anaphylaxis in Korean Adults: A Multicenter Retrospective Case Study 
Purpose
Differences in definitions of the condition, relevant triggers, and the geographical locations of study centers, cause estimates of the prevalence of anaphylaxis to vary. Recent epidemiological data indicate that the incidence of anaphylaxis is rising.
Methods
To investigate the causes and clinical features of anaphylaxis in Korean adults, factors associated with the severity of the condition, and serious outcomes, a retrospective medical record review was performed on adult patients diagnosed with anaphylaxis between 2007 and 2011 in 15 University Hospitals of South Korea.
Results
A total of 1,806 cases (52% male, age 16-86 years) were reported. Cutaneous symptoms (84.0%), combined with respiratory (53.9%) and/or cardiovascular (55.4%) symptoms, were the most frequent presentations. Using a recognized grading system, 1,776 cases could be classified as either mild, 340; moderate, 690; or severe, 746. Although eliciting factors varied significantly by age, gender, and regional and seasonal factors, drugs (46.5%; including nonsteroidal anti-inflammatory drugs, antibiotics, and radiocontrast media) were the most common cause of anaphylaxis, followed by foods (24.2%), insect stings (16.4%), exercise (5.9%), and unknown etiology (7.0%). All of age, multi-organ involvement, a history of allergic disease, and drug-induced anaphylaxis, were significant predictors of serious outcomes requiring hospital admission or prolongation of hospital stay. Epinephrine auto-injectors were prescribed for 7.4% of reported cases.
Conclusions
The principal causes of anaphylaxis in Korean adults were drugs, food, and insect stings. Drug-associated anaphylaxis, a history of allergic disease, multi-organ involvement, and older age, were identified as predictors of serious outcomes.
doi:10.4168/aair.2015.7.1.22
PMCID: PMC4274465  PMID: 25553259
Anaphylaxis; adult; epidemiology; multicenter study; severity; serious outcomes
5.  Incidence of fatal food anaphylaxis in people with food allergy: a systematic review and meta-analysis 
Clinical and Experimental Allergy  2013;43(12):1333-1341.
Background
Food allergy is a common cause of anaphylaxis, but the incidence of fatal food anaphylaxis is not known. The aim of this study was to estimate the incidence of fatal food anaphylaxis for people with food allergy and relate this to other mortality risks in the general population.
Methods
We undertook a systematic review and meta-analysis, using the generic inverse variance method. Two authors selected studies by consensus, independently extracted data and assessed the quality of included studies using the Newcastle-Ottawa assessment scale. We searched Medline, Embase, PsychInfo, CINAHL, Web of Science, LILACS or AMED, between January 1946 and September 2012, and recent conference abstracts. We included registries, databases or cohort studies which described the number of fatal food anaphylaxis cases in a defined population and time period and applied an assumed population prevalence rate of food allergy.
Results
We included data from 13 studies describing 240 fatal food anaphylaxis episodes over an estimated 165 million food-allergic person-years. Study quality was mixed, and there was high heterogeneity between study results, possibly due to variation in food allergy prevalence and data collection methods. In food-allergic people, fatal food anaphylaxis has an incidence rate of 1.81 per million person-years (95%CI 0.94, 3.45; range 0.63, 6.68). In sensitivity analysis with different estimated food allergy prevalence, the incidence varied from 1.35 to 2.71 per million person-years. At age 0–19, the incidence rate is 3.25 (1.73, 6.10; range 0.94, 15.75; sensitivity analysis 1.18–6.13). The incidence of fatal food anaphylaxis in food-allergic people is lower than accidental death in the general European population.
Conclusion
Fatal food anaphylaxis for a food-allergic person is rarer than accidental death in the general population.
doi:10.1111/cea.12211
PMCID: PMC4165304  PMID: 24118190
anaphylaxis; food allergy; mortality; systematic review
6.  Validation of Anaphylaxis in the Food and Drug Administration's Mini-Sentinel 
Pharmacoepidemiology and drug safety  2013;22(11):1205-1213.
Purpose
To develop and validate the positive predictive value (PPV) of an algorithm to identify anaphylaxis using health plan administrative and claims data. Previously published positive predictive values (PPVs) for anaphylaxis using ICD-9-CM codes range from 52-57%.
Methods
We conducted a retrospective study using administrative and claims data from eight health plans. Using diagnosis and procedure codes, we developed an algorithm to identify potential cases of anaphylaxis from the Mini-Sentinel Distributed Database between January 2009 and December 2010. A random sample of medical charts (N=150) was identified for chart abstraction. Two physician adjudicators reviewed each potential case. Using physician adjudicator judgments on whether the case met diagnostic criteria for anaphylaxis, we calculated a PPV for the algorithm.
Results
Of the 122 patients for whom complete charts were received, 77 were judged by physician adjudicators to have anaphylaxis. The PPV for the algorithm was 63.1% (95% CI: 53.9%-71.7%), using the clinical criteria by Sampson as the gold standard. The PPV was highest for inpatient encounters with ICD-9-CM codes of 995.0 or 999.4. By combining only the top performing ICD-9-CM codes, we identified an algorithm with a PPV of 75.0%, but only 66% of cases of anaphylaxis were identified using this modified algorithm.
Conclusions
The PPV for the ICD-9-CM-based algorithm for anaphylaxis was slightly higher than PPV estimates reported in prior studies, but remained low. We were able to identify an algorithm which optimized the PPV but demonstrated lower sensitivity for anaphylactic events.
doi:10.1002/pds.3505
PMCID: PMC4113322  PMID: 24038742
anaphylaxis; serious allergic reaction; validation; administrative data; Food and Drug administration; Mini-Sentinel
7.  Pediatric Anaphylaxis Management in the Prehospital Setting 
Purpose
Anaphylaxis is a life-threatening systemic allergic reaction that occurs after contact with an allergy-causing substance. Timely administration of intramuscular epinephrine is the treatment of choice for controlling symptoms and decreasing fatalities. Our purpose was to investigate the prehospital management of anaphylaxis among patients receiving care in an urban tertiary care pediatric emergency department (PED).
Methods
We performed a retrospective chart review from May, 2008 to January, 2010 of patients 18 years or younger who received care in the PED for anaphylaxis. Data were extracted by one investigator and included demographic information, patient symptoms, past medical history, medications administered (including route and provider), and final disposition.
Results
We reviewed 218 cases of anaphylaxis in 202 children. Mean age of patients was 7.4 years; 56% of patients were male. Two hundred and fourteen (98%) manifested symptoms in the skin/mucosal system, 68% had respiratory symptoms, 44% had gastrointestinal symptoms, and 2% had hypotension. Sixty-seven percent had a previous history of allergic reaction and 38% had a history of asthma. Seventy-six percent of the patients presented with anaphylaxis to food products, 8% to medications, 1% to stings, and 16% to unknown allergens. Reactions occurred at home or with family members 87% of the time, and at school 12% of the time. Only 36% of the patients who met criteria for anaphylaxis had epinephrine administered by emergency medical services (EMS). Among 26 patients with anaphylactic reactions at school, 69% received epinephrine by the school nurse. Of the 117 patients with known allergies who were with their parents at the time of anaphylactic reaction, 41% received epinephrine. Thirteen patients were seen by a physician prior to coming to the PED; all received epinephrine at the physician’s office. In total, epinephrine was given to 41% (89) of the 218 cases prior to coming to the PED.
Conclusions
Our evaluation revealed low rates of epinephrine administration by EMS providers and parents/patients. Education about anaphylaxis is imperative to encourage earlier administration of epinephrine.
doi:10.3109/10903127.2013.825352
PMCID: PMC3865171  PMID: 24028748
Anaphylaxis; Prehospital care; Pediatric Emergency Department; Emergency Medical Services; Pediatrics; Nurses
8.  402 Oral Mite Anaphylaxis is Caused by Mite-contaminated Okonomiyaki Mix in Japan 
Background
Anaphylaxis after the ingestion of foods contaminated with mites has recently been reported. It is an immediate and potentially life-threatening reaction in patients with previous allergic rhinitis and/or asthma following the ingestion of mite-contaminated foods. Case series and case reports thus far have shown that mite-contaminated wheat flour is the major cause of oral mite anaphylaxis. However, we have encountered 8 cases of oral mite anaphylaxis in our hospital not caused by mite-contaminated wheat flour but by mite-contaminated okonomiyaki mix.
Methods
To review the current literature, in addition to our patients, we performed a MEDLINE search of articles on oral mite anaphylaxis in Japan up to June 2011 and collected patient characteristics, interview contents, results on specific IgE against mites, wheat, and pollen and other antigens, results of skin prick tests including those using extracts from mites and/or culprit flours, and microscopic examination results.
Results
We found thirty oral mite anaphylaxis patients in Japan twenty-eight (93.3%) of whom ingested okonomiyaki or takoyaki, prepared at home using okonomiyaki mix (24 patients) or takoyaki mix (4 patients), respectively, which was previously opened and stored for months at ambient temperature. Takoyaki mix is similar to okonomiyaki mix, which is composed of flour, dried scallop, bonito, and mackerel. The other 2 patients ingested pancake mix. Microscopic examination of thirteen patients’ mixes revealed contaminating mites. Thyreophagus putrescentiae, Dermatophagoides pteronyssinus, Dermatophagoides farinae were found in mix samples of 4, 3, and 3 patients, respectively. The specific IgE against each mite is generally upregulated, which might be affected by cross-reactivities to other mites. Especially, the specific IgEs to Dermatophagoides pteronyssinus and Dermatophagoides farina were more than class 2 in all cases. It is suggested that mites are attracted to the flavors of okonomiyaki and takoyaki mixes and invade from a crack in a flour sack, and proliferate under favorable conditions.
Conclusions
Mite-contaminated flavored mix is a major cause of oral mite anaphylaxis in Japan.
doi:10.1097/01.WOX.0000412165.85477.6c
PMCID: PMC3512903
9.  Fecal immunochemical tests compared with guaiac fecal occult blood tests for population-based colorectal cancer screening 
More than 10% of cancer deaths in Canadian men and women are attributed to colorectal cancer. Moreover, the incidence and mortality rates of CRC in Canada are among the highest in the world. Evidence gained from randomized controlled trials conducted over the past two decades has supported screening as the best tool to decrease the burden of disease. Since 2008, Ontario’s ColonCancerCheck Program has used a test kit based on the guaiac fecal occult blood test (gFOBT). At the time the gFOBT was approved for use, however, the fecal immunochemical test (FIT) was undergoing evaluation in various settings. In 2010, Cancer Care Ontario’s FIT Guidelines Expert Panel was convened to evaluate the current evidence concerning FIT to inform the decision on how to replace the gFOBT with the FIT in Ontario’s ColonCancerCheck Program. The focus of this article is on the 13 FIT kits currently approved in Canada for processing in a laboratory setting.
Colorectal cancer (CRC) is the second most common cause of cancer deaths in Canadian men and women – accounting for almost 12% of all cancer deaths. In Ontario, it is estimated that 8100 persons were diagnosed with CRC in 2011, and 3250 died from the disease. CRC incidence and mortality rates in Ontario are among the highest in the world. Screening offers the best opportunity to reduce this burden of disease. The present report describes the findings and recommendations of Cancer Care Ontario’s Fecal Immunochemical Tests (FIT) Guidelines Expert Panel, which was convened in September 2010 by the Program in Evidence-Based Care. The purpose of the present guideline is to evaluate the existing evidence concerning FIT to inform the decision on how to replace the current guaiac fecal occult blood test with FIT in the Ontario ColonCancerCheck Program. Eleven articles were included in the present guideline, comprising two systematic reviews, five articles reporting on three randomized controlled trials and reports of four other studies. Additionally, one laboratory study was obtained that reported on several parameters of FIT tests that helped to inform the present recommendation. The performance of FIT is superior to the standard guaiac fecal occult blood test in terms of screening participation rates and the detection of CRC and advanced adenoma. Given greater specimen instability with the use of FIT, a pilot study should be undertaken to determine how to implement the FIT in Ontario.
PMCID: PMC3299236  PMID: 22408764
Cancer Care Ontario; Colorectal cancer screening; Fecal immunochemical tests; Guaiac fecal occult blood test
10.  Bicyclist and environmental factors associated with fatal bicycle-related trauma in Ontario. 
OBJECTIVE: To identify bicyclist and environmental factors associated with fatal bicycle-related trauma in Ontario. DESIGN: Retrospective study. SETTING: Ontario. PARTICIPANTS: Information was extracted from the provincial coroner's reports on 212 people who had died of bicycle-related injuries in Ontario between 1986 and 1991. OUTCOME MEASURES: Age, sex and helmet use of the bicyclist, time and place of the event, type of bicyclist or motorist error(s) and use of alcohol by bicyclist or motorist. RESULTS: Only 32% of the deaths involved bicyclists under 15 years of age. The male-female ratio was 3.5. Over 75% of the cases involved head injury; however, only 8 (4%) of the bicyclists had been wearing a helmet. In 91% of the cases death occurred as the result of a bicycle-motor vehicle collision. Most (65%) of the deaths for which the time was known occurred between 4 pm and 8 am. Bicyclist error was the main cause of crash for 26 (79%) of the children less than 10 years old; it was also the main cause of crash among the bicyclists aged 10 to 19 years (43 [55%]) and those aged 45 years or more (15 [44%]). However, motorist error was the most common cause of collision in the group of cyclists 20 to 44 years of age (42 [63%]). Alcohol was detected in the blood of 7% of the bicyclists killed; alcohol had been consumed by 30% of the motorists who claimed not to have seen the cyclist. CONCLUSIONS: Bicycle-related deaths result from factors that are generally avoidable. Identifiable risk factors other than lack of helmet use suggest that additional research is required to determine the benefits of preventive interventions aimed at reducing the number of such deaths. Age-specific strategies appear warranted.
PMCID: PMC1337492  PMID: 7804921
11.  The acute and long-term management of anaphylaxis: protocol for a systematic review 
Background
The European Academy of Allergy and Clinical Immunology is in the process of developing its Guideline for Food Allergy and Anaphylaxis, and this systematic review is one of seven inter-linked evidence syntheses that are being undertaken in order to provide a state-of-the-art synopsis of the current evidence base in relation to epidemiology, prevention, diagnosis and clinical management and impact on quality of life, which will be used to inform clinical recommendations.
The aims of this systematic review will be to assess the effectiveness of interventions for the acute management of anaphylaxis, and pharmacological and non-pharmacological approaches for the long-term management of anaphylaxis.
Methods
A highly sensitive search strategy has been developed, and validated study design filters will be applied to retrieve all articles pertaining to the management of anaphylaxis from electronic bibliographic databases. We will systematically review the literature on the acute management of anaphylaxis by assessing the effectiveness of epinephrine, H1-antihistamines (versus placebo), systemic glucocorticosteroids, methylxanthines or any other treatments for the emergency management of people experiencing anaphylaxis. The main interventions that have been studied in the context of long-term management are anaphylaxis management plans and allergen-specific immunotherapy.
Discussion
There is at present little in the way of robust evidence to guide decisions on the acute and/or long-term management of anaphylaxis. Given the risk of death and the considerable morbidity associated with anaphylaxis these evidence gaps need to be filled wherever possible; this systematic review will make a start in this area.
doi:10.1186/2045-7022-3-14
PMCID: PMC3626654  PMID: 23575342
Anaphylaxis; Management; Allergy; Emergency
12.  39 Analysis of Anaphylactic Reactions to Biological Agents Reported to the Italian Pharmacovigilance Database 
Background
Spontaneous reporting of adverse drug reactions (ADR) to biological agents used for cancer and immuno-mediated disease treatment is important for furthering knowledge regarding the safety of these new drugs. An analysis was carried out in Italy on reports of anaphylaxis caused by biological agents.
Methods
Data were extracted from the national Spontaneous Reporting Database. Since biological drugs refer to different ATC (Anatomical Therapeutic Classification) codes, in this study they have been extracted by the presence of "mab" and/or "cept" suffixes. Cases were defined as following: A) reports with the string “anaph” in the description of the event or in the WHO-ART (Adverse Reactions Terminology) coded preferred terms; B) reports with adverse reactions referring to at least 2 of selected System Organ Classes (skin, respiratory, cardiovascular and gastrointestinal disorders) with an onset within 24 hours after administration. All selected cases were reviewed and the case definition from the "Second Symposium on the Definition and Management of Anaphylaxis" was applied to evaluate the reports (JACI 2005;115(3):584–591).
Results
The Italian database up to March 2011 contains 3820 reports related to biologicals. According to selection criteria, a total of 334 reports were extracted: 65 for group A and 269 for group B. By application of the anaphylaxis case definition, 2 cases belonging to group A and 139 to group B were excluded after individual review. Out of 193 reports meeting the case definition, 8 (4.1%) were reported in children and adolescents up to 18 years of age. The most reported responsible drugs were infliximab with 83 (43%) cases, followed by cetuximab (41–21%) and rituximab (28–14%); other 11 different biologicals were associated with the remaining 32 cases (22%), with up to 8 reports each.
Conclusions
Spontaneous reporting is an important source to provide further knowledge on the reactogenicity of biological agents. Three-fourths of Italian reports of anaphylaxis concern 3 chimaeric antibodies containing a murine component. In our study, the best identification of cases of anaphylactic reactions came out of the combination of selected reported terms, application of case definition and expert review of individual reports.
doi:10.1097/01.WOX.0000411784.13086.4d
PMCID: PMC3512909
13.  Economic Appraisal of Ontario's Universal Influenza Immunization Program: A Cost-Utility Analysis 
PLoS Medicine  2010;7(4):e1000256.
Beate Sander and colleagues assess the cost-effectiveness of the program that provides free seasonal influenza vaccines to the entire population of Ontario, Canada.
Background
In July 2000, the province of Ontario, Canada, initiated a universal influenza immunization program (UIIP) to provide free seasonal influenza vaccines for the entire population. This is the first large-scale program of its kind worldwide. The objective of this study was to conduct an economic appraisal of Ontario's UIIP compared to a targeted influenza immunization program (TIIP).
Methods and Findings
A cost-utility analysis using Ontario health administrative data was performed. The study was informed by a companion ecological study comparing physician visits, emergency department visits, hospitalizations, and deaths between 1997 and 2004 in Ontario and nine other Canadian provinces offering targeted immunization programs. The relative change estimates from pre-2000 to post-2000 as observed in other provinces were applied to pre-UIIP Ontario event rates to calculate the expected number of events had Ontario continued to offer targeted immunization. Main outcome measures were quality-adjusted life years (QALYs), costs in 2006 Canadian dollars, and incremental cost-utility ratios (incremental cost per QALY gained). Program and other costs were drawn from Ontario sources. Utility weights were obtained from the literature. The incremental cost of the program per QALY gained was calculated from the health care payer perspective. Ontario's UIIP costs approximately twice as much as a targeted program but reduces influenza cases by 61% and mortality by 28%, saving an estimated 1,134 QALYs per season overall. Reducing influenza cases decreases health care services cost by 52%. Most cost savings can be attributed to hospitalizations avoided. The incremental cost-effectiveness ratio is Can$10,797/QALY gained. Results are most sensitive to immunization cost and number of deaths averted.
Conclusions
Universal immunization against seasonal influenza was estimated to be an economically attractive intervention.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Annual outbreaks (epidemics) of influenza—a viral disease of the nose, throat, and airways—make millions of people ill and kill about 500,000 individuals every year. In doing so, they impose a considerable economic burden on society in terms of health care costs and lost productivity. Influenza epidemics occur because small but frequent changes in the viral proteins to which the immune system responds mean that an immune response produced one year by exposure to an influenza virus provides only partial protection against influenza the next year. Annual immunization with a vaccine that contains killed influenza viruses of the major circulating strains can boost this natural immunity and greatly reduce a person's chances of catching influenza. Consequently, many countries run seasonal influenza vaccine programs. These programs usually target people at high risk of complications from influenza and individuals likely to come into close contact with them, and people who provide essential community services. So, for example, in most Canadian provinces, targeted influenza immunization programs (TIIPs) offer free influenza vaccinations to people aged 65 years or older, to people with chronic medical conditions, and to health care workers.
Why Was This Study Done?
Some experts argue, however, that universal vaccination might provide populations with better protection from influenza. In 2000, the province of Ontario in Canada decided, therefore, to introduce a universal influenza immunization program (UIIP) to provide free influenza vaccination to everyone older than 6 months, the first large program of this kind in the world. A study published in 2008 showed that, following the introduction of the UIIP, vaccination rates in Ontario increased more than in other Canadian provinces. In addition, deaths from influenza and influenza-related use of health care facilities decreased more in Ontario than in provinces that continued to offer a TIIP. But is universal influenza vaccination good value for money? In this study, the researchers evaluate the cost-effectiveness of the Ontario UIIP by comparing the health outcomes and costs associated with its introduction with the health outcomes and costs associated with a hypothetical continuation of targeted influenza immunization.
What Did the Researchers Do and Find?
The researchers used data on TIIP and UIIP vaccine uptake, physician visits, emergency department visits, hospitalizations for influenza, and deaths from influenza between 1997 and 2004 in Ontario and in nine Canadian states offering TIIPs, and Ontario cost data, in their “cost-utility” analysis. This type of analysis estimates the additional cost required to generate a year of perfect health (a quality-adjusted life-year or QALY) through the introduction of an intervention. QALYs are calculated by multiplying the time spent in a certain health state by a measure of the quality of that health state. The researchers report that the cost of Ontario's UIIP was about twice as much as the cost of a TIIP for the province. However, the introduction of the UIIP reduced the number of influenza cases by nearly two-thirds and reduced deaths from influenza by more than a quarter compared with what would have been expected had the province continued to offer a TIIP, an overall saving of 1,134 QALYs. Furthermore, the reduction in influenza cases halved influenza-related health care costs, mainly because of reductions in hospitalization. Overall, this means that the additional cost to Ontario of saving one QALY through the introduction of the UIIP was Can$10,797, an “incremental cost-effectiveness ratio” of $10,797 per QALY gained.
What Do These Findings Mean?
In Canada, an intervention is considered cost-effective from the point of view of a health care purchaser if it costs less than Canadian $50,000 to gain one QALY. These findings indicate, therefore, that for Ontario the introduction of the UIIP is economically attractive. Indeed, the researchers calculate that even if the costs of the UIIP were to double, the additional cost of saving one QALY by introducing universal immunization would remain below $50,000. Other “sensitivity” analyses undertaken by the researchers also indicate that universal immunization is likely to be effective and cost-effective in Ontario if other key assumptions and/or data included in the calculations are varied within reasonable limits. Given these findings, the researchers suggest that a UIIP might be an appealing intervention in other Canadian provinces and in other high-income countries where influenza transmission and health-care costs are broadly similar to those in Ontario.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000256.
A PLoS Medicine Research Article by Kwong and colleagues describes how the introduction of universal influenza immunization in Ontario altered influenza-related health care use and deaths in the province
Wikipedia pages are available on QALYs and on cost-utility analysis (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
Bandolier, an independent online journal about evidence-based health-care, provides information about QALYs and their use in cost-utility analysis
The UK National Institute for Health and Clinical Excellence has a webpage on Measuring effectiveness and cost-effectiveness: the QALY
doi:10.1371/journal.pmed.1000256
PMCID: PMC2850382  PMID: 20386727
14.  Postmortem findings after fatal anaphylactic reactions 
Journal of Clinical Pathology  2000;53(4):273-276.
Aims—To determine the frequency at which classic manifestations of anaphylaxis are present at necropsy after fatal anaphylactic reactions.
Methods—A register has been established of fatal anaphylactic reactions in the UK since 1992, traced from the certified cause of death and other sources. Details of the previous medical history and the reaction suggest anaphylaxis as the cause of death for 130 cases; a postmortem report was available for 56.
Results—The 56 deaths studied included 19 reactions to bee or wasp venom, 16 to foods, and 21 to drugs or contrast media. Death occurred within one hour of anaphylaxis in 39 cases. Macroscopic findings included signs of asthma (mucous plugging and/or hyperinflated lungs) (15 of 56), petechial haemorrhages (10 of 56), pharyngeal/laryngeal oedema (23 of 56), but for 23 of 56 there was nothing indicative of an allergic death. Mast cell tryptase was raised in 14 of 16 cases tested; three of three tested had detectable IgE specific for the suspected allergen.
Conclusions—In many cases of fatal anaphylaxis no specific macroscopic findings are present at postmortem examination. This reflects the rapidity and mode of death, which is often the result of shock rather than asphyxia. Investigations that might help determine whether anaphylaxis was the cause of death had rarely been performed. In the presence of a typical clinical history, absence of postmortem findings does not exclude the diagnosis of anaphylaxis.
Key Words: necropsy • anaphylaxis • asthma
doi:10.1136/jcp.53.4.273
PMCID: PMC1731177  PMID: 10823122
15.  Using death certificates to estimate the completeness of AIDS case reporting in Ontario in 1985-87. 
The completeness of AIDS (acquired immune deficiency syndrome) case reporting in Ontario was assessed by reviewing all AIDS death certificates compiled by the Registrar General between Jan. 1, 1985, and Dec. 31, 1987. Several demographic variables were used to match death certificates with cases reported to the provincial AIDS registry. The completeness of case reporting was then estimated by examining the ratio of reported deaths of patients with AIDS to the total number of deaths reviewed. The estimated completeness of case reporting was 81.1% in 1985, 71.5% in 1986 and 75.4% in 1987; the overall rate for 1985-87 was 75.2%. The difference in the completeness of case reporting from year to year was not statistically significant. There was a significant increase from 1985 to 1986 in the proportion of unreported cases in people who had never been married (p less than 0.02). Reporting was not associated with the patient's age, sex, occupation or place of residence. The deficiency in AIDS case reporting could adversely affect the long-term planning of health care resources and the development of programs to prevent and control the spread of AIDS.
PMCID: PMC1451353  PMID: 2776092
16.  The Effect of Universal Influenza Immunization on Mortality and Health Care Use 
PLoS Medicine  2008;5(10):e211.
Background
In 2000, Ontario, Canada, initiated a universal influenza immunization program (UIIP) to provide free influenza vaccines for the entire population aged 6 mo or older. Influenza immunization increased more rapidly in younger age groups in Ontario compared to other Canadian provinces, which all maintained targeted immunization programs. We evaluated the effect of Ontario's UIIP on influenza-associated mortality, hospitalizations, emergency department (ED) use, and visits to doctors' offices.
Methods and Findings
Mortality and hospitalization data from 1997 to 2004 for all ten Canadian provinces were obtained from national datasets. Physician billing claims for visits to EDs and doctors' offices were obtained from provincial administrative datasets for four provinces with comprehensive data. Since outcomes coded as influenza are known to underestimate the true burden of influenza, we studied more broadly defined conditions. Hospitalizations, ED use, doctors' office visits for pneumonia and influenza, and all-cause mortality from 1997 to 2004 were modelled using Poisson regression, controlling for age, sex, province, influenza surveillance data, and temporal trends, and used to estimate the expected baseline outcome rates in the absence of influenza activity. The primary outcome was then defined as influenza-associated events, or the difference between the observed events and the expected baseline events. Changes in influenza-associated outcome rates before and after UIIP introduction in Ontario were compared to the corresponding changes in other provinces. After UIIP introduction, influenza-associated mortality decreased more in Ontario (relative rate [RR] = 0.26) than in other provinces (RR = 0.43) (ratio of RRs = 0.61, p = 0.002). Similar differences between Ontario and other provinces were observed for influenza-associated hospitalizations (RR = 0.25 versus 0.44, ratio of RRs = 0.58, p < 0.001), ED use (RR = 0.31 versus 0.69, ratio of RRs = 0.45, p < 0.001), and doctors' office visits (RR = 0.21 versus 0.52, ratio of RRs = 0.41, p < 0.001). Sensitivity analyses were carried out to assess consistency, specificity, and the presence of a dose-response relationship. Limitations of this study include the ecological study design, the nonspecific outcomes, difficulty in modeling baseline events, data quality and availability, and the inability to control for potentially important confounders.
Conclusions
Compared to targeted programs in other provinces, introduction of universal vaccination in Ontario in 2000 was associated with relative reductions in influenza-associated mortality and health care use. The results of this large-scale natural experiment suggest that universal vaccination may be an effective public health measure for reducing the annual burden of influenza.
Comparing influenza-related mortality and health care use between Ontario and other Canadian provinces, Jeffrey Kwong and colleagues find evidence that Ontario's universal vaccination program has reduced the burden of influenza.
Editors' Summary
Background.
Seasonal outbreaks (epidemics) of influenza—a viral disease of the nose, throat, and airways—affect millions of people and kill about 500,000 individuals every year. These epidemics occur because of “antigenic drift”: small but frequent changes in the viral proteins to which the human immune system responds mean that an immune response produced one year by exposure to an influenza virus provides only partial protection against influenza the next year. Immunization can boost this natural immunity and reduce a person's chances of catching influenza. That is, an injection of killed influenza viruses can be used to prime the immune system so that it responds quickly and efficiently when exposed to live virus. However, because of antigenic drift, for influenza immunization to be effective, it has to be repeated annually with a vaccine that contains the major circulating strains of the influenza virus.
Why Was This Study Done?
Public-health organizations recommend targeted vaccination programs, so that elderly people, infants, and chronically ill individuals—the people most likely to die from pneumonia and other complications of influenza—receive annual influenza vaccination. Some experts argue, however, that universal vaccination might provide populations with better protection from influenza, both directly by increasing the number of vaccinated people and indirectly through “herd immunity,” which occurs when a high proportion of the population is immune to an infectious disease, so that even unvaccinated people are unlikely to become infected (because infected people rarely come into contact with susceptible people). In this study, the researchers compare the effects of the world's first free universal influenza immunization program (UIIP), which started in 2000 in the Canadian province of Ontario, on influenza-associated deaths and health care use with the effects of targeted vaccine programs on the same outcomes elsewhere in Canada.
What Did the Researchers Do and Find?
Using national records, the researchers collected data on influenza vaccination, on all deaths, and on hospitalizations for pneumonia and influenza in all Canadian provinces between 1997 and 2004. They also collected data on emergency department and doctors' office visits for pneumonia and influenza for Ontario, Quebec, Alberta, and Manitoba. They then used a mathematical model to estimate the baseline rates for these outcomes in the absence of influenza activity, and from these calculated weekly rates for deaths and health care use specifically resulting from influenza. In 1996–1997, 18% of the population was vaccinated against influenza in Ontario whereas in the other provinces combined the vaccination rate was 13%. On average, since 2000—the year in which UIIP was introduced in Ontario—vaccination rates have risen to 38% and 24% in Ontario and the other provinces, respectively. Since the introduction of UIIP, the researchers report, influenza-associated deaths have decreased by 74% in Ontario but by only 57% in the other provinces combined. Influenza-associated use of health care facilities has also decreased more in Ontario than in the other provinces over the same period.
What Do These Findings Mean?
These findings are limited by some aspects of the study design. For example, they depend on the accuracy of the assumptions made when calculating events due specifically to influenza, and on the availability and accuracy of vaccination and clinical outcome data. In addition, it is possible that influenza-associated deaths and health care use may have decreased more in Ontario than in the other Canadian provinces because of some unrecognized health care changes specific to Ontario but unrelated to the introduction of universal influenza vaccination. Nevertheless, these findings indicate that, compared to the targeted vaccination programs in the other Canadian provinces, the Ontarian UIIP is associated with reductions in influenza-associated deaths and health care use, particularly in people younger than 65 years old. This effect is seen at a level of vaccination unlikely to produce herd immunity so might be more marked if the uptake of vaccination could be further increased. Thus, although it is possible that Canada is a special case, these findings suggest that universal influenza vaccination might be an effective way to reduce the global burden of influenza.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050211.
Read the related PLoSMedicine Perspective by Cécile Viboud and Mark Miller
A related PLoSMedicine Research Article by Carline van den Dool and colleagues is also available
The Ontario Ministry of Health provides information on its universal influenza immunization program (in English and French)
The World Health Organization provides information on influenza and on influenza vaccines (in several languages)
The US Centers for Disease Control and Prevention provide information for patients and professionals on all aspects of influenza (in English and Spanish)
MedlinePlus provides a list of links to other information about influenza (in English and Spanish)
The UK National Health Service provides information about the science of immunization, including a simple explanatory animation of immunity
doi:10.1371/journal.pmed.0050211
PMCID: PMC2573914  PMID: 18959473
17.  Prescriptions for self-injectable epinephrine and follow-up referral in emergency department patients presenting with anaphylaxis 
Background
Anaphylaxis guidelines recommend that patients with a history of anaphylactic reaction should carry self-injectable epinephrine and should be referred to an allergist.
Objective
To evaluate how frequently patients dismissed from the emergency department after treatment for anaphylaxis received a prescription for self-injectable epinephrine or allergist referral.
Methods
A retrospective medical record review identified patients with anaphylaxis in a community-based study from 1990 through 2000. Records of patients with Hospital Adaptation of the International Classification of Diseases, Second Edition or International Classification of Diseases, Ninth Revision codes representing anaphylaxis were reviewed, and a random sample of patients with associated diagnoses was also reviewed. Patients who met the criteria for diagnosis of anaphylaxis were included in the study.
Results
Among 208 patients identified with anaphylaxis, 134 (64.4%) were seen in the emergency department and discharged home. On dismissal, 49 patients (36.6%; 95% confidence interval [CI], 28.4%–44.7%) were prescribed self-injectable epinephrine, and 42 patients (31.3%; 95% CI, 23.5%–39.2%) were referred to an allergist. Treatment with epinephrine in the emergency department (odds ratio, 3.6; 95% CI, 1.6 –7.9; P = .001) and insect sting as the inciting allergen (odds ratio, 4.0; 95% CI, 1.6 –10.5; P = .004) were significantly associated with receiving a prescription for self-injectable epinephrine. Patient age younger than 18 years was the only factor associated with referral to an allergist (P = .007).
Conclusions
Most patients dismissed after treatment for anaphylaxis did not receive a self-injectable epinephrine prescription or allergist referral. Emergency physicians may be missing an important opportunity to ensure prompt treatment of future anaphylactic reactions and specialized follow-up care.
PMCID: PMC2853171  PMID: 19119708
18.  Anaphylaxis in Children: Current Understanding and Key Issues in Diagnosis and Treatment 
Anaphylaxis is a severe allergic reaction that is rapid in onset and may cause death. Since it is unpredictable and potentially fatal, prompt recognition and treatment are vital to maximize a positive outcome. The occurrence of anaphylaxis is increasing across all ages in the United States, with increased risk of worse outcome in teenagers/young adults and in those with comorbid conditions such as asthma. Gaps in the assessment of patient-specific risk factors, identification and prevention of triggers, recognition of signs/symptoms, and pharmacologic treatment of anaphylaxis have been identified at the physician and caregiver/patient level. A PubMed literature search (January 2000–December 2011) was conducted to identify publications on childhood anaphylaxis using the following terms: food allergy, food allergens, food hypersensitivity, epinephrine, epinephrine auto-injectors, anaphylactic triggers, and anaphylaxis. This review will critically appraise these key issues and highlight strategies that might result in improved management of anaphylaxis in children.
doi:10.1007/s11882-012-0284-1
PMCID: PMC3492692  PMID: 22815131
Epinephrine; Food allergy; Food hypersensitivity; Pediatric; Children; Anaphylaxis; Diagnosis; Treatment
19.  Review of the use of cephalosporins in children with anaphylactic reactions from penicillins  
OBJECTIVE:
It is a widely accepted practice that children with anaphylaxis from penicillins should avoid cephalosporins. The purpose of the present study was to determine whether there is evidence in the literature to support this practice.
DATA SOURCES:
MEDLINE, EMBASE, Toxline, International Pharmaceutical Abstracts and PubMed were used to search the literature published from 1966 to 2001. The Canadian Medical Protective Association, Health Canada and the Boston Collaborative Drug Surveillance Program were also contacted to determine whether there were any unpublished cases of cross-reactivity between penicillins and cephalosporins.
DATA EXTRACTION:
Cases describing the use of cephalosporins in adults and children with positive penicillin skin tests or anaphylaxis from penicillin were evaluated. Case reports of anaphylaxis from cephalosporins in paediatric patients were identified.
DATA SYNTHESIS:
There have been five reported cases of serious reactions from cephalosporins in patients with a history of anaphylaxis from penicillins. All cases occurred in adults; three developed anaphylaxis from the older, first-generation cephalosporins, cephalothin and cephaloridine; one developed anaphylaxis from cefamandole; and one developed anaphylaxis from cefaclor. There have been 12 other published reports of anaphylaxis from cephalosporins in adults with a history of penicillin allergy or a positive penicillin skin test, but with no history of anaphylaxis from penicillin. In seven studies, in which a total of 158 patients with positive penicillin skin tests were administered cephalosporins, seven had apparent immunoglobulin E-mediated reactions when they were given a cephalosporin. When the class of cephalosporin was able to be determined, none of the reports of reactions from cephalosporins in patients with allergies to penicillin involved third-generation cephalosporins. There have been 13 case reports of anaphylaxis from cephalosporins in paediatric patients.
CONCLUSION:
There are no published case reports of anaphylaxis from cephalosporins in children with anaphylaxis from penicillin, and there are only a small number of such reports in adults. Anaphylaxis from cephalosporins appears to be incredibly rare in children. There is minimal evidence in the literature to support the avoidance of cephalosporins in children with anaphylaxis from penicillins.
PMCID: PMC2094874  PMID: 18159398
Anaphylaxis; Antibiotic allergy; Antibiotic hypersensitivity; Cephalosporins; Cross-reactivity; Drug allergy; Drug hypersensitivity; Penicillin
20.  Anaphylaxis following quadrivalent human papillomavirus vaccination 
Background
In 2007, Australia implemented the National human papillomavirus (HPV) Vaccination Program, which provides quadrivalent HPV vaccine free to all women aged 12–26 years. Following notification of 7 presumptive cases of anaphylaxis in the state of New South Wales, Australia, we verified cases and compared the incidence of anaphylaxis following HPV vaccination to other vaccines in comparable settings.
Methods
We contacted all patients with suspected anaphylaxis and obtained detailed histories from telephone interviews and a review of medical records. A multidisciplinary team determined whether each suspected case met the standardized Brighton definition. Some participants also received skin-prick allergy testing for common antigens and components of the HPV vaccine.
Results
Of 12 suspected cases, 8 were classified as anaphylaxis. Of these, 4 participants had negative skin-prick test results for intradermal Gardasil. From the 269 680 HPV vaccine doses administered in schools, 7 cases of anaphylaxis were identified, which represents an incidence rate of 2.6 per 100 000 doses (95% CI 1.0–5.3 per 100 000). In comparison, the rate of identified anaphylaxis was 0.1 per 100 000 doses (95% CI 0.003–0.7) for conjugated meningococcal C vaccination in a 2003 school-based program.
Interpretation
Based on the number of confirmed cases, the estimated rate of anaphylaxis following quadrivalent HPV vaccine was significantly higher than identified in comparable school-based delivery of other vaccines. However, overall rates were very low and managed appropriately with no serious sequelae.
doi:10.1503/cmaj.080916
PMCID: PMC2527382  PMID: 18762618
21.  Relationship between Vehicle Emissions Laws and Incidence of Suicide by Motor Vehicle Exhaust Gas in Australia, 2001–06: An Ecological Analysis 
PLoS Medicine  2010;7(1):e1000210.
In an ecological study, David Studdert and colleagues show that areas of Australia with fewer vehicles pre-dating stringent carbon monoxide emission laws have lower rates of suicide due to asphyxiation by motor vehicle exhaust gas.
Background
Globally, suicide accounts for 5.2% of deaths among persons aged 15 to 44 years and its incidence is rising. In Australia, suicide rates peaked in 1997 and have been declining since. A substantial part of that decline stems from a plunge in suicides by one particular method: asphyxiation by motor vehicle exhaust gas (MVEG). Although MVEG remains the second most common method of suicide in Australia, its incidence decreased by nearly 70% in the decade to 2006. The extent to which this phenomenon has been driven by national laws in 1986 and 1999 that lowered permissible levels of carbon monoxide (CO) emissions is unknown. The objective of this ecological study was to test the relationship by investigating whether areas of Australia with fewer noxious vehicles per capita experienced lower rates of MVEG suicide.
Methods and Findings
We merged data on MVEG suicides in Australia (2001–06) with data on the number and age of vehicles in the national fleet, as well as socio-demographic data from the national census. Poisson regression was used to analyse the relationship between the incidence of suicide within two levels of geographical area—postcodes and statistical subdivisions (SSDs)—and the population density of pre-1986 and pre-1999 passenger vehicles in those areas. (There was a mean population of 8,302 persons per postcode in the study dataset and 87,413 persons per SSD.) The annual incidence of MVEG suicides nationwide decreased by 57% (from 2.6 per 100,000 in 2001 to 1.1 in 2006) during the study period; the population density of pre-1986 and pre-1999 vehicles decreased by 55% (from 14.2 per 100 persons in 2001 to 6.4 in 2006) and 26% (from 44.5 per 100 persons in 2001 to 32.9 in 2006), respectively. Area-level regression analysis showed that the suicide rates were significantly and positively correlated with the presence of older vehicles. A percentage point decrease in the population density of pre-1986 vehicles was associated with a 6% decrease (rate ratio [RR] = 1.06; 95% confidence interval [CI] 1.05–1.08) in the incidence of MVEG suicide within postcode areas; a percentage point decrease in the population density of pre-1999 vehicles was associated with a 3% decrease (RR = 1.03; 95% CI 1.02–1.04) in the incidence of MVEG suicide.
Conclusions
Areas of Australia with fewer vehicles predating stringent CO emission laws experience lower rates of MVEG suicide. Although those emission laws were introduced primarily for environmental reasons, countries that lack them may miss the benefits of a serendipitous suicide prevention strategy.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Suicide (self-inflicted death) is a major, preventable public-health problem. About 1 million people die each year from suicide and about 20 times as many people attempt suicide. Globally, suicide rates have increased by nearly a half over the past 45 years and suicide is now among the three leading causes of death in people aged 15–44 years. Within this age group, 1 in 20 deaths is a suicide. Most people who commit suicide have a mental illness, usually depression or substance abuse, but suicide can also be triggered by a stressful event such as losing a partner. Often warning signs are present—a person who talks about killing themselves must always be taken seriously. Adequate prevention and treatment of mental illness and interventions that teach young people coping skills and improve their self-esteem have shown promise in reducing suicide rates, as have strategies (for example, restrictions on the sale of pain killers) that reduce access to common methods of suicide.
Why Was This Study Done?
In Australia, the suicide rate has been declining since 1997 when a record 2,722 suicides occurred. Fewer suicides by asphyxiation (oxygen deprivation) by motor vehicle gas exhaust (MVEG) account for much of this decline. MVEG contains carbon monoxide, a toxic gas that blocks oxygen transport around the body. Although MVEG suicide is still the second most common means of suicide in Australia, its incidence has dropped by two-thirds since 1997 but why? One possibility is that national laws passed in 1986 and 1999 that lowered the permissible level of carbon monoxide in vehicle exhaust for environmental reasons have driven the decline in MVEG suicides. Evidence from other countries suggests that this might be the case but no-one has directly investigated the relationship between MVEG suicide and the use of vehicles with reduced carbon monoxide emissions. In this ecological study (a study in which the effect of an intervention is studied on groups of people rather than on individuals), the researchers ask whether the number of pre-1986 and pre-1999 vehicles within particular geographic areas in Australia is correlated with the rates of MVEG suicide in those areas between 2001 and 2006.
What Did the Researchers Do and Find?
The researchers obtained data on MVEG suicides from the Australian National Coroners Information System and data on the number and age of vehicles on the road from the Australian Bureau of Statistics. MVEG suicides dropped from 498 in 2001 to 231 in 2006, they report, and 28% of passenger vehicles registered in Australia were made before 1986 in 2001 but only 12% in 2006; the percentage of registered vehicles made before 1999 fell from 89% to 60% over the same period. The researchers then used a statistical technique called Poisson regression to analyze the relationship within postcode areas between the incidence of MVEG suicide and the presence of pre-1986 and pre-1999 vehicles. This analysis showed that in areas where older vehicles were more numerous there were more MVEG suicides (a positive correlation). Specifically, the researchers calculate that if the proportion of pre-1986 vehicles on the road in Australia had stayed at 2001 levels throughout their study period, 621 extra MVEG suicides would have occurred in the country over that time.
What Do These Findings Mean?
These findings show that in areas of Australia that had fewer vehicles on the road predating stringent vehicle emission laws, there were lower rates of MVEG suicide between 2001 and 2006. Unfortunately, this study cannot provide any information on the actual age of vehicles used in MVEG suicides or on the relationship between vehicle age and attempted MVEG suicides. It also cannot reveal whether those areas that had the sharpest decreases in the density of older vehicles had the sharpest decreases in suicide rates because very few suicides occurred in most postcodes during the study. Most importantly, the design of this study means that the researchers cannot discount the possibility that the changes in Australia's emission laws have steered people towards other methods of taking their own lives. Nevertheless, the findings of this study suggest that the introduction of stringent vehicle emission laws for environmental reasons might, serendipitously, be a worthwhile long-term suicide prevention strategy in countries where MVEG suicide is common.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000210.
Another PLoS Medicine research article, by Shu-Sen Chang and colleagues, investigates the evolution of the epidemic of charcoal-burning suicide in Taiwan
The US National Institute of Mental Health provides information on suicide and suicide prevention
The UK National Health Service Choices Web site has detailed information about suicide and its prevention
The World Health Organization provides information on the global burden of suicide and on suicide prevention (in several languages)
MedlinePlus provides links to further resources about suicide (in English and Spanish)
Suicide Prevention Australia is a nonprofit, nongovernmental organization working as a public-health advocate in suicide prevention
The Australian Institute of Health and Welfare has recently published a review of suicide statistics in Australia
The National Coroners Information System is a database contains information on every death reported to an Australian coroner since July 2000 (January 2001 for Queensland)
doi:10.1371/journal.pmed.1000210
PMCID: PMC2796388  PMID: 20052278
22.  Pediatric fire deaths in Ontario 
Canadian Family Physician  2011;57(5):e169-e177.
Abstract
Objective
To identify the predictors of residential fire deaths in the Ontario pediatric population using systematically collected data from the Office of the Chief Coroner.
Design
Retrospective cohort study.
Setting
Ontario.
Participants
Children younger than 16 years of age who died in accidental residential fires in Ontario between January 1, 2001, and December 31, 2006.
Main outcome measures
The study retrospectively reviewed the coroner’s case files for 60 subjects who qualified according to the selection criteria. Reviewed documents included the coroner’s investigation statements, autopsy reports, toxicology reports, fire marshal’s reports, police reports, and Children’s Aid Society (CAS) reports. Information on a range of demographic, behavioural, social, and environmental factors was collected. Statistical tests, including relative risk, relative risk confidence intervals, and χ2 tests were performed to determine the correlation between factors of interest and to establish their significance.
Results
Thirty-nine fire events resulting in 60 deaths occurred between 2001 and 2006. Fire play and electrical failures were the top 2 causes of residential fires. More fires occurred during the night (midnight to 9 am) than during the day (9 am to midnight). Nighttime fires were most commonly due to electrical failures or unattended candles, whereas daytime fires were primarily caused by unsupervised fire play and stove fires. Smoke alarms were present at 32 of 39 fire events (82%), but overall alarm functionality was only 54%. Children from families with a history of CAS involvement were approximately 32 times more likely to die in fires.
Conclusion
Risk factors for pediatric fire death in Ontario include smoke alarm functionality, fire play, fire escape behaviour, and CAS involvement. Efforts to prevent residential fire deaths should target these populations and risk factors, and primary care physicians should consider education around these issues as a primary preventive strategy for families with young children.
PMCID: PMC3093605  PMID: 21571705
23.  Multicenter Study of Repeat Epinephrine Treatments for Food-Related Anaphylaxis 
Pediatrics  2010;125(4):e711-e718.
OBJECTIVE
We sought to establish the frequency of receiving >1 dose of epinephrine in children who present to the emergency department (ED) with food-related anaphylaxis.
PATIENTS AND METHODS
We performed a medical chart review at Boston hospitals of all children presenting to the ED for food-related acute allergic reactions between January 1, 2001, and December 31, 2006. We focused on causative foods, clinical presentations, and emergency treatments.
RESULTS
Through random sampling and appropriate weighting, the 605 reviewed cases represented a study cohort of 1255 patients. These patients had a median age of 5.8 years (95% confidence interval [CI]: 5.3– 6.3), and the cohort was 62% male. A variety of foods provoked the allergic reactions, including peanuts (23%), tree nuts (18%), and milk (15%). Approximately half (52% [95% CI: 48–57]) of the children met diagnostic criteria for food-related anaphylaxis. Among those with anaphylaxis, 31% received 1 dose and 3% received >1 dose of epinephrine before their arrival to the ED. In the ED, patients with anaphylaxis received antihistamines (59%), corticosteroids (57%), epinephrine (20%). Over the course of their reaction, 44% of patients with food-related anaphylaxis received epinephrine, and among this subset of patients, 12% (95% CI: 9–14) received >1 dose. Risk factors for repeat epinephrine use included older age and transfer from an outside hospital. Most patients (88%) were discharged from the hospital. On ED discharge, 43% were prescribed self-injectable epinephrine, and only 22% were referred to an allergist.
CONCLUSIONS
Among children with food-related anaphylaxis who received epinephrine, 12% received a second dose. Results of this study support the recommendation that children at risk for food-related anaphylaxis carry 2 doses of epinephrine.
doi:10.1542/peds.2009-2832
PMCID: PMC3531711  PMID: 20308215
food allergy; anaphylaxis; emergency department; epinephrine
24.  Paediatric anaphylaxis in a Singaporean children cohort: changing food allergy triggers over time 
Asia Pacific Allergy  2013;3(1):29-34.
Background
We have noticed changes in paediatric anaphylaxis triggers locally in Singapore.
Objective
We aimed to describe the demographic characteristics, clinical features, causative agents and management of children presenting with anaphylaxis.
Methods
This is a retrospective study of Singaporean children presenting with anaphylaxis between January 2005 and December 2009 to a tertiary paediatric hospital.
Results
One hundred and eight cases of anaphylaxis in 98 children were included. Food was the commonest trigger (63%), followed by drugs (30%), whilst 7% were idiopathic. Peanut was the top food trigger (19%), followed by egg (12%), shellfish (10%) and bird's nest (10%). Ibuprofen was the commonest cause of drug induced anaphylaxis (50%), followed by paracetamol (15%) and other nonsteroidal anti-inflammatory drugs (NSAIDs, 12%). The median age of presentation for all anaphylaxis cases was 7.9 years old (interquartile range 3.6 to 10.8 years), but food triggers occurred significantly earlier compared to drugs (median 4.9 years vs. 10.5 years, p < 0.05). Mucocutaneous (91%) and respiratory features (88%) were the principal presenting symptoms. Drug anaphylaxis was more likely to result in hypotension compared to food anaphylaxis (21.9% vs. 2.7%, Fisher's exact probability < 0.01). There were 4 reported cases (3.6%) of biphasic reaction occurring within 24 h of anaphylaxis.
Conclusion
Food anaphylaxis patterns have changed over time in our study cohort of Singaporean children. Peanuts allergy, almost absent a decade ago, is currently the top food trigger, whilst seafood and bird's nest continue to be an important cause of food anaphylaxis locally. NSAIDs and paracetamol hypersensitivity are unique causes of drug induced anaphylaxis locally.
doi:10.5415/apallergy.2013.3.1.29
PMCID: PMC3563018  PMID: 23403810
Anaphylaxis; Drug allergy; Food allergy; Paediatrics
25.  Preeclampsia as a Risk Factor for Diabetes: A Population-Based Cohort Study 
PLoS Medicine  2013;10(4):e1001425.
Denice Feig and colleagues assess the association between gestational diabetes, gestational hypertension, and preeclampsia and the development of future diabetes in a database analysis of pregnant women in Ontario, Canada.
Background
Women with preeclampsia (PEC) and gestational hypertension (GH) exhibit insulin resistance during pregnancy, independent of obesity and glucose intolerance. Our aim was to determine whether women with PEC or GH during pregnancy have an increased risk of developing diabetes after pregnancy, and whether the presence of PEC/GH in addition to gestational diabetes (GDM) increases the risk of future (postpartum) diabetes.
Methods and Findings
We performed a population-based, retrospective cohort study for 1,010,068 pregnant women who delivered in Ontario, Canada between April 1994 and March 2008. Women were categorized as having PEC alone (n = 22,933), GH alone (n = 27,605), GDM alone (n = 30,852), GDM+PEC (n = 1,476), GDM+GH (n = 2,100), or none of these conditions (n = 925,102). Our main outcome was a new diagnosis of diabetes postpartum in the following years, up until March 2011, based on new records in the Ontario Diabetes Database. The incidence rate of diabetes per 1,000 person-years was 6.47 for women with PEC and 5.26 for GH compared with 2.81 in women with neither of these conditions. In the multivariable analysis, both PEC alone (hazard ratio [HR] = 2.08; 95% CI 1.97–2.19) and GH alone (HR = 1.95; 95% CI 1.83–2.07) were risk factors for subsequent diabetes. Women with GDM alone were at elevated risk of developing diabetes postpartum (HR = 12.77; 95% CI 12.44–13.10); however, the co–presence of PEC or GH in addition to GDM further elevated this risk (HR = 15.75; 95% CI 14.52–17.07, and HR = 18.49; 95% CI 17.12–19.96, respectively). Data on obesity were not available.
Conclusions
Women with PEC/GH have a 2-fold increased risk of developing diabetes when followed up to 16.5 years after pregnancy, even in the absence of GDM. The presence of PEC/GH in the setting of GDM also raised the risk of diabetes significantly beyond that seen with GDM alone. A history of PEC/GH during pregnancy should alert clinicians to the need for preventative counseling and more vigilant screening for diabetes.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Diabetes is a chronic disease that occurs either when the pancreas does not produce enough insulin (a hormone that regulates blood sugar), known as type 1 diabetes, or when the body cannot effectively use the insulin it produces—type 2 diabetes. Raised blood sugar, is a common effect of uncontrolled diabetes and over time leads to serious complications and even death. Worryingly, the global burden of type 2 diabetes is increasing worldwide, and the World Health Organization estimates that 90% of the 347 million people with diabetes currently have type 2 diabetes. Previous studies have shown that type 2 diabetes can be prevented or delayed in high risk groups by a range of lifestyle and treatment interventions and so it is important to identify potential high risk groups to screen for type 2 diabetes.
Why Was This Study Done?
Gestational diabetes (a form of diabetes that is related to pregnancy) is a major risk factor for developing type 2 diabetes. Therefore, diabetes prevention strategies should target women with gestational diabetes. Likewise, other common disorders of pregnancy possibly associated with insulin resistance, such as preeclampsia (a condition in which affected women have high blood pressure, fluid retention, and protein in their urine) and gestational hypertension (high blood pressure associated with pregnancy), may lead to the future development of type 2 diabetes. So women with these conditions may also benefit from diabetes prevention strategies. Therefore, in this large database study from Ontario, Canada, the researchers examined whether pregnant women with preeclampsia or gestational hypertension had an increased risk of developing diabetes in the years following pregnancy even if they did not have gestational diabetes.
What Did the Researchers Do and Find?
The researchers used a comprehensive Canadian health database to identify all women age 15 to 50 years of age who delivered in an Ontario hospital between April 1994 and March 2008. They then identified women who had preeclampsia, gestational hypertension, or gestational diabetes through hospital records and outpatient information. The researchers then used records from the Ontario Diabetes Database to record whether these women went on to develop diabetes in the period from 180 days after delivery until March 2011.
Using these methods, the researchers identified 1,010,068 pregnant women suitable for analysis, of whom 22,933 had only preeclampsia, 27,605 had only gestational hypertension, and 30,852 had only gestational diabetes: 2,100 women had both gestational diabetes and gestational hypertension and 1,476 women had gestational diabetes and preeclampsia. Overall, 35,077 women developed diabetes (3.5%) in the follow-up period (median of 8.5 years) at a median age of 37 years. In a modeling analysis, the researchers found that women with gestational diabetes had a 15-fold increased rate of developing diabetes compared to women without gestational diabetes, gestational hypertension, and preeclampsia, while women with gestational diabetes plus either preeclampsia or gestational hypertension had a 20- to 21-fold increased rate. These results were slightly reduced after adjusting for age, income quintile, hypertension prior to pregnancy, and co-morbidity, giving a hazard ratio (HR) of 1.95 for gestational hypertension alone, an HR of 2.08 for preeclampsia alone, an HR of 12.77 for gestational diabetes alone, an HR of 18.49 for gestational diabetes plus gestational hypertension and finally, an HR of 15.75 for gestational diabetes plus preeclampsia.
These Findings Mean?
These findings suggest that both preeclampsia and gestational hypertension without gestational diabetes are associated with a 2-fold increased incidence of diabetes in the years following pregnancy after controlling for several important variables. When combined with gestational diabetes, these conditions were associated with a further elevation in diabetes incidence additional to the 13-fold increased incidence resulting from gestational diabetes alone. A limitation of this study was the lack of information on obesity and body mass index, factors which are also associated with increased risk of developing diabetes. Nevertheless, these findings highlight a possible new risk factor for diabetes, and suggest that clinicians should be aware of the need for preventative measures and vigilant screening for diabetes in women with a history of preeclampsia or gestational hypertension.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001425.
NHS Choices has information about preeclampsia, gestational diabetes, and gestational hypertension
Living with diabetes is a useful resource for patients with diabetes
The Preeclampsia Foundation has more information about preeclampsia
doi:10.1371/journal.pmed.1001425
PMCID: PMC3627640  PMID: 23610560

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