Multiscale Microstructure, Composition, and Stability of Surfactant/Polymer Foams.

Inclusion of polymer additives is a known strategy to improve foam stability, but questions persist about the amount of polymer incorporated in the foam and the resulting structural changes that impact material performance. Here, we study these questions in sodium dodecyl sulfate (SDS)/hydroxypropyl methylcellulose (HPMC) foams using a combination of flow injection QTOF mass spectrometry and small-angle neutron scattering (SANS) measurements leveraging contrast matching. Mass spectrometry results demonstrate polymer incorporation and retention in the foam during drainage by measuring the HPMC-to-SDS ratio. The results confirm a ratio matching the parent solution and stability over the time of our measurements. The SANS measurements leverage precise contrast matching to reveal detailed descriptions of the micellar structure (size, shape, and aggregation number) along with the foam film thickness. The presence of HPMC leads to thicker films, correlating with increased foam stability over the first 15-20 min after foam production. Taken together, mass spectrometry and SANS present a structural and compositional picture of SDS/HPMC foams and an approach amenable to systematic study for foams, gathering mechanistic insights and providing formulation guidance for rational foam design.

MCR Approach Revealing Protein, Water, and Lipid Depth Profile in Atopic Dermatitis Patients' Stratum Corneum via in Vivo Confocal Raman Spectroscopy.

Confocal Raman has been widely used for measuring the water concentration profile inside skin to calculate clinical end points, such as stratum corneum thickness. In this article, multivariate curve resolution was applied to resolve the pure components contained in high frequency (2500-4000 cm-1) in vivo confocal Raman data. Three components were identified by comparing with reference spectra of materials in skin. These three components are water, protein, and lipid. The score values associated with these three components were transformed to mass ratio by leveraging the response factors for protein and lipid in a calibration model utilizing the pure material spectra. The concentration profiles for protein and lipid as a function of depth across the stratum corneum are utilized as new clinical end points. Results from an in vivo study with individuals who experience atopic dermatitis symptoms successfully demonstrated a statistical difference between Raman spectra from nonlesion and lesion skin sites. Trends in the depth profiles of the skin components are consistent with previous literature reports.

Lack of association of Guillain-Barré syndrome with vaccinations.

BACKGROUND: Guillain-Barré syndrome (GBS) is an acute polyradiculoneuropathy, thought to be an autoimmune process. Although cases of GBS have been reported following a wide range of vaccines, a clear association has only been established with the 1976 H1N1 inactivated influenza vaccine. METHODS: We identified hospitalized GBS cases from Kaiser Permanente Northern California (KPNC) from 1995 through 2006. The medical record of each suspected case was neurologist-reviewed according to the Brighton Collaboration GBS case definition; only confirmed cases were included in the analyses, and cases of Miller Fisher syndrome were excluded. Using a case-centered design, we compared the odds of vaccination in the 6 and 10 weeks prior to onset of GBS to the odds of vaccination during the same time intervals in all vaccinated individuals in the entire KPNC population. RESULTS: We confirmed 415 incident cases of GBS (including Brighton levels 1, 2, and 3) during the study period (>30 million person-years). Incidence peaked during the winter months. The odds ratio of influenza vaccination within a 6-week interval prior to GBS, compared with the prior 9 months, was 1.1 (95% confidence interval [CI], .4-3.1). The risk in the 6-week interval compared to the prior 12 months for tetanus diphtheria combination, 23-valent pneumococcal polysaccharide, and for all vaccines combined was 1.4 (95% CI, .3-4.5), 0.7 (95% CI, .1-2.9), and 1.3 (95% CI, .8-2.3), respectively. CONCLUSIONS: In this large retrospective study, we did not find evidence of an increased risk of GBS following vaccinations of any kind, including influenza vaccination.

Immunization and Bell's palsy in children: a case-centered analysis.

Bell's palsy (BP) is an acute and idiopathic paralysis of the facial nerve, with an estimated incidence ranging from 11.5 per 100,000 person-years to 53.3 per 100,000 person-years in different populations. BP has been reported following immunization with inactivated trivalent influenza vaccine (TIV) and hepatitis B virus (HBV) vaccine. Epidemiologic studies examining this association among children are lacking. From 2001 through 2006, all children aged ≤18 years diagnosed with BP within the Kaiser Permanente Northern California population were identified using International Classification of Diseases, Ninth Revision, code 351.0. All electronically identified cases were reviewed and adjudicated by an otolaryngologist (n = 233). Using a case-centered approach, the authors examined the risk of BP during 3 risk intervals. Immunization with TIV (odds ratio (OR) = 0.7, 95% confidence interval (CI): 0.2, 2.8), HBV vaccine (OR = 0.8, 95% CI: 0.2, 2.4), or any vaccine (treating all vaccines combined; OR = 0.9, 95% CI: 0.6, 1.4) was not associated with increased risk of BP 1-28 days after immunization. Similarly, no association was found between vaccines and BP during the periods 1-14 and 29-56 days following immunization. Results of this study suggest that there is no association between immunization and BP in children.

Epidemiologic and clinical features of Bell's palsy among children in Northern California.

BACKGROUND: Bell's palsy (BP) is an acute, idiopathic, and usually unilateral paralysis of the facial nerve. Large population-based studies of BP among children are lacking. We determined epidemiologic and clinical features of BP among children enrolled in a large integrated health care delivery system. METHODS: From 2001 through 2006, all children ≤18 years of age diagnosed with BP within the population of Kaiser Permanente Northern California were identified using the International Classification of Diseases, 9th Revision, code 351.0. All cases were adjudicated by an otolaryngologist and categorized as definite, probable, or rejected. Using chart abstraction forms, epidemiologic and clinical features of BP were determined. RESULTS: Of a total of 977 cases initially identified, 822 (84.1%) were adjudicated as a definite or probable case. The overall incidence rate of BP during the study period was 18.8 (95% CI 17.6-20.2) per 100,000 person-years. The incidence rate increased by age and was higher in females than males across all age strata. There was no evidence for a seasonal pattern in the occurrence of BP (p for trend = 0.81). CONCLUSIONS: BP among children may be more common than previously recognized.

Autobiographical Therapeutic Performance as a Means of Improving Executive Functioning in Traumatized Adults.

This article describes the pilot project Shadows & Light Within: Untold Stories-a two-phase, multi-partner community-based project that explores the hypothesis that Autobiographical Therapeutic Performance can help traumatized individuals to improve executive functioning. A group of 10 individuals ranging in age from 32 to 69, with lived experiences at the intersection of trauma, mental health, and the court system, were paired with theater mentor-coaches for a 10-month creative group process, in which they shaped their stories into autobiographical performance pieces, through movement, improvisation, story-telling, and self-discovery. In the second phase of the project, their stories were merged into a theater production, weaving movement, song, and voice, and performed by an ensemble of experienced actors from the community. Pre- and post-interviews and self-report standardized measures of executive functioning were used to assist in establishing criteria and direction for future research. The results suggest that the individuals involved in this pilot may have improved executive functioning and acquired more ability to engage in human service programs designed to increase job readiness and enhance adaptive living skills.

Early thimerosal exposure and neuropsychological outcomes at 7 to 10 years.

BACKGROUND: It has been hypothesized that early exposure to thimerosal, a mercury-containing preservative used in vaccines and immune globulin preparations, is associated with neuropsychological deficits in children. METHODS: We enrolled 1047 children between the ages of 7 and 10 years and administered standardized tests assessing 42 neuropsychological outcomes. (We did not assess autism-spectrum disorders.) Exposure to mercury from thimerosal was determined from computerized immunization records, medical records, personal immunization records, and parent interviews. Information on potential confounding factors was obtained from the interviews and medical charts. We assessed the association between current neuropsychological performance and exposure to mercury during the prenatal period, the neonatal period (birth to 28 days), and the first 7 months of life. RESULTS: Among the 42 neuropsychological outcomes, we detected only a few significant associations with exposure to mercury from thimerosal. The detected associations were small and almost equally divided between positive and negative effects. Higher prenatal mercury exposure was associated with better performance on one measure of language and poorer performance on one measure of attention and executive functioning. Increasing levels of mercury exposure from birth to 7 months were associated with better performance on one measure of fine motor coordination and on one measure of attention and executive functioning. Increasing mercury exposure from birth to 28 days was associated with poorer performance on one measure of speech articulation and better performance on one measure of fine motor coordination. CONCLUSIONS: Our study does not support a causal association between early exposure to mercury from thimerosal-containing vaccines and immune globulins and deficits in neuropsychological functioning at the age of 7 to 10 years.

Resolving Water, Proteins, and Lipids from In Vivo Confocal Raman Spectra of Stratum Corneum through a Chemometric Approach.

Development of this in vivo confocal Raman spectroscopic method enables the direct measurement of water, proteins, and lipids with depth resolution in human subjects. This information is very important for skin-related diseases and characterizing skin care product performance. This protocol illustrates a method for confocal Raman spectra collection and the subsequent analysis of the spectral dataset leveraging chemometrics. The goal of this method is to establish a standard protocol for data collection and provide general guidance for data analysis. Preprocessing (e.g., removal of outlier spectra) is a critical step when processing large datasets from clinical studies. As an example, we provide guidance based on prior knowledge of a dataset to identify the types of outliers and develop specific strategies to remove them. A principal component analysis is performed, and the loading spectra are compared with spectra from reference materials to select the number of components used in the final multivariate curve resolution (MCR) analysis. This approach is successful for extracting meaningful information from a large spectral dataset.

Translating chemometric analysis into physiological insights from in vivo confocal Raman spectroscopy of the human stratum corneum.

The superficial layer of the skin, the stratum corneum (SC), consists of corneocytes surrounded by lipid regions and acts as a protective barrier for the body against water loss, toxic agents and microorganisms. As most substances permeate the stratum corneum through the lipid regions, lipid organization is considered crucial for the skin barrier function. Here, we investigate the potential of in vivo confocal Raman spectroscopy to describe the composition and organization of the SC. Confocal Raman spectroscopy is finding increasing use in the characterization of skin in biomedical, pharmaceutical and cosmetic applications. In this work, we analyze the spectra using chemometric methods and obtain principal components that correspond to the primary skin constituents: protein (keratin), natural moisturizing factor (NMF), water and lipid contributions in both ordered (orthorhombic) and disordered structural organization. By identifying these important components of the SC, these results highlight the utility of this in vivo, non-invasive, and depth resolved tool at the forefront of skin research.

A role for genetics in the immune response to the varicella vaccine.

BACKGROUND: A wide range in antibody titers has been found after immunization with the varicella vaccine, although the basis for these differences has not been described. METHODS: To evaluate the contribution of a genetic component in the immune response to the varicella vaccine, concordance for six-week postimmunization antibody titers was evaluated among 248 biologic siblings who participated in varicella vaccine clinical trials by comparing all pairs of siblings (151 pairs) to all possible unrelated, nonsibling pairs created from within this same cohort (30,477 pairs). RESULTS: Postimmunization antibody titers after 1 varicella vaccine dose were within the range observed historically among healthy vaccinees, with 85.4% of subjects having antibody responses greater than the approximate correlate of protection of 5 gpELISA units. Postimmunization antibody titers within sibling pairs clustered together more than or less than 10 gpELISA units when compared with within nonsibling pairs (P < 0.0001). Postimmunization titers within sibling pairs were also quantitatively closer together than were those within unrelated, nonsibling pairs (P = 0.022). The age-adjusted intraclass correlation coefficient indicated that the heritability of the varicella vaccine immune response is 45% (95% confidence interval of 15-75%). CONCLUSIONS: Similarities in siblings' response to varicella vaccine are supportive of the hypothesis that genetic factors play a role in the antibody response to the varicella vaccine.

Immunogenicity and safety of measles-mumps-rubella, varicella and Haemophilus influenzae type b vaccines administered concurrently with a fourth dose of heptavalent pneumococcal conjugate vaccine compared with the vaccines administered without heptavalent pneumococcal conjugate vaccine.

BACKGROUND: Prevnar [heptavalent pneumococcal conjugate vaccine (PCV7)] is licensed in the United States for routine administration in infants and may be coadministered with other infant vaccines. Safety and immunogenicity data on the coadministration of the fourth dose of PCV7 with measles-mumps-rubella (MMR), varicella and Haemophilus influenzae type b (Hib) vaccines are limited. METHODS: Children 12-15 months of age received either MMR with PCV7 (group 1) or MMR without PCV7 (group 2). All subjects received Hib and varicella vaccines. Group 2 received PCV7 6-9 weeks after MMR vaccination. Sera for analysis of all non-PCV7 antibodies were collected just before administration of MMR vaccine and 6 weeks later. Optimal antigen responses were assessed with the use of predetermined antibody titers. The primary end point was >90% response rate (all antigens). Noninferiority was defined as <10% difference between groups. Local and systemic reactions and postvaccination adverse events were monitored and compared between groups. RESULTS: A total of 694 subjects (347 per group) were enrolled. After immunization with MMR plus PCV7 concurrently, or MMR followed 6 weeks later by PCV7, the percentages of subjects seroconverting were significantly greater than 90% for all antigens. The difference between the 2 groups was significantly less than 10%. CONCLUSION: The immune response to MMR, Hib and varicella vaccines, when administered concurrently with a 4th (booster) dose of PCV7, was noninferior to that of these vaccines when given without PCV7. These results support concomitant administration of PCV7 with MMR, varicella and Hib as part of the recommended immunization schedule for children 12-15 months of age.

Encephalopathy after whole-cell pertussis or measles vaccination: lack of evidence for a causal association in a retrospective case-control study.

BACKGROUND: Whole-cell pertussis (wP) and measles vaccines are effective in preventing disease but have also been suspected of increasing the risk of encephalopathy or encephalitis. Although many countries now use acellular pertussis vaccines, wP vaccine is still widely used in the developing world. It is therefore important to evaluate whether wP vaccine increases the risk of neurologic disorders. METHODS: A retrospective case-control study was performed at 4 health maintenance organizations. Records from January 1, 1981, through December 31, 1995, were examined to identify children aged 0 to 6 years old hospitalized with encephalopathy or related conditions. The cause of the encephalopathy was categorized as known, unknown or suspected but unconfirmed. Up to 3 controls were matched to each case. Conditional logistic regression was used to analyze the relative risk of encephalopathy after vaccination with diphtheria-tetanus-pertussis (DTP) or measles-mumps-rubella (MMR) vaccines in the 90 days before disease onset as defined by chart review compared with an equivalent period among controls indexed by matching on case onset date. RESULTS: Four-hundred fifty-two cases were identified. Cases were no more likely than controls to have received either vaccine during the 90 days before disease onset. When encephalopathies of known etiology were excluded, the odds ratio for case children having received DTP within 7 days before onset of disease was 1.22 (95% confidence interval [CI] = 0.45-3.31, P = 0.693) compared with control children. For MMR in the 90 days before onset of encephalopathy, the odds ratio was 1.23 (95% confidence interval = 0.51-2.98, P = 0.647). CONCLUSIONS: In this study of more than 2 million children, DTP and MMR vaccines were not associated with an increased risk of encephalopathy after vaccination.

Effectiveness of heptavalent pneumococcal conjugate vaccine in children younger than 5 years of age for prevention of pneumonia: updated analysis using World Health Organization standardized interpretation of chest radiographs.

BACKGROUND: A World Health Organization (WHO) working group in 2001 developed a method for standardizing interpretation of chest radiographs in children for epidemiologic purposes. We reevaluated radiographs from the Kaiser Permanente Pneumococcal Efficacy trial using this method. METHODS: Seven-valent pneumococcal conjugate vaccine was evaluated in a randomized, controlled study including 37,868 infants. Effectiveness against pneumonia was previously evaluated using the original treating radiologist reading. There were 2841 sets of radiographs from this trial and all available radiographs were scanned and read blindly by 2 WHO crosstrained readers (A and B); discordance between the 2 primary readers was resolved through a consensus reading by an adjudicating panel of 2 radiologists. RESULTS: Of the 2841 radiographs, 2446 were available for scanning and were reviewed using WHO-defined descriptive categories. Two hundred fifty of the 2446 radiographs were read as positive by both readers. An additional 129 were read as positive by reader A only and 142 by reader B only for a total of 521 radiographs that were read as positive by one or both of the reviewers. The concordance rate between the 2 reviewers was 250 of 521 (48%). Of the 271 discordant radiographs, 45 of 129 (34.9%) of reader A and 66 of 142 (46.5%) for reader B were finalized as positive by the adjudicating panel. Overall, 361 radiographs were finalized as positive (12.7%). With these 361 images as the standard, the sensitivity and specificity of reader A were 82% and 97%, respectively, and for reader B, 88% and 97%, respectively. Kappa between the 2 readers was 0.58. Of 25 control radiographs read as positive by both A and B, 80% were also read as positive by the panel and all 25 control negative radiographs were read as negative by the panel. Using original readings by point-of-care radiologists, efficacy against first episode of radiograph confirmed pneumonia was 17.7% (95% confidence interval [CI] = 4.8-28.9%) in intent-to-treat and 20.5% (95% CI = 4.4-34%) in per protocol. Using the WHO method, the efficacy against first episode of radiograph confirmed pneumonia adjusting for age, gender and year of vaccination of 25.5% (95% CI = 6.5-40.7%, P = 0.011) for intent-to-treat and 30.3% (95% CI = 10.7-45.7%, P = 0.0043) for per protocol. CONCLUSION: Using WHO criteria for reading of radiographs increased point estimates of vaccine efficacy presumably as a result of improved specificity.

Efficacy, immunogenicity and safety of heptavalent pneumococcal conjugate vaccine in low birth weight and preterm infants.

OBJECTIVE: To determine the efficacy, immunogenicity and safety of the heptavalent CRM197 pneumococcal conjugate vaccine (PCV) in low birth weight (LBW) and preterm (PT) infants against invasive pneumococcal disease caused by vaccine types. METHODS: In a randomized double blind trial of 37,868 infants given either PCV or meningococcal type C conjugate vaccine (MCV), 1756 infants <750 g <2500 g (LBW) and 4340 infants from 32 to <38 weeks old (PT) were identified. Risk of invasive pneumococcal disease in LBW and PT infants was compared with risk in normal birth weight (NBW) and full term (FT) infants. Local and systemic events observed within 48 h of recent vaccine were assessed by telephone interviews and similar comparisons made. Premature infant Emergency Department visits and hospitalization were also identified and compared with FT and NBW infants. RESULTS: Initiation of immunization and intervals between doses were similar for all groups. The risk ratio for invasive pneumococcal diseases for LBW infants compared with NBW infants was 2.6 (P = 0.03), and for PT compared with FT infants the risk ratio was 1.6 (P = 0.06). Vaccine efficacy for both groups was 100%. PCV was as immunogenic in LBW and PT as in NBW and FT infants. Fever and local events after PCV vaccination were similar when adjusted for clustering among multiple doses per child. When stratified for individual doses there was more redness and swelling for LBW infants and more swelling for PT infants after Dose 3. Isolated local and systemic reactions were more commonly seen with PCV than with MCV, a pattern similar to that in NBW and FT infants. Hospitalization rates were similar for PCV and MCV recipients. CONCLUSION: These data support the use of PCV in LBW infants and PT infants.

Lack of association between receipt of conjugate haemophilus influenzae type B vaccine (HbOC) in infancy and risk of type 1 (juvenile onset) diabetes: long term follow-up of the HbOC efficacy trial cohort.

We evaluated the effect of infant vaccination with HbOC Haemophilus influenzae type b (Hib) conjugate vaccine on the risk of onset of type 1 juvenile diabetes later in life by examining data from a large controlled prospective Phase III clinical efficacy trial conducted within Northern California Kaiser Permanente between 1988 and 1990. The overall study population included children who were offered the Hib conjugate vaccine (acceptors and refusers) as well as a cohort of children who were systemically excluded from the trial on the basis of their birth date. These children are now 10 to 12 years of age. We found no evidence that vaccination with Hib conjugate vaccine in infancy is associated with risk of diabetes later in life.

Impact of the pneumococcal conjugate vaccine on otitis media.

CONTEXT: The heptavalent pneumococcal conjugate vaccine (PCV) is recommended for infants to protect against invasive disease, but its impact on otitis might also have public health importance. OBJECTIVE: To examine the impact of PCV on the incidence of otitis media, frequent otitis media and tympanostomy tube procedures and to assess whether the effectiveness of the vaccine wanes after age 24 months and varies by race, sex or season. DESIGN, SETTING AND PATIENTS: From 1995 to 1998, 37 868 children at Kaiser Permanente in Northern California were randomized to receive PCV or a control vaccine in a double blind trial and were followed through April 1999. INTERVENTIONS: Children received a primary series at 2, 4 and 6 months of age and a booster at 12 to 15 months. MAIN OUTCOME MEASURES: Visits for otitis, frequent visits for otitis and tympanostomy tube procedures. Otitis was ascertained from diagnosis checklists routinely marked by physicians. RESULTS: Control children averaged 1.8 otitis visits per year. Children given PCV had fewer otitis visits than control children in every age group, sex, race and season examined. Intention-to-treat analysis permitted rejection of the null hypothesis that PCV is ineffective against otitis media (P < 0.0001). In children who completed the primary series per protocol, PCV reduced otitis visits by 7.8% [95% confidence interval (CI), 5.4 to 10.2%] and antibiotic prescriptions by 5.7% (CI 4.2 to 7.2%). Frequent otitis was reduced by amounts that increased with otitis frequency, from a 10% reduction in the risk of 3 visits to a 26% reduction in the risk of 10 visits within a 6-month period. Tube placements were reduced by 24% (CI 12 to 35%). CONCLUSION: In children followed up to 3.5 years, PCV provided a moderate amount of protection against ear infections while reducing frequent otitis media and tube procedures by greater amounts.

Safety of cold-adapted live attenuated influenza vaccine in a large cohort of children and adolescents.

OBJECTIVE: To determine the safety of cold-adapted trivalent intranasal influenza virus vaccine (CAIV) in children and adolescents. STUDY DESIGN: A randomized, double blind, placebo-controlled safety trial in healthy children age 12 months to 17 years given CAIV (FluMist; MedImmune Vaccines, Inc.) or placebo (randomization, 2:1). Children <9 years of age received a second dose of CAIV or placebo 28 to 42 days after the first dose. Enrolled children were then followed for 42 days after each vaccination for all medically attended events. Prespecified outcomes included 4 prespecified diagnostic groups and 170 observed individual diagnostic categories. The relative risk and the 2-sided 90% confidence interval were calculated for each diagnostic group and individual category by clinical setting, dose and age. More than 1500 relative risk analyses were performed. RESULTS: A total of 9689 evaluable children were enrolled in the study. Of the 4 prespecified diagnostic categories (acute respiratory tract events, systemic bacterial infection, acute gastrointestinal tract events and rare events potentially associated with wild-type influenza), none was associated with vaccine. Of the biologically plausible individual diagnostic categories, 3, acute gastrointestinal events, acute respiratory events and abdominal pain, had different analyses that demonstrated increased and decreased relative risks, making their association with the vaccine unlikely. For reactive airway disease a significant increased relative risk was observed in children 18 to 35 months of age with a relative risk of 4.06 (90% confidence interval, 1.29 to 17.86) in this age group. The individual diagnostic categories of upper respiratory infection, musculoskeletal pain, otitis media with effusion and adenitis/adenopathy had at least one analysis that achieved a significant increased risk ratio. All of these events were infrequent. CONCLUSION: CAIV was generally safe in children and adolescents. The observation of an increased risk of asthma/reactive airway disease in children <36 months of age is of potential concern. Further studies are planned to evaluate the risk of asthma/reactive airway disease after vaccine.

Effectiveness of heptavalent pneumococcal conjugate vaccine in children younger than five years of age for prevention of pneumonia.

OBJECTIVE: To determine the effectiveness of the Wyeth heptavalent pneumococcal conjugate vaccine against clinical and radiograph-confirmed pneumonia in children. METHODS: The heptavalent CRM(197) pneumococcal conjugate vaccine (PCV) was given to infants at 2, 4, 6 and 12 to 15 months of age in a randomized, double blind trial. Children were randomized to receive either the CRM(197) PCV (vaccine group) or the meningococcal type C CRM(197) conjugate vaccine (control group). The primary outcome of this trial was invasive pneumococcal disease. In addition children with the clinical diagnosis of pneumonia in the study population were identified through review of automated inpatient, emergency and outpatient databases. The subset of the cohort of these children who had chest radiographs obtained at the time of diagnosis was identified, and the original reading of their radiographs by the radiologist was obtained from automated databases. Rates of clinically diagnosed pneumonia, of pneumonia with a radiograph obtained regardless of result, of pneumonia with positive radiograph (consolidation, empyema or parenchymal infiltrate) and of pneumonia with only perihilar infiltrates were compared between vaccinated and nonvaccinated groups. In addition risk of disease pneumonia was evaluated by race and ethnicity. RESULTS: The incidence of a first pneumonia episode in the control group was 55.9 per 1000 person-years. A radiograph was obtained in 61% of episodes, a positive radiograph in 21% and perihilar findings in an additional 5%. In per protocol follow-up of children given PCV, first episodes of all clinically diagnosed pneumonia were reduced by 4.3% [95% confidence interval (CI), -3.5, 11.5%, = 0.27], episodes with a radiograph were reduced by 9.8% (CI 0.1, 18.5%, < 0.05) and episodes with a positive radiograph were reduced by 20.5% (CI 4.4, 34.0, = 0.02). In the intent to treat analysis including all episodes after randomization, episodes with a positive radiograph were reduced by 17.7%, =.01). The greatest impact was in the first year of life with a 32.2% reduction and a 23.4% reduction in the first 2 years, but only a 9.1% reduction in children >2 years of age. Asians, blacks and Hispanics were at higher risk of pneumonia than were whites, but there was no evidence of ethnic variation in PCV effectiveness. Ten of the 11 cases of pneumococcal pneumonia with a positive blood culture were in the control group. CONCLUSION: The pneumococcal conjugate vaccine tested was effective in reducing the risk of pneumonia in young children.

Impact of vaccination on the epidemiology of varicella: 1995-2009.

BACKGROUND: When varicella vaccine was licensed in the United States in 1995, there were concerns that childhood vaccination might increase the number of adolescents susceptible to varicella and shift disease toward older age groups where it can be more severe. METHODS: We conducted a series of 5 cross-sectional studies in 1994 to 1995 (prevaccine), 2000, 2003, 2006, and 2009 in Kaiser Permanente of Northern California to assess changes in varicella epidemiology in children and adolescents, as well as changes in varicella hospitalization in people of all ages. For each study, information on varicella history and varicella occurrence during the past year was obtained by telephone survey from a sample of ∼8000 members 5 to 19 years old; varicella hospitalization rates were calculated for the entire membership. RESULTS: Between 1995 and 2009, the overall incidence of varicella in 5- to 19-year-olds decreased from 25.8 to 1.3 per 1000 person-years, a ∼90% to 95% decline in the various age categories (5-9, 10-14, and 15-19 years of age). The proportion of varicella-susceptible children and adolescents also decreased in all age groups, including in 15- to 19-year-olds (from 15.6% in 1995 to 7.6% in 2009). From 1994 to 2009, age-adjusted varicella hospitalization rates in the general member population decreased from 2.13 to 0.25 per 100,000, a ∼90% decline. CONCLUSIONS: In the 15 years after the introduction of varicella vaccine, a major reduction in varicella incidence and hospitalization was observed with no evidence of a shift in the burden of varicella to older age groups.

Long-term effectiveness of varicella vaccine: a 14-Year, prospective cohort study.

BACKGROUND: Varicella vaccine was licensed in the United States in 1995 for individuals ≥12 months of age. A second dose was recommended in the United States in June 2006. Varicella incidence and vaccine effectiveness were assessed in a 14-year prospective study conducted at Kaiser Permanente Northern California. METHODS: A total of 7585 children vaccinated with varicella vaccine in their second year of life in 1995 were followed up prospectively for breakthrough varicella and herpes zoster (HZ) through 2009. A total of 2826 of these children received a second dose in 2006-2009. Incidences of varicella and HZ were estimated and compared with prevaccine era rates. RESULTS: In this cohort of vaccinated children, the average incidence of varicella was 15.9 per 1000 person-years, nine- to tenfold lower than in the prevaccine era. Vaccine effectiveness at the end of the study period was 90%, with no indication of waning over time. Most cases of varicella were mild and occurred early after vaccination. No child developed varicella after a second dose. HZ cases were mild, and rates were lower in the cohort of vaccinated children than in unvaccinated children during the prevaccine era (relative risk: 0.61 [95% confidence interval: 0.43-0.89]). CONCLUSIONS: This study confirmed that varicella vaccine is effective at preventing chicken pox, with no waning noted over a 14-year period. One dose provided excellent protection against moderate to severe disease, and most cases occurred shortly after the cohort was vaccinated. The study data also suggest that varicella vaccination may reduce the risks of HZ in vaccinated children.