Trials Databases Research Articles

Development of a Core Outcome Set for Dysphagia Interventions in Parkinson’s disease (COS-DIP): study protocol

IntroductionCurrent clinical trials on swallowing disorders (dysphagia) in Parkinson’s disease (PD) apply a high variety of outcomes and different outcome measures making comparative effectiveness research challenging. Furthermore, views of patients...

The impact of pre-biopsy MRI and additional testing on prostate cancer screening outcomes: A rapid review.

This work aims to examine the latest evidence on the impact of pre-biopsy MRI, in addition to prostate-specific antigen (PSA) testing, on health outcomes and quality of life. We conducted a literature search including PubMed and Cochrane Central Register of Controlled Trials (CENTRAL) databases, with a limited scan of (i) guidelines and (ii) references from trial reports, from January 2005 to 25th January 2023. Two independent reviewers selected randomised controlled trials (RCT) and cohort studies which met our inclusion criteria. One hundred thirty-seven articles were identified, and seven trial articles were selected. Trial interventions were as follows: (i) PSA blood test, (ii) additional tests such as pre-biopsy multiparametric magnetic resonance imaging (mpMRI) and Biparametric MRI (bpMRI), and (iii) MRI targeted biopsy and standard biopsy. Compared with standard biopsy, MRI-based interventions led to increased detection of clinically significant cancers in three studies and decreased detection of clinically insignificant cancer (Gleason grade 3 + 3) in four studies. However, PROstate Magnetic resonance Imaging Study (PROMIS) and Stockholm3 with MRI (STHLM3-MRI) studies reported different trends depending on the scenario studied in PROMIS (MRI triage and MRI directed biopsy vs. MRI triage and standard biopsy) and thresholds used in STHLM3-MRI (≥0·11 and ≥0·15). MRI also helped 8%-49% of men avoid biopsy, in six out of seven studies, but not in STHLM3-MRI at ≥0.11. Interestingly, the proportion of men who experienced sepsis and UTI was low across studies. This review found that a combination of approaches, centred on the use of pre-biopsy MRI, may improve the detection of clinically significant cancers and reduce (i) the diagnosis of clinically insignificant cancers and (ii) unnecessary biopsies, compared with PSA testing and standard biopsy alone. However, the impact of such interventions on longer term outcomes such as prostate cancer-specific mortality has not yet been assessed.

Management Modalities of Primary Bladder Neck Obstruction in Young Adult Men: A Systematic Review and Meta-analysis.

This systematic review was done to critically appraise the various evidence available in the literature for the presenting symptoms, diagnosis, and management modalities for primary bladder neck obstruction diagnosed on invasive urodynamics in young adult men 18-50 years of age. A search was conducted on PubMed, Embase, and Cochrane Central Register of Controlled Trials databases until July 2022 to find English-language studies relevant to the topic. A total of 10 studies were included. The estimated difference in International Prostate Symptom Score between baseline and 3 months in the subgroup of medical and surgical treatment was found to be -8.82 and -11.25, respectively (P = .37), and after 12 months, it was found to be -7.69 and -17.70 respectively (P .001). The pooled estimate for the difference in Qmax between baseline and 3 months after medical and surgical treatments in the subgroup was found to be 2.92 and 7.03, respectively (P = .18), and after 12 months, it was found to be 4.54 and 7.74, respectively (P .001). The pooled estimate of the difference in post-void residue before and after 3 months of medical and surgical treatments in a subgroup was found to be -31.15 and -70, respectively (P .001), and after 12 months, it was found to be -31.49 and -156.00, respectively (P .001). Quality of life scores improved in both subgroups. The alpha-blockers are effective in managing primary bladder neck obstruction in the short term, while bladder neck incision is preferred for better longterm outcomes.

The Performance of Pulmonary Function Tests in Predicting Systemic Sclerosis—Interstitial Lung Disease in the European Scleroderma Trial and Research Database

Background and Objectives: In SSc, ILD is a major cause of morbidity and mortality. We aimed to investigate the performance of DLCO (diffusing capacity of lung carbon monoxide) and FVC (forced vital capacity) delta change (Δ) and baseline values in predicting the development of SSc-ILD. Methods: Longitudinal data of DLCO, FVC, and ILD on the HRCT of SSc patients from the EUSTAR database were evaluated at baseline (t0) and after 12 (±4) (t1) and 24 (±4) (t2) months. Results: 474/17805 patients were eligible for the study (403 females); 46 (9.7%) developed ILD at t2. Positivity for anti-topoisomerase antibodies (117 patients) showed an association with ILD development at t2 (p = 0.0031). Neither the mean t0 to t1 change (Δ) of DLCO nor the mean t0 to t1 FVCΔ predicted the appearance of ILD at t2. Investigating the possible role of baseline DLCO and FVC values in predicting ILD appearance after 24 (±4) months, we observed a moderate predictive capability of t0 DLCO < 80%, stronger than that of FVC < 80%. Conclusions: We suggest that an impaired baseline DLCO may be predictive of the appearance of ILD after 2 years of follow-up. This result advances the hypothesis that a reduction in gas exchange may be considered an early sign of lung involvement. However, further rigorous studies are warranted to understand the predictive role of DLCO evaluation in the course of SSc.

Neuroprotection strategies in traumatic brain injury: Studying the effectiveness of different clinical approaches.

This review delves into clinical strategies aimed at addressing the complexities of traumatic brain injury (TBI), specifically focusing on pharmaceutical interventions and stem cell therapies as potential avenues for enhancing TBI outcomes. A thorough review of clinical strategies for TBI management, encompassing pharmaceutical and nonpharmaceutical interventions, was performed. PubMed, MEDLINE and clinical trial databases were searched to identify relevant studies and clinical trials. Inclusion criteria consisted of studies involving pharmaceutical agents and other clinical approaches (i.e., stem cell therapies) targeting neuroinflammation, excitotoxicity, oxidative stress, and neurodegeneration in TBI. Data from clinical trials and ongoing research initiatives were analyzed to assess the current status and potential of these clinical approaches. Many trials have been conducted to face the challenge that is TBI. These interventions are designed to target critical aspects of secondary brain injury, encompassing neuroinflammation, excitotoxicity, oxidative stress, and neurodegeneration. Despite this, there is no panacea or definitive remedy for this condition. Combining therapies in a patient-tailored approach seems to be our best chance to improve these patients' outcomes, but systematic protocols are needed. Clinical strategies represent dynamic and continually evolving pathways in TBI management. This review provides an extensive overview of the existing landscape of clinical approaches and promising new studies and outlines their influence on patient outcomes. By highlighting challenges and presenting opportunities, it contributes to the ongoing mission to advance clinical care for individuals impacted by TBI.

Mobile and Computer-Based Applications for Rehabilitation Monitoring and Self-Management After Knee Arthroplasty: Scoping Review.

Successful post-knee replacement rehabilitation requires adequate access to health information, social support, and periodic monitoring by a health professional. Mobile health (mHealth) and computer-based technologies are used for rehabilitation and remote monitoring. The extent of technology use and its function in post-knee replacement rehabilitation care in low and middle-income settings are unknown. To inform future mHealth intervention development, we conducted a scoping review to map the features and functionality of existing technologies and determine users' perspectives on telerehabilitation and technology for self-management. We followed the Joanna Briggs Institute methodology for scoping reviews. We searched the Embase, Medline, PsycINFO via OVID, and Cochrane Central Register of Controlled Trials databases for manuscripts published from 2001 onward. We included original research articles reporting the use of mobile or computer-based technologies by patients, health care providers, researchers, or family members. Studies were divided into the following 3 categories based on the purpose: validation studies, clinical evaluation, and end user feedback. We extracted general information on study design, technology features, proposed function, and perspectives of health care providers and patients. The protocol for this review is accessible in the Open Science Framework. Of the 5960 articles, 158 that reported from high-income settings contributed to the qualitative summary (64 studies on mHealth or telerehabilitation programs, 28 validation studies, 38 studies describing users' perceptions). The highest numbers of studies were from Europe or the United Kingdom and North America regarding the use of a mobile app with or without wearables and reported mainly in the last decade. No studies were from low and middle-income settings. The primary functions of technology for remote rehabilitation were education to aid recovery and enable regular, appropriate exercises; monitoring progress of pain (n=19), activity (n=20), and exercise adherence (n=30); 1 or 2-way communication with health care professionals to facilitate the continuum of care (n=51); and goal setting (n=23). Assessment of range of motion (n=16) and gait analysis (n=10) were the commonly validated technologies developed to incorporate into a future rehabilitation program. Few studies (n=14) reported end user involvement during the development stage. We summarized the reasons for satisfaction and dissatisfaction among users across various technologies. Several existing mobile and computer-based technologies facilitate post-knee replacement rehabilitation care for patients and health care providers. However, they are limited to high-income settings and may not be extrapolated to low-income settings. A systematic needs assessment of patients undergoing knee replacement and health care providers involved in rehabilitation, involving end users at all stages of development and evaluation, with clear reporting of the development and clinical evaluation can make post-knee replacement rehabilitation care in resource-poor settings accessible and cost-effective.

P974 Incidence of Perianal Complications in Clinical Trials for Therapies for Moderate to Severe Inflammatory Bowel Disease

Abstract Background Crohn’s disease (CD) and ulcerative colitis (UC) are chronic inflammatory bowel diseases (IBDs) with distinct clinical consequences. Distinct from patients with UC is that nearly 25% of patients with CD patients have or will develop perianal disease. Predictors for the development of new perianal disease or complications from existing perianal disease are not well described but such occurrences are included as adverse events (AEs) in clinical trials for IBD. We performed a systematic review and meta-analysis of perianal AEs in pivotal trials of therapies for IBD. Methods We conducted a search of PubMed, EMBASE, MEDLINE, Medline Plus, and CDSR library databases for registry and pivotal Phase II-III clinical trials of therapies for IBD. Safety data from clinicaltrials.gov was reviewed to identify incidence of perianal AEs using the terms "abscess" and "fistula." Reported perianal AEs included the following: anal abscess, fissure, fistula; perianal abscess, fistula; perineal abscess; perirectal and rectal abscess; subcutaneous (gluteal) abscess. Results Perianal AE incidence across all trials reviewed was 0.47% (91/19,327 patients). Perianal AEs were more likely to occur in patients with CD (0.77%, 70/9,046) than UC (0.20%, 21/10,281). Perianal AEs occurred more frequently in populations of drug-exposed patients than in patients exposed to placebo. In drug-exposed patients with UC, 0.22% (16/7,415) of patients experienced a perianal AE vs 0.17% (5/2,935) of patients exposed to placebo. In drug-exposed patients with CD, 0.76% (55/7,271) of patients experienced a perianal AE vs 0.61% (15/2,465) of patients exposed to placebo. The results are summarized in Table 1. Conclusion We found that perianal AEs occur in pivotal UC and CD clinical trials. Expectedly, the frequency of perianal AEs was higher in trials of CD than those for UC. However, the development of perianal AEs in trials of UC suggests that these patients may have been misclassified and have CD. Available data do not allow distinction between development of a perianal AE in a patient with known perianal disease or progression of undiagnosed clinical or subclinical perianal disease, nor does it allow for distinction in a patient not responding to the experimental agent. The finding that perianal AEs occurred more frequently with drug exposure than placebo may be due to fistula healing with consequential abscess formation or unique mechanistic effects that worsen perianal disease. These results highlight a probable rate of misclassification of patients with UC in pivotal trials, and suggest the possibility of subclinical perianal disease in some patients. Further clarification and study of these AEs and their implications are warranted.

P089 Development and preliminary evaluation of a suicidal risk assessment protocol in a research trial using the Patient Health Questionnaire (PHQ-9)

Abstract Background People with Inflammatory Bowel Disease (IBD) have an increased risk of depression and self-harm. Participants in IBD research trials often disclose severe depression symptoms, including thoughts of self-harm and suicidal ideation, in validated self-administered questionnaires such as the Patient Health Questionnaire-9 (PHQ-9). However, there is no standard protocol for responding to such disclosure in research trials and the opportunity to support people at risk is potentially missed. We developed and evaluated a risk assessment protocol for the IBD-BOOST randomised controlled trial (ISRCTN71618461). Methods Participants completed the PHQ-9 scale at baseline, six-month and 12-month follow-up. Responding to item 9: ‘Thoughts that you would be better off dead or of hurting yourself in some way’, if a participant indicated ‘More than half the days’ or ‘Nearly every day’, the trial database automatically alerted the research team to risk assess the participant. Trial risk assessors, trained in the protocol, contacted participants by telephone, completed the risk assessment protocol (Figure 1) and signposted participants to appropriate professional services. Risk assessments were completed at the first occurrence of a PHQ-9 item 9 response. Risk assessments were reviewed by the Chief Investigator and summarised to trial governing committees. Results 780 participants were randomised. Overall, there were 58 PHQ-9 risk alerts during the trial (baseline, six- or 12-month follow-up), 41 of which were new alerts and required risk assessment. One participant declined assessment so 40 risk assessments were completed. 24 participants were assessed as low-risk and 16 participants as medium-risk, with 12 declaring previous suicide attempts. No participants were rated as high-risk. The mean time for the risk assessment phone call was 14 minutes (range 5-36 minutes) and total time spent on calls was approximately nine hours. Trial participants who received a risk assessment expressed appreciation for being contacted and all except two wished to receive information about professional support services. In a focus group, trial risk assessors reported positive experiences of conducting the risk assessment with suggestions for improvement, which resulted in minor modifications to the protocol. Conclusion Our evaluation demonstrated that it was viable for a research trial team to successfully conduct a risk-assessment protocol for trial participants reporting thoughts of self-harm, with training and support from senior colleagues. Resources are required for training and delivery, but it is not unduly onerous. Trial participants appeared to find completing the assessment acceptable. The revised protocol will be made available for researchers to use.

Kisspeptin and its Current Clinical Status- A Systematic Review.

Kisspeptin was initially known as metastin for its role in suppressing metastasis in melanoma and breast cancer. Later, based on its ability to stimulate GPR54, its importance in maintaining an intact hypothalamic-pituitary-ovarian axis was recognised, which is the basis for the widespread application of the drug in several conditions such as secondary amenorrhea, regulation of puberty onset, ovarian function, trophoblast invasion, fertility regulation, parturition, and lactation. This systematic study aims to evaluate the current status of kisspentin in clinical trials. The keywords 'kisspeptin' or 'metastin' were used in the clinicaltrials.gov website and Clinical Trial Registry of India (CTRI) to find eligible clinical trials or records carried out without time constraints until February 26, 2023. A total of 33 records were identified through clinical trial databases. All records were screened, and four trials were rejected as they failed to meet the inclusion criteria. Finally, 29 (87.9%) reports of interventional clinical trials with kisspeptin were reviewed. Kisspeptin can be viewed as a multipurpose drug with considerably fewer side effects due to its effects simulating normal physiological processes in our body.

Efficacy of baricitinib in patients with moderate-to-severe rheumatoid arthritis up to 6.5 years of treatment: results of a long-term study.

To evaluate the long-term efficacy of once-daily baricitinib 4 mg or 2 mg in patients with active rheumatoid arthritis who had inadequate response (IR) to MTX, csDMARDs or bDMARDs. Data from three completed phase III studies-RA-BEAM (MTX-IR), RA-BUILD (csDMARD-IR) and RA-BEACON (bDMARD-IR)-and one completed long-term extension study (RA-BEYOND) were analysed up to 6.5 years [340 weeks (RA-BEAM) and 336 weeks (RA-BUILD and RA-BEACON)]. Low disease activity (LDA) [Simplified Disease Activity Index (SDAI) ≤11], clinical remission (SDAI ≤3.3) and physical function [Health Assessment Questionnaire Disability Index (HAQ-DI) ≤0.5] were the main outcomes assessed. Completer and non-responder imputation (NRI) analyses were conducted on each population. At week 340 or 336, LDA was achieved in 37%/83% of MTX-IR, 35%/83% of csDMARD-IR and 23%/73% of bDMARD-IR patients treated with baricitinib 4 mg, assessed by NRI/completer analyses, respectively. Remission was achieved in 20%/40% of MTX-IR, 13%/32% of csDMARD-IR and 9%/30% of bDMARD-IR patients treated with baricitinib 4 mg, assessed by NRI/completer analyses, respectively. HAQ-DI ≤0.5 was reached in 31%/51% of MTX-IR, 25%/46% of csDMARD-IR and 24%/38% of bDMARD-IR patients treated with baricitinib 4 mg, assessed by NRI/completer analyses, respectively. Treatment with baricitinib 4 mg or 2 mg demonstrated efficacy up to 6.5 years with maintained LDA/remission results across SDAI, CDAI and DAS28-hsCRP consistent with previously reported data, and was well tolerated. United States National Library of Medicine clinical trials database www.clinicaltrials.gov; RA-BEYOND; NCT01885078.

The distribution of human epidermal growth factor receptor 2 (HER2) expression and the efficacy and safety of treatments in HER2-expressing advanced or metastatic gastroesophageal cancer: A systematic literature review (SLR).

405 Background: HER2 overexpression plays an important role in determining treatment options for patients with gastroesophageal cancer (GEC). HER2 overexpression has historically been defined dichotomously as HER2-positive (HER2+) or HER2-negative. An emerging potentially clinically relevant category is HER2-low, which could be targeted with HER2-directed antibody drug conjugates. However, data on the epidemiology and outcomes associated with HER2-low GEC are limited. Methods: An SLR of PubMed, Embase, and Cochrane Central Register of Controlled Trials databases was conducted to identify clinical trials, observational studies, and meta-analyses reporting clinical outcomes or distribution of HER2 expression by IHC and ISH in advanced or metastatic (a/m) GEC. Key inclusion criteria were: English language, published between 2013-2023, and sample size ≥100 HER2-expressing patients. HER2+ was defined as IHC score of 3+ or IHC 2+ and ISH+. HER2-low was defined as IHC 1+ or IHC 2+ and ISH-. Weighted averages were calculated for the proportion of patients who were HER2+ and HER2-low to estimate of the proportion of patients in each HER2 expression category. Results were categorized by patient population (all GEC or gastric cancer [GC] only). Results: Of 2,701 non-duplicated records screened, 174 studies met inclusion criteria. Distribution of HER2 expression was reported in 111 studies, 5 of which reported on the frequency of HER2 expression of IHC 1+ and/or IHC 2+ and ISH+. HER2 expression status varied by patient population, with a weighted average of 26.9% for HER2-low and 13.1-16.5% for HER2+ across groups (Table). Different cutoffs for HER2 amplification via ISH also affected the proportion of patients in each HER2 category across studies. Efficacy and safety outcomes were stratified by HER2 status or IHC results in 74 studies. However, only 3 observational studies reported outcomes separately for the HER2-low population, and results were inconclusive. Conclusions: The distribution of HER2 expression in a/m GEC in the identified studies is highly heterogenous, likely due to variability in IHC scoring and patient populations. Few studies with sufficient samples size (≥100 patients with HER2-expression a/mGEC) reported outcomes for HER2-low a/m GEC, and those that were identified were of low quality. The HER2-low a/m GEC population constitutes an unmet need for effective therapy. There is a need for consistent use of a standardized definition of HER2-low in a/mGEC and additional studies to better evaluate treatment options and outcomes for this patient population. [Table: see text]

Effect of COVID-19 on the prevalence of bystanders performing cardiopulmonary resuscitation: A systematic review and meta-analysis.

The importance of bystander cardiopulmonary resuscitation (CPR) during out-of-hospital cardiac arrests is especially important in the context of coronavirus disease 2029 (COVID-19) because it can significantly influence survival outcomes. The objective of this meta-analysis was to examine the primary outcomes of bystander CPR during the pandemic and pre-pandemic periods. A search was conducted in the PubMed Central, Scopus, and EMBASE databases, as well as the Cochrane Central Register of Controlled Trials database, up to December 10, 2023. In cases where the value of I² was greater than or equal to 50% or the Q-test indicated that the p-value was less than or equal to 0.05, the studies were considered to be heterogeneous. Sensitivity assessment was performed using the leave-one-out methodology. The study protocol was registered in PROSPERO with the ID number CRD42023494912. Twenty-five articles were included in this meta-analysis. Pooled analysis showed that bystander CPR frequency during the COVID-19 pandemic was 38.8%, compared to 44.8% for the pre-pandemic period (odds ratio: 1.04; 95% confidence interval: 0.93-1.16; p = 0.48). The article's conclusions indicate that the COVID-19 pandemic influenced a reduction in bystander CPR compared to the pre-pandemic period, but this difference was not statistically significant. Further research is recommended to understand attitudes, including the fears of witnesses, before performing CPR on patients with suspected or confirmed infectious diseases. The study highlights the importance of bystander intervention in emergency situations and the impact of a pandemic on public health response behaviors.

Implementing the time-to-event continual reassessment method in the presence of partial orders in a phase I head and neck cancer trial

BackgroundIn this article we describe the methodology of the time-to-event continual reassessment method in the presence of partial orders (PO-TITE-CRM) and the process of implementing this trial design into a phase I trial in head and neck cancer called ADePT-DDR. The ADePT-DDR trial aims to find the maximum tolerated dose of an ATR inhibitor given in conjunction with radiotherapy in patients with head and neck squamous cell carcinoma.MethodsThe PO-TITE-CRM is a phase I trial design that builds upon the time-to-event continual reassessment method (TITE-CRM) to allow for the presence of partial ordering of doses. Partial orders occur in the case where the monotonicity assumption does not hold and the ordering of doses in terms of toxicity is not fully known.ResultsWe arrived at a parameterisation of the design which performed well over a range of scenarios. Results from simulations were used iteratively to determine the best parameterisation of the design and we present the final set of simulations. We provide details on the methodology as well as insight into how it is applied to the trial.ConclusionsWhilst being a very efficient design we highlight some of the difficulties and challenges that come with implementing such a design. As the issue of partial ordering may become more frequent due to the increasing investigations of combination therapies we believe this account will be beneficial to those wishing to implement a design with partial orders.Trial registrationADePT-DDR was added to the European Clinical Trials Database (EudraCT number: 2020-001034-35) on 2020-08-07.

Delivering COVID-19 vaccine trials at speed: the implementation of a phase IV UK multi-centre randomised controlled trial to determine safety and immunogenicity of COVID-19 vaccines co-administered with seasonal influenza vaccines (ComFluCOV)

BackgroundIn February 2021, the UK Department of Health and Social Care sought evidence on the safety and immunogenicity of COVID-19 and influenza vaccine co-administration to inform the 2021/2022 influenza vaccine policy. Co-administration could support vaccine uptake and reduce healthcare appointments. ComFluCOV was a randomised controlled trial designed to provide this evidence. This report outlines the methods used to deliver the trial in 6 months to answer an urgent public health question as part of the COVID-19 pandemic response.MethodsComFluCOV was commissioned by the Department of Health and Social Care and was managed by the Bristol Trials Centre, a UK-registered clinical trials unit. It was classed as an Urgent Public Health trial which facilitated fast-track regulatory approvals. Trial materials and databases were developed using in-house templates and those used in other COVID-19 vaccine trials. Participants were recruited by advertising, and via a trial website. Electronic trial systems enabled daily review of participant data. Weekly virtual meetings were held with stakeholders and trial sites.ResultsComFluCOV was delivered within 6 months from inception to reporting, and trial milestones to inform the Department of Health and Social Care policy were met. Set-up was achieved within 1 month. Regulators provided expedited reviews, with feedback ahead of submission. Recruitment took place at 12 sites. Over 380 site staff were trained. Overall, 679 participants were recruited in two months. The final report to the Department of Health and Social Care was submitted in September 2021, following a preliminary safety report in May 2021. Trial results have been published.ConclusionThe rapid delivery of ComFluCOV was resource intensive. It was made possible in part due to a unique set of circumstances created by the pandemic situation including measures put in place to support urgent public health research and public support for COVID-19 vaccine research. Elements of the trial could be adopted to increase efficiency in ‘non-pandemic’ situations including working with a clinical trials unit to enable immediate mobilisation of a team of experienced researchers, greater sharing of resources between clinical trials units, use of electronic trial systems and virtual meetings.Trial registrationISRCTN14391248, submitted on 17/03/2021. Registered on 30/03/2021.

ADVANCEMENT IN THE TREATMENT OF ALZHEIMER'S DISEASE, 2023

Background: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by extracellular amyloid β deposition and intercellular neurofibrillary tangles. AD is a complex disease with a strong genetic component, and it is classified into three phases by the Food and Drug Administration (US-FDA): pre-pathology, plaque formation, and neural destruction. A number of therapeutic agents have been developed to reduce AD pathology and improve cognition. Objectives: The objective of this paper was to review recent advancements in AD treatment and cure. Methodology: A literature search was conducted using the keywords "therapeutic developments for AD" and "natural products as a drug for AD." Publications related to AD were retrieved, and the NCBI Clinical trial database was also searched to check drug status. Results: Monoclonal antibodies against amyloid β plaques, tau protein, and microtubule-associated protein have shown positive results in animal models, but they have failed in clinical trials. This is likely due to the fact that these antibodies are designed to target specific proteins that are not always present in the human brain. Conclusion: Based on the findings of this review, it is suggested that medicines based on natural extracts and combination therapy would be least toxic and more effective than single therapy. This is because combination therapy targets multiple pathways involved in AD pathogenesis. There is also a dire need to initiate AD research in Pakistan and facilitate the Pakistani community in early diagnosis and cure.

Risk Factors for the Development of Persistent Scaphoid Non-Union After Surgery for an Established Non-Union.

Between 2014 and 2020, candidates for scaphoid non-union (SNU) surgery were enrolled in a prospective randomized trial (Scaphoid Nonunion and Low Intensity Pulsed Ultrasound [SNAPU] trial) evaluating the effect of low-intensity pulsed ultrasound on postoperative scaphoid healing. At trial completion, 114/134 (85%) of these patients went on to union, and 20/134 (15%) went on to persistent SNU (PSNU). The purpose of this study was to use this prospectively gathered data to identify patient-, fracture-, and surgery-specific risk factors that may be predictive of PSNU in patients who undergo surgery for SNU. Data were extracted from the SNAPU trial database. The inclusion and exclusion criteria of this study were the same as that of the SNAPU trial. Nineteen patient-, fracture-, and surgery-specific risk factors were determined a priori. A stepwise multivariable logistic regression model was used to identify independent risk factors for PSNU. Three risk factors were found to be independently significant predictors of PSNU: age at the time of surgery, dominant hand injury, and previous surgery on the affected scaphoid. With every decade of a patient's life, dominant hand injury, and previous scaphoid surgery, the odds of union are reduced by 1.72 times, 7.35 times, and 4.24 times, respectively. We identified three independent risk factors for PSNU: age at SNU surgery, dominant hand injury, and previous surgery on the affected scaphoid. The findings of this study are significant and may contribute to shared decision-making and prognostication between the patient, surgeon, and affiliated members of their care team.

NEUROLOGICAL COMPLICATIONS FOLLOWING PEDIATRIC CONGENITAL CARDIAC SURGERY: A SYSTEMATIC REVIEW AND META-ANALYSIS

Objectives: The study was designed to ascertain the incidence of neurological complications in children following cardiac surgery for congenital heart defects (CHD). Methods: An extensive search was conducted using Medical Subject Headings in the Cochrane Controlled Trials databases, PubMed, and Embase in July 2023. Data extraction was done using a customized data extraction sheet, adhering to Cochrane’s standard methodological procedures. As the heterogeneity was high among the included studies, random-effect models were employed during the meta-analysis. Results: Seventeen articles were included in our analysis, encompassing a total sample size of 23,930 pediatric patients who underwent congenital cardiac surgeries. The calculated incidence of neurological complications following these procedures was found to be 0.21 (95% confidence interval: 0.14–0.28). A random-effects model employing the DerSimonian-Laird estimator was utilized for the meta-analysis. The assessment of heterogeneity revealed Tau of 0.134, an I2 value of 99.63%, and an H2 value of 267.078, indicating heterogeneity (p<0.001). Conclusion: The study highlights the substantial incidence of neurological complications following congenital cardiac surgery, with infants <1 year old being at a higher risk.

Expansion of Clinical Research

The bureaucratically perverted Idea of expanding the Clinical Trials database can not only be corrected, but fundamentally advanced through information provided by patients themselves via the Internet. But in order to prevent the distortion of the Idea in the future, methods of processing Information are required based on the INVARIANT Medical Theory using the Mathematical Theory of Numbers and Sets, which will direct Artificial Intelligence to process an array of data about all sick people on Earth.

Cost-Effectiveness and Impact on Health Care Utilization of Interventions to Improve Medication Adherence and Outcomes in Asthma and Chronic Obstructive Pulmonary Disease: A Systematic Literature Review

BackgroundPoor adherence to asthma and chronic obstructive pulmonary disease (COPD) maintenance therapies impairs health outcomes. Proven and cost-effective programs to promote adherence and persistence are not yet in widespread, regular use. Implementation costs are a potential barrier to uptake of such programs. ObjectiveWe undertook a systematic literature review and narrative synthesis of studies investigating the cost-effectiveness of treatment adherence-promoting programs or that determined their impact on healthcare budget directly or via healthcare resource utilization (HCRU). MethodsWe identified relevant publications using MEDLINE and PREMEDLINE (PubMed), EMBASE (Embase.com, Elsevier) and EconLit for publications between January 2000 and July 2021. Clinical trial databases and selected conference proceedings were also searched. ResultsOf 1,910 potentially relevant articles, 26 met prespecified inclusion criteria and underwent data extraction. Eleven reported a direct assessment of adherence, 15 included economic evaluations, and 17 described HCRU. None included analysis of biologic medication use. Where studied, interventions were often found to be highly cost-effective, with dominant incremental cost-effectiveness ratios in some cases. Reductions in direct costs and HCRU – healthcare visits, hospital admissions and/or the use of medications (including add-on/reliever treatment and antibiotics) – were reported frequently. Reported use of maintenance treatments improved in some studies. Counseling and/or digitally informed programs were used in all cases where favorable outcomes were observed. ConclusionAdherence-promoting interventions are mostly cost-effective and often result in reduced HCRU and associated costs. Multidisciplinary care involving one-to-one advice and digitally enhanced communications appear to offer the greatest benefit.

Efficacy and safety of bicyclol for treating patients with antituberculosis drug-induced liver injury.

BACKGROUND: Bicyclol was used for treating idiosyncratic acute drug-induced liver injury (DILI) in a phase II trial. This study was aimed at evaluating the efficacy and safety of bicyclol 25 and 50 mg thrice a day (TID) for treating acute DILI caused by anti-TB drugs in the light of the trial results.METHODS: We analysed clinical data of patients with TB drug-induced DILI in the trial database. The primary endpoint was reduction in serum alanine aminotransferase (ALT) levels after 4 weeks of treatment compared to baseline.RESULTS: Overall, 148 patients were included, with respectively 48, 52 and 48 patients included in the control (456 mg polyene phosphatidylcholine TID), high-dose (50 mg bicyclol TID) and low-dose (25 mg bicyclol TID) groups. ALT levels decreased by respectively â-"149.0 (IQR â-"299.3 to â-"98.3 (), â-"225.5 (IQR â-"309.3 to â-"181.8 ) and â-"242.5 (IQR â-"364.8 to â-"153.8) U/L in the control, high-dose and low-dose groups (P < 0.001). The ALT normalisation rates at weeks 1, 2, 4, 6 and 8 were higher in the high- and low-dose groups, while adverse events and serious adverse events were similar across groups.CONCLUSIONS: Bicyclol (25 and 50 mg TID) is effective and safe in treating anti-TB DILI, and bicyclol 50 mg TID showed higher efficacy.