Maternal Interventions Vigilance may speed progress against the Sustainable Development Goals’ maternal, neonatal, and child health targets

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Above photo provided by the Bill & Melinda Gates Foundation.

 

Maternal Interventions Vigilance may speed progress against the Sustainable Development Goals’ maternal, neonatal, and child health targets By Ajoke Sobanjo-ter Meulen

 

Over the past three decades, major reductions in maternal and child deaths were achieved, but continued progress is needed to meet the Sustainable Development Goals by 2030.

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OCTOBER 2019 MEMBER NEWSLETTER

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Above photo, Photo by Ellery Lamm / Save the Children. A mother watches over her 5-month-old baby, Shahida, who has pneumonia in a hospital in Barisal district. Save the Children is helping to train healthcare providers to diagnose and treat pneumonia at the community level.

 

 A COMMENT FROM THE COORDINATOR 

 

This month, we will hear from PIN Member Ajoke Sobanjo-ter Meule as she describes the impact that maternal vaccination could have in reducing newborn deaths. We will also hear how parents and caregivers can have a larger role in helping reduce deaths related to childhood pneumonia. The Pneumonia Careseeking Scorecard reports that only 55% of children with pneumonia symptoms across 60 countries are taken to an appropriate healthcare provider. The scorecard urges: 1) increased awareness among parents and caregivers for the signs and symptoms of pneumonia; 2) greater policies and programs that support timely care; and 3) identification of vulnerable geographic areas and increasing careseeking support for those areas. View the full scorecard here.

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Prevalence of Immunodeficiency in Children With Invasive Pneumococcal Disease in the Pneumococcal Vaccine Era A Systematic Review

By Coen Butters, Linny Kimly Phuong, BPharm(Hons), Theresa Cole, Amanda Gwee. Published in JAMA Pediatrics. September 30, 2019.  

 

Despite increasing access to vaccination, invasive pneumococcal disease (IPD) is responsible for approximately 826 000 deaths worldwide in children younger than 5 years each year. To allow early identification and prevention, an improved understanding of risk factors for IPD is needed. To review the literature on the prevalence of primary immunodeficiency (PID) in children younger than 18 years presenting with IPD without another predisposing condition and to inform guidelines for immunologic evaluation after the first episode of IPD based on published evidence. A literature search of PubMed, Embase (inception [1974] to February 28, 2019), and MEDLINE (inception [1946] to February 28, 2019) was conducted using the terms Streptococcus pneumonia, Streptococcus pneumoniae, pneumococcal infection, Streptococcus infection, pneumococcal meningitis, immunodeficiency, immune response, immunocompromised, susceptib*, precursor, predispose*, recurren*, newborn, neonat*, infan*, toddler, child, preschooler, adolescen*, and pediatric. Publications reporting original data on immunodeficiency in children with microbiologically confirmed primary or recurrent IPD were included. Strength of clinical data was graded according to the 5-point scale of the Oxford Centre for Evidence-Based Medicine. In 6022 unique children with primary IPD, 5 of 393 (1.3%) to 17 of 162 (10.5%) of all children and 14 of 53 (26.4%) of those older than 2 years had a PID identified. Higher rates of PID, up to 10 of 15 (66.7%), were found in children with recurrent IPD. Antibody deficiency was the most common immunodeficiency, followed by complement deficiency, asplenia, and rarer defects in T-cell signaling. The site of infection was a key indicator for the risk of underlying PID, with the greatest risk of PID in children with meningitis or complicated pneumonia. Results of this study suggest that invasive pneumococcal disease, and particularly recurrent IPD, is an important marker of underlying PID in children without other risk factors. The findings also suggest that children older than 2 years with pneumococcal meningitis or complicated pneumonia and all children with recurrent IPD should be referred for an immune evaluation.

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View the accompanying editorial ‘Invasive Pneumococcal Disease—Not Evenly Shared by All Children’ By Stephen I. Pelton, Rotem Lapidot, and Inci Yildirim.

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Identifying residual hotspots and mapping lower respiratory infection morbidity and mortality in African children from 2000 to 2017

By Robert C. Reiner, Catherine A. Welgan, Daniel C. Casey, Christopher E. Troeger, Mathew M. Baumann, QuynhAnh P. Nguyen, Scott J. Swartz, Brigette F. Blacker, Aniruddha Deshpande, Jonathan F. Mosser, Aaron E. Osgood-Zimmerman, Lucas Earl, Laurie B. Marczak, Sandra B. Munro, Molly K. Miller-Petrie, Grant Rodgers Kemp, Joseph Frostad, Kirsten E. Wiens, Paulina A. Lindstedt, David M. Pigott, Laura Dwyer-Lindgren, Jennifer M. Ross, Roy Burstein, Nicholas Graetz, Puja C. Rao, Ibrahim A. Khalil, Nicole Davis Weaver, Sarah E. Ray, Ian Davis, Tamer Farag, Oliver J. Brady, Moritz U. G. Kraemer, David L. Smith, Samir Bhatt, Daniel J. Weiss, Peter W. Gething, Nicholas J. Kassebaum, Ali H. Mokdad, Christopher J. L. Murray & Simon I. Hay. Published in Nature Microbiology. September 30, 2019.  

Lower respiratory infections (LRIs) are the leading cause of death in children under the age of 5, despite the existence of vaccines against many of their aetiologies. Furthermore, more than half of these deaths occur in Africa. Geospatial models can provide highly detailed estimates of trends subnationally, at the level where implementation of health policies has the greatest impact. We used Bayesian geostatistical modelling to estimate LRI incidence, prevalence and mortality in children under 5 subnationally in Africa for 2000–2017, using surveys covering 1.46 million children and 9,215,000 cases of LRI. Our model reveals large within-country variation in both health burden and its change over time. While reductions in childhood morbidity and mortality due to LRI were estimated for almost every country, we expose a cluster of residual high risk across seven countries, which averages 5.5 LRI deaths per 1,000 children per year. The preventable nature of the vast majority of LRI deaths mandates focused health system efforts in specific locations with the highest burden.

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Oral Lefamulin vs Moxifloxacin for Early Clinical Response Among Adults With Community-Acquired Bacterial Pneumonia

By Elizabeth Alexander, Lisa Goldberg, Anita F. Das, Gregory J. Moran, Christian Sandrock, Leanne B. Gasink, Patricia Spera, Carolyn Sweeney, Susanne Paukner, Wolfgang W. Wicha, Steven P. Gelone, Jennifer Schranz. JAMA. September 27, 2019.

 

Is 5-day oral lefamulin noninferior to 7-day oral moxifloxacin in the management of community-acquired bacterial pneumonia? In this randomized clinical trial that included 738 patients, the early clinical response at 96 hours (within a 24-hour window) after the first dose of study drug was 90.8% in the lefamulin group and 90.8% in the moxifloxacin group, a difference that met the noninferiority margin of 10%. This study demonstrated the noninferiority of oral lefamulin to oral moxifloxacin for the treatment of community-acquired bacterial pneumonia.

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View the accompanying editorial ‘Lefamulin—A New Antibiotic for Community-Acquired Pneumonia’ by Preeti N. Malani.

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Bubble continuous positive airway pressure for children with high-risk conditions and severe pneumonia in Malawi: an open label, randomised, controlled trial

By Eric D McCollum, Tisungane Mvalo, Michelle Eckerle, Andrew G Smith, Davie Kondowe, Don Makonokaya, Dhananjay Vaidya, Veena Billioux, Alfred Chalira, Norman Lufesi, Innocent Mofolo, Mina Hosseinipour

The Lancet Respiratory Medicine. September 24, 2019

 

Pneumonia is the leading cause of death among children globally. Most pneumonia deaths in low-income and middle-income countries (LMICs) occur among children with HIV infection or exposure, severe malnutrition, or hypoxaemia despite antibiotics and oxygen. Non-invasive bubble continuous positive airway pressure (bCPAP) is considered a safe ventilation modality that might improve child pneumonia survival. bCPAP outcomes for high-risk African children with severe pneumonia are unknown. Since most child pneumonia hospitalisations in Africa occur in non-tertiary district hospitals without daily physician oversight, we aimed to examine whether bCPAP improves severe pneumonia mortality in such settings. This open-label, randomised, controlled trial was done in the general paediatric ward of Salima District Hospital, Malawi. We enrolled children aged 1–59 months old with WHO-defined severe pneumonia and either HIV infection or exposure, severe malnutrition, or an oxygen saturation of less than 90%. Children were randomly assigned 1:1 to low-flow nasal cannula oxygen or nasal bCPAP. Non-physicians administered care; the primary outcome was hospital survival. Primary analyses were by intention-to-treat and interim and adverse events analyses per protocol. This trial is registered with ClinicalTrials.gov, number NCT02484183, and is closed. We screened 1712 children for eligibility between June 23, 2015, and March 21, 2018. The data safety and monitoring board stopped the trial for futility after 644 of the intended 900 participants were enrolled. 323 children were randomly assigned to oxygen and 321 to bCPAP. 35 (11%) of 323 children who received oxygen died in hospital, as did 53 (17%) of 321 who received bCPAP (relative risk 1·52; 95% CI 1·02–2·27; p=0·036). 13 oxygen and 17 bCPAP patients lacked hospital outcomes and were considered lost to follow-up. Suspected adverse events related to treatment occurred in 11 (3%) of 321 children receiving bCPAP and 1 (<1%) of 323 children receiving oxygen. Four bCPAP and one oxygen group deaths were classified as probable aspiration episodes, one bCPAP death as probable pneumothorax, and six non-death bCPAP events included skin breakdown around the nares. bCPAP treatment in a paediatric ward without daily physician supervision did not reduce hospital mortality among high-risk Malawian children with severe pneumonia, compared with oxygen. The use of bCPAP within certain patient populations and non-intensive care settings might carry risk that was not previously recognised. bCPAP in LMICs needs further evaluation before wider implementation for child pneumonia care.

 

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Pneumonia Careseeking Scorecard 2019

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What proportion of children with symptoms of pneumonia are taken to an appropriate healthcare provider?

 

This is a question that all countries should be asking as the answer is critical for the achievement of the Sustainable Development Goal for child survival (SDG 3.2) and progress towards Universal Health Coverage (UHC). Pneumonia is the leading cause of death among children under five years in most countries. Increasing the proportion of children who seek care when they are sick will be an essential tool to increase treatment rates and drive child pneumonia deaths to below 3 per 1,000 live births (the GAPPD target) and overall child deaths to below 25 per 1,000 live births (the SDG 3.2 target). Careseeking for a child exhibiting the symptoms of pneumonia is now the official indicator for “child treatment” in the UHC Service Coverage Index developed by the World Health Organization (WHO) and the World Bank. This means that countries seeking to achieve UHC must ensure that more than 90% of children with pneumonia symptoms are taken to an appropriate healthcare provider.

 

View the full report here.

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First tertiary hospital "Gabriel Touré" of Bamako, Mali.

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Levels and trends in child mortality 2019

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Above photo, credit to UNICEF, WHO, World Bank Group and United Nations

 

The United Nations Inter-agency Group for Child Mortality Estimation (UN IGME) produces estimates of child and young adolescent mortality annually, reconciling the differences across data sources and taking into account the systematic biases associated with the various types of data on child and adolescent mortality. This report presents UN IGME’s latest estimates – through 2018 – of neonatal, infant and under-five mortality as well as mortality among children aged 5–14 years. It assesses progress in the reduction of child and young adolescent mortality at the country, regional and global levels, and provides an overview of the methods used to estimate the mortality indicators above.

 

Please view the full report here. 

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Gavi sets US$7·4 billion replenishment target

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Above, photo provided by Daphnee Cook / Save the Children. Susan, 4 months, receives a vaccination with the help of her mother Rebecca, 33.

 

By Ann Danaiya Usher

 

Published September 7, 2019

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Rapid Molecular Tests for Influenza, Respiratory Syncytial Virus, and Other Respiratory Viruses: A Systematic Review of Diagnostic Accuracy and Clinical Impact Studies

By Laura M Vos, Andrea H L Bruning, Johannes B Reitsma, Rob Schuurman, Annelies Riezebos-Brilman, Andy I M Hoepelman, Jan Jelrik Oosterheert

Clinical Infectious Diseases. October 1, 2019.

 

We systematically reviewed available evidence from Embase, Medline, and the Cochrane Library on diagnostic accuracy and clinical impact of commercially available rapid (results <3 hours) molecular diagnostics for respiratory viruses as compared to conventional molecular tests. Quality of included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies criteria for diagnostic test accuracy (DTA) studies, and the Cochrane Risk of Bias Assessment and Risk of Bias in Nonrandomized Studies of Interventions criteria for randomized and observational impact studies, respectively. Sixty-three DTA reports (56 studies) were meta-analyzed with a pooled sensitivity of 90.9% (95% confidence interval [CI], 88.7%–93.1%) and specificity of 96.1% (95% CI, 94.2%–97.9%) for the detection of either influenza virus (n = 29), respiratory syncytial virus (RSV) (n = 1), influenza virus and RSV (n = 19), or a viral panel including influenza virus and RSV (n = 14). The 15 included impact studies (5 randomized) were very heterogeneous and results were therefore inconclusive. However, we suggest that implementation of rapid diagnostics in hospital care settings should be considered.

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Low Admission Plasma Gelsolin Concentrations Identify Community-acquired Pneumonia Patients at High Risk for Severe Outcomes

By Wesley H Self, Richard G Wunderink, Mark J DiNubile, Thomas P Stossel, Susan L Levinson, Derek J Williams, Evan J Anderson, Anna M Bramley, Seema Jain, Kathryn M Edwards, Carlos G Grijalva

Clinical Infectious Diseases. October 1, 2019.

 

Plasma gelsolin (pGSN) is an abundant circulating protein that neutralizes actin exposed by damaged cells, modulates inflammatory responses, and enhances alveolar macrophage antimicrobial activity. We investigated whether adults with low pGSN at hospital admission for community-acquired pneumonia (CAP) were at high risk for severe outcomes.

Admission pGSN concentrations in 455 adults hospitalized with CAP were measured using enzyme-linked immunosorbent assay. Patients were grouped into the following 4 hierarchical, mutually exclusive categories based on maximum clinical severity experienced during their hospitalization: general floor care without intensive care unit (ICU) admission, invasive respiratory or vasopressor support (IRVS), or death; ICU care without IRVS or death; IRVS without death; or death. Admission pGSN concentrations were compared across these discrete outcome categories. Additionally, outcomes among patients in the lowest quartile of pGSN concentration were compared to those in the upper 3 quartiles.

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Interaction With Nontypeable Haemophilus influenzae Alters Progression of Streptococcus pneumoniae From Colonization to Disease in a Site-Specific Manner

By Joseph A Lewnard, Noga Givon-Lavi, Ron Dagan

The Journal of Infectious Diseases. October 15, 2019.

 

Pneumococci and nontypeable Haemophilus influenzae (NTHi) often cocolonize children. The impact of species interactions on disease risk across the upper respiratory mucosa is not known.

We analyzed data from 4104 acute conjunctivitis (AC) cases, 11 767 otitis media (OM) cases, and 1587 nasopharyngeal specimens collected from Israeli children before pneumococcal conjugate vaccine introduction. We compared pneumococcal serotype distributions with NTHi present and absent, and compared single-species and mixed-species rates of serotype-specific progression from colonization to AC and OM.

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Passage Adaptation Correlates With the Reduced Efficacy of the Influenza Vaccine

By Hui Chen, Jacob Josiah Santiago Alvarez, Sock Hoon Ng, Rasmus Nielsen, Weiwei Zhai

Clinical Infectious Diseases. October 1, 2019.

 

As a dominant seasonal influenza virus, H3N2 virus rapidly evolves in humans and is a constant threat to public health. Despite sustained research efforts, the efficacy of H3N2 vaccine has decreased rapidly. Even though antigenic drift and passage adaptation (substitutions accumulated during vaccine production in embryonated eggs) have been implicated in reduced vaccine efficacy (VE), their respective contributions to the phenomenon remain controversial.

We utilized mutational mapping, a powerful probabilistic method for studying sequence evolution, to analyze patterns of substitutions in different passage conditions for an unprecedented amount of H3N2 hemagglutinin sequences (n = 32 278).

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Stockpiled Avian Influenza A(H7N9) Vaccines Induce Robust, Nonneutralizing Functional Antibodies Against Antigenically Drifted Fifth-Wave A(H7N9) Viruses

By Weimin Zhong, Min Z Levine

The Journal of Infectious Diseases. October 15, 2019.

 

Human infections caused by avian influenza A(H7N9) viruses have raised concerns of a pandemic. The capability of the current stockpiled A(H7N9) vaccines to induce cross-protective, nonneutralizing functional antibodies against antigenically drifted A(H7N9) viruses has not been evaluated before. Here we show that vaccination with either MF59- or AS03-adjuvanted inactivated A(H7N9) vaccines elicited robust, cross-reactive antibody-dependent cell-mediated cytotoxicity–mediating and neuraminidase-inhibiting functional antibodies against the antigenically drifted A(H7N9) viruses that emerged recently during the fifth-wave outbreak in China, including a highly pathogenic A(H7N9) human isolate. Such cross-reactive humoral immunity may provide vital first-line defense against fatal outcomes in case of an A(H7N9) pandemic.

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Prevention of Influenza Hospitalization Among Adults in the United States, 2015–2016: Results From the US Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN)

By Jill M Ferdinands, Manjusha Gaglani, Emily T Martin, Don Middleton, Arnold S Monto, Kempapura Murthy, Fernanda P Silveira, H Keipp Talbot, Richard Zimmerman, Elif Alyanak, Courtney Strickland, Sarah Spencer, Alicia M Fry, HAIVEN Study Investigators

The Journal of Infectious Diseases. October 15, 2019.

 

Evidence establishing effectiveness of influenza vaccination for prevention of severe illness is limited. The US Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN) is a multiyear test-negative case-control study initiated in 2015–2016 to estimate effectiveness of vaccine in preventing influenza hospitalization among adults.

Adults aged ≥18 years admitted to 8 US hospitals with acute respiratory illness and testing positive for influenza by polymerase chain reaction were cases; those testing negative were controls. Vaccine effectiveness was estimated with logistic regression adjusting for age, comorbidities, and other confounding factors and stratified by frailty, 2-year vaccination history, and clinical presentation.

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Relative Effectiveness of Cell-Cultured and Egg-Based Influenza Vaccines Among Elderly Persons in the United States, 2017–2018

By Hector S Izurieta, Yoganand Chillarige, Jeffrey Kelman, Yuqin Wei, Yun Lu, Wenjie Xu, Michael Lu, Douglas Pratt, Steve Chu, Michael Wernecke, Thomas MaCurdy, Richard Forshee

The Journal of Infectious Diseases. October 15, 2019.

 

The low influenza vaccine effectiveness (VE) observed during the A(H3N2)-dominated 2017–2018 season may be due to vaccine virus adaptation to growth in eggs. We compared the effectiveness of cell-cultured and egg-based vaccines among Medicare beneficiaries.

Retrospective cohort study on Medicare beneficiaries aged ≥65 years who received an influenza vaccine (cell-cultured, egg-based quadrivalent; egg-based high-dose, adjuvanted, or standard-dose trivalent) during the 2017–2018 season. We used Poisson regression to evaluate relative VE (RVE) in preventing influenza-related hospital encounters.

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Passage Adaptation Correlates With the Reduced Efficacy of the Influenza Vaccine

By Hui Chen, Jacob Josiah Santiago Alvarez, Sock Hoon Ng, Rasmus Nielsen, Weiwei Zhai

Clinical Infectious Diseases. October 1, 2019.

 

As a dominant seasonal influenza virus, H3N2 virus rapidly evolves in humans and is a constant threat to public health. Despite sustained research efforts, the efficacy of H3N2 vaccine has decreased rapidly. Even though antigenic drift and passage adaptation (substitutions accumulated during vaccine production in embryonated eggs) have been implicated in reduced vaccine efficacy (VE), their respective contributions to the phenomenon remain controversial.

We utilized mutational mapping, a powerful probabilistic method for studying sequence evolution, to analyze patterns of substitutions in different passage conditions for an unprecedented amount of H3N2 hemagglutinin sequences (n = 32 278).

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Things We Do For No Reason: Routine Blood Culture Acquisition for Children Hospitalized with Community-Acquired Pneumonia

By David P Johnson, Vivian Lee, Anand Gourishankar, Prabi Rajbhandari, Matthew Schefft, Marquita Genies. Published in Journal of Hospital Medicine. Published September 18, 2019.  

 

Inspired by the ABIM Foundation's Choosing Wisely® campaign, the "Things We Do for No Reason™" (TWDFNR) series reviews practices that have become common parts of hospital care but may provide little value to our patients. Practices reviewed in the TWDFNR series do not represent "black and white" conclusions or clinical practice standards but are meant as a starting place for research and active discussions among hospitalists and patients. We invite you to be part of that discussion.

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Seven Versus 14 Days of Antibiotic Therapy for Uncomplicated Gram-negative Bacteremia: A Noninferiority Randomized Controlled Trial

By Dafna Yahav, Erica Franceschini, Fidi Koppel, Adi Turjeman, Tanya Babich, Roni Bitterman, Ami Neuberger, Nesrin Ghanem-Zoubi, Antonella Santoro, Noa Eliakim-Raz, Barak Pertzov, Tali Steinmetz, Anat Stern, Yaakov Dickstein, Elias Maroun, Hiba Zayyad, Jihad Bishara, Danny Alon, Yonatan Edel, Elad Goldberg, Claudia Venturelli, Cristina Mussini, Leonard Leibovici, Mical Paul, Bacteremia Duration Study Group

Clinical Infectious Diseases. October 1, 2019.

 

Gram-negative bacteremia is a major cause of morbidity and mortality in hospitalized patients. Data to guide the duration of antibiotic therapy are limited.

This was a randomized, multicenter, open-label, noninferiority trial. Inpatients with gram-negative bacteremia, who were afebrile and hemodynamically stable for at least 48 hours, were randomized to receive 7 days (intervention) or 14 days (control) of covering antibiotic therapy. Patients with uncontrolled focus of infection were excluded. The primary outcome at 90 days was a composite of all-cause mortality; relapse, suppurative, or distant complications; and readmission or extended hospitalization (>14 days). The noninferiority margin was set at 10%.

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