‘Who is Helsinki?’ Sex workers advise improving communication for good participatory practice in clinical trials

After premature closures in 2004 of biomedical human immunodeficiency virus (HIV) prevention trials involving sex workers in Africa and Asia, the Joint United Nations Programme on HIV/AIDS (UNAIDS) and Global Advocacy for HIV Prevention (AVAC) undertook consultations to establish better participatory guidelines for such trials in order to address ethical concerns. This study investigated sex workers’ knowledge and beliefs about research ethics and good participatory practices (GPP) and the perspectives of sex workers on research participation. A 33-question survey based on criteria identified by UNAIDS and AVAC was translated into three other languages. Participants were recruited through mailing lists and contacts with existing sex work networks. In total, 74 responses from Europe, the Americas and Asia were received. Thirty percent of respondents reported first-hand involvement in biomedical HIV prevention trials. Seventy percent indicated a lack of familiarity with codes of ethics for research. This paper focuses exclusively on communication issues described in survey responses. Communication was an important theme: the absence of clear communication between trial participants and investigators contributed to premature trial closures in at least two sites. Sex workers had recommendations for how researchers might implement GPP through improved communication, including consultation at the outset of planning, explaining procedures in non-technical terms and establishing clear channels for feedback from participants

Pituitary insufficiency after operation of supratentorial intra- and extraaxial tumors outside of the sellar–parasellar region?

Recent studies investigating pituitary function after non-sellar brain tumor surgery showed that up to 38.2% of patients have pituitary insufficiency (PI). It has been assumed that the operation causes the PI, but preoperative hormone testing, which would have been necessary to prove this assumption, was not performed. The objective of this study is to answer the question if indeed microsurgery is the culprit of PI in patients with operatively treated non-sellar brain tumors. In this prospective trial, 54 patients with supratentorial non-sellar tumors were included. The basal levels of cortisol, prolactin, testosterone, estrogen, IGF-1, fT3, fT4, STH, TSH, ACTH, FSH, and LH were recorded preoperatively on days 1 and 7 after surgery. If basal hormone screening revealed an abnormality, a releasing hormone assay was performed. Before surgery, 24 of the 54 patients (44.4%) already had PI. Additional 25 patients showed either hypocortisolism or hypothyreoidism. As those patients had been pre-treated with dexamethasone and l-thyroxine, these findings were considered not to represent PI but drug effects. Hormone testing on days 1 and 7 after surgery revealed no changes. With 44.4% PI is a frequent finding in brain tumor patients already before surgery. The factors causing preoperative PI remain yet to be identified. The endocrine results after surgery are unchanged which rules out that surgery is the cause of PI

The whole is greater than the sum of the parts: Recognising missed opportunities for an optimal response to the rapidly maturing TB-HIV co-epidemic in South Africa

<p>Abstract</p> <p>Background</p> <p>Despite widely acknowledged WHO guidelines for the integration of TB and HIV services, heavily burdened countries have been slow to implement these and thus significant missed opportunities have arisen.</p> <p>Discussion</p> <p>The individual-centred, rights-based paradigm of the SA National AIDS Policy, remains dissonant with the compelling public-health approach of TB control. The existence of independent and disconnected TB and HIV services results in a wastage of scarce health resources, an increased burden on patients' time and finances, and ignores evidence of patients' preference for an integrated service. The current situation translates into a web of unacceptable, ongoing missed opportunities such as failure to maximize collaborative disease surveillance, VCT, adherence support, infection control, and positive prevention. TB services present a readily identifiable cohort for HIV provider-initiated testing. Integrating HAART and DOTS will promote efficient usage of health workers' time and a more navigable experience for patients, ultimately ensuring increased TB treatment completion rates and MDR-TB prevention. As direct observation evolves into a more supportive, empowering experience for patients, adherence to both TB drugs and HAART will be bolstered. Little attention has been paid to the transmission of TB within HIV services. Low cost infection control interventions include: triaging patients, scheduling new and follow-up patients separately; well-ventilated, sheltered waiting rooms; and the use of personal respirators by patients and staff. A more patient-centred approach to TB care may be able to recruit the active participation of TB patients in positive prevention efforts, including maximizing personal infection control, limiting exposure of social contacts to TB during the intensive phase of treatment, advocating isoniazid prophylaxis within the home and patient-centred education efforts to reduce overall transmission. Several model programmes demonstrated synergy, in which the impact of the "whole" or integrated response was greater than the sum of the non-integrated parts.</p> <p>Summary</p> <p>The full potential of an integrated TB-HIV service has not been fully harvested. Missed opportunities discount existing efforts in both programmes, will perpetuate the burden of disease, and prevent major gains in future interventions. This paper outlines simple, readily-implementable strategies to narrow the gap and reclaim existing missed opportunities.</p

Rapid ethical assessment on informed consent content and procedure in Hintalo-Wajirat, Northern Ethiopia: a qualitative study

Background Informed consent is a key component of bio-medical research involving human participants. However, obtaining informed consent is challenging in low literacy and resource limited settings. Rapid Ethical Assessment (REA) can be used to contextualize and simplify consent information within a given study community. The current study aimed to explore the effects of social, cultural, and religious factors during informed consent process on a proposed HPV-serotype prevalence study. Methodology A qualitative community-based REA was conducted in Adigudom and Mynebri Kebeles, Northern Ethiopia, from July to August 2013. Data were collected by a multi-disciplinary team using open ended questions concerning informed consent components in relation to the parent study. The team conducted one-to-one In-Depth Interviews (IDI) and Focus Group Discussions (FGDs) with key informants and community members to collect data based on the themes of the study. Tape recorded data were transcribed in Tigrigna and then translated into English. Data were categorized and thematically analyzed using open coding and content analysis based on pre-defined themes. Results The REA study revealed a number of socio-cultural issues relevant to the proposed study. Low community awareness about health research, participant rights and cervical cancer were documented. Giving a vaginal sample for testing was considered to be highly embarrassing, whereas giving a blood sample made participants worry that they might be given a result without the possibility of treatment. Verbal consent was preferred to written consent for the proposed study. Conclusion This rapid ethical assessment disclosed important socio-cultural issues which might act as barriers to informed decision making. The findings were important for contextual modification of the Information Sheet, and to guide the best consent process for the proposed study. Both are likely to have enabled participants to understand the informed consent better and consequently to comply with the study

Accelerated Evolution of Mitochondrial but Not Nuclear Genomes of Hymenoptera: New Evidence from Crabronid Wasps

Mitochondrial genes in animals are especially useful as molecular markers for the reconstruction of phylogenies among closely related taxa, due to the generally high substitution rates. Several insect orders, notably Hymenoptera and Phthiraptera, show exceptionally high rates of mitochondrial molecular evolution, which has been attributed to the parasitic lifestyle of current or ancestral members of these taxa. Parasitism has been hypothesized to entail frequent population bottlenecks that increase rates of molecular evolution by reducing the efficiency of purifying selection. This effect should result in elevated substitution rates of both nuclear and mitochondrial genes, but to date no extensive comparative study has tested this hypothesis in insects. Here we report the mitochondrial genome of a crabronid wasp, the European beewolf (Philanthus triangulum, Hymenoptera, Crabronidae), and we use it to compare evolutionary rates among the four largest holometabolous insect orders (Coleoptera, Diptera, Hymenoptera, Lepidoptera) based on phylogenies reconstructed with whole mitochondrial genomes as well as four single-copy nuclear genes (18S rRNA, arginine kinase, wingless, phosphoenolpyruvate carboxykinase). The mt-genome of P. triangulum is 16,029 bp in size with a mean A+T content of 83.6%, and it encodes the 37 genes typically found in arthropod mt genomes (13 protein-coding, 22 tRNA, and two rRNA genes). Five translocations of tRNA genes were discovered relative to the putative ancestral genome arrangement in insects, and the unusual start codon TTG was predicted for cox2. Phylogenetic analyses revealed significantly longer branches leading to the apocritan Hymenoptera as well as the Orussoidea, to a lesser extent the Cephoidea, and, possibly, the Tenthredinoidea than any of the other holometabolous insect orders for all mitochondrial but none of the four nuclear genes tested. Thus, our results suggest that the ancestral parasitic lifestyle of Apocrita is unlikely to be the major cause for the elevated substitution rates observed in hymenopteran mitochondrial genomes

A systematic review of the reporting of Data Monitoring Committees' roles, interim analysis and early termination in pediatric clinical trials

<p>Abstract</p> <p>Background</p> <p>Decisions about interim analysis and early stopping of clinical trials, as based on recommendations of Data Monitoring Committees (DMCs), have far reaching consequences for the scientific validity and clinical impact of a trial. Our aim was to evaluate the frequency and quality of the reporting on DMC composition and roles, interim analysis and early termination in pediatric trials.</p> <p>Methods</p> <p>We conducted a systematic review of randomized controlled clinical trials published from 2005 to 2007 in a sample of four general and four pediatric journals. We used full-text databases to identify trials which reported on DMCs, interim analysis or early termination, and included children or adolescents. Information was extracted on general trial characteristics, risk of bias, and a set of parameters regarding DMC composition and roles, interim analysis and early termination.</p> <p>Results</p> <p>110 of the 648 pediatric trials in this sample (17%) reported on DMC or interim analysis or early stopping, and were included; 68 from general and 42 from pediatric journals. The presence of DMCs was reported in 89 of the 110 included trials (81%); 62 papers, including 46 of the 89 that reported on DMCs (52%), also presented information about interim analysis. No paper adequately reported all DMC parameters, and nine (15%) reported all interim analysis details. Of 32 trials which terminated early, 22 (69%) did not report predefined stopping guidelines and 15 (47%) did not provide information on statistical monitoring methods.</p> <p>Conclusions</p> <p>Reporting on DMC composition and roles, on interim analysis results and on early termination of pediatric trials is incomplete and heterogeneous. We propose a minimal set of reporting parameters that will allow the reader to assess the validity of trial results.</p