National Trends in Hepatitis C Infection by Opioid Use Disorder Status Among Pregnant Women at Delivery Hospitalization - United States, 2000-2015.

Hepatitis C virus (HCV) is transmitted primarily through parenteral exposures to infectious blood or body fluids that contain blood (e.g., via injection drug use, needle stick injuries) (1). In the last 10 years, increases in HCV infection in the general U.S. population (1) and among pregnant women (2) are attributed to a surge in injection drug use associated with the opioid crisis. Opioid use disorders among pregnant women have increased (3), and approximately 68% of pregnant women with HCV infection have opioid use disorder (4). National trends in HCV infection among pregnant women by opioid use disorder status have not been reported to date. CDC analyzed hospital discharge data from the 2000-2015 Healthcare Cost and Utilization Project (HCUP) to determine whether HCV infection trends differ by opioid use disorder status at delivery. During this period, the national rate of HCV infection among women giving birth increased >400%, from 0.8 to 4.1 per 1,000 deliveries. Among women with opioid use disorder, rates of HCV infection increased 148%, from 87.4 to 216.9 per 1,000 deliveries, and among those without opioid use disorder, rates increased 271%, although the rates in this group were much lower, increasing from 0.7 to 2.6 per 1,000 deliveries. These findings align with prior ecological data linking hepatitis C increases with the opioid crisis (2). Treatment of opioid use disorder should include screening and referral for related conditions such as HCV infection.

Recent and occult hepatitis B virus infections among blood donors in the United States.

BACKGROUND: Characteristics of US blood donors with recent (RBI) or occult (OBI) hepatitis B virus (HBV) infection are not well defined. METHODS: Donors with RBI and OBI were identified by nucleic acid and serologic testing among 34.4 million donations during 2009-2015. Consenting donors were interviewed and their HBV S-gene sequenced. RESULTS: The overall rate of HBV-infected donors was 7.95 per 100,000; of these, 0.35 per 100,000 and 1.70 per 100,000 were RBI and OBI, respectively. RBI (n = 120) and OBI (n = 583) donors constituted 26% of all HBV-infected (n = 2735) donors. Detection of HBV DNA in 92% of OBI donors required individual donation nucleic acid testing. Donors with OBI compared to RBI were older (mean age, 48 vs 39 years; p < 0.0001) with lower median viral loads (9 vs. 529 IU/mL; p < 0.0001). A higher proportion of OBI than RBI donors were born or resided in an endemic country (39% vs. 5%; p = 0.0078). Seventy-seven percent of all RBI and OBI donors had multiple sex partners, an HBV-risk factor. Of 40 RBI and 10 OBI donors whose S gene was sequenced, 33 (83%) and 6 (60%), respectively, carried HBV subgenotype A2; 18 (55%) and 2 (33%), respectively, shared an identical sequence. Infection with 1 or more putative HBV-immune-escape mutants was identified in 5 (50%) of OBI but no RBI donors. CONCLUSION: RBI and OBI continue to be identified at low rates, confirming the importance of comprehensive HBV DNA screening of US blood donations. HBV-infected donors require referral for care and evaluation and contact tracing; their HBV strains may provide important information on emergent genotypes.

Update: Recommendations of the Advisory Committee on Immunization Practices for Use of Hepatitis A Vaccine for Postexposure Prophylaxis and for Preexposure Prophylaxis for International Travel.

Postexposure prophylaxis (PEP) with hepatitis A (HepA) vaccine or immune globulin (IG) effectively prevents infection with hepatitis A virus (HAV) when administered within 2 weeks of exposure. Preexposure prophylaxis against HAV infection through the administration of HepA vaccine or IG provides protection for unvaccinated persons traveling to or working in countries that have high or intermediate HAV endemicity. The Advisory Committee on Immunization Practices (ACIP) Hepatitis Vaccines Work Group conducted a systematic review of the evidence for administering vaccine for PEP to persons aged >40 years and reviewed the HepA vaccine efficacy and safety in infants and the benefits of protection against HAV before international travel. The February 21, 2018, ACIP recommendations update and supersede previous ACIP recommendations for HepA vaccine for PEP and for international travel. Current recommendations include that HepA vaccine should be administered to all persons aged ≥12 months for PEP. In addition to HepA vaccine, IG may be administered to persons aged >40 years depending on the provider's risk assessment. ACIP also recommended that HepA vaccine be administered to infants aged 6-11 months traveling outside the United States when protection against HAV is recommended. The travel-related dose for infants aged 6-11 months should not be counted toward the routine 2-dose series. The dosage of IG has been updated where applicable (0.1 mL/kg). HepA vaccine for PEP provides advantages over IG, including induction of active immunity, longer duration of protection, ease of administration, and greater acceptability and availability.

Hepatitis C Virus in Women of Childbearing Age, Pregnant Women, and Children.

INTRODUCTION: Perinatal transmission is an increasingly important mode of hepatitis C virus transmission. The authors characterized U.S. births among hepatitis C virus-infected women and evaluated trends in hepatitis C virus testing and positivity in women of childbearing age, pregnant women, and children aged less than 5years. METHODS: In 2017, National Center for Health Statistics birth certificate data (48 states and District of Columbia) were analyzed to assess the number of hepatitis C virus-infected women delivering live births in 2015, and commercial laboratory data were analyzed to assess hepatitis C virus testing and positivity among women of childbearing age, pregnant women, and children aged <5years from 2011 to 2016. RESULTS: In 2015, a total of 0.38% (n=14,417) of live births were delivered by hepatitis C virus-infected women. Births delivered by hepatitis C virus-infected women, compared with births overall, occurred more often in women who were aged 20-29years (60.7% vs 50.9%); white, non-Hispanic (80.2% vs 52.8%); covered by Medicaid or other government insurance (79.2% vs 43.9%); and had rural residence (26.0% vs 14.0%). From 2011 to 2016 laboratory data, among women of childbearing age, hepatitis C virus testing increased by 39%, from 6.1% to 8.4%, and positivity increased by 36%, from 4.4% to 6.0%. Among pregnant women, hepatitis C virus testing increased by 135%, from 5.7% to 13.4%, and positivity increased by 39%, from 2.6% to 3.6%. Among children, hepatitis C virus testing increased by 25%, from 0.47% to 0.59%, and positivity increased by 13%, from 3.6% to 4.0%. CONCLUSIONS: The potential for perinatal hepatitis C virus transmission exists. Expanded hepatitis C virus testing guidelines may address the burden of disease in this population.

Safety of currently licensed hepatitis B surface antigen vaccines in the United States, Vaccine Adverse Event Reporting System (VAERS), 2005-2015.

INTRODUCTION: Currently four recombinant hepatitis B (HepB) vaccines are in use in the United States. HepB vaccines are recommended for infants, children and adults. We assessed adverse events (AEs) following HepB vaccines reported to the Vaccine Adverse Event Reporting System (VAERS), a national spontaneous reporting system. METHODS: We searched VAERS for reports of AEs following single antigen HepB vaccine and HepB-containing vaccines (either given alone or with other vaccines), from January 2005 - December 2015. We conducted descriptive analyses and performed empirical Bayesian data mining to assess disproportionate reporting. We reviewed serious reports including reports of special interest. RESULTS: VAERS received 20,231 reports following HepB or HepB-containing vaccines: 10,291 (51%) in persons <2 years of age; 2588 (13%) in persons 2-18 years and 5867 (29%) in persons >18 years; for 1485 (7.3%) age was missing. Dizziness and nausea (8.4% each) were the most frequently reported AEs following a single antigen HepB vaccine: fever (23%) and injection site erythema (11%) were most frequent following Hep-containing vaccines. Of the 4444 (22%) reports after single antigen HepB vaccine, 303 (6.8%) were serious, including 45 deaths. Most commonly reported cause of death was Sudden Infant Death Syndrome (197). Most common non-death serious reports following single antigen HepB vaccines among infants aged <1 month, were nervous system disorders (15) among children aged 1-23 months; infections and infestation (8) among persons age 2-18 years blood and lymphatic systemic disorders; and general disorders and administration site conditions among persons age >18 years. Most common vaccination error following single antigen HepB was incorrect product storage. CONCLUSIONS: Review current U.S.-licensed HepB vaccines administered alone or in combination with other vaccines did not reveal new or unexpected safety concerns. Vaccination errors were identified which indicate the need for training and education of providers on HepB vaccine indications and recommendations.

Cost-effectiveness of active-passive prophylaxis and antiviral prophylaxis during pregnancy to prevent perinatal hepatitis B virus infection.

UNLABELLED: In an era of antiviral treatment, reexamination of the cost-effectiveness of strategies to prevent perinatal hepatitis B virus (HBV) transmission in the United States is needed. We used a decision tree and Markov model to estimate the cost-effectiveness of the current U.S. strategy and two alternatives: (1) Universal hepatitis B vaccination (HepB) strategy: No pregnant women are screened for hepatitis B surface antigen (HBsAg). All infants receive HepB before hospital discharge; no infants receive hepatitis B immunoglobulin (HBIG). (2) Current strategy: All pregnant women are screened for HBsAg. Infants of HBsAg-positive women receive HepB and HBIG ≤12 hours of birth. All other infants receive HepB before hospital discharge. (3) Antiviral prophylaxis strategy: All pregnant women are screened for HBsAg. HBsAg-positive women have HBV-DNA load measured. Antiviral prophylaxis is offered for 4 months starting in the third trimester to women with DNA load ≥10(6) copies/mL. HepB and HBIG are administered at birth to infants of HBsAg-positive women, and HepB is administered before hospital discharge to infants of HBsAg-negative women. Effects were measured in quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICER). Compared to the universal HepB strategy, the current strategy prevented 1,006 chronic HBV infections and saved 13,600 QALYs (ICER: $6,957/QALY saved). Antiviral prophylaxis dominated the current strategy, preventing an additional 489 chronic infections, and saving 800 QALYs and $2.8 million. The results remained robust over a wide range of assumptions. CONCLUSION: The current U.S. strategy for preventing perinatal HBV remains cost-effective compared to the universal HepB strategy. An antiviral prophylaxis strategy was cost saving compared to the current strategy and should be considered to continue to decrease the burden of perinatal hepatitis B in the United States.

Chronic Liver Disease-Associated Hospitalizations Among Adults with Diabetes, National Inpatient Sample, 2001-2012.

OBJECTIVE: Many people with diabetes have a variety of diabetes-related complications. Among the variety of conditions associated with diabetes, however, liver diseases are less well recognized. As such, we aimed to describe chronic liver disease (CLD)-associated hospitalization rates among U.S. adults with diabetes from 2001-2012. METHODS: We used a nationally representative database of hospitalizations, the National Inpatient Sample, to determine CLD-associated hospitalization rates among U.S. adults aged ≥ 18 years with and without diabetes, from 2001-2012. Hospitalizations listing an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code for CLD on the discharge record were selected for analysis and were further classified by diabetes status based on concurrent presence of a diabetes ICD-9-CM code. We calculated average annual age-adjusted hospitalization rates and 95% confidence intervals (CIs), and conducted a test for trend. RESULTS: For 2001-2012, the total age-adjusted CLD-associated hospitalization rate among adults with diabetes (1,680.9 per 100,000 population; 95% CI 1,577.2, 1,784.6) was approximately four times the rate of adults without diabetes (424.2 per 100,000 population; 95% CI 413.4, 435.1). Total age-adjusted hospitalization rates of adults with and without diabetes increased 59% and 48%, respectively, from 2001-2002 to 2011-2012 (p<0.001). Hepatitis C- and chronic hepatitis and cirrhosis-associated hospitalizations comprised the largest proportion of total CLD-associated hospitalizations among adults with and without diabetes. CONCLUSION: Providers should be aware of the potential existence of CLD among adults with diabetes and counsel patients on preventive methods to avoid progressive liver damage.

Antiviral treatment among pregnant women with chronic hepatitis B.

OBJECTIVE: To describe the antiviral treatment patterns for chronic hepatitis B (CHB) among pregnant and nonpregnant women. METHODS: Using 2011 MarketScan claims, we calculated the rates of antiviral treatment among women (aged 10-50 years) with CHB. We described the pattern of antiviral treatment during pregnancy and ≥1 month after delivery. RESULTS: We identified 6274 women with CHB during 2011. Among these, 64 of 507 (12.6%) pregnant women and 1151 of 5767 (20.0%) nonpregnant women received antiviral treatment (P < 0.01). Pregnant women were most commonly prescribed tenofovir (73.4%) and lamivudine (21.9%); nonpregnant women were most commonly prescribed tenofovir (50.2%) and entecavir (41.3%) (P < 0.01). Among 48 treated pregnant women with an identifiable delivery date, 16 (33.3%) were prescribed an antiviral before pregnancy and continued treatment for at least one month after delivery; 14 (29.2%) started treatment during the third trimester and continued at least one month after delivery. CONCLUSION: Among this insured population, pregnant women with CHB received an antiviral significantly less often than nonpregnant women. The most common antiviral prescribed for pregnant women was tenofovir. These data provide a baseline for assessing changes in treatment patterns with anticipated increased use of antivirals to prevent breakthrough perinatal hepatitis B virus infection.

Cost-effectiveness of ensuring hepatitis B protection for previously vaccinated healthcare personnel.

OBJECTIVE: To examine the cost-effectiveness of pre- and postexposure approaches for ensuring hepatitis B protection among previously vaccinated healthcare personnel (HCP). DESIGN: A decision-analytic model was developed for alternative strategies of ensuring hepatitis B protection under assumptions of 68% and 95% long-term protection after a primary vaccination series. Costs and quality-adjusted life years (QALYs) lost from infections were estimated, and incremental cost-effectiveness ratios (ICERs) were calculated relative to a no intervention alternative over 10 years of intervention. Separate analyses were performed for trainees and nontrainees, using the healthcare system perspective. Trainees face higher risk of exposure and likely received primary vaccination as infants. SETTING: General healthcare settings. PARTICIPANTS: Trainee and nontrainee HCP. INTERVENTIONS: Preexposure testing for antibody to hepatitis B surface antigen followed by additional vaccination for HCP without protective antibody levels; postexposure evaluation and management for HCP reporting blood or body fluid exposures RESULTS: The preexposure strategy prevents more infections and has higher costs than the postexposure strategy or no intervention. For trainees, 10-year preexposure evaluation ICERs are $832,875 and $144,457 per QALY for 95% and 68% long-term vaccine protection, respectively. Trainee 10-year postexposure evaluation ICERs are $1,146,660 and $191,579 per QALY under the 95% and 68% long-term protection assumptions, respectively. For nontrainees, 10-year ICERs are $745,739 and $1,129,286 per QALY for the preexposure and postexposure evaluation strategies, respectively. CONCLUSIONS: ICERs may inform decision makers as they decide whether the added cost of the preexposure strategy provides sufficient value in preventing infections.

Cost-effectiveness of testing hepatitis B-positive pregnant women for hepatitis B e antigen or viral load.

OBJECTIVE: To estimate the cost-effectiveness of testing pregnant women with hepatitis B (hepatitis B surface antigen [HBsAg]-positive) for hepatitis B e antigen (HBeAg) or hepatitis B virus (HBV) DNA, and administering maternal antiviral prophylaxis if indicated, to decrease breakthrough perinatal HBV transmission from the U.S. health care perspective. METHODS: A Markov decision model was constructed for a 2010 birth cohort of 4 million neonates to estimate the cost-effectiveness of two strategies: testing HBsAg-positive pregnant women for 1) HBeAg or 2) HBV load. Maternal antiviral prophylaxis is given from 28 weeks of gestation through 4 weeks postpartum when HBeAg is positive or HBV load is high (10 copies/mL or greater). These strategies were compared with the current recommendation. All neonates born to HBsAg-positive women received recommended active-passive immunoprophylaxis. Effects were measured in quality-adjusted life-years (QALYs) and all costs were in 2010 U.S. dollars. RESULTS: The HBeAg testing strategy saved $3.3 million and 3,080 QALYs and prevented 486 chronic HBV infections compared with the current recommendation. The HBV load testing strategy cost $3 million more than current recommendation, saved 2,080 QALYs, and prevented 324 chronic infections with an incremental cost-effectiveness ratio of $1,583 per QALY saved compared with the current recommendations. The results remained robust over a wide range of assumptions. CONCLUSION: Testing HBsAg-positive pregnant women for HBeAg or HBV load followed by maternal antiviral prophylaxis if HBeAg-positive or high viral load to reduce perinatal hepatitis B transmission in the United States is cost-effective.

Hepatitis B vaccine response among infants born to hepatitis B surface antigen-positive women.

PURPOSE: Annually, an estimated 25,000 infants are born to hepatitis B surface antigen (HBsAg)-positive women in the United States. Hepatitis B (HepB) vaccine and hepatitis B immune globulin (HBIG) are recommended at birth, followed by completion of vaccine series and post-vaccination serologic testing (PVST). In a large cohort of infants born to HBsAg-positive women, factors influencing vaccine response were evaluated. METHODS: Data were from HBsAg-negative infants born to HBsAg-positive women in the Enhanced Perinatal Hepatitis B Prevention Program (EPHBPP) from 2008 to 2013. Vaccine non-responders were defined as infants with antibody to hepatitis B surface antigen (anti-HBs) <10mIU/mL at PVST after receiving ≥3 vaccine doses. Multivariable analyses modeled statistically significant predictor variables associated with non-response. RESULTS: A total of 17,951 maternal-infant pairs were enrolled; 8654 HBsAg-negative infants born to HBsAg-positive mothers received ≥3 doses of vaccine with anti-HBs results. 8199 (94.7%) infants responded to a primary HepB series; 199 (94.8%) to a second series. Factors associated with anti-HBs <10mIU/mL included gestational age <37 weeks, vaccine birth dose >12h after birth, timing of final vaccine dose <6 months after birth, receipt of 3 vs. 4 vaccine doses, and PVST interval >6 months from final vaccine dose in bivariate analysis. PVST interval >6 months from final vaccine dose (OR=2.7, CI=2.0, 3.6) was significantly associated with anti-HBs <10mIU/mL; the proportion increased from 2% at 1-2 months to 21.6% at 15-16 months after the final dose. Receipt of a 4th dose improved the response rate (OR=0.5, CI=0.3, 0.8). CONCLUSIONS: Ninety-five percent of a large cohort of uninfected infants born to HBsAg-positive mothers in the United States responded to primary HepB vaccine series. The proportion of infants with anti-HBs <10mIU/mL increased with longer interval between the final vaccine dose and PVST. Optimal timing of PVST is within 1-2 months of final vaccine dose to avoid unnecessary revaccination.

Cost-effectiveness analysis of the national Perinatal Hepatitis B Prevention Program.

OBJECTIVE: To analyze the cost-effectiveness of the national Perinatal Hepatitis B Prevention Program (PHBPP) over the lifetime of the 2009 US birth cohort and compare the costs and outcomes of the program to a scenario without PHBPP support. PHBPP's goals are to ensure all infants born to hepatitis B (HepB) surface antigen-positive women receive timely postexposure prophylaxis, complete HepB vaccine series, and obtain serologic testing after series completion. METHODS: A decision analytic tree and a long-term Markov model represented the risk of perinatal and childhood infections under different prevention alternatives, and the long-term health and economic consequences of HepB infection. Outcome measures were the number of perinatal infections and childhood infections from infants born to HepB surface antigen-positive women, quality-adjusted life-years (QALYs), lifetime costs, and incremental cost per QALY gained. The health outcomes and total costs of each strategy were compared incrementally. Costs were evaluated from the health care system perspective and expressed in US dollars at a 2010 price base. RESULTS: In all analyses, the PHBPP increased QALYs and led to higher reductions in the number of perinatal and childhood infections than no PHBPP, with a cost-effectiveness ratio of $2602 per QALY. In sensitivity analyses, the cost-effectiveness ratio was robust to variations in model inputs, and there were instances where the program was both more effective and cost saving. CONCLUSIONS: This study indicated that the current PHBPP represents a cost-effective use of resources, and ensuring the program reaches all pregnant women could present additional public health benefits.

Seroprotection after recombinant hepatitis B vaccination among newborn infants: a review.

INTRODUCTION: Hepatitis B vaccination starting at birth provides a safety net for infants exposed to hepatitis B virus (HBV) during delivery or in early life. Hepatitis B vaccine is recommended in the United States for infants prior to birthing facility discharge, and within the first 12h of life for infants born to hepatitis B surface antigen (HBsAg)-positive mothers. We performed a literature review and summarized the response to recombinant hepatitis B vaccine among infants. METHODS: Studies published between 1987 and 2011 assessing seroprotection from recombinant hepatitis B vaccine starting within the first 30 days of life were eligible. Seroprotection was defined using an antibody to hepatitis B surface antigen (anti-HBs) threshold of 10mIU/mL at series completion. Infant seroprotection was compared in trial arms varying by maternal hepatitis B antigen status (e antigen [HBeAg], HBsAg), hepatitis B immune globulin (HBIG) administration, birth weight, vaccine dosage, schedule, and age at first dose. RESULTS: Forty-three studies were included. The median seroprotection proportion overall was 98% (range 52%, 100%). The final median seroprotection proportions did not vary appreciably by maternal HBsAg status, HBIG administration, or schedule. Higher compared to lower dosage resulted in earlier increases in anti-HBs but not in final seroprotection proportions. Infants with birth weights <2000g compared to ≥2000g had lower median seroprotection proportions (93% and 98%, respectively). Median seroprotection proportions were also lower when infants with birth weights <2000g were vaccinated at 0-3 days of age compared to 1 month of age or older (68% versus 95%, respectively). CONCLUSION: High levels of protection from recombinant hepatitis B vaccine are achieved in term infants vaccinated at birth, effectively preventing transmission of HBV and resultant morbidity and mortality. Implications, if any, for long-term protection are unknown for differences in responses among infants vaccinated at birth compared to ages older than 1 month.

Increased risk of acute hepatitis B among adults with diagnosed diabetes mellitus.

INTRODUCTION: The risk of acute hepatitis B among adults with diabetes mellitus is unknown. We investigated the association between diagnosed diabetes and acute hepatitis B. METHODS: Confirmed acute hepatitis B cases were reported in 2009-2010 to eight Emerging Infections Program (EIP) sites; diagnosed diabetes status was determined. Behavioral Risk Factor Surveillance System respondents residing in EIP sites comprised the comparison group. Odds ratios (ORs) comparing acute hepatitis B among adults with diagnosed diabetes versus without diagnosed diabetes were determined by multivariate logistic regression, adjusting for age, sex, and race/ethnicity, and stratified by the presence or absence of risk behaviors for hepatitis B virus (HBV) infection. RESULTS: During 2009-2010, EIP sites reported 865 eligible acute hepatitis B cases among persons aged ≥23 years; 95 (11.0%) had diagnosed diabetes. Comparison group diabetes prevalence was 9.1%. Among adults without hepatitis B risk behaviors and with reported diabetes status, the OR for acute hepatitis B comparing adults with and without diabetes was 1.9 (95% confidence interval [CI] = 1.4, 2.6); ORs for adults ages 23-59 and ≥60 years were 2.1 (95% CI = 1.6, 2.8) and 1.5 (95% = CI 0.9, 2.5), respectively. CONCLUSIONS: Diabetes was independently associated with an increased risk for acute hepatitis B among adults without HBV risk behaviors.

Medication overdoses leading to emergency department visits among children.

BACKGROUND: The high prevalence of medication use increases the potential for medication overdoses, especially among children. PURPOSE: This paper describes the burden of unintentional pediatric medication overdoses in order to target new prevention efforts. METHODS: Data were analyzed in 2007 and 2008 from the National Electronic Injury Surveillance System, collected January 1, 2004, through December 31, 2005, to estimate the number of emergency department visits resulting from unintentional medication overdoses among children aged

Outbreak of adverse reactions associated with contaminated heparin.

BACKGROUND: In January 2008, the Centers for Disease Control and Prevention began a nationwide investigation of severe adverse reactions that were first detected in a single hemodialysis facility. Preliminary findings suggested that heparin was a possible cause of the reactions. METHODS: Information on clinical manifestations and on exposure was collected for patients who had signs and symptoms that were consistent with an allergic-type reaction after November 1, 2007. Twenty-one dialysis facilities that reported reactions and 23 facilities that reported no reactions were included in a case-control study to identify facility-level risk factors. Unopened heparin vials from facilities that reported reactions were tested for contaminants. RESULTS: A total of 152 adverse reactions associated with heparin were identified in 113 patients from 13 states from November 19, 2007, through January 31, 2008. The use of heparin manufactured by Baxter Healthcare was the factor most strongly associated with reactions (present in 100.0% of case facilities vs. 4.3% of control facilities, P<0.001). Vials of heparin manufactured by Baxter from facilities that reported reactions contained a contaminant identified as oversulfated chondroitin sulfate (OSCS). Adverse reactions to the OSCS-contaminated heparin were often characterized by hypotension, nausea, and shortness of breath occurring within 30 minutes after administration. Of 130 reactions for which information on the heparin lot was available, 128 (98.5%) occurred in a facility that had OSCS-contaminated heparin on the premises. Of 54 reactions for which the lot number of administered heparin was known, 52 (96.3%) occurred after the administration of OSCS-contaminated heparin. CONCLUSIONS: Heparin contaminated with OSCS was epidemiologically linked to adverse reactions in this nationwide outbreak. The reported clinical features of many of the cases further support the conclusion that contamination of heparin with OSCS was the cause of the outbreak.