Opioid Tapering in Fibromyalgia Patients: Experience from an Interdisciplinary Pain Rehabilitation Program.

OBJECTIVE: Despite current guideline recommendations against the use of opioids for the treatment of fibromyalgia pain, opioid use is reported in approximately 30% of the patient population. There is a lack of information describing the process and results of tapering of chronic opioids. The purpose of this study is to describe opioid tapering and withdrawal symptoms in fibromyalgia patients on opioids. DESIGN, SETTING, AND SUBJECTS: This retrospective research study included a baseline analysis of 159 patients consecutively admitted to the Mayo Clinic Pain Rehabilitation Center from 2006 through 2012 with a pain diagnosis of fibromyalgia completing a 3-week outpatient interdisciplinary pain rehabilitation program. Opioid tapering analysis included 55 (35%) patients using daily opioids. METHODS: Opioid tapering was individualized to each patient based on interdisciplinary pain rehabilitation team determination. Opioid withdrawal symptoms were assessed daily, utilizing the Clinical Opioid Withdrawal Scale. RESULTS: Patients taking daily opioids had a morphine equivalent mean dose of 99 mg/day. Patients on < 100 mg/day were tapered off over a mean of 10 days compared with patients on > 200 mg/day over a mean of 28 days (P < 0.001). Differences in peak withdrawal symptoms were not statistically significant based on the mean equivalent dose (P = 22). Patients taking opioids for <2 years did not differ in length of tapering (P =0.63) or peak COWS score (P =0.80) compared with >2 years duration. Patients had significant improvements in pain-related measures including numeric pain scores, depression catastrophizing, health perception, interference with life, and perceived life control at program completion. CONCLUSION: Fibromyalgia patients on higher doses of opioids were tapered off over a longer period of time but no differences in withdrawal symptoms were seen based on opioid dose. Duration of opioid use did not affect the time to complete opioid taper or withdrawal symptoms. Despite opioid tapering, pain-related measures improved at the completion of the rehabilitation program.

Palatability, adherence and prescribing patterns of antiretroviral drugs for children with human immunodeficiency virus infection in Canada.

PURPOSE: To assess the impact of perceived palatability of antiretroviral drugs on adherence to therapy of children infected by human immunodeficiency virus and on prescribing patterns by their caring physicians. DESIGN: Two arms--retrospective chart review and a cross-sectional survey. SETTING: Tertiary-care pediatric human immunodeficiency virus clinic during a 17-year period. PARTICIPANTS: Children with human immunodeficiency virus infection and physicians actively caring for children with human immunodeficiency virus infection in seven provinces in Canada were surveyed regarding their perception of the palatability of 8-liquid and 15 non-liquid antiretroviral medications and its effect on drug selection. MAIN OUTCOME MEASURE: Effect of taste preferences of antiretroviral drugs on adherence to treatment by infected children and on drug selection by their caring physicians. RESULTS: Forty of 119 children (34%) refused at least once to an antiretroviral medication. In 5%, treatment was discontinued because of poor palatability. Ritonavir was the least palatable drug (50% of children; p = 0.01). Ritonavir use (OR 4.80 [95%CI 1.34-17.20]) and male gender (OR 7.25 [95%CI 2.30-22.90]) were independent predictors of drug discontinuation because of poor taste. Physicians also perceived liquid ritonavir as the least palatable (p = 0.01) and the most likely to be discontinued (p = 0.01). However, they commonly prescribed it as first-line therapy (p = 0.06). CONCLUSIONS: A third of children infected with human immunodeficiency virus fail to adhere to their treatment because of poor drug taste. Physicians are aware of that, but this does not prevent them from selecting the least palatable drugs as first-line therapy.

Dietary soy supplement on fibromyalgia symptoms: a randomized, double-blind, placebo-controlled, early phase trial.

Most patients with fibromyalgia use complementary and alternative medicine (CAM). Properly designed controlled trials are necessary to assess the effectiveness of these practices. This study was a randomized, double-blind, placebo-controlled, early phase trial. Fifty patients seen at a fibromyalgia outpatient treatment program were randomly assigned to a daily soy or placebo (casein) shake. Outcome measures were scores of the Fibromyalgia Impact Questionnaire (FIQ) and the Center for Epidemiologic Studies Depression Scale (CES-D) at baseline and after 6 weeks of intervention. Analysis was with standard statistics based on the null hypothesis, and separation test for early phase CAM comparative trials. Twenty-eight patients completed the study. Use of standard statistics with intent-to-treat analysis showed that total FIQ scores decreased by 14% in the soy group (P = .02) and by 18% in the placebo group (P < .001). The difference in change in scores between the groups was not significant (P = .16). With the same analysis, CES-D scores decreased in the soy group by 16% (P = .004) and in the placebo group by 15% (P = .05). The change in scores was similar in the groups (P = .83). Results of statistical analysis using the separation test and intent-to-treat analysis revealed no benefit of soy compared with placebo. Shakes that contain soy and shakes that contain casein, when combined with a multidisciplinary fibromyalgia treatment program, provide a decrease in fibromyalgia symptoms. Separation between the effects of soy and casein (control) shakes did not favor the intervention. Therefore, large-sample studies using soy for patients with fibromyalgia are probably not indicated.

Prenatal HIV testing: women's experiences of informed consent in Toronto, Ontario.

OBJECTIVE: All Canadian jurisdictions have human immunodeficiency virus (HIV) testing programs requiring that clinicians discuss HIV testing with all pregnant women and seek their consent to be tested. Our goal was to evaluate how the informed consent process was being carried out in Ontario. METHODS: Between November 2002 and February 2004, women in postpartum wards in three Toronto teaching hospitals were invited to participate in the study. A structured questionnaire was administered on the ward, medical records were reviewed, and data from the Central Public Health Laboratory were examined to verify whether or not the women had been tested. RESULTS: Of 446 women invited, 299 (67%) participated. All except one participant had at least one prenatal visit, and 92% had more than five visits. Seventy-four percent of participants recalled a clinician talking to them about testing, and 70% of these felt that they were given the option to refuse the test. Twenty-one women overall (7%) believed that they were not tested during pregnancy or were not certain whether they had been tested or not, but actually had been tested. Women who felt that their care provider did not have an opinion about whether they should undergo testing were more likely to decline. Eighty-six percent were completely satisfied with the testing experience. CONCLUSION: Informed consent for prenatal HIV testing is generally being obtained in a manner consistent with provincial guidelines. Our findings raise concern, however, that a significant number of women are not offered testing or in some cases are tested without their consent. Increases in testing rates could be achieved by offering the test to all women and emphasizing that carrying out testing is a recommended part of medical care.

Consideration for routine outpatient pediatric cochlear implantation: A retrospective chart review of immediate post-operative complications.

INTRODUCTION: Cochlear implantation is well accepted as the treatment of choice for prelingual deafness in children [1]. However, the safety of routinely performing this procedure on an outpatient basis is debated. We aim to assess immediate postoperative complications that would affect a surgeon's decision to perform pediatric cochlear implantation on an outpatient basis. METHODS: A retrospective chart review was conducted which included all children 17 years old or younger who underwent cochlear implantation from 2004 to 2014 in a private neurotology practice. The immediate postoperative complication rates and types of complications were then examined. RESULTS: A total of 579 cochlear implants were placed in children ages 1-17 years old from 2004 to 2014. The most common complications were nausea/vomiting and dizziness/imbalance. The odds ratio of developing complications in the group ages 1-3 years old versus all other age patients was found to be statistically insignificant (OR 0.90, 95% CI 0.61 to 1.32, p = 0.58). The odds ratio of developing a complication after bilateral implantation compared to unilateral implantation was statistically significant (OR 1.96, 95% CI 1.18 to 3.28, p = 0.01). There was no difference in complication rates when comparing lateral wall and perimodiolar insertions. A total of 6 of 579 (1%) cochlear implants resulted in a complication requiring unplanned medical attention. CONCLUSIONS: Overall, this series offers a decade of experience in pediatric cochlear implantation that shows a low incidence of the need for unplanned medical attention in the immediate postoperative period. The most common complication seen is Post-operative nausea and vomiting (PONV) that appears to be amenable to outpatient management even in the youngest populations. This supports providers routinely performing pediatric cochlear implantation on an outpatient basis.

Medical records and women's self-report are not reliable sources for determining whether prenatal HIV testing was done.

OBJECTIVE: To determine whether medical records and the self-report of a postpartum patient provide reliable information about whether or not prenatal HIV testing has been done. METHODS: Women on the postpartum wards at three Toronto teaching hospitals who gave informed consent were included in the study. The presence or absence of prenatal HIV testing was determined by interviews with postpartum women, review of hospital charts, and search of the Public Health Provincial Laboratory and Prenatal Testing databases. RESULTS: Two hundred ninety-nine women were enrolled. All had had at least one prenatal visit, and 92% had copies of prenatal records in their hospital charts. Health records and patient reports were both unreliable for determining who had and who had not had HIV testing. HIV status was documented on 55% of the charts; on 46% it was noted that testing was performed, and on 46% there was documentation of pre& or post&test counselling. In interviews, 73% of the women reported having an HIV test during this pregnancy. Using the laboratory databases as the gold standard of whether testing had truly been done, medical record sensitivity and specificity were 65% and 62% respectively, and self-report sensitivity and specificity were 87% and 52% respectively. Using medical records resulted in an underestimation and self-reports an overestimation of the number of women who had been tested. CONCLUSIONS: Both medical records and patient self-report are unreliable at the time of labour and delivery for determining whether or not a woman has been tested for HIV in pregnancy. Clinical and public health decisions may therefore be compromised by a lack of accurate testing information at the bedside.

Insulin sensitivity and beta-cell function in protease inhibitor-treated and -naive human immunodeficiency virus-infected children.

Previous pediatric studies have failed to demonstrate a clear association between protease inhibitor (PI) therapy and abnormal glucose homeostasis in HIV-infected children. To define more precisely the impact of PI therapy on glucose homeostasis in this population, we performed the insulin-modified frequent-sampling iv glucose tolerance test on 33 PI-treated and 15 PI-naive HIV-infected children. Other investigations included fasting serum lipids; glucose, insulin, and C-peptide; single-slice abdominal computed tomography; and, in a subset of PI-treated children, an oral glucose tolerance test. There were no differences between the two groups with respect to fasting serum insulin or C-peptide, homeostatic model assessment insulin resistance, or quantitative insulin sensitivity check index. The mean insulin sensitivity index of PI-treated and PI-naive children was 6.93 +/- 6.37 and 10.58 +/- 12.93 x 10(-4)min(-1) [microU/ml](-1), respectively (P = 0.17). The mean disposition index for the two groups was 1840 +/- 1575 and 3708 +/- 3005 x 10(-4)min(-1) (P = 0.013), respectively. After adjusting for potential confounding variables using multiple regression analysis, the insulin sensitivity index and disposition index of PI-treated children were significantly lower than that of PI-naive children (P = 0.01 for both). In PI-treated but not PI-naive children, insulin sensitivity correlated inversely with visceral adipose tissue area (r = -0.43, P = 0.01) and visceral to sc adipose tissue ratio (r = -0.49, P = 0.004). Mildly impaired glucose tolerance was noted in four of 21 PI-treated subjects tested. Our results demonstrate not only that PI therapy reduces insulin sensitivity in HIV-infected children but also that it impairs the beta-cell response to this reduction in insulin sensitivity and, in a subset of children, leads to the development of impaired glucose tolerance. The presence of insulin resistance, dyslipidemia, and the significant correlation of reduced insulin sensitivity with increased visceral adipose tissue content suggest that PI-containing highly active antiretroviral therapy is associated with the emergence of early features of a metabolic syndrome-like phenotype.

Serum lipids, glucose homeostasis and abdominal adipose tissue distribution in protease inhibitor-treated and naive HIV-infected children.

OBJECTIVE: To determine the extent and degree of abnormalities of serum lipids, glucose homeostasis and abdominal adipose tissue distribution in protease inhibitor (PI)-treated and PI-naive HIV-infected children. DESIGN: A cross-sectional study involving HIV-infected children, 3-18 years of age, in a paediatric tertiary care centre. MAIN OUTCOME MEASURES: Total, HDL and LDL-cholesterol, triglycerides, glucose, insulin, proinsulin and C-peptide were determined in the fasting state. Insulin resistance was assessed using the homeostatic model assessment-insulin resistance (HOMA-IR). Abdominal adipose tissue distribution was determined by single-slice computed tomography at the umbilical level. RESULTS: Thirty PI-treated and 20 PI-naive children were evaluated (76% prepubertal). PI-treated children had significantly higher total cholesterol (P = 0.0021), LDL-cholesterol (P = 0.019) and triglycerides (P = 0.0018). Serum glucose, insulin, proinsulin and C-peptide, the insulin : glucose ratio, HOMA-IR and abdominal adipose tissue distribution were similar in the two groups. Clinical and immunological HIV categories, viral load, CD4 cell count and stavudine therapy were not significantly associated with serum lipids, insulin resistance or abdominal adipose tissue distribution. The predictor variable most strongly associated with fasting serum insulin and HOMA-IR was the Tanner stage. Age was the most significant predictor variable of the visceral : subcutaneous adipose tissue ratio. CONCLUSION: In this cohort of predominantly prepubertal HIV-infected children, PI therapy was associated with an atherogenic dyslipidemia but not with insulin resistance or abnormal abdominal adipose tissue distribution. The results suggest that children, particularly prepubertal children, are less susceptible than adults to PI-induced changes in glucose homeostasis and abdominal adipose tissue distribution.

Nosocomial transmission of congenital tuberculosis in a neonatal intensive care unit.

Congenital tuberculosis is uncommon, and nosocomial transmission from a congenitally infected infant to another infant has not been reported in the English literature. We report an investigation of 2 infants with tuberculosis who were cared for in the same neonatal intensive care unit. Isolates from both infants were genetically indistinguishable. Transmission between the 2 infants was likely due to contaminated respiratory equipment.

Response to a protease-inhibitor (ritonavir)-containing combination antiretroviral regimen in HIV-infected children.

INTRODUCTION: The number of antiretroviral agents available for children who are failing existing therapy is limited. Data are lacking on the use of various combination regimens and the resulting viral load dynamics in such children. METHODS: Between March 1998 and March 2000, HIV-infected children younger than 18 years of age were studied in an open trial. The study regimen included ritonavir, with at least two drugs to which the virus was known or presumed to be sensitive. Subjects were ritonavir-naive and were included if they had high viral loads while receiving antiretroviral therapy. Patients had clinical assessments, CD4 counts and viral load monitoring. RESULTS: Fifteen antiretroviral-experienced HIV-infected children were enrolled. Approximately 87% (13 of 15) had perinatally-acquired HIV; median age was 7.9 years (range 1.6 to 14.8). At enrolment, the median CD4 count was 557 cells/mm(3) (range 57 to 1702) and the median viral load was 72,600 copies/mL (range 3626 to 796,440). The majority of children (73.3%) had increases in CD4 counts within 12 weeks. During this period, the median increase in CD4 counts over baseline was 30.0%. Approximately 73% (eight of 11) of subjects with initial improvements in CD4 counts had sustained increases at 32 to 48 weeks. Over the first 12 weeks, 60% (nine of 15) had greater than 0.5 log(10) decreases in viral load. The improvement was sustained in 88.9% (eight of nine) of these patients at 32 to 48 weeks. Three patients discontinued therapy due to taste aversion. CONCLUSIONS: Among pediatric patients with high viral loads while on existing therapy, the ritonavir-containing regimen was generally well tolerated. In a significant proportion of patients, modification of therapy was associated with sustained improvements in viral loads and CD4 counts over 32 to 48 weeks.

High uptake of HIV testing in pregnant women in Ontario, Canada.

In 1999, Ontario implemented a policy to offer HIV counseling and testing to all pregnant women and undertook measures to increase HIV testing. We evaluated the effectiveness of the new policy by examining HIV test uptake, the number of HIV-infected women identified and, in 2002, the HIV rate in women not tested during prenatal care. We analyzed test uptake among women receiving prenatal care from 1999 to 2010. We examined HIV test uptake and HIV rate by year, age and health region. In an anonymous, unlinked study, we determined the HIV rate in pregnant women not tested. Prenatal HIV test uptake in Ontario increased dramatically, from 33% in the first quarter of 1999 to 96% in 2010. Test uptake was highest in younger women but increased in all age groups. All health regions improved and experienced similar test uptake in recent years. The HIV rate among pregnant women tested in 2010 was 0.13/1,000; in Toronto, the rate was 0.28 per 1,000. In the 2002 unlinked study, the HIV rate was 0.62/1,000 among women not tested in pregnancy compared to 0.31/1,000 among tested women. HIV incidence among women who tested more than once was 0.05/1,000 person-years. In response to the new policy in Ontario, prenatal HIV testing uptake improved dramatically among women in all age groups and health regions. A reminder to physicians who had not ordered a prenatal HIV test appeared to be very effective. In 2002, the HIV rate in women who were not tested was twice that of tested women: though 77% of pregnant women had been tested, only 63% of HIV-infected women were tested. HIV testing uptake was estimated at 98% in 2010.

Perinatal exposure to antiretroviral therapy is associated with increased blood mitochondrial DNA levels and decreased mitochondrial gene expression in infants.

BACKGROUND: The effects of perinatal antiretroviral therapy (ART) on infant mitochondrial function are not well known. We compared blood mitochondrial DNA (mtDNA) levels and mtDNA gene expression (mtRNA) in human immunodeficiency virus (HIV)-uninfected, ART-exposed infants born to HIV-positive mothers with mtDNA levels and mtDNA gene expression in control infants born to uninfected women. METHODS: In this prospective cohort study, longitudinal mtDNA:nuclear DNA and mtRNA:beta-actin mRNA ratios were compared in blood samples obtained at various time points from birth to 8 months, using generalized estimating equation linear regression models. RESULTS: Log(10) mtDNA levels at birth were higher in ART-exposed infants, compared with levels in control infants, although the difference did not reach statistical significance (P = .07 for comparison of samples obtained 0-3 days after birth). ART-exposed infants' mtDNA levels increased further during the zidovudine prophylaxis period-from age 4 days to age 6 weeks-(P = .001) and remained significantly higher than the levels observed in control infants until the end of the study. In contrast, log(10) mtRNA levels at birth were lower in ART-exposed infants than in control infants (P = .03), but were not statistically different later. CONCLUSIONS: When control infants and ART-exposed infants were compared, the mtDNA level was increased but mitochondrial gene expression was decreased in ART-exposed infants. These differences persisted after zidovudine was discontinued, suggesting that changes in mitochondrial proliferation and/or expression take place during and after ART exposure. These changes are likely the effects of the antiretroviral drugs on mitochondria. The clinical relevance and long-term impact of these alterations must be studied.

Randomized controlled trial of short-term withdrawal of i.v. immunoglobulin therapy for selected children with human immunodeficiency virus infection.

BACKGROUND: The aim of the present paper was to determine whether monthly i.v. immunoglobulin (IVIG) could be safely discontinued in antiretroviral-treated human immunodeficiency virus (HIV)-infected children. METHODS: In a double-blind cross-over trial, children < or =18 years with HIV infection, well controlled on antiretroviral therapy, were randomized to alternating courses of 3 consecutive months of IVIG (400 mg/kg once a month) and 3 consecutive months of placebo for 1 year. The primary outcome was days of fever per month. Secondary outcomes were frequency of serious infections, changes in HIV viral load (VL), CD4+ counts and IgG levels. RESULTS: Fifteen children were enrolled. Using the revised pediatric HIV clinical classification system of the Centers for Disease Control and Prevention, eight were severely symptomatic (C), four were moderately symptomatic (B) and three were mildly symptomatic (A). There were no statistically significant outcome measures. The mean number of days of fever per month with IVIG versus placebo was 0.55 days versus 1.48 days (P = 0.11). The difference was 0.9 days (95% confidence interval: +2.05 to -0.25). There were no serious infections in either period. For the IVIG versus placebo periods, mean CD4 counts were 970 cells/microL versus 906 cells/microL (P = 0.12), VL 2.90 log(10) copies/mL versus 2.82 log(10) copies/mL (P = 0.70) and IgG levels were 17.41 g/L versus 16.6 g/L (P = 0.13). CONCLUSION: In antiretroviral-treated HIV-infected children short-term withdrawal of monthly IVIG was not associated with a significant increase in incidence of infections or a decline in immunologic function (CD4 count, viral load and IgG levels). These results suggest that monthly IVIG can be safely discontinued in HIV-infected children who are clinically stable and receiving combination antiretroviral therapy.

Evaluation and treatment of the human immunodeficiency virus-1--exposed infant.

In developed countries, care and treatment are available for pregnant women and infants that can decrease the rate of perinatal human immunodeficiency virus type 1 (HIV-1) infection to 2% or less. The pediatrician has a key role in prevention of mother-to-child transmission of HIV-1 by identifying HIV-exposed infants whose mothers' HIV infection was not diagnosed before delivery, prescribing antiretroviral prophylaxis for these infants to decrease the risk of acquiring HIV-1 infection, and promoting avoidance of HIV-1 transmission through human milk. In addition, the pediatrician can provide care for HIV-exposed infants by monitoring them for early determination of HIV-1 infection status and for possible short- and long-term toxicities of antiretroviral exposure, providing chemoprophylaxis for Pneumocystis pneumonia, and supporting families living with HIV-1 infection by providing counseling to parents or caregivers.

Adverse outcomes in primary hemophagocytic lymphohistiocytosis.

PURPOSE: Hemophagocytic lymphohistiocytosis (HLH) is a rare condition characterized by abnormal proliferation of macrophages. Although the mortality rate in children diagnosed with primary HLH is high, little has been described about the nature of adverse events. This review evaluates unfavorable events in children with primary HLH to suggest methods of improving outcomes. METHODS: Charts of patients who met diagnostic criteria for primary HLH at the Hospital for Sick Children between January 1985 and June 2000 were retrospectively reviewed. The primary outcome measure was an adverse event, defined as death, the subsequent diagnosis of malignancy, or developmental delay. RESULTS: Twenty children were diagnosed with primary HLH. The median age at diagnosis was 6.5 months (range 1-78 months). Nineteen children received chemotherapy and two underwent matched sibling donor bone marrow transplantation. Of the 20 children, 12 (60%) died. These deaths were attributed to progressive HLH in 4 cases and invasive infection in 8 cases. These infections consisted of disseminated cytomegalovirus infection (n = 1), sepsis (n = 1), and invasive fungal infections (n = 6). Eight children survived. Two were subsequently diagnosed with malignancy. Two others were found to have significant developmental delay. CONCLUSIONS: The overall mortality rate was 60% in our series of 20 children with primary HLH; 50% of deaths were directly attributable to invasive fungal infection. Developmental delay and the diagnosis of malignancy are important events in this cohort.

Epidemiologic modeling to evaluate prevention of mother-infant HIV transmission in Ontario.

OBJECTIVES: To evaluate the impact of the Ontario HIV screening program to reduce mother-infant HIV transmission, this study estimated the proportion of preventable transmissions that were prevented. METHODS: Using an iterative spreadsheet model, incidences of HIV infection, AIDS, and AIDS mortality in Ontario women were estimated by exposure category. The number of HIV-infected infants born to HIV-infected mothers was then estimated from conception and abortion rates of HIV-infected women of childbearing age and surveillance data. Finally, the proportion of HIV-infected mothers who received antiretroviral prophylaxis (ARP) was assessed. RESULTS: HIV prevalence in 2001 among women of childbearing age was 1.05 per 1000. From 1984-2001, 764 infants were born to HIV-infected mothers and 180 were infected. From mid-1994-2001, 214 (39%) of the estimated 544 HIV-infected mothers were diagnosed; almost all received ARP. Of 118 preventable infections among infants born in this period, 39 (33%) were prevented. In 2001, only 46% of preventable infections were prevented and 11 preventable transmissions occurred. CONCLUSIONS: HIV prevalence among women in Ontario increased >4-fold from 1990 to 2001. Fewer than half of HIV-infected mothers received ARP and preventable HIV infections continue to occur. Measures to further increase uptake of prenatal HIV screening must be instituted.

Children hospitalized with severe acute respiratory syndrome-related illness in Toronto.

OBJECTIVE: An outbreak of severe acute respiratory syndrome (SARS) occurred in the greater Toronto area between February and June 2003. We describe the clinical, laboratory, and epidemiologic features of children who were admitted to the Hospital for Sick Children, Toronto, with a presumptive diagnosis of suspect or probable SARS. METHODS: A prospective investigational study protocol was established for the management of children with a presumptive diagnosis of suspect or probable SARS. All were ultimately classified as having probable SARS, suspect SARS, or another cause on the basis of their epidemiologic exposure, clinical and radiologic features, and results of microbiologic investigations. RESULTS: Twenty-five children were included; 10 were classified as probable SARS and 5 were classified as suspect SARS, and in 10 another cause was identified. The exposure consisted of direct contact with at least 1 adult probable SARS case in 11 children, travel from a World Health Organization-designated affected area in Asia in 9 children, and presence in a Toronto area hospital in which secondary SARS spread had occurred in 5 children. The predominant clinical manifestations of probable cases were fever, cough, and rhinorrhea. With the exception of 1 teenager, none of the children developed respiratory distress or an oxygen requirement, and all made full recoveries. Mild focal alveolar infiltrates were the predominant chest radiograph abnormality. Lymphopenia; neutropenia; thrombocytopenia; and elevated alanine aminotransferase, aspartate aminotransferase, and creatine kinase were present in some cases. Nasopharyngeal swab specimens were negative for the SARS-associated coronavirus by an in-house reverse transcriptase-polymerase chain reaction in all 25 children. CONCLUSIONS: Our results indicate that SARS is a relatively mild and nonspecific respiratory illness in previously healthy young children. The presence of fever in conjunction with a SARS exposure history should prompt one to consider SARS as a possible diagnosis in children irrespective of the presence or absence of respiratory symptoms. Reverse-transcriptase polymerase chain reaction analysis of nasopharyngeal specimens seems to be of little utility for the diagnosis of SARS during the early symptomatic phase of this illness in young children.