Displaying publications 41 - 60 of 157 in total

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  1. Jalaludin MY, Barrientos-Pérez M, Hafez M, Lynch J, Shehadeh N, Turan S, et al.
    Clin Trials, 2020 02;17(1):87-98.
    PMID: 31450961 DOI: 10.1177/1740774519870190
    BACKGROUND: The prevalence of type 2 diabetes is increasing in youths and differs from adult-onset type 2 diabetes in its characteristics and progression. Currently, only two drugs are approved for youth-onset type 2 diabetes and many patients are not meeting glycemic targets. Clearly, there is an urgent need to complete clinical trials in youths with type 2 diabetes to increase the therapeutic choice for these patients. However, factors such as limited patient numbers, unwillingness of patients to participate in trials, failure to meet strict inclusion and exclusion criteria, and poor clinic attendance have limited the size and number of trials in this complicated patient demographic.

    RECOMMENDATIONS: This is a narrative opinion piece on the design of clinical trials in youth-onset type 2 diabetes prepared by researchers who undertake this type of study in different countries. The review addresses possible ways to enhance trial designs in youth-onset type 2 diabetes to meet regulatory requirements, while minimizing the barriers to patients' participation. The definition of adolescence, recruitment of sufficient patient numbers, increasing flexibility in selection criteria, improving convenience of trial visits, requirements of a control group, possible endpoints, and trial compliance are all considered. The authors recommend allowing extrapolation from adult data, using multiple interventional arms within future trials, broadening inclusion criteria, and focusing on endpoints beyond glucose control, among others, in order to improve the successful completion of more trials in this population.

    CONCLUSIONS: Improvements in trial design will enable better recruitment and retention and thereby more evidence for treatment outcomes for youth-onset type 2 diabetes.

    Matched MeSH terms: Clinical Trials as Topic/methods*
  2. See HY, Mohamed MS, Mohd Noor SN, Low WY
    Account Res, 2019 01;26(1):49-64.
    PMID: 30526066 DOI: 10.1080/08989621.2018.1556646
    The review of clinical trials with human participants in Malaysia is governed by a decentralized control system. The clinical trial protocols are reviewed by 13 registered research ethics committees (RECs) in Malaysia. A governmental body, the National Pharmaceutical Control Bureau, is responsible for the inspection and oversight of these registered RECs to ensure that they comply with the regulatory requirements. However, this study highlights that each REC in Malaysia has a different standard operating procedure and ethical review process. Other procedural challenges identified include inadequate membership, poor mechanism for research monitoring after ethical approval, and insufficient resources. Establishments of a national standard of REC and a central ethics committee are suggested to ensure procedural compliance in the oversight of clinical trials in Malaysia. While there is a growing concern that procedural compliance may not have a direct impact on the protection of human subjects, our key point is that an ethical review system compliant with the national standards could serve as a strong framework to support and enhance the ethical quality of decision-making and judgement. We believe that being aware of how influential procedural compliance can be would help committees improve the ethical quality of their research review.
    Matched MeSH terms: Clinical Trials as Topic/ethics*
  3. Murayama A, Ueda M, Shrestha S, Tanimoto T, Ozaki A
    Cancer Cell, 2021 09 13;39(9):1165-1166.
    PMID: 34358449 DOI: 10.1016/j.ccell.2021.07.008
    Matched MeSH terms: Clinical Trials as Topic/legislation & jurisprudence
  4. Mizuno H, Fukuda S, Fukumura A, Nakamura YK, Jianping C, Cho CK, et al.
    J Radiat Res, 2017 May 01;58(3):372-377.
    PMID: 27864507 DOI: 10.1093/jrr/rrw108
    A dose audit of 16 facilities in 11 countries has been performed within the framework of the Forum for Nuclear Cooperation in Asia (FNCA) quality assurance program. The quality of radiation dosimetry varies because of the large variation in radiation therapy among the participating countries. One of the most important aspects of international multicentre clinical trials is uniformity of absolute dose between centres. The National Institute of Radiological Sciences (NIRS) in Japan has conducted a dose audit of participating countries since 2006 by using radiophotoluminescent glass dosimeters (RGDs). RGDs have been successfully applied to a domestic postal dose audit in Japan. The authors used the same audit system to perform a dose audit of the FNCA countries. The average and standard deviation of the relative deviation between the measured and intended dose among 46 beams was 0.4% and 1.5% (k = 1), respectively. This is an excellent level of uniformity for the multicountry data. However, of the 46 beams measured, a single beam exceeded the permitted tolerance level of ±5%. We investigated the cause for this and solved the problem. This event highlights the importance of external audits in radiation therapy.
    Matched MeSH terms: Clinical Trials as Topic*
  5. Higuchi A, Ku NJ, Tseng YC, Pan CH, Li HF, Kumar SS, et al.
    Lab Invest, 2017 Oct;97(10):1167-1179.
    PMID: 28869589 DOI: 10.1038/labinvest.2017.100
    Cardiovascular disease remains the leading cause of death and disability in advanced countries. Stem cell transplantation has emerged as a promising therapeutic strategy for acute and chronic ischemic cardiomyopathy. The current status of stem cell therapies for patients with myocardial infarction is discussed from a bioengineering and biomaterial perspective in this review. We describe (a) the current status of clinical trials of human pluripotent stem cells (hPSCs) compared with clinical trials of human adult or fetal stem cells, (b) the gap between fundamental research and application of human stem cells, (c) the use of biomaterials in clinical and pre-clinical studies of stem cells, and finally (d) trends in bioengineering to promote stem cell therapies for patients with myocardial infarction. We explain why the number of clinical trials using hPSCs is so limited compared with clinical trials using human adult and fetal stem cells such as bone marrow-derived stem cells.
    Matched MeSH terms: Clinical Trials as Topic*
  6. Hall DA, Smith H, Hibbert A, Colley V, Haider HF, Horobin A, et al.
    Trends Hear, 2018;22:2331216518814384.
    PMID: 30488765 DOI: 10.1177/2331216518814384
    Subjective tinnitus is a chronic heterogeneous condition that is typically managed using intervention approaches based on sound devices, psychologically informed therapies, or pharmaceutical products. For clinical trials, there are currently no common standards for assessing or reporting intervention efficacy. This article reports on the first of two steps to establish a common standard, which identifies what specific tinnitus-related complaints ("outcome domains") are critical and important to assess in all clinical trials to determine whether an intervention has worked. Using purposive sampling, 719 international health-care users with tinnitus, health-care professionals, clinical researchers, commercial representatives, and funders were recruited. Eligibility was primarily determined by experience of one of the three interventions of interest. Following recommended procedures for gaining consensus, three intervention-specific, three-round, Delphi surveys were delivered online. Each Delphi survey was followed by an in-person consensus meeting. Viewpoints and votes involved all stakeholder groups, with approximately a 1:1 ratio of health-care users to professionals. "Tinnitus intrusiveness" was voted in for all three interventions. For sound-based interventions, the minimum set included "ability to ignore," "concentration," "quality of sleep," and "sense of control." For psychology-based interventions, the minimum set included "acceptance of tinnitus," "mood," "negative thoughts and beliefs," and "sense of control." For pharmacology-based interventions, "tinnitus loudness" was the only additional core outcome domain. The second step will next identify how those outcome domains should best be measured. The uptake of these intervention-specific standards in clinical trials will improve research quality, enhance clinical decision-making, and facilitate meta-analysis in systematic reviews.
    Matched MeSH terms: Clinical Trials as Topic/standards*
  7. Tomashek KM, Wills B, See Lum LC, Thomas L, Durbin A, Leo YS, et al.
    PLoS Negl Trop Dis, 2018 10;12(10):e0006497.
    PMID: 30286085 DOI: 10.1371/journal.pntd.0006497
    Dengue is a major public health problem worldwide. Although several drug candidates have been evaluated in randomized controlled trials, none has been effective and at present, early recognition of severe dengue and timely supportive care are used to reduce mortality. While the first dengue vaccine was recently licensed, and several other candidates are in late stage clinical trials, future decisions regarding widespread deployment of vaccines and/or therapeutics will require evidence of product safety, efficacy and effectiveness. Standard, quantifiable clinical endpoints are needed to ensure reproducibility and comparability of research findings. To address this need, we established a working group of dengue researchers and public health specialists to develop standardized endpoints and work towards consensus opinion on those endpoints. After discussion at two working group meetings and presentations at international conferences, a Delphi methodology-based query was used to finalize and operationalize the clinical endpoints. Participants were asked to select the best endpoints from proposed definitions or offer revised/new definitions, and to indicate whether contributing items should be designated as optional or required. After the third round of inquiry, 70% or greater agreement was reached on moderate and severe plasma leakage, moderate and severe bleeding, acute hepatitis and acute liver failure, and moderate and severe neurologic disease. There was less agreement regarding moderate and severe thrombocytopenia and moderate and severe myocarditis. Notably, 68% of participants agreed that a 50,000 to 20,000 mm3 platelet range be used to define moderate thrombocytopenia; however, they remained divided on whether a rapid decreasing trend or one platelet count should be case defining. While at least 70% agreement was reached on most endpoints, the process identified areas for further evaluation and standardization within the context of ongoing clinical studies. These endpoints can be used to harmonize data collection and improve comparability between dengue clinical trials.
    Matched MeSH terms: Clinical Trials as Topic/methods*; Clinical Trials as Topic/standards
  8. Lai LC
    Malays J Pathol, 2008 Dec;30(2):67-71.
    PMID: 19291914 MyJurnal
    HbA1c is used for assessing glycaemic control in patients with diabetes. It is also used for treatment goals and as a target for therapeutic intervention. The Direct Control and Complications Trial in the USA showed that HbA1c can be used to predict the risk of complications. Hence, it is important for HbA1c assays to be standardised. The National Glycohemoglobin Standardization Program (NGSP) in the USA was formed in 1996 so that HbA1c results from different laboratories would be comparable to those reported in the DCCT study. There were also HbA1c standardisation programmes in Sweden and Japan. These three standardisation programmes are, in fact, direct comparison methods (DCMs), and yield different HbA1c results. In 1994, the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) established a Working Group on Standardisation of HbA1c. This working group has developed a global HbA1c reference system with very much improved intra-assay and inter-assay coefficients of variation. Recommendations have been made to report HbA1c results as IFCC-HbA1c values in SI units (mmol HbA1c/mol Hb) and NGSP-HbA1c (%) as well as estimated average glucose (eAG), once a tight relationship has been shown to exist between eAG and HbA1c.
    Matched MeSH terms: Clinical Trials as Topic
  9. Sharmila S
    Med J Malaysia, 2005 Jul;60 Suppl B:136-7.
    PMID: 16108195
    Matched MeSH terms: Clinical Trials as Topic
  10. Leake DW, Hii JL
    PMID: 2699084
    Insecticide-impregnated bednets appear to be a potentially cost-effective intervention against endemic malaria in the tropics, but this has yet to be confirmed by field trials. There are two aspects to consider in assessing such trials: (1) the extent to which subjects use nets regularly and properly, and (2) the effectiveness of nets which are truly used regularly and properly in reducing malaria transmission. The second aspect is currently of primary concern, to determine if human-vector relationships for a particular at-risk population are such that bednets can be effective. But to give bednets a "fair" test in this regard requires regular and proper use in the first place. The study described here suggests they did not get a "fair" test in one field trial in Sabah, East Malaysia. The study also strongly suggests that direct observations, rather than post hoc questioning of subjects, may be essential to accurately gauge bednet usage rates. Accurate usage rates are required to determine what proportion of a population needs to use nets to reduce malaria transmission, and to evaluate the effectiveness of promotional programs over time. Direct observations can also yield valuable data on night-time activities that increase malaria risk, such as television viewing that keeps people awake and out of bednets.
    Matched MeSH terms: Clinical Trials as Topic
  11. Chuan OK, Ping WW, Fook CW
    Med J Malaysia, 1976 Jun;30(4):296-8.
    PMID: 790111
    Matched MeSH terms: Clinical Trials as Topic
  12. Balan S, Hassali MA, Mak VS
    Br J Clin Pharmacol, 2015 Dec;80(6):1269-80.
    PMID: 26314841 DOI: 10.1111/bcp.12750
    AIM: The aim of this review was to provide an updated overview of awareness, knowledge and views of off-label prescribing in children.

    METHOD: A literature search using electronic databases including PubMed, Medline, Scopus, Science Direct, Springer Link, Proquest, Ebsco Host and Google Scholar was conducted. Additional articles were identified by reviewing the bibliography of retrieved articles. The articles were searched with any of the following medical subject headings (MeSH) terms in the title: attitude, awareness, knowledge, experience, view, off-label, pediatric, paediatric and children. The inclusion criteria were full text articles published in English between January 2004 and February 2015 and reported outcome related to awareness, knowledge and views regarding off-label prescribing in children. Editorials, reviews, notes, conference proceedings, letters and studies reporting prevalence of off-label prescribing were excluded. The articles were scrutinized using thematic analysis.

    RESULTS: Eleven studies conducted among doctors, community pharmacists, paediatric nurses, parents and children met the inclusion criteria. Nine themes were developed through document analysis which included main domains such as knowledge, awareness and views on off-label drug use in children, choice of information sources, reasons and suggestions to reduce off-label prescribing, concern regarding obtaining consent and participation in clinical trials.

    CONCLUSION: The studies reviewed reported that the majority of doctors and community pharmacists were familiar with the term off-label prescribing but knowledge among parents was low. Awareness on off-label prescribing in children remains low among all study participants. There is a mismatch between views on off-label prescribing in children of study participants and the finding of previous studies.

    Matched MeSH terms: Clinical Trials as Topic
  13. Lee JL, Mohamed Shah N, Makmor-Bakry M, Islahudin FH, Alias H, Noh LM, et al.
    J Clin Immunol, 2020 07;40(5):682-698.
    PMID: 32417999 DOI: 10.1007/s10875-020-00788-5
    PURPOSE: We conducted a systematic review and meta-regression analysis to evaluate the impact of increasing immunoglobulin G (IgG) trough levels on the clinical outcomes in patients with PID receiving intravenous immunoglobulin G (IVIG) treatment.

    METHODS: Systematic search was conducted in PubMed and Cochrane. Other relevant articles were searched by reviewing the references of the reviewed article. All clinical trials with documented IgG trough levels and clinical outcome of interest in patients receiving IVIG treatment were eligible to be included in this review. Meta-regression analysis was conducted using Comprehensive Meta-analysis Software. Additional sensitivity analyses were undertaken to evaluate the robustness of the overall results.

    RESULTS: Twenty-eight clinical studies with 1218 patients reported from year 2001 to 2018 were included. The mean IVIG dose used ranges from 387 to 560 mg/kg every 3 to 4 weekly, and mean IgG trough obtained ranges from 660 to 1280 mg/dL. Random-effects meta-regression slope shows that IgG trough level increases significantly by 73 mg/dL with every increase of 100 mg/kg dose of IVIG (p 

    Matched MeSH terms: Clinical Trials as Topic
  14. Waters MFR, Pettit JHS
    Int J Lepr, 1965;33(3):280-96.
    PMID: 5322767
    A controlled clinical trial, using the "double blind " technic, is reported of combined dapsone and ditophal therapy compared with dapsone and placebo in the treatment of pure lepromatous and near lepromatous leprosy. Twenty-five untreated, matched pairs were admitted, and the final analysis was made on 23 pairs and 47 patients studied for one year. Dapsone and ditophal were commenced simultaneously, and over the treatment period 0-1.5 months, a statistically significant (at the 1 per cent level) greater decrease in the percentage of solid-staining bacilli occurred in the smears of pure lepromatous patients treated with ditophal and dapsone than occurred in the smears of patients treated with placebo and dapsone. Therefore, it is evident that combined therapy resulted in a faster rate of killing of leprosy bacilli than did dapsone alone. However, only one method of clinical assessment of the pure lepromatous pairs favored combined therapy; the two other methods of clinical assessment used, and the bacterial index and biopsy index results, all failed to reveal any significant differences between the two treatment groups. In addition, the incidence and severity of erythema nodosum leprosum did not differ in the two groups. Since the more rapid death of bacilli early in treatment had little effect on the rate of improvement of patients after 12 months, the widespread use of ditophal with dapsone does not appear to be justified. Special circumstances are envisaged, however, in which ditophal would be a useful adjunct to treatment. The small number (11) of near-lepromatous patients studied showed a high incidence of lepra reactions, and 4 underwent histologic change during their year in the trial. There was no evidence that the addition of ditophal to dapsone treatment increased the rate of improvement, clinically, histologically or bacteriologically, in this type of leprosy, which, because it is so unstable, appears unsuitable for formal clinical drug trials. Although the majority of the patients included were light-skinned Chinese, no contact dermatitis or other toxic effects of ditophal were observed.
    Matched MeSH terms: Clinical Trials as Topic
  15. Saokaew S, Wilairat P, Raktanyakan P, Dilokthornsakul P, Dhippayom T, Kongkaew C, et al.
    PMID: 27694558 DOI: 10.1177/2156587216669628
    Kaempferia parviflora (Krachaidum) is a medicinal plant in the family Zingiberaceae. Its rhizome has been used as folk medicine for many centuries. A number of pharmacological studies of Krachaidum had claimed benefits for various ailments. Therefore, this study aimed to systematically search and summarize the clinical evidences of Krachaidum in all identified indications. Of 683 records identified, 7 studies were included. From current clinical trials, Krachaidum showed positive benefits but remained inconclusive since small studies were included. Even though results found that Krachaidum significantly increased hand grip strength and enhanced sexual erotic stimuli, these were based on only 2 studies and 1 study, respectively. With regard to harmful effects, we found no adverse events reported even when Krachaidum 1.35 g/day was used. Therefore, future studies of Krachaidum are needed with regards to both safety and efficacy outcomes.
    Matched MeSH terms: Clinical Trials as Topic
  16. Thorlacius L, Garg A, Ingram JR, Villumsen B, Theut Riis P, Gottlieb AB, et al.
    Br J Dermatol, 2018 03;178(3):715-721.
    PMID: 29080368 DOI: 10.1111/bjd.16093
    BACKGROUND: A core outcomes set (COS) is an agreed minimum set of outcomes that should be measured and reported in all clinical trials for a specific condition. Hidradenitis suppurativa (HS) has no agreed-upon COS. A central aspect in the COS development process is to identify a set of candidate outcome domains from a long list of items. Our long list had been developed from patient interviews, a systematic review of the literature and a healthcare professional survey, and initial votes had been cast in two e-Delphi surveys. In this manuscript, we describe two in-person consensus meetings of Delphi participants designed to ensure an inclusive approach to generation of domains from related items.

    OBJECTIVES: To consider which items from a long list of candidate items to exclude and which to cluster into outcome domains.

    METHODS: The study used an international and multistakeholder approach, involving patients, dermatologists, surgeons, the pharmaceutical industry and medical regulators. The study format was a combination of formal presentations, small group work based on nominal group theory and a subsequent online confirmation survey.

    RESULTS: Forty-one individuals from 13 countries and four continents participated. Nine items were excluded and there was consensus to propose seven domains: disease course, physical signs, HS-specific quality of life, satisfaction, symptoms, pain and global assessments.

    CONCLUSIONS: The HISTORIC consensus meetings I and II will be followed by further e-Delphi rounds to finalize the core domain set, building on the work of the in-person consensus meetings.

    Matched MeSH terms: Clinical Trials as Topic
  17. Otto S, Díaz VAJ, Weilenmann D, Cuculi F, Nuruddin AA, Leibundgut G, et al.
    BMC Cardiovasc Disord, 2023 Mar 31;23(1):176.
    PMID: 37003986 DOI: 10.1186/s12872-023-03187-x
    BACKGROUND: A decade ago, the iopromide-paclitaxel coated balloon (iPCB) was added to the cardiologist's toolbox to initially treat in-stent restenosis followed by the treatment of de novo coronary lesions. In the meantime, DES technologies have been substantially improved to address in-stent restenosis and thrombosis, and shortened anti-platelet therapy. Recently, sirolimus-coated balloon catheters (SCB) have emerged to provide an alternative drug to combat restenosis.

    METHODS: The objective of this study is to determine the safety and efficacy of a novel crystalline sirolimus-coated balloon (cSCB) technology in an unselective, international, large-scale patient population. Percutaneous coronary interventions of native stenosis, in-stent stenosis, and chronic total occlusions with the SCB in patients with stable coronary artery disease or acute coronary syndrome were included. The primary outcome variable is the target lesion failure (TLF) rate at 12 months, defined as the composite rate of target vessel myocardial infarction (TV-MI), cardiac death or ischemia-driven target lesion revascularization (TLR). The secondary outcome variables include TLF at 24 months, ischemia driven TLR at 12 and 24 months and all-cause death, cardiac death at 12 and 24 months.

    DISCUSSION: Since there is a wealth of patient-based all-comers data for iPCB available for this study, a propensity-score matched analysis is planned to compare cSCB and iPCB for the treatment of de novo and different types of ISR. In addition, pre-specified analyses in challenging lesion subsets such as chronic total occlusions will provide evidence whether the two balloon coating technologies differ in their clinical benefit for the patient.

    TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT04470934.

    Matched MeSH terms: Clinical Trials as Topic
  18. Marques Da Costa ME, Zaidi S, Scoazec JY, Droit R, Lim WC, Marchais A, et al.
    Commun Biol, 2023 Sep 18;6(1):949.
    PMID: 37723198 DOI: 10.1038/s42003-023-05320-0
    Pediatric patients with recurrent and refractory cancers are in most need for new treatments. This study developed patient-derived-xenograft (PDX) models within the European MAPPYACTS cancer precision medicine trial (NCT02613962). To date, 131 PDX models were established following heterotopical and/or orthotopical implantation in immunocompromised mice: 76 sarcomas, 25 other solid tumors, 12 central nervous system tumors, 15 acute leukemias, and 3 lymphomas. PDX establishment rate was 43%. Histology, whole exome and RNA sequencing revealed a high concordance with the primary patient's tumor profile, human leukocyte-antigen characteristics and specific metabolic pathway signatures. A detailed patient molecular characterization, including specific mutations prioritized in the clinical molecular tumor boards are provided. Ninety models were shared with the IMI2 ITCC Pediatric Preclinical Proof-of-concept Platform (IMI2 ITCC-P4) for further exploitation. This PDX biobank of unique recurrent childhood cancers provides an essential support for basic and translational research and treatments development in advanced pediatric malignancies.
    Matched MeSH terms: Clinical Trials as Topic
  19. Ong HT, Cheah JS
    N Z Med J, 2004 Feb 20;117(1189):U773.
    PMID: 15014562
    Numerous trials and meta-analyses have been conducted over the last five years to identify an ideal anti-hypertensive drug. These reports, and the JNC 7 and European hypertension guidelines, have generated some controversy and confusion. A review of the comparative anti-hypertensive drug trials shows that the differences between drugs are minor and not consistently demonstrated by different studies. However, much data have now accumulated on the safety and value of diuretics, beta blockers, calcium-channel blockers (CCBs), angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs) in reducing blood pressure and preventing clinical disease. The importance of tight blood pressure control in reducing adverse events has been clearly shown, and clinicians should concentrate on achieving target blood pressure levels, which often requires a combination of anti-hypertensive drugs. The choice of anti-hypertensive drug should be guided by the presence of concomitant clinical disease, as evidence has accumulated on the special efficacy of certain drugs in reducing damage to particular organ systems. In the absence of any associated clinical disease, it is good to initiate anti-hypertensive therapy with diuretics, provided the metabolic parameters are regularly reviewed.
    Matched MeSH terms: Clinical Trials as Topic
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