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Our goal is to review a number of methodologies which have been used to improve safety in healthcare since the release of the Institute of Medicine report in 1998 which documented that error was a significant cause of mortality in the USA. Multifaceted approaches have each led to reduction in error. Methods for error reduction included in this review are “Just Culture,” increased transparency and accountability, error reporting and investigation, second-victim programs, training in quality and safety methods, standardization and bundles, electronic health records, computerized order entry, barcode scanning, clinical decision support, predictive analytics, and situational awareness. Newer fields with the potential to improve patient safety include human factors engineering, indication-based prescribing, and Safety II. While each intervention has led to incremental improvement, continued expansion of these programs is necessary to eliminate medical error.

Background Mycobacterium porcinum is a non-tuberculous mycobacterium (NTM) identified in potable water. The identification and clinical impact of M. porcinum in patients with cystic fibrosis (CF) has not been described. In our institution, M. porcinum was isolated exclusively during hospitalization in a cluster of patients with CF. Methods Patients with CF who were hospitalized between September 2016 and September 2018 and could expectorate sputum were included, and samples were processed per institutional guidelines. Post-hospitalization and one-year clinical outcomes on those who isolated M. porcinum in respiratory cultures were reviewed. Whole genome sequencing was performed on M. porcinum isolates obtained from patients and environmental sources to identify source of acquisition. Results Review of 14 CF patients with 16 M. porcinum isolates revealed rapid time to culture positivity within 0.8 (0.04–8.0) days after admission. M. porcinum was isolated in teenagers and adults irrespective of baseline pulmonary function, body mass index, or CF genotype. Whole genome sequencing suggested all isolates belong to the same M. porcinum strain and confirmed the source of acquisition to the ice machine. Review of patients’ clinical course, including three patients who underwent lung transplantation, suggested a pseudo-outbreak with minimal clinical impact. Conclusions NTM, including M. porcinum, are ubiquitous in potable water and institutional water reservoirs. Our findings suggest M. porcinum is a transient colonizer rather than a pathogen. Challenges exist in discerning the role of NTM as a contributor of pulmonary morbidity in patients with CF, and adherence to established guidelines regarding NTM related pulmonary disease remains important.

BACKGROUND: In 2015, ACIP recommended 16–23 year olds may be vaccinated with serogroup B meningococcal (MenB) vaccine based on individual clinical decision-making (Category B). OBJECTIVE: To assess among US pediatricians (Peds) and family physicians (FPs): 1) practices regarding MenB vaccine delivery; 2) factors influencing a decision to recommend vaccine; 3) factors associated with discussing MenB vaccine at 16–18 year-old routine visits. DESIGN/METHODS: We surveyed a nationally representative sample of Peds and FPs by e-mail and internet from 10–12/2016. RESULTS: The response rate was 72% (660/916). During routine visits, 51% of Peds and 31% of FPs reported always/often discussing MenB vaccine. Among those who discussed often/always, 91% recommended vaccination; among those who never/rarely discussed, 11% recommended. 73% of Peds and 41% of FPs currently administered MenB vaccine. While many providers reported not knowing about factors influencing recommendation decisions, serogroup B meningococcal disease outbreaks (89%), disease incidence (62%), and effectiveness (52%), safety (48%), and duration of protection of MenB vaccine (39%) increased likelihood of recommending while the Category B recommendation (45%) decreased likelihood. Those somewhat/not at all aware of MenB vaccine [Risk Ratio 0.32 (95% CI 0.25–0.41)] and those practicing in an HMO [0.39 (0.18–0.87)] were less likely whereas those aware of disease outbreaks in their state [1.25 (1.08–1.45)] were more likely to initiate a discussion about MenB vaccine. CONCLUSION(S): Primary care physicians have significant gaps in knowledge about serogroup B meningococcal disease and MenB vaccine and this appears to be a major driver of the decision not to discuss the vaccines.

Palivizumab was licensed in June 1998 by the Food and Drug Administration for the reduction of serious lower respiratory tract infection caused by respiratory syncytial virus (RSV) in children at increased risk of severe disease. Since that time, the American Academy of Pediatrics has updated its guidance for the use of palivizumab 4 times as additional data became available to provide a better understanding of infants and young children at greatest risk of hospitalization attributable to RSV infection. The updated recommendations in this policy statement reflect new information regarding the seasonality of RSV circulation, palivizumab pharmacokinetics, the changing incidence of bronchiolitis hospitalizations, the effect of gestational age and other risk factors on RSV hospitalization rates, the mortality of children hospitalized with RSV infection, the effect of prophylaxis on wheezing, and palivizumab-resistant RSV isolates. This policy statement updates and replaces the recommendations found in the 2012 Red Book.

Since the last policy statement from the American Academy of Pediatrics (AAP) concerning meningococcal vaccine was published in 2011, 2 meningococcal conjugate vaccines have been licensed for use in infants (Hib-MenCY-TT and MenACWY-CRM). The Centers for Disease Control and Prevention (CDC) has published new recommendations, “Prevention and Control of Meningococcal Disease: Recommendations of the Advisory Committee on Immunization Practices,” which have been endorsed by the AAP. However, the CDC recommendations were published before licensure of MenACWY-CRM for infant use. This policy statement updates the AAP recommendations for use of meningococcal vaccines in children and adolescents. A more comprehensive review of background and technical information can be found in the CDC publication.

Sales of raw or unpasteurized milk and milk products are still legal in at least 30 states in the United States. Raw milk and milk products from cows, goats, and sheep continue to be a source of bacterial infections attributable to a number of virulent pathogens, including Listeria monocytogenes, Campylobacter jejuni, Salmonella species, Brucella species, and Escherichia coli O157. These infections can occur in both healthy and immunocompromised individuals, including older adults, infants, young children, and pregnant women and their unborn fetuses, in whom life-threatening infections and fetal miscarriage can occur. Efforts to limit the sale of raw milk products have met with opposition from those who are proponents of the purported health benefits of consuming raw milk products, which contain natural or unprocessed factors not inactivated by pasteurization. However, the benefits of these natural factors have not been clearly demonstrated in evidence-based studies and, therefore, do not outweigh the risks of raw milk consumption. Substantial data suggest that pasteurized milk confers equivalent health benefits compared with raw milk, without the additional risk of bacterial infections. The purpose of this policy statement was to review the risks of raw milk consumption in the United States and to provide evidence of the risks of infectious complications associated with consumption of unpasteurized milk and milk products, especially among pregnant women, infants, and children.

1. Richard E. McClead, MD, MHA* 2. Michael Brady, MD* 1. *The Ohio State University, Nationwide Children’s Hospital, Columbus, OH. 1. 1. Throop C, 2. Stockmeier C. SECsm & SSERsm Patient Safety Measurement System for Healthcare . Throop C, Stockmeier C. Virginia Beach, VA: Healthcare Performance Improvement, LLC; 2009. Available at: http://hpiresults.com/docs/PatientSafetyMeasurementSystem.pdf. Accessed July 18, 2016 2. 1. Kimberlin DW, 2. Brady MT, 3. Jackson MA, 4. Long SS Salmonella Infections . In: Kimberlin DW, Brady MT, Jackson MA, Long SS, eds. Red Book®: 2015 Report of the Committee on Infectious Diseases. 30th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2015:695–701 3. 1. Muething SE, 2. Goudie A, 3. Schoettker PJ, 4. et al Quality Improvement Initiative to Reduce Serious Safety Events and Improve Patient Safety Culture . Muething SE, Goudie A, Schoettker PJ, et al. Pediatrics. 2012;130(2):e423–e431 [OpenUrl][1][Abstract/FREE Full Text][2] In 1996, the Joint Commission (TJC) adopted a formal policy regarding serious adverse patient events, known as sentinel events. The purpose of this sentinel event policy was to help hospitals experiencing such events improve patient safety. TJC defines a sentinel event as a “patient safety event (not primarily related to the natural course of the patient’s illness or underlying condition) that reaches the patient and results in any of the following: 1) death; 2) permanent harm; or 3) severe temporary harm.” TJC also lists a number of other conditions that are sentinel (Table) because they require immediate investigation and response by the hospital, and these investigations and responses are subject to review by TJC for appropriateness. View this table: Table. Definition of Sentinel Events TJC considers sentinel events as patient safety events that result in patient harm. However, not all sentinel events occur because of a medical error and not all harm that results from medical errors are sentinel events. The Solutions for Patient Safety (SPS) National Children’s Network of more than 90 children’s hospitals is focused on reducing patient harm that results from adverse patient safety events. SPS uses the Healthcare Performance Improvement LLC (HPI) (Virginia Beach, VA) classification of patient safety events. In contrast to sentinel events that are identified by event type, the HPI classification is outcome-based. This classification schema is described in the white paper by Throop and Stockmeier. HPI describe 3 types of patient safety events: 1) serious … [1]: {openurl}?query=rft.jtitle%253DPediatrics.%26rft_id%253Dinfo%253Adoi%252F10.1542%252Fpeds.2011-3566%26rft_id%253Dinfo%253Apmid%252F22802607%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=ABST&journalCode=pediatrics&resid=130/2/e423&atom=%2Fpedsinreview%2F37%2F10%2F448.atom

Routine childhood immunizations against infectious diseases are an integral part of our public health infrastructure. They provide direct protection to the immunized individual and indirect protection to children and adults unable to be immunized via the effect of community immunity. All 50 states, the District of Columbia, and Puerto Rico have regulations requiring proof of immunization for child care and school attendance as a public health strategy to protect children in these settings and to secondarily serve as a mechanism to promote timely immunization of children by their caregivers. Although all states and the District of Columbia have mechanisms to exempt school attendees from specific immunization requirements for medical reasons, the majority also have a heterogeneous collection of regulations and laws that allow nonmedical exemptions from childhood immunizations otherwise required for child care and school attendance. The American Academy of Pediatrics (AAP) supports regulations and laws requiring certification of immunization to attend child care and school as a sound means of providing a safe environment for attendees and employees of these settings. The AAP also supports medically indicated exemptions to specific immunizations as determined for each individual child. The AAP views nonmedical exemptions to school-required immunizations as inappropriate for individual, public health, and ethical reasons and advocates for their elimination.

This policy statement provides recommendations for the prevention of serogroup B meningococcal disease through the use of 2 newly licensed serogroup B meningococcal vaccines: MenB-FHbp (Trumenba; Wyeth Pharmaceuticals, a subsidiary of Pfizer, Philadelphia, PA) and MenB-4C (Bexsero; Novartis Vaccines, Siena, Italy). Both vaccines are approved for use in persons 10 through 25 years of age. MenB-FHbp is licensed as a 2- or 3-dose series, and MenB-4C is licensed as a 2-dose series for all groups. Either vaccine is recommended for routine use in persons 10 years and older who are at increased risk of serogroup B meningococcal disease (category A recommendation). Persons at increased risk of meningococcal serogroup B disease include the following: (1) persons with persistent complement component diseases, including inherited or chronic deficiencies in C3, C5–C9, properdin, factor D, or factor H or persons receiving eculizumab (Soliris; Alexion Pharmaceuticals, Cheshire, CT), a monoclonal antibody that acts as a terminal complement inhibitor by binding C5 and inhibiting cleavage of C5 to C5A; (2) persons with anatomic or functional asplenia, including sickle cell disease; and (3) healthy persons at increased risk because of a serogroup B meningococcal disease outbreak. Both serogroup B meningococcal vaccines have been shown to be safe and immunogenic and are licensed by the US Food and Drug Administration for individuals between the ages of 10 and 25 years. On the basis of epidemiologic and antibody persistence data, the American Academy of Pediatrics agrees with the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention that either vaccine may be administered to healthy adolescents and young adults 16 through 23 years of age (preferred ages are 16 through 18 years) to provide short-term protection against most strains of serogroup B meningococcal disease (category B recommendation).

Newborn male circumcision is a minor surgical procedure that has generated significant controversy. Accumulating evidence supports significant health benefits, most notably reductions in urinary tract infections, acquisition of HIV and a number of other sexually transmitted infections, penile cancer, phimosis, paraphimosis, balanitis and lichen sclerosis. While circumcision, like any surgical procedure, has risks for complications, they occur in less than 1 in 500 infants circumcised and most are minor and require minimal intervention. The CDC and the American Academy of Pediatrics (AAP) believe that health benefits of circumcision outweigh the risks. For this reason, the AAP believes that parents should be allowed to make the decision concerning circumcision of their male infants after receiving non-biased information on health risks and health benefits.

Additional strategies are needed to protect children from vaccine-preventable diseases. In particular, very young infants, as well as children who are immunocompromised, are at especially high risk for developing the serious consequences of vaccine-preventable diseases and cannot be immunized completely. There is some evidence that children who become infected with these diseases are exposed to pathogens through household contacts, particularly from parents or other close family contacts. Such infections likely are attributable to adults who are not fully protected from these diseases, either because their immunity to vaccine-preventable diseases has waned over time or because they have not received a vaccine. There are many challenges that have added to low adult immunization rates in the United States. One option to increase immunization coverage for parents and close family contacts of infants and vulnerable children is to provide alternative locations for these adults to be immunized, such as the pediatric office setting. Ideally, adults should receive immunizations in their medical homes; however, to provide greater protection to these adults and reduce the exposure of children to pathogens, immunizing parents or other adult family contacts in the pediatric office setting could increase immunization coverage for this population to protect themselves as well as children to whom they provide care.

The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention and the American Academy of Pediatrics approved updated recommendations for the use of quadravalent (serogroups A, C, W-135, and Y) meningococcal conjugate vaccines (Menactra [Sanofi Pasteur, Swiftwater, PA] and Menveo [Novartis, Basel, Switzerland]) in adolescents and in people at persistent high risk of meningococcal disease. The recommendations supplement previous Advisory Committee on Immunization Practices and American Academy of Pediatrics recommendations for meningococcal vaccinations. Data were reviewed pertaining to immunogenicity in high-risk groups, bactericidal antibody persistence after immunization, current epidemiology of meningococcal disease, meningococcal conjugate vaccine effectiveness, and cost-effectiveness of different strategies for vaccination of adolescents. This review prompted the following recommendations: (1) adolescents should be routinely immunized at 11 through 12 years of age and given a booster dose at 16 years of age; (2) adolescents who received their first dose at age 13 through 15 years should receive a booster at age 16 through 18 years or up to 5 years after their first dose; (3) adolescents who receive their first dose of meningococcal conjugate vaccine at or after 16 years of age do not need a booster dose; (4) a 2-dose primary series should be administered 2 months apart for those who are at increased risk of invasive meningococcal disease because of persistent complement component (eg, C5–C9, properdin, factor H, or factor D) deficiency (9 months through 54 years of age) or functional or anatomic asplenia (2–54 years of age) and for adolescents with HIV infection; and (5) a booster dose should be given 3 years after the primary series if the primary 2-dose series was given from 2 through 6 years of age and every 5 years for persons whose 2-dose primary series or booster dose was given at 7 years of age or older who are at risk of invasive meningococcal disease because of persistent component (eg, C5–C9, properdin, factor H, or factor D) deficiency or functional or anatomic asplenia.

The purpose of this statement is to update recommendations for routine use of trivalent seasonal influenza vaccine and antiviral medications for the prevention and treatment of influenza in children. The key points for the upcoming 2011–2012 season are that (1) the influenza vaccine composition for the 2011–2012 season is unchanged from the 2010–2011 season, (2) annual universal influenza immunization is indicated, (3) a simplified dosing algorithm for administration of influenza vaccine to children 6 months through 8 years of age has been created, (4) most children presumed to have egg allergy can safely receive influenza vaccine in the office without need for an allergy consultation, and (5) an intradermal trivalent inactivated influenza vaccine has been licensed for the 2011–2012 season for use in people 18 through 64 years of age. Pediatricians, nurses, and all health care personnel have leadership roles in the prevention of influenza through vaccine use and public education. In addition, pediatricians should promptly identify influenza infections to enable rapid treatment, when indicated, to reduce childhood morbidity and mortality.

The American Academy of Pediatrics and the Centers for Disease Control and Prevention are amending previous recommendations and making additional recommendations for the use of tetanus toxoid, reduced-content diphtheria toxoid, and acellular pertussis vaccine (Tdap). Review of the results from clinical trials and other studies has revealed no excess reactogenicity when Tdap is given within a short interval after other tetanus- or diphtheria-containing toxoid products, and accrual of postmarketing adverse-events reports reveals an excellent safety record for Tdap. Thus, the recommendation for caution regarding Tdap use within any interval after a tetanus- or diphtheria-containing toxoid product is removed. Tdap should be given when it is indicated and when no contraindication exists. In further efforts to protect people who are susceptible to pertussis, the American Academy of Pediatrics and Centers for Disease Control and Prevention recommend a single dose of Tdap for children 7 through 10 years of age who were underimmunized with diphtheria-tetanus-acellular pertussis (DTaP). Also, the age for recommendation for Tdap is extended to those aged 65 years and older who have or are likely to have contact with an infant younger than 12 months (eg, health care personnel, grandparents, and other caregivers).

The purpose of this statement is to update current recommendations for routine use of trivalent seasonal influenza vaccine and antiviral medications for the prevention and treatment of influenza in children. The 2009 influenza A (H1N1) pandemic virus is expected to circulate, with infants and children at increased risk of severe illness and death. This year's trivalent seasonal influenza vaccine contains A/California/7/2009 (H1N1)-like antigen (derived from the 2009 pandemic influenza A [H1N1] virus); A/Perth/16/2009 (H3N2)-like antigen; and B/Brisbane/60/2008-like antigen. Pediatricians continue to have a leadership role in the prevention of influenza through vaccine use and public education. In addition, pediatricians should promptly identify influenza infections to enable rapid treatment of influenza, when indicated, to reduce childhood morbidity and mortality.

Routine use of the 7-valent pneumococcal conjugate vaccine (PCV7), available since 2000, has resulted in a dramatic reduction in the incidence of invasive pneumococcal disease (IPD) attributable to serotypes of Streptococcus pneumoniae contained in the vaccine. However, IPD caused by nonvaccine pneumococcal serotypes has increased, and nonvaccine serotypes are now responsible for the majority of the remaining cases of IPD occurring in children. A 13-valent pneumococcal conjugate vaccine has been licensed by the US Food and Drug Administration, which, in addition to the 7 serotypes included in the original PCV7, contains the 6 pneumococcal serotypes responsible for 63% of IPD cases now occurring in children younger than 5 years. Because of the expanded coverage provided by PCV13, it will replace PCV7. This statement provides recommendations for (1) the transition from PCV7 to PCV13; (2) the routine use of PCV13 for healthy children and children with an underlying medical condition that increases the risk of IPD; (3) a supplemental dose of PCV13 for (a) healthy children 14 through 59 months of age who have completed the PCV7 series and (b) children 14 through 71 months of age with an underlying medical condition that increases the risk of IPD who have completed the PCV7 series; (4) “catch-up” immunization for children behind schedule; and (5) PCV13 for certain children at high risk from 6 through 18 years of age. In addition, recommendations for the use of pneumococcal polysaccharide vaccine for children at high risk of IPD are also updated.

TPS7587Background: Follicular lymphoma (FL) is the most prevalent lymphoma in the US. Though outcomes have improved substantially, this disease is characterized by an incurable clinical course requ...

Palivizumab was licensed in June 1998 by the US Food and Drug Administration for prevention of serious lower respiratory tract disease caused by respiratory syncytial virus (RSV) in pediatric patients who are at increased risk of severe disease. Safety and efficacy have been established for infants born at or before 35 weeks' gestation with or without chronic lung disease of prematurity and for infants and children with hemodynamically significant heart disease. The American Academy of Pediatrics (AAP) published a policy statement on the use of palivizumab in November 1998 (American Academy of Pediatrics, Committee on Infectious Diseases and Committee on Fetus and Newborn. Pediatrics. 1998;102[5]:1211–1216) and revised it in December 2003 (American Academy of Pediatrics, Committee on Infectious Diseases and Committee on Fetus and Newborn. Pediatrics. 2003;112[6 pt 1]:1442–1446), and an AAP technical report on palivizumab was published in 2003 (Meissner HC, Long SS; American Academy of Pediatrics, Committee on Infectious Diseases and Committee on Fetus and Newborn. Pediatrics. 2003;112[6 pt 1]:1447–1452). On the basis of the availability of additional data regarding seasonality of RSV disease as well as the limitations in available data on risk factors for identifying children who are at increased risk of serious RSV lower respiratory tract disease, AAP recommendations for immunoprophylaxis have been updated in an effort to ensure optimal balance of benefit and cost from this expensive intervention. This statement updates and replaces the 2003 AAP statement and the 2006 Red Book and is consistent with the 2009 Red Book recommendations.

This statement updates and replaces the 2007 American Academy of Pediatrics statement for prevention of rotavirus gastroenteritis. In February 2006, a live oral human-bovine reassortant rotavirus vaccine (RV5 [RotaTeq]) was licensed as a 3-dose series for use in infants in the United States. The American Academy of Pediatrics recommended routine use of RV5 in infants in the United States. In April 2008, a live, oral, human attenuated rotavirus vaccine (RV1 [Rotarix]) was licensed as a 2-dose series for use in infants in the United States. The American Academy of Pediatrics recommends routine immunization of infants in the United States with rotavirus vaccine. The American Academy of Pediatrics does not express a preference for either RV5 or RV1. RV5 is to be administered orally in a 3-dose series with doses administered at 2, 4, and 6 months of age; RV1 is to be administered orally in a 2-dose series with doses administered at 2 and 4 months of age. The first dose of rotavirus vaccine should be administered from 6 weeks through 14 weeks, 6 days of age. The minimum interval between doses of rotavirus vaccine is 4 weeks. All doses should be administered by 8 months, 0 days of age. Recommendations in this statement also address the maximum ages for doses, contraindications, precautions, and special situations for administration of rotavirus vaccine.

Objective—The frequency of do-not-resuscitate (DNR) orders and hospice enrollment in children/adolescents living with acquired immune deficiency syndrome (AIDS) and followed in Pediatric AIDS Clinical Trials Group (PACTG) Study 219C was examined, and evaluated for any association with racial disparities or enhanced quality of life (QOL), particularly psychological adjustment. Methods—A cross-sectional analysis of children with AIDS enrolled in this prospective multicenter observational study between 2000 and 2005 was conducted to evaluate the incidence of DNR/hospice overall and by calendar time. Linear regression models were used to compare caregivers' reported QOL scores within 6 domains between those with and without DNR/hospice care, adjusting for confounders. Results—Seven hundred twenty-six (726) children with AIDS had a mean age of 12.9 years (standard deviation [SD] = 4.5), 51% were male, 60% black, 25% Hispanic. Twenty-one (2.9%) had either a DNR order (n = 16), hospice enrollment (n = 7), or both (n = 2). Of 41 children who died, 80% had no DNR/hospice care. Increased odds of DNR/hospice were observed for those with CD4% less than 15%, no current antiretroviral use, and prior hospitalization. No differences by race were detected. Adjusted mean QOL scores were significantly lower for those with DNR/ hospice enrollment than those without across all domains except for psychological status and health care utilization. Poorer psychological status correlated with higher symptom distress, but not with DNR/hospice enrollment after adjusting for symptoms. Conclusions—Children who died of AIDS rarely had DNR/hospice enrollment. National guidelines recommend that quality palliative care be integrated routinely with HIV care. Further research is needed to explore the barriers to palliative care and advance care planning in this population.

Background: There is equivocal evidence of in utero nucleoside reverse transcriptase inhibitor (NRTI) exposure and the occurrence of mitochondrial dysfunction (MD) in HIV-uninfected children born of HIV-infected women. Methods: The primary analysis included 1037 HIV-uninfected children born in 19912002 and enrolled in Pediatric AIDS Clinical Trials Group protocols 219/219C. Possible cases with unexplained signs of MD according to the Enquete Perinatale Francaise criteria were identified through retrospective review. Associations between overall in utero NRTI exposure, and trimester of first in utero NRTI exposure and possible MD were estimated with exact logistic regression. Results: Cases (n = 20) were significantly more likely to be male and to be born in earlier years than non-cases (n = 1017). There was no association between overal I in utero NRTI exposure and MD. In unadjusted models there were higher odds of first in utero exposure in the third trimester to lamivudine (3TC) [odds ratio (OR), 3.76 versus 3TC unexposed; 95% confidence interval (CI), 1.09-11.78] and to zidovudine (ZDV) and 3TC in combination (ZDV/3TC) (OR, 3.29 vs. ZDV/3TC unexposed; 95% CI, 0.96-10.25) among cases than noncases. When adjusted for year of birth the odds of first exposure in the third trimester to 3TC (OR, 10.57; 95% CI, 1.93-75.61) and ZDV/3TC (OR, 9.84; 95% CI, 1.77-71.68) were significantly higher among cases than non-cases. Incomplete data precluded control of possible confounding by maternal viral load and psychoactive drug use. Conclusions: Our study suggests that first exposure to 3TC or ZDV/3TC in the third trimester may be associated with the occurrence of possible MD. Further studies that rigorously assess MD and better control confounding are needed. (C) 2007 Lippincott Williams & Wilkins.

The purpose of this statement is to update recommendations for routine use of influenza vaccine in children for the 2006–2007 influenza season. The American Academy of Pediatrics recommends annual influenza immunization for (1) children with high-risk conditions who are 6 months and older; (2) healthy children 6 through 59 months of age; (3) household contacts and out-of-home caregivers of children with high-risk conditions and all healthy children younger than 5 years; and (4) health care professionals. Other children, adolescents, and adults can be immunized to decrease the impact of influenza as indicated in the Red Book: 2006 Report of the Committee on Infectious Diseases.

The purpose of this statement is to provide the rationale and recommendations for adolescent use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccines. Despite universal immunization of children with multiple doses of pediatric diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccine, pertussis remains endemic with a steady increase in the number of reported cases. Two peaks in the incidence of pertussis occur in pediatric patients: infants younger than 6 months of age who are inadequately protected by the current immunization schedule and adolescents 11 through 18 years of age whose vaccine-induced immunity has waned. Significant medical and public health resources are being consumed in postexposure management of adolescent cases, contacts, and outbreaks with little beneficial effect on individuals or the epidemiology of disease. Two Tdap products were licensed in 2005 for use in people 10 through 18 years of age (Boostrix) and 11 through 64 years of age (Adacel). The American Academy of Pediatrics recommends the following: 1. Adolescents 11 to 18 years of age should receive a single dose of Tdap instead of tetanus and diphtheria toxoids (Td) vaccine for booster immunization. The preferred age for Tdap immunization is 11 to 12 years. 2. Adolescents 11 to 18 years of age who have received Td but not Tdap are encouraged to receive a single dose of Tdap. An interval of at least 5 years between Td and Tdap is suggested to reduce the risk of local and systemic reactions; however, intervals of less than 5 years can be used, particularly in settings of increased risk of acquiring pertussis, having complicated disease, or transmitting infection to vulnerable contacts. Data support acceptable safety with an interval as short as approximately 2 years. 3. Tdap and tetravalent meningococcal conjugate vaccine (MCV4 [Menactra]) should be administered during the same visit if both vaccines are indicated. If this is not feasible, MCV4 and Tdap can be administered using either sequence. When not administered simultaneously, the American Academy of Pediatrics suggests a minimum interval of 1 month between vaccines. The rationale for this strategy is to provide direct protection of immunized adolescents. With implementation of vaccine recommendations, indirect benefitalso is likely to extend to unimmunized peers and other age groups. The strategy of universal Tdap immunization at 11 to 12 years of age is cost-effective.

Purpose. The stability of sildenafil citrate 2.5 mg/mL in two extemporaneously prepared oral suspensions stored at 4 and 25 °C was studied. Methods. Thirty 25-mg tablets of sildenafil citrate were ground to powder, and the powder was combined with a 1:1 mixture of Ora-Sweet and Ora-Plus or a 1:1 mixture of methylcellulose 1% and Simple Syrup, NF, to produce two 2.5-mg/mL suspensions. Five plastic bottles of each suspension were stored in amber plastic prescription bottles at 4 or 25 °C. Samples were collected on days 0, 7, 14, 28, 42, 56, 70, and 91 for analysis of sildenafil content by high-performance liquid chromatography; pH was also measured. Samples were visually observed against black and white backgrounds. Results. The mean concentration of sildenafil citrate exceeded 98% of the initial concentration in all samples at both temperatures throughout the 91-day study period. No changes in pH, odor, or physical appearance were observed. Conclusion. Sildenafil citrate 2.5 mg/mL in two extemporaneously compounded oral suspensions was stable for 91 days in plastic prescription bottles at 4 and 25 °C.

OBJECTIVE Nevirapine-based therapy is associated with increased frequency of adverse events among women with CD4+ cell count of 250 cells/microL or greater. We evaluated the safety of nevirapine-based antiretroviral therapy in human immunodeficiency virus (HIV)-1-infected pregnant women. METHODS We retrospectively evaluated 23 pregnancies managed with nevirapine-based regimens from July 2001 to April 2005. The incidence of adverse events was determined and analyzed by CD4+ cell count of either less than or greater than or equal to 250 cells/microL, and gestational age when nevirapine was initiated. Liver function abnormality was graded according to the National Institute of Allergy and Infectious Diseases Division of AIDS toxicity guidelines. RESULTS Five of 23 patients (21.7%) started nevirapine-based therapy after 27 weeks of gestation. All 3 cases of adverse events occurred in this group within 6 weeks of initiating therapy and with CD4+ cell count greater than 250 cells/microL. A significant difference was noted in the proportion of patients who developed toxicity while starting nevirapine in the third trimester (3/5, 60%; 95% confidence interval 14.66-94.73) compared with those starting nevirapine earlier in pregnancy (0/18, 0%; 95% confidence interval 0.0-18.53; P < .006). Two patients developed rash, eosinophilia, and liver function abnormality, with one developing clinical hepatitis and renal failure. A third patient had abnormal elevation of liver enzymes but was asymptomatic. CONCLUSION The incidence of adverse events with nevirapine may be lower than previously reported (13% versus 29%) and may be primarily noted with initiating the drug late in pregnancy. Further study of nevirapine in larger cohorts of HIV-infected pregnant women is warranted to determine the relationship between nevirapine hepatotoxicity and trimester use. LEVEL OF EVIDENCE II-3.

In histologic assessment, the absence of basal lamina is a useful feature for distinguishing invasive malignancy from benign and in situ lesions. As this feature is not possible to assess in routine H&E sections, pathologists have instead relied on histochemical and immunohistochemical stains to show components of the basal lamina such as laminin or type IV collagen. Standard image-processing software with the necessary image-processing toolbox (Matlab v5, Mathworks, Natick, MA) was used in a unique combination of color image processing and pattern recognition techniques to accentuate the collagenous stroma surrounding glands, which approximates basal lamina, in a series of benign, in situ, and invasive breast proliferations. Distinct differences in pattern were found between benign and invasive lesions, and also between in situ and malignant lesions, corresponding to that observed with type IV collagen immunostaining. Compared with immunostaining, this computer-generated method had a sensitivity of 0.96, specificity of 0.89, positive predictive value of 0.92, negative predictive value of 0.89, positive likelihood ratio of 9.1, and negative likelihood ratio of 0.042. Digital image processing serves as a less expensive and faster way of visualizing basal lamina and represents a useful adjunct to identify invasive malignancy in routinely stained sections. In addition, digital visualization of basal lamina is readily amenable to quantitative assessment, and the method provides a basis for the development of computer-based cancer diagnosis.

Neonates represent a unique and highly vulnerable patient population. Advances in medical technology that have occurred over the last few decades have improved the survival and quality of life for neonates, particularly those infants born with extreme prematurity or with congenital defects. Although immunologic immaturity and altered cutaneous barriers play some role in the vulnerability of neonates to nosocomial infections, clearly, therapeutic interventions that have proven to be lifesaving for these fragile infants also appear to be associated with the majority of infectious complications resulting in neonatal morbidity and mortality. Rates of infections in neonatal intensive care units (NICUs) have varied from 6% to 40% of neonatal patients, with the highest rates in those facilities having larger proportions of very low-birth-weight infants (birthweightor =1000 grams) or neonates requiring surgery. Efforts to protect the vulnerable NICU infants include the following: (1) optimal infection control practices, especially good hand hygiene and good nursery design; (2) prudent use of invasive interventions with particular attention to early removal of invasive devices after they are no longer essential; and (3) judicious use of antimicrobial agents, with an emphasis on targeted (narrow spectrum) rather than broad-spectrum antibiotics and appropriate indications (proven or suspected bacterial infections).

Provision of some form of child care outside of the home is certainly not a new phenomenon. In the past, most out-of-home care was provided by a relative, a friend, or someone who had a specific relationship with the family of the child. The frequency of utilization of child care centers for out-of-home care and the different formats of out-of-home care services has increased within recent decades and will vary by geographic location. Also, there is an increased utilization of temporary child care such as "mother's day out" or baby-sitting services provided at churches, grocery stores, and other places. Child care centers represent special risks for transmission of infectious agents because young children exhibit high susceptibility to many community-acquired viruses and bacteria; they lack developmental understanding required for good hygiene; and they frequently receive antibiotics (appropriately and inappropriately). Infections acquired in child care centers can significantly impact the health of the children who acquire the infection and also result in significant economic impacts on the child's family, particularly if 1 or more of the parents has to lose time from work. In the United States, it is estimated that families who have children in child care lose 13 days of work per year for all types of infections. Interventions that have proven valuable for reducing infections within child care centers include the following: (1) formal written policies for infection control within the child care center, (2) formal education of child care center staff concerning infection control practices (needs to be repeated; preferably on a recurring basis), (3) good hand hygiene by both staff and children, (4) appropriate cleaning of contaminated surfaces, (5) separation of food preparation and diaper changing, (6) exclusion of certain ill children, (7) cohorting ill children when exclusion is not possible, (8) ensuring adequate age-appropriate immunization of child care attendees and staff, and (9) optimal ratios of children to staff.

* Abbreviations: UNEP — : United Nations Environmental Programme WHO — : World Health Organization Vaccines remain one of the most effective ways to prevent infectious disease and deaths globally.1 Universal childhood immunization provides herd immunity against many infectious agents and is a policy that has achieved dramatic reductions in common childhood illnesses. Thimerosal, which contains ethyl mercury, has been used as a preservative in vaccines to prevent contamination of multidose vials from bacteria and fungi since the 1930s.2 Although there are clear neurotoxic effects of methyl mercury absorption, ethyl mercury has not been associated with those consequences. Nevertheless, before data were available on risks of thimerosal in vaccines, in 1999 the American Academy of Pediatrics and the US Public Health Service recommended moving toward removing thimerosal use in preservatives as a precautionary measure.3 Thus, thimerosal as … Address correspondence to Walter A. Orenstein, MD, 1462 Clifton Rd, Suite 446, Atlanta, GA 30322. E-mail: worenst{at}emory.edu

There is limited evidence about longer-term effects of combination antiretroviral therapy that includes protease inhibitors (PIs) on the immunological status of HIV-1-infected children. Better understanding might help to resolve questions on when to initiate treatment.The change in percentage of CD4-positive T lymphocytes (CD4%) was investigated in 1012 previously treated HIV-1-infected children (aged 0-17 years) who were enrolled in research clinics in the USA before 1996 and followed up to 2000. 702 started PI-based combination therapy. Data analyses ignored subsequent treatment changes.Among the 1012 children, the median CD4% increased from 22% to 28% between 1996, when PIs were first prescribed, and 2000. For the 702 who started PI-based therapy, the mean CD4% increase after 3 years was largest among participants with the greatest immunosuppression (15.7%, 10.6%, 5.1%, and 2.0% for participants with CD4% before therapy of5%, 5-14%, 15-24%, and25%; p0.0001). After adjustment for pre-PI CD4%, the mean increase was largest among the youngest participants (9.2%, 8.0%, and 4.3% for ages5 years, 5-9 years, and10 years; p=0.001). However, only a minority of significantly immunocompromised participants (33%, 26%, and 49% of those with pre-PI CD4% of5%, 5-14%, or 15-24%) achieved CD4% values above 25%, whereas 84% of those with pre-PI values above 25% maintained such values.Although PI-based therapy was associated with substantial improvements in CD4%, initiation before severe immunosuppression and at younger ages may be more effective for recovery or maintenance of normal CD4%. Randomised investigation of when to start combination therapy in children, particularly infants, is needed.

Two varicella-containing vaccines are licensed for use in the United States: monovalent varicella vaccine (Varivax [Merck & Co, Inc, West Point, PA]) and quadrivalent measles-mumps-rubella-varicella vaccine (MMRV) (ProQuad [Merck & Co, Inc]). It is estimated from postlicensure data that after vaccination at 12 through 23 months of age, 7 to 9 febrile seizures occur per 10 000 children who receive the MMRV, and 3 to 4 febrile seizures occur per 10 000 children who receive the measles-mumps-rubella (MMR) and varicella vaccines administered concurrently but at separate sites. Thus, 1 additional febrile seizure is expected to occur per approximately 2300 to 2600 children 12 to 23 months old vaccinated with the MMRV, when compared with separate MMR and varicella vaccine administration. The period of risk for febrile seizures is from 5 through 12 days after receipt of the vaccine(s). No increased risk of febrile seizures is seen among patients 4 to 6 years of age receiving MMRV. Febrile seizures do not predispose to epilepsy or neurodevelopmental delays later in life and are not associated with long-term health impairment. The American Academy of Pediatrics recommends that either MMR and varicella vaccines separately or the MMRV be used for the first dose of measles, mumps, rubella, and varicella vaccines administered at 12 through 47 months of age. For the first dose of measles, mumps, rubella, and varicella vaccines administered at ages 48 months and older, and for dose 2 at any age (15 months to 12 years), use of MMRV generally is preferred over separate injections of MMR and varicella vaccines.

We appreciate the opportunity to comment on the issues raised by an AstraZeneca employee regarding the revised American Academy of Pediatrics (AAP) Guidance on the use of palivizumab for respiratory syncytial virus (RSV) prophylaxis. First, we agree preterm infants experience an RSV hospitalization rate that increases with decreasing gestational age. The critical question is, “How great is the increase in risk for preterm infants relative to term infants?” In the prospective study of 132 000 infants by Hall et al1 and reproduced in Table 1 of the newly published AAP Technical Report,2 the risk of RSV hospitalization over a 6-month season for infants born at ≥37 weeks is 5.3 per 1000 (95% confidence interval [CI], 4.9–5.8). Corresponding rates for infants with gestational age ≥35, 32–34, 29–31, and

This policy statement contains provisional recommendations for use of the quadrivalent human papillomavirus vaccine in girls and women. A full policy statement from the American Academy of Pediatrics is forthcoming.

This comprehensive update of the epidemiology, transmission, manifestations, treatment, and prevention of influenza virus infection in children reviews important aspects of this infection for the pediatric health-care provider. Influenza is an extremely common epidemic infection that has a major impact in pediatrics, particularly for chronically-ill and hospitalized children. currently-available therapies and vaccines provide a modest opportunity to limit the impact of influenza on these at-risk pediatric populations. However, newer therapeutic agents and vaccine strategies may provide an opportunity in the near future to affect more significantly the influenza-related morbidity and mortality among children and adults.

Optimal management of human immunodeficiency virus type 1 (HIV-1)-infected children requires a commitment from the healthcare delivery system, healthcare providers, and affected families and caregivers. When adequate resources are available (as in most industrialised nations), an aggressive approach to early identification of at-risk populations, early diagnosis, and early and aggressive therapy is associated with marked health benefits and cost efficiency. Much of the morbidity and high costs associated with HIV-1 care are related to the management of HIV-1—related complications. Some, but not all, of these could be prevented or lessened by earlier identification of HIV-1 infection and use of antiretroviral therapy for prophylaxis against opportunistic infections. Prevention of any opportunistic infection is always preferable to treatment. The greatest optimism for those caring for HIV-1—infected children has been provided by the success of antiretroviral therapy in preventing mother-to-infant HIV-1 transmission. A goal of reducing perinatal transmission of HIV-1 in industrialised nations from 25% to 2% or less is very reasonable. The recent success in Thailand provides hope that less privileged areas of the world with high burdens of HIV-1 infection might also be capable of benefiting from intervention strategies that will be accessible to them.

The purpose of this statement is to update recommendations for routine use of seasonal influenza vaccine and antiviral medications for the prevention and treatment of influenza in children. Highlights for the upcoming 2013–2014 season include (1) this year’s trivalent influenza vaccine contains an A/California/7/2009 (H1N1) pdm09-like virus (same as 2012–2013); an A/Texas/50/2012 (H3N2) virus (antigenically like the 2012–2013 strain); and a B/Massachusetts/2/2012-like virus (a B/Yamagata lineage like 2012–2013 but a different virus); (2) new quadrivalent influenza vaccines with an additional B virus (B/Brisbane/60/2008-like virus [B/Victoria lineage]) have been licensed by the US Food and Drug Administration; (3) annual universal influenza immunization is indicated with either a trivalent or quadrivalent vaccine (no preference); and (4) the dosing algorithm for administration of influenza vaccine to children 6 months through 8 years of age is unchanged from 2012–2013. As always, pediatricians, nurses, and all health care personnel should promote influenza vaccine use and infection control measures. In addition, pediatricians should promptly identify influenza infections to enable rapid antiviral treatment, when indicated, to reduce morbidity and mortality.

* Abbreviations: AAP — : American Academy of Pediatrics CBC — : complete blood cell COFN — : Committee on Fetus and Newborn COID — : Committee on Infectious Diseases GBS — : group B streptococcal MMWR — : Morbidity and Mortality Weekly Report In 2010, the Centers for Disease Control and Prevention in collaboration with the American Academy of Family Physicians, American Academy of Pediatrics (AAP), American College of Nurse-Midwives, American College of Obstetricians and Gynecologists, and American Society for Microbiology published revised group B streptococcal (GBS) guidelines entitled “Prevention of perinatal group B streptococcal disease: revised guidelines from CDC 2010” in the Morbidity and Mortality Weekly Report ( MMWR ).1 The recommendations were endorsed by all the collaborating organizations including AAP after review by the Committee on Infectious Diseases (COID) and the Committee on Fetus and Newborn (COFN) and after AAP Board approval. In the report, a revised algorithm for “Secondary prevention of early-onset group B streptococcal disease” was included. This algorithm represented the expert opinions of the technical working group (based on current literature available at that time). In 2011, the COID and the COFN published a policy statement in Pediatrics that was in agreement with the 2010 GBS guidelines and included the same algorithm.2 In the spring of 2012, the COFN published a clinical report containing management guidelines entitled “Management of neonates with suspected or proven early-onset neonatal sepsis.”3 The 2012 COFN document includes guidance on laboratory evaluations and treatment duration, which were not addressed in the 2010 GBS prevention guidelines. The algorithms at the end of the COFN report differed from those in the 2010 guidelines published in the MMWR .1 The discordance in the algorithms prompted questions by the pediatric community as to which recommendations … Address correspondence to Michael T. Brady, MD, 700 Children’s Dr, AB 7048, Columbus, OH 43205. E-mail: michael.brady{at}nationwidechildrens.org