Subject Recruitment Research Articles

Comparison of Histopathology (Incisional Biopsy) Vs Fine Needle Aspiration Cytology in Diagnosing Tuberculous Cervical Lymphadenopathy

Objectives: To evaluate and compare the sensitivity and specificity between Fine Needle Aspiration Cytology (FNAC) and histopathology of incisional biopsy in diagnosing blood culture positive tuberculous lymphadenopathy (LAD). Methods: : This descriptive study was conducted in the Department of Pathology at Jinnah Teaching Hospital (JTH) Peshawar from January 2021 to August 2022. The study samples included were collected from thepatients at tertiary care Hospitals who were acid fast bacillus(AFB) positive and blood culture positive. The culture and sensitivity and Zn staining was carried out at JTH Peshawar. Seventy subjects with AFB and culture positive with high clinical suspicion of tuberculous LAD were included in the study. After the recruitment of subjects according to the inclusion criteria, subjects underwent FNAC followed by incisional biopsy for histopathology carried out at JTH Peshawar. Subjects’ blood was checked and screened for Hepatitis B and C, TLC, DLC and ESR at Microbiology and Haematology laboratories of JTH Peshawar respectively. The data was then organised and analysed in SPSS software version. 26. Results: Out of the seventy subjects included in the study, 30 were males while 40 were females. Subjects had a mean age of 33.5 years. The sensitivity of FNAC was 89%, however the Specificity came out to be 59%. Conclusion: Our study obviates the use of FNAC as a good screening test however due to the low specificity or in cases where there is a high clinical suspicion of TB, the results need to be confirmed by Incisional biopsy for histopathology. However, further studies are required for not only understanding the medical condition.

Trends in Israeli clinical trials registration “MyTrial”

BackgroundClinical trial registration is critical for research transparency and integrity. Since 2005, the Declaration of Helsinki has required prospective registration of trials before subject recruitment. In Israel, the MyTrial registry was established in 2015 to register interventional trials and became mandatory in 2016 for ethical approval. The study aimed to analyze the registration practices, challenges, and trends in clinical trial registration in Israel using the local registry “MyTrial”.MethodsA total of 3,895 clinical trial records from 2011 to December 2022 were retrieved from the MyTrial platform and subjected to descriptive analysis.ResultsA significant increase occurred from 2016 to 2021 due to mandated registration, with a peak in 2020 (733 trials) and a decrease in 2022 (462 trials), likely due to COVID-19. Most of the trials included drugs (56%) or medical devices (33%). Geographically, 53% were from central Israel. Only 39% of the patients were registered at both MyTrial and ClinicalTrials.gov. 65% had no blinding. 47% featured unregistered products. 56% had not started recruitment. Since 2016, the number of advanced therapy trials has steadily increased, reaching 19 in 2022. There are gaps between registered trials and official government reports.ConclusionThese findings provide valuable insights into the current landscape of clinical trial registration in Israel and highlight the need for improvements in compliance with prospective registration and adherence to the WHO-ICTRP standards.

An SMS-Guided Basal Insulin Titration in People with Type 2 Diabetes New on Insulin.

The shortage of general practitioners (GPs) and the increasing prevalence of type 2 diabetes create significant pressure on primary healthcare services. To enable that medical services are available to allthat need it, innovative solutions are needed. One of those, a Short Message Service (SMS)-supported basal insulin titration service is investigated in this study. The primary objective was to determine the percentage of subjects who achieved stable fasting blood glucose (FBG) within their individual target range with this service after week 16. This single-arm, 16-week study aimed to enroll 111 adults diagnosed with type 2 diabetes that needed insulin. The study subjects measured their FBG 4 consecutive days to establish a baseline, then received SMS prompts for daily FBG measurements and evening insulin injections until their FBG stabilized within the target range. Adjusting the insulin based on the FBG. Once stabilization was achieved, subjects continued with their optimal insulin dose for the remainder of the study. Sixteen weeks after the baseline, subjects measured FBG for 4days before visit 4, where these values were read by the healthcare provider. Out of the planned 111 subjects, only 30 were enrolled, with one withdrawal prior to service activation. Challenges in subject recruitment were attributed to the COVID-19 outbreak, limited eligibility, competing studies, and new medications delaying insulin initiation. Subjects were on average 59.97years old, had an HbA1c of 9.29% a FBG of 205.64mg/dl, and had diabetes for 10years. Among the 29 subjects who started the service, 72% achieved successful titration at visit 4, with a median time of 49days. Notable improvements were observed in HbA1c levels (decreased by 1.58%) and FBG levels (decreased by 64mg/dl) over the 16-week study period. No adverse events or device-related issues were reported. Despite recruitment challenges, guided basal insulin titration holds promise for insulin therapy initiation in individuals. The findings emphasize the potential of tele-medical approaches, specifically through remote messaging, in managing diabetes and improving therapy adherence.

A non-parametric approach to predict the recruitment for randomized clinical trials: an example in elderly inpatient settings

BackgroundAccurate prediction of subject recruitment, which is critical to the success of a study, remains an ongoing challenge. Previous prediction models often rely on parametric assumptions which are not always met or may be difficult to implement. We aim to develop a novel method that is less sensitive to model assumptions and relatively easy to implement.MethodsWe create a weighted resampling-based approach to predict enrollment in year two based on recruitment data from year one of the completed GRIPS and PACE clinical trials. Different weight functions accounted for a range of potential enrollment trajectory patterns. Prediction accuracy was measured by Euclidean distance for enrollment sequence in year two, total enrollment over time, and total weeks to enroll a fixed number of subjects, against the actual year two enrollment data. We compare the performance of the proposed method with an existing Bayesian method.ResultsWeighted resampling using GRIPS data resulted in closer prediction evidenced by better coverage of observed enrollment with the prediction intervals and smaller Euclidean distance from actual enrollment in year 2, especially when enrollment gaps were filled prior to the weighted resampling. These scenarios also produced more accurate predictions for total enrollment and number of weeks to enroll 50 participants. These same scenarios outperformed an existing Bayesian method for all 3 accuracy measures. In PACE data, using a reduced year 1 enrollment resulted in closer prediction evidenced by better coverage of observed enrollment with the prediction intervals and smaller Euclidean distance from actual enrollment in year 2, with the weighted resampling scenarios better reflecting the seasonal variation seen in year (1) The reduced enrollment scenarios resulted in closer prediction for total enrollment over 6 and 12 months into year (2) These same scenarios also outperformed an existing Bayesian method for relevant accuracy measures.ConclusionThe results demonstrate the feasibility and flexibility for a resampling-based, non-parametric approach for prediction of clinical trial recruitment with limited early enrollment data. Application to a wider setting and long-term prediction accuracy require further investigation.

Acute Sympathetic Blockade Improves Insulin-Mediated Microvascular Blood Flow in the Forearm of Adult Human Subjects With Obesity.

Obesity is associated with resistance to the metabolic (glucose uptake) and vascular (nitric-oxide mediated dilation and microvascular recruitment) actions of insulin. These vascular effects contribute to insulin sensitivity by increasing tissue delivery of glucose. Studies by us and others suggest that sympathetic activation contributes to insulin resistance to glucose uptake. Here we tested the hypothesis that sympathetic activation contributes to impaired insulin-mediated vasodilation in adult subjects with obesity. In a randomized crossover study, we used a euglycemic hyperinsulinemic clamp in 12 subjects with obesity to induce forearm arterial vasodilation (forearm blood flow) and microvascular recruitment (contrast-enhanced ultrasonography) during an intrabrachial infusion of saline (control) or phentolamine (sympathetic blockade). Insulin increased forearm blood flow on both study days (from 2.21±1.22 to 4.89±4.21 mL/100 mL per min, P=0.003 and from 2.42±0.89 to 7.19±3.35 mL/100 mL per min, P=0.002 for the intact and blocked day, respectively). Sympathetic blockade with phentolamine resulted in a significantly greater increase in microvascular flow velocity (∆microvascular flow velocity: 0.23±0.65 versus 2.51±3.01 arbitrary intensity units (AIU/s) for saline and phentolamine respectively, P=0.005), microvascular blood volume (∆microvascular blood volume: 1.69±2.45 versus 3.76±2.93 AIU, respectively, P=0.05), and microvascular blood flow (∆microvascular blood flow: 0.28±0.653 versus 2.51±3.01 AIU2/s, respectively, P=0.0161). To evaluate if this effect was not due to nonspecific vasodilation, we replicated the study in 6 subjects with obesity comparing intrabrachial infusion of phentolamine to sodium nitroprusside. At doses that produced similar increases in forearm blood flow, insulin-induced changes in microvascular flow velocity were greater during phentolamine than sodium nitroprusside (%microvascular flow velocity=58% versus 29%, respectively, P=0.031). We conclude that sympathetic activation impairs insulin-mediated microvascular recruitment in adult subjects with obesity.

Investigation of bias in the automated assessment of school violence

ObjectivesNatural language processing and machine learning have the potential to lead to biased predictions. We designed a novel Automated RIsk Assessment (ARIA) machine learning algorithm that assesses risk of violence and aggression in adolescents using natural language processing of transcribed student interviews. This work evaluated the possible sources of bias in the study design and the algorithm, tested how much of a prediction was explained by demographic covariates, and investigated the misclassifications based on demographic variables. MethodsWe recruited students 10–18 years of age and enrolled in middle or high schools in Ohio, Kentucky, Indiana, and Tennessee. The reference standard outcome was determined by a forensic psychiatrist as either a “high” or “low” risk level. ARIA used L2-regularized logistic regression to predict a risk level for each student using contextual and semantic features. We conducted three analyses: a PROBAST analysis of risk in study design; analysis of demographic variables as covariates; and a prediction analysis. Covariates were included in the linear regression analyses and comprised of race, sex, ethnicity, household education, annual household income, age at the time of visit, and utilization of public assistance. ResultsWe recruited 412 students from 204 schools. ARIA performed with an AUC of 0.92, sensitivity of 71%, NPV of 77%, and specificity of 95%. Of these, 387 students with complete demographic information were included in the analysis. Individual linear regressions resulted in a coefficient of determination less than 0.08 across all demographic variables. When using all demographic variables to predict ARIA’s risk assessment score, the multiple linear regression model resulted in a coefficient of determination of 0.189. ARIA performed with a lower False Negative Rate (FNR) of 15.2% (CI [0 – 40]) for the Black subgroup and 12.7%, CI [0 – 41.4] for Other races, compared to an FNR of 26.1% (CI [14.1 – 41.8]) in the White subgroup. ConclusionsBias assessment is needed to address shortcomings within machine learning. In our work, student race, ethnicity, sex, use of public assistance, and annual household income did not explain ARIA’s risk assessment score of students. ARIA will continue to be evaluated regularly with increased subject recruitment.

An investigation of the association between parenting style and child’s dental caries: a cross-sectional study

To investigate the association between parenting style and child’s dental caries. Parents presenting with their children to the Department of Pediatric Dentistry at Tufts University School of Dental Medicine for an initial exam or re-care appointment completed a demographic survey and the parenting styles and dimensions questionnaire. Recruitment of subjects started in May 2019 and ended in February of 2020. Child’s decayed, missing, and filled teeth (dmft) index, diet score, sex, and age were recorded, as were parent’s race, education level, and form of payment. Adjustment for confounders was done using multivariable negative binomial regression. The sample size was 210 parent/child dyads. In the multivariable analysis, parenting style and child’s dmft were not significantly associated (p > 0.05). Parents with an education level less than high school (p = 0.02) and at the high school graduate level (p = 0.008) were significantly associated with children who had higher dmft, compared to parents with a college degree or higher. Children with excellent diet scores had significantly lower dmft than children with a diet score in the “needs improvement” category (p = 0.003). There was no significant evidence that parenting style is associated with child’s dental caries. Parent’s education level and child’s diet score were significantly associated with child’s dmft, less than high school (p = 0.02) and at the level of high school graduate (p = 0.008). Pediatric dental professionals should be aware of these risk indicators.

Community-engaged artificial intelligence research: A scoping review.

The degree to which artificial intelligence healthcare research is informed by data and stakeholders from community settings has not been previously described. As communities are the principal location of healthcare delivery, engaging them could represent an important opportunity to improve scientific quality. This scoping review systematically maps what is known and unknown about community-engaged artificial intelligence research and identifies opportunities to optimize the generalizability of these applications through involvement of community stakeholders and data throughout model development, validation, and implementation. Embase, PubMed, and MEDLINE databases were searched for articles describing artificial intelligence or machine learning healthcare applications with community involvement in model development, validation, or implementation. Model architecture and performance, the nature of community engagement, and barriers or facilitators to community engagement were reported according to PRISMA extension for Scoping Reviews guidelines. Of approximately 10,880 articles describing artificial intelligence healthcare applications, 21 (0.2%) described community involvement. All articles derived data from community settings, most commonly by leveraging existing datasets and sources that included community subjects, and often bolstered by internet-based data acquisition and subject recruitment. Only one article described inclusion of community stakeholders in designing an application-a natural language processing model that detected cases of likely child abuse with 90% accuracy using harmonized electronic health record notes from both hospital and community practice settings. The primary barrier to including community-derived data was small sample sizes, which may have affected 11 of the 21 studies (53%), introducing substantial risk for overfitting that threatens generalizability. Community engagement in artificial intelligence healthcare application development, validation, or implementation is rare. As healthcare delivery occurs primarily in community settings, investigators should consider engaging community stakeholders in user-centered design, usability, and clinical implementation studies to optimize generalizability.

Coerced consent in clinical research: study protocol for a randomized controlled trial

BackgroundDespite the low-risk nature of participation in most clinical anesthesia trials, subject recruitment on the same day as surgery is often restricted due to the concerns of researchers and local research ethics boards that same-day consent may not afford adequate time and opportunity for patients to weigh and make decisions, as well as perceptions of patient vulnerability immediately prior to surgery that could impact the voluntary nature and the rigor of the informed consent process. However, specialties such as anesthesiology, critical care, interventional radiology, and emergency medicine have a varied pattern of practice and patient acquaintance that does not typically afford the luxury of time or, in many cases, advance consent for participation in research. Indeed, the initial encounter between anesthesiologists and patients undergoing elective procedures routinely occurs on the day of surgery. Concerns of coercion related to same-day consent for clinical anesthesia research trials have not been borne out in the literature, and represent a significant obstacle to clinical researchers, as well as to the patients who are denied opportunities for potential benefit through participation in research studies.MethodsWe describe the protocol for a prospective randomized controlled trial examining the voluntariness of patient consent, solicited either in advance of surgery or on the same day, to participate in an anesthesia research study at Women’s College Hospital. One hundred fourteen patients scheduled to undergo ambulatory anterior cruciate ligament repair facilitated by general anesthesia with an adductor canal block will be randomized for recruitment either (a) in the pre-operative assessment clinic before the day of surgery or (b) on the day of surgery, to be approached for consent to participate in a fabricated research study of adjunct medications in adductor canal blocks. Regardless of allocation, patients in both groups will receive the same routine standard of care and will complete a post-operative questionnaire to signal perceptions of undue influence in the process of providing informed consent for the fabricated trial.DiscussionThis study will inform trial design and practice guidelines surrounding the amount of time patients ought to be afforded in order to make durable decisions to participate (or not) in clinical research studies. This is expected to impact trial recruitment in a variety of clinical settings where researchers have only brief opportunities to interface with patients.Trial registrationThe trial was registered prospectively on the Open Science Framework (OSF), registration #46twc, on 2023-Mar-17.

A randomized trial of collaborative support for opioid taper after trauma hospitalization

The COTAT (Collaborative Opioid Taper After Trauma) Study was a randomized trial of an opioid taper support program using a physician assistant (PA) to provide pain and opioid treatment guidance to primary care providers assuming care for adult patients with moderate to severe trauma discharged from a Level I trauma center on opioid therapy. Patients were recruited, assessed, and randomized individually by a surgery research recruitment team one to two days prior to discharge to home. Participants randomized to the opioid taper support program were contacted by phone within a few days of discharge by the PA interventionist to confirm enrollment and their primary care provider (PCP). The intervention consisted of PA support as needed to the PCP concerning pain and opioid care at weeks 1, 2, 4, 8, 12, 16, and 20 after discharge or until the PCP office indicated they no longer needed support or the patient had tapered off opioids. The PA was supervised by a pain physician-psychiatrist, a family physician, and a trauma surgeon. Patients randomized to usual care received standard hospital discharge instructions and written information on managing opioid medications after discharge. Trial results were analyzed using repeated measures analysis. 37 participants were randomized to the intervention and 36 were randomized to usual care. The primary outcomes of the trial were pain, enjoyment, general activity (PEG score) and mean daily opioid dose at 3 and 6 months after hospital discharge. Treatment was unblinded but assessment was blinded. No significant differences in PEG or opioid outcomes were noted at either time point. Physical function at 3 and 6 months and pain interference at 6 months were significantly better in the usual care group. No significant harms of the intervention were noted. COVID-19 (corona virus 2019) limited recruitment of high-risk opioid tolerant subjects, and limited contact between the PA interventionist and the participants and the PCPs. Our opioid taper support program failed to improve opioid and pain outcomes, since both control and intervention groups tapered opioids and improved PEG scores after discharge. Future trials of post-trauma opioid taper support with populations at higher risk of persistent opioid use are needed. This trial is registered at clinicaltrials.gov under NCT04275258 19/02/2020. This trial was funded by a grant from the Centers for Disease Control and Prevention to the University of Washington Harborview Injury Prevention & Research Center (R49 CE003087, PI: Monica S. Vavilala, MD). The funder had no role in the analysis or interpretation of the data.

A Vector Theory of Assessing Clinical Trials: An Application to Bioequivalence.

A novel idea is introduced regarding the statistical comparisons of endpoints in clinical trials. Currently, the (dis)similarity of measured endpoints is not assessed. Instead, statistical analysis is directly applied, which can lead to multiplicity issues, reduced statistical power, and the recruitment of more subjects. The Vector-Based Comparison (VBC) approach originates from vector algebra and considers clinical endpoints as "vectors". In the general case of N clinical endpoints, a Cartesian coordinate system is defined, and the most important primary endpoint (E1) is set. Following an explicitly defined procedure, the pairwise relationships of the remaining N-1 endpoints with E1 are estimated, and the N-1 endpoints are decomposed into axes perpendicular to E1. The angle between vectors provides insight into the level of dependency between variables. Vectors that are perpendicular to each other are considered independent, and only these are used in the statistical analysis. In this work, VBC is applied to bioequivalence studies of three anti-hypertensive drugs: amlodipine, irbesartan, and hydrochlorothiazide. The results suggest that VBC is a reproducible, easily applicable method allowing for the discrimination and utilization of the endpoint component expressing different attributes. All clinical characteristics are assessed with increased statistical power, without inflation of type I error.

If you build it, they will come: Success of the EROS (Engendering Reproductive Health Within Oncologic Survivorship)—ECOG-ACRIN E1Q11 in recruitment of minority patients.

11124 Background: The average recruitment of minority subjects in oncology trials is 4%. The ECOG-ACRIN EROS trial was designed to be inclusive of minority subjects by inviting Minority/Underserved NCI Community Oncology Research Program (MU-NCORP) sites first, with remaining sites fulfilled by inviting NCORP sites. Our objective is to examine if the EROS study recruited more than 4% minority patients, and if MU-NCORP sites provided higher rates of minority recruitment than NCORP sites. Methods: The EROS trial is a clustered randomized trial performed at 17 NCI Community Oncology Research Program (NCORP) sites (including 8 NCORP sites and 9 Minority/Underserved NCORP sites) from 2016-2023. Eligible subjects included reproductively capable women aged 15-55 with new cancer diagnosis. Intervention included RH didactics and decision aids. With respect to self-reported minority status, patients were classified into one of two categories, White and non-Hispanic/Latino or minority (non-White or Hispanic/Latino). Chi-square tests were used to evaluate distribution difference between groups and binomial tests were used for testing proportions against reference points. Results: Of the 434 patients enrolled to the trial, MU-NCORP sites recruited 266/434 (61.3%) and NCORP sites 168/434 (38.7%) patients. Among all enrolled patients, 422 patients’ race/ethnicity status could be classified. 202/422 (47.9%) self-reported as Hispanic/Latino or non-White (p<.0001 0.48 against 0.04). In MU-NCORP (174/258) 67.4% and NCORP sites (28/164) 17.1% were of minority status. (p < .0001). Conclusions: The EROS trial was designed with minority inclusion for generalizability of results. Prioritization to include MU-NCORP sites in the EROS trial did result in substantially increased minority recruitment, with the overall minority recruitment rate above usual cancer trials. Such strategy may be followed to increase minority recruitment to oncology trials.

Sustainable consumption from a domestic food purchasing perspective among Generation Z

The relevance of the study is the global consumer trend towards sustainability. Sustainable consumption has positive environmental, social, and economic impacts, which makes it a key issue in the context of food consumption. Preference for regional, and domestic products can significantly support sustainable consumption. The study focused on the demographically and economically important Generation Z from the perspective of sustainable consumption. The main research objective of the study is to analyze the Hungarian food purchasing habits of Generation Z and to segment Generation Z according to the Hungarian food consumption criteria to characterize potential target groups. During the research, qualitative and quantitative data collection was carried out. The study focuses on the presentation of the results of the latter. In the quantitative survey, we conducted a pre-tested standardized questionnaire online survey. Subject recruitment was carried out using a snowball sampling method, resulting in 518 evaluable questionnaires. In a quantitative study, distinct segments of Hungarian food consumers were characterized according to their food consumption preferences. The research also demonstrated that the groups of Generation Z according to Hungarian food consumption preferences differ significantly from each other in terms of their perception of Hungarian food. The research concludes that Generation Z is a group of domestic food consumers with specific characteristics, who could be the main base for sustainable consumption. For those who have not yet developed this motivation, the main reasons are an unsophisticated preference system and a lack of education. Systematic marketing activities aimed at the first component of attitudes are therefore most needed to attract these segments.

Lung Volume and Ventilation Distribution After Bariatric Surgery: High-Flow Nasal Cannula Versus CPAP.

Patients with obesity are at increased risk of postoperative pulmonary complications. CPAP has been used successfully to prevent and treat acute respiratory failure, but in many clinical scenarios, high-flow nasal cannula (HFNC) therapy is emerging as a possible alternative. We aimed to compare HFNC and CPAP in a sequential study measuring their effects on gas exchange, lung volumes, and gas distribution within the lungs measured through electrical impedance tomography (EIT). We enrolled 15 subjects undergoing laparoscopic bariatric surgery. Postoperatively they underwent the following oxygen therapy protocol (10 min/step): baseline air-entrainment mask, HFNC at increasing (40, 60, 80, and 100 L/min) and decreasing flows (80, 60, and 40 L/min), washout air-entrainment mask and CPAP (10 cm H2O). Primary outcome was the change in end-expiratory lung impedance (ΔEELI) measured by EIT data processing. Secondary outcomes were changes of global inhomogeneity (GI) index and tidal impedance variation (TIV) measured by EIT, arterial oxygenation, carbon dioxide content, pH, respiratory frequency, and subject's comfort. Thirteen subjects completed the study. Compared to baseline, ΔEELI was higher during 10 cm H2O CPAP (P = .001) and HFNC 100 L/min (P = .02), as well as during decreasing flows HFNC 80, 60, and 40 L/min (P = .008, .004, and .02, respectively). GI index was lower during HFNC 100 compared to HFNC 60increasing (P = .044), HFNC 60decreasing (P = .02) HFNC 40decreasing (P = .01), and during 10 cm H2O CPAP compared to washout period (P = .01) and HFNC 40decreasing (P = .03). TIV was higher during 10 cm H2O CPAP compared to baseline (P = .008). Compared to baseline, breathing frequency was lower at HFNC 60increasing, HFNC 100, and HFNC 80decreasing (P = .01, .02, and .03, respectively). No differences were detected regarding arterial oxygenation, carbon dioxide content, pH, and subject's comfort. HFNC at a flow of 100 L/min induced postoperative pulmonary recruitment in bariatric subjects, with no significant differences compared to 10 cm H2O CPAP in terms of lung recruitment and ventilation distribution.

Use of a Trial Innovation Network (TIN) Recruitment Innovation Center (RIC) Survey to Improve Subject Recruitment and Enrollment in an Adolescent Concussion Study: CARE4Kids (P2-14.004)

Use of a Trial Innovation Network (TIN) Recruitment Innovation Center (RIC) Survey to Improve Subject Recruitment and Enrollment in an Adolescent Concussion Study: CARE4Kids (P2-14.004)

Promoting post-traumatic growth in cancer patients: a randomized controlled trial of guided written disclosure.

BackgroundCancer is a life-threatening disease that triggers not only vulnerability to distressing symptoms but also a meaning-making process that may lead to post-traumatic growth. As people often struggle to integrate cancer illness into their meaning system to reach an adaptive meaning, psychological interventions focused on a reappraisal of the illness experience can facilitate this process. This multicenter randomized controlled trial (RCT) was primarily aimed at assessing the efficacy of a writing intervention known as a guided disclosure protocol (GDP), compared to a generic writing intervention, in promoting post-traumatic growth in stage I-III breast and colon cancer patients at the end of their adjuvant chemotherapy.MethodsBetween January 2016 and August 2020 recruitment of eligible subjects took place during follow-up clinical consultations. Assessment occurred at baseline (T0), after the intervention (T1, 3 months from baseline), and at 6 months from baseline (T2). Both interventions consisted of three 20-min writing sessions to be performed once every two weeks. Change in post-traumatic growth was assessed using the Posttraumatic Growth Inventory, meaning with the Constructed Meaning Scale, and psychological distress with the Impact of Event Scale and the Hospital Anxiety and Depression Scale.ResultsIn the five participating centers, 102 eligible patients were randomized and 72 participants completed follow-up evaluation. Most patients were women (79.4%), had breast cancer (68.6%), and stage I (27.5%), or stage II (44.1%) disease. Mean differences did not reach statistical significance for any of the dependent variables. However, an effect of the GDP, although not statistically relevant, was observed after the intervention in terms of enhanced post-traumatic growth and increased distress measured with the Impact of Event Scale.ConclusionThis is the first RCT investigating the efficacy of a GDP in cancer patients having post-traumatic growth as the primary aim. Though GDP is a promising intervention in promoting post-traumatic growth, the lack of statistical significance of our findings may be due to the study being underpowered, hence this trial should be replicated with an adequate sample size, paying attention to supporting recruitment.Clinical trial registration: ClinicalTrials.gov, identifier: 2015/0024360.

Protocol for the "magnitude of cigarette substitution after initiation of e-cigarettes and its impact on biomarkers of exposure and potential harm in dual users" (MAGNIFICAT) study.

Many smokers who use e-cigarettes (ECs) to quit continue smoking alongside vaping. The impact on health among individuals who simultaneously smoke conventional cigarettes (CCs) and use ECs remains unclear. The varying patterns of dual use present differing levels of overall toxin exposure and relative risks concerning smoking-related diseases. Understanding these complexities is vital to assessing the implications for human health. Herein we describe a protocol designed to analyze the impact of different level of substituting CCs with ECs on exposure to toxicants. We'll use biomarkers to measure this exposure and assess harm reduction in dual users through clinical endpoints, harm-related biomarkers, and behavioral correlations. We expect to observe progressive changes with varying patterns of dual use. For this purpose, we planned to recruit a group of 250 smokers who will be asked to reduce their CC consumption by adopting ECs (intervention group). A separate group of 50 smokers will continue to smoke CC (reference group). Study groups will be followed up for 6 months during which biospecimens will be collected for biomarker analyses, and clinical endpoints will be assessed. The trial is structured to characterize subjects' usage patterns over time using robust biomarkers of exposure and a standardized mobile phone application to facilitate the precise categorization of dual users along the risk continuum based on their usage behaviors. Subject recruitment will start in February 2024 and enrolment is expected to be completed by August 2024. Results will be reported early in 2025. Study findings may provide valuable insights into health benefits or risks associated with varying patterns of dual use. The study protocol and informed consent forms will be approved by the local Ethical Review Boards. Study results will be disseminated through articles published in reputable, peer-reviewed, open access, scientific journals, presentations at conferences, and the University website.

The Effect of Initial Anti-tuberculosis Drug Therapy on Transminase Enzymes

Tuberculosis is still a health problem in the world. TB treatment is carried out in 2 phases, namely early and advanced. This study aims to determine changes in serum transaminase enzyme levels (SGOT and SGPT) in pulmonary TB patients before and after initial drug administration. This study was observational with a cohort study design study. Observations were conducted in tuberculosis patients who received initial ATD therapy for 2 months for SGOT and SGPT enzyme levels before and after treatment. The subject of the study was a new case of a pulmonary TB patient aged ?16 years. Subjects received initial therapy in the form of isoniazid, rifampicin, pyrazinamide, and ethambutol. Recruitment of subjects through successive sampling methods with informed consent. Using a spectrophotometer, SGOT and SGPT enzyme tests were performed on the median blood serum cubital vein. Data analysis using the Wilcoxon Test. The study involved 19 subjects (10 men and 9 women) aged 16-65 years. Before ATD, the mean SGOT was 22.84 IU/L, and SGPT was 21.37 IU/L. After ATD, SGOT increased to 58.63 IU/L (p = 0.023), and SGPT to 80.84 IU/L (p = 0.007). Of the 19 subjects, 8 experienced a significant increase in SGOT and 5 SGPT. Five cases showed an increase in SGPT in line with SGOT, and 3 cases showed an increase in SGOT without SGPT. One case saw an increase in SGOT and SGPT of more than 5 times the reference value. This study confirms an increase in transaminase enzymes during initial therapy with first-line ATD.

Re: "A Novel Randomized Trial Protocol for Evaluating Wound Healing Interventions" by Bull et al.

This response critically evaluates the study "A Novel Randomized Trial Protocol for Evaluating Wound Healing Interventions," highlighting key concerns and proposing improvements. The study's departure from standard analytical principles, characterized by inadequate power and a lack of cohort comparisons, raises questions about the reliability of its conclusions. Rigorous adherence to established randomized controlled trial methodologies is crucial for valid evidence in wound healing research. Additionally, the inclusion of a run-in phase presents challenges in subject recruitment, resulting in a significant loss of eligible participants. Streamlining study designs to minimize such barriers is imperative for ensuring feasibility and achieving sufficient statistical power. The use of a laser-assisted wound measurement (LAWM) device, though validated for area measurement, overlooks wound depth, introducing potential bias. This limitation underscores the need for meticulous consideration of measurement tools to ensure comprehensive and accurate data collection. The study's proposed outcome protocol neglects crucial wound healing parameters like wound bed quality and tunnelling/undermining. Advocating for customized scoring systems based on wound etiology could address these oversights, enhancing the study's clinical relevance. This critical response emphasizes the importance of methodological rigor and comprehensive outcome assessments in advancing wound healing research. Addressing these concerns will contribute to a more robust evidence base, fostering improved translational outcomes in wound healing interventions. On behalf of Bull et al, Harding & Clements categorically respond to the concerns raised.

Genesis of Clinical Trial Failure: A Review

Clinical Trials are often labelled as failure or negative when the anticipated results are not observed. The negative results can be due to multiple factors such as primary and secondary endpoints not being met higher incidence of adverse reactions, and sluggish recruitment of trial subjects due to stringent inclusion and exclusion criteria, higher dropout rates due to changed biochemical parameters such as raised liver or hepatic enzymes. Trial Failures are reported globally but within developing countries, the reports are meagre. Inclusion in trials imposes a financial burden on patients and hence dropout rates proportionately increase. Recruitment of patients is often better in open trials as compared to blind studies as drug awareness imposes better confidence in the recruited subjects. The oncology trials that use biomarkers in patient selection have higher overall success probabilities than trials without biomarkers. Complexities in drug development and the inherent uncertainties in medical research also play an important role in a high rate of clinical trial failures.