How do tsetse recognise their hosts? The role of shape in the responses of tsetse (Glossina fuscipes and G. palpalis) to artificial hosts

Palpalis-group tsetse, particularly the subspecies of Glossina palpalis and G. fuscipes, are the most important transmitters of human African trypanomiasis (HAT), transmitting .95% of cases. Traps and insecticide-treated targets are used to control tsetse but more cost-effective baits might be developed through a better understanding of the fly’s host-seeking behaviour.Electrocuting grids were used to assess the numbers of G. palpalis palpalis and G. fuscipes quanzensis attracted to and landing on square or oblong targets of black cloth varying in size from 0.01 m2 to 1.0 m2. For both species, increasing the size of a square target from 0.01 m2 (dimensions = 0.1 x 0.1 m) to 1.0 m2 (1.0 x 1.0 m) increased the catch ,4x however the numbers of tsetse killed per unit area of target declined with target size suggesting that the most cost efficient targets are not the largest. For G. f. quanzensis, horizontal oblongs, (1 m wide x 0.5 m high) caught, 1.8x more tsetse than vertical ones (0.5 m wide x 1.0 m high) but the opposite applied for G. p. palpalis. Shape preference was consistent over the range of target sizes. For G. p. palpalis square targets caught as many tsetse as the oblong; while the evidence is less strong the same appears to apply to G. f. quanzensis. The results suggest that targets used to control G. p. palpalis and G. f. quanzensis should be square, and that the most cost-effective designs, as judged by the numbers of tsetse caught per area of target, are likely to be in the region of 0.25 x 0.25 m2. The preference of G. p. palpalis for vertical oblongs is unique amongst tsetse species, and it is suggested that this response might be related to its anthropophagic behaviour and hence importance as a vector of HAT

Evolution number of litigation cases and expenditure with monoclonal antibodies (MoAbs) (Bevacizumab, Cetuximab and Panitumumab) and tirosine kinase inhibitor (Regorafenib) for the treatment of cancer in Minas Gerais-Brazil : A preliminary analysis from 2009 to 2016

Introduction: The last decade was marked by the widespread use of molecular biological agents in combination with 5-FU / oxaliplatin or irinotecan-containing regimens in the treatment of cancer. Such biological medicines have significantly increased the costs of oncological treatment, leading to concerns about the future sustainability of drug policy and, as a consequence, health systems with universal access to health care. In the case of Brazil, the tree MoAbs BEVACIZUMAB(BEVA), CETUXIMAB(CETUX), PANITUMUMAB(PANIT) and one tirosin kinase inhibitor REGORAFENIB(REGORA) compared in this study can only be used by the patient when there is a litigation against the State, since they are not incorporated into the Single System of Health-SUS. Objectives: To evaluate the evolution number of litigation cases and expenditure with monoclonal antibodies(MoAbs) (Bevacizumab, Cetuximab and Panitumumab) and tirosin kinase inhibitor (Regorafenib) for the treatment of cancer in Minas Gerais-Brazil. Method: Retrospective descriptive study whose judicial information was extracted from the database of the Minas Gerais State Secretariat - SES-MG. The judicial actions were filed against the State of Minas Gerais for Cancer treatment and refer to the period from January 2009 to December 2016. The study was cut from the judicialized MoAbs (BEVA, CETUX, PANIT) and tirosin kinase inhibitor (REGORA) for the treatment of Colorectal Cancer (CCR). The cost of the treatments was calculated based on the prices of the Câmara de Regulação do Mercado de Medicamentos (CMED) ANVISA, taking into account the official dollar exchange rate of the Central Bank on January 31, 2018 and there is no adjustment for inflation. Results and discussion: Preliminary results showed that in the period between 2009 and 2016, 1024 lawsuits were filed against the State of Minas Gerais for cancer treatment, making 766 for BEVA, 206 for CETUX, 35 for PANIT and 17 for REGORA . The total cost obtained considering a 6-month overall survival for each patient was $ 22,260,536. In Brazil, the growing number of litigation and drug costs (BEVA, CETUX, PANIT and REGORA) per year is worrying, considering the increase of 5.100% for judicial actions and 1899% for treatment costs in the period 2009 to 2016 (TABLE 1). Conclusion: The exponential increase in lawsuits against the State of Minas Gerais demonstrates the growing pressure on the resources available to attend a reduced number of patients, who are available to judicialize treatments outside universal health coverage, which is already guaranteed right by the Brazilian constitution

The Maastricht Ultrasound Shoulder pain trial (MUST): Ultrasound imaging as a diagnostic triage tool to improve management of patients with non-chronic shoulder pain in primary care

<p>Abstract</p> <p>Background</p> <p>Subacromial disorders are considered to be one of the most common pathologies affecting the shoulder. Optimal therapy for shoulder pain (SP) in primary care is yet unknown, since clinical history and physical examination do not provide decisive evidence as to the patho-anatomical origin of the symptoms. Optimal decision strategies can be furthered by applying ultrasound imaging (US), an accurate method in diagnosing SP, demonstrating a clear relationship between diagnosis and available therapies. Yet, the clinical cost-effectiveness of applying US in the management of SP in primary care has not been studied. The aim of this paper is to describe the design and methods of a trial assessing the cost-effectiveness of ultrasound imaging as a diagnostic triage tool to improve management of primary care patients with non-chronic shoulder pain.</p> <p>Methods/Design</p> <p>This randomised controlled trial (RCT) will involve 226 adult patients with suspected subacromial disorders recruited by general practitioners. During a Qualification period of two weeks, patients receive care as usual as advised by the Dutch College of General Practitioners, and patients are referred for US. Patients with insufficient improvement qualify for the RCT. These patients are then randomly assigned to the intervention or the control group. The therapies used in both groups are the same (corticosteroid injections, referral to a physiotherapist or orthopedic surgeon) except that therapies used in the intervention group will be tailored based on the US results. Ultrasound diagnosed disorders include tendinopathy, calcific tendinitis, partial and full thickness tears, and subacromial bursitis. The primary outcome is patient-perceived recovery at 52 weeks, using the Global Perceived Effect questionnaire. Secondary outcomes are disease specific and generic quality of life, cost-effectiveness, and the adherence to the initial applied treatment. Outcome measures will be assessed at baseline, 13, 26, 39 and 52 weeks after inclusion. An economic evaluation will be performed from both a health care and societal perspective with a time horizon of 52 weeks.</p> <p>Discussion</p> <p>The results of this trial will give unique evidence regarding the cost-effectiveness of US as a diagnostic triage tool in the management of SP in primary care.</p

Impact of district mental health care plans on symptom severity and functioning of patients with priority mental health conditions: the Programme for Improving Mental Health Care (PRIME) cohort protocol

Background: The Programme for Improving Mental Health Care (PRIME) sought to implement mental health care plans (MHCP) for four priority mental disorders (depression, alcohol use disorder, psychosis and epilepsy) into routine primary care in five low- and middle-income country districts. The impact of the MHCPs on disability was evaluated through establishment of priority disorder treatment cohorts. This paper describes the methodology of these PRIME cohorts. Methods: One cohort for each disorder was recruited across some or all five districts: Sodo (Ethiopia), Sehore (India) , Chitwan (Nepal), Dr. Kenneth Kaunda (South Africa) and Kamuli (Uganda), comprising 17 treatment cohorts in total (N = 2182). Participants were adults residing in the districts who were eligible to receive mental health treatment according to primary health care staff, trained by PRIME facilitators as per the district MHCP. Patients who screened positive for depression or AUD and who were not given a diagnosis by their clinicians (N = 709) were also recruited into comparison cohorts in Ethiopia, India, Nepal and South Africa. Caregivers of patients with epilepsy or psychosis were also recruited (N = 953), together with or on behalf of the person with a mental disorder, depending on the district. The target sample size was 200 (depression and AUD), or 150 (psychosis and epilepsy) patients initiating treatment in each recruiting district. Data collection activities were conducted by PRIME research teams. Participants completed follow-up assessments after 3 months (AUD and depression) or 6 months (psychosis and epilepsy), and after 12 months. Primary outcomes were impaired functioning, using the 12-item World Health Organization Disability Assessment Schedule 2.0 (WHODAS), and symptom severity, assessed using the Patient Health Questionnaire (depression), the Alcohol Use Disorder Identification Test (AUD), and number of seizures (epilepsy). Discussion: Cohort recruitment was a function of the clinical detection rate by primary health care staff, and did not meet all planned targets. The cross-country methodology reflected the pragmatic nature of the PRIME cohorts: while the heterogeneity in methods of recruitment was a consequence of differences in health systems and MHCPs, the use of the WHODAS as primary outcome measure will allow for comparison of functioning recovery across sites and disorders

Development of the autoinflammatory disease damage index (ADDI)

OBJECTIVES: Autoinflammatory diseases cause systemic inflammation that can result in damage to multiple organs. A validated instrument is essential to quantify damage in individual patients and to compare disease outcomes in clinical studies. Currently, there is no such tool. Our objective was to develop a common autoinflammatory disease damage index (ADDI) for familial Mediterranean fever, cryopyrin-associated periodic syndromes, tumour necrosis factor receptor-associated periodic fever syndrome and mevalonate kinase deficiency. METHODS: We developed the ADDI by consensus building. The top 40 enrollers of patients in the Eurofever Registry and 9 experts from the Americas participated in multiple rounds of online surveys to select items and definitions. Further, 22 (parents of) patients rated damage items and suggested new items. A consensus meeting was held to refine the items and definitions, which were then formally weighted in a scoring system derived using decision-making software, known as 1000minds. RESULTS: More than 80% of the experts and patients completed the online surveys. The preliminary ADDI contains 18 items, categorised in the following eight organ systems: reproductive, renal/amyloidosis, developmental, serosal, neurological, ears, ocular and musculoskeletal damage. The categories renal/amyloidosis and neurological damage were assigned the highest number of points, serosal damage the lowest number of points. The involvement of (parents of) patients resulted in the inclusion of, for example, chronic musculoskeletal pain. CONCLUSIONS: An instrument to measure damage caused by autoinflammatory diseases is developed based on consensus building. Patients fulfilled a significant role in this process

RNAi screening identifies Trypanosoma brucei stress response protein kinases required for survival in the mouse

Protein kinases (PKs) are a class of druggable targets in Trypanosoma brucei, the causative agent of Human African Trypanosomiasis (sleeping sickness), yet little is known about which PKs are essential for survival in mammals. A recent kinome-wide RNAi screen with 176 individual bloodstream form Trypanosoma brucei lines identified PKs required for proliferation in culture. In order to assess which PKs are also potential virulence factors essential in vivo, lines were pooled, inoculated into mice, and screened for loss of fitness after 48 h RNAi. The presence of trypanosomes in the bloodstream was assessed using RNAi target sequencing (RITseq) and compared to growth in culture. We identified 49 PKs with a significant loss of fitness in vivo in two independent experiments, and a strong correlation between in vitro and in vivo loss of fitness for the majority. Nine PKs had a more pronounced growth defect in vivo, than in vitro. Amongst these PKs were several with putative functions related to stress responses mediated through the PI3K/TOR or MAPK signaling cascades, which act to protect the parasite from complement-mediated and osmotic lysis. Identification of these virulence-associated PKs provides new insights into T. brucei-host interaction and reveals novel potential protein kinase drug targets