Evaluation Program Research Articles

Evaluation of Public Health Mass Campaign: Hesitancy and Event Ratios Method

Several public health interventions administer drugs and vaccines to large number of people for preemptive or reactive intervention. These vaccines and drugs were developed in very narrow conditions in clinical trials and we therefore have to continuously monitor the efficacy in the field. This paper proposes a method to evaluate the efficacy in the field using data collected from the intervention coverage survey and surveillance. The design is closely related to cohort prospective studies except that the sample size is not fixed upfront and the measure of association not affected by the population denominator. It uses two new terms: hesitancy ratio denoted β, which is the ratio of the target that does to receive the intervention to the target that received it; event ratio is denoted by α is the ratio of health event or disease being prevented absolute incidence in the intervention group to that is in control group. It further shows that risk ratio (RR) can be calculated from these two parameters by taking their products. i.e. RR = α β. This method is therefore called Hesitancy and Event Ratios (HER) Method. We can conclude that this method is scientifically sound and can be used in the evaluation of public health intervention in the field. We recommend that this method be included in routine monitoring of programs for efficacy evaluation.

Supporting patients in the transition to the revised pexidartinib dosing regimen: perspectives from the multidisciplinary clinical and allied health professional team

Pexidartinib is a colony-stimulating factor-1 receptor inhibitor approved in the United States for treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery. Because of the risk of severe and potentially fatal hepatotoxicity, pexidartinib is only available through a Risk Evaluation and Mitigation Strategy (REMS) program. Pexidartinib pharmacokinetics are influenced by the fat content of meals: compared with the fasted state, consuming a high-fat meal with pexidartinib increases pexidartinib absorption by 100%; a low-fat meal increases absorption by approximately 60%. Pexidartinib was initially authorized to be taken at 800 mg/day on an empty stomach; therefore, if this same dose of pexidartinib is taken with food, there is a risk of overexposure and potential toxicity. To reduce the risk of hepatotoxicity and improve patient compliance, pexidartinib has undergone a revised dosing regimen, from 800 mg/day (400 mg twice daily) fasted to 500 mg/day (250 mg twice daily) with a low-fat meal (approximately 11–14 g of total fat). The objective of this report is to educate clinical and allied health professionals on the revised dosing regimen and the importance of patient compliance with a low-fat meal. Healthcare professionals need to understand the rationale for the switch from pexidartinib dosing on an empty stomach to dosing with a low-fat meal and how meal composition and timing influence pharmacokinetics. Finally, we provide guidance for the healthcare team of prescribing providers, nurses, pharmacists, and dietitians who are caring for patients with TGCT on pexidartinib. It is important for healthcare providers to deliver consistent messaging on the low-fat meal requirement and help patients fit pexidartinib into their regular meal schedules. Consulting a dietitian may be helpful for patients, especially those with complex dietary needs. We provide an overview of the roles and responsibilities of each healthcare professional and outline steps to best support patients, including key questions and answers related to the revised dosing regimen. This report provides the information necessary to guide the multidisciplinary team caring for patients with TGCT and to support them through the pexidartinib dosing regimen change.

Automated Insulin Delivery in Women with Pregnancy Complicated by Type 1 Diabetes

BackgroundHybrid closed-loop insulin therapy has shown promise for management of type 1 diabetes during pregnancy; however, its efficacy is unclear.MethodsIn this multicenter, controlled trial, we randomly assigned pregnant women with type 1 diabetes and a glycated hemoglobin level of at least 6.5% at nine sites in the United Kingdom to receive standard insulin therapy or hybrid closed-loop therapy, with both groups using continuous glucose monitoring. The primary outcome was the percentage of time in the pregnancy-specific target glucose range (63 to 140 mg per deciliter [3.5 to 7.8 mmol per liter]) as measured by continuous glucose monitoring from 16 weeks’ gestation until delivery. Analyses were performed according to the intention-to-treat principle. Key secondary outcomes were the percentage of time spent in a hyperglycemic state (glucose level >140 mg per deciliter), overnight time in the target range, the glycated hemoglobin level, and safety events.ResultsA total of 124 participants with a mean (±SD) age of 31.1±5.3 years and a mean baseline glycated hemoglobin level of 7.7±1.2% underwent randomization. The mean percentage of time that the maternal glucose level was in the target range was 68.2±10.5% in the closed-loop group and 55.6±12.5% in the standard-care group (mean adjusted difference, 10.5 percentage points; 95% confidence interval [CI], 7.0 to 14.0; P<0.001). Results for the secondary outcomes were consistent with those of the primary outcome; participants in the closed-loop group spent less time in a hyperglycemic state than those in the standard-care group (difference, −10.2 percentage points; 95% CI, −13.8 to −6.6); had more overnight time in the target range (difference, 12.3 percentage points; 95% CI, 8.3 to 16.2), and had lower glycated hemoglobin levels (difference, −0.31 percentage points; 95% CI, −0.50 to −0.12). Little time was spent in a hypoglycemic state. No unanticipated safety problems associated with the use of closed-loop therapy during pregnancy occurred (6 instances of severe hypoglycemia, vs. 5 in the standard-care group; 1 instance of diabetic ketoacidosis in each group; and 12 device-related adverse events in the closed-loop group, 7 related to closed-loop therapy).ConclusionsHybrid closed-loop therapy significantly improved maternal glycemic control during pregnancy complicated by type 1 diabetes. (Funded by the Efficacy and Mechanism Evaluation Program; AiDAPT ISRCTN Registry number, ISRCTN56898625.)

Recruitment and Retention of Racially and Ethnically Minoritized Graduate Students in Educational Measurement Programs

ABSTRACT Building on the extant literature on recruitment and retention within the field of STEM and undergraduate education, we sought to explore the recruitment and retention experiences of racially and ethnically minoritized students enrolled in graduate level assessment, measurement, and/or evaluation programs in the United States. Using a mixed methods approach, surveys were completed by 98 students and eleven participated in follow up semi-structured interviews. Doctoral students reported that (1) recruitment practices of educational measurement programs tend to be minimal or nonexistent; (2) having strong and consistent mentorship from faculty within and (often) external to their academic programs is critical; (3) struggles with lack of funding (both the fear of prior to enrollment and reality of post enrollment) was a significant source of stress; and (4) many doctoral programs fail to offer the comprehensive curriculum students feel they need to be prepared for the job market. Recommendations for future practice are discussed.

Asset Assessment of Concrete Structure

Infrastructures which were constructed in the last century are approaching or have exceeded their design life. It is essential to maintain, repair and rehabilitate existing structures to ensure safety and develop a sensible rehabilitation plan. This paper suggests an inspection program for the condition evaluation of existing structures, particularly for structures that are approaching or exceeding their design/campaign lives. Cracking on concrete bridges is often induced by static and cyclic temperature loading. Throughout the service life of the structure, cracks will initiate, propagate, coalesce and form a greater damaged zone. Depending on the location and severity of the crack network; corrosion of reinforcement, debonding between concrete and reinforcement, and spalling of concrete may occur. The implementation of regular inspection or monitoring of structural condition is an essential component of asset management. Early detection of damaged zones can ease scheduling and reduce the cost of repair, which in turn also allows extension of structural lifespan without compromising safety. Similarly, for industrial properties, asset management and rehabilitation programs are paramount as they can significantly reduce capital expenditures in asset maintenance, if implemented prior to or at the early onset of structural degradation. This paper illustrates the use of NDT techniques for the condition assessment of a prestressed concrete bridge, as well as concrete storage silos. Both of which were either approaching or have exceeded their design campaign life and were needing a proper rehabilitation plan. The assessment included crack movement monitoring, crack depth determination, concrete strength estimation, and the detection of debonding between rebar and concrete.

Pengaruh Green Business dan Good Corporate Governance Terhadap Kinerja Keuangan: Corporate Social Responsibility sebagai Pemoderasi

The aim of this study was conducted to find out whether green business using the annual reports of companies that received the Pollution Control, Evaluation and Ranking Program Award (PROPER) corporate social responsibility is influenced by the characteristics of the board of commissioners (number of independent commissioners, diversity of the board of commissioners, and concentration of ownership) and whether financial performance (ROA, ROE and Tobin's Q) is moderated by corporate social responsibility, in companies listed on the Indonesia Stock Exchange in the period 2015 to 2022. The population used is all companies listed on the Stock Exchange Indonesia for five consecutive years. The sampling method was selected using purposive sampling, namely non-financial companies included in Pefindo 25. This study used a quantitative approach. The samples used in this study were 22 companies with 110 observations. The data analysis method uses panel data regression (Eviews 9) with Descriptive Statistical Tests, Model Conformity Tests, namely the Chow test and Hausman test, followed by the F test, the Goodness of Fit test, the hypothesis test, and finally the t test. The results of research on green economy and good corporate governance which are proxied by the number of independent commissioners, the diversity of the board of commissioners and the majority ownership of the company have a positive effect on financial performance. moderated by corporate social responsibility has no positive effect on financial performance proxied by ROA, ROE and leverage.

Integration between Geoinformatics and Programming for Evaluation of Potential Hydropower of Red Sea Hills in Egypt

Integration between Geoinformatics and Programming for Evaluation of Potential Hydropower of Red Sea Hills in Egypt

81.2 A Novel Outpatient Program for Evaluation of Youth With Somatic Symptom and Related Disorders

81.2 A Novel Outpatient Program for Evaluation of Youth With Somatic Symptom and Related Disorders

Ondansetron for irritable bowel syndrome with diarrhoea: randomised controlled trial

Background Irritable bowel syndrome with diarrhoea is characterised by frequent, loose or watery stools with associated urgency, resulting in marked reduction of quality of life. Ondansetron, a 5-hydroxytryptamine-3 receptor antagonist, has been shown to benefit patients with irritable bowel syndrome with diarrhoea. Objective To evaluate the effect of ondansetron in irritable bowel syndrome with diarrhoea. Design Phase III, parallel-group, randomised, double-blind, multicentre, placebo-controlled trial in 400 patients, with embedded mechanistic studies. Setting Hospital, primary care and community. Participants Eighty participants meeting Rome IV criteria for irritable bowel syndrome with diarrhoea. Intervention Ondansetron 4 mg (dose titrated up to two tablets three times a day) or matched placebo for 12 weeks. Main outcome measures Clinical – Primary patient-reported end point was % ‘Food and Drug Administration-defined responders’ over 12 weeks. Secondary end points were worst abdominal pain intensity, worst urgency, stool consistency, stool frequency, anxiety, depression and dyspepsia at 12 and 16 weeks. Main outcome measures Mechanistic – Whole gut transit time, faecal water, protease (FP), bile acids and assessment of rectal sensitivity using a barostat. Results Clinical – The study closed early due to slow recruitment. Between 1 January 2018 and 11 May 2020, 80 patients were recruited and randomised (20% of target), 37 to ondansetron, 43 to placebo. Discontinuations (4 ondansetron; 2 placebo) meant 75 completed the 12-week trial treatment. There were four protocol violations. In the intention-to-treat analysis, 15 (40.5%) on ondansetron were primary end-point responders (95% CI 24.7% to 56.4%), and 12 (27.9%) on placebo (95% CI 14.5% to 41.3%), p = 0.19, adjusted OR 1.93 (0.73, 5.11). Pain intensity reduction occurred in 17 (46.0%) on ondansetron (95% CI 29.9% to 62.0%) and 16 (37.2%) on placebo (95% CI 22.8% to 51.7%), p = 0.32. Improvement in stool consistency occurred in 25 (67.6%) on ondansetron (95% CI 52.5% to 82.7%) and 22 (51.2%) on placebo (95% CI 36.2% to 66.1%), p = 0.07. Use of rescue medication, loperamide, was lower on ondansetron [7 (18.9%) vs. 17 (39.5%)]. Average stool consistency in the final month of treatment reduced significantly more on ondansetron, adjusted mean difference –0.5 [standard error (SE) 0.25, 95% CI (–1.0 to –0.02), p = 0.042]. Ondansetron improved dyspepsia score (SFLDQ), adjusted mean difference –3.2 points [SE 1.43, 95% CI (–6.1 to –0.4), p = 0.028]. There were no serious adverse events. Mechanistic – mean (SD). Ondansetron increased whole gut transit time between baseline and week 12 by 3.8 (9.1) hours on ondansetron, significantly more than on placebo –2.2 (10.3), p = 0.01. Mean volume to reach urgency threshold using the barostat increased on ondansetron by 84 (61) ml and 38 (48) ml on placebo, n = 8, p = 0.26. Ondansetron did not significantly alter protease, faecal water or bile acids. Changes in referral pathways substantially reduced referrals, impairing recruitment, which meant the study was underpowered. Conclusion Our results are consistent with previous studies and confirmed ondansetron improves stool consistency and urgency but showed minor effect on pain. We plan to undertake a simplified version of this trial overcoming the changed referral pathways by recruiting in primary care, using software linked to primary care records to identify and randomise patients with irritable bowel syndrome with diarrhoea to ondansetron or placebo and remotely follow their progress; thus minimising barriers to recruitment. Trial registration This trial is registered as ISRCTN17508514. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation programme and will be published in full in Efficacy and Mechanism Evaluation; Vol. 10, No. 9. See the NIHR Journals Library website for further project information.

Integration of an App-Based Cognitive Evaluation Program into Radiosurgery Practice: Outcomes and Patient Survey Analysis from a Prospective Observational Study.

Cognitive decline is a significant consequence of stereotactic radiosurgery (SRS) in patients with brain metastases. This is often underrecognized and understudied outside of a formal clinical trial setting as traditional methods are often logistically difficult and need specialized personnel and additional time. To address these challenges, we implemented a prospective study (NCT05504681), incorporating an innovative app-based solution to monitor patient assessments over time, collect patient data easily, and be suitable for cross-cultural use in multiple languages for monitoring post-SRS cognitive decline. Patients undergoing SRS from December 2021 to October 2022 were enrolled in this study and completed feedback surveys. The assessments consisted of learning and memory (Hopkins verbal learning test-revised [HVLT-R]), attention and processing speed (Digit symbols modalities test [SDMT]), verbal fluency (Controlled oral word association test [COWAT]) and executive function (Trail making test [TMT]). Baseline and 3-month follow-up testing were conducted in conjunction with routine imaging and clinical assessments. Neurocognitive deterioration (ND) was defined as a decrease of ≥2 standard errors of the mean in any of the tests, without evidence of new intracranial disease. Any differences between the baseline and follow-up assessments were confirmed using the reliable change index. A total of 30 patients with median age of 68 (range: 47-87) were enrolled. The median KPS was 90 and 60% were female. 43% of participants had a high school or equivalent level of education. 19 (63%) patients were Hispanic and 43% tested in Spanish. The median number of treated lesions was 2 (1-13) and 7 (23%) patients were treated to ≥5 lesions. The median mean left and right hippocampal doses were 0.3 Gy (0-3 Gy) and 0.2 Gy (0-5.2 Gy), respectively. Overall, 50% of patients met criteria for ND at 3 months. 20% of patients showed ND in HVLT-R-immediate recall (IMM), 23% in HVLT-R-delayed recall (DR), 13% in HVLT-R-recognition (Rec), 3% in COWAT and 20% in TMT. None of the patients had ND in SDMT. The mean relative decline was 28% for HVLT-R- IMM, 34% for HVLT-R-DR, 6% for HVLT-R- Rec, 25% for COWAT, and 21% for TMT. There was no significant association between the number of treated lesions and ND. Based on the feedback results, the majority of patients found the system easy to use (94%) and relevant to their care (73%). Most patients reported that app-based evaluation improved discussions with clinicians (77%), made them feel more in control of their care (79%), and they would recommend the system to other patients (87%). Our study showed a high incidence of ND using an app-based tool in a patient who underwent SRS and from diverse education and language backgrounds. Patient survey results demonstrated that the tool was easy to use and relevant to the patient's care, especially due to improvements in discussions with clinicians and a sense of being in control of their own care.

Entre flores e amores: o perfil e o comportamento do consumidor com o objetivo de sedução

Abstract Since the fifth century B.C., flowers have been associated with seduction, however, no studies were found that could reveal how flowers are bought with this intention. In order to investigate the profile and behavior of consumers of flowers with the purpose of seduction, a descriptive exploratory study was carried out with 108 consumers at the time they purchased flowers with the intention of seduction. The study revealed that among people who bought flowers for this purpose, the frequency was on average of 1.7 times a year, with 64.7% of these consumers defining themselves as male people. No statistical variation was observed between heterosexual, bisexual and homosexual groups. Single and married people had higher purchase rates, with roses being the preferred flowers. Tropical flowers may represent a trend to be explored in market segmentation. The purchase of flowers for seduction was mostly associated with affective relationships such as boyfriends/girlfriends or spouses and the use of flowers in the search for new relationships or even fortuitous cases was also evidenced. Most respondents who reported that have received flowers described that it was a positive influence and contributed to feeling seduced. Finally, it is possible to consider market segmentation, however, it is urgent that the sector be organized in order to elaborate a diagnosis of potential consumption, elaborate consumer acceptance tests, define groups to be segmented, establish targeted marketing campaigns and create evaluation programs for consumer loyalty.

Burnout in Preclinical Medical Students

Objectives: The prevalence of burnout is progressively rising among medical students. The objective of this study was to evaluate the occurrence and determinants of burnout among preclinical medical students in Muscat. Methods: This cross-sectional analytical research was conducted at one of Oman's top medical universities from October 2019 to April 2020. A cohort of 350 preclinical medical students in their 2nd, 3rd, and 4th years of study participated in this study. The assessment of burnout was based on self-reports from the participants, using the Maslach Burnout Inventory-Student Survey. Various variables were coded and analyzed. Results: A total of 350 students completed the survey (response rate: 83.3%). Burnout was reported by 125 (35.7%) students. Regarding specific domains of burnout, most students demonstrated higher rates of cynicism (n: 236; 67.4%) and emotional exhaustion (n: 221; 63.1%) and lower rates of academic efficacy (n: 197; 56.3%). Burnout was significantly more common among older students (p-value &lt; 0.001), students living apart from their family (p-value: 0.042), students who did not participate in regular exercises (p-value &lt; 0.001), those who spent fewer hours studying per day (p-value &lt; 0.001), those who regretted their decision to study medicine (p-value: 0.023), those who were dissatisfied with examination results (p-value &lt; 0.001), teaching strategies (p-value: 0.029), those with lower cumulative grade point averages (p-value &lt; 0.001), and those with a history of academic probation (p-value &lt; 0.001). Conclusions: Preclinical medical students displayed high rates of burnout. Continuous evaluation programs and educational initiatives are recommended to help such students to develop better burnout management and coping strategies.

Bilateral versus single internal thoracic coronary artery bypass grafting: the ART RCT

Background There is debate whether the use of more arterial grafts during coronary artery bypass graft surgery provides advantages to the standard operation using the left internal thoracic artery plus vein grafts. We review data from the Arterial Revascularisation Trial to determine whether there is support for the multiple arterial graft hypothesis. Methods Patients undergoing coronary artery bypass graft for clinical reasons and who provided written informed consent were randomised to standard coronary artery bypass graft using the single internal thoracic artery or use of bilateral internal thoracic arteries. Additional vein grafts could be used. The primary outcome was all-cause mortality at 10 years and exploratory analyses were carried out to test the multiple arterial graft hypothesis. Results A total of 3102 patients were enrolled (1548 bilateral internal thoracic artery and 1554 single internal thoracic artery). Follow-up to 10 years for vital status was 98% complete. In the bilateral group, 14% of patients received a single internal thoracic artery only and use of radial artery grafts occurred in about 20% of patients in both groups. Aspirin was used in 81% of the patients, beta-blockers in 74%, statins in 90% and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in 73%. At 10 years, death rates were 20.3% and 21.2% in the bilateral internal thoracic artery and single internal thoracic artery groups, respectively (hazard ratio 0.96, 95% confidence intervals 0.82 to 1.12; p = 0.62) and composite of all-cause mortality, myocardial infarction or stroke 24.9% and 27.3%, respectively (hazard ratio 0.90, 95% confidence interval 0.79 to 1.03; p = 0.12). Exploratory analyses using the ‘as-treated’ approach indicate that outcomes were better in patients who received multiple arterial grafts (adding the right internal thoracic and/or radial arteries) compared with a single arterial graft. This effect appeared to be greater in patients with diabetes and those aged 70 years or less. Use of total arterial grafting without vein grafts may provide the best outcomes. Limitations The elevated cross-over rate between bilateral internal thoracic artery and single internal thoracic artery and the non-randomised use of radial artery grafts may have contributed to a loss of power to detect a difference in mortality between the two groups. Moreover, secondary analyses are prone to bias as they compare non-randomised groups. Conclusions The Arterial Revascularisation Trial is one of the largest long-term studies in cardiac surgery. The primary analysis did not show a mortality benefit for bilateral internal thoracic artery at 10 years, perhaps due to high crossover rates in the bilateral internal thoracic artery group and concomitant use of the radial artery. Secondary analyses suggest a mortality benefit for patients receiving multiple arterial grafts compared with single arterial graft with possible greater effects in patients with diabetes and separately in patients aged 70 years or above. The trial will follow patients to 15 years and the continuing Randomized Comparison of the Clinical Outcome of Single versus Multiple Arterial Grafts trial will further test the multiple arterial graft hypothesis. Trial registration This trial is registered as ISRCTN46552265. Funding This project was funded by the British Heart Foundation, the UK. Medical Research Council and the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation programme and will be published in full in Efficacy and Mechanism Evaluation; Vol. 10, No. 7. See the NIHR Journals Library website for further project information.

Effect of some non-genetic factors on productive and reproductive traits of Mehsana buffaloes

The records of 7782 Mehsana buffaloes sired by 184 sires maintained at Dudhsagar Research and Development Association (DURDA), Dudhsagar Dairy, Mehsana, Gujarat born during 1989 to 2012 were collected and analysed to examine the effect of non-genetic factors viz. period and season of calving and age at first calving. The least squares analysis was used for estimation of various non-genetic factors on First Lactation Milk Yield (FLMY), First Lactation Fat Yield (FLFY), Average Fat Percentage (AFP) and Age at First Calving (AFC). The least squares mean with standard error of FLMY, FLMY, AFP and AFC were estimated to be 1900.68±7.65 lit., 135.04±0.57 kg, 7.11±0.11 percentage and 1407.18±4.36 days, respectively. Highly significant (P≤0.01) effect of all the non-genetic factors (period and season of calving and age at first alving group) under study was observed on FLMY, FLMY and AFP in Mehsana buffaloes. Further, highly significant (P≤0.01) effect of season and period of birth was recorded on AFC. It is worthy to note that in Mehsana breed evaluation programme these factors should be considered as they have great influence of them.

Landscape of the Radiosensitizing Properties of Targeted Agents from the NCI CTEP Portfolio across Genomically Diverse 3D Tumor Models

Clinical translation of molecular targeted radiosensitizers remains challenging. To improve the robustness of preclinical data, we sought to broadly examine across a wide spectrum of genomic cancer features the radiosensitizing properties of targeted drugs from the NCI Cancer Therapy Evaluation Program (CTEP). As part of a U01 Consortium, we adapted a robotic high-throughput platform for testing ionizing radiation (IR) plus drug combinations in 3D cultures derived from non-small cell lung carcinoma (NSCLC), head/neck (HNSCC), and pancreatic cancers. All cell lines were annotated, mycoplasma free, and re-authenticated. Signal windows were established for all 3D growth formats. CTEP drugs were added in four concentrations 24 hours prior to IR exposure of 384-well plates. Five days after IR, cell viability was assessed, an endpoint previously benchmarked using colony formation. Each data point was based on 4-6 technical replicates with 2 biological repeats. A multistep statistical method combining Wilcoxon signed-rank and Spearman rank-order correlation tests together with adjusted Benjamini-Hochberg corrections for multiple comparisons was used to identify radiosensitization hits. Select validation experiments of hits were carried out. We screened 73 3D tumor models with 34-42 CTEP drugs each plus IR (n = 10,744 cell line/drug concentration combinations). IR/drug patterns were comparable for the three cancer types. DNA damage response (DDR) inhibitors constituted the most active class of radiosensitizers with DNA-PKcs, PARP, and ATR being the top targets. In contrast, the majority of the other agents radiosensitized only a minority of models. Highlighting NSCLC, out of 1,120 cell line/drug combinations, 328 (29.3%) were associated with statistically significant radiosensitization. PARP inhibitors, of particular interest for clinical translation in this space, demonstrated relatively broad radiosensitization for talazoparib (62%) and olaparib (44%) but less so for veliparib (28%), which correlated with differential PARP trapping potentials. Radiosensitization was evident even for tumor genotypes associated with radioresistance such as mutant KRAS, KEAP1, and STK11. Interestingly, single-agent activity of olaparib was more pronounced in 11/30 3D cultures compared to 2D growth conditions but with only 2/11 having known homologous recombination defects. Lastly, for HPV negative HNSCC (735 combinations), there was radiosensitization in subsets of models for IAP, ATR, and AKT targets, which are under clinical investigation. We present a unique resource for examining radiosensitizing drug properties in 3D cultures. The observed radiosensitization patterns strongly argue for the use of larger panels of clinically relevant tumor models rather than a few non-representative cell lines. Our data highlight the urgent need for predictive biomarkers to guide IR/drug combinations, even for some DDR inhibitors.

B-266 Analytical Performance Comparison of Two Genotyping Assays for HIV-1 Drug Resistance Using Sanger Sequencing

Abstract Background The first case of Acquired Immunodeficiency Syndrome (AIDS) was registered in the United States in early 1980. Two years later, was identified the Human Immunodeficiency Virus (HIV-1), which causes AIDS. Compared to other diseases, the treatment of AIDS achieved an important advance in just over 30 years, in which several drugs were used and replaced. However, resistance to antiretrovirals (ARVs) remains a problem in clinical practice. There are about 20 approved HIV-1 treatment drugs belonging to four different classes: Protease Inhibitors (PI), Nucleoside Reverse Transcriptase Inhibitors (NRTI), Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI), and Integrase Strand Transfer Inhibitor (INSTI). ARVs resistance is caused by mutations in molecular targets of these drugs: protease, reverse transcriptase, and integrase enzymes. Virus genotyping that includes these regions is extremely important to identify the resistance mutations to ARVs therapies, being able to direct treatments. Thus, this study aimed to evaluate the analytical performance of the Applied Biosystems HIV-1 Genotyping Kit with Integrase compared to in-house Sanger genotyping method. Methods Viral RNA isolation from 20 individuals was performed by QIAamp Viral RNA Kit (Qiagen), according to the manufacturer’s instructions. HIV-1 genotyping was performed using both methods: in-house Sanger genotyping and Applied Biosystems HIV-1 Genotyping Kit with Integrase (Thermo Fisher), according to the manufacturer’s instructions. All results were submitted to SeqScape software to evaluate sequencing metrics. The consensus sequence was generated for each sample and analyzed at the online Stanford HIVdb Program (version 9.4) for drug resistance evaluation. Results The 54 mutations analyzed were distributed among the targets: PI (27.8%; 15/54), NRTI (24.1%; 13/54), NNRTI (22.2%; 12/54), and INSTI (25.9%; 14/54). The in-house method evaluated the susceptibility to PI drugs (ATV, DRV, FPV, IDV, LPV, NFV, SQV, and TPV), NRTI (ABC, AZT, D4T, DDI, FTC, 3TC, and TDF), and NNRTI (DOR, EFV, ETR, NVP, and RPV). In addition to protease and reverse transcriptase targets, the commercial kit also evaluated INSTI (BIC, CAB, DTG, EVG, and RAL) drugs. Four of 20 individuals evaluated had viral loads below 1000 copies/mL and have no results in both methods, as expected due to the detection limit of both assays. Furthermore, due to sequencing limitations using the in-house methodology, three samples were not included in the analysis as it didn't show any results. It was observed 92.3% agreement (n = 12/13) in the analyzed samples. A sensitivity of 100% and precision of 99% were found in the commercial kit using the in-house kit as a reference. The evaluation of the intra-assay (repeatability) and inter-assay (reproducibility) indicated 100% of agreement. Conclusions The Applied Biosystems HIV-1 Genotyping Kit with Integrase showed satisfactory performance in the detection of the main antiretroviral resistance mutations.

İşitme Engelli Öğrencilerle Çalışan Öğretmenlerin Mesleki Yeterliliklerine Yönelik Görüşlerinin Değerlendirilmesi

Introduction: Special education policy is based upon integration in Türkiye. Hence, the professional competencies of teachers working with hearing-impaired students in the field of hearing impairments have a prominent role in this policy. This study aims to identify the teacher needs for the teacher competency training program in hearing impairments to be developed for teachers of hearing-impaired students. Method: Qualitative research design was adopted in this study, and the data were collected by semi-structured interview on the professional knowledge and skills teachers need while teaching hearing-impaired students at different levels (primary, secondary, and high school) in the central districts of Sakarya. The data were analyzed by content analysis. Findings: Through the data, the main themes of knowledge about the hearing impaired, communication models and hearing aids, teaching methods and techniques, and academic and professional skills were unfolded. Discussion: In the literature, there are many studies that reveal the necessity and importance of needs analysis in studies to determine and develop teacher competencies and research results that are consistent with the findings of this study. Conclusion and Suggestions: As a result of this research, what teachers with hearing-impaired students state about the education of hearing impaired are as follows: Definitions, classification and developmental characteristics of hearing-impaired children, diagnosis and evaluation processes, educational approaches and program adaptation, individualized education program (IEP) development and implementation, material preparation and educational environments using technology, communication models, hearing aids and assistive technologies, environment adaptation and effective classroom management. In addition, it was found that teachers neither have sufficient knowledge about family education nor find themselves sufficient in issues regarding hearing-impaired students, so they wanted to receive training. Based on the study results, suggestions, such as supporting teachers with pre-service and in-service training and providing them with expert support, were made.

Neuromuscular Electrical Stimulation for Intermittent Claudication (NESIC): multicentre, randomized controlled trial.

This was an open, multicentre, randomized controlled trial. Patients with intermittent claudication attending vascular surgery outpatient clinics were randomized (1:1) to receive either neuromuscular electrical stimulation (NMES) or not in addition to local standard care available at study centres (best medical therapy alone or plus supervised exercise therapy (SET)). The objective of this trial was to investigate the clinical efficacy of an NMES device in addition to local standard care in improving walking distances in patients with claudication. The primary outcome was change in absolute walking distance, measured by a standardized treadmill test at 3 months. Secondary outcomes included intermittent claudication (IC) distance, adherence, quality of life, and haemodynamic changes. Of 200 participants randomized, 160 were included in the primary analysis (intention to treat, Tobit regression model). The square root of absolute walking distance was analysed (due to a right-skewed distribution) and, although adjunctive NMES improved it at 3 months, no statistically significant effect was observed. SET as local standard care seemed to improve distance compared to best medical therapy at 3 months (3.29 units; 95 per cent c.i., 1.77 to 4.82; P < 0.001). Adjunctive NMES improved distance in mild claudication (2.88 units; 95 per cent c.i., 0.51 to 5.25; P = 0.02) compared to local standard care at 3 months. No serious adverse events relating to the device were reported. Supervised exercise therapy is effective and NMES may provide further benefit in mild IC.This trial was supported by a grant from the Efficacy and Mechanism Evaluation Program, a Medical Research Council and National Institute for Health and Care Research partnership. Trial registration: ISRCTN18242823.

Enhancing the Standardized Field Sobriety Test to detect cannabis impairment: An observational study

Objective The purpose of this study was to explore various tests of impairment that could potentially be added to the Standardized Field Sobriety Test (SFST) to enhance its sensitivity to identify drivers whose abilities are adversely affected by cannabis. Methods An observational study was conducted in which participants were invited to use their own cannabis at the research facility. Once prior to cannabis use and at four times during the 150 min after cannabis use, participants performed the three tests of the Standardized Field Sobriety Test (SFST) (i.e., Horizontal Gaze Nystagmus, Walk and Turn, and One Leg Stand) as well as the Modified Romberg Balance and Finger to Nose tests. In addition, assessments were made of physiological indicators (i.e., eyelid, leg and body tremors, rebound dilation, lack of convergence) and vital signs (pulse, blood pressure and body temperature). Participants also completed a digit-symbol substitution task at each testing interval. With the exception of vital signs and the digit symbol task, all tests and assessments were administered and scored by certified Drug Recognition Experts using the standard procedures of the Drug Evaluation and Classification Program. Results Twenty minutes after vaping cannabis (mean THC concentration = 6.34 ng/mL), participants displayed performance deficits on a variety of tasks; 67% met the criterion for suspected impairment on the SFST. Addition of the Finger-to-Nose (FTN) test along with observations of head movements and jerks (HMJ) increased the percentage of participants who met the criterion for suspected impairment by 33% and improved the sensitivity of the test from 0.67 to 0.88. Conclusions The results of this study support supplementing the SFST with the Finger-to-Nose test and observations of HMJ to assist in the detection of drivers who are adversely affected by the use of cannabis. The observational study design and the use of assessors who were not blinded as to the use of cannabis by participants limits the strength of the evidence. Further research, including randomized trials and field studies of drivers, is required to confirm and validate this enhanced version of the SFST.

Onasemnogene Abeparvovec for Treating Pre-symptomatic Spinal Muscular Atrophy: An External Assessment Group Perspective of the Partial Review of NICE Highly Specialised Technology Evaluation 15.

As part of the National Institute for Health and Care Excellence (NICE) highly specialised technology (HST) evaluation programme, Novartis submitted evidence to support the use of onasemnogene abeparvovec as a treatment option for patients with pre-symptomatic 5q spinal muscular atrophy (SMA) with a bi-allelic mutation in the survival of motor neuron (SMN) 1 gene and up to three copies of the SMN2 gene. The Liverpool Reviews and Implementation Group at the University of Liverpool was commissioned to act as the External Assessment Group (EAG). This article summarises the EAG's review of the evidence submitted by the company and provides an overview of the NICE Evaluation Committee's final decision, published in April 2023. The primary source of evidence for this evaluation was the SPR1NT trial, a single-arm trial including 29 babies. The EAG and committee considered that the SPR1NT trial results suggested that onasemnogene abeparvovec is effective in treating pre-symptomatic SMA; however, long-term efficacy data were unavailable and efficacy in babies aged over 6 weeks remained uncertain. Cost-effectiveness analyses conducted by the company and the EAG (using a discounted price for onasemnogene abeparvovec) explored various assumptions; all analyses generated incremental cost-effectiveness ratios (ICERs) that were less than £100,000 per quality-adjusted life-year (QALY) gained. The committee recommended onasemnogene abeparvovec as an option for treating pre-symptomatic 5q SMA with a bi-allelic mutation in the SMN1 gene and up to three copies of the SMN2 gene in babies aged ≤12 months only if the company provides it according to the commercial arrangement (i.e. simple discount patient access scheme).