Search

Acute exacerbations of chronic obstructive airways disease (COAD) are a common cause of admission to hospital, and have a high mortality. Nasal intermittent positive pressure ventilation (NIPPV) has been used successfully in patients with respiratory failure due to neuromuscular and skeletal disorders, but the outcome of treatment in patients with COAD is less well known. We carried out a prospective randomised controlled trial of conventional treatment versus conventional treatment plus NIPPV, in 60 patients with acute ventilatory failure due to exacerbations of COAD. For the NIPPV group there was a rise in pH, compared with a fall in the controls (mean difference of change between the groups 0.046 [95% CI 0.06-0.02, p < 0.001]), and a larger fall in PaCO2 (mean difference in change between the groups 1.2 kPa [95% CI 0.45 to 2.03, p < 0.01]). Median visual analogue scores over the first 3 days of admission showed less breathlessness in the NIPPV group (2.3 cm [range 0.1-5.5]) than in the control group (4.5 cm [range 0.9-8.8]) (p < 0.025). Survival rates at 30 days were compared for intention-to-treat and efficacy populations. In the efficacy mortality comparison, mortality in the NIPPV group was reduced: 1/26 vs 9/30 (relative risk = 0.13, CI = 0.02-0.95, p = 0.014). This effect was less in the intention-to-treat analysis: 3/30 vs 9/30 (relative risk = 0.33, CI = 0.10-1.11, p = 0.106). In patients with acute ventilatory failure due to COAD who received NIPPV there was a significant rise in pH, a reduction in PaCO2 and breathlessness, and reduced mortality. [ABSTRACT FROM AUTHOR]

Background: Although measles was declared eliminated from the United States in 2000, the frequency of measles outbreaks has increased in recent years. The ability to predict the locations of future cases could aid efforts to prevent and contain measles in the United States., Methods: We estimated county-level measles risk using a machine learning model with 17 predictor variables, which was trained on 2014 and 2018 United States county-level measles case data and tested on data from 2019. We compared the predicted and actual locations of 2019 measles cases., Results: The model accurately predicted 95 % (specificity) of United States counties without measles cases and 72 % (sensitivity) of the United States counties that experienced ≥1 measles case in 2019, accounting for 94 % of all measles cases in 2019. Among the top 30 counties with the highest risk scores, the model accurately predicted 22 (73 %) counties with a measles case in 2019, corresponding to 72 % of all measles cases., Conclusions: This machine learning model accurately predicted a majority of the United States counties at high risk for measles and could be used as a framework by state and national health agencies in their measles prevention and containment efforts., Competing Interests: Declaration of competing interest Stephanie A. Kujawski, Boshu Ru, Nelson Lee Afanador, Richard Baumgartner, and Manjiri Pawaskar are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA who may own stock and/or stock options in Merck & Co., Inc., Rahway, NJ, USA. James H. Conway reports consultancy and advisory activities with Merck, Pfizer, Moderna, and GSK; vaccine clinical research studies with AstraZeneca and Moderna (no compensation received); grant funding support from the US Centers for Disease Control and Prevention (CDC); and a leadership role in the Pediatric Infectious Disease Society Vaccine Advocacy Committee., (Copyright © 2024 Stephanie A. Kujawski, Boshu Ru, Nelson Lee Afanador, James H. Conway, Richard Baumgartner, Manjiri Pawaskar, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Published by Elsevier Ltd.. All rights reserved.)

Introduction: In 2005, the United States Advisory Committee on Immunization Practices (ACIP) recommended routine vaccination against invasive meningococcal disease (IMD) caused by serogroups A, C, W, and Y (MenACWY) for all 11-12-year-olds, as well as 2-10-year-olds at high risk. In 2010, a booster dose was recommended for all 16-year-olds, as well as for high-risk patients every 3-5 years. In 2015, optional (as opposed to routine) vaccination against meningococcal serogroup B (MenB) at the preferred age of 16-18 years was recommended (Category B, later changed to shared clinical decision-making). In 2023, a vaccine (MenABCWY) against the five serogroups primarily responsible for IMD in the U.S. became available., Areas Covered: This review summarizes the evolution of public policy that led to each milestone vaccine recommendation, reviews epidemiologic data published following the recommendations, and discusses the current state of meningococcal immunization policy., Expert Opinion: The use of MenABCWY has the potential to consolidate policy, improve coverage rates for the five serogroups, address disparities in vaccination coverage, and simplify vaccine delivery.

Health care providers engaging in cross-cultural work will likely experience culture shock, a psychological, behavioral, and physiologic response to new cultural environments that can significantly affect travelers. Culture shock has the potential for both negative and positive outcomes. Well-being, health, and professionalism can be negatively influenced during the peak of culture shock, but the experience may also positively promote transformative learning and professional identity formation. Culture shock has been carefully researched for different types of sojourners, such as undergraduate students and business personnel, but minimally for health care providers. This article defines culture shock, describes different health care-related cross-cultural opportunities, identifies factors contributing to culture shock, describes complexities related to measuring culture shock, depicts common cross-cultural challenges encountered by traveling health care providers, and offers tangible guidance to help prepare for culture shock. We conclude with a call for further research and resource development to support the well-being of an increasingly global health care workforce. [ Pediatr Ann . 2023;52(9):e335-e343.] .

Background: Cervical cancer is ranked globally in the top three cancers for women younger than 45 years, with the average age of death at 59 years of age. The highest burden of disease is in low-to-middle income countries (LMICs), responsible for 90% of the 311,000 cervical cancer deaths in 2018. This growing health disparity is due to the lack of quality screening and treatment programs, low human papillomavirus (HPV) vaccination rates, and high human immunodeficiency virus (HIV) co-infection rates. To address these gaps in care, we need to develop a clear understanding of the resources and capabilities of LMICs' health care facilities to provide prevention, early diagnosis through screening, and treatment for cervical cancer., Objectives: This project aimed to assess baseline available cervical cancer prevention, early diagnosis, and treatment resources, at facilities designated as Health Center III or above, in Gulu, Uganda., Methods: We adapted the World Health Organization's Harmonized Health Facility Assessment for our own HFA and grading scale, deploying it in October 2021 for a cross-sectional analysis of 21 health facilities in Gulu., Results: Grading of Health Center IIIs (n = 16) concluded that 37% had "excellent" or "good" resources available, and 63% of facilities had "poor" or "fair" resources available. Grading of Health Center IVs and above (n = 5) concluded that 60% of facilities had "excellent" or "good" resources, and 40% had "fair" resources available., Discussion: The analysis of health facilities in Gulu demonstrated subpar resources available for cervical cancer prevention, early diagnosis, and treatment. Focused efforts are needed to expand health centers' resources and capability to address rising cervical cancer rates and related health disparities in LMICs. The development process for this project's HFA can be applied to global cervical cancer programming to determine gaps in resources and indicate areas to target improved health equity., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Chongsuwat et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Neisseria meningitidis causes invasive meningococcal disease and, globally, significant morbidity, with serogroup B (MenB) being the most common cause of endemic disease and outbreaks in several regions. Extensive use of the four-component serogroup B meningococcal vaccine (4CMenB; Bexsero, GSK) and its inclusion in immunization programs in several countries have generated substantial safety data during the 9 years since its first authorization in 2013., Areas Covered: 4CMenB safety data from clinical trials and post-marketing surveillance studies (2011 to 2022), and spontaneously reported adverse events of medical interest from the GSK global safety database. We discuss these safety findings in relation to the benefit of 4CMenB vaccination and implications for further enhancing vaccine confidence., Expert Opinion: 4CMenB has been consistently well tolerated across clinical trials and post-licensure surveillance studies, despite a higher incidence of fever reported in infants than with other pediatric vaccines. Surveillance data have not identified any significant safety issues, consistent with an acceptable safety profile of 4CMenB. These findings highlight the need to balance the risk of relatively common, transient, post-immunization fever with the benefit of affording protection that reduces the risk of uncommon but potentially fatal meningococcal infection.

Background: In 1995, the CDC recommended one-dose routine varicella immunization for children <12 years of age, expanding its recommendation to two doses in 2006. Today, with widespread varicella vaccination coverage, an estimated 3.5 million cases of varicella, 9,000 hospitalizations, and 100 deaths are prevented annually in the United States. Since varicella infections are now uncommon, health care providers (HCPs) may not recognize varicella infections and may prescribe inappropriate treatment., Methods: An online survey of HCPs was conducted to assess recognition and management of varicella infections. Responses to eight varicella vignettes describing patients with varying varicella symptoms were analyzed and descriptive analyses performed. Stratified analysis comparing responses of those licensed before and in/after 1996 was also performed., Results: 153 HCPs (50 nurse practitioners, 103 doctors) completed the survey. Mean age of respondents was 44 years. 62% were female, and 82% were licensed before 1996. Varicella infection was correctly diagnosed 79% of the time. HCPs correctly recognized uncomplicated varicella vignettes 85% of the time versus 61% of the time for complicated varicella vignettes. Antibiotics were recommended 17% of the time and antivirals 18% of the time, of which 25% and 69% (respectively) were not appropriate per guidelines. HCPs licensed before 1996 were better able to recognize varicella compared to those licensed later, but prescribed more antimicrobials medications to treat varicella., Conclusions: Although most HCPs recognized varicella infection, a sizable proportion could not recognize cases with complications, and some of the varicella cases were inappropriately treated with antibiotics and/or antivirals. Additional HCP training and high vaccination coverage are important strategies to avoid inaccurate diagnoses and minimize unnecessary exposure to antimicrobial/antiviral therapies., Competing Interests: This work was supported by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. M. Pawaskar, S. Samant, and S. Surati are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and stockholders of Merck & Co., Inc., Kenilworth, NJ, USA. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Our objective was to estimate the impact of universal varicella vaccination (UVV) on the use and costs of antibiotics and antivirals for the management of varicella among children in the United States (US)., Methods: A decision tree model of varicella vaccination, infections and treatment decisions was developed. Results were extrapolated to the 2017 population of 73.5 million US children. Model parameters were populated from published sources. Treatment decisions were derived from a survey of health care professionals' recommendations. The base case modelled current vaccination coverage rates in the US with additional scenarios analyses conducted for 0%, 20%, and 80% coverage and did not account for herd immunity benefits., Results: Our model estimated that 551,434 varicella cases occurred annually among children ≤ 18 years in 2017. Antivirals or antibiotics were prescribed in 23.9% of cases, with unvaccinated children receiving the majority for base case. The annual cost for varicella antiviral and antibiotic treatment was approximately $14 million ($26 per case), with cases with no complications accounting for $12 million. Compared with the no vaccination scenario, the current vaccination rates resulted in savings of $181 million (94.7%) for antivirals and $78 million (95.0%) for antibiotics annually. Scenario analyses showed that higher vaccination coverage (from 0% to 80%) resulted in reduced annual expenditures for antivirals (from $191 million to $41 million), and antibiotics ($82 million to $17 million)., Conclusions: UVV was associated with significant reductions in the use of antibiotics and antivirals and their associated costs in the US. Higher vaccination coverage was associated with lower use and costs of antibiotics and antivirals for varicella management., Competing Interests: M. Pawaskar and S. Samant, are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and own stocks in Merck & Co., Inc., Kenilworth, 257 NJ, USA. P. Veeranki, and C. Harley, are employees of PRECISIONheor, which received financial support from Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA for the execution of this research. Though they received no payment for their work on this study, J. H. Conway reports grants and personal fees from Sanofi Pasteur, Pfizer, Merck, GSK, and Centers for Disease Control outside of the submitted work while J. Fergie reports personal fees from Merck Sharp & Dohme Corp, outside the submitted work.

Background: Schools are primary venues of influenza amplification with secondary spread to communities. We assessed K-12 student absenteeism monitoring as a means for early detection of influenza activity in the community., Materials and Methods: Between September 2014 and March 2020, we conducted a prospective observational study of all-cause (a-TOT), illness-associated (a-I), and influenza-like illness-associated (a-ILI) absenteeism within the Oregon School District (OSD), Dane County, Wisconsin. Absenteeism was reported through the electronic student information system. Students were visited at home where pharyngeal specimens were collected for influenza RT-PCR testing. Surveillance of medically-attended laboratory-confirmed influenza (MAI) occurred in five primary care clinics in and adjoining the OSD. Poisson general additive log linear regression models of daily counts of absenteeism and MAI were compared using correlation analysis., Findings: Influenza was detected in 723 of 2,378 visited students, and in 1,327 of 4,903 MAI patients. Over six influenza seasons, a-ILI was significantly correlated with MAI in the community (r = 0.57; 95% CI: 0.53-0.63) with a one-day lead time and a-I was significantly correlated with MAI in the community (r = 0.49; 0.44-0.54) with a 10-day lead time, while a-TOT performed poorly (r = 0.27; 0.21-0.33), following MAI by six days., Discussion: Surveillance using cause-specific absenteeism was feasible and performed well over a study period marked by diverse presentations of seasonal influenza. Monitoring a-I and a-ILI can provide early warning of seasonal influenza in time for community mitigation efforts., Competing Interests: JLT has received past research funding from Quidel Corporation. Quidel provided in-kind Sofia analyzers and Influenza A+B FIA tests to the Wisconsin research team. This does not alter our adherence to PLOS ONE policies on sharing data and materials. Quidel did not direct or exert any influence over study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Clinical trials of pharmacologic treatments of coronavirus disease 2019 (COVID-19) are being rapidly designed and implemented in adults. Children are often not considered during development of novel treatments for infectious diseases until very late. Although children appear to have a lower risk compared with adults of severe COVID-19 disease, a substantial number of children globally will benefit from pharmacologic treatments. It will be reasonable to extrapolate efficacy of most treatments from adult trials to children. Pediatric trials should focus on characterizing a treatment's pharmacokinetics, optimal dose, and safety across the age spectrum. These trials should use an adaptive design to efficiently add or remove arms in what will be a rapidly evolving treatment landscape, and should involve a large number of sites across the globe in a collaborative effort to facilitate efficient implementation. All stakeholders must commit to equitable access to any effective, safe treatment for children everywhere., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Human rights violations (HRVs) are common in conflict and displacement contexts. Women are especially vulnerable to HRVs in these contexts, and perinatal health is acutely sensitive to related stressors and health care barriers. However, how HRVs affect immediate and long-term perinatal health in chronic displacement settings has not been closely investigated. Furthermore, it remains unclear whether and how HRVs in these contexts are tied directly to displacement circumstances or other marginalizing factors affecting local migrant and minority populations generally., Methods: We investigated these questions using novel survey data from 577 women at the northern Thai-Myanmar border, where thousands of people have fled conflict in Shan State, Myanmar, for refuge in a range of precarious settings in Thailand, including unofficial refugee camps, villages, and worksites. We compared HRV exposures by ethnicity, country of birth, legal documentation, and residential setting. We then analyzed perinatal outcomes associated with HRV frequency, timing, and type., Results: Birth in Myanmar, and ethnic minority and precarious legal status more broadly, predicted higher HRV prevalence. HRV frequency significantly predicted unmet antenatal care and lower birth weight, along with HRVs related to labor exploitation and violence or conflict. HRVs timed closer to pregnancies were more adversely associated with perinatal outcomes. Resource/property deprivation was the strongest predictor of pregnancy complications., Conclusions: Human rights must be urgently attended to, through expanded HRV screenings and responsive care, and policy changes to further protect migrant workers, displaced persons, and others in precarious legal status situations.

Background: The COVID-19 pandemic and stay-at-home orders have caused an unprecedented decrease in the administration of routinely recommended vaccines. However, the impact of this decrease on overall vaccination coverage in a specific birth cohort is not known., Methods: We projected measles vaccination coverage for the cohort of children becoming one year old in 2020 in the United States, for different durations of stay-at-home orders, along with varying catch-up vaccination efforts., Results: A 15% sustained catch-up rate outside stay-at-home orders (compared to what would be expected via natality information) may be necessary to achieve projected vaccination coverage similar to previous years. Permanent decreases in vaccine administration could lead to projected vaccination coverage levels below 80%., Conclusion: Modeling measles vaccination coverage under a range of scenarios provides useful information about the potential magnitude and impact of under-immunization. Sustained catch-up efforts are needed to assure that measles vaccination coverage remains high., Competing Interests: Declaration of Competing Interest CC, MP, MN, CR, LF, and YTC are employees and shareholders of Merck & Co. JHC reports personal fees from Merck Vaccines, grants from Sanofi Pasteur Vaccines, personal fees from GSK vaccines, personal fees from Pfizer vaccines., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose of Review: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), continues to affect individuals, communities, and health systems worldwide. Here, we highlight how COVID-19 threatens to jeopardize the tremendous gains made over the last few decades on improving children's health globally., Recent Findings: In contrast to adults, children with COVID-19 are less likely to develop severe disease requiring hospitalization or die as a direct result of infection. However, the pandemic will likely have other important health impacts disproportionately affecting vulnerable children globally. Possible effects include worsening of poverty and food insecurity; disruption of already strained routine child health services; damage to already imperiled healthcare workforces; a wave of mental health challenges; interruption of education; and increased risks of violence, abuse, exploitation, and neglect. These challenges notwithstanding, the response to COVID-19 may also provide opportunities, such as for health system strengthening, that could improve child health after the pandemic., Summary: The negative impacts of COVID-19 on global child health may be substantial. However, these are not foregone conclusions and much can be done to mitigate the worst outcomes. Child health providers should advocate for an equitable response to COVID-19 that prioritizes the health of vulnerable children and furthers the gains made in global child health., Competing Interests: Conflict of InterestThe authors have no financial relationships relevant to this article to disclose. JHC acts as an advisor/consultant for GSK, Pfizer, Moderna, and Merck Vaccines and is a principal investigator or co-principal investigator for immunization projects with funding from Sanofi Pasteur and the United States Centers for Disease Control. All other authors have no conflicts of interest relevant to this article to disclose., (© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2021.)

Antimicrobial resistance resulting from antibiotic overuse represents an increasing public health challenge. The purpose of this study was to investigate antibiotic self-medication practices in a rural, indigenous Guatemalan population, and to compare self-prescribing patterns in rural and semi-urban populations using a One Health integrated approach, a framework acknowledging that health arises at the interface of humans, animals, and the environment. We conducted a mixed methods study using semi-structured interviews in and around San Lucas Tolimán, Guatemala. Antibiotic self-medication was common in both rural and semi-urban populations, regardless of demographic characteristics. Antibiotic usage in animals, while less common, almost always occurred without a veterinary consult. Although subjects recognized that self-medication could be harmful to health, they face significant barriers to accessing appropriate care. These patterns of use have impacts on the rise of antimicrobial resistance locally, and have the potential to contribute to the spread of such resistance globally.

Background: Acellular pertussis vaccines were initially licensed based on placebo-controlled efficacy trials, but such trials are no longer ethical. The effectiveness of current pertussis vaccines among properly vaccinated children <5 years is so high that a randomized trial is infeasible. Fluctuations in pertussis incidence and characteristics of the US vaccine marketplace make selection of suitable controls for a case-control study problematic. To satisfy an FDA requirement to evaluate rates of pertussis following licensure of Pentacel® vaccine, we used a case-cohort study design with a novel method for characterizing the cohort population., Methods: This prospective, observational study was conducted in Wisconsin from 2010 to 2014 among Wisconsin residents <60 months of age who received ≤four doses of pertussis vaccine (surveillance population). Cases were identified by the Wisconsin Division of Public Health. Characteristics and pertussis vaccinations of the surveillance population were estimated by ongoing random telephonic survey. The primary objective was to determine rates of pertussis disease among those who received only Pentacel vaccine (Group 1) vs those who received a single brand of vaccine other than Pentacel vaccine (Group 2)., Results: 1195 pertussis cases were identified. It was estimated that the surveillance population accrued a total of 1,133,403 person-years (Group 1, 39%; Group 2, 41%; Group 3 [those not in Group 1 or Group 2], 20%). Pertussis rates were similar in Group 1 (98.9/100,000) and Group 2 (96.2/100,000); rate ratios were 1.03 (unadjusted; 90% CI, 0.92-1.15) and 0.99 (adjusted; 90% CI, 0.89-1.12). Persons with one or more delayed vaccinations had a 66% higher risk of pertussis (90% CI, 39-96%)., Discussion: Pertussis protection was not found to differ for recipients of the newly licensed vs other available pertussis vaccines. Delayed vaccination substantially increased risk of pertussis. Sample survey methodology was able to characterize the study cohort and enable an otherwise-infeasible study. Clinical Trial Registry number: ClinicalTrials.gov, NCT01129362., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Drs. Decker, Greenberg, and Pool were employees of Sanofi Pasteur at the time of the study; Dr. Decker has since retired. Drs Conway and Eickhoff are employees of the University of Wisconsin, which received funding from Sanofi Pasteur to conduct this study. Dr. Davis was an employee of the Wisconsin Division of Public Health. Drs. Conway, Decker, Greenberg, and Pool participated in the conception, design, oversight, analysis, and reporting of the study; Dr. Davis participated in design, oversight, and data collection for the study; Dr. Eickhoff participated in design, analysis, and reporting of the study. Apart from Dr. Davis, who died in 2018, all authors wrote or revised the manuscript; approve of the final manuscript; and attest they meet the ICMJE criteria for authorship., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Blastomyces dermatitidis is a dimorphic fungus endemic to the United States and Canada. Although both Histoplasma and Blastomyces are found in similar geographic regions, Blastomyces is many times more likely to cause dissemination in the immunocompetent host, frequently involving the bone. However, given the indolent nature of this fungal infection and more prevalent bacterial etiologies of osteomyelitis, diagnosis and treatment are often significantly delayed. We review 2 pediatric cases that initially presented with isolated orthopedic symptoms without documented fever or pulmonary complaints, although both had signs of pulmonary infection on imaging. These cases demonstrate the importance of a high level of suspicion as well as appropriate diagnostic workup, including surgical pathology with fungal stains, when evaluating osteomyelitis in patients exposed to a Blastomyces-endemic region.

Background: Human papillomavirus (HPV) vaccines have been recommended as primary prevention of HPV-related cancers for over 10 years in the United States, and evidence reveals decreased incidence of HPV infections following vaccination. However, concerns have been raised that HPV vaccines could decrease fertility. This study examined the relationship between HPV immunization and self-reported infertility in a nationally representative sample., Methods: Data from the 2013-2016 National Health and Nutrition Examination Survey were analyzed to assess likelihood of self-reported infertility among women aged 20 to 33, who were young enough to have been offered HPV vaccines and old enough to have been queried about infertility (n = 1114). Two logistic regression models, stratified by marital history, examined potential associations between HPV vaccination and infertility. Model 1 assessed the likelihood of infertility among women who had never been pregnant or whose pregnancies occurred prior to HPV vaccination. Model 2 accounted for the possibility of latent and/or non-permanent post-vaccine infertility by including all women 20-33 years old who reported any 12-month period of infertility., Results: 8.1% reported any infertility. Neither model revealed any association between HPV vaccination at any age and self-reported infertility, regardless of marital status., Conclusion: There was no evidence of increased infertility among women who received the HPV vaccine. These results provide further evidence of HPV vaccine safety and should give providers confidence in recommending HPV vaccination. Further research should explore protective effects of HPV vaccines on female and male fertility., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Dr. Conway has been engaged as a consultant and/or participated in advisory boards with: Sanofi Pasteur, GSK, Pfizer, and Merck Vaccines and has served as a principal investigator for a Sanofi Pasteur project related to pertussis vaccines. Dr. LoConte has served on advisory boards for Bayer and Celgene and been a consultant for Abbvie. No other authors have any potential conflicts of interest to disclose]., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

An intramolecular Ir(III)-catalyzed regiodivergent oxyamination of unactivated alkenes provides valuable γ-lactams, γ-lactones and δ-lactams. The regioselectivity is controlled by the electronically tunable cyclopentadienyl Ir(III)-complexes enabling oxyamination via either 5-exo or 6-endo pathways. With respect to the mechanism, we propose a highly reactive [3.1.0] bicycle intermediate derived from Ir(V) nitrene-mediated aziridination to be a key intermediate toward the synthesis of γ-lactams.

Alkenyl N-pivaloylhydroxamates undergo an Ir(III)-catalyzed diamination of the alkene with simple exogenous secondary amines under extraordinarily mild reaction conditions. The regioselectivity of the diamination is controlled by the solvent and the electronics of the cyclopentadienyl (Cp x ) ligand on Ir. On the basis of a set of mechanistic experiments, we propose that the relative rates of Ir(V)-nitrenoid formation versus attack on the amido-Ir-coordinated alkene by the exogenous amine determine the outcome of the reaction.

Musculoskeletal infections, including osteomyelitis, septic arthritis, and pyomyositis, are a substantial cause of morbidity in children and adolescents. The increased virulence of infectious agents and the increased prevalence of antimicrobial-resistant pathogens, particularly methicillin-resistant Staphylococcus aureus, have resulted in a more complicated clinical course for diagnosis and management, which is evidenced by an increased length of hospital stays, incidence of complications, and number of surgical interventions. Musculoskeletal infections are a challenge for surgeons because they vary substantially in their presentation and in their required treatment, which is based on the causative organism, the location of the infection, and the age of the patient. The necessity for a prompt diagnosis is complicated by several diseases that may mimic musculoskeletal infection, including transient synovitis, autoimmune arthritis, and tumors. Recent innovations in diagnosis and management have provided surgeons with new options to differentiate musculoskeletal infections from these rapidly evolving disease pathologies. As diagnostic and treatment modalities improve, collaboration among surgeons from multiple disciplines is required to develop evidence-based clinical practice guidelines that minimize the effect of musculoskeletal infection and optimize clinical outcomes for patients.

Improving childhood vaccination coverage and timeliness is a key health policy objective in many developing countries such as Uganda. Of the many factors known to influence uptake of childhood immunizations in under resourced settings, parents' understanding and perception of childhood immunizations has largely been overlooked. The aims of this study were to survey mothers' knowledge and attitudes towards childhood immunizations and then determine if these variables correlate with the timely vaccination coverage of their children. From September to December 2013, we conducted a cross-sectional survey of 1,000 parous women in rural Sheema district in southwest Uganda. The survey collected socio-demographic data and knowledge and attitudes towards childhood immunizations. For the women with at least one child between the age of one month and five years who also had a vaccination card available for the child (N = 302), the vaccination status of this child was assessed. 88% of these children received age-appropriate, on-time immunizations. 93.5% of the women were able to state that childhood immunizations protect children from diseases. The women not able to point this out were significantly more likely to have an under-vaccinated child (PR 1.354: 95% CI 1.018-1.802). When asked why vaccination rates may be low in their community, the two most common responses were "fearful of side effects" and "ignorance/disinterest/laziness" (44% each). The factors influencing caregivers' demand for childhood immunizations vary widely between, and also within, developing countries. Research that elucidates local knowledge and attitudes, like this study, allows for decisions and policy pertaining to vaccination programs to be more effective at improving child vaccination rates.

Background: During October 2011-December 2012, concurrent with a statewide pertussis outbreak, 443 Bordetella parapertussis infections were reported among Wisconsin residents. We examined clinical features of patients with parapertussis and the effect of antibiotic use for treatment and prevention., Methods: Patients with polymerase chain reaction results positive for B. parapertussis reported during October 2011-May 2012 were interviewed regarding presence and durations of pertussis-like symptoms and receipt of azithromycin treatment. Data regarding acute cough illnesses and receipt of azithromycin prophylaxis among parapertussis patient household members (HHMs) were also collected. Using multivariate repeated measures log-binomial regression analysis, we examined associations of treatment receipt by the HHM with the earliest illness onset and prophylaxis receipt among other HHMs with the presence of any secondary cough illnesses in the household., Results: Among 218 patients with parapertussis, pertussis-like symptoms were frequently reported. Illness durations were significantly shorter among patients with treatment initiated 0-6 days after cough onset, compared with nonrecipients (median durations: 10 vs 19 days, P = .002). Among 361 HHMs from 120 households, compared with nonrecipients, prompt prophylaxis of HHMs was associated with no secondary cough illnesses (relative risk: 0.16; 95% confidence interval, .04-.69)., Conclusions: Bordetella parapertussis infection causes pertussis-like illness that might be misclassified as pertussis if B. parapertussis testing is not performed. Prompt treatment might shorten illness duration, and prompt HHM prophylaxis might prevent secondary illnesses. Further study is needed to evaluate antibiotic effectiveness for preventing parapertussis and to determine risks and benefits of antibiotic use., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Vaccines are one of the greatest public health achievements, preventing both mortality and morbidity. However, overall immunization rates are still below the 90% target for Healthy People 2020. There remain significant disparities in immunization rates between children of different racial/ethnic groups, as well as among economically disadvantaged populations. There are systemic issues and challenges in providing access to immunization opportunities. In addition, vaccine hesitancy contributes to underimmunization. Multiple strategies are needed to improve immunization rates, including improving access to vaccines and minimizing financial barriers to families. Vaccine status should be assessed and vaccines given at all possible opportunities., (Copyright © 2015 Elsevier Inc. All rights reserved.)

On February 22, 2013, the Advisory Committee on Immunization Practices (ACIP) revised recommendations for vaccination of pregnant women to recommend tetanus-diphtheria-acellular pertussis vaccine (Tdap) during every pregnancy, optimally at 27-36 weeks of gestation, to prevent pertussis among their newborns. Since 2004, influenza vaccination has been recommended for pregnant women in any trimester to prevent influenza and associated complications for mother and newborn. To evaluate vaccination of pregnant women in Wisconsin after the 2013 Tdap recommendation, health insurance claims data for approximately 49% of Wisconsin births were analyzed. The percentage of women who received Tdap during pregnancy increased from 13.8% of women delivering during January 2013 (63.1% of whom received Tdap 2-13 weeks before delivery) to 51.0% of women delivering during March 2014 (90.9% of whom received Tdap 2-13 weeks before delivery). Among women delivering during November 2013-March 2014, 49.4% had received influenza vaccine during pregnancy. After the 2013 recommendation, Tdap vaccination among pregnant women increased but plateaued at rates similar to influenza vaccination rates. Prenatal care providers should implement, evaluate, and improve Tdap and influenza vaccination programs, and strongly recommend that pregnant patients receive these vaccines to prevent severe illness and complications among mothers and infants.

Context: Vaccination coverage rates can be improved through the application of complete and accurate immunization information systems (IISs)., Objective: Evaluate the completeness and accuracy of Wisconsin's IIS, the Wisconsin Immunization Registry (WIR)., Design: Cross-sectional evaluation, comparing vaccination medical records (MRs) from provider clinics with WIR records., Participants: Medical records of patients born during 2009 were randomly selected from 251 Wisconsin clinics associated with the Vaccines for Children Program., Main Outcome Measures: Completeness: percentage of patients with client records in the WIR, percentage of patients up-to-date (%UTD) with the 4:3:1:3:3:1:4 vaccination series, and percentage of patients' MR vaccinations matched by administration date (±10 days) and type to vaccinations documented in the WIR. Accuracy: percentages of matched vaccinations with the same administration date, same trade name (TN), and same lot number., Results: Of the 1863 selected patient MRs, 98% (n = 1833) had WIR client records and 97% of their 30 899 vaccinations were documented in the WIR. The %UTD was 49.3% using the MR only, 76.5% using the WIR only, and 75.2% as estimated by the National Immunization Survey. Among matched vaccinations, 99% had the same administration date, 96% had the same TN, and 95% had the same lot number. Compared with patients from clinics that entered data into the WIR using data exchange from electronic health records, patients from clinics that entered data using the Web-based user interface were less likely to have client records in the WIR (odds ratio: 0.3; 95% confidence interval: 0.1-0.9) and less likely to have accurate TNs (odds ratio: 0.3; 95% confidence interval: 0.1-0.5)., Conclusions: The WIR was complete and accurate among this sample of children born during 2009 and provided a vaccination coverage assessment similar to the National Immunization Survey. Our results provide support for the expectation that meaningful use and other initiatives that increase data exchange from electronic health records to IISs will improve IIS data quality.

A resin-bound dinuclear zinc(II) complex for the selective capture of pyrophosphopeptides is reported. The metal complex binds diphosphate esters over other anionic groups, such as monophosphate esters, sulfate esters, and carboxylic acids, with high specificity. Immobilization of the compound provided a reagent capable of binding and retaining nanomolar quantities of pyrophosphopeptide in the presence of cell lysate. The high affinity and specificity of the reagent makes it an attractive tool for the study of in vivo pyrophosphorylation., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: We estimated the vaccine effectiveness (VE) of tetanus-diphtheria-acellular pertussis vaccine (Tdap) for preventing pertussis among adolescents during a statewide outbreak of pertussis in Wisconsin during 2012., Methods: We used the population-based Wisconsin Immunization Registry (WIR) to construct a cohort of Wisconsin residents born during 1998-2000 and collect Tdap vaccination histories. Reports of laboratory-confirmed pertussis with onset during 2012 were matched to WIR clients. Incidence rate ratios (IRRs) of pertussis and Tdap VE estimates [(1 - IRR)*100%], by year of Tdap vaccine receipt and brand (Boostrix/Adacel), were estimated using Poisson regression., Results: Tdap VE decreased with increasing time since receipt, with VEs of 75.3% (95% confidence interval [CI], 55.2%-86.5%) for receipt during 2012, 68.2% (95% CI, 60.9%-74.1%) for receipt during 2011, 34.5% (95% CI, 19.9%-46.4%) for receipt during 2010, and 11.9% (95% CI, -11.1% to 30.1%) for receipt during 2009/2008; point estimates were higher among Boostrix recipients than among Adacel recipients. Among Tdap recipients, increasing time since receipt was associated with increased risk, and receipt of Boostrix (vs Adacel) was associated with decreased risk of pertussis (adjusted IRR, 0.62 [95% CI, .52-.74])., Conclusions: Our results demonstrate waning immunity following vaccination with either Tdap brand. Boostrix was more effective than Adacel in preventing pertussis in our cohort, but these findings may not be generalizable to adolescent cohorts that received different diphtheria-tetanus-acellular pertussis vaccines (DTaP) during childhood and should be further examined in studies that include childhood DTaP history., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

A highly selective and convenient method for the synthesis of pyrophosphopeptides in solution is reported. The remarkable compatibility with functional groups (alcohol, thiol, amine, carboxylic acid) in the peptide substrates suggests that the intrinsic nucleophilicity of the phosphoserine residue is much higher than previously appreciated. Because the methodology operates in polar solvents, including water, a broad range of pyrophosphopeptides can be accessed. We envision these peptides will find widespread applications in the development of mass spectrometry and antibody-based detection methods for pyrophosphoproteins.

Objective: Web sites describing residency programs are initial sources of information for applicants. The correlation of global health content on pediatric residency program Web sites with reported curricula is unknown. To determine the accuracy of global health education, information on program Web sites was compared with queried program content responses., Study Design: The Fellowship and Residency Electronic Interactive Database was used to assess pediatric residency programs' Web sites for global health education, applying American Academy of Pediatrics consensus guidelines. The authors developed a questionnaire using these consensus guidelines and contacted each program to assess Web site findings, and χ(2) tests were used to compare data from these 2 sources., Results: Of 194 programs, 177 had operational Web sites, of which 98 participated in the questionnaire (55%). Ninety-three of 177 programs (53%) reported global health education on Web sites, whereas 80 of 98 programs (82%) reported global health education through direct questioning (P < .001). Results include provision of resident salaries during global health elective (Web site 5% vs questionnaire 98%, P < .001), mandatory training before global health elective (8% vs 20%, P = .02), presence of global health elective curriculum (24% vs 75%, P < .001), postexperience debriefing (16% vs 29%, P = .05), and bidirectional resident exchange (2% vs 13%, P = .01)., Conclusions: Results indicate continued expansion of pediatric global health education, but significant differences exist between information on Web sites and data obtained through direct questioning. Accurate representation of global health opportunities would allow for more informed decision-making among prospective applicants. Findings also suggest substantial variability in global health curricula that needs to be addressed through improved planning and cooperation among training programs., (Published by Mosby, Inc.)

Pertussis remains difficult to control. Imperfect sensitivity of diagnostic tests and lack of specific guidance regarding interpretation of negative test results among patients with compatible symptoms may contribute to its spread. In this study, we examined whether additional pertussis cases could be identified if persons with negative pertussis test results were routinely investigated. We conducted interviews among 250 subjects aged ≤18 years with pertussis polymerase chain reaction (PCR) results reported from 2 reference laboratories in Wisconsin during July-September 2010 to determine whether their illnesses met the Centers for Disease Control and Prevention's clinical case definition (CCD) for pertussis. PCR validity measures were calculated using the CCD as the standard for pertussis disease. Two Bayesian latent class models were used to adjust the validity measures for pertussis detectable by 1) culture alone and 2) culture and/or more sensitive measures such as serology. Among 190 PCR-negative subjects, 54 (28%) had illnesses meeting the CCD. In adjusted analyses, PCR sensitivity and the negative predictive value were 1) 94% and 99% and 2) 43% and 87% in the 2 types of models, respectively. The models suggested that public health follow-up of reported pertussis patients with PCR-negative results leads to the detection of more true pertussis cases than follow-up of PCR-positive persons alone. The results also suggest a need for a more specific pertussis CCD.

Background: In 2006, routine two-dose varicella vaccination for all children was recommended, including a second dose catch-up program for older children and adolescents. Recent studies have shown that a second dose of the vaccine provides incremental protection against varicella disease., Methods: This study is a cross-sectional analysis of data collected in the National Immunization Survey-Teen 2010 combined with publicly available data related to state immunization requirements. Bivariate and multivariable logistic regression analyses were performed to examine individual-level and state-level factors associated with receipt of two doses of varicella vaccine among 10,542 adolescents 13 to 17 years of age with no history of varicella., Results: Overall, 58.1% of adolescents without any history of varicella had received two doses of varicella vaccine. Coverage varied widely among states, ranging from 19.7% in South Dakota to 85.3% in Rhode Island. In the multivariable model, receipt of two doses of varicella vaccine was significantly associated with younger age, higher maternal education level, private health insurance, more frequent health care visits, receipt of both quadrivalent meningococcal conjugate and tetanus, diphtheria, and acellular pertussis vaccinations, and residing in a state with two-dose policies for middle school entry. Vaccines for Children program-eligible adolescents were less likely to have received two doses., Conclusion: Two-dose varicella vaccination coverage remained low among adolescents in 2010, despite the universal recommendation. Programs that are aimed specifically at Vaccines for Children program-eligible adolescents, state policies requiring two doses for middle school entry, and broad education and implementation of the adolescent vaccination platform may help to improve varicella vaccination coverage.

The objectives of this study were to develop an animal model to study Listeria monocytogenes infection during the peri-parturient period and identify sources of maternal shedding of the pathogen. Peri-parturient mice were infected intragastrically with L. monocytogenes that expressed bacterial luciferase. Mice were then imaged in vivo over time. Secreted breast milk samples from mice infected after parturition were enriched and plated for culture and imaging. Bioluminescence imaging technology was able to detect luciferase emitting L. monocytogenes in vaginal secretions and maternal and fetal organs at 72 and 96 h post infection in mice infected prior to, or just after, parturition. The results from this study clearly show that L. monocytogenes is shed in vaginal secretions and disseminates to the mammary chain, from which it can be shed in the milk of peri-parturient mice.

It is well known that two regular tetrahedra can be combined with a single regular octahedron to tile (complete fill) three-dimensional Euclidean space . This structure was called the "octet truss" by Buckminster Fuller. It was believed that such a tiling, which is the Delaunay tessellation of the face-centered cubic (fcc) lattice, and its closely related stacking variants, are the only tessellations of that involve two different regular polyhedra. Here we identify and analyze a unique family comprised of a noncountably infinite number of periodic tilings of whose smallest repeat tiling unit consists of one regular octahedron and six smaller regular tetrahedra. We first derive an extreme member of this unique tiling family by showing that the "holes" in the optimal lattice packing of octahedra, obtained by Minkowski over a century ago, are congruent tetrahedra. This tiling has 694 distinct concave (i.e., nonconvex) repeat units, 24 of which possess central symmetry, and hence is distinctly different and combinatorically richer than the fcc tetrahedra-octahedra tiling, which only has two distinct tiling units. Then we construct a one-parameter family of octahedron packings that continuously spans from the fcc to the optimal lattice packing of octahedra. We show that the "holes" in these packings, except for the two extreme cases, are tetrahedra of two sizes, leading to a family of periodic tilings with units composed four small tetrahedra and two large tetrahedra that contact an octahedron. These tilings generally possess 2,068 distinct concave tiling units, 62 of which are centrally symmetric.

Accumulation of inspissated secretions that are difficult to clear and congest the airways is a feature of lung disease in patients with cystic fibrosis (CF). These secretions restrict airflow, harbour infection and limit the delivery of inhaled drugs including gene therapy vectors to the underlying target cells. Unfractionated heparin (UFH) has mucolytic properties suggesting that it may be a useful therapeutic agent for lung disease in these patients. For the pulmonary delivery of UFH to patients with CF, the dry powder inhaler has potential advantages over systems using nebulised suspensions. However, spray-dried particles in the appropriate size range (1-5 microm) may absorb atmospheric moisture, causing aggregation. UFH has been cospray-dried with L-leucine (1%, w/w) to produce particles that are less cohesive than UFH alone and show good aerosolisation performance. Rheological analysis has shown that spray-dried UFH and UFH cospray-dried with L-leucine significantly (p < 0.05) reduce the elasticity and yield stress of CF sputum. The superior physical properties of UFH/L-leucine indicate this is the preferred formulation for development as an inhaled mucolytic.

Objectives: To determine the current status of immunisation coverage in Western Kenya before intervention, to identify strengths and weaknesses of the existing programme in order to design educational interventions that could improve the services provided and find out the training needs of the mid-level managers of Kenya Expanded Programme of Immunisation., Design: Cross-sectional descriptive study., Setting: All thirty nine districts in Rift Valley, Western and Nyanza provinces., Subjects: Mid-level managers of Kenya Expanded Programme on Immunisation in the 39 districts and the provinces. These included Provincial Logisticians, Provincial Medical Officers of Health, District Medical Officers of Health, District Public Health Nurses, District Records and Health Information Officers, District Disease Surveillance Officers, and District Public Health Officers., Main Outcome Measures: Number of staff trained on EPI, coverage rates and perceived training needs of the mid-level managers., Results: A total of eighty eight mid-level managers participated in the interviews. Most of these were District Public Health Nurses (40.9%) and District Health Information and Records Officers (23.9%). Only 49 (25%) of the District Health Management Team members had undergone training at the supervisory level. Eighteen districts (43.6%) had no member of the District Health Management Team that had ever been trained at the supervisory level. Using rates of Pentavalent 1 and measles coverage, Nyanza Province had the highest immunisation dropout rate (Pentavalent 1--measles) whereas Rift Valley Province had the lowest. The annual cumulative coverage for all the provinces by antigen was 80% for Pentavalent 1 and 2 and 60% for measles. The most requested need for inclusion in the training curriculum was maintenance of the cold chain equipment., Conclusions: Most of the members in the study area have not been trained on Expanded Programme on Immunisation and may be ill-equipped to manage the complicated programmes needed to maximise delivery of services. The immunisation coverage in this area is low while the dropout rates are high. We therefore recommend that all the mid-level managers of Expanded Programme on Immunisation in this area be trained comprehensively through the Merck Vaccine Network--Africa programme using the World Health Organisation approved mid-level managers course.

An analytical algorithm has been recently described for converting planar scintigraphic images of aerosol distributions in the lungs to an equivalent three-dimensional (3D) representation. The recovery of the volumetric information has opened up to planar imaging the possibility of measuring aerosol deposition per airway generation. This paper investigates the accuracy and precision of the generation analysis achievable with planar imaging using simulation. Typical generation parameters--such as the bronchial and conducting airway deposition fractions (BADF and CADF)--have been derived. The accuracy of the technique has been measured by the coefficient of variation (COV) of the estimates from the known values used in the simulation. The results have also been compared to those obtained from 3D imaging (single photon emission computed tomography or SPECT). Finally, the technique has been applied to two aerosol studies conducted on a healthy volunteer, to demonstrate its implementation on clinical data. The accuracy of the BADF and CADF estimates from planar imaging were 42% and 41%, respectively; the corresponding values from SPECT were 32% and 22%. In conclusion, approximate estimates of airway distribution parameters can be derived from planar imaging. However, the errors are significantly higher than with SPECT.

Toxoplasmosis is an infrequent infection with a high mortality rate in hematopoietic stem cell transplant recipients, and is usually caused by reactivation of prior, latent infection upon intensive immunosuppression. We report a case of fatal disseminated toxoplasmosis, diagnosed at autopsy, in a 7-year-old boy who received a cord blood graft for recurrent acute lymphoblastic leukemia. This case represents both the first reported case of toxoplasmosis in an engrafted cord blood recipient, and also of graft failure due to toxoplasmosis. Recommendations for toxoplasmosis diagnosis, treatment, and prophylaxis in stem cell transplant recipients are reviewed.

An analytical algorithm is described for converting planar scintigraphic images of aerosol distributions in the lungs to an equivalent three-dimensional (3D) representation. The recovery of volumetric information should benefit regional quantification. The technique has been validated using simulated planar images of eleven known aerosol distributions in ten realistic lungs. Global and regional 3D parameters, such as the total activity deposition (A), the penetration index (PI) and the relative penetration index (rPI), were quantified on the planar images and on their 3D representation. Random and systematic errors of the estimation were measured. Finally, the performance of planar imaging was compared with that of single-photon emission computed tomography (SPECT). SPECT images were simulated for the same aerosol distributions in the same subjects and quantified for A, PI, and rPI. The systematic errors in A, PI and rPI obtained from planar imaging were 8.9%, 64.8%, and 54.1%, respectively, using the two-dimensional (2D) analysis; they improved significantly to 4.4%, 19.0%, and 25.5% with the 3D analysis (p < 0.01). The corresponding values for SPECT were 5.2%, 9.8%, and 15.7%, significantly better for PI and rPI (p < 0.01). The random errors of A were similar for all techniques being about 5%; those of PI and rPI measurements were significantly higher for planar imaging (