Assessment of Knowledge and Awareness Among the Stakeholders of Clinical Research at the Site: A Collaborative, Electronic-Survey Approach to Identify the Indicators of Quality.

BACKGROUND: There has been a concern about the quality of clinical trials conducted in terms of data integrity, accuracy or ethical conduct. This study aimed to assess the tangible gap existing in knowledge and application of rules and guidelines among the Researcher, Research staff (RS) and Ethics Committee (EC) members - the three research stakeholders at the study sites. METHODS: A validated e-questionnaire with details for demography, role, years of experience, affiliation and questions on knowledge and understanding about their clinical research functions based on the New Drugs and Clinical Trials (NDCT) Rules 2019, including: 'Role and responsibility, Regulations, Reporting timelines, Documentation, Conflict of interest and Miscellaneous' was circulated among the seven research sites of one organization with their fourteen Institutional ECs, as part of planned annual survey. Responses with >60% correct answers were arbitrarily considered to represent adequate knowledge. RESULTS: Of 201 participants, there were 27.4% Researchers, 50.2% were from the EC and 22.4% RS. A greater proportion of the Researchers (43.6%) had >5 years of experience. The mean ± SD of correct answers obtained was 66.9 ± 14.77 and was statistically significant (p<0.05) among the groups, highest for the EC members (71.4 ± 11.51), those with 2-5 years of experience (68.4 ± 14.40), and least for the RS (56.8 ± 11.93). Researchers (> 90%) were aware of their role in the clinical trial agreement and the importance of the trial registration in the Clinical Trials Registry India. There were gaps in the knowledge on Informed Consent (IC) process and post-trial access. Awareness regarding the IC process was adequate among the RS (84%). Awareness that the responsibility of all delegation at the site finally lies with the Researchers was adequate (60%), but 20% incorrectly believed that the sponsor can have access to subject identification details. Deficiencies were noted regarding documentation, NDCT rules -2019 and serious adverse event (SAE) reporting process. Five percent answered that Data Clarification Forms were generated after reviewing the case report forms. The awareness that NDCT rules-2019 was not for medical devices, student projects or Investigator Initiated Studies was inadequate (56%). The EC members' awareness of roles and responsibilities was adequate (≥ 90%). Knowledge gaps were noted in EC monitoring of the ongoing trials (32%) and SAE reporting on the SUGAM portal (8.8%), where stakeholders can access the regulator's web services using a single window interface for clinical trial related activities. CONCLUSION: There are gaps in the knowledge of the 3 stakeholders at the site. Identifying and rectifying the gray areas will improve the site's performance. There is a need for regular training and assessments.

A Multicenter Clinical Diagnostic Accuracy Study of SureStatus, an Affordable, WHO Emergency Use-Listed, Rapid, Point-Of-Care Antigen-Detecting Diagnostic Test for SARS-CoV-2.

Access to reverse transcription-PCR (RT-PCR) testing, the gold standard for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection, is limited throughout the world, due to restricted resources, available infrastructure, and high costs. Antigen-detecting rapid diagnostic tests (Ag-RDTs) overcome some of these barriers, but independent clinical validations in settings of intended use are scarce. To inform the World Health Organization's (WHO) emergency use listing (EUL) procedure and ensure affordable, high-quality Ag-RDTs, we assessed the performance and ease of use of the SureStatus for SARS-CoV-2. For this prospective, multicenter diagnostic accuracy study, we recruited unvaccinated participants with presumed SARS-CoV-2 infection in India and Germany from December 2020 to March 2021, when the Alpha (B.1.1.7) variant was predominantly circulating. Paired swabs were performed for (i) routine clinical RT-PCR testing (sampling was either nasopharyngeal [NP] or combined NP and oropharyngeal [NP/OP]) and (ii) Ag-RDT (sampling was NP). Performance of the Ag-RDT was compared to RT-PCR overall and by predefined subgroups, e.g., cycle threshold (CT) value, symptoms, and days from symptom onset. To understand the usability, a system usability scale (SUS) questionnaire and ease-of-use (EoU) assessment were performed. A total of 1,119 participants were included in the analysis, of whom 205 (18.3%) were RT-PCR positive. SureStatus detected 169 out of 205 RT-PCR-positive participants, reporting a sensitivity of 82.4% (95% confidence interval [CI]: 76.6% to 87.1%) and a specificity of 98.5% (95% CI: 97.4% to 99.1%). In the first 7 days post-symptom onset, the sensitivity was 90.7% (95% CI: 83.5% to 94.9%), when CT values were low and viral loads were high. The test was characterized as easy to use (SUS, 85/100) and considered suitable for point-of-care settings, although quality concerns were raised due to visibly contaminated packaging of swabs included in the test kits. The SureStatus diagnostic test can be considered a reliable test during the first week of SARS-CoV-2 infection, with high sensitivity in combination with excellent usability. IMPORTANCE Our manufacturer-independent, prospective diagnostic accuracy study assessed clinical performance in participants presumed to have a SARS-CoV-2 infection at three study sites in two countries. We assessed the accuracy overall and in predefined subgroups (CT values and symptom duration). SureStatus performed with high sensitivity. Its sensitivity was particularly high in the first 3 days after symptom onset and when CT values were low (i.e., the viral load was high). The system usability and ease-of-use assessment complements the accuracy assessment of the test and highlights critical factors to facilitate the widespread use of SureStatus in point-of-care settings. The high sensitivity demonstrated by the evaluated Ag-RDT within the first days of symptoms, when most transmission occurs, supports the role of Ag-RDTs for public health-relevant screening. Evidence from this study was used to inform the World Health Organization Emergency Use Listing procedure.

Risk factors predisposing to acute stroke in India: a prospective study.

BACKGROUND: Stroke is an important neurological disorder with significant morbidity and mortality. In India, the risk factors for stroke (obesity, diabetes mellitus, alcoholism, hypertension, and sedentary lifestyle) are mounting with economic growth and increasing the disease burden. OBJECTIVE: To assess the severity and risk factors of stroke in India and identify any new predisposing factors. METHODS: A multicentric (six tertiary care hospitals across India) prospective observational study (from September 2016 to July 2017) was conducted on 526 stroke patients, presenting within the first 24 h to examine the risk factors for ischemic and hemorrhagic strokes. Severity was determined using the National Institutes of Health Stroke Scale (NIHSS). RESULTS: Predominantly male (72.3%), 75% of the sample was >50 years old, with a mean body mass index (BMI) of 25.8 ±â€Š4.3 kg/m2 and 14.6% obese patients. Hypertension and diabetes mellitus were the commonest comorbidities, followed by a history of ischemic heart disease and familial history of stroke. 20.5% of patients had mild strokes, 57.4% had moderate, 8.4% experienced moderate-severe strokes, whereas 7.2% had severe strokes. Regarding the admission diagnoses, 56.8% were ischemic, 18.6% were hemorrhagic, 1.1% had a transient ischemic attack, 6.6% suffered recurrent strokes, and 17% were other forms. CONCLUSION: The foremost risk factors for stroke in India, hypertension and diabetes, need to be controlled and treated like other global high-risk populations for stroke prevention. The NIHSS scores highlight the relationship between risk factors and stroke severity.

Correlation Between Ambulatory Blood Pressure Monitoring and Office Blood Pressure Measurement in Patients with Hypertension: A Community Study.

BACKGROUND: The current gold standard for blood pressure (BP) measurements is based on office BP measurements (OBPMs) by a sphygmomanometer or a digital device. Ambulatory BP measurement (ABPM) is a noninvasive method for continuous monitoring of BP over a period during routine activities of the patient. Thus, ABPM offers multiple BP readings during the patients' daily routine as compared to the single reading by OBPM at rest. A good correlation exists between mean 24-hour BP readings and the prediction of cardiovascular events. The present multicenter observational study was aimed to assess the correlation between ABPM and OBPM in patients with newly diagnosed, controlled, or uncontrolled hypertension in the community setting. Our hypothesis was to test if ABPM provides any further value in those hypertensive patients in whom the office blood pressure levels are controlled. A supplementary hypothesis was whether obtaining ABPM in patients with newly diagnosed or uncontrolled hypertension yields any value over and beyond OBPM. Another objective was to find out the applicability of ABPM in the community setting where the medical care is provided by primary care family physicians and not by specialists. MATERIALS AND METHODS: Materials and Methods A total of 1000 patients were analysed for this study. Those with controlled hypertension were assigned to Group A, and those with newly diagnosed/untreated hypertension comprised Group B. Group A was followed up during Visit 2 and Group B was followed up during Visit 2 and either Visit 3 or Visit 4 to assess the BP measurements by ABPM and OBPM. RESULTS: The correlation between ABPM and OBPM showed minimal variation in the BP readings of Group A subjects at Visit 2. A variation in BP readings was observed in Group B at Visit 2. Furthermore, the correlation was established between ABPM and OBPM noted for Group B subjects during Visit 3, and minimal variation was noted during Visit 4. CONCLUSIONS: Conclusions A good correlation was observed between ABPM and OBPM during both visits in patients in Groups A and B. However, a notable variation was noted in the diastolic BP readings. Thus, large-scale clinical studies are required to detect the prevalence of hypertension, masked hypertension, and dipping patterns associated with hypertension and other related medical co-morbidities.

Potential for a biopesticide bait to control black beetle, Heteronychus arator (Coleoptera: Scarabaeidae).

BACKGROUND: Yersinia entomophaga is an entomopathogenic bacterium that is active against scarab beetles, among other insects. In New Zealand, the African black beetle, Heteronychus arator (Coleoptera: Scarabaeidae), is a major pest of pastures and arable crops but very few control options exist and no insecticides are registered for use in established pastures. RESULTS: In laboratory bioassays, H. arator adults were susceptible to a bait containing Y. entomophaga at low doses. This bait was more effective against H. arator adults during spring than autumn in small-scale field plots (320 mm diameter). A large-scale field trial (40 × 40 m plots) reduced adult numbers substantially: approximately twice as many beetles were captured in pitfall traps from untreated plots compared with plots treated with the Y. entomophaga bait at 70 kg ha-1 . This single bait application in spring also reduced subsequent larval populations in summer. CONCLUSIONS: Heteronychus arator is a difficult pest to manage using chemical insecticides. This biopesticide with Y. entomophaga as the active ingredient offers a new solution for New Zealand pastures, with potential for application to other crops affected by H. arator and for control of other pests. © 2020 Society of Chemical Industry.

Development of a Yersinia entomophaga bait for control of larvae of the porina moth (Wiseana spp.), a pest of New Zealand improved grassland systems.

BACKGROUND: Porina is the common name for moths and larvae of the genus Wiseana (Lepidoptera: Hepialidae), some of which are significant pasture pests in New Zealand. Because of environmental concerns and the non-target effects of insecticide control measures, biological alternatives for the control of insect pests such as porina are required. RESULTS: Using a food preference assay and time-lapse photography, a range of low-cost food ingredients were assessed for their palatability to porina larvae. Lead candidates were combined into extruded bait variants, allowing assessment of their palatability to porina larvae. A composite bait consisting of palatable ingredients was developed, into which the porina-active entomopathogen Yersinia entomophaga was incorporated. A 7 day minimum median lethal dose of approximately 6.0 × ±1 × 106 Y. entomophaga cells per 0.02 g of bait was defined. Field trials showed that the mean change in larval density over time differed between treatments, with Y. entomophaga bait applied at 87 kg ha-1 resulting in a mean 65% reduction in larval density relative to the control plots, and diflubenzuron treatment resulting in a mean 77% reduction relative to the control plots. The mean dry matter yields over the course of the trial were highest for diflubenzuron (5029 kg ha-1 ), followed by the Y. entomophaga (4783 kg ha-1 ) and control (4673 kg ha-1 ) treatments. CONCLUSIONS: The bacterium Y. entomophaga applied as a composite bait offers an environmentally sustainable approach for porina pest control. © 2019 Society of Chemical Industry.

Evaluation of the Parasight Platform for Malaria Diagnosis.

The World Health Organization estimates that nearly 500 million malaria tests are performed annually. While microscopy and rapid diagnostic tests (RDTs) are the main diagnostic approaches, no single method is inexpensive, rapid, and highly accurate. Two recent studies from our group have demonstrated a prototype computer vision platform that meets those needs. Here we present the results from two clinical studies on the commercially available version of this technology, the Sight Diagnostics Parasight platform, which provides malaria diagnosis, species identification, and parasite quantification. We conducted a multisite trial in Chennai, India (Apollo Hospital [n = 205]), and Nairobi, Kenya (Aga Khan University Hospital [n = 263]), in which we compared the device to microscopy, RDTs, and PCR. For identification of malaria, the device performed similarly well in both contexts (sensitivity of 99% and specificity of 100% at the Indian site and sensitivity of 99.3% and specificity of 98.9% at the Kenyan site, compared to PCR). For species identification, the device correctly identified 100% of samples with Plasmodium vivax and 100% of samples with Plasmodium falciparum in India and 100% of samples with P. vivax and 96.1% of samples with P. falciparum in Kenya, compared to PCR. Lastly, comparisons of the device parasite counts with those of trained microscopists produced average Pearson correlation coefficients of 0.84 at the Indian site and 0.85 at the Kenyan site.

Hematological and biochemical parameters in apparently healthy Indian population: defining reference intervals.

Clinical reference intervals among Indian population are poorly defined. Therefore, there is an urgent need to establish local clinical laboratory reference intervals for healthy Indian population. The present study aimed to identify the 95 % reference interval for hematological and biochemical parameters in apparently healthy Indian population. We undertook a multicentric cross-sectional study conducted at Apollo Hospitals Educational and Research Foundation across India. Of which 10,665 reference individuals identified as healthy by physicians. The 95 % of the reference distribution was estimated using 2.5th and 97.5th percentile reference limits. The 95 % reference intervals for hemoglobin (Males: 12.3-17 g/dL; Females: 9.9-14.3 g/dL), platelet count (Males: 1.3-3.8; Females: 1.3-4.2 Lakhs/µL), erythrocyte sedimentation rate (Males: 2-22; Females: 4-55 mm/h), serum uric acid in males: 3.5-8.2 mg/dL, gamma glutamyl transferase (Males: 13-61 U/L), fasting blood glucose (Males: 78-110 mg/dL), total cholesterol (Males: 115-254 mg/dL), low density lipoprotein (Males: 60-176 mg/dL) and triglycerides (Males: 55-267 mg/dL, Females: 52-207 mg/dL) were different from currently used reference values. Additionally need for gender based partitioning were observed for triglycerides and gamma glutamyl transferase. The observed findings are of clinical significance and it needs to be validated with additional community based studies.