RESUMEN
The oral polio vaccine (OPV) contains live-attenuated polioviruses that induce immunity by causing low virulence infections in vaccine recipients and their close contacts. Widespread immunization with OPV has reduced the annual global burden of paralytic poliomyelitis by a factor of 10,000 or more and has driven wild poliovirus (WPV) to the brink of eradication. However, in instances that have so far been rare, OPV can paralyze vaccine recipients and generate vaccine-derived polio outbreaks. To complete polio eradication, OPV use should eventually cease, but doing so will leave a growing population fully susceptible to infection. If poliovirus is reintroduced after OPV cessation, under what conditions will OPV vaccination be required to interrupt transmission? Can conditions exist in which OPV and WPV reintroduction present similar risks of transmission? To answer these questions, we built a multi-scale mathematical model of infection and transmission calibrated to data from clinical trials and field epidemiology studies. At the within-host level, the model describes the effects of vaccination and waning immunity on shedding and oral susceptibility to infection. At the between-host level, the model emulates the interaction of shedding and oral susceptibility with sanitation and person-to-person contact patterns to determine the transmission rate in communities. Our results show that inactivated polio vaccine (IPV) is sufficient to prevent outbreaks in low transmission rate settings and that OPV can be reintroduced and withdrawn as needed in moderate transmission rate settings. However, in high transmission rate settings, the conditions that support vaccine-derived outbreaks have only been rare because population immunity has been high. Absent population immunity, the Sabin strains from OPV will be nearly as capable of causing outbreaks as WPV. If post-cessation outbreak responses are followed by new vaccine-derived outbreaks, strategies to restore population immunity will be required to ensure the stability of polio eradication.
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Brotes de Enfermedades/prevención & control , Inmunidad Colectiva , Poliomielitis/prevención & control , Vacuna Antipolio de Virus Inactivados/administración & dosificación , Vacuna Antipolio Oral/administración & dosificación , Poliovirus/inmunología , Salud Global , Humanos , Inmunidad Activa , Esquemas de Inmunización , Vacunación Masiva/estadística & datos numéricos , Modelos Estadísticos , Poliomielitis/epidemiología , Poliomielitis/inmunología , Poliomielitis/transmisiónRESUMEN
In Pakistan, annual poliovirus investment decisions drive quantities of supplemental immunization campaigns districts receive. In this article, we assess whether increased spending on poliovirus surveillance is associated with greater likelihood of correctly identifying districts at high risk of polio with assignment of an elevated "risk ranking." We reviewed programmatic documents from Pakistan for the period from 2012-2017, recording whether districts had been classified as "high risk" or "low risk" in each year. Through document review, we developed a decision tree to describe the ranking decisions. Then, integrating data from the World Health Organization and Global Polio Eradication Initiative, we constructed a Bayesian decision network reflecting investments in polio surveillance and immunization campaigns, surveillance metrics, disease incidence, immunization rates, and occurrence of polio cases. We test these factors for statistical association with the outcome of interest-a change in risk rank between the beginning and the end of the one-year time period. We simulate different spending scenarios and predict their impact on district risk ranking in future time periods. We find that per district spending increases are associated with increased identification of cases of acute flaccid paralysis (AFP). However, the low specificity of AFP investment and the largely invariant ranking of district risk means that even large increases in surveillance spending are unlikely to promote major changes in risk rankings at the current stage of the Pakistan polio eradication campaign.
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Enfermedades Virales del Sistema Nervioso Central/diagnóstico , Enfermedades Virales del Sistema Nervioso Central/virología , Erradicación de la Enfermedad/métodos , Programas de Inmunización/economía , Mielitis/diagnóstico , Mielitis/virología , Enfermedades Neuromusculares/diagnóstico , Enfermedades Neuromusculares/virología , Poliomielitis/epidemiología , Poliomielitis/prevención & control , Poliomielitis/transmisión , Vigilancia de la Población , Medición de Riesgo/métodos , Teorema de Bayes , Simulación por Computador , Toma de Decisiones , Árboles de Decisión , Geografía , Costos de la Atención en Salud , Humanos , Incidencia , Poliovirus , Riesgo , Vacunación , Organización Mundial de la SaludRESUMEN
The development of epoxy thermosets from renewable resources is of paramount importance in a sustainable development context. In this paper, a novel bio-based epoxy monomer derived from limonene was synthesized without epichlorohydrine and characterized. In fact, this paper depicts the synthesis of bis-limonene oxide (bis-LO). However, intern epoxy rings generally exhibit a poor reactivity and allow reaction with anhydride. Therefore, we used a reaction model with hexahydro-4-methylphthalic anhydride to compare reactivity of terminal and interepoxy functions. We also studied the influence of methyl group on intern epoxy functions. Furthermore, the influence of epoxy:anhydride stoichiometry and initiator amount was studied. These studies allow to propose an optimized formulation of bis-LO. Finally, a bis-LO-based thermoset was obtained and characterized.
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Compuestos Epoxi/química , Limoneno/química , Anhídridos/química , Biopolímeros/química , Rastreo Diferencial de Calorimetría , Espectroscopía de Resonancia Magnética , Estructura Molecular , Espectroscopía Infrarroja por Transformada de Fourier , TermogravimetríaRESUMEN
BACKGROUND: Wild type 2 poliovirus was last observed in 1999. The Sabin-strain oral polio vaccine type 2 (OPV2) was critical to eradication, but it is known to revert to a neurovirulent phenotype, causing vaccine-associated paralytic poliomyelitis. OPV2 is also transmissible and can establish circulating lineages, called circulating vaccine-derived polioviruses (cVDPVs), which can also cause paralytic outbreaks. Thus, in April 2016, OPV2 was removed from immunization activities worldwide. Interrupting transmission of cVDPV2 lineages that survive cessation will require OPV2 in outbreak response, which risks seeding new cVDPVs. This potential cascade of outbreak responses seeding VDPVs, necessitating further outbreak responses, presents a critical risk to the OPV2 cessation effort. METHODS: The EMOD individual-based disease transmission model was used to investigate OPV2 use in outbreak response post-cessation in West African populations. A hypothetical outbreak response in northwest Nigeria is modeled, and a cVDPV2 lineage is considered established if the Sabin strain escapes the response region and continues circulating 9 months post-response. The probability of this event was investigated in a variety of possible scenarios. RESULTS: Under a broad range of scenarios, the probability that widespread OPV2 use in outbreak response (~2 million doses) establishes new cVDPV2 lineages in this model may exceed 50% as soon as 18 months or as late as 4 years post-cessation. CONCLUSIONS: The risk of a cycle in which outbreak responses seed new cVDPV2 lineages suggests that OPV2 use should be managed carefully as time from cessation increases. It is unclear whether this risk can be mitigated in the long term, as mucosal immunity against type 2 poliovirus declines globally. Therefore, current programmatic strategies should aim to minimize the possibility that continued OPV2 use will be necessary in future years: conducting rapid and aggressive outbreak responses where cVDPV2 lineages are discovered, maintaining high-quality surveillance in all high-risk settings, strengthening the use of the inactivated polio vaccine as a booster in the OPV2-exposed and in routine immunization, and gaining access to currently inaccessible areas of the world to conduct surveillance.
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Brotes de Enfermedades/prevención & control , Poliomielitis/prevención & control , Vacuna Antipolio Oral/uso terapéutico , Poliovirus/efectos de los fármacos , Humanos , Poliomielitis/epidemiología , Vacuna Antipolio Oral/administración & dosificaciónRESUMEN
BACKGROUND: Pakistan is one of only three countries where poliovirus circulation remains endemic. For the Pakistan Polio Eradication Program, identifying high risk districts is essential to target interventions and allocate limited resources. METHODS: Using a hierarchical Bayesian framework we developed a spatial Poisson hurdle model to jointly model the probability of one or more paralytic polio cases, and the number of cases that would be detected in the event of an outbreak. Rates of underimmunization, routine immunization, and population immunity, as well as seasonality and a history of cases were used to project future risk of cases. RESULTS: The expected number of cases in each district in a 6-month period was predicted using indicators from the previous 6-months and the estimated coefficients from the model. The model achieves an average of 90% predictive accuracy as measured by area under the receiver operating characteristic (ROC) curve, for the past 3 years of cases. CONCLUSIONS: The risk of poliovirus has decreased dramatically in many of the key reservoir areas in Pakistan. The results of this model have been used to prioritize sub-national areas in Pakistan to receive additional immunization activities, additional monitoring, or other special interventions.
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Erradicación de la Enfermedad , Modelos Biológicos , Modelos Estadísticos , Poliomielitis/prevención & control , Poliovirus , Teorema de Bayes , Preescolar , Brotes de Enfermedades/prevención & control , Humanos , Programas de Inmunización , Pakistán/epidemiología , Poliomielitis/epidemiología , Vacunas contra Poliovirus/administración & dosificación , Probabilidad , Curva ROC , RiesgoRESUMEN
The synthesis of polymers from renewable resources is a burning issue that is actively investigated. Polyepoxide networks constitute a major class of thermosetting polymers and are extensively used as coatings, electronic materials, adhesives. Owing to their outstanding mechanical and electrical properties, chemical resistance, adhesion, and minimal shrinkage after curing, they are used in structural applications as well. Most of these thermosets are industrially manufactured from bisphenol A (BPA), a substance that was initially synthesized as a chemical estrogen. The awareness on BPA toxicity combined with the limited availability and volatile cost of fossil resources and the non-recyclability of thermosets implies necessary changes in the field of epoxy networks. Thus, substitution of BPA has witnessed an increasing number of studies both from the academic and industrial sides. This review proposes to give an overview of the reported aromatic multifunctional epoxide building blocks synthesized from biomass or from molecules that could be obtained from transformed biomass. After a reminder of the main glycidylation routes and mechanisms and the recent knowledge on BPA toxicity and legal issues, this review will provide a brief description of the main natural sources of aromatic molecules. The different epoxy prepolymers will then be organized from simple, mono-aromatic di-epoxy, to mono-aromatic poly-epoxy, to di-aromatic di-epoxy compounds, and finally to derivatives possessing numerous aromatic rings and epoxy groups.
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Productos Biológicos/química , Compuestos Epoxi/síntesis química , Resinas Epoxi/síntesis química , Polímeros/síntesis química , Compuestos de Bencidrilo/química , Compuestos de Bencidrilo/toxicidad , Productos Biológicos/aislamiento & purificación , Biomasa , Ácidos Cafeicos/química , Ácidos Cafeicos/aislamiento & purificación , Cardanólidos/química , Cardanólidos/aislamiento & purificación , Catecoles/química , Catecoles/aislamiento & purificación , Tecnología Química Verde , Lignina/química , Lignina/aislamiento & purificación , Fenoles/química , Fenoles/toxicidad , Taninos/química , Taninos/aislamiento & purificación , Temperatura , Terpenos/química , Terpenos/aislamiento & purificaciónRESUMEN
BACKGROUND: The world is closer than ever to a polio-free Africa. In this end-stage, it is important to ensure high levels of population immunity to prevent polio outbreaks. Here, we introduce a new method of assessing vaccination campaign effectiveness and estimating immunity at the district-level. We demonstrate how this approach can be used to plan the vaccination campaigns prospectively to better manage population immunity in Northern Nigeria. METHODS: Using Nigerian acute flaccid paralysis surveillance data from 2004-2014, we developed a Bayesian hierarchical model of campaign effectiveness and compared it to lot-quality assurance sampling data. We then used reconstructed sero-specific population immunity based on campaign history and compared district estimates of immunity to the occurrence of confirmed poliovirus cases. RESULTS: Estimated campaign effectiveness has improved across northern Nigeria since 2004, with Kano state experiencing an increase of 40 % (95 % CI, 26-54 %) in effectiveness from 2013 to 2014. Immunity to type 1 poliovirus has increased steadily. On the other hand, type 2 immunity was low and variable until the recent use of trivalent oral polio vaccine. We find that immunity estimates are related to the occurrence of both wild and vaccine-derived poliovirus cases and that campaign effectiveness correlates with direct measurements using lot-quality assurance sampling. Future campaign schedules highlight the trade-offs involved with using different vaccine types. CONCLUSIONS: The model in this study provides a novel method for assessing vaccination campaign performance and epidemiologically-relevant estimates of population immunity. Small-area estimates of campaign effectiveness can then be used to evaluate prospective campaign plans. This modeling approach could be applied to other countries as well as other vaccine preventable diseases.
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Teorema de Bayes , Poliomielitis/inmunología , Poliomielitis/prevención & control , Vacuna Antipolio Oral , Vacunación , África , Humanos , Nigeria/epidemiología , Poliomielitis/epidemiología , Estudios ProspectivosRESUMEN
BACKGROUND: Since the launch of the Global Polio Eradication Initiative, all but three countries (Nigeria, Pakistan, and Afghanistan) have apparently interrupted all wild poliovirus (WPV) transmission, and only one of three wild serotypes has been reported globally since 2012. Countrywide supplemental immunization campaigns in Nigeria produced dramatic reduction in WPV Type 1 paralysis cases since 2010 compared to the 2000's, and WPV1 has not been observed in Nigeria since July 24, 2014. This article presents the development and calibration of a spatial metapopulation model of wild poliovirus Type 1 transmission in Kano State, Nigeria, which was the location of the most recent WPV1 case and 5 out of 6 of the reported WPV1 paralytic cases in Nigeria in 2014. METHODS: The model is calibrated to data on the case counts and age at onset of paralysis from 2003-2009. The features of the data drive model development from a simple susceptible-exposed-infective-recovered (SEIR) model to a spatial metapopulation model featuring seasonal forcing and age-dependent transmission. The calibrated parameter space is then resampled, projected forward, and compared to more recent case counts to estimate the probability that Type 1 poliovirus has been eliminated in Kano state. RESULTS: The model indicates a 91 % probability that Type 1 poliovirus has been eliminated from Kano state as of October 2015. This probability rises to >99 % if no WPV1 paralysis cases are detected for another year. The other states in Nigeria have experienced even longer case-free periods (the only other state with a WPV1 case was Yobe, on April 19, 2014), and Nigeria is the last remaining country in Africa to experience endemic WPV1 transmission, so these results can be interpreted as an upper bound on the probability that WPV1 transmission is currently interrupted continent-wide. CONCLUSIONS: While the results indicate optimism that WPV1 transmission has been interrupted in Kano state, the model also assumes that frequent SIAs with high coverage continue to take place in Kano state through the end of the certification period. We conclude that though WPV1 appears to be on the brink of continent-wide elimination (WHO officially removed Nigeria from the list of polio-endemic countries on September 25, 2015), it is important for the polio program to maintain vigilance in surveillance and vaccination activities to prevent WPV1 resurgence through the WHO's 3-year eradication certification period.
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Monitoring the quality of supplementary immunization activities (SIAs) is a key tool for polio eradication. Regular monitoring data, however, are often unreliable, showing high coverage levels in virtually all areas, including those with ongoing virus circulation. To address this challenge, lot quality assurance sampling (LQAS) was introduced in 2009 as an additional tool to monitor SIA quality. Now used in 8 countries, LQAS provides a number of programmatic benefits: identifying areas of weak coverage quality with statistical reliability, differentiating areas of varying coverage with greater precision, and allowing for trend analysis of campaign quality. LQAS also accommodates changes to survey format, interpretation thresholds, evaluations of sample size, and data collection through mobile phones to improve timeliness of reporting and allow for visualization of campaign quality. LQAS becomes increasingly important to address remaining gaps in SIA quality and help focus resources on high-risk areas to prevent the continued transmission of wild poliovirus.
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Investigación sobre Servicios de Salud , Inmunización Secundaria/métodos , Muestreo para la Garantía de la Calidad de Lotes/estadística & datos numéricos , Poliomielitis/prevención & control , Vacunas contra Poliovirus/administración & dosificación , Vacunas contra Poliovirus/inmunología , HumanosRESUMEN
BACKGROUND: One of the challenges facing the Global Polio Eradication Initiative is efficiently directing limited resources, such as specially trained personnel, community outreach activities, and satellite vaccinator tracking, to the most at-risk areas to maximize the impact of interventions. A validated predictive model of wild poliovirus circulation would greatly inform prioritization efforts by accurately forecasting areas at greatest risk, thus enabling the greatest effect of program interventions. METHODS: Using Nigerian acute flaccid paralysis surveillance data from 2004-2013, we developed a spatial hierarchical Poisson hurdle model fitted within a Bayesian framework to study historical polio caseload patterns and forecast future circulation of type 1 and 3 wild poliovirus within districts in Nigeria. A Bayesian temporal smoothing model was applied to address data sparsity underlying estimates of covariates at the district level. RESULTS: We find that calculated vaccine-derived population immunity is significantly negatively associated with the probability and number of wild poliovirus case(s) within a district. Recent case information is significantly positively associated with probability of a case, but not the number of cases. We used lagged indicators and coefficients from the fitted models to forecast reported cases in the subsequent six-month periods. Over the past three years, the average predictive ability is 86 ± 2% and 85 ± 4% for wild poliovirus type 1 and 3, respectively. Interestingly, the predictive accuracy of historical transmission patterns alone is equivalent (86 ± 2% and 84 ± 4% for type 1 and 3, respectively). We calculate uncertainty in risk ranking to inform assessments of changes in rank between time periods. CONCLUSIONS: The model developed in this study successfully predicts districts at risk for future wild poliovirus cases in Nigeria. The highest predicted district risk was 12.8 WPV1 cases in 2006, while the lowest district risk was 0.001 WPV1 cases in 2013. Model results have been used to direct the allocation of many different interventions, including political and religious advocacy visits. This modeling approach could be applied to other vaccine preventable diseases for use in other control and elimination programs.
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Erradicación de la Enfermedad/estadística & datos numéricos , Recursos en Salud/organización & administración , Modelos Estadísticos , Poliomielitis/prevención & control , Poliomielitis/virología , Poliovirus , Teorema de Bayes , Femenino , Geografía Médica , Humanos , Nigeria/epidemiología , Distribución de Poisson , Poliomielitis/epidemiología , Poliomielitis/inmunología , Poliomielitis/transmisión , Riesgo , Factores de Tiempo , IncertidumbreRESUMEN
BACKGROUND: Systemic mastocytosis (SM) is a clonal disorder of mast cells (MCs) frequently associated with vertebral osteoporosis (OP) and subsequent vertebral fractures (VFs). The natural history of this OP remains unclear. Importantly, we do not know whether OP represents an early event triggered alongside MC abnormalities, and whether MC clonality is sufficient to trigger osteoporosis. OBJECTIVE: To describe OP in patients with medullar clonality in cutaneous mastocytosis (CM) and monoclonal mast cell activation syndrome (MMAS) and to compare their osteoporosis characteristics with those of nonadvanced SM patients (bone marrow mastocytosis and indolent systemic mastocytosis). METHODS: We retrospectively analyzed clinical, biological, and densitometric data of 27 CM, 13 MMAS, and 135 SM patients from the Mastocytosis Expert Center (CEREMAST) in Toulouse, France. RESULTS: The OP (respectively 3.7, 30.8, and 34.1%) and VFs (0.0%, 15.4%, and 20%) were less frequent in CM than in MMAS and SM, despite the presence of clonal MCs in the bone marrow. Most patients with OP and VFs in the non-SM groups had the usual risk factors for OP. Interestingly, the only non-SM patient with a typical SM-like OP had high bone marrow tryptase, developed bone marrow KIT mutation during follow-up, and had a family history of SM. Our data show that OP is not a common clinical finding in CM but is frequent in MMAS. When OP and VFs occur in CM and MMAS patients, they differ from the usual phenotype of SM bone fragility. CONCLUSIONS: Our findings suggest that, in most CM patients, the meaning and management of OP differs from that of OP in MMAS and nonadvanced SM. Prospective longitudinal studies and the validation of predictors are needed to identify CM and MMAS patients developing SM-related OP.
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Mastocitosis Cutánea , Mastocitosis Sistémica , Osteoporosis , Humanos , Osteoporosis/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Adulto , Prevalencia , Estudios Retrospectivos , Anciano , Mastocitosis Cutánea/epidemiología , Mastocitosis Sistémica/epidemiología , Mastocitos/inmunología , Francia/epidemiología , Médula Ósea/patología , Proteínas Proto-Oncogénicas c-kit/genética , Fracturas de la Columna Vertebral/epidemiologíaRESUMEN
OBJECTIVES: Tropheryma whipplei infection can manifest as inflammatory joint symptoms, which can lead to misdiagnosis of inflammatory rheumatic disease and the use of disease-modifying antirheumatic drugs. We investigated the impact of diagnosis and treatment of Tropheryma whipplei infection in patients with inflammatory rheumatic disease. METHODS: We initiated a registry including patients with disease-modifying antirheumatic drugs-treated inflammatory rheumatic disease who were subsequently diagnosed with Tropheryma whipplei infection. We collected clinical, biological, treatment data of the inflammatory rheumatic disease, of Tropheryma whipplei infection, and impact of antibiotics on the evolution of inflammatory rheumatic disease. RESULTS: Among 73 inflammatory rheumatic disease patients, disease-modifying antirheumatic drugs initiation triggered extra-articular manifestations in 27% and resulted in stabilisation (51%), worsening (34%), or improvement (15%) of inflammatory rheumatic disease. At the diagnosis of Tropheryma whipplei infection, all patients had rheumatological symptoms (mean age 58 years, median inflammatory rheumatic disease duration 79 months), 84% had extra-rheumatological manifestations, 93% had elevated C-reactive protein, and 86% had hypoalbuminemia. Treatment of Tropheryma whipplei infection consisted mainly of doxycycline plus hydroxychloroquine, leading to remission of Tropheryma whipplei infection in 79% of cases. Antibiotic treatment of Tropheryma whipplei infection was associated with remission of inflammatory rheumatic disease in 93% of cases and enabled disease-modifying antirheumatic drugs and glucocorticoid discontinuation in most cases. CONCLUSIONS: Tropheryma whipplei infection should be considered in inflammatory rheumatic disease patients with extra-articular manifestations, elevated C-reactive protein, and/or hypoalbuminemia before disease-modifying antirheumatic drugs initiation or in inflammatory rheumatic disease patients with an inadequate response to one or more disease-modifying antirheumatic drugs. Positive results of screening and diagnostic tests for Tropheryma whipplei infection involve antibiotic treatment, which is associated with complete recovery of Tropheryma whipplei infection and rapid remission of inflammatory rheumatic disease, allowing disease-modifying antirheumatic drugs and glucocorticoid discontinuation.
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Antirreumáticos , Hipoalbuminemia , Enfermedades Reumáticas , Enfermedad de Whipple , Humanos , Persona de Mediana Edad , Tropheryma/fisiología , Glucocorticoides/uso terapéutico , Proteína C-Reactiva , Hipoalbuminemia/tratamiento farmacológico , Antibacterianos/uso terapéutico , Enfermedades Reumáticas/complicaciones , Enfermedades Reumáticas/tratamiento farmacológico , Antirreumáticos/uso terapéutico , Enfermedad de Whipple/diagnóstico , Enfermedad de Whipple/tratamiento farmacológico , Enfermedad de Whipple/epidemiologíaRESUMEN
Stopping treatment for osteoporosis with denosumab (Dmab) leads to a major and rapid loss in bone mineral density (BMD) and a risk of vertebral fracture. Subsequent treatment with bisphosphonate (Bp) does not completely prevent this bone loss. We carried out a prospective pilot study to find out whether the gradual dose reduction with denosumab could prevent this bone loss. We proposed a therapeutic protocol consisting in reducing the doses of Dmab to women treated with Dmab for postmenopausal osteoporosis. Six months after the last dose of Dmab 60 mg, the subsequent injection was performed with a reduced dose of 30 mg, and the month-12 injection was a 15-mg injection. BMD and serum C-terminal telopeptide of type I collagen (CTX) were measured at the start of treatment with Dmab (T0), at the last dose with 60 mg (T1), and at 6 months (T2) and 12 months (T3) after the last 15 mg Dmab injection. We included 13 patients aged 68.7 ± 3 years, and treated with Dmab for 45.2 ± 5 months. At the lumbar spine, 39% of the initial gain in BMD was preserved 1 year after the last dose (15 mg). Conversely, at the hip, the bone loss at the end of the treatment reduction protocol was equivalent to the initial gain. The mean CTX level was 166 ± 152 pg/mL 6 months after the last dose (T2; 15 mg), and 549 ± 425 pg/mL 12 months after the last dose (T3; 15 mg). One patient presented two vertebral fractures, 8 months after the last dose of Dmab (15 mg). Gradual dose reduction of denosumab (30 mg then 15 mg) does not prevent bone loss in the hip and partially maintains the initial gain at the spine. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.
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Primary hypertrophic osteoarthropathy (PHO), or pachydermoperiostosis, is characterized by a clinical association including digital clubbing, periostosis and pachydermia. SLCO2A1 and HPGD genes are both responsible for PHO. The pathology is classically defined as an autosomal recessive disorder with clinical variability ranging from a mild to more severe phenotype. However, the hypothesis for an autosomal dominant form suggested for a long time was only demonstrated for the first time in 2021 for SLCO2A1. We aimed to detect a second pathogenic variant by a deep sequencing of the entire SLCO2A1 and HPGD genes, associated with functional transcription analysis in PHO patients harboring only one heterozygous variant. Among 10 PHO patients, 4 presented a single pathogenic or probably pathogenic novel variant in SLCO2A1 in heterozygous status (NM_005630.3: c.234+1G > A, c.1523_1524delCT, c.1625G > A and c.31delC), and the others carried homozygous pathogenic variants. For heterozygous forms, we found no additional pathogenic variant in HPGD or SLCO2A1. PHO can be a dominant form with age at disease onset later than that for the recessive form. This dominant form is not exceptional in young adults. In conclusion, both modes of inheritance of PHO explain the clinical variability and the difference in age at disease onset. Molecular analysis is especially required in the incomplete form to distinguish it from secondary hypertrophic osteoarthropathy.
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Transportadores de Anión Orgánico , Osteoartropatía Hipertrófica Primaria , Humanos , Osteoartropatía Hipertrófica Primaria/genética , Osteoartropatía Hipertrófica Primaria/diagnóstico , Osteoartropatía Hipertrófica Primaria/patología , Transportadores de Anión Orgánico/genética , Fenotipo , Heterocigoto , LinajeRESUMEN
Background: Psoriatic arthritis (PsA) is associated with increased cardiovascular morbidity and mortality. The aims of our real-life study were to compare the prevalence of cardiovascular risk factors (CVRFs) and cardiovascular events (CVEs) among patients with PsA with a control population, to evaluate the impact of correcting factors in equations that assess cardiovascular risk (CVR) in PsA, and to determine the percentage of patients who reach the LDLc target as indicated by the European guidelines. Methods: In this observational cross-sectional monocentric case-control study, we used a standardized procedure to systematically assess patients with PsA aged 25-85 years who met the Classification for Psoriatic Arthritis (CASPAR) criteria. Controls were extracted from the MOnitoring NAtionaL du rISque Artériel (MONALISA) study. We compared the prevalence of CVRFs, CVEs, the CVR, and the percentage of patients reaching recommended LDLc target in both populations. The CVR was first assessed using SCORE and QRISK2 equations. Then, the SCORE equation was corrected by applying a 1.5 multiplication factor, as recommended by EULAR for rheumatoid arthritis (SCORE-PsA), and the QRISK2 was corrected using the "rheumatoid arthritis" item (QRISK2-PsA). Results: A total of 207 PsA and 414 controls were included. CVRFs and CVEs were more frequent in the PsA group. After controlling for age and gender, atherothrombotic disease was increased in the PsA population (SCORE p = 0.002, QRISK2 p = 0.001). Using the SCORE-PsA increased the percentage of patients with a high or very high CVR from 39.3 to 45.3% in the PsA group. Similarly, using the QRISK2-PsA increased the percentage of patients with a CVR ≥ 10% from 44.9 to 53.2%. The percentages of patients with PsA with high LDLc in the high and very high CVR groups were not significantly different from controls, despite a trend in favor of patients with PsA. Of the 83 PsA with a QRISK2 ≥ 10%, only 22.9% were treated with statin vs. 35.8% of the 134 controls. The QRISK2-PsA score did not alter these results. Conclusion: In real-life, patients with PsA have a higher prevalence of CVRFs, as well as a higher prevalence of CVEs compared to the general population. The CVR is higher in the PsA population than in the controls either using the SCORE and QRISK2 equations or using the corrected SCORE- PsA and QRISK2-PsA equations.
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AIM: To describe the presenting features, bone characteristics and molecular genetics in a large monocentric cohort of children and young adults with idiopathic primary osteoporosis. METHODS: Sixty-six patients (19 children, 47 adults; 28 males, 38 females; age at referral: 3.8 to 65 years) diagnosed with primary osteoporosis were included in this study; patients with features of osteogenesis imperfecta or other known syndromes associated with osteoporosis were excluded. For each patient, the following data were collected by retrospective chart review: family and personal history of fracture and osteoporosis, mineral homeostasis parameters and markers of bone formation and resorption, bone mineral density (BMD) of the lumbar spine (LS-BMD), the total body less head (TB-BMD), and total hip levels (TH-BMD) measured by DXA. As part of the initial assessment process, a bone fragility gene panel sequencing was performed in all of these patients. RESULTS: There was a higher predominance of males in the children (63%) and of females in the adults (66%) (p = 0.030). Compared to the adults, the children had a significantly lower frequency of vertebral fractures (26 vs 57%, p = 0.022) and a higher frequency of peripheral fractures (84 vs 53%; p = 0.019). Bone fragility gene panel sequencing allowed the identification of the heterozygous pathogenic variant in 27% of patients (most frequently in LRP5, WNT1 and COL1A1 or 2 genes) and the heterozygous p.(Val667Met) LRP5 variant in 11% of them. The frequency of pathogenic variants tended to be higher in the children compared to the adults without reaching statistical significance (42 vs 19%; p = 0.053). The frequency of the p.(Val667Met) LRP5 variant was similar in children and adults. No significant differences were found regarding the various clinical, biological and radiological characteristics of the patients according to genotype. CONCLUSION: In this study, we reported the presenting features and bone characteristics in a large cohort of children and young adults with idiopathic primary osteoporosis. Bone fragility gene panel sequencing allowed the identification of genetic variants in a significant proportion of these patients. Molecular diagnosis in these patients is important in order to be able to offer genetic counselling and organise patient management.
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OBJECTIVES: To estimate the fraction of anaemia attributable to malaria and sickle cell disease (SCD) among children aged 6-59 months in Nigeria. DESIGN: Cross-sectional analysis of data from Nigeria's 2018 Demographic and Health Survey (DHS). SETTING: Nigeria. PARTICIPANTS: 11 536 children aged 6-59 months from randomly selected households were eligible for participation, of whom 11 142 had complete and valid biomarker data required for this analysis. Maternal education data were available from 10 305 of these children. PRIMARY OUTCOME MEASURE: Haemoglobin concentration. RESULTS: We found that 70.6% (95% CI: 62.7% to 78.5%) of severe anaemia was attributable to malaria compared with 12.4% (95% CI: 11.1% to 13.7%) of mild-to-severe and 29.6% (95% CI: 29.6% to 31.8%) of moderate-to-severe anaemia and that SCD contributed 0.6% (95% CI: 0.4% to 0.9%), 1.3% (95% CI: 1.0% to 1.7%) and 10.6% (95% CI: 6.7% to 14.9%) mild-to-severe, moderate-to-severe and severe anaemia, respectively. Sickle trait was protective against anaemia and was associated with higher haemoglobin concentration compared with children with normal haemoglobin (HbAA) among malaria-positive but not malaria-negative children. CONCLUSIONS: This approach used offers a new tool to estimate the contribution of malaria to anaemia in many settings using widely available DHS data. The fraction of anaemia among young children in Nigeria attributable to malaria and SCD is higher at more severe levels of anaemia. Prevention of malaria and SCD and timely treatment of affected individuals would reduce cases of severe anaemia.
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Anemia de Células Falciformes , Malaria , Preescolar , Humanos , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/epidemiología , Estudios Transversales , Demografía , Hemoglobinas , Malaria/complicaciones , Malaria/epidemiología , Nigeria/epidemiología , LactanteRESUMEN
The bidirectional interaction between undernutrition and infection can be devastating to child health. Nutritional deficiencies impair immunity and increase susceptibility to infection. Simultaneously, infections compound undernutrition by increasing metabolic demand and impairing nutrient absorption. Treatment of acute malnutrition (wasting) can reverse some of its deleterious effects and reduce susceptibility to infectious diseases. Nutrition-specific approaches may be packaged with other interventions, including immunization, to support overall child health. To understand how mass nutritional supplementation, treatment of wasting, and vaccination affect the dynamics of a vaccine-preventable infection, we developed a population-level, compartmental model of measles transmission stratified by age and nutrition status. We simulated a range of scenarios to assess the potential reductions in measles infection and mortality associated with targeted therapeutic feeding for children who are wasted and with a mass supplementation intervention. Nutrition interventions were assumed to increase engagement with the health sector, leading to increased vaccination rates. We found that the combination of wasting treatment and mass supplementation coverage followed by an increase in vaccination coverage of non-wasted children from a baseline of 75% to 85%, leads to 34% to 57% and 65% to 77% reduction in measles infection and mortality and 56% to 60% reduction in overall mortality among wasted children, compared with the wasting treatment alone. Our work highlights the synergistic benefits that may be achieved by leveraging mass nutritional supplementation as a touch point with the health system to increase rates of vaccination and improve child survival beyond what would be expected from the additive benefits of each intervention.
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Desnutrición , Sarampión , Niño , Suplementos Dietéticos , Humanos , Lactante , Sarampión/prevención & control , Vacuna Antisarampión/uso terapéutico , VacunaciónRESUMEN
Treatment with asfotase alfa has transformed the prognosis of hypophosphatasia in children and improves the bone and muscle signs in adults. The doses used in adults are the same as in children, whereas bone remodeling is different between them. We report on the cases of two patients treated with 1 mg/kg/day of asfotase alfa who developed spinal cord compression from spinal ossifications during treatment. The first patient, 50 years old, presented after 2 years of treatment with quadraparesis secondary to an increase in ossifications of the cervical vertebral ligaments. The neurological damage was resolved after laminectomy, and the patient was then treated for 18 months with doses of 80 mg per week, without recurrence of the bone and muscle signs. The second patient, 26 years old, 78 kg, developed pain and cervical stiffness with pyramidal tract irritation secondary to ossifications of the vertebral ligaments. This improved with a reduction of doses to 80 mg/week, which then, after 6 months of follow-up, enabled maintained improvement of the bone and muscle pain that was initially obtained. To our knowledge, these are the first reported cases of increased spinal ligamentous ossifications with neurological complications. Biological monitoring in adults does not seem to enable asfotase alfa doses to be adjusted. The levels of serum alkaline phosphatase (ALP) while on the recommended treatment of 1 mg/kg/day are significantly supraphysiological (5000 to 20,000 IU) and the assays of pyrophosphate and pyridoxal phosphate are not correlated with clinical efficacy. In both of our patients, the treatment with 80 mg of asfotase alfa per week, which was proposed after the occurrence of spinal complications, seemed as effective, after a follow-up of 18 months and 6 months, as the initial treatment for improving the bone and muscle signs, and could be provided as "attack" doses after healing of the pseudoarthroses. © 2021 American Society for Bone and Mineral Research © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.