Search

To elaborate normative values for a clinical psychophysical taste test (“Taste Strips”). The “Taste Strips” are a psychophysical chemical taste test. So far, no definitive normative data had been published and only a fairly small sample size has been investigated. In light of this shortcoming for this easy, reliable and quick taste testing device, we attempted to provide normative values suitable for the clinical use. Normative value acquisition study, multicenter study. The investigation involved 537 participants reporting a normal sense of smell and taste (318 female, 219 male, mean age 44 years, age range 18–87 years). The taste test was based on spoonshaped filter paper strips (“Taste Strips”) impregnated with the four (sweet, sour, salty, and bitter) taste qualities in four different concentrations. The strips were placed on the left or right side of the anterior third of the extended tongue, resulting in a total of 32 trials. With their tongue still extended, patients had to identify the taste from a list of four descriptors, i. e., sweet, sour, salty, and bitter (multiple forcedchoice). To obtain an impression of overall gustatory function, the number of correctly identified tastes was summed up for a “taste score”. Taste function decreased significantly with age. Women exhibited significantly higher taste scores than men which was true for all age groups. The taste score at the 10th percentile was selected as a cut-off value to distinguish normogeusia from hypogeusia. Results from a small series of patients with ageusia confirmed the clinical usefulness of the proposed normative values. The present data provide normative values for the “Taste Strips” based on over 500 subjects tested. [ABSTRACT FROM AUTHOR]

We determined how the quality of trial design and its reporting in scientific papers published in Anaesthesia has changed in the last 25 years. All articles between the years 1983–87 and 2003–07 were reviewed and classified according to methodology. Reporting and trial design of all prospective, comparative clinical interventional trials were compared between the two time periods using 12 criteria. Fewer articles now originate from the United Kingdom and Ireland than 25 years ago. Although fewer human interventional trials are now published in Anaesthesia, the quality of these trials has improved in terms of study design, bias control and proper disclosure. Significant improvements were observed in all criteria of trial design except for the declaration of non-primary adverse outcomes and the minimisation of the risk of type I errors. Further improvements could still be made with respect to sample size calculation, description of the method of randomisation, and blinding. [ABSTRACT FROM AUTHOR]

The article discusses the White Paper of adaptive dose-ranging study to address the early phase drug development issues through simulation methods. The author provides the evaluation metrics including the detection of dose-response (DR), identification of clinical outputs, selection of target dose and estimation of DR profile within the observed dose range.

Efficient and effective recruitment and retention of participants is the largest single component of the study workload and forms an essential component in the conduct of clinical trials. In this paper, we present five principles to guide the processes of both recruitment and retention. These principles include the selection of an appropriate population to adequately answer the research question, followed by the establishment of a sampling process that accurately represents that population. Creation of systematic and effective recruitment mechanisms should be supported by implementation of follow-up mechanisms that promote participant retention. Finally, all activities related to recruitment and retention must be conducted within the framework of ethics and privacy regulations. Adherence to these principles will assist the researcher in achieving the goals of the study within the available resources. [ABSTRACT FROM AUTHOR]

The ideal approach for the design and analysis of clinical trials is to select a single primary endpoint that provides a complete characterization of the disease under study and permits an efficient evaluation of the effect of a test drug. However, this is often not possible for a number of diseases or clinical trials. This paper examines some practical clinical decision-making scenarios for the selection and analysis of efficacy outcome measures in clinical trials with inherent multiplicity components. Copyright © 2003 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: Regulations, study design complexity and amounts of collected and shared data in clinical trials render efficient data handling procedures inevitable. Recent research suggests that electronic data capture can be key in this context but evidence is insufficient. This randomized controlled parallel group study tested the hypothesis that time efficiency is superior when electronic (eCRF) instead of paper case report forms (pCRF) are used for data collection. We additionally investigated predictors of time saving effects and data integrity.Methods: This study was conducted on top of a clinical weight loss trial performed at a clinical research facility over six months. All study nurses and patients participating in the clinical trial were eligible to participate and randomly allocated to enter cross-sectional data obtained during routine visits either through pCRF or eCRF. A balanced randomization list was generated before enrolment commenced. 90 and 30 records were gathered for the time that 27 patients and 2 study nurses required to report 2025 and 2037 field values, respectively. The primary hypothesis, that eCRF use is faster than pCRF use, was tested by a two-tailed t-test. Analysis of variance and covariance were used to evaluate predictors of entry performance. Data integrity was evaluated by descriptive statistics.Results: All randomized patients were included in the study (eCRF group n = 13, pCRF group n = 14). eCRF, as compared to pCRF, data collection was associated with significant time savings  across all conditions (8.29 ± 5.15 min vs. 10.54 ± 6.98 min, p = .047). This effect was not defined by participant type, i.e. patients or study nurses (F(1,112) = .15, p = .699), CRF length (F(2,112) = .49, p = .609) or patient age (Beta = .09, p = .534). Additional 5.16 ± 2.83 min per CRF were saved with eCRFs due to data transcription redundancy when patients answered questionnaires directly in eCRFs. Data integrity was superior in the eCRF condition (0 versus 3 data entry errors).Conclusions: This is the first study to prove in direct comparison that using eCRFs instead of pCRFs increases time efficiency of data collection in clinical trials, irrespective of item quantity or patient age, and improves data quality.Trial Registration: Clinical Trials NCT02649907 . [ABSTRACT FROM AUTHOR]

Adverse drug reactions (ADRs) are a significant problem in children, affecting one in ten children in hospital. Within the community, one in 500 children will experience an adverse drug reaction each year. Pharmacovigilance has been useful in detecting suspected ADRs. However, most ADRs are unreported and often not suspected. Education of health professionals in relation to drug toxicity improves the reporting rate of suspected ADRs. Clinical trials are useful to evaluate the efficacy of drugs. They are, however, not the best way of looking at ADRs where surveillance following the widespread use of a drug is more appropriate. Alongside work by the regulatory agencies, independent investigators have helped collate data. This information has been useful in developing guidelines to prevent further cases of drug toxicity. Greater awareness and understanding of drug toxicity in children should result in more rational prescribing. [ABSTRACT FROM AUTHOR]

Background: Participant recruitment and retention are long-standing problems in clinical trials. Although there are a large number of factors impacting on recruitment and retention, some of the problems may reflect the fact that trial design and delivery is not sufficiently 'patient-centred' (i.e., sensitive to patient needs and preferences). Most trials collect process and outcome measures, but it is unclear whether patient experience of trial participation itself is routinely measured. We conducted a structured scoping review of studies reporting standardised assessment of patient experience of participation in a trial.Methods: A structured search of Medline, PsycINFO, Embase and CINAHL (Cumulative Index to Nursing and Allied Health Literature) and hand searching of included studies were conducted in 2016. Additional sources included policy documents, relevant websites and experts. We extracted data on trial context (type, date and location) and measure type (number of items and mode of administration), patient experience domains measured, and the results reported. We conducted a narrative synthesis.Results: We identified 22 journal articles reporting on 21 different structured measures of participant experience in trials. None of the studies used a formal definition of patient experience. Overall, patients reported relatively high levels of global satisfaction with the trial process as well as positive outcomes (such as the likelihood of future participation or recommendation of the trial to others).Conclusions: Current published evidence is sparse. Standardised assessment of patient experience of trial participation may provide opportunities for researchers to enhance trial design and delivery. This could complement other methods of enhancing the patient-centredness of trials and might improve recruitment, retention, and long-term patient engagement with trials. [ABSTRACT FROM AUTHOR]

Background: Neurological injuries remain the leading cause of death in comatose patients resuscitated from out-of-hospital cardiac arrest (OHCA). Adequate blood pressure is of paramount importance to optimize cerebral perfusion and to minimize secondary brain injury. Markers measuring global cerebral ischemia caused by cardiac arrest and consecutive resuscitation and reflecting the metabolic variations after successful resuscitation are needed to assist a more individualized post-resuscitation care. Currently, no technique is available for bedside evaluation of global cerebral energy state, and until now blood pressure targets have been based on limited clinical evidence. Recent experimental and clinical studies indicate that it might be possible to evaluate cerebral oxidative metabolism from measuring the lactate-to-pyruvate (LP) ratio of the draining venous blood. In this study, jugular bulb microdialysis and immediate bedside biochemical analysis are introduced as new diagnostic tools to evaluate the effect of higher mean arterial blood pressure on global cerebral metabolism and the degree of cellular damage after OHCA.Methods/design: This is a single-center, randomized, double-blinded, superiority trial. Sixty unconscious patients with sustained return of spontaneous circulation after OHCA will be randomly assigned in a one-to-one fashion to low (63 mm Hg) or high (77 mm Hg) mean arterial blood pressure target. The primary end-point will be a difference in mean LP ratio within 48 h between blood pressure groups. Secondary end-points are (1) association between LP ratio and all-cause intensive care unit (ICU) mortality and (2) association between LP ratio and survival to hospital discharge with poor neurological function.Discussion: Markers measuring cerebral ischemia caused by cardiac arrest and consecutive resuscitation and reflecting the metabolic changes after successful resuscitation are urgently needed to enable a more personalized post-resuscitation care and prognostication. Jugular bulb microdialysis may provide a reliable global estimate of cerebral metabolic state and can be implemented as an entirely new and less invasive diagnostic tool for ICU patients after OHCA and has implications for early prognosis and treatment.Trial Registration: ClinicalTrials.gov (ClinicalTrials.gov Identifier: NCT03095742 ). Registered March 30, 2017. [ABSTRACT FROM AUTHOR]

Based on current data and experience, the joint working group of the European Society of Minimally Invasive Neurological Therapy (ESMINT) and the European Society of Neuroradiology (ESNR) make suggestions on trial design and conduct aimed to investigate therapeutic effects of mechanical thrombectomy (MT). We anticipate that this roadmap will facilitate the setting up and conduct of successful trials in close collaboration with our neighbouring disciplines. [ABSTRACT FROM AUTHOR]

A new era of stroke treatment may have begun with mechanical thrombectomy (MT) by fully deployed closed-cell self-expanding stents (stent-triever). Multiple case series and the first randomised controlled trials (RCTs) have now been published. More studies are under way involving large numbers of patients, which in turn has resulted in less strict 'pragmatic' study protocols. Problems with current trials include a lack of standardisation in the conduct of the recanalisation procedure, the definition of primary endpoints such as the grade of arterial recanalisation and tissue reperfusion, and the post-surgical care provided. In Part 1 of this two part series, we outline the current situation and the major research questions. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect of magnesium sulfate for prevention of eclampsia on blood loss at time of cesarean delivery (CD). Methods: We conducted an electronic based search using the following databases: MEDLINE, PUBMED and the Cochrane Library. The search terms were “magnesium sulfate”, “preeclampsia” and “randomized”. Inclusion criteria were randomized controlled trials of women with preeclampsia who delivered with or without magnesium sulfate therapy for seizure prophylaxis. Only trials with placebo or no treatment comparison groups were included. Primary outcome was postpartum hemorrhage. Secondary outcomes were estimated blood loss, change in hemoglobin, blood transfusion and eclampsia. Results: Five trials met inclusion criteria. The incidence of postpartum hemorrhage was similar between the two groups [magnesium sulfate: 754/4482 (17%); no magnesium sulfate: 775/4427 (18%); RR 0.97, 95% CI 0.88–1.06]. There was no statistical difference between any of the other blood loss outcomes reported in the included studies. The rate of eclampsia with magnesium sulfate was significantly lower than with placebo (42/5604, 0.7%, versus 107/5600, 1.9%; RR 0.40, 95% CI 0.28–0.57). Conclusions: Magnesium sulfate does not appear to affect blood loss intrapartum and postpartum in women with preeclampsia. Magnesium sulfate, therefore, should be continued during CD, given the benefit of seizure prophylaxis without any increased risk of hemorrhage. [ABSTRACT FROM PUBLISHER]

This study aimed to comparatively evaluate the disinfecting potential of sodium hypochlorite, diode laser, and photodynamic therapy in non-vital teeth with or without periapical rarefaction. Forty-five patients with the diagnosis of pulp necrosis with apical rarefaction were randomly assigned to three groups (n = 15) based on the disinfection protocol. Access cavities were prepared and pre-instrumentation microbial samples were taken using a paper point. Working length determination followed by cleaning and shaping with rotary files was performed. The canals were lubricated with ethylenediaminetetraacetic acid (EDTA) during instrumentation and finally rinsed with copious amounts of saline. Canals in group 1 were irrigated with 5 mL of 5.25% NaOCl, those in group 2 received irradiation with 808-nm diode laser (30 s, 7W), and those in group 3 were soaked with methylene blue photosensitizer (5 min) before irradiation with 660-nm diode laser (3 min). Post-disinfection microbial samples were collected using a paper point. Pre- and post-disinfection live bacterial counts were analyzed using a flow cytometer. The data were statistically analyzed using one-way ANOVA and Student's t-test. Comparison of pre-instrumentation mean live bacterial count showed no significant difference between the groups (p > 0.05). The mean live bacterial count post-disinfection was 41.07%, 46.99%, and 34.45% in groups 1–3 respectively. A significant reduction in the bacterial count was seen following disinfection in all the groups (p < 0.05). It can be concluded that both diode laser and photodynamic therapy were equally effective as 5.25% NaOCl in reducing the bioburden in root canals. Trial registration: CTRI/2018/03/012667. [ABSTRACT FROM AUTHOR]

Program theory reconstruction is an often-overlooked aspect of social intervention research. In this paper, we argue that intervention research benefits if the research design is informed by the specific intervention's program theory (i.e., the idea of how the intervention is supposed to lead to the intended outcomes). The purpose of this paper is to offer a comprehensive and accessible guide to program theory reconstruction in research on social interventions and to provide arguments as to how program theory reconstruction can be used to benefit intervention studies. First, we summarize what program theory is and its role in intervention research. Second, we provide a direct "how-to" for researchers, practitioners, and students who may be unfamiliar with the methods of program theory reconstruction but are interested in undertaking a program theory reconstruction. Finally, we conclude with how program theory reconstruction can benefit intervention research. [ABSTRACT FROM AUTHOR]

Competing risks data are commonly encountered in randomized clinical trials and observational studies. This paper considers the situation where the ending statuses of competing events have different clinical interpretations and/or are of simultaneous interest. In clinical trials, often more than one competing event has meaningful clinical interpretations even though the trial effects of different events could be different or even opposite to each other. In this paper, we develop estimation procedures and inferential properties for the joint use of multiple cumulative incidence functions (CIFs). Additionally, by incorporating longitudinal marker information, we develop estimation and inference procedures for weighted CIFs and related metrics. The proposed methods are applied to a COVID‐19 in‐patient treatment clinical trial, where the outcomes of COVID‐19 hospitalization are either death or discharge from the hospital, two competing events with completely different clinical implications. [ABSTRACT FROM AUTHOR]

Polypharmacy, the use of multiple and potentially inappropriate medications, is an increasing problem among older adults. The global polypharmacy prevalence is 34.6% in patients with COVID-19, and polypharmacy in COVID-19 increases with age. The present paper proposes that polypharmacy in older adults with COVID-19 and other comorbid conditions is linked to the medication outcome reporting bias of randomized controlled trials. Outcome reporting bias can occur when treatment efficacy is reported as relative risk reductions, which overestimates medication benefits and exaggerates disease/illness risk reductions compared to unreported absolute risk reductions. The comorbidities common in patients with COVID-19 include high blood pressure, cardiovascular disease, dementia or cerebrovascular disease, and diabetes. Accordingly, the present paper reassesses the relative and absolute risk reductions in clinical trials from a small convenience sample of antihypertension, statin, anticoagulant, and antihyperglycemic medications. Examples demonstrate a wide gap between reported relative risk reductions and unreported absolute risk reductions in medication clinical trials. This paper concludes that medication clinical trial outcome reporting bias is an important upstream factor that contributes to biased medication benefits and poor clinical decision making, leading to polypharmacy in older adults with COVID-19 and other comorbid conditions. Public health campaigns are urgently needed to educate the public about the link between polypharmacy and medication outcome reporting bias. [ABSTRACT FROM AUTHOR]

Background: This review aimed to analyze the relapse in orthognathic surgery. Methods: PubMed, Scopus, and Web of Science databases were used to find papers that matched our topic dating from 1 January 2012 up to November 2022. Inclusion criteria were (1) human studies, (2) open access studies, (3) studies concerning the correlation between orthognathic surgery and relapse. Exclusion criteria were: (1) in vitro or animal studies, (2) off-topic studies, (3) reviews, (4) other languages than English. Results: A total of 482 results were obtained resulting in 323 publications after duplicate removal (158). After screening and eligibility phases 247 records were excluded: 47 reviews, 5 in animals, 35 in vitro, 180 off-topic. The authors successfully retrieved the remaining 78 papers and evaluated their eligibility. A total of 14 studies from these were ultimately included in the review. Conclusion: Using cephalometric examinations and digital study models, these studies reveal that the relapse after orthognathic surgery is an event that occurs in most of the cases. The limitation of our research is that most of the studies are retrospective and use small sample sizes. A future research goal should be to conduct long-term clinical trials with larger numbers of samples. [ABSTRACT FROM AUTHOR]

The field of tissue engineering involves various methodologies employed to improve or replace biological tissues with extracellular matrices (ECMs). Significant progress has been made, particularly in the fabrication of three-dimensional (3D) scaffolds for replacing damaged tissues or organs. The current review broadly focuses on the various research works carried out involving the use of biomaterials (biopolymers, bio-ceramics and dopants) in this area. A detailed discussion on several scaffold-making modern technologies has also been provided, along with a demonstration of different characterization techniques. Though a number of review papers have been published on biomaterials and fabrication techniques, a very small number focuses on the clinical trials carried out and the commercialization of scaffolds in the biomedical field. Thus, a critical analysis and detailed discussion of some of the clinical trials, market growth, and future demands have been presented in this paper. [ABSTRACT FROM AUTHOR]

Background: Severe and enduring anorexia nervosa (SE-AN) is amongst the most impairing of all mental illnesses. Collective uncertainties about SE-AN nosology impacts treatment refinement. Qualitative research, particularly lived experience literature, can contribute to a process of revision and enrichment of understanding the SE-AN experience and further develop treatment interventions. Poor outcomes to date, as evidenced in clinical trials and mortality for people with SE-AN (1 in 20) demonstrate the need for research that informs conceptualisations and novel treatment directions. This interpretative, meta-ethnographic meta-synthesis aimed to bridge this gap. Methods: A systematic search for qualitative studies that explored the AN experiences of people with a duration of greater than 3 years was undertaken. These studies included those that encompassed phenomenology, treatment experiences and recovery. Results: 36 papers, comprising 382 voices of SE-AN experiences informed the meta-ethnographic findings. Four higher order constructs were generated through a synthesis of themes and participant extracts cited in the extracted papers: (1) Vulnerable sense of self (2) Intra-psychic processes (3) Global impoverishment (4) Inter-psychic temporal processes. Running across these meta-themes were three cross cutting themes (i) Treatment: help versus harm, (ii) Shifts in control (iii) Hope versus hopelessness. These meta-themes were integrated into conceptualisations of SE-AN that was experienced as a recursive process of existential self-in-relation to other and the anorexia nervosa trap. Conclusions: The alternative conceptualisation of SE-AN proposed in this paper poses a challenge to current conceptualisations of AN and calls for treatments to engage with the complex intra and inter-psychic processes of the SE-AN, more fully. In doing so, clinicians and researchers are asked to continue to be bold in testing novel ideas that may challenge our own rigidity and attachment to dominant paradigms to best serve the individual person with SE-AN. The 'global impoverishment of self', found in this synthesis of AN experiences, should inform proposed diagnostic criteria for SE-AN. [ABSTRACT FROM AUTHOR]

In 2019, the National Health Interview survey found that nearly 59% of adults reported pain some, most, or every day in the past 3 months, with 39% reporting back pain, making back pain the most prevalent source of pain, and a significant issue among adults. Often, identifying a direct, treatable cause for back pain is challenging, especially as it is often attributed to complex, multifaceted issues involving biological, psychological, and social components. Due to the difficulty in treating the true cause of chronic low back pain (cLBP), an over-reliance on opioid pain medications among cLBP patients has developed, which is associated with increased prevalence of opioid use disorder and increased risk of death. To combat the rise of opioid-related deaths, the National Institutes of Health (NIH) initiated the Helping to End Addiction Long-TermSM (HEAL) initiative, whose goal is to address the causes and treatment of opioid use disorder while also seeking to better understand, diagnose, and treat chronic pain. The NIH Back Pain Consortium (BACPAC) Research Program, a network of 14 funded entities, was launched as a part of the HEAL initiative to help address limitations surrounding the diagnosis and treatment of cLBP. This paper provides an overview of the BACPAC research program's goals and overall structure, and describes the harmonization efforts across the consortium, define its research agenda, and develop a collaborative project which utilizes the strengths of the network. The purpose of this paper is to serve as a blueprint for other consortia tasked with the advancement of pain related science. [ABSTRACT FROM AUTHOR]

FLASH radiation therapy (FLASH-RT), delivered with ultrahigh dose rate (UHDR), may allow patients to be treated with less normal tissue toxicity for a given tumor dose compared with currently used conventional dose rate. Clinical trials are being carried out and are needed to test whether this improved therapeutic ratio can be achieved clinically. During the clinical trials, quality assurance and credentialing of equipment and participating sites, particularly pertaining to UHDR-specific aspects, will be crucial for the validity of the outcomes of such trials. This report represents an initial framework proposed by the NRG Oncology Center for Innovation in Radiation Oncology FLASH working group on quality assurance of potential UHDR clinical trials and reviews current technology gaps to overcome. An important but separate consideration is the appropriate design of trials to most effectively answer clinical and scientific questions about FLASH. This paper begins with an overview of UHDR RT delivery methods. UHDR beam delivery parameters are then covered, with a focus on electron and proton modalities. The definition and control of safe UHDR beam delivery and current and needed dosimetry technologies are reviewed and discussed. System and site credentialing for large, multi-institution trials are reviewed. Quality assurance is then discussed, and new requirements are presented for treatment system standard analysis, patient positioning, and treatment planning. The tables and figures in this paper are meant to serve as reference points as we move toward FLASH-RT clinical trial performance. Some major questions regarding FLASH-RT are discussed, and next steps in this field are proposed. FLASH-RT has potential but is associated with significant risks and complexities. We need to redefine optimization to focus not only on the dose but also on the dose rate in a manner that is robust and understandable and that can be prescribed, validated, and confirmed in real time. Robust patient safety systems and access to treatment data will be critical as FLASH-RT moves into the clinical trials. [ABSTRACT FROM AUTHOR]

Background: Despite the enormous success of anterior cruciate ligament (ACL) reconstruction, acute neuropathic pain can develop postoperatively and is both distressing and difficult to treat once established. Pregabalin, an anticonvulsant agent that selectively affects the nociceptive process, has been used as a pain relief agent. The purpose of this systematic review of randomized controlled trials (RCTs) was to evaluate the pain control effect of pregabalin versus placebo after ACL reconstruction. Method: A search of the literature was performed from inception to June 2022, using PubMed, Scopus, Google Scholar, Web of Science, Cochrane and EBSCO. Studies considered for inclusion were RCTs that reported relevant outcomes (postoperative pain scores, cumulative opioid consumption, adverse events) following administration of pregabalin in patients undergoing ACL reconstruction. Result: Five placebo-controlled RCTs involving 272 participants met the inclusion criteria. 75 mg and 150 mg oral pregabalin was used in included trials. Two studies used a single dose of pregabalin one hour before anesthesia induction. Two studies used pregabalin 1 hour before anesthesia induction and 12 hours after. One study used daily pregabalin 7 days before and 7 days after surgery. Out of five papers, three papers found significantly lower pain intensity and cumulative opioid consumption in pregabalin group compared with placebo group. However, a decrease in pain scores was found in all trials. Pregabalin administration was associated with dizziness and nausea. Conclusion: The use of pregabalin may be a valuable asset in pain management after ACL reconstruction. However, future studies with larger sample size and longer follow-up period are required. [ABSTRACT FROM AUTHOR]

Background: While there have been several school‐based physical activity (PA) interventions targeting improvement in cardiovascular disease (CVD) risk factors, few have assessed long‐term effects. The aim of this paper was therefore to determine intervention effects on CVD risk factors 5 years after cessation. Methods: Two schools were assigned to intervention (n = 125) or control (n = 134). The intervention school offered 210 min/week more PA than the control school over two consecutive years (fourth and fifth grades). Follow‐up assessment was conducted 5‐year post‐intervention (10th grade) where 180–210 (73%–85%) children provided valid data. Outcomes were CVD risk factors: triglyceride, total‐to‐high‐density‐lipoprotein‐cholesterol ratio (TC:HDL ratio), insulin resistance, blood pressure (BP), waist circumference, and cardiorespiratory fitness (VO2peak). Variables were analyzed individually and as a composite score through linear mixed models, including random intercepts for children. Results: Analyses revealed significant sustained 5‐year intervention effects for HDL (effect sizes [ES] = 0.22), diastolic BP (ES = 0.48), VO2peak (ES = 0.29), and composite risk score (ES = 0.38). These effects were similar to the immediate results following the intervention. In contrast, while TC:HDL ratio initially decreased post‐intervention (ES = 0.27), this decrease was not maintained at 5‐year follow‐up (ES = 0.09), whereas WC was initially unchanged post‐intervention (ES = 0.02), but decreased at 5‐year follow‐up (ES = 0.44). Conclusion: The significant effects of a 2‐year school‐based PA intervention remained for CVD risk factors 5 years after cessation of the intervention. As cardiometabolic health can be maintained long‐term after school‐based PA, this paper demonstrates the sustainability and potential of schools in the primary prevention of future CVD risk in children. [ABSTRACT FROM AUTHOR]

For the analysis of a time‐to‐event endpoint in a single‐arm or randomized clinical trial it is generally perceived that interpretation of a given estimate of the survival function, or the comparison between two groups, hinges on some quantification of the amount of follow‐up. Typically, a median of some loosely defined quantity is reported. However, whatever median is reported, is typically not answering the question(s) trialists actually have in terms of follow‐up quantification. In this paper, inspired by the estimand framework, we formulate a comprehensive list of relevant scientific questions that trialists have when reporting time‐to‐event data. We illustrate how these questions should be answered, and that reference to an unclearly defined follow‐up quantity is not needed at all. In drug development, key decisions are made based on randomized controlled trials, and we therefore also discuss relevant scientific questions not only when looking at a time‐to‐event endpoint in one group, but also for comparisons. We find that different thinking about some of the relevant scientific questions around follow‐up is required depending on whether a proportional hazards assumption can be made or other patterns of survival functions are anticipated, for example, delayed separation, crossing survival functions, or the potential for cure. We conclude the paper with practical recommendations. [ABSTRACT FROM AUTHOR]

The natural history of spinal muscular atrophy has been radically changed by the advent of improved standards of care and the availability of disease-modifying therapies. The aim of this paper is to provide the current therapeutic scenario including new perspectives and to report the challenges related to new phenotypes a few years after the therapies have become available. The paper also includes a review of real-world data that provides information on safety and efficacy in individuals that were not included in clinical trials. Special attention is paid to future perspectives both in terms of new drugs that are currently investigated in clinical trials or providing details on current developments in the use of the available drugs, including combination therapies or new modalities of dose or administration. Conclusion: Clinical trials and real world data support the efficacy and safety profiles of the available drugs. At the moment there is not enough published evidence about the superiority of one product compared to the others. What is Known: • Safety and efficacy results of clinical trials have led in the last 6 years to the marketing of three drugs for spinal muscular atrophy, with different mechanisms of action. What is New: • Since the drug's approval, real-world data allow us to have data on bigger and heterogeneous groups of patients in contrast with those included in clinical trials. • In addition to the new molecules, combinations of therapies are currently being evaluated. [ABSTRACT FROM AUTHOR]

As medical device development becomes increasingly global, the opportunities and potential advantages offered by international clinical trial and regulatory approval strategies are also growing. In particular, medical device clinical trials involving sites in both the United States and Japan and intended to support marketing in both countries may warrant particular consideration, given the similarities in their regulatory systems, patients and clinical practice patterns, and market sizes. Since 2003, the US-Japan Harmonization By Doing (HBD) initiative has been focused on identifying and addressing clinical and regulatory barriers to medical devices access in both countries via collaboration between governmental, academic, and industry stakeholders. Through the efforts of HBD participants, US-Japanese clinical trials have been conducted and the resulting data have supported regulatory approval for marketing in both countries. Based on these experiences, this paper outlines some of the key factors to consider when developing a global clinical trial involving US and Japanese participation. These considerations include the mechanisms for consultation with regulatory authorities on clinical trial strategies, the regulatory framework for clinical trial notification and approval, recruitment and conduct of clinical sites, and lessons learned from specific US-Japanese clinical trial experiences. The goal of this paper is to promote global access to promising medical technologies by assisting potential clinical trial sponsors in understanding when an international strategy may be appropriate and successful. • Perspectives on how to maximize opportunities for global clinical trials for medical devices • US and Japanese regulatory processes for device clinical study consultations and applications • Lessons from actual US-Japanese clinical trials supporting cardiovascular device approval • Leveraging existing multi-stakeholder collaborations via Harmonization by Doing (HBD) program [ABSTRACT FROM AUTHOR]

Background: Many studies were conducted to evaluate the association between dietary glycemic index, glycemic load and children obesity. The aim of this study was to review these studies. Methods: We searched the ISI and PubMed databases for studies that evaluated the association between dietary glycemic index, glycemic load and obesity in children. At first, the studies containing the words "glycemic index", "glycemic load", "glycaemic index" or "glycaemic load" plus "child", "children", "young", "youth" or "adolescent" were selected. Among 1001 selected studies, articles were accepted if they had considered obesity or related factors as their main dependent variables. Findings: Twenty studies were included. Although the cross-sectional results were inconsistent, stronger studies had found a direct relation between dietary glycemic index, glycemic load and children obesity. Cohort studies had shown positive, neutral and negative associations between these dietary factors and obesity in children. However, although most clinical trials had reported a positive effect of dietary glycemic index on childhood obesity, they had not shown the similar effect for glycemic load. Conclusion: There is not enough evidence for making a certain conclusion. Therefore, further studies in this field are suggested. [ABSTRACT FROM AUTHOR]

Introduction: Clinical trials require sufficient samples recruited within limited time and budget constraints. Trials with minors are additionally burdened by the requirement for youth assent and parental permission. This paper details the use of Facebook ads and traditional paper mailings to enroll 797 adolescent girls for a longitudinal, web-based, drug abuse prevention trial. Data on sample representativeness and retention are also provided.Methods: Facebook ads appeared on the pages of females aged 13 or 14years who reside in the U.S. Ads linked girls to a recruitment website. Girls who wanted more information submitted contact information and were mailed information packets to their homes containing, among other things, youth assent and parent permission forms. Returned forms were verified for accuracy and validity.Results: The Facebook ad campaign reached 2,267,848 girls and had a unique click-through rate of 3.0%. The campaign cost $41,202.37 with an average cost of $51.70 per enrolled girl. Information packets were mailed to 1,873 girls. Approximately one-half of girls returned the forms, and 797 girls were enrolled. The Facebook campaign's success varied by ad type, month, and day of the week. Baseline data revealed comparability to national data on demographic and substance use variables.Conclusions: Results suggest that Facebook ads provide a useful initial point of access to unparalleled numbers of adolescents. Clinical trials may benefit from a two-fold recruitment strategy that uses online ads to attract interested adolescents followed by traditional recruitment methods to communicate detailed information to adolescents and parents. [ABSTRACT FROM AUTHOR]

Abstract: Ovarian cancer is a heterogeneous, rapidly progressive, highly lethal disease of low prevalence. The etiology remains poorly understood. Numerous risk factors have been identified, the most prominent involving an inherited predisposition in 10% of cases. Women with germline mutations associated with Hereditary Breast/Ovarian Cancer and Lynch syndromes have dramatically elevated risks (up to 46% and 12%, respectively). Risk-reducing salpingo-oophorectomy is the best method to prevent ovarian cancer in these high-risk women. Significant risk reduction is also seen in the general population who use oral contraceptives. Since up to 89% patients with early-stage disease have symptoms prior to diagnosis, increased awareness of the medical community may facilitate further workup in patients who otherwise would have had a delay. Despite enormous effort, there is no proof that routine screening for ovarian cancer in either the high-risk or general populations with serum markers, sonograms, or pelvic examinations decreases mortality. Further evaluation is needed to determine whether any novel biomarkers, or panels of markers, have clinical utility in early detection. Prospective clinical trials have to be designed and completed prior to offering of any of these new diagnostic tests. CA125 is currently the only biomarker recommended for monitoring of therapy as well as detection of recurrence. This commentary provides an overview on the background, screening and surveillance of ovarian cancer. [Copyright &y& Elsevier]

The use of statistics in medical diagnoses and biomedical research may affect whether an individual may live or die, whether their health is protected or jeopardized. Because society depends on sound statistical practice, all practitioners of statistics, whatever their training or occupation, have social obligations to perform their work in a professional, competent, and ethical manner. [ABSTRACT FROM AUTHOR]

A review of 75 original articles from clinical cancer research in Norway is presented. Articles published in 1993 and with at least one Norwegian author were included in the review. Sixty papers were observational, whereas 15 were experimental. Of the observational studies 44 were retrospective. Most of the papers concerned prognostic factors. Prior hypotheses were explicitly defined in 16 papers only, and less than half of the articles described inclusion and exclusion criteria. Sample size calculations were performed in four papers only. The choice of statistical method was considered to be suitable in 22 of the 58 articles presenting statistical inferences. Problems related to multiple significance testing were rarely addressed, although the median number of p-values reported was as high as 8. Confidence intervals for main findings were presented in 14 papers. For proper planning of studies, as well as for analysis and interpretation of study results, statistical advice is indeed required. [ABSTRACT FROM AUTHOR]

The methodology of randomized clinical trials is essential for the critical assessment and registration of therapeutic interventions. The CONSORT (Consolidated Standards of Reporting Trials) statement was developed to alleviate the problems arising from the inadequate reporting of randomized controlled trials. The present article reflects on the items that we believe should be included in the CONSORT checklist in the context of conducting and reporting trials in allergen-specific immunotherapy. Only randomized, blinded (in particular blinding of patients, health care providers, and outcome assessors), placebo-controlled Phase III studies in this article. Our analysis focuses on the definition of patients’ inclusion and exclusion criteria, allergen standardization, primary, secondary and exploratory outcomes, reporting of adverse events and analysis. [ABSTRACT FROM AUTHOR]

Background: Patient-reported outcomes (PROs) are the consequences of disease and/or its treatment as reported by the patient. The importance of PRO measures in clinical trials for new drugs, biological agents, and devices was underscored by the release of the US Food and Drug Administration's draft guidance for industry titled “Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims.” The intent of the guidance was to describe how the FDA will evaluate the appropriateness and adequacy of PRO measures used as effectiveness end points in clinical trials... [ABSTRACT FROM AUTHOR]

This discussion of Michael Parsons's exposition of the Independent Tradition's clinical theory of technique compares and contrasts the British Independent and American Relational perspectives in regard to their approach to technique. In this discussion I will consider the question whether, given strong object relational influences on relational psychoanalytic theory, we are able to locate systematic differences in the way that Independent and Relational analysts attempt to work, to be with, and to relate to their patients in the psychoanalytic situation. Overlapping historical roots of the two traditions are considered, along with apparent differences in the ways in which the contributions of common ancestors, such as Ferenzci, are applied. I suggest that the integration of American Interpersonal School ideas with Object Relations theory in American Relational Psychoanalysis led to a different therapeutic sensibility, different ways of thinking about and participating in the analytic process from those that are reflected in the Independent Tradition as Dr. Parsons describes it. The discussion includes an imaginative reconsideration of clinical process along relational lines, in an attempt to clarify different emphases in technique between the two schools. [ABSTRACT FROM AUTHOR]

The article presents the recommended design features of future clinical trials of antibacterial agents for community-acquired pneumonia (CAP). The efficaciousness of new antibiotics for the treatment of CAP has been assessed and compared with that of established antibiotics in noninferiority clinical trials. But the U.S. Food and Drug Administration is reassessing the appropriateness of a noninferiority trial design for CAP. Based on the pertinent data, there is a definitive and substantial treatment effect of antibiotic therapy for CAP. The evidence supporting a treatment effect of antibiotics includes higher mortality rates among patients with CAP, immediate decline in the mortality due to CAP, higher rates of treatment failure among patients infected with organisms and many others.

The article focuses on the guidelines released by the Food & Drug Administration (FDA), which demonstrates the flexibility and willingness of the department to engage regulated entities in the U.S. It provides specific definitions for source documentation and direct data entry, and recommendations on how to use computerized systems in clinical investigations. It also includes advice for clinical sites, analytical laboratories, and central laboratories. INSET: FDA Regulations vs Guidances.

This article has two major purposes. First, we propose a methodology that can help biostatistical reviewers of nonsequential randomized clinical trials, armed only with the single summary statistic from the trial, ask the "what if" question "Could a group sequential design have reached a definitive conclusion earlier?" As a side benefit of this research, four-stage group sequential designs that are optimal in some sense are obtained to serve as reference designs for assessing an actual design against a reasonable alternative design with the same power as the original. Four-stage designs were chosen as a practical limit on the number of stages most practitioners would consider, given the inconvenience of interim analysis, including the need to close studies to accrual while the required follow-up information is collected. Since journal editors and the public can subject the trial to close scrutiny after the fact, this new capability could alter the mind-set of some investigators designing clinical trials. Two real examples that were heavily criticized for staying open too long will be presented. [ABSTRACT FROM AUTHOR]

Background: A number of studies indicate a link between cannabis-use and psychosis as well as more severe psychosis in those with existing psychotic disorders. There is currently insufficient evidence to decide the optimal way to treat cannabis abuse among patients with psychosis. Objectives: The major objective for the CapOpus trial is to evaluate the additional effect on cannabis abuse of a specialized addiction treatment program adding group treatment and motivational interviewing to treatment as usual. Design: The trial is designed as a randomized, parallel-group, observer-blinded clinical trial. Patients are primarily recruited through early-psychosis detection teams, community mental health centers, and assertive community treatment teams. Patients are randomized to one of two treatment arms, both lasting six months: 1) specialized addiction treatment plus treatment as usual or 2) treatment as usual. The specialized addiction treatment is manualized and consists of both individual and group-based motivational interviewing and cognitive behavioral therapy, and incorporates both the family and the case manager of the patient. The primary outcome measure will be changes in amount of cannabis consumption over time. Other outcome measures will be psychosis symptoms, cognitive functioning, quality of life, social functioning, and cost-benefit analyses. Trial registration: ClinicalTrials.gov NCT00484302. [ABSTRACT FROM AUTHOR]

The article discusses the adaptive dose-ranging designs. The author focuses on several aspects in pharmacology including the objectives of such trials, the decision criteria of each objective, the simulation method and accrual and long-term endpoints. Some recommendations regarding the clinical study of drug development is also presented.

Background: Based on a recognized need for research to examine the premise that nonsurgical approaches can be used effectively to treat signs and symptoms of scoliosis, a scientific society on scoliosis orthopaedic and rehabilitation treatment (SOSORT) was established in Barcelona in 2004. SOSORT has a primary goal of implementing multidisciplinary research to develop quantitative, objective data to address the role of conservative therapies in the treatment of scoliosis. This international working group of clinicians and scientists specializing in treatment of scoliosis met in Milan, Italy in January 2005. Methods: As a baseline for developing a consensus for language and goals for proposed multicenter clinical studies, we developed questionnaires to examine current beliefs, before and after the meeting, regarding (1) the aims of physical exercises; (2) standards of treatment; and (3) the impact of such treatment performed by specialists in the field. Results: The responses to the questionnaires show that, in principle, specialists in scoliosis physiotherapy do not disagree and that several features can be regarded, currently, as standard features in the rehabilitation of scoliosis patients. These features include autocorrection in 3D, training in ADL, stabilizing the corrected posture, and patient education. [ABSTRACT FROM AUTHOR]

The article discusses the 21st anniversary of the Anaesthesia and Intensive Care Jeanette Thirlwell Best Paper Award. It mentions that inaugural Anaesthesia and Intensive Care Junior Investigator Award for 2017 has been awarded to Leigh White of the School of Medicine, University of Wollongong. It also reveals that editorial board of the journal appoints a selection committee of three of its members to adjudicate on the best paper.

The article comments on the study "Prevention of Cardiovascular Events With an Antihypertensive Regimen of Amlodipine Adding Perindopril as Required Versus Atenolol Adding Bendroflumethiazide as Required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm: A Multicentre Randomised Controlled Trial," by B. Dahlof, P. S. Sever, N. R. Poulter and colleagues. It explains that the trial suggests that atenolol is not an acceptable therapy for the treatment hypertension. Further, it suggests that a strategy using a calcium channel blockers is more effective than the β-blocker atenolol. It argues that the trial was not a trial of combination agent therapy and should not be interpreted as such. It also states the blood pressure in the trial was poorly controlled.

The article focuses on various studies related to women's health. Randomized trials, conducted by researcher P.M. Ridker and colleagues, have shown that low-dose aspirin decreases the risk of a first myocardial infarction in men, with little effect on the risk of ischemic stroke. There are few similar data in women. Researchers randomly assigned 39,876 initially healthy women 45 years of age or older to receive 100 mg of aspirin on alternate days or placebo and then monitored them for 10 years for a first major cardiovascular event. In this large, primary-prevention trial among women, aspirin lowered the risk of stroke without affecting the risk of myocardial infarction or death from cardiovascular causes, leading to a non-significant finding with respect to the primary end point. To evaluate combinations of L-thyroxine plus liothyronine in hypothyroid patients that match the proportions present in normal secretions of the human thyroid gland, H.F. Escobar-Morreale and colleagues conducted a randomized trial on 28 women with overt primary hypothyroidism.

Because of its B-cell depleting effect, rituximab has entered clinical trials in several autoimmune conditions. This study assesses the efficacy and safety of rituximab in 57 adults with chronic immune thrombocytopenic purpura (ITP). All patients had platelet counts <30 × 109/l, all had received two or more previous ITP treatments and 31 had undergone splenectomy. Patients received rituximab 375 mg/m2 weekly for 4 weeks. Thirty-one patients (54%) responded, achieving a platelet count >50 × 109/l: 18 achieved a complete response (CR: platelet count >150 × 109/l) and 13 a partial response (PR: platelet count 50–150 × 109/l). Twenty-nine responses occurred within 8 weeks of the first infusion. Sixteen of 18 CR patients (28% overall), including eight who had failed splenectomy, continued in CR after a median of 72·5 weeks; 15 of 16 are >1 year from the first infusion. Only two of 13 maintained a PR. Thirty-three patients experienced grade 1–2 adverse events and one a grade 3 event, but they all completed treatment. Circulating B cells fell to <0·03 × 109/l. No changes in immunoglobulin levels or infectious complications were seen. In summary, rituximab was well tolerated with no immediate complications and induced a lasting, substantial response in 32% of adults with chronic ITP. [ABSTRACT FROM AUTHOR]

Discusses the use of angiotensin-converting enzyme (ACE) inhibitor in reducing cardiovascular events and myocardial infarction based on the European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease clinical trial. Benefits of the ACE-inhibitor therapy; Statistics on patients who are involved in the trial; Association of the reduction in vascular events with small changes in systolic blood pressure and diastolic blood pressure.

Visual selective attention is the ability to attend to relevant visual information and ignore irrelevant stimuli. Little is known about its typical and atypical development in early childhood. Experiment 1 investigates typically developing toddlers’ visual search for multiple targets on a touch-screen. Time to hit a target, distance between successively touched items, accuracy and error types revealed changes in 2- and 3-year-olds’ vulnerability to manipulations of the search display. Experiment 2 examined search performance by toddlers with Fragile X syndrome (FXS) or Williams syndrome (WS). Both of these groups produced equivalent mean time and distance per touch as typically developing toddlers matched by chronological or mental age; but both produced a larger number of errors. Toddlers with WS confused distractors with targets more than the other groups; while toddlers with FXS perseverated on previously found targets. These findings provide information on how visual search typically develops in toddlers, and reveal distinct search deficits for atypically developing toddlers. [ABSTRACT FROM AUTHOR]

According to an article in Pulse International, China is expected to become the world leader in research and clinical trials by 2025. Currently, the United States and China publish the most research papers, but China's progress in various fields, including clinical trials, is rapidly increasing. Other countries such as Japan, South Korea, Brazil, and India are also making significant advancements in clinical trials. The article emphasizes the importance of collaboration between academia and the pharmaceutical industry for successful clinical trials and the need for biotechnology plants in Pakistan. The author also discusses the different phases of clinical trials and the challenges faced in conducting research. The article concludes by highlighting the importance of integrity, ethics, and transparency in research, as well as the potential economic benefits of clinical research organizations. [Extracted from the article]

According to Prof. Javed Akram, President of the Pakistan Society of Internal Medicine, China is expected to become the world leader in research and clinical trials by 2025. Currently, the United States and China publish the most research papers, but China's progress in these fields is significant. Other countries, such as Japan, South Korea, Brazil, and India, are also prioritizing clinical trials. Prof. Akram emphasized the importance of collaboration between academia and the pharmaceutical industry for successful clinical trials and research publications. He also discussed various clinical trials conducted in Pakistan, including those related to COVID-19 and the need for biotechnology plants. Prof. Akram highlighted the phases of clinical trials, the challenges faced, and the importance of integrity, ethics, and transparency in research. [Extracted from the article]

The increasing digitisation of healthcare services has transformed healthcare provision into a data-centric enterprise. Thinking with Joan Tronto and her notion of care, we study medical data practices in the context of a health-tech company developing an algorithmically driven platform to match patients and their physicians with clinical trials. What does it mean to pose the patient in the centre in such a context? In this paper, we show how the enactments of patient-centrism translate to multidimensional enactments of data care for a diversity of domain experts handling medical data, informed by the values and backgrounds of each 'data handler' situated within the concerns of their domain expertise. Where data experts engage solely with the patients' data to facilitate data creation for the platform's algorithmic system, the quest for data quality depends on the preceding practices of care and affective labour about and for the patients. We show how patients get help to torque their medical records and histories into data to fit the demands of the system to ensure access to experimental treatments and clinical trials. We demonstrate how patient-centrism manifests as care for data quality, shaped throughout by differentiated concerns for regulatory compliance. Finally, we argue that regulatory compliance constitutes a care practice across data work that is diversified in its enactments by the experts' domain concerns and backgrounds. [ABSTRACT FROM AUTHOR]