An analysis of the experiences of bereaved relatives and health care providers following palliative sedation: a study protocol for a qualitative international multicenter case study.

BACKGROUND: Patients at the end-of-life may experience refractory symptoms of which pain, delirium, vomiting and dyspnea are the most frequent. Palliative sedation can be considered a last resort option to alleviate one or more refractory symptoms. There are only a limited number of (qualitative) studies exploring the experiences of relatives of sedated patients and their health care professionals (HCPs). The aims of this study protocol are: 1) to elicit the experiences of bereaved relatives and health care professionals of patients treated with palliative sedation and 2) to explore the understanding of the decision-making process to start palliative sedation across care settings in 5 European countries. METHODS: This study protocol is part of the larger HORIZON 2020 Palliative Sedation project. Organisational case study methodology will be used to guide the study design. In total, 50 cases will be conducted in five European countries (10 per country). A case involves a semi-structured interview with a relative and an HCP closely involved in the care of a deceased patient who received some type of palliative sedation at the end-of-life. Relatives and health care professionals of deceased patients participating in a linked observational cohort study of sedated patients cared for in hospital wards, palliative care units and hospices will be recruited. The data will be analyzed using a framework analysis approach. The first full case will be analyzed by all researchers after being translated into English using a pre-prepared code book. Afterwards, bimonthly meetings will be organized to coordinate the data analysis. DISCUSSION: The study aims to have a better understanding of the experiences of relatives and professional caregivers regarding palliative sedation and this within different settings and countries. Some limitations are: 1) the sensitivity of the topic may deter some relatives from participation, 2) since the data collection and analysis will be performed by at least 5 different researchers in 5 countries, some differences may occur which possibly makes it difficult to compare cases, but using a rigorous methodology will minimize this risk.

Features of durable response and treatment efficacy for capecitabine monotherapy in advanced breast cancer: real-world evidence from a large single-centre cohort.

PURPOSE: In metastatic breast cancer (MBC) population treated with capecitabine monotherapy, we investigated clinical-pathological features as possible biomarkers for the oncological outcome. METHODS: Retrospective study of consecutive MBC patients treated at University Hospitals Leuven starting capecitabine between 1999 and 2017. The primary endpoint was the durable response (DR), defined as non-progressive disease for > 52 weeks. Other main endpoints were objective response rate (ORR), time to progression (TTP) and overall survival (OS). RESULTS: We included 506 patients; mean age at primary breast cancer diagnosis was 51.2 years; 18.2% had de novo MBC; 98.8% were pre-treated with taxanes and/or anthracycline. DR was reached in 11.6%. Patients with DR, as compared to those without DR, were more likely oestrogen receptor (ER) positive (91.5% vs. 76.8%, p = 0.010) at first diagnosis, had a lower incidence of lymph node (LN) involvement (35.6% vs. 49.9%, p = 0.039) before starting capecitabine, were more likely to present with metastases limited to ≤ 2 involved sites (54.2% vs. 38.5%, p = 0.020) and time from metastasis to start of capecitabine was longer (mean 3.5 vs. 2.7 years, p = 0.020). ORR was 22%. Median TTP and OS were 28 and 58 weeks, respectively. In multivariate analysis (only performed for TTP), ER positivity (hazard ratio (HR) = 0.529, p < 0.0001), HER2 negativity (HR = 0.582, p = 0.024), absence of LN (HR = 0.751, p = 0.008) and liver involvement (HR = 0.746, p = 0.013), older age at capecitabine start (HR = 0.925, p < 0.0001) and younger age at diagnosis of MBC (HR = 0.935, p = 0.001) were significant features of longer TTP. CONCLUSION: Our data display relevant clinical-pathological features associated with DR and TTP in patients receiving capecitabine monotherapy for MBC.

Early integrated palliative care in chronic heart failure and chronic obstructive pulmonary disease: protocol of a feasibility before-after intervention study.

BACKGROUND: Patients with chronic heart failure (CHF) and patients with chronic obstructive pulmonary disease (COPD) are amenable to integrated palliative care (PC); however, despite the recommendation by various healthcare organizations, these patients have limited access to integrated PC services. In this study, we present the protocol of a feasibility prospective study that aims to explore if an "early integrated PC" intervention can be performed in an acute setting (cardiology and pulmonology wards) and whether it will have an effect on (i) the satisfaction of care and (ii) the quality of life and the level of symptom control of CHF/COPD patients and their informal caregivers. METHODS: A before-after intervention study with three phases, (i) baseline phase where the control group receives standard care, (ii) training phase where the personnel is trained on the application of the intervention, and (iii) intervention phase where the intervention is applied, will be carried out in cardiology and pulmonology wards in the University Hospital Leuven for patients with advanced CHF/COPD and their informal caregivers. Eligible patients (both control and intervention group) and their informal caregivers will be asked to complete the Palliative Outcome Scale, the CANHELP Lite, and the Advance Care Planning Questionnaire at the inclusion moment and 3 months after hospital discharge. DISCUSSION: The present study will assess the feasibility of carrying out PC-focused studies in acute wards for CHF/COPD patients and draw lessons for the further integration of PC alongside standard treatment. Further, it will measure the quality of life and quality of care of patients and thus shed light on the care needs of this population. Finally, it will evaluate the potential efficacy of the "early integrated palliative care" by comparing against existing practices. TRIAL REGISTRATION: Current Controlled Trials ISRCTN24796028 (date of registration August 30, 2018).

Professionals' perceptions and current practices of integrated palliative care in chronic heart failure and chronic obstructive pulmonary disease: a qualitative study in Belgium.

BACKGROUND: Patients with Chronic Heart Failure (CHF) and patients with Chronic Obstructive Pulmonary Disease (COPD) share similar symptom burden with cancer patients, however, they are unlikely to receive palliative care (PC) services. This article examines the perceptions of health care professionals and the current practices of integrated palliative care (IPC) in Belgium. METHODS: Cardiologists and pulmonologists, working in primary care hospitals in Belgium, participated in this study with semi-structured interviews based on IPC indicators. One researcher collected, transcribed verbatim the interviews and carried out their thematic analysis. To increase the reliability of the coding, a second researcher coded a random 30% of the interviews. RESULTS: A total of 22 CHF/COPD specialists participated in the study. The results show that IPC and its potential benefits are viewed positively. A number of IPC components like the holistic approach (physical, psychological, social, spiritual aspects) via multidisciplinary teams, prognosis discussion and illness limitations, patient goals assessment, continuous goal adjustment, reduction of suffering and advanced care planning are partially implemented in several health centers. However, PC specialists are absent from such implementations and PC is still an end-of-life care. CONCLUSIONS: Misconceptions about PC and its association to death and end-of-life appear to be decisive factors for the exclusion of PC specialists and the late initiation of PC itself. The implementation of IPC components is not associated to PC, and as such, leads to suboptimal results. Improved education and enhanced communication is expected to alleviate existing challenges and thus improve the quality of life for the patients.

Estimate of choline nutritional requirements for chicks from 1 to 21 days of age.

Choline is an essential nutrient in poultry diets because it performs various important metabolic functions. The objective of this study was to re-evaluate the choline requirements of male broiler chickens from 1 to 21 days of age at two levels of methionine. Two assays using 2,160 Cobb® chickens (1,080 in each assay) were conducted. The study design was completely randomized and consisted of six treatments and six replicates, with 30 animals per experimental unit. The semipurified basal diet was formulated with corn, soya bean meal, soya protein concentrate, starch and sugar, providing 390 mg/kg choline and 0.593% digestible methionine (requirement level) in Assay 1 and a reduction of about one-quarter in the requirement level of digestible methionine (0.440%) in Assay 2. Choline chloride (62.5%) was added by a supplementation technique to both basal diets to compose crescent levels of choline supplementation (715, 1,040, 1,365, 1,690 and 2,015 mg/kg). The weight gain responses were fitted using quadratic polynomial (QP) and broken-line (BL) models. The ideal intake of choline (mg/bird.day) was estimated from the first intercept of the QP with the BL plateau (BL + QP). The results showed that the diet with the 25% reduction in digestible methionine limited the maximum weight gain by approximately 10%. The choline requirements of broilers from 1 to 7, 1 to 14 and 1 to 21 days of age were 27,013, 44,458 and 62,535 mg/bird.day, respectively, for the requirement level of digestible methionine and 26,796, 41,820 and 56,578 mg/bird.day for the broilers receiving the diet with the 25% reduction in digestible methionine.

Replacing corn with sorghum in the diet alters intestinal microbiota without altering chicken performance.

Sorghum grain can be used to replace corn in broiler diets. However, the effects related to an abrupt change between these grains are not yet clear. The aim of this study was to evaluate the performance and intestinal health of broilers fed diets containing corn and/or sorghum during different periods of rearing. To accomplish this aim, 2100 male chicks were fed the following experimental diets: C100% (corn-based diet); S100% (sorghum-based diet); C:S50% (diet based on corn and sorghum 1:1); PC-S (corn-based diet in the pre-starter phase and sorghum-based diet in subsequent phases); and PS-C (sorghum-based diet in the pre-starter phase and corn-based diet in subsequent phases). The study was conducted with two simultaneous trials in a randomized block design as follows: a performance trial up to 40 days occurred in floor pens (n = 8), and the metabolism trial occurred in cages (n = 10). Performance, jejunal morphometry, number of goblet cells, apparent metabolizable energy (AME), apparent metabolizable energy corrected for nitrogen (AMEn) and the coefficient of apparent metabolizability of dry matter (CMDM) of the diets, and the intestinal microbiota of small intestine and caeca at 10 and 21 days of age (16S gene sequencing) were evaluated. The different experimental diets did not affect performance, jejunal epithelium, AME, AMEn or CMDM. However, the experimental diets altered the percentages of the genera Clostridium, Weissella, Bacillus and Alkaliphilus in the small intestine. In addition, the genera Lactobacillus and Desulfotomaculum in the caeca were altered. The age also affected the microbiota of the intestinal segments. In conclusion, feeding sorghum in place of corn as well as the grain change after the pre-starter phase does not alter broiler performance. However, sorghum alters the intestinal microbiota, resulting in a lower percentage of Clostridium and a higher percentage of Lactobacillus in the small intestine and caeca, respectively.

Integrated palliative care in Europe: a qualitative systematic literature review of empirically-tested models in cancer and chronic disease.

BACKGROUND: Integrated Palliative Care (PC) strategies are often implemented following models, namely standardized designs that provide frameworks for the organization of care for people with a progressive life-threatening illness and/or for their (in)formal caregivers. The aim of this qualitative systematic review is to identify empirically-evaluated models of PC in cancer and chronic disease in Europe. Further, develop a generic framework that will consist of the basis for the design of future models for integrated PC in Europe. METHODS: Cochrane, PubMed, EMBASE, CINAHL, AMED, BNI, Web of Science, NHS Evidence. Five journals and references from included studies were hand-searched. Two reviewers screened the search results. Studies with adult patients with advanced cancer/chronic disease from 1995 to 2013 in Europe, in English, French, German, Dutch, Hungarian or Spanish were included. A narrative synthesis was used. RESULTS: 14 studies were included, 7 models for chronic disease, 4 for integrated care in oncology, 2 for both cancer and chronic disease and 2 for end-of-life pathways. The results show a strong agreement on the benefits of the involvement of a PC multidisciplinary team: better symptom control, less caregiver burden, improvement in continuity and coordination of care, fewer admissions, cost effectiveness and patients dying in their preferred place. CONCLUSION: Based on our findings, a generic framework for integrated PC in cancer and chronic disease is proposed. This framework fosters integration of PC in the disease trajectory concurrently with treatment and identifies the importance of employing a PC-trained multidisciplinary team with a threefold focus: treatment, consulting and training.

Bayesian meta-analysis of diagnostic tests allowing for imperfect reference standards.

There is an increasing interest in meta-analyses of rapid diagnostic tests (RDTs) for infectious diseases. To avoid spectrum bias, these meta-analyses should focus on phase IV studies performed in the target population. For many infectious diseases, these target populations attend primary health care centers in resource-constrained settings where it is difficult to perform gold standard diagnostic tests. As a consequence, phase IV diagnostic studies often use imperfect reference standards, which may result in biased meta-analyses of the diagnostic accuracy of novel RDTs. We extend the standard bivariate model for the meta-analysis of diagnostic studies to correct for differing and imperfect reference standards in the primary studies and to accommodate data from studies that try to overcome the absence of a true gold standard through the use of latent class analysis. Using Bayesian methods, improved estimates of sensitivity and specificity are possible, especially when prior information is available on the diagnostic accuracy of the reference test. In this analysis, the deviance information criterion can be used to detect conflicts between the prior information and observed data. When applying the model to a dataset of the diagnostic accuracy of an RDT for visceral leishmaniasis, the standard meta-analytic methods appeared to underestimate the specificity of the RDT.

Using conventional HIV tests on oral fluid.

There is need for more evaluations of non-invasive tests in order to broaden the reach of testing programs and to perform large scale epidemiological studies. In this study, three different human immunodeficiency virus (HIV) enzyme linked immunosorbent assays (ELISAs) and one line immunoassay were evaluated to detect HIV antibodies in oral fluid samples. Specimens were collected, after informed consent was obtained, with the Oracol (MMD, Worcester, England) device. A total IgG quantitation test was performed to demonstrate the quality of the sample. Assessment of a modified protocol of the Vironostika HIV Ag/Ab, Enzygnost Anti-HIV 1/2 Plus Genscreen HIV-1/2 Version 2 and a line immune confirmatory assay the INNO-LIA HIV I/II score was done, using oral fluid specimens of 325 HIV positive and negative individuals. For the ELISAs, the addition of an extra internal oral fluid control was evaluated as well as different cut-offs, time between sampling and testing and the effect of drinking water just before sampling. Finally, the confirmatory test and some testing algorithms and combination of tests were discussed. The results obtained from the oral fluid specimens were compared with the gold standard on paired serum specimens. Firstly, there was no significant difference observed between the use of the kit controls and the oral fluid controls. New protocols and calculation of cut-offs were defined for two of the three ELISAs. High sensitivities and specificities were obtained with all three ELISAs without any statistical difference between the three tests. Secondly, no statistically significant difference was observed when samples were stored for different time periods between sampling and testing, meaning that a period of seven days at room temperature before testing is still acceptable. Thirdly, drinking water before sample collection did not interfere with the testing, although lower optical densities were observed. None of the positive samples were missed. In addition, the line immunoassay INNO-LIA HIV I/II score test is a promising test for confirmation of reactive oral fluid specimen, but more samples need to be validated in order to adapt the interpretation rules specifically for oral fluid specimens. Different choices/algorithms adapted for the purpose of testing can be proposed. In conclusion, it can be said that the commercial ELISAs with adapted protocol and cut-off values are suitable tools for making HIV test performance accessible to people. With this non-invasive sampling method, more eligible individuals can and will be selected for further HIV test on blood.

Pain management in palliative cancer patients: a prospective observational study on the use of high dosages of transdermal buprenorphine.

INTRODUCTION: Despite guidelines and recommendations, a large proportion of patients with cancer still have inadequate pain control. Transdermal opioid administration can overcome problems such as swallowing and compliance, because only one application every three days is needed. Transdermal buprenorphine was documented to provide effective pain relief in cancer and non-cancer patients. A ceiling effect was described in animals at supratherapeutic dose levels. OBJECTIVES: This prospective observational pilot study was designed to explore the need for doses of transdermal buprenorphine beyond the recommended maximum dose of 140 microg/h, in a cohort of palliative patients with cancer pain. METHODS: 36 consecutive palliative patients with uncontrolled cancer pain were prescribed transdermal buprenorphine after having received adequate information on the disease, its evolution, the pain and the drug. They gave written informed consent for participation in this observational study. Pain intensity and use of breakthrough medication were registered by the patient and the health care provider. RESULTS: Pain was judged to be satisfactory controlled, by the patient and the health care providers, in 21 of 28 evaluable patients at a dose lower than or equal to 140 microg/h. The success rate was higher in the hospitalized patient group. The observation of adequate pain control in two patients treated with doses up to 210 microg/h supports the hypothesis that buprenorphine dose titration above 140 microg/h can be clinically effective and well tolerated. This also refutes the assumption of a clinically relevant ceiling effect. CONCLUSIONS: Transdermal buprenorphine control cancer pain in the majority of palliative patients.

Defining pseudoprogression in glioblastoma multiforme.

BACKGROUND AND PURPOSE: Pseudoprogression is a frequent phenomenon observed since the introduction of postoperative therapy with radiotherapy and temozolomide (RT/TMZ) in glioblastoma multiforme (GBM) patients. However, the criteria defining pseudoprogression, its incidence, the time of occurrence and its impact on therapy and outcome remain poorly defined. METHODS: The objective of this study is to compare two sets of criteria (liberal and stringent), defining pseudoprogression, in a cohort of patients treated before and after the introduction of RT/TMZ in the standard postoperative treatment. This retrospective review includes 136 unselected and consecutively treated patients with pathologically diagnosed GBM. RESULTS: Pseudoprogression was observed in 10 (12%) cases applying the stringent criteria, and in 18 (23%) patients when using the liberal criteria, in the cohort treated with RT/TMZ. Pseudoprogression was observed in only one patient treated with RT alone. The median time to pseudoprogression was 4 weeks after the end of RT. Patients with pseudoprogression had a median survival time of 28 months, compared with 12 months for patients without pseudoprogression. CONCLUSIONS: The incidence of pseudoprogression after RT/TMZ strongly depends on the applied criteria. However, regardless of the stringency of the criteria, the impact on survival remains the same.

Treatment outcomes for human African Trypanosomiasis in the Democratic Republic of the Congo: analysis of routine program data from the world's largest sleeping sickness control program.

OBJECTIVE: To enable the human African trypanosomiasis (HAT) control program of the Democratic Republic of the Congo to generate data on treatment outcomes, an electronic database was developed. The database was piloted in two provinces, Bandundu and Kasai Oriental. In this study, we analysed routine data from the two provinces for the period 2006-2008. METHODS: Data were extracted from case declaration cards and monthly reports available at national and provincial HAT coordination units and entered into the database. RESULTS: Data were retrieved for 15 086 of 15 741 cases reported in the two provinces for the period (96%). Compliance with post-treatment follow-up was very poor in both provinces; only 25% had undergone at least one post-treatment follow-up examination, <1% had undergone the required four follow-up examinations. Relapse rates among those presenting for follow-up were high in Kasai (18%) but low in Bandundu (0.3%). CONCLUSIONS: High relapse rates in Kasai and poor compliance with post-treatment follow-up in both provinces are important problems that the HAT control program urgently needs to address. Moreover, in analogy to tuberculosis control programs, HAT control programs need to adopt a recording and reporting routine that includes reporting on treatment outcomes.

Eficiência de uma fitase bacteriana na liberação de fósforo fítico em dietas de frangos de corte / Efficiency of a bacterial phytase to release phytate phosphorus in broiler chicken diets

Foi avaliada a eficiência de uma fitase (FT) bacteriana na liberação de fósforo fítico utilizando-se curvas de calibração para características ósseas e de desempenho em frangos de corte. O delineamento experimental foi inteiramente ao acaso, com seis tratamentos e seis repetições até 28 dias de idade. O tratamento-controle foi uma dieta à base de milho e farelo de soja deficiente em fósforo (P). Dois tratamentos corresponderam às dietas basais acrescidas de P suplementar, 0,05 por cento e 0,10 por cento, e os outros à dieta basal com 66, 99 e 131 FTU/kg de ração. A curva padrão é definida pelo efeito da adição de P suplementar consumido sobre características ósseas e de desempenho, e os resultados dos tratamentos com fitase são confrontados com a curva para cálculo de P liberado. A adição de P suplementar influenciou o ganho de peso, o peso vivo e o consumo de ração de forma quadrática, bem como miligramas de cinzas ósseas de forma linear. A curva padrão adotada foi da variável miligramas de cinzas ósseas, pois a resposta linear melhor descreve a curva. As inclusões de 66, 99 e 131 FTU/kg liberaram, respectivamente, 0,048 por cento, 0,049 por cento e 0,062 por cento de P. A fitase bacteriana é eficiente na liberação de fósforo fítico e possui viabilidade econômica.

The objective was to determine the efficiency of a bacterial phytase to release phytate phosphorus using calibration curves for performance and bone characteristics in broiler chickens. A completely randomized design with 6 treatments and 6 replicates was used in an experiment with chickens from 1 to 28 days of age. The control treatment was a diet based on corn and soybean meal deficient in phosphorus. Two treatments consisted of the basal diet supplemented with additional phosphorus (0.05 percent and 0.10 percent), and the other treatments received 66, 99 and 131 FTU/kg of feed. The standard curves represented the effect of the levels of additional P intake on performance and bone variables. Then, the responses of the phytase treatments were compared to the standard curves to calculate the P released. The increasing levels of supplemental P had a quadratic effect on weight gain, live weight and feed intake, and linear effect on mg of bone ash. The standard curve elected was mg of bone ash because linear response better represents the curve. Inclusion of 66, 99 and 131 FTU/kg released 0.048 percent, 0.049 percent and 0.062 percent. The bacterial phytase is efficient in releasing phytate, which may be of economical significance.

Stellate ganglion block for the management of hot flashes and sleep disturbances in breast cancer survivors: an uncontrolled experimental study with 24 weeks of follow-up.

BACKGROUND: We studied the stellate ganglion block (SGB) recently suggested for the treatment of severe vasomotor symptoms and sleep disturbances in breast cancer survivors. Following an initial pilot study, which focused on the acceptability and safety of SGB for this important problem, we evaluated its short- and long-term efficacy. MATERIALS AND METHODS: Postmenopausal breast cancer survivors with severe vasomotor symptoms resistant to standard nonhormonal pharmacological intervention were eligible. Diaries were used to measure daily hot flash scores (frequency and intensity) and sleep quality (Pittsburgh Sleep Quality Index) during scheduled visits at baseline, 1, 4, 12 and 24 weeks following the SGB. Efficacy data were analyzed using longitudinal regression models. RESULTS: Thirty-four patients participated and none refused the SGB procedure. Most patients received more than one SGB. The pilot study found SGB to be safe. In the main study, hot flash scores were reduced from baseline by 64% [95% confidence interval (CI) -74% to -49%] and 47% (95% CI -62% to -27%) at weeks 1 and 24, respectively. The odds ratio of better sleep quality relative to baseline was 3.4 at week 1 (95% CI 1.6-7.2) and 4.3 at week 24 (95% CI 1.9-9.8). CONCLUSION: In the short term, SGB appears to be an effective treatment with acceptable morbidity for some breast cancer survivors with therapy-resistant vasomotor symptoms and/or sleep disturbances. Although sleep quality was maintained out to 24 weeks the efficacy of SGB for hot flashes was reduced over time. A randomized controlled trial is needed to confirm these findings.

False-negative tests in breast cancer management.

We review the sensitivity of different diagnostic tests for breast cancer management based on recent experience in a 34-year-old patient. False-negative tests at diagnosis of early disease and of relapse resulted in diagnostic and therapeutic delays. Initial mammography and breast ultrasonography were falsely negative despite a palpable breast lump. Clinical examination and axillary ultrasound missed macroscopically involved lymph nodes. At relapse, metastatic lesions were missed despite symptoms, three years after primary treatment. CA 15-3 was normal; bone and liver metastases were missed by standard and more advanced imaging techniques including liver ultrasonography, nuclear bone scan and PET -CT scan. Worsening of clinical symptoms, lab results and abnormal tissue biopsies finally led to the diagnosis of extensive metastatic disease. Genetic screening showed an abnormality within the BRCA-1 region of unknown clinical importance. This review highlights 1) that diagnostic tests managing symptomatic breast cancer patients may have a low sensitivity, 2) the importance of clinical findings and other markers for disease, such as lactate dehydrogenase and 3) the need for diagnostic biopsies for clinically suspect symptoms despite normal imaging and biochemistry.

MGMT promoter hypermethylation correlates with a survival benefit from temozolomide in patients with recurrent anaplastic astrocytoma but not glioblastoma.

AIMS: To investigate the correlation between O(6)-methylguanine-DNA-methyltransferase (MGMT) promoter methylation and benefit from temozolomide in patients with recurrent high-grade glioma. PATIENTS AND METHODS: A real-time, quantitative, methylation-specific PCR assay was performed on archival tissue blocks from patients treated with temozolomide at the first recurrence. RESULTS: A subgroup of 38 patients who were chemotherapy-naive at recurrence was analysed (22 glioblastoma, 12 anaplastic astrocytoma [AA] and 4 anaplastic oligoastrocytoma [AOA]); none had 1p/19q loss. Among 10 (26%) patients with a hypermethylated MGMT promoter, none experienced disease progression within the first two treatment cycles compared with 12 of 28 (43%) patients with an unmethylated promoter (p=0.016). By Cox multivariate analysis, tumour grade and MGMT promoter methylation correlated with time to progression (p<0.05); MGMT promoter methylation correlated with superior overall survival in AA/AOA but not in glioblastoma. CONCLUSIONS: MGMT promoter methylation predicted a survival benefit in patients with 1p/19q intact AA/AOA treated with temozolomide at recurrence.

Exploring HIV risk perception and behaviour in the context of antiretroviral treatment: results from a township household survey.

The objective of this cross-sectional household survey was to assess factors influencing HIV risk perception, behaviour and intervention uptake in a community characterised by high HIV prevalence and availability of antiretroviral therapy (ART). The survey was conducted in Khayelitsha, South Africa and involved two-stage sampling with self-weighting clusters and random selection of households within clusters. One man and woman between 14 and 49 years old was interviewed in each household; 696 men and 879 women were interviewed for a response rate of 84% and 92% respectively. Ninety-three percent and 94% were sexually active with median age of sexual debut 15.3 and 16.5 years. Eighty-three percent and 82% reported a partner at the time of interview and 29% and 8% had additional partner(s). Forty-one percent and 33% reported condom use during the last sexual encounter. Thirty-seven percent of men not using condoms did not as they believed their partner to be faithful, whilst 27% of women did not as their partner refused. Twenty-eight percent and 53% had been tested for HIV. Having undergone HIV testing was not associated with condom usage, whilst current relationship status was the strongest association with condom usage for both men and women. In spite of a relatively high uptake of condoms and testing as well as ART availability, the HIV epidemic has continued unabated in Khayelitsha. Even greater coverage of preventive interventions is required, together with a national social and political environment that builds on the availability of both preventive and treatment services.

Diagnostic tests for kala-azar: a multi-centre study of the freeze-dried DAT, rK39 strip test and KAtex in East Africa and the Indian subcontinent.

Three diagnostic tests for visceral leishmaniasis (VL), the freeze-dried direct agglutination test (FD-DAT), the rK39 dipstick and a urine latex antigen test (KAtex), were evaluated for use in primary care in East Africa and the Indian subcontinent. Clinical suspects were prospectively recruited and tissue, blood and urine samples were taken. Direct microscopic examination of tissue smear, and FD-DAT, rK39 and KAtex were performed. Sensitivity and specificity with 95% credible intervals were estimated using Bayesian latent class analysis. On the Indian subcontinent both the FD-DAT and the rK39 strip test exceeded the 95% sensitivity and 90% specificity target, but not so in East Africa. Sensitivity of the FD-DAT was high in Ethiopia and Kenya but lower in Sudan, while its specificity was below 90% in Kenya. Sensitivity of the rK39 was below 80% in the three countries, and its specificity was only 70% in Ethiopia. KAtex showed moderate to very low sensitivity in all countries. FD-DAT and rK39 can be recommended for clinical practice on the Indian subcontinent. In East Africa, their clinical use should be carefully monitored. More work is needed to improve existing formats, and to develop better VL diagnostics.

Intrathecal vs. intramuscular administration of human antitetanus immunoglobulin or equine tetanus antitoxin in the treatment of tetanus: a meta-analysis.

BACKGROUND: Mortality caused by tetanus is still a serious health problem in developing countries. Apart from immunization, early treatment with equine antitetanus serum (ATS) or human tetanus immunoglobulin (TIG) is the real treatment that can avoid death. On pathophysiological grounds intrathecal administration would be preferred because of high concentrations of the antiserum in cerebrospinal fluid and thus around the nerve roots. Many studies concluded on its effectiveness whereas others did not find any superiority of this method. However, most of those studies were not random and/or had no sufficient weight. OBJECTIVE: To assess the efficacy of intrathecal therapy with ATS in neonates and adults. METHODS: Meta-analysis: Clinical trials were identified by searching Medline, the Cochrane library and Current Contents. Published randomized studies in English or French comparing intrathecal therapy and intramuscular therapy (IMS) were analysed with Revman, R, and Stata software. Treatment effects were evaluated by relative risk (RR) between intrathecal vs. intramuscular administration. RESULTS: A total of 942 patients were included in 12 trials, 484 in the intrathecal group and 458 in the intramuscular one. The combined RR of mortality for intrathecal vs. IMS was 0.71 (95% CI, 0.62-0.81). The superiority of intrathecal therapy also emerged when the analysis was performed in subcategories of both adults and neonates and for high and low dose of intrathecal serotherapy. Intrathecal administration of ATS or TIG is more beneficial than intramuscular administration in the treatment of tetanus.

Intestinal bacterial community and growth performance of chickens fed diets containing antibiotics.

This study was conducted to relate the performance of broiler chickens fed diets containing growth-promoting antibiotics to changes in the intestinal microbiota. The technique of denaturing gradient gel electrophoresis (DGGE) of amplicons of the region V3 of 16S rDNA was used to characterize the microbiota. Two experiments were conducted, one with broilers raised in battery cages and the other with broilers raised in floor pens. Antibiotics improved the performance of the chickens raised in floor pens only. Avilamycin, bacitracin methylene disalicylate, and enramycin induced changes in the composition of the intestinal bacterial community of the birds in both experiments. The number of bacterial genotypes found in the intestinal tract of chickens was not reduced by the antibiotics supplemented in either environment. However, the changes in the composition of the intestinal bacterial community induced by antibiotics may be related to improvement in growth performance. This was indicated by the suppression of 6 amplicons and the presence of 4 amplicons exclusive to the treatment that had the best performance in the floor pen experiment.