Beyond flu: Trends in respiratory infection outbreaks in Ontario healthcare settings from 2007 to 2017, and implications for non-influenza outbreak management.

BACKGROUND: Outbreaks cause significant morbidity and mortality in healthcare settings. Current testing methods can identify specific viral respiratory pathogens, yet the approach to outbreak management remains general. OBJECTIVES: Our aim was to examine pathogen-specific trends in respiratory outbreaks, including how attack rates, case fatality rates and outbreak duration differ by pathogen between hospitals and long-term care (LTC) and retirement homes (RH) in Ontario. METHODS: Confirmed respiratory outbreaks in Ontario hospitals and LTC/RH reported between September 1, 2007, and August 31, 2017, were extracted from the integrated Public Health Information System (iPHIS). Median attack rates and outbreak duration and overall case fatality rates of pathogen-specific outbreaks were compared in both settings. RESULTS: Over the 10-year surveillance period, 9,870 confirmed respiratory outbreaks were reported in Ontario hospitals and LTC/RH. Influenza was responsible for most outbreaks (32% in LTC/RH, 51% in hospitals), but these outbreaks were shorter and had lower attack rates than most non-influenza outbreaks in either setting. Human metapneumovirus, while uncommon (<4% of outbreaks) had high case fatality rates in both settings. CONCLUSION: Attack rates and case fatality rates varied by pathogen, as did outbreak duration. Development of specific outbreak management guidance that takes into account pathogen and healthcare setting may be useful to limit the burden of respiratory outbreaks.

COVID-19 Workplace Outbreaks by Industry Sector and Their Associated Household Transmission, Ontario, Canada, January to June, 2020.

OBJECTIVE: To analyze workplace outbreaks by industry sector in the first wave of the pandemic, and associated household cases. METHODS: Number, size, and duration of outbreaks were described by sector, and outbreak cases were compared to sporadic cases in the same time frame. Address matching identified household cases with onset ≥2 days before, ≥2 days after, or within 1 day of the workplace outbreak case. RESULTS: There were 199 outbreaks with 1245 cases, and 68% of outbreaks and 80% of cases belonged to (1) Manufacturing, (2) Agriculture, Forestry, Fishing, Hunting, (3) Transportation and Warehousing. There were 608 household cases associated with 339 (31%) outbreak cases, increasing the burden of illness by 56%. CONCLUSIONS: Workplace outbreaks primarily occurred in three sectors. Prevention measures should target industry sectors at risk to prevent spread in and out of the workplace.

Epidemiology, clinical characteristics, household transmission, and lethality of severe acute respiratory syndrome coronavirus-2 infection among healthcare workers in Ontario, Canada.

INTRODUCTION: Protecting healthcare workers (HCWs) from Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a priority to maintain a safe and functioning healthcare system. Our objective was to describe and compare the epidemiology, clinical characteristics, and lethality of SARS-CoV-2 infections among HCWs compared to non-HCWs. METHODS: Using reportable disease data at Public Health Ontario, we conducted a population-based cross-sectional study comparing demographic, exposure, and clinical variables between HCWs and non-HCWs with SARS-CoV-2 infections as of 30 September 2020. We calculated rates of infections over time and determined the frequency of within household transmissions using natural language processing based on residential address. We evaluated the risk of death using a multivariable logistic regression model adjusting for age, sex, comorbidities, symptoms, and long-term care home exposure. RESULTS: There were 7,050 (12.5%) HCW SARS-CoV-2 infections in Ontario, Canada, of whom 24.9% were nurses, 2.3% were physicians, and the remaining 72.8% other specialties, including personal support workers. Overall HCWs had an infection rate of 1,276 per 100,000 compared to non-HCWs of 346 per 100,000 (3.7 times higher). This difference decreased from a 7 times higher rate in April to no difference in September 2020. Twenty-six percent of HCWs had a household member with SARS-CoV-2 infection; 6.8% were probable acquisitions, 12.3% secondary transmissions, and 6.9% unknown direction of transmission. Death among HCWs was 0.2% compared to 6.1% of non-HCWs. The risk of death in HCWs remained significantly lower than non-HCWs after adjustment (adjusted odds ratio 0.09; 95%CI 0.05-0.17). CONCLUSION: HCWs represent a disproportionate number of diagnosed SARS-CoV-2 infections in Ontario, however this discrepancy is at least partially explained by limitations in testing earlier in the pandemic for non-HCWs. We observed a low risk of death in HCWs which could not be completely explained by other factors.

Investigating the relationship between vancomycin-resistant Enterococcus control practices and the incidence of health care-associated Clostridioides difficile infections in Ontario.

We evaluated the impact of discontinuing vancomycin-resistant Enterococcus (VRE) screening and use of contact precautions on the incidence of health care-associated Clostridioides difficile infection (HA-CDI) in acute teaching hospitals in Ontario, Canada. Among hospitals that stopped VRE screening and contact precaution measures, there was a significant change in HA-CDI rates after the discontinuation of practices (incidence rate ratios, 1.11; 95% confidence interval, 1.01-1.22). No change in rate was observed among hospitals that continued VRE control practices. Screening and use of contact precautions for VRE may provide hospitals additional advantages for broadened HA-CDI control and prevention.

Predictors and variability of antibiotic prescribing amongst family physicians.

BACKGROUND: Rising rates of antimicrobial resistance are driven by overuse of antibiotics. Characterizing physician antibiotic prescribing variability can inform interventions to optimize antibiotic use. OBJECTIVES: To describe predictors of overall antibiotic prescribing as well as the inter-physician variability in antibiotic prescribing amongst family physicians. METHODS: We conducted a 5 year cohort study of antibiotic prescribing rates by family physicians in Ontario, Canada using a repository of electronic medical records. Using multilevel logistic regression models fitted with random intercepts for physicians, we evaluated the association of patient-, physician- and clinic-level characteristics with antibiotic prescribing rates. RESULTS: We included 3956921 physician-patient encounters, 322129 unique patients and 313 physicians from 41 family medicine clinics. Physicians prescribed a median of 54 (interdecile range 28-95) antibiotics per 1000 encounters. Female children aged 3-5 years were most likely to receive antibiotics compared with men ≥65 years (OR 4.01, 95% CI 3.89-4.13). The only significant physician-level predictor was median daily patient visits of ≥20 compared with <10 (OR 1.28, 95% CI 1.06-1.55). The median ORs without and with patient characteristics were 1.68 and 1.69, respectively. Thus, the odds of receiving an antibiotic varied by 1.7-fold for the same patient simply by virtue of encountering two different physicians. CONCLUSIONS: We observed substantial inter-physician variability in antibiotic prescribing that could not be explained by sociodemographic and clinical patient differences, suggesting that risk adjustment of antibiotic prescribing practices may not be required for audit and feedback of family physicians working in similar practice settings.

Comparing prescribing and dispensing databases to study antibiotic use: a validation study of the Electronic Medical Record Administrative data Linked Database (EMRALD).

BACKGROUND: Monitoring and studying community antibiotic use is a critical component in combating rising antimicrobial resistance. OBJECTIVES: To validate an electronic medical record dataset containing antibiotic prescriptions and to quantify some important differences between prescribing and dispensing databases. METHODS: We evaluated antibiotics prescribed and dispensed to patients ≥65 years of age during 2011-15. We compared the EMRALD prescribing database with the validated Ontario Drug Benefit (ODB) dispensing database. Using ODB as the gold standard and limiting to EMRALD physicians, we calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) with 95% CIs. We also compared the relative change in antibiotic use prescribed by all physicians to this population over time between the databases using Poisson regression models. RESULTS: In this population, 74% of all antibiotics dispensed were from non-EMRALD physicians. Trends in use were discordant over time. When we limited ODB to EMRALD prescribers only to assess the validity of EMRALD data, we observed good sensitivity and excellent specificity for correctly identifying antibiotics at 85% (95% CI 84%-85%) and 98% (95% CI 98%-98%), respectively. The PPV was 78% (95% CI 78%-78%) and the NPV was 99% (95% CI 99%-99%). All performance measures were higher among the highest prescribing physicians. CONCLUSIONS: We demonstrated EMRALD is well suited for studying antibiotic prescribing by EMRALD physicians. However, due to the frequency with which patients receive antibiotic prescriptions from their non-primary care physicians, we caution against the use of non-population-based prescribing databases to infer antibiotic use rates or trends over time.

Regional variability in outpatient antibiotic use in Ontario, Canada: a retrospective cross-sectional study.

BACKGROUND: Regional variability in antibiotic use is associated with both antibiotic overuse and antimicrobial resistance. Our objectives were to benchmark outpatient antibiotic use and to evaluate geographic variability among health regions in the province of Ontario, Canada. METHODS: This was a cross-sectional study of antibiotics dispensed from outpatient retail pharmacies in Ontario between March 2016 and February 2017. We analyzed variability in the number of antibiotic prescriptions dispensed per 1000 population among Ontario's 14 health regions with crude and adjusted Poisson regression models. Adjusted models controlled for rurality, 4 physician characteristics and 6 population characteristics. RESULTS: There were 8 352 578 antibiotics dispensed during the 1-year study period or 621 per 1000 population. The most commonly prescribed antibiotic classes were narrow-spectrum penicillins, macrolides, first-generation cephalosporins and second-generation fluoroquinolones, with adult women receiving the highest rate of prescriptions: 985 antibiotic prescriptions per 1000 population. There was geographic variability in total and class-specific antibiotic use. In the health region with the highest use 778 antibiotics were dispensed per 1000 population whereas in the health region with the lowest use 534 antibiotics were dispensed per 1000 population. The adjusted marginal standardized antibiotic prescription rates for the health regions with the highest and lowest use were 787 (95% confidence interval [CI] 658-934) and 546 (95% CI 494-606) antibiotic prescriptions per 1000 population, respectively. INTERPRETATION: We described baseline antibiotic usage in Ontario over a 12-month period, noting variability among some health regions. Our findings highlight the need for interventions to optimize antibiotic use and slow the emergence of antimicrobial resistance.

Proposed Core Set of Items for Measuring Disease Activity in Systemic Juvenile Idiopathic Arthritis.

OBJECTIVE: To date, there are no standardized disease activity tools for systemic juvenile idiopathic arthritis (sJIA). We developed a core set of disease activity measures for sJIA. METHODS: We conducted a validation study in patients with sJIA recruited from 3 Canadian institutions. Disease activity scores were based on questionnaires, clinical factors, and laboratory measures. The physician's global assessment was our criterion standard. We determined the strength of association of each item with the criterion standard. We then surveyed international experts to determine the top 10 items. Finally, we used the experts' responses to generate a proposed core set of disease activity measures. RESULTS: We enrolled 57 subjects - 26 with moderately or severely active disease, and 31 with mildly active or inactive disease. Items that most strongly correlated with the criterion standard were number of active joints (r = 0.79), parent's global assessment of disease activity (r = 0.53), erythrocyte sedimentation rate (ESR; r = 0.62), and C-reactive protein (CRP; r = 0.61). The response rate from international experts was 82% (154/187). Items with the most votes, in descending order, were number of active joints, number of days with fever in the preceding 2 weeks, patient's and parent's global assessments of disease activity, sJIA rash, ESR, CRP, and hemoglobin level. CONCLUSION: We propose a core set of items for measuring disease activity in sJIA. Future research should be aimed at further validation of this core set in the international context.

Using expert process to combat Clostridium difficile infections.

In 2008, Clostridium difficile rates were increasing in Ontario, Canada, and in response, hospitals were mandated by the Ontario Ministry of Health to publicly report their C difficile infection (CDI) rates. In order to assist hospitals which had ongoing CDI outbreaks, a process of an external infection control resource team (ICRT) was introduced. This article describes the function and process of the ICRT, managed by Public Health Ontario, and reviews the lessons learned over the first 5 years of operation. These lessons may assist other hospitals in managing their own infection prevention and control outbreak.

Public health response to a large-scale endoscopy infection control lapse in a nonhospital clinic.

OBJECTIVE: To determine whether transmission of blood-borne pathogens (BBPs) (hepatitis B virus [HBV], hepatitis C virus [HCV] and HIV) occurred as a result of endoscopy reprocessing failures identified during an inspection of a nonhospital endoscopy clinic in 2011. METHODS: The present analysis was a retrospective cohort study. Registered notification letters were mailed to 6992 patients who underwent endoscopy from 2002 to 2011 at one Canadian nonhospital endoscopy clinic, informing them of the infection control lapse and offering BBP testing. Multimedia communications and a telephone line supplemented notification. A retrospective study of patients with BBPs was performed with viral genetic testing and risk factor assessment for eligible patients. Risk for infection among patients whose procedure was within seven days of a known positive patient was compared with those whose procedure was performed more than seven days after a known postive patient. The seven-day period was selected as the period most likely to present a risk for transmission based on the documented cleaning procedures at the clinic and the available literature on virus survival. RESULTS: Ninety-five percent (6628 of 6992) of patients/estates were contacted and 5042 of 6728 (75%) living patients completed BBP testing. Three were newly diagnosed with HBV and 14 with HCV. Twenty-three and 48 tested positive for previously known HBV or HCV, respectively, 367 were immune to HBV due to natural infection and one was immune to HBV due to immunization. None tested positive for HIV. Sequencing did not reveal any relationships among the 46 unique case patients with viral genetic test results available. Ninety-three percent of patients reported alternative risk factors for BBP. An increased risk for infection among those who underwent a procedure within seven days of a known HBV or HCV case was not demonstrated. CONCLUSIONS: Endoscopy reprocessing failures were not associated with an increased risk for BBP among individuals tested.

OBJECTIF: Lors de l'inspection d'une clinique d'endoscopie non hospitalière en 2011, déterminer si des pathogènes à diffusion hématogène (PDH; virus de l'hépatite B [VHB], virus de l'hépatite C [VHC] et VIH) sont transmis à cause de la défaillance du retraitement de l'endoscopie. MÉTHODOLOGIE: Dans la présente étude de cohorte rétrospective, les chercheurs ont posté une lettre recommandée à 6 992 patients qui avaient subi une endoscopie entre 2002 et 2011 dans une clinique canadienne d'endoscopie non hospitalière pour les informer d'une défaillance du contrôle des infections et leur offrir un test de dépistage des PDH. Les communications multimédias et les appels téléphoniques ont complété cet avis. Les chercheurs ont effectué une étude rétrospective des patients ayant des PDH au moyen de tests génétiques viraux et d'une évaluation des facteurs de risque des patients admissibles. Ils ont comparé le risque d'infection entre les patients dont l'intervention avait eu lieu dans les sept jours suivant celle d'un patient positif connu ceux dont l'intervalle dépassait sept jours. Cette période de sept jours était la plus susceptible de constituer un risque de transmission compte tenu des mesures de nettoyage attestées à la clinique et les publications sur la survie des virus. RÉSULTATS: Les chercheurs ont pris contact avec 95 % (6 628 cas sur 6 692) des patients et des successions, et 5 042 des 6 728 (75 %) patients vivants ont effectué le test de dépistage des PDH. Trois ont obtenu un nouveau diagnostic de VHB et 14, de VHC. De plus, 23 et 48 ont obtenu des résultats positifs à un VHB ou à un VHC déjà connu, respectivement, 367 étaient immuns au VHB en raison d'une infection naturelle et un, grâce à la vaccination. Aucun n'a obtenu de résultat positif au VIH. Le séquençage a révélé l'absence de lien entre les 46 cas uniques de patients pour qui les résultats du test génétique étaient disponibles. Aussi, 93 % des patients ont signalé d'autres facteurs de risques de PDH. Par ailleurs, on n'a pu démontrer d'augmentation du risque d'infection chez les personnes qui avaient subi une intervention dans les sept jours suivant un cas connu de VHB ou de VHC. CONCLUSIONS: L'échec de retraitement de l'endoscopie ne s'associait pas à une augmentation du risque de PDH chez les personnes qui subissaient un test de dépistage.

Determining mortality rates attributable to Clostridium difficile infection.

To determine accuracy of measures of deaths attributable to Clostridium difficile infection, we compared 3 measures for 2007-2008 in Ontario, Canada: death certificate; death within 30 days of infection; and panel review. Data on death within 30 days were more feasible than panel review and more accurate than death certificate data.

Humoral and cell-mediated immunity to pandemic H1N1 influenza in a Canadian cohort one year post-pandemic: implications for vaccination.

We evaluated a cohort of Canadian donors for T cell and antibody responses against influenza A/California/7/2009 (pH1N1) at 8-10 months after the 2nd pandemic wave by flow cytometry and microneutralization assays. Memory CD8 T cell responses to pH1N1 were detectable in 58% (61/105) of donors. These responses were largely due to cross-reactive CD8 T cell epitopes as, for those donors tested, similar recall responses were obtained to A/California 2009 and A/PR8 1934 H1N1 Hviruses. Longitudinal analysis of a single infected individual showed only a small and transient increase in neutralizing antibody levels, but a robust CD8 T cell response that rose rapidly post symptom onset, peaking at 3 weeks, followed by a gradual decline to the baseline levels seen in a seroprevalence cohort post-pandemic. The magnitude of the influenza-specific CD8 T cell memory response at one year post-pandemic was similar in cases and controls as well as in vaccinated and unvaccinated donors, suggesting that any T cell boosting from infection was transient. Pandemic H1-specific antibodies were only detectable in approximately half of vaccinated donors. However, those who were vaccinated within a few months following infection had the highest persisting antibody titers, suggesting that vaccination shortly after influenza infection can boost or sustain antibody levels. For the most part the circulating influenza-specific T cell and serum antibody levels in the population at one year post-pandemic were not different between cases and controls, suggesting that natural infection does not lead to higher long term T cell and antibody responses in donors with pre-existing immunity to influenza. However, based on the responses of one longitudinal donor, it is possible for a small population of pre-existing cross-reactive memory CD8 T cells to expand rapidly following infection and this response may aid in viral clearance and contribute to a lessening of disease severity.

Seroprevalence of pandemic influenza H1N1 in Ontario from January 2009-May 2010.

BACKGROUND: We designed a seroprevalence study using multiple testing assays and population sources to estimate the community seroprevalence of pH1N1/09 and risk factors for infection before the outbreak was recognized and throughout the pandemic to the end of 2009/10 influenza season. METHODS: Residual serum specimens from five time points (between 01/2009 and 05/2010) and samples from two time points from a prospectively recruited cohort were included. The distribution of risk factors was explored in multivariate adjusted analyses using logistic regression among the cohort. Antibody levels were measured by hemagglutination inhibition (HAI) and microneutralization (MN) assays. RESULTS: Residual sera from 3375 patients and 1024 prospectively recruited cohort participants were analyzed. Pre-pandemic seroprevalence ranged from 2%-12% across age groups. Overall seropositivity ranged from 10%-19% post-first wave and 32%-41% by the end of the 2009/10 influenza season. Seroprevalence and risk factors differed between MN and HAI assays, particularly in older age groups and between waves. Following the H1N1 vaccination program, higher GMT were noted among vaccinated individuals. Overall, 20-30% of the population was estimated to be infected. CONCLUSIONS: Combining population sources of sera across five time points with prospectively collected epidemiological information yielded a complete description of the evolution of pH1N1 infection.

Estimating background rates of Guillain-Barré Syndrome in Ontario in order to respond to safety concerns during pandemic H1N1/09 immunization campaign.

BACKGROUND: The province of Ontario, Canada initiated mass immunization clinics with adjuvanted pandemic H1N1 influenza vaccine in October 2009. Due to the scale of the campaign, temporal associations with Guillain-Barré syndrome (GBS) and vaccination were expected. The objectives of this analysis were to estimate the number of background GBS cases expected to occur in the projected vaccinated population and to estimate the number of additional GBS cases which would be expected if an association with vaccination existed. The number of influenza-associated GBS cases was also determined. METHODS: Baseline incidence rates of GBS were determined from published Canadian studies and applied to projected vaccine coverage data to estimate the expected number of GBS cases in the vaccinated population. Assuming an association with vaccine existed, the number of additional cases of GBS expected was determined by applying the rates observed during the 1976 Swine Flu and 1992/1994 seasonal influenza campaigns in the United States. The number of influenza-associated GBS cases expected to occur during the vaccination campaign was determined based on risk estimates of GBS after influenza infection and provincial influenza infection rates using a combination of laboratory-confirmed cases and data from a seroprevalence study. RESULTS: The overall provincial vaccine coverage was estimated to be between 32% and 38%. Assuming 38% coverage, between 6 and 13 background cases of GBS were expected within this projected vaccinated cohort (assuming 32% coverage yielded between 5-11 background cases). An additional 6 or 42 cases would be expected if an association between GBS and influenza vaccine was observed (assuming 32% coverage yielded 5 or 35 additional cases); while up to 31 influenza-associated GBS cases could be expected to occur. In comparison, during the same period, only 7 cases of GBS were reported among vaccinated persons. CONCLUSIONS: Our analyses do not suggest an increased number of GBS cases due to the vaccine. Awareness of expected rates of GBS is crucial when assessing adverse events following influenza immunization. Furthermore, since individuals with influenza infection are also at risk of developing GBS, they must be considered in such analyses, particularly if the vaccine campaign and disease are occurring concurrently.

Syndromic surveillance for influenzalike illness.

Emergency department data are currently being used by several syndromic surveillance systems to identify outbreaks of natural or man-made illnesses, and preliminary results suggest that regular outbreaks might be detected earlier with such data than with traditional reporting. This article summarizes a retrospective study of 5 influenza seasons in Ottawa,Canada; time-series analysis was used to look for an association between consultation to the emergency department for influenzalike illness and the isolation of influenza virus in the community. The population studied included both children and adults consulting to 3 local hospitals. In 4 seasons, visits to the emergency department involving children younger than 5 years consulting mainly for fever and for respiratory symptoms peaked 1 to 4 weeks before the isolation of influenza virus in the community. If monitored regularly for the presence of key symptoms, pediatric hospitals might be efficient and cost-effective sentinels of influenza and of other infectious diseases.

Evidence for local transmission and reactivation of tuberculosis in the Toronto Somali community.

To further understand the molecular and clinical epidemiology of tuberculosis in the Toronto Somali community, molecular fingerprinting using IS6110 restriction fragment length polymorphism typing or spoligotyping was performed on M. tuberculosis isolates obtained from Somali-Canadians who developed active disease from 1997 to 2001. Molecular fingerprints were further compared with those obtained from Somalis residing in Denmark. 142 Somali TB patients were reported, for whom, 80 isolates were fingerprinted. 25% of isolates were clustered. Three clusters involving 2 patients each were identified out of the17 isolates that underwent spoligotyping. Of the 63 isolates typed by the IS6110 method, 6 clusters (4 of 2 patients and 2 of 3 patients) were identified. 57% of these isolates were found to be identical to Danish isolates. Our study suggests that a combination of reactivation and recent transmission are responsible for the high incidence rates of tuberculosis in this community. We recommend that ongoing surveillance and treatment programmes be directed towards this community.

The financial impact of controlling a respiratory virus outbreak in a teaching hospital: lessons learned from SARS.

BACKGROUND: Outbreaks of Severe Acute Respiratory Syndrome (SARS) in 2003 and renewed concerns regarding pandemic influenza have resulted in widespread planning for future respiratory disease outbreaks. Such planning should include accurate cost estimates for any proposed disease control strategies. From the acute care hospital perspective, such estimates typically take into account the cost of supplies and equipment, but rarely consider indirect costs such as lost revenue due to the scaling down of programs. METHODS: Retrospective cost analysis. Costs and savings were calculated from the hospital perspective using financial records. Costs were categorized to determine the major areas of expenditure and savings. RESULTS: We report that controlling a SARS outbreak in a teaching hospital over an 8-week period cost dollar12 million Canadian. Lost revenue and labour accounted for two thirds of the costs incurred while excess spending on services, materials, supplies and renovation of existing space accounted for the remaining one third. CONCLUSIONS: Cost estimates that consider only excess expenditures may considerably underestimate the true cost of infection control strategies.

Effect of intracranial bleeds on the health and quality of life of boys with hemophilia.

OBJECTIVES: To compare the health, physical function, and quality of life (QoL) of boys with hemophilia with and without a history of intracranial hemorrhage (ICH). STUDY DESIGN: Of 172 patients with hemophilia A or B, 18 (10%) had at least one episode of ICH. For outcome assessments, 16 of 18 (89%) boys with ICH and 32 controls, matched (1:2) for age and severity of hemophilia, were available. The outcome measures were neurologic function, physical function, and QoL. RESULTS: The median age of the boys at the first ICH was 5.9 months (range, 1 day to 2.7 years). Boys with ICH had a higher incidence of inhibitors and lower mean household income. Neurologic examination was abnormal in seven of 16 (44%) boys with ICH and nine of 32 (28%) controls (P=.3). The mean physical function in boys with ICH was lower (82%+/-25%) compared with controls (93.5%+/-12%, P=.045). The QoL was decreased in boys with ICH compared with controls (6.8+/-3.2 vs 8.5+/-1.4, P=.02), whereas health-related QoL was not significantly different between groups. CONCLUSION: The poorer long-term outcomes of boys with hemophilia appropriately treated for ICH, especially in the domain of QoL, suggest that new strategies to prevent ICH and to manage ICH effectively in this population are needed.