OC 8718 WHAT DID WE LEARN FROM PANACEA 1 CLINICAL TRIALS?

BackgroundThe Pan African Consortium for the Evaluation of Anti-Tuberculosis Antibiotics (PanACEA) was designed to build clinical tuberculosis (TB) trial capacity whilst conducting clinical trials on novel and existing agents to shorten and simplify TB treatment. One of the objectives was to conduct, mentor and monitor observational and clinical studies at sites in 6 Sub-Saharan TB-endemic countries (Gabon, Kenya, South Africa, Tanzania, Uganda and Zambia)MethodsLearning through experience. All centres in the 6 countries self-assessed their requirements for capacity development in the following fields: a) clinical staff availability and experience; b) TB laboratory infrastructure and staff; c) safety laboratory infrastructure and staff; d) clinical site facilities and equipment; e) pharmacy facilities and staff; IT facilities; and f) overall training needs of site personnel.ResultsFrom March 2011 – June 2014, we conducted four epidemiological studies (characterising TB patient populations in preparation for future studies) and five phase II studies (GCP standard intervention trials).By working together in epidemiological and clinical trials, the sites identified their needs for resources and training as well as developing capabilities to perform independent large-scale TB clinical trials beyond PanACEA-initiated trials. Through the ReMoxTB study, for example, laboratories were brought to an international standard for safety and mycobacterial expertise. Furthermore, through developing skill-sets related to EBA studies, sites have since then attracted other sponsors for further studies.Sites could be mentored to perform GCP-compliant clinical TB trials that is built on sound physical infrastructure, training and strong on-site leadership.ConclusionThe learning-by-doing approach meant that staff could be trained whilst acquiring new core competencies and revealing operational gaps. Our experience of conducting TB trials within an environment of mentoring, networking and training has provided a platform for establishing future sustainable research centres that has capacities to conduct highly regulated studies.

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Cancer Clinical Trials in Africa—An Untapped Opportunity: Recommendations From AORTIC 2019 Conference Special Interest Group in Clinical Trials

JCO Global Oncology ◽

10.1200/go.21.00096 ◽

2021 ◽

pp. 1358-1363

Author(s):

Abiola Ibraheem ◽

Colin Pillai ◽

Ifeoma Okoye ◽

J. Joshua Smith ◽

Diane Reidy-Lagunes ◽

...

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Sub Saharan Africa ◽

Cancer Clinical Trials ◽

Future Directions ◽

Secondary Purpose ◽

Health Care Burden ◽

Sub Saharan ◽

Cancer Disparity ◽

And Training

Cancer is now a formidable health care burden in sub-Saharan Africa (SSA) due to lifestyle westernization and longer life expectancy. The exponential increase in cancer incidence coupled with high mortality rate is not comparable with that seen in westernized countries. To address global cancer disparity, globalization of cancer clinical trials to involve sub-Saharan Africa can serve as a platform where innovative targeted therapies can be made available to patients in the environ. In the 2019 African Organization for Research and Training in Cancer (AORTIC) conference held at Maputo, Mozambique, a group of clinical trialists spanning across multiple continents highlighted the opportunities in Africa for the conduct of cancer clinical trials. The secondary purpose of the meeting was to address the belief that Africa was incapable of conducting interventional cancer trials but showed the in-continent strengths, such as available capacities, trained local clinical trialists with clinical trial experiences, clinical trial consortia, local capabilities, mapping out logistics, ethical consideration, political will, real-time benefits of clinical trials to clinical practice, and future directions for trials.

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Omega-3 Polyunsaturated Fatty Acids and Stroke Burden

International Journal of Molecular Sciences ◽

10.3390/ijms20225549 ◽

2019 ◽

Vol 20 (22) ◽

pp. 5549

Author(s):

Yuji Ueno ◽

Nobukazu Miyamoto ◽

Kazuo Yamashiro ◽

Ryota Tanaka ◽

Nobutaka Hattori

Keyword(s):

Fatty Acids ◽

Clinical Trials ◽

Polyunsaturated Fatty Acids ◽

Large Scale ◽

Molecular Mechanisms ◽

Experimental Studies ◽

Epidemiological Studies ◽

Dietary Intakes ◽

Neuroprotective Effects ◽

Incidence And Mortality

Stroke is a major leading cause of death and disability worldwide. N-3 polyunsaturated fatty acids (PUFAs) including eicosapentaenoic acid and docosahexaenoic acid have potent anti-inflammatory effects, reduce platelet aggregation, and regress atherosclerotic plaques. Since the discovery that the Greenland Eskimo population, whose diet is high in marine n-3 PUFAs, have a lower incidence of coronary heart disease than Western populations, numerous epidemiological studies to explore the associations of dietary intakes of fish and n-3 PUFAs with cardiovascular diseases, and large-scale clinical trials to identify the benefits of treatment with n-3 PUFAs have been conducted. In most of these studies the incidence and mortality of stroke were also evaluated mainly as secondary endpoints. Thus, a systematic literature review regarding the association of dietary intake of n-3 PUFAs with stroke in the epidemiological studies and the treatment effects of n-3 PUFAs in the clinical trials was conducted. Moreover, recent experimental studies were also reviewed to explore the molecular mechanisms of the neuroprotective effects of n-3 PUFAs after stroke.

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Current Status of the Sm14/GLA-SE Schistosomiasis Vaccine: Overcoming Barriers and Paradigms towards the First Anti-Parasitic Human(itarian) Vaccine

10.20944/preprints201810.0334.v1 ◽

2018 ◽

Author(s):

Miriam Tendler ◽

Marilia S. Almeida ◽

Monica M. Vilar ◽

Patricia M. Pinto ◽

Gabriel Limaverde-Sousa

Keyword(s):

Clinical Trials ◽

Phase Ii ◽

Large Scale ◽

Lipid A ◽

Social Inequalities ◽

Parasitic Infection ◽

Current Status ◽

Control Approach ◽

Phase Ii Studies ◽

The Impact

Schistosomiasis, a disease historically associated with poverty, lack of sanitation and social inequalities, is a chronic, debilitating parasitic infection, affecting hundreds of millions of people in endemic countries. Although schistosomiasis control approach has shown that chemotherapy is capable of reducing morbidity in humans, rapid re-infection is a reminder that the impact of drug treatment on transmission control or elimination initiatives is marginal. In addition, and regardless of more than two decades of well-executed control activities based on large-scale chemotherapy, the disease is expanding in many areas including Brazil. The development of the Sm14/GLA-SE schistosomiasis vaccine is an emblematic open knowledge innovation that has successfully completed Phase I and Phase IIa clinical trials, with Phase II/III trials underway in the African continent and to be followed in Brazil. Discovery and experimental phases were long term achievements leading to a robust collection of data that are strongly supporting the presently ongoing Clinical Phase. This paper reviews the development of the Sm14 vaccine formulated with GLA-SE (Glucopyranosyl Lipid A), from the earlier experimental developments to clinical trials including the recent status of Phase II studies.

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Current Status of the Sm14/GLA-SE Schistosomiasis Vaccine: Overcoming Barriers and Paradigms towards the First Anti-Parasitic Human(itarian) Vaccine

Tropical Medicine and Infectious Disease ◽

10.3390/tropicalmed3040121 ◽

2018 ◽

Vol 3 (4) ◽

pp. 121 ◽

Cited By ~ 9

Author(s):

Miriam Tendler ◽

Marília Almeida ◽

Monica Vilar ◽

Patrícia Pinto ◽

Gabriel Limaverde-Sousa

Keyword(s):

Clinical Trials ◽

Phase Ii ◽

Large Scale ◽

Lipid A ◽

Parasitic Infection ◽

Current Status ◽

Clinical Phase ◽

Knowledge Innovation ◽

Phase Ii Studies ◽

The Impact

Schistosomiasis, a disease historically associated with poverty, lack of sanitation and social inequality, is a chronic, debilitating parasitic infection, affecting hundreds of millions of people in endemic countries. Although chemotherapy is capable of reducing morbidity in humans, rapid re-infection demonstrates that the impact of drug treatment on transmission control or disease elimination is marginal. In addition, despite more than two decades of well-executed control activities based on large-scale chemotherapy, the disease is expanding in many areas including Brazil. The development of the Sm14/GLA-SE schistosomiasis vaccine is an emblematic, open knowledge innovation that has successfully completed phase I and phase IIa clinical trials, with Phase II/III trials underway in the African continent, to be followed by further trials in Brazil. The discovery and experimental phases of the development of this vaccine gathered a robust collection of data that strongly supports the ongoing clinical phase. This paper reviews the development of the Sm14 vaccine, formulated with glucopyranosyl lipid A (GLA-SE), from the initial experimental developments to clinical trials including the current status of phase II studies.

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Ongoing randomized clinical trials for the treatment of thrombosis in the antiphospholipid syndrome

Hämostaseologie ◽

10.1055/s-0037-1619507 ◽

2001 ◽

Vol 21 (02) ◽

pp. 77-81 ◽

Cited By ~ 2

Author(s):

G. Finazzi

Keyword(s):

Clinical Trials ◽

Large Scale ◽

Low Dose ◽

Randomized Clinical Trials ◽

Oral Anticoagulants ◽

Collaborative Study ◽

Clinical Problem ◽

Vascular Events ◽

Dose Oral ◽

Adverse Pregnancy

SummaryThrombotic events are a major clinical problem for patients with antiphospholipid antibodies (APA). However, current recommendations for their prevention and treatment are still based on retrospective studies. Data from large scale, prospective clinical trials are required to ultimately identify the optimal management of these patients. To date, at least four randomized studies are underway. The WAPS and PAPRE clinical trials are aimed to establish the correct duration and intensity of oral anticoagulation in APA patients with major arterial or venous thrombosis. The WARSS-APASS is a collaborative study to evaluate the efficacy and safety of aspirin or low-dose oral anticoagulants in preventing the recurrence of ischemic stroke. The recently announced UK Trial compares low-dose aspirin with or without low-intensity anticoagulation for the primary prevention of vascular events in APA-positive patients with SLE or adverse pregnancy history, but still thrombosis-free. It is hoped that the results of these trials will be available soon since clinicians urgently need more powerful data to treat their patients with the APA syndrome.

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Uric Acid and Hypertension: Prognostic Role and Guide for Treatment

Journal of Clinical Medicine ◽

10.3390/jcm10030448 ◽

2021 ◽

Vol 10 (3) ◽

pp. 448

Author(s):

Federica Piani ◽

Arrigo F. G. Cicero ◽

Claudio Borghi

Keyword(s):

Clinical Trials ◽

Uric Acid ◽

Mendelian Randomization ◽

Strong Association ◽

Epidemiological Studies ◽

Hypertensive Disease ◽

Genetic Studies ◽

Lowering Therapy ◽

The Relationship

The relationship between serum uric acid (SUA) and hypertension has been a subject of increasing interest since the 1870 discovery by Frederick Akbar Mahomed. Several epidemiological studies have shown a strong association between high SUA levels and the presence or the development of hypertension. Genetic analyses have found that xanthine oxidoreductase (XOR) genetic polymorphisms are associated with hypertension. However, genetic studies on urate transporters and Mendelian randomization studies failed to demonstrate a causal relationship between SUA and hypertension. Results from clinical trials on the role of urate-lowering therapy in the management of patients with hypertension are not uniform. Our study sought to analyze the prognostic and therapeutic role of SUA in the hypertensive disease, from uric acid (UA) biology to clinical trials on urate-lowering therapies.

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Lack of an association between gallstone disease and bilirubin levels with risk of colorectal cancer: a Mendelian randomisation analysis

British Journal of Cancer ◽

10.1038/s41416-020-01211-x ◽

2021 ◽

Author(s):

Richard Culliford ◽

Alex J. Cornish ◽

Philip J. Law ◽

Susan M. Farrington ◽

Kimmo Palin ◽

...

Keyword(s):

Colorectal Cancer ◽

Large Scale ◽

Causal Effect ◽

Gallstone Disease ◽

Epidemiological Studies ◽

Mendelian Randomisation ◽

Linear Relationships ◽

Potential Risk Factors ◽

The Relationship ◽

Circulating Levels

Abstract Background Epidemiological studies of the relationship between gallstone disease and circulating levels of bilirubin with risk of developing colorectal cancer (CRC) have been inconsistent. To address possible confounding and reverse causation, we examine the relationship between these potential risk factors and CRC using Mendelian randomisation (MR). Methods We used two-sample MR to examine the relationship between genetic liability to gallstone disease and circulating levels of bilirubin with CRC in 26,397 patients and 41,481 controls. We calculated the odds ratio per genetically predicted SD unit increase in log bilirubin levels (ORSD) for CRC and tested for a non-zero causal effect of gallstones on CRC. Sensitivity analysis was applied to identify violations of estimator assumptions. Results No association between either gallstone disease (P value = 0.60) or circulating levels of bilirubin (ORSD = 1.00, 95% confidence interval (CI) = 0.96–1.03, P value = 0.90) with CRC was shown. Conclusions Despite the large scale of this study, we found no evidence for a causal relationship between either circulating levels of bilirubin or gallstone disease with risk of developing CRC. While the magnitude of effect suggested by some observational studies can confidently be excluded, we cannot exclude the possibility of smaller effect sizes and non-linear relationships.

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Multimorbidity clusters in patients with chronic obstructive airway diseases in the EpiChron Cohort

Scientific Reports ◽

10.1038/s41598-021-83964-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jonás Carmona-Pírez ◽

Beatriz Poblador-Plou ◽

Ignatios Ioakeim-Skoufa ◽

Francisca González-Rubio ◽

Luis Andrés Gimeno-Feliú ◽

...

Keyword(s):

Substance Use ◽

Chronic Conditions ◽

Large Scale ◽

Mental Health Problems ◽

Epidemiological Studies ◽

Chronic Obstructive ◽

High Morbidity ◽

Airway Diseases ◽

Obstructive Sleep ◽

Obstructive Airway Diseases

AbstractChronic obstructive airway diseases such as chronic obstructive pulmonary disease (COPD), asthma, rhinitis, and obstructive sleep apnea (OSA) are amongst the most common treatable and preventable chronic conditions with high morbidity burden and mortality risk. We aimed to explore the existence of multimorbidity clusters in patients with such diseases and to estimate their prevalence and impact on mortality. We conducted an observational retrospective study in the EpiChron Cohort (Aragon, Spain), selecting all patients with a diagnosis of allergic rhinitis, asthma, COPD, and/or OSA. The study population was stratified by age (i.e., 15–44, 45–64, and ≥ 65 years) and gender. We performed cluster analysis, including all chronic conditions recorded in primary care electronic health records and hospital discharge reports. More than 75% of the patients had multimorbidity (co-existence of two or more chronic conditions). We identified associations of dermatologic diseases with musculoskeletal disorders and anxiety, cardiometabolic diseases with mental health problems, and substance use disorders with neurologic diseases and neoplasms, amongst others. The number and complexity of the multimorbidity clusters increased with age in both genders. The cluster with the highest likelihood of mortality was identified in men aged 45 to 64 years and included associations between substance use disorder, neurologic conditions, and cancer. Large-scale epidemiological studies like ours could be useful when planning healthcare interventions targeting patients with chronic obstructive airway diseases and multimorbidity.

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Precision Agriculture for Resource Use Efficiency in Smallholder Farming Systems in Sub-Saharan Africa: A Systematic Review

Sustainability ◽

10.3390/su13031158 ◽

2021 ◽

Vol 13 (3) ◽

pp. 1158

Author(s):

Cecilia M. Onyango ◽

Justine M. Nyaga ◽

Johanna Wetterlind ◽

Mats Söderström ◽

Kristin Piikki

Keyword(s):

Resource Use ◽

Precision Agriculture ◽

Large Scale ◽

English Language ◽

Management Practices ◽

Smallholder Farmers ◽

Management Strategies ◽

Sub Saharan Africa ◽

Smallholder Farming ◽

Sub Saharan

Opportunities exist for adoption of precision agriculture technologies in all parts of the world. The form of precision agriculture may vary from region to region depending on technologies available, knowledge levels and mindsets. The current review examined research articles in the English language on precision agriculture practices for increased productivity among smallholder farmers in Sub-Saharan Africa. A total of 7715 articles were retrieved and after screening 128 were reviewed. The results indicate that a number of precision agriculture technologies have been tested under SSA conditions and show promising results. The most promising precision agriculture technologies identified were the use of soil and plant sensors for nutrient and water management, as well as use of satellite imagery, GIS and crop-soil simulation models for site-specific management. These technologies have been shown to be crucial in attainment of appropriate management strategies in terms of efficiency and effectiveness of resource use in SSA. These technologies are important in supporting sustainable agricultural development. Most of these technologies are, however, at the experimental stage, with only South Africa having applied them mainly in large-scale commercial farms. It is concluded that increased precision in input and management practices among SSA smallholder farmers can significantly improve productivity even without extra use of inputs.

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Manual on the proper use of sodium astatide ([211At]NaAt) injections in clinical trials for targeted alpha therapy (1st edition)

Annals of Nuclear Medicine ◽

10.1007/s12149-021-01619-2 ◽

2021 ◽

Author(s):

Tadashi Watabe ◽

Makoto Hosono ◽

Seigo Kinuya ◽

Takahiro Yamada ◽

Sachiko Yanagida ◽

...

Keyword(s):

Clinical Trials ◽

Japanese Society ◽

Radiation Safety ◽

Safety Management ◽

Evaluation Methodology ◽

Targeted Alpha Therapy ◽

Safety Issues ◽

Safety Standards ◽

And Training ◽

Alpha Therapy

AbstractWe present the guideline for use of [211At] sodium astatide (NaAt) for targeted alpha therapy in clinical trials on the basis of radiation safety issues in Japan. This guideline was prepared by a study supported by the Ministry of Health, Labour, and Welfare, and approved by the Japanese Society of Nuclear Medicine on 8th Feb, 2021. The study showed that patients receiving [211At]NaAt do not need to be admitted to a radiotherapy room and outpatient treatment is possible. The radiation exposure from the patient is within the safety standards of the ICRP and IAEA recommendations for the general public and caregivers. Precautions for patients and their families, safety management associated with the use of [211At]NaAt, education and training, and disposal of medical radioactive contaminants are also included in this guideline. Treatment using [211At]NaAt in Japan should be carried out according to this guideline. Although this guideline is applied in Japan, the issues for radiation protection and evaluation methodology shown here are considered internationally useful as well.

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