Fattori di rischio di mortalit\ue0 per infezioni acute delle basse vie aeree nei bambini di paesi a basso e medio reddito: revisioni sistematiche e metanalisi

Nel mondo i decessi per infezioni acute delle basse vie aeree (acute lower respiratory infections (ALRI)) prima dei cinque anni di et\ue0 sono in continua diminuzione, ma il loro numero - quasi un milione nel 2013 - \ue8 ancora inaccettabilmente elevato. Circa il 95% di questi decessi avviene in paesi a basso e medio reddito. La ricerca attuale nel campo delle ALRI si concentra principalmente su strategie volte a combattere gli agenti eziologici e sullo sviluppo di vaccini. In questa tesi si \ue8 voluto adottare un approccio pi\uf9 globale ed esplorare la vasta gamma di fattori coinvolti nella complessa catena causale che va dal contatto con l\u2019agente eziologico alla morte. Obiettivo: valutare l\u2019evidenza scientifica esistente sui diversi fattori di rischio di morte per ALRI nei bambini minori di cinque anni di paesi a basso e medio reddito. La tesi \ue8 costituita da due distinte revisioni sistematiche: la prima, di carattere pi\uf9 generale, sintetizza l\u2019evidenza esistente in letteratura sui determinanti personali, socio-economici, ambientali e relativi all\u2019assistenza sanitaria, che possono aumentare il rischio di morte per ALRI; la seconda analizza in maniera specifica l\u2019evidenza disponibile sull\u2019associazione tra ipossia e morte per ALRI. Metodologia: per entrambe le revisioni si sono seguite strettamente le linee guida generali per eseguire revisioni sistematiche PRISMA e quelle specifiche per le revisioni di studi osservazionali MOOSE. Si \ue8 costruita una strategia di ricerca per ogni revisione, si sono consultate cinque banche elettroniche di dati bibliografici, e due autori in parallelo hanno selezionato gli studi per l\u2019inclusione. La valutazione della qualit\ue0 degli studi inclusi \ue8 stata realizzata utilizzando una checklist predefinita. Dove possibile si \ue8 proceduto alla metanalisi e alla valutazione dell\u2019eterogeneit\ue0 (attraverso l\u2019analisi per sottogruppi e la metaregressione). Si sono stimati i bias di pubblicazione e sono state eseguite analisi di sensibilit\ue0 pre-definite. Risultati: tra le 10.655 citazioni per la prima revisione, sono stati selezionati 77 studi realizzati in 39 paesi (198.359 bambini). Nella revisione sull\u2019ipossia gli studi selezionati sono stati 18 su un totale di 11.627 citazioni (20.224 bambini). Questo lavoro ha dimostrato che numerosi fattori di rischio aumentano le probabilit\ue0 di morte per ALRI nei bambini, tra cui fattori legati alla clinica, come l\u2019ipossia, (Odds Ratio 5,47; intervallo di confidenza al 95% 3,93\u20137,63 per livelli di saturazione di ossigeno < 90% e 3,66; 1,42\u20139,47 per livelli<92%) e fattori relativi all\u2019ospite, come l\u2019et\ue0 inferiore ai due mesi (5,22; 1,70\u201216,03), la malnutrizione severa (4,27; 3,47\u20125,25), la presenza di malattie croniche (4,76; 3,27\u20126.93) e l\u2019infezione da HIV (4,68; 3,72\u20125,90); sono risultati associati con la mortalit\ue0 anche il basso livello di educazione della madre (1,43; 1,13\u20121,82), il basso livello socio-economico (1,62; 1,32\u20122,00), l\u2019esposizione al fumo passivo (1,52; 1,20\u20121,93) e ai residui dei combustibili (3,02; 2,11\u20124,31). Le vaccinazioni di routine sono risultate associate ad una riduzione della mortalit\ue0 (0,46; 0,36\u20120,58). La revisione ha messo in luce una mancanza di studi sui fattori legati all\u2019assistenza sanitaria, alle barriere di accesso e alla qualit\ue0 delle cure. Conclusioni: questo lavoro supporta le attuali raccomandazioni di OMS e UNICEF per ridurre la mortalit\ue0 per ALRI e rileva l\u2019opportunit\ue0 di includere tra le strategie in atto, anche interventi di prevenzione e trattamento delle malattie croniche e strategie volte a promuovere l\u2019educazione e lo sviluppo socio-economico. Il lavoro, oltre a confermare la raccomandazione di misurare la saturazione di ossigeno nelle ALRI severe e somministrarlo quando la saturazione \ue8 inferiore al 90%, depone a favore della somministrazione di ossigeno gi\ue0 a una saturazione inferiore al 92%

Compound Heterozygosity for a Recessive Glycine Substitution and a Splice Site Mutation in the COL7A1 Gene Causes an Unusually Mild Form of Localized Recessive Dystrophic Epidermolysis Bullosa

Type VII collagen is the major component of anchoring fibrils, adhesion structures of stratified epithelia that span the basement membrane region and papillary dermis. Mutations in the gene COL7A1 encoding type VII collagen cause dystrophic epidermolysis bullosa, a clinically heterogeneous autosomal dominant or recessive blistering disorder of the skin and mucous membranes. In this report, we investigate three siblings affected by an unusually mild form of localized recessive dystrophic epidermolysis bullosa who were shown to be compound heterozygotes for novel mutations affecting COL7A1. The maternally inherited mutation is a G→C transversion that converts a codon for glycine to a codon for arginine (G1347R). The paternal mutation is a neutral G→A transition at the last base of exon 70 (5820G→A) that alters the correct splicing of COL7A1 pre-mRNA, giving rise to an aberrant mRNA carrying the in-frame skipping of exon 70 in addition to the full-length RNA transcript carrying the G→A substitution. Consistent with the normal levels of COL7A1 mRNA transcripts detected by northern analysis, immunoblotting and immunofluorescence studies evidenced that the patient keratinocytes synthesize and secrete normal amounts of stable type VII collagen, which is correctly deposited at the dermal–epidermal junction. In addition, mutated type VII collagen molecules assemble to form numerous, normally shaped anchoring fibrils, as shown by electron microscopic examination. The combination of a recessive glycine substitution with a splice site mutation that permits partially correct splicing therefore leads to a normal expression of mutated type VII collagen molecules with marginally altered biologic activity, and to the extremely mild phenotype observed in our patients

Indirect methods to estimate hidden population

Estimating the prevalence of the so-called "hidden populations" can be challenging, because the identification of its members is difficult due to their socially sanctionable or illegal behaviors. This article provides a critical review of the most widely used methods for estimating the size of a hard-to-reach population. All are indirect methods, based on incomplete data sources. Depending on the available data, one method can be more appropriate than another. Besides, each method must fulfill a number of requirements, and each one may be subject to specific risk of bias. To choose the most suitable method, an accurate evaluation of the available data is necessary, and. if possible several methods should be used simultaneously to be able to compare the results and to critically evaluate if these results fit with the reality. En determinadas situaciones podemos encontrar dificultades a la hora de calcular prevalencias en algunas poblaciones. Es el caso de personas que tienen comportamientos que son difíciles de identificar debido a que pueden estar sancionados socialmente o ser ilegales. Es lo que llamamos poblacio-nes ocultas. Este artículo proporciona una revisión crítica de los métodos más utilizados para calcular el tamaño de una población de difícil acceso. Se trata de métodos indirectos, que estiman la prevalencia de una población oculta basándose en fuentes de datos incompletas. Se exponen diferentes métodos, cada uno de ellos tiene diferentes indicaciones para ser utilizado, dependiendo de los datos de los que dispongamos. Además, precisan de una serie de requisitos para poder ser aplicados y cada uno está expuesto a di-ferentes tipos de sesgos. Por estos motivos, hay que valorar correctamente los datos disponibles para aplicar el método más preciso, y si fuese posible, utilizar simultáneamente varios métodos para poder comparar los resultados obtenidos, además de valorar críticamente los resultados y comprobar si se ajustan a la realidad.Palabras clave: Poblaciones Vulnerables, Métodos Epidemiológicos, Vigilancia Epidemiológica, Recogida de Datos.Financiación: parcialmente financiado por “Ministerio de Economía y Competitividad, Actuación de Formación Posdoctoral” (FPDI-2013-15827).S

Hypoxaemia as a Mortality Risk Factor in Acute Lower Respiratory Infections in Children in Low and Middle-Income Countries: Systematic Review and Meta-Analysis.

To evaluate the association between hypoxaemia and mortality from acute lower respiratory infections (ALRI) in children in low- and middle-income countries (LMIC).Systematic review and meta-analysis.Observational studies reporting on the association between hypoxaemia and death from ALRI in children below five years in LMIC.Medline, Embase, Global Health Library, Lilacs, and Web of Science to February 2015.Quality In Prognosis Studies tool with minor adaptations to assess the risk of bias; funnel plots and Egger's test to evaluate publication bias.Out of 11,627 papers retrieved, 18 studies from 13 countries on 20,224 children met the inclusion criteria. Twelve (66.6%) studies had either low or moderate risk of bias. Hypoxaemia defined as oxygen saturation rate (SpO2) <90% associated with significantly increased odds of death from ALRI (OR 5.47, 95% CI 3.93 to 7.63) in 12 studies on 13,936 children. An Sp02 <92% associated with a similar increased risk of mortality (OR 3.66, 95% CI 1.42 to 9.47) in 3 studies on 673 children. Sensitivity analyses (excluding studies with high risk of bias and using adjusted OR) and subgroup analyses (by: altitude, definition of ALRI, country income, HIV prevalence) did not affect results. Only one study was performed on children living at high altitude.The results of this review support the routine evaluation of SpO2 for identifying children with ALRI at increased risk of death. Both a Sp02 value of 92% and 90% equally identify children at increased risk of mortality. More research is needed on children living at high altitude. Policy makers in LMIC should aim at improving the regular use of pulse oximetry and the availability of oxygen in order to decrease mortality from ALRI

Risk factors for mortality from acute lower respiratory infections (ALRI) in children under five years of age in low and middle-income countries: a systematic review and meta-analysis of observational studies.

OBJECTIVE:To evaluate risk factors for death from acute lower respiratory infections (ALRI) in children in low- and middle-income countries. DESIGN:Systematic review and meta-analysis. STUDY SELECTION:Observational studies reporting on risk factors for death from ALRI in children below five years in low- and middle income countries. DATA SOURCES:Medline, Embase, Global Health Library, Lilacs, and Web of Science to January 2014. RISK OF BIAS ASSESSMENT:Quality In Prognosis Studies tool with minor adaptations to assess the risk of bias; funnel plots and Egger's test to evaluate publication bias. RESULTS:Out of 10,655 papers retrieved, 77 studies from 39 countries (198,359 children) met the inclusion criteria. Host and disease characteristics more strongly associated with ALRI mortality were: diagnosis of very severe pneumonia as per WHO definition (odds ratio 9.42, 95% confidence interval 6.37‒13.92); age below two months (5.22, 1.70‒16.03); diagnosis of Pneumocystis Carinii (4.79, 2.67‒8.61), chronic underlying diseases (4.76, 3.27‒6.93); HIV/AIDS (4.68, 3.72‒5.90); and severe malnutrition (OR 4.27, 3.47‒5.25). Socio-economic and environmental factors significantly associated with increased odds of death from ALRI were: young maternal age (1.84, 1.03‒3.31); low maternal education (1.43, 1.13‒1.82); low socio-economic status (1.62, 1.32‒2.00); second-hand smoke exposure (1.52, 1.20 to 1.93); indoor air pollution (3.02, 2.11‒4.31). Immunisation (0.46, 0.36‒0.58) and good antenatal practices (0.50, 0.31‒0.81) were associated with decreased odds of death. CONCLUSIONS:Host and disease characteristics as well as socio-economic and environmental determinants affect the risk of death from ALRI in children. Together with the prevention and treatment of chronic diseases, interventions to modify underlying risk factors such as poverty, lack of female education, and poor environmental conditions, should be considered among the strategies to reduce ALRI mortality in children in low- and middle-income countries

Subgroup analysis in the population living at 0–1,499 meters above sea level.

<p>Subgroup analysis in the population living at 0–1,499 meters above sea level.</p

Association between hypoxemia and death.

<p>Notes: seventeen studies were able to be pooled in the meta-analysis. The remaining study that could not be meta-analysed used an SpO2 cut-off of 92% and found an HR of 12.2 (95% CI 1.6–92.0).29.</p

Risk of bias in the included studies.

<p>Red = High risk of bias. Yellow = Moderate risk of bias. Green = Low risk of bias. White = Unknown risk of bias.</p

Sensitivity analyses.

<p>Sensitivity analyses.</p