Ethnic differences in the +405 and -460 vascular endothelial growth factor polymorphisms and peripheral neuropathy in patients with diabetes residing in a North London, community in the United Kingdom.

BACKGROUND: There are marked ethnic differences in the susceptibility to the long-term diabetic vascular complications including sensory neuropathy. The vascular endothelial growth factor (VEGF) +405 (C/G) and -460 (T/C) polymorphisms are associated with retinopathy and possibly with nephropathy, however no information is available on their relationship with peripheral neuropathy. Therefore, we examined the prevalence of these VEGF genotypes in a multi-ethnic cohort of patients with diabetes and their relationship with evident peripheral diabetic neuropathy. METHODS: In the current investigation, we studied 313 patients with diabetes mellitus of African-Caribbean, Indo-Asian and Caucasian ethnic origin residing in an inner-city community in London, United Kingdom attending a single secondary care centre. Genotyping was performed for the VEGF +405 and VEGF -460 polymorphisms using a pyrosequencing technique. RESULTS: Forty-nine patients (15.6%) had clinical evidence of peripheral neuropathy. Compared to Caucasian patients, African-Caribbean and Indo-Asian patients had lower incidence of neuropathy (24.6%, 14.28%, 6.7%, respectively; P = 0.04). The frequency of the VEGF +405 GG genotype was more common in Indo-Asian patients compared to African-Caribbean and Caucasian patients (67.5%, 45.3%, 38.4%, respectively; p ≤ 0.02). The G allele was more common in patients with type 2 diabetes of Indo-Asian origin compared to African-Caribbean and Caucasian origin (p ≤ 0.02). There was no difference between the ethnic groups in VEGF -460 genotypes. The distributions of the VEGF +405 and VEGF -460 genotypes were similar between the diabetic patients with and without neuropathy. CONCLUSIONS: In this cohort of patients, VEGF +405 and VEGF -460 polymorphisms were not associated with evident diabetic peripheral neuropathy, however an association was found between VEGF +405 genotypes and Indo-Asian which might have relevance to their lower rates of ulceration and amputation. This finding highlights the need for further investigation of any possible relationship between VEGF genotype, circulating VEGF concentrations and differential vulnerability to peripheral neuropathy amongst diabetic patients of different ethnic backgrounds

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Prevalência, comportamentos de risco e níveis de informação sobre a esquistossomose urinária em escolares da Área de Saúde 1o de Junho, na Cidade de Maputo, Moçambique

Para determinar a prevalência, identificar os comportamentos de risco e os níveis de informação sobre a esquistossomose urinária, realizou-se um estudo transversal, entre outubro e novembro de 1996, em três escolas primárias da Área de Saúde 1º de Junho, na cidade de Maputo, Moçambique. Efetuaram-se inquéritos epidemiológicos e recolheram-se amostras únicas de urina de 434 escolares de ambos os sexos, selecionados ao acaso, da segunda a quinta classes. A idade média foi de 11,3 anos (amplitude 6-16). A prevalência encontrada foi de 11,3% (49/434). O grupo etário de 15 e mais anos apresentou a prevalência mais elevada (13,6%), enquanto o de 10 a 14 anos, a maior intensidade de infecção (204 ovos/10 ml de urina). Apenas 18,9% dos escolares já tinham ouvido falar na doença. Destes, só 19,5% (16/82) sabiam como esta se manifestava. Cerca de 50% dos escolares reportaram contatos freqüentes com potenciais focos de transmissão de esquistossomose. Os resultados sugerem que a esquistossomose urinária é um problema de saúde pública nas escolas da Área de Saúde 1º de Junho

Prevalência, comportamentos de risco e níveis de informação sobre a esquistossomose urinária em escolares da Área de Saúde 1º de Junho, na Cidade de Maputo, Moçambique

Para determinar a prevalência, identificar os comportamentos de risco e os níveis de informação sobre a esquistossomose urinária, realizou-se um estudo transversal, entre outubro e novembro de 1996, em três escolas primárias da Área de Saúde 1º de Junho, na cidade de Maputo, Moçambique. Efetuaram-se inquéritos epidemiológicos e recolheram-se amostras únicas de urina de 434 escolares de ambos os sexos, selecionados ao acaso, da segunda a quinta classes. A idade média foi de 11,3 anos (amplitude 6-16). A prevalência encontrada foi de 11,3% (49/434). O grupo etário de 15 e mais anos apresentou a prevalência mais elevada (13,6%), enquanto o de 10 a 14 anos, a maior intensidade de infecção (204 ovos/10 ml de urina). Apenas 18,9% dos escolares já tinham ouvido falar na doença. Destes, só 19,5% (16/82) sabiam como esta se manifestava. Cerca de 50% dos escolares reportaram contatos freqüentes com potenciais focos de transmissão de esquistossomose. Os resultados sugerem que a esquistossomose urinária é um problema de saúde pública nas escolas da Área de Saúde 1º de Junho

Epidemiology, clinical features and risk factors for human rabies and animal bites during an outbreak of rabies in Maputo and Matola cities, Mozambique, 2014: Implications for public health interventions for rabies control.

In Mozambique, the majority of rabies outbreaks are unreported and data on the epidemiological features of human rabies and animal bites are scarce. An outbreak of human rabies in adjacent Maputo and Matola cities in 2014 prompted us to investigate the epidemiology, clinical features and risk factors of human rabies and animal bites in the two cities.We reviewed cases of human rabies and animal bites from April to July 2014, and carried out a community investigation in July and August in the neighborhoods where cases of human rabies resided. This investigation included collection of clinical, demographic and epidemiological information and a case control study to investigate the risk factors associated with human rabies. Fourteen cases of human rabies were detected in Maputo (n = 10) and Matola (n = 3) cities and neighbouring Boane district (n = 1) between April and August 2014, all of whom had been admitted to hospital. All had a recent history of dog bite. Of the 14 rabid dogs, only one had been immunized. 819 cases of animal bites were registered, of which 64.6% (529/819) were from Maputo City. Dogs were responsible for 97.8% (801/819) of all animal bites, but only 27.0% (126/467) were immunized. Factors significantly associated with human rabies were: age <15 years (p = 0.05), bite by stray dog (p = 0.002), deep wound (p = 0.02), bite in the head (p = 0.001), bite by unimmunized dog (p = 0.01), no use of soap and water (p = 0.001), and no post-exposure prophylaxis (p = 0.01).Implementation of control measures for rabies is poor in Maputo and Matola cities, where cases of human rabies were strongly associated with bites by stray and unvaccinated dogs and irregular implementation of post-exposure measures

IMPLICAÇÕES DE SUPORTE DE INICIATIVAS DE SAÚDE GLOBAIS NO SISTEMA DE SAÚDE DE MOÇAMBIQUE

Over 70% of financial support to the health system in Mozambique comes from international health partners. During the last decade, substantial support was allocated through the Global Health Initiatives, however, the concrete implications of these Global Health Initiatives on national health system are not known. Drawing upon qualitative methods, between March 2007 to May 2011, 26 senior managers from the national level, 66 health managers and providers from Gaza, Zambézia and Nampula provinces were interviewed. We also conducted an extensive review of the documents that report the context of national health policy, degree of implementation and the role of international aid. As results, during the last years, Health Programs have been boosted by funds from the Global Health Initiatives and thus the volume of interventions to control selected diseases has increased markedly. Despite this increase, the National Health System remains poor in many aspects (infrastructure, personnel, monitoring and evaluation, health information systems, etc). Many Non-Governamental Organizations supported by these Global Initiatives continue to attract qualified public health personnel, helping to weaken the system and induce geo-discrepancies and inequities while rendering ineffective monitoring and evaluation systems. The Ministry of Health still plays a marginal role in terms of management and control of funds and therefore the implementation of existing strategic plans is full of uncertainties. The unpredictability of promised disbursements mainly due to the weak capacity of the Ministry of Health accountability system aggravates the situation. Very recently, some Global Health Initiatives started to strengthen the national health system, but the impact of these efforts will only be visible in the long term. The exaggerated emphasis on supporting disease specific interventions limits the integration approach to the health of the population. Global Health Initiatives should be based on a long-term commitment and support approaches that are consistent with the Compact of the International Health Partnership, which focuses on strengthening the National Health System as a whole.Mais de 70% do suporte financeiro ao sistema de saúde de Moçambique provém de parceiros de saúde internacionais. Durante a última década, apoio substancial foi alocado através das Iniciativas de Saúde Globais. Porém, as implicações concretas dessas Iniciativas sobre o sistema nacional de saúde não são conhecidas, daí a necessidade de se analizar, como objectivo, as implicações das Iniciativas de Saúde Globais para o Sistema Nacional de Saúde. Baseando-se em métodos qualitativos, entre Março de 2007 a Maio de 2011, 26 gestores seniores de saúde ao nível nacional e 66 gestores e provedores de saúde de Gaza, Zambézia e Nampula foram entrevistados. Também foi conduzida análise de documentos que relatam o contexto do sector de saúde nacional, políticas, grau de implementação e o papel da ajuda internacional. Como resultados, nos últimos anos, os Programas de Saúde foram impulsionados por fundos destas Iniciativas e assim o volume de actividades de controlo de doenças seleccionadas aumentou de forma marcante. Apesar deste aumento, o Sistema Nacional de Saúde ainda permanece pobre em muitos aspectos (infra-estruturas, pessoal qualificado, monitoria e avaliação, sistemas de informação de saúde, entre outros). Muitas Organizações Não-Governamentais apoiadas pelas Iniciativas de Saúde Globais continuam a atrair o pessoal de saúde pública qualificado, contribuindo para enfraquecer o sistema e induzem a geo-discrepância e iniquidades para além de tornar ineficazes os sistemas de monitoria e avaliação. O Ministério da Saúde ainda joga um papel marginal em termos de gestão e controlo dos fundos e, portanto, a execução dos planos estratégicos existentes é repleto de incertezas, situação agravada pela imprevisibilidade dos desembolsos prometidos. Muito recentemente, algumas destas iniciativas mudaram seu foco passando a apoiar no fortaleciemento do sistema de saúde, mas o impacto destes esforços só será visível a longo prazo. A ênfase exagerada de suporte no controlo de doenças seleccionadas limita a abordagem de integração para a saúde da população. Recomenda-se que Iniciativas de Saúde Globais devem basear-se em compromissos de longo prazo e apoiarem abordagens que estão em consonância com o Compacto de Parceria para Saúde que centra-se no fortalecimento do Sistema Nacional de Saúde como um todo

Epidemiological link between cases of human rabies admitted to Maputo Central Hospital and animal bite and human rabies cases identified at the community level.

<p>The left circles represent the dogs linked to cases initially identified at Maputo Central Hospital. The rectangles with numbered human rabies case (H.R. case #) inside at the right represent human rabies cases identified at Maputo Central Hospital. The rectangles at the right with non numbered human rabies case (H.R. case) or animal bite (A.B. case) represents cases of human rabies and animal bites identified during the community investigation.</p

Frequency of signs and symptoms in cases of human rabies.

<p>Frequency of signs and symptoms in cases of human rabies.</p

Frequency of cases of animal bite and rabies deaths in Maputo city and Province, April to July 2014.

<p>Frequency of cases of animal bite and rabies deaths in Maputo city and Province, April to July 2014.</p