The concept of vulnerability is a cornerstone of the theoretical basis and practical application of ethics in human subjects research. Risks to humans participating in research must be minimized; ...that is, subjects must be offered protection from risks. Vulnerable subjects require additional protections.
This paper reviews the ethical and conceptual basis of vulnerability within the context of human subjects research and suggests a basic approach that institutional review boards (IRBs) can use when considering if the research includes adequate safeguards to protect the rights and welfare of subjects who are likely to be vulnerable.
Two distinct approaches to describing the features that make a person vulnerable are the categorical approach and the contextual approach. The categorical approach considers certain groups or populations as vulnerable. This approach is not optimal because it does not address persons with multiple vulnerabilities, does not account for variation in the degree of vulnerability within the group based on individual characteristics, and classifies certain persons as vulnerable rather than identifying situations in which individuals might be considered vulnerable. The alternate contextual approach allows for a more nuanced understanding of the nature of the vulnerability than the categorical approach and therefore a more focused approach to safeguards. The IRB is charged with ensuring that additional safeguards to protect the rights and welfare of subjects who are likely to be vulnerable are included in the study under review. To make this determination, the IRB might be advised to consider two questions: (1) is inclusion necessary? and (2) if so, are safeguards adequate?
Although vulnerability is often presented as a yes/no consequence related to some characteristic of a group, a more accurate approach is to consider vulnerability as occurring along a spectrum of seriousness and as a consequence of situations and context. With this idea in mind, investigators and IRBs are advised to take a stepwise approach to determining if the study meets the regulatory and ethical admonition to ensure that safeguards protect the rights and welfare of vulnerable subjects.
Gold nanoparticles (AuNPs) have been extensively studied within biomedicine due to their biocompatibility and low toxicity. In particular, AuNPs have been widely used to deliver photosensitiser ...agents for photodynamic therapy (PDT) of cancer. Here we review the state-of-the-art for the functionalisation of the gold nanoparticle surface with both photosensitisers and targeting ligands for the active targeting of cancer cell surface receptors. From the initial use of the AuNPs as a simple carrier of the photosensitiser for PDT, the field has significantly advanced to include: the use of PEGylated modification to provide aqueous compatibility and stealth properties for in vivo use; gold metal-surface enhanced singlet oxygen generation; functionalisation of the AuNP surface with biological ligands to specifically target over-expressed receptors on the surface of cancer cells and; the creation of nanorods and nanostars to enable combined PDT and photothermal therapies. These versatile AuNPs have significantly enhanced the efficacy of traditional photosensitisers for both in vitro and in vivo cancer therapy. From this review it is apparent that AuNPs have an important future in the treatment of cancer.
Allergic rhinitis (AR), a chronic inflammatory disease of the upper airway, is one of the most common chronic diseases in the United States and is estimated to affect up to 60 million people. ...Pediatric Allergies in America is the largest and most comprehensive survey to date of pediatric patients and parents of patients with allergy, as well as health care providers (HCPs), regarding AR in children and its treatment. The goals of the survey were to determine the prevalence of AR in the US pediatric population and to collect information on what effect the condition has on patients in terms of symptom burden, quality of life, productivity, disease management, and pharmacologic treatment. This national survey screened 35,757 households to identify 500 children with HCP-diagnosed nasal allergies and 504 children without nasal allergies who were between the ages of 4 and 17 years. Parents of young children, as well as children 10 to 17 years of age, were questioned about the condition and its treatment. In parallel, 501 HCPs were interviewed. This survey has captured previously unavailable data on the prevalence of nasal allergies and their most common and most bothersome symptoms, on the effect of nasal allergies on the quality of life of children, and on medication use, including both over-the-counter and prescription medications, and has identified factors affecting satisfaction with treatment. The Pediatric Allergies in America survey also identifies distinct areas for improvement in the management of AR in children. In fact, based on the results of this survey, it appears that HCPs overestimate patients' and parents' satisfaction with disease management and the benefit of medications used for the treatment of nasal allergies in children. Findings from this national survey have identified important challenges to the management of AR, suggesting that its burden on children in the United States has been significantly underestimated.
John Calvin was a leader of the European Reformation of the sixteenth century and the influence of his thought remains crucial in our world. This collection explores the origins of Calvin's thought ...and the theological, historical, and cultural circumstances in which they have evolved from Geneva to our times.
Statins are highly effective drugs prescribed to millions of people to lower LDL-cholesterol and decrease cardiovascular risk. The benefits of statin therapy seen in randomized clinical trials will ...only be replicated in real-life if patients adhere to the prescribed treatment regimen. But, about half of patients discontinue statin therapy within the first year, and adherence decreases with time. Patient, physician and healthcare system-related factors play a role in this problem. Recent studies have focused more on the patients’ perspectives on non-adherence. Adverse events are cited as the most common cause of statin discontinuation; thus, the healthcare provider must be willing to ally and dialogue with patients to address concerns and assess the risks and benefits of continued statin therapy.
Inadequate water and sanitation during childbirth are likely to lead to poor maternal and newborn outcomes. This paper uses existing data sources to assess the water and sanitation (WATSAN) ...environment surrounding births in Tanzania in order to interrogate whether such estimates could be useful for guiding research, policy and monitoring initiatives.
We used the most recent Tanzania Demographic and Health Survey (DHS) to characterise the delivery location of births occurring between 2005 and 2010. Births occurring in domestic environments were characterised as WATSAN-safe if the home fulfilled international definitions of improved water and improved sanitation access. We used the 2006 Service Provision Assessment survey to characterise the WATSAN environment of facilities that conduct deliveries. We combined estimates from both surveys to describe the proportion of all births occurring in WATSAN-safe environments and conducted an equity analysis based on DHS wealth quintiles and eight geographic zones.
42.9% (95% confidence interval: 41.6%-44.2%) of all births occurred in the woman's home. Among these, only 1.5% (95% confidence interval: 1.2%-2.0%) were estimated to have taken place in WATSAN-safe conditions. 74% of all health facilities conducted deliveries. Among these, only 44% of facilities overall and 24% of facility delivery rooms were WATSAN-safe. Combining the estimates, we showed that 30.5% of all births in Tanzania took place in a WATSAN-safe environment (range of uncertainty 25%-42%). Large wealth-based inequalities existed in the proportion of births occurring in domestic environments based on wealth quintile and geographical zone.
Existing data sources can be useful in national monitoring and prioritisation of interventions to improve poor WATSAN environments during childbirth. However, a better conceptual understanding of potentially harmful exposures and better data are needed in order to devise and apply more empirical definitions of WATSAN-safe environments, both at home and in facilities.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
To estimate the burden of diarrhoeal diseases from exposure to inadequate water, sanitation and hand hygiene in low‐ and middle‐income settings and provide an overview of the impact on ...other diseases.
Methods
For estimating the impact of water, sanitation and hygiene on diarrhoea, we selected exposure levels with both sufficient global exposure data and a matching exposure‐risk relationship. Global exposure data were estimated for the year 2012, and risk estimates were taken from the most recent systematic analyses. We estimated attributable deaths and disability‐adjusted life years (DALYs) by country, age and sex for inadequate water, sanitation and hand hygiene separately, and as a cluster of risk factors. Uncertainty estimates were computed on the basis of uncertainty surrounding exposure estimates and relative risks.
Results
In 2012, 502 000 diarrhoea deaths were estimated to be caused by inadequate drinking water and 280 000 deaths by inadequate sanitation. The most likely estimate of disease burden from inadequate hand hygiene amounts to 297 000 deaths. In total, 842 000 diarrhoea deaths are estimated to be caused by this cluster of risk factors, which amounts to 1.5% of the total disease burden and 58% of diarrhoeal diseases. In children under 5 years old, 361 000 deaths could be prevented, representing 5.5% of deaths in that age group.
Conclusions
This estimate confirms the importance of improving water and sanitation in low‐ and middle‐income settings for the prevention of diarrhoeal disease burden. It also underscores the need for better data on exposure and risk reductions that can be achieved with provision of reliable piped water, community sewage with treatment and hand hygiene.
Objectif
Estimer la charge des maladies diarrhéiques provenant de l'exposition à l'eau, l'assainissement et l'hygiène des mains inadéquats, dans les pays à revenus faibles et intermédiaires et fournir un aperçu de l'impact sur d'autres maladies.
Méthodes
Pour l'estimation de l'impact de l'eau, de l'assainissement et de l'hygiène sur la diarrhée, nous avons sélectionné des niveaux d'exposition avec à la fois des données suffisantes d'exposition mondiale et une relation exposition‐risque correspondante. Les données d'exposition mondiale ont été estimées pour l'année 2012 et les estimations du risque ont été prises à partir des analyses systématiques les plus récentes. Nous avons estimé les décès attribuables et les années de vie ajustées sur l'incapacité (DALY) par pays, âge et sexe pour l'eau, l'assainissement et l'hygiène des mains, séparément et comme un ensemble de facteurs de risque. Les estimations d'incertitude ont été calculées sur la base de l'incertitude entourant les estimations d'exposition et les risques relatifs.
Résultats
En 2012, une estimation de 502 000 décès par diarrhée causés par l'eau non potable et 280 000 décès dus à un assainissement inadéquat, a été calculée. L'estimation la plus probable de la charge de morbidité due à l'hygiène inadéquate des mains s’élève à 297 000 décès. Un total de 842 000 décès par diarrhée causés par cet ensemble de facteurs de risque a été estimé, ce qui équivaut à 1,5% de la charge de morbidité totale et 58% des maladies diarrhéiques. Chez les enfants de moins de cinq ans, 361 000 décès pourraient être évités, ce qui représente 5,5% des décès dans ce groupe d’âge.
Conclusions
Cette estimation confirme l'importance de l'amélioration de l'eau et de l'assainissement dans les pays à revenus faibles et intermédiaires pour la prévention de la charge des maladies diarrhéiques. Il souligne également la nécessité d'améliorer les données sur l'exposition et les réductions du risque qui peuvent être obtenues grâce à la fourniture de raccordement à l'eau fiable, à des égouts communautaires avec traitement et à l'hygiène des mains.
Objetivo
Calcular la carga de diarreas por exposición a agua, saneamiento e higiene de manos inadecuados en lugares con ingresos bajos y medios, y ofrecer una visión general del impacto sobre otras enfermedades.
Métodos
Para calcular el impacto del agua, saneamiento e higiene sobre la diarrea, hemos seleccionados niveles de exposición que tuviesen suficientes datos de exposición global y una relación exposición‐riesgo conjunta. Los datos de exposición global se calcularon para el año 2012, y los cálculos de riesgo se obtuvieron de los análisis sistemáticos más recientes. Hemos calculado las muertes atribuibles y los años de vida ajustados por la discapacidad (AVADs) por país, edad y sexo para agua, saneamiento y lavado de manos inadecuados de forma separada, y como un conglomerado de factores de riesgo. Los cálculos de incertidumbre se hicieron basándose en la incerteza alrededor de los cálculos de exposición y los riesgos relativos.
Resultados
En el 2012, se calculó que 502 000 muertes por diarrea estaban causadas por beber un agua inadecuada y 280 000 muertes por un saneamiento inadecuada. El cálculo de carga de enfermedad más probable por una higiene de manos inadecuada es de 297 000 muertes. En total, se calculó que 842 000 de muertes eran causadas por este conglomerado de factores de riesgo, siendo responsables de un 1.5% de la carga total de enfermedades y del 58% de las enfermedades diarreicas. En niños menores de cinco años, 361 000 muertes podrían prevenirse, representando un 5.5% de las muertes en este grupo de edad.
Conclusiones
Este cálculo confirma la importancia de mejorar la calidad del agua y del saneamiento en lugares con ingresos bajos y medios para prevenir la carga de enfermedad por diarreas. También subestima la necesidad de mejores datos sobre exposición y la reducción del riesgo que podría alcanzarse con el suministro de agua fiable mediante redes de tuberías, sistemas de alcantarillado comunitario con tratamiento de residuos e higiene de manos.
Three large new trials of unprecedented scale and cost, which included novel factorial designs, have found no effect of basic water, sanitation and hygiene (WASH) interventions on childhood stunting, ...and only mixed effects on childhood diarrhea. Arriving at the inception of the United Nations' Sustainable Development Goals, and the bold new target of safely managed water, sanitation and hygiene for all by 2030, these results warrant the attention of researchers, policy-makers and practitioners.
Here we report the conclusions of an expert meeting convened by the World Health Organization and the Bill and Melinda Gates Foundation to discuss these findings, and present five key consensus messages as a basis for wider discussion and debate in the WASH and nutrition sectors. We judge these trials to have high internal validity, constituting good evidence that these specific interventions had no effect on childhood linear growth, and mixed effects on childhood diarrhea. These results suggest that, in settings such as these, more comprehensive or ambitious WASH interventions may be needed to achieve a major impact on child health.
These results are important because such basic interventions are often deployed in low-income rural settings with the expectation of improving child health, although this is rarely the sole justification. Our view is that these three new trials do not show that WASH in general cannot influence child linear growth, but they do demonstrate that these specific interventions had no influence in settings where stunting remains an important public health challenge. We support a call for transformative WASH, in so much as it encapsulates the guiding principle that - in any context - a comprehensive package of WASH interventions is needed that is tailored to address the local exposure landscape and enteric disease burden.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Parenting plan evaluators are expert witnesses who offer their opinion. Courts in common law jurisdictions generally do not accept evidence of an opinion as it is not considered to be reliable ...evidence from which to establish a fact. An exception to that general principle is expert opinion evidence. In short, an opinion from a person with specialized knowledge or expertise about the area in which they are an expert may be sufficiently reliable to form an evidentiary basis from which to make a finding of fact, provided the opinion meets certain criteria. These criteria will be discussed in this article, as well as what is relevant, reliable and persuasive evidence. The relevant legal principles will be examined in an historical and contemporary, theoretical and practical context. The authors reflect on their considerable experience as consumers of expert evidence and apply this to parenting plan evaluations, as well as considering future challenges in the field.
Objective
To assess the impact of inadequate water and sanitation on diarrhoeal disease in low‐ and middle‐income settings.
Methods
The search strategy used Cochrane Library, MEDLINE & PubMed, Global ...Health, Embase and BIOSIS supplemented by screening of reference lists from previously published systematic reviews, to identify studies reporting on interventions examining the effect of drinking water and sanitation improvements in low‐ and middle‐income settings published between 1970 and May 2013. Studies including randomised controlled trials, quasi‐randomised trials with control group, observational studies using matching techniques and observational studies with a control group where the intervention was well defined were eligible. Risk of bias was assessed using a modified Ottawa–Newcastle scale. Study results were combined using meta‐analysis and meta‐regression to derive overall and intervention‐specific risk estimates.
Results
Of 6819 records identified for drinking water, 61 studies met the inclusion criteria, and of 12 515 records identified for sanitation, 11 studies were included. Overall, improvements in drinking water and sanitation were associated with decreased risks of diarrhoea. Specific improvements, such as the use of water filters, provision of high‐quality piped water and sewer connections, were associated with greater reductions in diarrhoea compared with other interventions.
Conclusions
The results show that inadequate water and sanitation are associated with considerable risks of diarrhoeal disease and that there are notable differences in illness reduction according to the type of improved water and sanitation implemented.
Objectif
Evaluer l'impact de l'eau et de l'assainissement inadéquats sur les maladies diarrhéiques dans les régions à revenus faibles et intermédiaires.
Méthodes
La stratégie de recherche a utilisé Cochrane Library, MEDLINE, PubMed, Global Health, Embase et BIOSIS, complétés par la recherche dans les listes de références des revues systématiques publiées antérieurement, pour identifier les études rapportant sur des interventions examinant l'effet de l'amélioration de l'eau potable et de l'assainissement dans les régions à revenus faibles et intermédiaires, publiées entre 1970 et mai 2013. Les études comprenant des essais randomisés contrôlés, des essais quasi‐randomisés avec un groupe témoins, des études d'observation utilisant des techniques d'appariement et des études observationnelles avec un groupe témoins où l'intervention a été bien définie, étaient éligibles. Le risque de biais a été évalué à l'aide d'une échelle modifiée d'Ottawa‐Newcastle. Les résultats de l’étude ont été combinés en utilisant une méta‐analyse et une méta‐régression pour déduire des estimations du risque globales et spécifiques à l'intervention.
Résultats
Sur 6819 rapports identifiés sur l'eau potable, 61 études répondaient aux critères d'inclusion et sur 12 515 rapports sur l'assainissement, 11 études ont été incluses. Dans l'ensemble, l'amélioration de l'eau potable et de l'assainissement a été associée à une diminution des risques de diarrhée. Des améliorations spécifiques, telles que l'utilisation de filtres à eau, la fourniture de raccordement à l'eau courante de haute qualité et à des égouts, ont été associées à des réductions plus importantes de la diarrhée par rapport à d'autres interventions.
Conclusions
Les résultats montrent que l'eau et l'assainissement inadéquats sont associés à des risques considérables de maladies diarrhéiques et qu'il existe des différences notables dans la réduction des maladies selon le type d'amélioration de l'eau et de l'assainissement mis en place.
Objetivo
Evaluar el impacto del agua y saneamiento inadecuados sobre la enfermedad diarreica en lugares con ingresos medios y bajos.
Métodos
La estrategia de búsqueda utilizó la Biblioteca de Cochrane, MEDLINE & PubMed, Global Health, Embase y BIOSIS suplementado con una búsqueda en las listas de las referencias de revisiones sistemáticas previamente publicadas, con el fin de identificar estudios en los que se reportasen intervenciones que examinaran el efecto de mejoras en el agua para consumo y el saneamiento en lugares con ingresos medios y bajos, publicados entre 1970 y Mayo 2013. Los estudios elegibles incluían ensayos aleatorizados controlados, ensayos cuasi‐aleatorizados con grupo control, estudios observacionales pareados y estudios observacionales con un grupo control en donde la intervención estaba bien definida. El riesgo de sesgo se evaluó utilizando la escala de Ottawa‐Newcastle modificada. Los resultados del estudio se combinaron utilizando el meta‐análisis y la meta‐regresión para derivar los cálculos específicos de riesgo generales y específicos de la intervención.
Resultado
De 6,819 registros identificados para agua de consumo humano, 61 estudios cumplieron con los criterios de inclusión y de 12,515 registros identificados para saneamiento, se incluyeron 11 estudios. En general, las mejoras en el agua para consumo y el saneamiento estaban asociadas con una disminución en el riesgo de diarrea. Las mejoras específicas, tales como el uso de filtros de agua, el suministro de agua de calidad mediante conexión al acueducto y al alcantarillado, estaban asociadas con mayores reducciones en la diarrea, comparadas con otras intervenciones.
Conclusiones
Los resultados muestran que un suministro de agua y saneamiento inadecuados estaban asociadas con riesgos considerables de enfermedad diarreica, y que existen diferencias notables en la reducción de la enfermedad según el tipo de mejoras en el agua y el saneamiento implementados.
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