Process and strategies for patient engagement and outreach in the Sickle Cell Disease (SCD) community to promote clinical trial participation.

INTRODUCTION: Sickle cell disease (SCD) is the most common inherited blood disorder in the United States. The Cure Sickle Cell Initiative (CureSCi) was created by the National Heart, Lung and Blood Institute (NHLBI) to improve the lives of people with SCD by accelerating the advancement of safe and promising genetic therapies, engaging the SCD community and healthcare providers, and encouraging collaboration among stakeholders. CureSCi is a collaborative, patient-focused research effort that includes patients at every level of the Initiative. Patient engagement is a key component, particularly during the development of clinical trials. OBJECTIVE: To describe the processes and strategies utilized by the CureSCi to engage individuals living with SCD about genetic therapy clinical trials. METHODS: The CureSCi Patient Engagement team conducted nine Community Outreach visits in 2019, each of which was structured to include separate group interviews with patients and medical providers. A set of guidance questions was developed for each audience and the interviews lasted approximately 60 minutes. RESULTS: Patients were asked about their participation in a clinical trial, and approximately 50% had participated in a trial. SCD individuals reported trusting their medical provider to provide them with information relevant to trials. Medical providers emphasized the individual, family, and health aspects of SCD that warrant additional investigation. Providers reported barriers encountered by patients as transportation, childcare support, infertility, and trust in the healthcare system. CONCLUSION: Lessons learned from the community have helped to influence recommendations for clinical trial design and key messaging development for the Cure Sickle Cell Initiative.

Analyzing the functional effects of dynamic and static splints after radial nerve injury.

The radial nerve is a commonly injured upper extremity peripheral nerve. The inability to extend the wrist results in a loss of hand function and dexterity that affects patients' ability to perform their activities of daily living. There is no strong evidence to support a particular splint design for improving dexterity. This cohort study compared whether a static or dynamic splint can improve hand dexterity when assessed with the 9-hole peg test (9-HPT) after radial nerve injury. Thirty-four subjects with radial nerve palsy participated in the study. The test was repeated three times for each subject, first without the splint, and then while wearing the control static wrist splint, and finally while wearing the dynamic splint. The 9-HPT was used as the outcome measure. The 9-HPT times were 36.4±4.8seconds without a wrist splint and improved when using the static and the dynamic splints to 33.5±4.5seconds (P<0.01) and 25.7±3.5seconds (P<0.01) respectively. The use of a dynamic splint after radial nerve palsy can provide the patient with greater manual dexterity when compared to using no splint or a static splint.

Linking ICF components to outcome measures for orthotic intervention for CMC OA: A systematic review.

STUDY DESIGN: Systematic review. INTRODUCTION/PURPOSE: The purpose of this study was to systematically review outcome measures used for assessment of orthotic intervention in the conservative management of thumb carpometacarpal osteoarthritis to determine if they characterize International Classification of Functioning, Disability, and Health (ICF) components. The determinants of patient satisfaction regarding the orthotic intervention were also extracted from the studies. METHODS: A comprehensive literature search was conducted. Outcome measures in the included studies were linked to the ICF. Determinants of patient satisfaction regarding the orthotic intervention were also extracted. RESULTS: Nine studies met inclusion criteria. Eight (47.1%) outcomes were linked to body structures and functions, 8 (47.1%) to activity limitations and participation restrictions, and 1 (5.9%) outcome fell into the nondefinable quality of life category. Four studies assessed patient satisfaction. DISCUSSION/CONCLUSIONS: This systematic review on orthotic intervention for thumb carpometacarpal osteoarthritis found opportunities related to assessment and outcome measures when present studies are linked to the ICF. LEVEL OF EVIDENCE: 2a.

Detection and subtyping of dengue 1-4 and yellow fever viruses by means of a multiplex RT-nested-PCR using degenerated primers.

OBJECTIVE: Differential diagnosis of infections that cause similar diseases and may be active simultaneously in the same geographical areas is greatly needed. Dengue and yellow fever viruses (DENV and YFV) are transmitted by the same species of mosquito and both can cause haemorrhagic fever symptoms. These viruses are active mainly in regions where expensive and sophisticated technologies are not available. Our objective was to develop a simple, reliable and easy-to-perform method to detect and identify these viruses. METHODS: We slightly modified a generic RT-PCR able to detect the mentioned viruses and other members of this genus: specific primers for each one of these viruses were designed and included in the nested reaction instead of one of the generic ones. The reaction was optimized and viruses are amplified giving rise to bands of different sizes distinguishable in agarose gels. RESULTS: This test is able to detect and identify the four DENVs and YFV to a high level of sensitivity and specificity and can be used with clinical samples. This simple, reliable and easy-to-perform method able to detect and identify dengue 1-4 and YFV can be used in poor endemic countries.

Generic RT-nested-PCR for detection of flaviviruses using degenerated primers and internal control followed by sequencing for specific identification.

Flaviviruses are a widespread and numerous group of arboviruses that can cause serious illness in humans. The continuous and slow spread of certain flaviviruses, such as Dengue viruses, and the recent entry and spread of West Nile virus to the American continent, point to the need to control these infections. This control requires the use of suitable techniques for diagnostic and surveillance programmes. A generic RT-nested-PCR that is, theoretically, able to detect each member of the group has been designed. The identification of the detected virus is carried out by sequencing. The introduction of an internal control would reduce the number of false negative results and could be used to quantify the viral load in clinical samples where the method works well.

The mechanism for lindane-induced inhibition of steroidogenesis in cultured rat Leydig cells.

The in vitro effect of the gamma-isomer of hexachlorocyclohexane, lindane, on rat Leydig cell steroidogenesis was studied. Leydig cells from mature male rats were incubated with human chorionic gonadotropin (hCG, 1 IU) for 3 h at 34 degrees C in the presence of different doses of lindane (2-200 microg/ml; 2-200 ppm). Results demonstrate that lindane produces a dose-dependent inhibition of testosterone production in hCG-stimulated Leydig cells. The decreased testosterone synthesis was accompanied with a half-reduced LH/hCG receptor number without any modification in the K(d) value. In addition, lindane also decreased cAMP production. These effects were not due to a detrimental action of lindane on cell viability. Results of this study demonstrate a direct inhibitory action of lindane on testicular steroidogenesis, at least in part, through a reduction in the classical second messenger production involved in this pathway.

Human Dengue antibodies against structural and nonstructural proteins.

Antibodies against dengue virus type 2 and 4 proteins in acute-phase sera of 10 primary and 10 secondary dengue fever and dengue hemorrhagic fever patients were studied by Western blotting. In the first group the immune response was barely detectable, while in the second group more proteins were detected, with a very strong reaction. Anti-NS1 and -NS3 antibodies were detected mainly in secondary cases. Anti-E, -NS3, and -NS5 antibodies were detected in a high number of cases. The possibility of implementing early diagnostic assays for antigen detection is suggested.