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Health controversies involve complex exchanges of disagreements over health and medicine. They unfold differently in different parts of the world, and they often extend over long periods of time. In contemporary argumentation theory, proposals have recently been emerging for "disagreement management at large scale" and for an explicit focus on design of disagreement management methods. Lewinski and Aakhus characterize large-scale disagreement as polylogic: formed of complex networks of players holding contrasting positions that are attacked and defended in multiple places. Large-scale disagreements such as health controversies are important sites for emergence of new disagreement management methods, including new ways of arriving at conclusions about questions of fact (affecting positions) and new formats for coming to decisions about questions of policy (affecting places). The controversy over myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), spanning a period of very rapid change in reasoning about health, has been deeply entangled with the design of new institutional places for managing disagreements about health. It serves well to illustrate both the large, multi-scale structure of health controversies and the importance of long-term disagreement management strategies.
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Dissidências e Disputas , Humanos , Síndrome de Fadiga Crônica/terapia , Negociação , Comunicação em Saúde/métodos , Fatores de Tempo , Política de SaúdeRESUMO
Domestic Abuse Coordinators (DACs) work strategically across National Health Service (NHS) hospital and other off-site clinical settings to support clinical staff in domestic abuse enquiry and response, and to co-lead the development and implementation of effective clinical policies and procedures for the management of domestic abuse and the support of survivors. Drawing on data from a large NHS acute trust in central London, we analyse the impact of the DAC role in increasing the rate of referrals of high-risk domestic abuse cases, and generate plausible estimates of the budget impact of the DAC role in respect of costs accrued to NHS trusts. Using eight quarters of clinical data and an interrupted time series design, we find that evidence that implementation of a DAC role is linked with an increase in the rate of high-risk referrals of between 18% and 21% per quarter, indicating improved responses to victim-survivors at highest risk of imminent harm. Under a range of reasonable assumptions, initiation of the DAC role is shown to be cost-saving to an employing acute trust. Future work should seek to quantify the direct impacts to survivor health and wellbeing of the implementation of the DAC role.
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Orçamentos , Medicina Estatal , Humanos , Hospitais , Análise de Séries Temporais Interrompida , Encaminhamento e ConsultaRESUMO
AIMS: Genetic discrimination in insurance is a significant clinical, research and consumer issue. Recently, the Australian life insurance industry introduced a partial moratorium on the use of genetic test results. However, in Aotearoa New Zealand, both life and health insurers can still use genetic results legally to discriminate against applicants. We aimed to document experiences and concerns of New Zealand-based health professionals (HPs) around the potential misuse of genetic test results for insurance purposes. METHODS: We administered an online survey to New Zealand HPs who discuss genetic testing with patients, their experiences regarding the use of genetic test results in insurance and views on regulation. RESULTS: Twenty-three New Zealand HPs responded, 15 of whom worked in genetics clinics, representing >60% of the total New Zealand clinical genetics workforce. Eleven respondents reported having patients who experienced adverse outcomes related to insurance based on genetic results. Respondents reported patients sometimes/often delayed (n=11) or refused (n=4) genetic testing due to insurance concerns. Over 80% of those who answered (n=17/21) believe insurers' use of genetic results should be legally regulated. CONCLUSION: New Zealand HPs have concerns about insurance companies using genetic test results in underwriting, including the effect on patients, and strongly believe government legislation is required.
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Testes Genéticos , Seleção Tendenciosa de Seguro , Humanos , Nova Zelândia , Austrália , Seguro de Vida , Seguro SaúdeRESUMO
Vaccination guidelines for dogs and cats indicate that core vaccines (for dogs, rabies, distemper, adenovirus, parvovirus; for cats, feline parvovirus, herpes virus-1, calicivirus) are essential to maintain health, and that non-core vaccines be administered according to a clinician's assessment of a pet's risk of exposure and susceptibility to infection. A reliance on individual risk assessment introduces the potential for between-practice inconsistencies in non-core vaccine recommendations. A study was initiated to determine non-core vaccination rates of dogs (Leptospira, Borrelia burgdorferi, Bordetella bronchiseptica, canine influenza virus) and cats (feline leukemia virus) in patients current for core vaccines in veterinary practices across the United States. Transactional data for 5,531,866 dogs (1,670 practices) and 1,914,373 cats (1,661 practices) were retrieved from practice management systems for the period November 1, 2016 through January 1, 2020, deidentified and normalized. Non-core vaccination status was evaluated in 2,798,875 dogs and 788,772 cats that were core-vaccine current. Nationally, median clinic vaccination rates for dogs were highest for leptospirosis (70.5%) and B. bronchiseptica (68.7%), and much lower for canine influenza (4.8%). In Lyme-endemic states, the median clinic borreliosis vaccination rate was 51.8%. Feline leukemia median clinic vaccination rates were low for adult cats (34.6%) and for kittens and 1-year old cats (36.8%). Individual clinic vaccination rates ranged from 0 to 100% for leptospirosis, B. bronchiseptica and feline leukemia, 0-96% for canine influenza, and 0-94% for borreliosis. Wide variation in non-core vaccination rates between clinics in similar geographies indicates that factors other than disease risk are driving the use of non-core vaccines in pet dogs and cats, highlighting a need for veterinary practices to address gaps in patient protection. Failure to implement effective non-core vaccination strategies leaves susceptible dogs and cats unprotected against vaccine-preventable diseases.
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Doenças do Gato , Doenças do Cão , Vacina Antirrábica , Animais , Doenças do Gato/prevenção & controle , Gatos , Cães , Feminino , Hospitais Veterinários , Humanos , Estados Unidos , Vacinação/veterináriaRESUMO
Mechanisms of interaction between Bordetella pertussis and other viral agents are yet to be fully explored. We studied the inflammatory cytokine expression patterns among children with both viral-bacterial infections. Nasopharyngeal aspirate (NPA) samples were taken from children, aged < 1 year, positive for Rhinovirus, Bordetella pertussis and for Rhinovirus and Bordetella pertussis. Forty cytokines were evaluated in NPA by using human cytokine protein arrays and a quantitative analysis was performed on significantly altered cytokines. Forty cytokines were evaluated in NPA by using human cytokine protein arrays and a quantitative analysis was performed on significantly altered cytokines. Our results show that co-infections display a different inflammatory pattern compared to single infections, suggesting that a chronic inflammation caused by one of the two pathogens could be the trigger for exacerbation in co-infections.
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Citocinas/biossíntese , Infecções por Picornaviridae/metabolismo , Rhinovirus , Coqueluche/metabolismo , Idade de Início , Antibacterianos/uso terapêutico , Coinfecção , Citocinas/genética , Progressão da Doença , Características da Família , Feminino , Regulação da Expressão Gênica , Humanos , Lactente , Recém-Nascido , Inflamação , Mediadores da Inflamação/sangue , Masculino , Nasofaringe/metabolismo , Nasofaringe/microbiologia , Nasofaringe/virologia , Infecções por Picornaviridae/genética , Fatores Socioeconômicos , Coqueluche/tratamento farmacológico , Coqueluche/genéticaRESUMO
BACKGROUND: Providing understandable information to patients is necessary to achieve the aims of the Informed Consent process: respecting and promoting patients' autonomy and protecting patients from harm. In recent decades, new, primarily digital technologies have been used to apply and test innovative formats of Informed Consent. We conducted a systematic review to explore the impact of using digital tools for Informed Consent in both clinical research and in clinical practice. Understanding, satisfaction and participation were compared for digital tools versus the non-digital Informed Consent process. METHODS: We searched for studies on available electronic databases, including Pubmed, EMBASE, and Cochrane. Studies were identified using specific Mesh-terms/keywords. We included studies, published from January 2012 to October 2020, that focused on the use of digital Informed Consent tools for clinical research, or clinical procedures. Digital interventions were defined as interventions that used multimedia or audio-video to provide information to patients. We classified the interventions into 3 different categories: video only, non-interactive multimedia, and interactive multimedia. RESULTS: Our search yielded 19,579 publications. After title and abstract screening 100 studies were retained for full-text analysis, of which 73 publications were included. Studies examined interactive multimedia (29/73), non-interactive multimedia (13/73), and videos (31/73), and most (34/38) studies were conducted on adults. Innovations in consent were tested for clinical/surgical procedures (26/38) and clinical research (12/38). For research IC, 21 outcomes were explored, with a positive effect on at least one of the studied outcomes being observed in 8/12 studies. For clinical/surgical procedures 49 outcomes were explored, and 21/26 studies reported a positive effect on at least one of the studied outcomes. CONCLUSIONS: Digital technologies for informed consent were not found to negatively affect any of the outcomes, and overall, multimedia tools seem desirable. Multimedia tools indicated a higher impact than videos only. Presence of a researcher may potentially enhance efficacy of different outcomes in research IC processes. Studies were heterogeneous in design, making evaluation of impact challenging. Robust study design including standardization is needed to conclusively assess impact.
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Consentimento Livre e Esclarecido , Multimídia , Adulto , Humanos , Projetos de PesquisaRESUMO
BACKGROUND: Monovalent meningococcal C conjugate vaccine (MCCV) was introduced into the routine immunization program in many countries in Europe and worldwide following the emergence of meningococcal serogroup C (MenC) in the late 1990s. This systematic literature review summarizes the immediate and long-term impact and effectiveness of the different MCCV vaccination schedules and strategies employed. METHODS: We conducted a systematic literature search for peer-reviewed, scientific publications in the databases of MEDLINE (via PubMed), LILACS, and SCIELO. We included studies from countries where MCCV have been introduced in routine vaccination programs and studies providing the impact and effectiveness of MCCV published between 1st January 2001 and 31st October 2017. RESULTS: Forty studies were included in the review; 30 studies reporting impact and 17 reporting effectiveness covering 9 countries (UK, Spain, Italy, Canada, Brazil, Australia, Belgium, Germany and the Netherlands). Following MCCV introduction, significant and immediate reduction of MenC incidence was consistently observed in vaccine eligible ages in all countries with high vaccine uptake. The reduction in non-vaccine eligible ages (especially population > 65 years) through herd protection was generally observed 3-4 years following introduction. Vaccine effectiveness (VE) was mostly assessed through screening methods and ranged from 38 to 100%. The VE was generally highest during the first year after vaccination and waned over time. The VE was better maintained in countries employing catch-up campaigns in older children and adolescents, compared to routine infant only schedules. CONCLUSIONS: MCCV were highly effective, showing a substantial and sustained decrease in MenC invasive meningococcal disease. The epidemiology of meningococcal disease is in constant transition, and some vaccination programs now include adolescents and higher valent vaccines due to the recent increase in cases caused by serogroups not covered by MCCV. Continuous monitoring of meningococcal disease is essential to understand disease evolution in the setting of different vaccination programs.
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Infecções Meningocócicas , Vacinas Meningocócicas , Adolescente , Idoso , Austrália , Bélgica , Brasil , Canadá , Criança , Europa (Continente) , Alemanha , Humanos , Programas de Imunização , Lactente , Itália , Infecções Meningocócicas/epidemiologia , Infecções Meningocócicas/prevenção & controle , Países Baixos , Espanha , Vacinação , Vacinas ConjugadasRESUMO
BACKGROUND: People increasingly search online for health information. Particularly, parents of patients often use the Internet as a source for health information. We conducted a survey to investigate the online searching behavior of parents of patients < 18 years, admitted for surgery in an Italian pediatric hospital. METHODS: The cross-sectional survey was nested in a prospective cohort study on surgical procedures. Parents of patients undergoing surgical procedures at Bambino Gesù Children's Hospital, Rome, Italy, were enrolled and contacted by phone after the procedure. We recorded socio-demographic data, sex, length of stay following surgery, proximity of residence to the hospital, use of the internet to search for information on the surgery before and after the intervention and effect of information found online. RESULTS: The majority (91%) of parents of children undergoing surgical intervention used the internet. Of these, 74.3% of parents searched for information before surgery, and 26.1% searched for information after. Most parents searched for information on the care provider's website. Two thirds of parents reported that information found online had increased their understanding of the child's condition. Multivariate analyses indicated that families living far from the hospital (> 43 km) were more likely to search for health information (OR 2.3; 95% CI 1.34-4.00), as were families of patients undergoing a major surgery (OR = 2.1; 95% CI 1.04-4.11). CONCLUSIONS: Parents of children undergoing surgery often search online for information on their child's intervention, in particular those whose child is scheduled for a major surgery and those living far from the hospital. A survey like the present one allows to understand parents' information needs, to better guide them in online information seeking and to better tailor information provided on the care provider's website.
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Comportamento de Busca de Informação , Internet , Pais/psicologia , Procedimentos Cirúrgicos Operatórios , Criança , Estudos Transversais , Feminino , Hospitais Pediátricos , Humanos , Itália , Masculino , Estudos Prospectivos , Inquéritos e QuestionáriosRESUMO
INTRODUCTION: Diabetes mellitus (DM) is a highly prevalent, chronic condition in adults worldwide. Little is known about the potential role of diabetes as an effect modifier of vaccine protective responses. AREAS COVERED: We conducted a literature review of the immunogenicity, efficacy and effectiveness of immunization in individuals, in studies that compared subjects with DM (DM+) and without DM (DM-). We found few published studies, which were only for vaccines against hepatitis B, influenza, pneumococcal disease, or varicela zoster. Except for a consistent attenuation of the immune response to hepatitis B vaccine among DM+ individuals, we found little other consistent evidence for DM as an effect modifier of vaccine responses. EXPERT OPINION: There are substantial gaps in our knowledge of the impact of DM on the immune response to immunization or effect of vaccination.
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Diabetes Mellitus/imunologia , Vacinação , Vacinas/imunologia , Adulto , Humanos , Imunogenicidade da Vacina , Vacinas/administração & dosagemRESUMO
It is necessary to conduct Clinical Trials in children, including for novel vaccines. Children cannot legally provide valid consent, but can assent to research participation. Informed consent and assent communications are frequently criticized for their lack of comprehensibility and often, researchers do not involve patients in informed consent design. We tested a blended research-design approach to co-design multimedia informed consent prototypes for experimental vaccine studies targeted at the pediatric population. We report details on the methodology utilized, and the insights, ideas, and prototype solutions we generated using social media data analysis, a survey, and workshops. A survey of clinical trial researchers indicated that while the most did not use technology for informed consent, they considered its utilization favorable. Social media analysis enabled researchers to quickly understand where community perspectives were concordant and discordant and build their understanding of the types of topics that they may want to focus on during the design workshops. Participatory design workshops for children and their families reaped insights, ideas, and prototypes for a range of tools including apps and websites. Participants felt that the prototypes were better able to communicate necessary content than the original text document format. We propose using a participatory, mixed-methods approach to design informed consent so that it is better adapted to patients' needs. Such an approach would be helpful in better addressing the needs of different segments of the populations involved in clinical trials. Further evidence should be gained about the impact of this strategy in improving recruitment, decreasing withdrawals and litigations, and improving patient satisfaction during clinical trials.
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BACKGROUND: Ankle-foot orthoses may be used in pre-ambulatory children with cerebral palsy; however, their effect on the acquisition of walking is unknown. This case report aims to evaluate the effect of an ankle-foot orthosis-footwear combination on the acquisition of walking in a single subject with cerebral palsy. CASE DESCRIPTION AND METHODS: This study reports the orthotic management of a single child with spastic bilateral cerebral palsy over a 15-month period, during which time the ability to independently stand and walk was acquired. Custom rigid ankle-foot orthoses were prescribed. Gait speed and Edinburgh Visual Gait Score were assessed with and without the orthoses. FINDINGS AND OUTCOMES: The subject developed the ability to stand and walk using an ankle-foot orthosis-footwear combination with a walker frame, and to a limited extent without a walker frame. The subject remained unable to take independent steps unless wearing the ankle-foot orthosis-footwear combination. Clinically significant differences in gait speed and Edinburgh Visual Gait Score were observed. CONCLUSION: An ankle-foot orthosis-footwear combination may aid the development of independent walking in some children with cerebral palsy. Further research on the effects of orthoses on the acquisition of walking ability in children with cerebral palsy is needed. CLINICAL RELEVANCE: Custom rigid ankle-foot orthoses combined with footwear may aid the development of independent standing and walking in some children with bilateral spastic cerebral palsy. This intervention may be considered in clinical practice and future research in this patient group.
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Paralisia Cerebral/terapia , Órtoses do Pé , Transtornos Neurológicos da Marcha/terapia , Espasticidade Muscular/terapia , Tornozelo/fisiopatologia , Paralisia Cerebral/fisiopatologia , Terapia Combinada , Feminino , Pé/fisiopatologia , Transtornos Neurológicos da Marcha/fisiopatologia , Humanos , Lactente , Espasticidade Muscular/fisiopatologiaRESUMO
INTRODUCTION: Hair loss as a result of chemotherapy for early breast cancer (EBC) is a frequent and distressing side effect. Minimising hair loss may improve mood and body image. Our aim was to determine scalp cooling (SC) efficacy in EBC patients receiving contemporary chemotherapy regimen, to inform future patients choice to use SC or not. METHODS AND RESULTS: Prospective cohort study of 60 stage 1-3 EBC patients recommended to receive taxane or anthracycline-taxane chemotherapy regimens. The primary outcome was incidence of minimal hair-loss (MHL - defined as 60% Dean grade 1 or 2). Patients were categorised by chemotherapy (3 groups) and randomised 1:1 within each group to two scalp cooling temperature settings using the Dignitana Dignicap machine (secondary endpoint). Patients reported degree of hair loss using the Dean score on day 1 of each cycle and following the last chemotherapy. RESULTS: On an intention-to-treat basis, 33% of patients reported MHL, thus our primary endpoint was not achieved. Patients receiving taxane-only chemotherapy had the highest rate of MHL (45%). No other factors (including hair type, age, body weight, temperature setting) predicted for MHL. Patient-reported anxiety reduced significantly in all patients, but no difference was observed for depression or body image irrespective of degree of hair loss. SC-related adverse events were uniformly of low grade and all resolved. We would recommend the use of SC for all patients receiving taxane-based chemotherapy, with its use for those patients recommended for anthracycline-taxane regimens being made on an individual basis. Trial Registration anztr.org.au ACTRN12615001106527.
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Alopecia/prevenção & controle , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Hipotermia Induzida/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Alopecia/induzido quimicamente , Alopecia/epidemiologia , Estudos de Coortes , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida/psicologia , Couro Cabeludo/fisiopatologiaRESUMO
Avian influenza viruses (AIVs) continue to pose a global threat. Waterfowl are the main reservoir and are responsible for the spillover of AIVs to other hosts. This study was conducted as part of routine surveillance activities in Bangladesh and it reports on the serological and molecular detection of H5N1 AIV subtype. A total of 2169 cloacal and 2191 oropharyngeal swabs as well as 1725 sera samples were collected from live birds including duck and chicken in different locations in Bangladesh between the years of 2013 and 2014. Samples were tested using virus isolation, serological tests and molecular methods of RT-PCR. Influenza A viruses were detected using reverse transcription PCR targeting the virus matrix (M) gene in 41/4360 (0.94%) samples including both cloacal and oropharyngeal swab samples, 31 of which were subtyped as H5N1 using subtype-specific primers. Twenty-one live H5N1 virus isolates were recovered from those 31 samples. Screening of 1,868 blood samples collected from the same birds using H5-specific ELISA identified 545/1603 (34%) positive samples. Disconcertingly, an analysis of 221 serum samples collected from vaccinated layer chicken in four districts revealed that only 18 samples (8.1%) were seropositive for anti H5 antibodies, compared to unvaccinated birds (n=105), where 8 samples (7.6%) were seropositive. Our result indicates that the vaccination program as currently implemented should be reviewed and updated. In addition, surveillance programs are crucial for monitoring the efficacy of the current poultry vaccinations programs, and to monitor the circulating AIV strains and emergence of AIV subtypes in Bangladesh.
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Galinhas/virologia , Patos/virologia , Virus da Influenza A Subtipo H5N1/isolamento & purificação , Influenza Aviária/epidemiologia , Doenças das Aves Domésticas/epidemiologia , Animais , Bangladesh/epidemiologia , Virus da Influenza A Subtipo H5N1/genética , Virus da Influenza A Subtipo H5N1/patogenicidade , Influenza Aviária/virologia , Aves Domésticas , Doenças das Aves Domésticas/virologiaRESUMO
BACKGROUND: Rapid diagnostic tests (RDTs) for Plasmodium falciparum malaria use antibodies to detect either HRP-2 antigen or pLDH antigen, and can improve access to diagnostics in developing countries. OBJECTIVES: To assess the diagnostic accuracy of RDTs for detecting P. falciparum parasitaemia in persons living in endemic areas who present to ambulatory healthcare facilities with symptoms suggestive of malaria by type and brand. SEARCH STRATEGY: We undertook a comprehensive search of the following databases: Cochrane Infectious Diseases Group Specialized Register; MEDLINE; EMBASE; MEDION; Science Citation Index; Web of Knowledge; African Index Medicus; LILACS; IndMED; to January 14, 2010. SELECTION CRITERIA: Studies comparing RDTs with a reference standard (microscopy or polymerase chain reaction) in blood samples from a random or consecutive series of patients attending ambulatory health facilities with symptoms suggestive of malaria in P. falciparum endemic areas. DATA COLLECTION AND ANALYSIS: For each study, a standard set of data was extracted independently by two authors, using a tailored data extraction form. Comparisons were grouped hierarchically by target antigen, and type and brand of RDT, and combined in meta-analysis where appropriate. MAIN RESULTS: We identified 74 unique studies as eligible for this review and categorized them according to the antigens they detected. Types 1 to 3 include HRP-2 (from P. falciparum) either by itself or with other antigens. Types 4 and 5 included pLDH (from P. falciparum) either by itself or with other antigens. In comparisons with microscopy, we identified 71 evaluations of Type 1 tests, eight evaluations of Type 2 tests and five evaluations of Type 3 tests. In meta-analyses, average sensitivities and specificities (95% CI) were 94.8% (93.1% to 96.1%) and 95.2% (93.2% to 96.7%) for Type 1 tests, 96.0% (94.0% to 97.3%) and 95.3% (87.3% to 98.3%) for Type 2 tests, and 99.5% (71.0% to 100.0%) and 90.6% (80.5% to 95.7%) for Type 3 tests, respectively. Overall for HRP-2, the meta-analytical average sensitivity and specificity (95% CI) were 95.0% (93.5% to 96.2%) and 95.2% (93.4% to 99.4%), respectively. For pLDH antibody-based RDTs verified with microscopy, we identified 17 evaluations of Type 4 RDTs and three evaluations of Type 5 RDTs. In meta-analyses, average sensitivity for Type 4 tests was 91.5% (84.7% to 95.3%) and average specificity was 98.7% (96.9% to 99.5%). For Type 5 tests, average sensitivity was 98.4% (95.1% to 99.5%) and average specificity was 97.5% (93.5% to 99.1%). Overall for pLDH, the meta-analytical average sensitivity and specificity (95% CI) were 93.2% (88.0% to 96.2%) and 98.5% (96.7% to 99.4%), respectively. For both categories of test, there was substantial heterogeneity in study results. Quality of the microscopy reference standard could only be assessed in 40% of studies due to inadequate reporting, but results did not seem to be influenced by the reporting quality.Overall, HRP-2 antibody-based tests (such as the Type 1 tests) tended to be more sensitive and were significantly less specific than pLDH-based tests (such as the Type 4 tests). If the point estimates for Type 1 and Type 4 tests are applied to a hypothetical cohort of 1000 patients where 30% of those presenting with symptoms have P. falciparum, Type 1 tests will miss 16 cases, and Type 4 tests will miss 26 cases. The number of people wrongly diagnosed with P. falciparum would be 34 with Type 1 tests, and nine with Type 4 tests. AUTHORS' CONCLUSIONS: The sensitivity and specificity of all RDTs is such that they can replace or extend the access of diagnostic services for uncomplicated P. falciparum malaria. HRP-2 antibody types may be more sensitive but are less specific than pLDH antibody-based tests, but the differences are small. The HRP-2 antigen persists even after effective treatment and so is not useful for detecting treatment failures.
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Testes Diagnósticos de Rotina/métodos , Doenças Endêmicas , Malária Falciparum/diagnóstico , Parasitemia/diagnóstico , Plasmodium falciparum , Antígenos de Protozoários/análise , Biomarcadores/análise , Humanos , L-Lactato Desidrogenase/análise , Malária Falciparum/epidemiologia , Malária Falciparum/imunologia , Parasitemia/epidemiologia , Parasitemia/imunologia , Plasmodium falciparum/enzimologia , Plasmodium falciparum/imunologia , Proteínas de Protozoários/análise , Sensibilidade e EspecificidadeRESUMO
Gold particles have been formed in water-in-oil microemulsions doped with a photodestructible surfactant. UV light-induced nanoparticle flocculation has been achieved after photolysis of the photosurfactant, leading to a reduction in the steric stabilization provided by the surfactant layer.
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The Wilms' tumour suppressor gene, WT1, is mutated in 10-15% of Wilms' tumours and encodes zinc-finger proteins with diverse cellular functions critical for nephrogenesis, genitourinary development, haematopoiesis and sex determination. Here we report that a novel alternative WT1 transcript, AWT1, is co-expressed with WT1 in renal and haematopoietic cells. AWT1 maintains WT1 exonic structure between exons 2 and 10, but deploys a new 5'-exon located in intron 1 of WT1. The AWT1 gene predicts proteins of approximately 33 kDa, comprising all exon 5 and exon 9 splicing variants previously characterized for WT1. Although WT1 is not genomically imprinted in kidney, we have previously shown monoallelic expression of a WT1 antisense transcript (WT1-AS) that is consistent with genomic imprinting. Here we demonstrate that both WT1-AS and the novel AWT1 transcript are imprinted in normal kidney with expression confined to the paternal allele. Wilms' tumours display biallelic AWT1 expression, indicating relaxation of imprinting of AWT1 in a subset of WTs. Our findings define human chromosome 11p13 as a new imprinted locus, and also suggest a possible molecular basis for the strong bias of paternal allele mutations and variable penetrance observed in syndromes with inherited WT1 mutations.
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Processamento Alternativo/genética , Impressão Genômica , Perda de Heterozigosidade/genética , Proteínas WT1/genética , Tumor de Wilms/genética , Sequência de Bases , Células Cultivadas , Éxons/genética , Humanos , Íntrons/genética , Rim/metabolismo , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Metilação , Dados de Sequência Molecular , Mutação/genética , Proteínas WT1/metabolismo , Tumor de Wilms/metabolismoRESUMO
Wilms' tumour (WT) has a diverse and complex molecular aetiology, with several different loci identified by cytogenetic and molecular analyses. One such locus is on chromosome 7p, where cytogenetic abnormalities and loss of heterozygosity (LOH) indicate the presence of a Wilms' tumour suppressor gene. In order to isolate a candidate gene for this locus, we have characterized the breakpoint regions at a novel constitutional chromosome translocation (t(1;7)(q42;p15)), found in a child with WT and skeletal abnormalities. We identified two genes that were interrupted by the translocation: the parathyroid hormone-responsive B1 gene (PTH-B1) at 7p and obscurin at 1q. With no evidence for LOH at 1q42, we focused on the characterization of PTH-B1. We detected novel alternately spliced isoforms of PTH-B1, which were expressed in a wide range of adult and foetal tissues. Importantly, expression of two isoforms were disrupted in the WT of the t(1;7) patient. We also identified an additional splice isoform expressed only in 7p LOH tumours. The disruption of PTH-B1 by the t(1;7), together with aberrant splicing in sporadic WTs, suggests that PTH-B1 is a candidate for the 7p Wilms' tumour suppressor gene.