Assessing sociodemographic differences in human papillomavirus vaccine impact studies in the United States: a systematic review using narrative synthesis.

OBJECTIVES: Sociodemographic disparities in the incidence and mortality of human papillomavirus (HPV)-associated conditions have been well documented in the pre-HPV vaccine era. It is still unknown if the introduction of routine vaccination has been effective in reducing these prevaccine era inequalities. The purpose of this review was to determine the utilization of sociodemographic variables to assess for disparities in population-level HPV vaccine impact research and to evaluate the current evidence for disparities in the reduction of HPV-associated conditions after vaccine introduction in the United States (US). STUDY DESIGN: A systematic review of the literature from January 2007 through March 2018 was carried out to identify studies evaluating the impact HPV vaccines have had on the rates of HPV infection, genital warts, and cervical dysplasia (cervical intraepithelial neoplasia grades 1+) in the US. An in-depth review was then performed to synthesize these data and to assess the way prior studies have reported and evaluated for potential disparities in the vaccine's impact within various racial, ethnic, and/or socio-economic subgroups of the population. METHODS: Vaccine impact studies measure the change in the population-level burden of disease prelicensure versus postlicensure of the vaccine. We systematically searched PubMed/Medline and Embase, combining search terms related to the HPV vaccine, sentinel surveillance, and HPV-associated conditions. Eligible studies were those with population-level, postvaccine introduction data that were conducted in the US. Finally, a cited reference search was conducted for all included articles using the Web of Science platform that accesses three major citation indexes: Science Citation Index, Social Sciences Citation Index, and Arts and Humanities Citation Index. This allowed us to screen not only the articles that were cited by our final collection of studies but also the articles that used our selected studies as one of their references. The study protocol is registered in PROSPERO (#CRD42018107579). RESULTS: Overall, 23 of the 4139 references retrieved assessed the population-level impact of HPV vaccines between January 1, 2007, and March 29, 2018. Among these, 13 (57%) reported sociodemographic data. Only two articles reported stratified results by sociodemographic factors, thereby allowing assessment for potential disparate impact. One of these studies described differences in the impact of the vaccine by race, ethnicity, and income. CONCLUSION: Although approximately half of the studies that assessed the impact of the HPV vaccine measured sociodemographic characteristics, few presented results in a way that allowed for the identification of potential differences in impact between the relevant subgroups of the population. Determining to what extent, if any, vaccines are reducing known sociodemographic disparities is an important public health priority and an essential step in developing immunization strategies that are beneficial for all.

Practice parameter: treatment of nervous system Lyme disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology.

OBJECTIVE: To provide evidence-based recommendations on the treatment of nervous system Lyme disease and post-Lyme syndrome. Three questions were addressed: 1) Which antimicrobial agents are effective? 2) Are different regimens preferred for different manifestations of nervous system Lyme disease? 3) What duration of therapy is needed? METHODS: The authors analyzed published studies (1983-2003) using a structured review process to classify the evidence related to the questions posed. RESULTS: The panel reviewed 353 abstracts which yielded 112 potentially relevant articles that were reviewed, from which 37 articles were identified that were included in the analysis. CONCLUSIONS: There are sufficient data to conclude that, in both adults and children, this nervous system infection responds well to penicillin, ceftriaxone, cefotaxime, and doxycycline (Level B recommendation). Although most studies have used parenteral regimens for neuroborreliosis, several European studies support use of oral doxycycline in adults with meningitis, cranial neuritis, and radiculitis (Level B), reserving parenteral regimens for patients with parenchymal CNS involvement, other severe neurologic symptomatology, or failure to respond to oral regimens. The number of children (> or =8 years of age) enrolled in rigorous studies of oral vs parenteral regimens has been smaller, making conclusions less statistically compelling. However, all available data indicate results are comparable to those observed in adults. In contrast, there is no compelling evidence that prolonged treatment with antibiotics has any beneficial effect in post-Lyme syndrome (Level A).

Predictors of outcome of myocarditis.

Heart failure from myocarditis may be transient or may progress to unremitting severe cardiac failure. This study was performed to determine the outcomes and prognostic features of pediatric patients with myocarditis. Patients with the diagnosis of myocarditis between 1990 and 2001 were identified through the coding system of Yale-New Haven Hospital. A total of 28 patients were included, with ages ranging from 1 day to 20 years. Before discharge, 11 patients developed unremitting severe cardiac failure. Of the remaining 17 patients, at the time of discharge 10 had normal systolic function and 7 had decreased systolic function. Unremitting cardiac failure developed in 9 of 14 patients (64%) with an ejection fraction < 30% and in only 2 of 14 (14%) of those with an ejection fraction > or = 30% on admission (p < 0.01). Furthermore, shortening fraction < 15%, left ventricular dilatation, and moderate to severe mitral regurgitation on admission as well as arrhythmia were significantly associated with development of unremitting severe cardiac failure. In this series of patients with myocarditis, by the time of discharge 39% of the patients had developed unremitting severe cardiac failure, 25% had depressed systolic function, and 36% had normal systolic function. Predictive factors at admission for poor outcome were ejection fraction < 30%, shortening fraction < 15%, left ventricular dilatation, and moderate to severe mitral regurgitation.

The effectiveness of the varicella vaccine in clinical practice.

BACKGROUND: A live attenuated varicella vaccine was approved for use in the United States in March 1995 and is recommended for all susceptible persons 12 months of age or older. METHODS: To assess the effectiveness of the varicella vaccine, we conducted a case-control study with two controls per child with chickenpox, matched according to both age and pediatric practice. Children with potential cases of chickenpox were identified by active surveillance of pediatric practices in the New Haven, Connecticut, area. Research assistants visited the children on day 3, 4, or 5 of the illness, assessed the severity of the illness, and collected samples from lesions to test for varicella-zoster virus by polymerase chain reaction (PCR). RESULTS: From March 1997 through November 2000, data collection was completed for 330 potential cases, of which 243 (74 percent) were in children who had positive PCR tests for varicella-zoster virus. Of the 56 vaccinated children with chickenpox, 86 percent had mild disease, whereas only 48 percent of the 187 unvaccinated children with chickenpox had mild disease (P<0.001). Among the 202 children with PCR-confirmed varicella-zoster virus and their 389 matched controls, 23 percent of the children with chickenpox and 61 percent of the matched controls had received the vaccine (vaccine effectiveness, 85 percent; 95 percent confidence interval, 78 to 90 percent; P<0.001). Against moderately severe and severe disease the vaccine was 97 percent effective (95 percent confidence interval, 93 to 99 percent). The effectiveness of the vaccine was virtually unchanged (87 percent) after adjustment for potential confounders by means of conditional logistic regression. CONCLUSIONS: Varicella vaccine is highly effective as used in clinical practice.

Willingness of directors of child care centers to care for children with chronic infections.

Directors of 150 child care centers were surveyed about their willingness to accept children with HIV or hepatitis B infection. Among 100 respondents 58% agreed to accept HIV-positive children and 23% would accept hepatitis B-positive children.

Lyme disease.

Lyme disease, which is caused by Borrelia burgdorferi and transmitted in the United States primarily by Ixodes scapularis (the deer tick), is the most common vector borne disease in the United States. Its most frequent manifestation, a characteristic, expanding annular rash (erythema migrans), sometimes accompanied by myalgia, arthralgia, and malaise, occurs in nearly 90% of persons with symptomatic infection. Other manifestations of Lyme disease include seventh cranial nerve palsy, aseptic meningitis, and arthritis. Extensive coverage in the press about the serious effects of Lyme disease has led to widespread anxiety about this illness that is far out of proportion to the actual morbidity that it causes. This problem is exacerbated by the frequent use of serological tests to eliminate the possible diagnosis of Lyme disease in persons with only nonspecific symptoms (such as arthralgia or fatigue) who have a very low probability that Lyme disease is the cause of their symptoms. Consequently, misdiagnosis is frequent and is the most common cause of failure of treatment. The prognosis for most persons with Lyme disease is excellent.

The scholarship of application.

The scholarship of application encompasses a broad range of different types of scholarship in the sciences and humanities that involves translation of new knowledge to practical applications to solve problems of individuals and of society. The authors discuss this form of scholarship broadly, but focus on how it applies to patient-oriented research and to service performed by physicians. They distinguish between a clinician's use of his or her expertise (not scholarship) and a clinician's activities such as systematically assessing the effectiveness of different techniques and communicating the findings in a way that allows others to benefit (scholarship). They (1) review the importance of scholarship of application (i.e., society depends on the application of new knowledge), with special attention to the benefits to academic institutions; (2) discuss incentives for such scholarship (e.g., readiness of funding for directly applicable research) and disincentives (e.g., shortcomings in methods; lower prestige); (3) explain how it should be evaluated (create a more expansive peer-review process); (4) explain how it should be rewarded (rewards should be similar to those given for other forms of scholarship); and (5) describe how it should be nurtured (rigorous training in methodology, protected time for research, tangible support). They conclude that the interdependence of academic institutions and of society requires that the scholarship of application be conducted with rigor and relevance, and that institutions must develop strategies to promote applied scholarship.

Prospective cohort study of children born to human immunodeficiency virus-infected mothers, 1985 through 1997: trends in the risk of vertical transmission, mortality and acquired immunodeficiency syndrome indicator diseases in the era before highly active antiretroviral therapy.

OBJECTIVES: To assess changes in the risk of vertical transmission of HIV and changes in both mortality and morbidity among children in southern Connecticut with HIV infection after the introduction of treatment of HIV-infected pregnant women with antiretroviral drugs and of regimens to prevent or to treat AIDS indicator diseases in infected children. METHODS: The risk of vertical transmission of HIV, the rates of death and of AIDS indicator diseases and temporal trends in each were determined for children born in the first 5 years of a prospective, longitudinal cohort study (Period 1: December 1, 1985, through November 30, 1990) compared with those for children born during the latter 7 years of the study (Period 2: December 1, 1990, through November 30, 1997). RESULTS: Of 347 infants enrolled, HIV infection status could be determined for 341; 44 (12.9%) were infected. The risk of vertical transmission declined from 20.7% among children born in Period 1 to 6.5% among children born in period 2 (rate ratio, 3.2; 95% confidence interval, 1.7 to 6.0; P = 0.0001). Of the 21 infected children who died, 11(52%) were < or =18 months of age and 18 (86%) were < or =36 months of age at the times of death. Approximately one-fourth of infected children born during each period died at < or =18 months of age. Among those < or =36 months of age, 15 deaths occurred during 878 person months of observation for those born in Period 1 compared with 3 deaths that occurred during 334 person months for those born in Period 2 (rate ratio, 1.9; 95% confidence interval, 0.5 to 10.3; P = 0.45). Of the 44 children infected with HIV, 32 had one or more AIDS indicator diseases (a total of 67 episodes), 73% of which occurred when the children were < or =36 months of age. Among children born in Period 2, none developed Pneumocystis carinii pneumonia and the rates of Mycobacterium avium complex disease and of wasting syndrome declined, but the differences in rates of disease were not statistically significant. CONCLUSION: A substantial and statistically significant decline in the risk of vertical transmission of HIV-1 occurred during the 12-year study period. In contrast although there was a trend toward a decrease in mortality among HIV-infected children < or =36 months of age and changes in the overall rates of AIDS indicator diseases among children born in Period 1 compared with Period 2, the differences were not statistically significant.

Group-specific antibody levels surrounding invasive pneumococcal illness in children infected with human immunodeficiency virus.

Pneumococcal antibody levels surrounding systemic pneumococcal illness (SPI) were measured in children infected with human immunodeficiency virus (HIV). Archived serum samples were collected from 28 HIV-infected children who had 34 cases of SPI, caused by pneumococcal groups 4, 6, 9, 14, 19, and 23. Serum samples collected within 23 weeks before and 13 weeks after the SPI were assayed by ELISA for antipneumococcal polysaccharide (PnPs) IgG antibody to 6 representative pneumococcal serotypes. There was a wide range (0. 16-30.80 microg/mL) of pre-SPI anti-PnPs antibody levels to the presumed infecting serotypes, with a geometric mean level of 0.83 microg/mL (n=34). Seventy-six percent of the antibody values were <2.0 microg/mL, and 95% were <5.0 microg/mL. Homologous seroresponses (>/=4-fold rise in anti-PnPs antibody) were detected in only 4 (27%) of 15 paired serum samples. Heterologous, noninfecting group seroresponses were detected frequently (72%) in the paired serum samples from these 4 homologous group seroresponders.

Long-term outcomes of persons with Lyme disease.

CONTEXT: Few data exist about the long-term outcomes of patients with Lyme disease. OBJECTIVE: To assess the long-term outcomes of patients with Lyme disease. DESIGN: Two-part project including a community-based longitudinal cohort study and a matched cohort study. SETTING AND PARTICIPANTS: Six hundred seventy-eight patients identified from a random sample of all reports of Connecticut residents with suspected Lyme disease submitted to the Connecticut Department of Public Health from 1984-1991 were evaluated in the longitudinal study; for a random subsample of 212 patients from the larger study, 212 age-matched controls without Lyme disease also were enrolled. MAIN OUTCOME MEASURES: Self-reports or parents' reports of symptoms and ability to perform certain daily activities since diagnosis of Lyme disease; scores on the 36-Item Short-Form Health Survey and the Center for Epidemiologic Studies-Depression scale, for adults, by case-definition status and between patients and controls. RESULTS: Of the 678 patients, 51.6% were female, 34.4% were children, and 64.3% met the national surveillance case definition for Lyme disease. Most patients (85.6%) were treated with antimicrobial agents. Interviews were conducted a median of 51 months after diagnosis (range, 15-135 months). An increased frequency of symptoms (eg, pain, fatigue) or of difficulty with daily activities (eg, performing housework, exercising) was reported by 69% of the patients, although few (19%) of these problems were attributed to Lyme disease. Whenever there was a statistically significant difference in the frequencies of either increased symptoms or increased difficulties with typical activities between those who did or did not meet the surveillance case definition, in all instances the greater frequency of problems was in the group that did not meet the case definition. The frequencies of reports of both increased symptoms and increased difficulties with typical activities among patients who had been diagnosed as having Lyme disease were similar to those among age-matched controls without Lyme disease. CONCLUSIONS: In this cohort, although many patients reported increases in symptoms and/or increased difficulties with typical daily activities between 1 and 11 years after diagnosis of Lyme disease, the frequencies of these reports were similar to the frequencies of such reports among age-matched controls without Lyme disease.

Pneumococcal vaccines: history, current status, and future directions.

Streptococcus pneumoniae is the leading cause of community-acquired pneumonia and bacterial meningitis. Although effective antimicrobial drugs have reduced case fatality, the pneumococcus remains a leading global cause of morbidity and mortality. Therefore, prevention of infection by vaccination with the pneumococcal polysaccharide vaccine is recommended for persons at high risk for serious pneumococcal disease, such as the elderly and individuals with certain underlying medical conditions. Pneumococcal polysaccharide vaccines are safe and effective for the prevention of invasive infection among immunocompetent children and adults but are not immunogenic in infants. Conjugation of pneumococcal polysaccharides to a carrier protein improves immune responses among infants, and conjugate vaccines are currently being evaluated in large efficacy trials. The role of pneumococcal conjugate vaccines in adults has not been determined. Pneumococcal vaccines directed against pneumococcal proteins and DNA vaccines that induce anti-pneumococcal antibodies have been evaluated in animal models and may someday provide complementary or alternative methods for preventing pneumococcal infection. Improved utilization of the pneumococcal polysaccharide vaccine and continued development of improved vaccines are essential, and the emergence of drug-resistant strains of S. pneumoniae highlights the importance of preventing pneumococcal infections by vaccination.

Chest radiographs in the pediatric emergency department for children < or = 18 months of age with wheezing.

There are no widely accepted predictors of pneumonia in wheezing infants and toddlers who present to the emergency department (ED). A 10-month retrospective review of ED visits of wheezing children < or = 18 months of age revealed the following chest radiograph (CXR) results: normal (21%), findings consistent with uncomplicated bronchiolitis or asthma (61%), focal infiltrates (18%), and other abnormalities (< 1%). Patients with focal infiltrates on CXR were more likely to have the following: a history of fever (p = 0.03, OR 2.1, 95% CI 1.0, 4.4), temperature > or = 38.4 degrees (p = 0.01, OR 2.5, 95% CI 1.1, 5.8) or crackles on examination (p < 0.0005, OR 3.9, 95% CI 1.7, 9.0). Selective use of CXRs has the potential to save health care dollars and limit unnecessary radiation.

Lyme arthritis in children: clinical epidemiology and long-term outcomes.

OBJECTIVE: Although Lyme disease has become a relatively common cause of arthritis among children in areas of the country in which the disease is endemic, little information is available about the clinical epidemiology and long-term outcomes of children with Lyme arthritis. We conducted a long-term follow-up study to determine the clinical epidemiology of Lyme arthritis in children as well as their long-term outcomes. PATIENTS AND METHODS: All children seen between 1982 and 1991 at the Pediatric Rheumatology Clinic at Newington Children's Hospital (Newington, CT) with an initial diagnosis of Lyme disease were identified. Medical records were reviewed and structured telephone interviews were conducted to obtain demographic, clinical, and follow-up data. RESULTS: A total of 90 children (63% boys) with a mean age of 8.3 years (range, 1.8-16 years) at the time of diagnosis of Lyme arthritis were evaluated. Lyme arthritis was preceded by early Lyme disease in 23 (26%) of the children; however, only 8 (35%) of these children had been treated with appropriate antimicrobial therapy at that early stage. Ninety percent of the children had arthritis of at least one knee, while small joints were rarely involved. For the 31 children who underwent arthrocentesis, the mean white blood cell count in the synovial fluid was 38 000 cells/mm3 (range, 7000-99 000 cells/mm3) with predominantly neutrophils. For the 79 children for whom an erythrocyte sedimentation rate was determined, the highest level for 61 (77%) was >20 mm/h and for 36 (46%) was >50 mm/h. Antimicrobial therapy was initiated 2 days to 5.5 years (median, 2 months) after the onset of symptoms. However, 5 of the children were never treated with antimicrobials. Fifty-one percent of the patients had a single episode of arthritis, while 49% reported recurrent episodes of arthritis over a period of 1 week to 8 years (median, 6 months). Two children (2%) developed chronic arthritis and underwent arthroscopic synovectomy. At the time of the telephone follow-up evaluation, performed 2 to 12 years (median, 7 years) after the onset of the Lyme arthritis, 4 children had ongoing musculoskeletal complaints that resulted in mild to moderate impairment of school or sports activities, but none of the children had evidence of active arthritis. CONCLUSION: The results of this investigation suggest that the prognosis for children with Lyme arthritis who are treated with appropriate antimicrobial therapy is excellent.