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Cancers May 2023Quality pharmacological treatment can improve survival in many types of cancer. Drug repurposing offers advantages in comparison with traditional drug development... (Review)
Review
Quality pharmacological treatment can improve survival in many types of cancer. Drug repurposing offers advantages in comparison with traditional drug development procedures, reducing time and risk. This systematic review identified the most recent randomized controlled clinical trials that focus on drug repurposing in oncology. We found that only a few clinical trials were placebo-controlled or standard-of-care-alone-controlled. Metformin has been studied for potential use in various types of cancer, including prostate, lung, and pancreatic cancer. Other studies assessed the possible use of the antiparasitic agent mebendazole in colorectal cancer and of propranolol in multiple myeloma or, when combined with etodolac, in breast cancer. We were able to identify trials that study the potential use of known antineoplastics in other non-oncological conditions, such as imatinib for severe coronavirus disease in 2019 or a study protocol aiming to assess the possible repurposing of leuprolide for Alzheimer's disease. Major limitations of these clinical trials were the small sample size, the high clinical heterogeneity of the participants regarding the stage of the neoplastic disease, and the lack of accounting for multimorbidity and other baseline clinical characteristics. Drug repurposing possibilities in oncology must be carefully examined with well-designed trials, considering factors that could influence prognosis.
PubMed: 37296934
DOI: 10.3390/cancers15112972 -
Lung Cancer (Amsterdam, Netherlands) Aug 2019This network meta-analysis (NMA), based on 12 phase-III studies with 9,236 metastatic NSCLC patients, aims to compare the efficacy of treatments including at least one... (Meta-Analysis)
Meta-Analysis
Immune checkpoint inhibitors, alone or in combination with chemotherapy, as first-line treatment for advanced non-small cell lung cancer. A systematic review and network meta-analysis.
This network meta-analysis (NMA), based on 12 phase-III studies with 9,236 metastatic NSCLC patients, aims to compare the efficacy of treatments including at least one immune-checkpoint inhibitor (ICI) with or without chemotherapy, as frontline therapy for advanced NSCLC patients. The NMA includes direct randomized evidence on treatments of interest along with indirect evidence from randomized studies with chemotherapy as the common comparator. Studies were identified by searching PubMed, and the abstracts of most recent main oncology congresses. The primary endpoint, Hazard-Ratio (HR) of Progression-free Survival (PFS), was estimated by a frequentist-approach NMA. Results are presented in the overall cohort (all-comers or PD-L1-positive) irrespective of histology, and by histology, PD-L1 expression level and sex. According to the primary PFS-NMA in the overall cohort, the combination of chemotherapy, first with pembrolizumab, second with atezolizumab exhibit significantly higher benefit than any other treatment examined. This superior PFS benefit is found for both squamous and non-squamous patients. Similarly for OS, the combination of pembrolizumab/chemotherapy, and atezolizumab/bevacizumab/chemotherapy-(ABC), followed by pembrolizumab-monotherapy and atezolizumab/chemotherapy, are the best treatments in the overall cohort, driven by the non-squamous histology. In the PD-L1-high patients again the combination of chemotherapy with atezolizumab or pembrolizumab, exhibit significant PFS benefit, followed by pembrolizumab-monotherapy. PFS benefit of these ICI/chemotherapy combinations are also found in PD-L1-negative and PD-L1-intermediate patients(1%≤PD-L1 < 50%). Of note, ABC is evaluated only for OS in non-squamous patients while the pembrolizumab-monotherapy PFS benefit and the atezolizumab/chemotherapy OS benefit are probably under-estimated since most of the data stems from non-significant interim analyses of ongoing studies [KN042;IM131/132/150]. In conclusion, the addition of chemotherapy to ICIs enhanced their treatment efficacy as first-line treatment for advanced NSCLC patients. The combination of chemotherapy with either pembrolizumab or atezolizumab show consistently higher efficacy than chemotherapy-alone or any other ICI-combination or monotherapy, particularly in non-squamous patients.
Topics: Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; B7-H1 Antigen; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Female; Gene Expression; Humans; Liver Neoplasms; Lung Neoplasms; Male; Molecular Targeted Therapy; Mutation; Neoplasm Metastasis; Neoplasm Staging; Prognosis
PubMed: 31319971
DOI: 10.1016/j.lungcan.2019.05.029 -
Osteoporosis International : a Journal... Jan 2023The role of exercise in preventing osteoporotic fractures is vague, and further recommendations for optimized exercise protocols are very rare. In the present work, we... (Meta-Analysis)
Meta-Analysis Review
Exercise and the prevention of major osteoporotic fractures in adults: a systematic review and meta-analysis with special emphasis on intensity progression and study duration.
UNLABELLED
The role of exercise in preventing osteoporotic fractures is vague, and further recommendations for optimized exercise protocols are very rare. In the present work, we provided positive evidence for exercise effects on the number of osteoporotic fractures in adults, albeit without observing any significant relevance of intensity progression or study duration.
INTRODUCTION
Osteoporotic fractures are a major challenge confronting our aging society. Exercise might be an efficient agent for reducing osteoporotic fractures in older adults, but the most promising exercise protocol for that purpose has yet to be identified. The present meta-analysis thus aimed to identify important predictors of the exercise effect on osteoporotic fractures in adults.
METHODS
We conducted a systematic search of six literature databases according to the PRISMA guideline that included controlled exercise studies and reported the number of low-trauma major osteoporotic fractures separately for exercise (EG) and control (CG) groups. Primary study outcome was incidence ratio (IR) for major osteoporotic fractures. Sub-analyses were conducted for progression of intensity (yes vs. no) during the trial and the study duration (≤ 12 months vs. > 12 months).
RESULTS
In summary, 11 studies with a pooled number of 9715 participant-years in the EG and 9592 in the CG were included. The mixed-effects conditional Poisson regression revealed positive exercise effects on major osteoporotic fractures (RR: 0.75, 95% CI: 0.54-0.94, p = .006). Although studies with intensity progression were more favorable, our subgroup analysis did not determine significant differences for diverging intensity progression (p = .133) or study duration (p = .883). Heterogeneity among the trials of the subgroups (I ≤ 0-7.1%) was negligible.
CONCLUSION
The present systematic review and meta-analysis provided significant evidence for the favorable effect of exercise on major osteoporotic fractures. However, diverging study and exercise characteristics along with the close interaction of exercise parameters prevented the derivation of reliable recommendations for exercise protocols for fracture reductions.
PROSPERO ID
CRD42021250467.
Topics: Humans; Aged; Osteoporotic Fractures; Exercise; Exercise Therapy; Aging; Quality of Life
PubMed: 36355068
DOI: 10.1007/s00198-022-06592-8 -
Photodiagnosis and Photodynamic Therapy Sep 2017Photodynamic therapy (PDT) is an effective treatment for actinic keratoses and early skin cancers, and the only office procedure to control field cancerization.... (Review)
Review
Photodynamic therapy (PDT) is an effective treatment for actinic keratoses and early skin cancers, and the only office procedure to control field cancerization. Procedure-associated pain limits widespread PDT use and by early termination of treatment can decrease overall therapeutic efficacy. Here we review and assess reported interventions on PDT-associated pain, in order to identify the most promising methods to manage treatment-associated pain and identify focus for future studies. Literature search was performed using MEDLINE, EMBASE, and the Cochrane Library by two independent reviewers to select publications that assessed and compared pain quantitatively during PDT treatment for actinic keratoses, basal cell carcinomas, and/or in situ squamous cell carcinomas. A total of 48 studies reporting on pain during PDT were identified and were comprised of two main categories of interventions: pain-controlling therapies and PDT parameter (photosensitizer or photo-irradiation) adjustments. Of these interventions: nerve block, subcutaneous infiltration anesthesia, cold analgesia, and transcutaneous electrical nerve stimulation, but not topical anesthetic gels, were associated with less PDT-related pain; 5-aminolevulinic acid (ALA) tended to be more painful than methyl-5-aminolevulinate (MAL); daylight PDT was less painful than conventional PDT; and lower irradiance delivery produced lower pain scores in general. There is no single crystalized protocol for management of PDT-related pain. Evidence suggests that continuous activation of low levels of PpIX with methods using lower irradiance and possibly shorter incubation times are associated with decreased pain without loss of PDT efficacy. Protocols to reduce pain should be standardized and large controlled trials are needed.
Topics: Anesthesia, Local; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Clinical Trials as Topic; Humans; Keratosis, Actinic; Nerve Block; Pain; Pain Measurement; Photochemotherapy; Photosensitizing Agents; Skin Diseases; Transcutaneous Electric Nerve Stimulation
PubMed: 28716738
DOI: 10.1016/j.pdpdt.2017.07.002 -
Journal of Medical Internet Research Jul 2022Given the growing significance of conversational agents (CAs), researchers have conducted a plethora of relevant studies on various technology- and usability-oriented... (Review)
Review
BACKGROUND
Given the growing significance of conversational agents (CAs), researchers have conducted a plethora of relevant studies on various technology- and usability-oriented issues. However, few investigations focus on language use in CA-based health communication to examine its influence on the user perception of CAs and their role in delivering health care services.
OBJECTIVE
This review aims to present the language use of CAs in health care to identify the achievements made and breakthroughs to be realized to inform researchers and more specifically CA designers.
METHODS
This review was conducted by following the protocols of the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 statement. We first designed the search strategy according to the research aim and then performed the keyword searches in PubMed and ProQuest databases for retrieving relevant publications (n=179). Subsequently, 3 researchers screened and reviewed the publications independently to select studies meeting the predefined selection criteria. Finally, we synthesized and analyzed the eligible articles (N=11) through thematic synthesis.
RESULTS
Among the 11 included publications, 6 deal exclusively with the language use of the CAs studied, and the remaining 5 are only partly related to this topic. The language use of the CAs in these studies can be roughly classified into six themes: (1) personal pronouns, (2) responses to health and lifestyle prompts, (3) strategic wording and rich linguistic resources, (4) a 3-staged conversation framework, (5) human-like well-manipulated conversations, and (6) symbols and images coupled with phrases. These derived themes effectively engaged users in health communication. Meanwhile, we identified substantial room for improvement based on the inconsistent responses of some CAs and their inability to present large volumes of information on safety-critical health and lifestyle prompts.
CONCLUSIONS
This is the first systematic review of language use in CA-based health communication. The results and limitations identified in the 11 included papers can give fresh insights into the design and development, popularization, and research of CA applications. This review can provide practical implications for incorporating positive language use into the design of health CAs and improving their effective language output in health communication. In this way, upgraded CAs will be more capable of handling various health problems particularly in the context of nationwide and even worldwide public health crises.
Topics: Communication; Delivery of Health Care; Health Communication; Humans; Language; Life Style
PubMed: 35802407
DOI: 10.2196/37403 -
European Journal of Hospital Pharmacy :... Dec 2023Extended infusion (EI) of beta-lactam antibiotics may offer clinical benefits aligned with improved probability of target attainment for critical...
BACKGROUND
Extended infusion (EI) of beta-lactam antibiotics may offer clinical benefits aligned with improved probability of target attainment for critical pharmacokinetic/pharmacodynamic parameters that correlate with efficacy. There is much research interest in prolonged and continuous infusions (collectively, extended infusions) of beta-lactams to improve patient outcomes, particularly in critically ill patients in intensive care. While definitive clinical trial data demonstrating beneficial outcomes is awaited, there has been limited focus on the stability of the agents given by EI, which may be an equally critical parameter. EI may allow for savings in nursing time due to reduced need for drug reconstitution. We set out to examine the data for stability for EI at room temperature, consistent with the requirements of 'A Standard Protocol for Deriving and Assessment of Stability- Part 1 Aseptic Preparation (Small Molecules)', which allows a 5% loss of active pharmaceutical ingredient (API) applicable for those territories that use the British Pharmacopoeia also for a 10% loss applicable in much of rest of the world.
METHODS
Searches using preferred reporting items for systematic reviews and meta-analyses (PRISMA) principles for stability data on freshly prepared beta-lactam antimicrobials for extended administration at room temperature (at or above 23°C) were conducted in November 2021 and updated in December 2022.
RESULTS
We found data to support the extension of the shelf life of 12 key beta-lactam antibiotics once reconstituted (aztreonam, amoxicillin, benzylpenicillin, flucloxacillin, piperacillin/tazobactam, cefazolin, cefmetazole, ceftaroline, ceftazidime, ceftriaxone, imipenem and meropenem) compliant with the NHS protocol, and data for five other agents (ticarcillin, cefepime, cefiderocol, cefoxitin and doripenem) which would be acceptable in regions outside the UK beyond that listed in the Summary of Product Characteristics.This review has not been registered under PROSPERO.
Topics: Humans; Anti-Bacterial Agents; beta Lactam Antibiotics; Inpatients; Temperature; Ceftazidime
PubMed: 37848286
DOI: 10.1136/ejhpharm-2023-003855 -
The Journal of Antimicrobial... Dec 2022Surveillance is a useful tool for tracking antimicrobial resistance (AMR) trends, patterns, therapeutic and policy interventions. Proper correlation of surveillance data... (Review)
Review
AIMS
Surveillance is a useful tool for tracking antimicrobial resistance (AMR) trends, patterns, therapeutic and policy interventions. Proper correlation of surveillance data gives meaningful insight into the underlying epidemiology and facilitates development of rational interventions. This comprehensive review aims to identify, classify and assess gaps in Global Antimicrobial Resistance and Use Surveillance System (GLASS) reporting and national action plan (NAP) implementation in Africa.
METHODS
Articles published in English were searched across five electronic databases (PubMed, Scopus, Embase, AJOL and Cochrane) and grey literature. Articles were screened against inclusion/exclusion criteria and data from eligible studies were retrieved and analysed. This systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) on 31 July 2020 under protocol CRD42020192165.
RESULTS
Of the 4304 records found, only 32 met the initial inclusion criteria (4 peer reviews and 28 were grey literature). From these records, 41 surveillance systems were identified (30 national and 11 transnational). After final review of reported outcomes, only 23 national surveillance systems met the inclusion criteria. Indicators recorded from these systems shows lack of external quality assessment (EQA) in some systems and limited reporting of parameters such as infection origin, patient population and pathogen types.
CONCLUSIONS
The outcome of the review shows that although AMR surveillance has been implemented in 23 out of the 47 countries in the region, a number of limitations exist in the surveillance methods and reporting protocols that can impair the usefulness, validity and trustworthiness of data generated from these surveillance systems.
Topics: Humans; Africa; Anti-Infective Agents; Policy
PubMed: 36227707
DOI: 10.1093/jac/dkac342 -
BMJ Clinical Evidence Jan 2016About 10% of adults have suffered an attack of asthma, and up to 5% of these have severe disease that responds poorly to treatment. Patients with severe disease have an... (Review)
Review
INTRODUCTION
About 10% of adults have suffered an attack of asthma, and up to 5% of these have severe disease that responds poorly to treatment. Patients with severe disease have an increased risk of death, but patients with mild to moderate disease are also at risk of exacerbations. Most guidelines about the management of asthma follow stepwise protocols. This overview does not endorse or follow any particular protocol, but presents the evidence about a specific intervention, magnesium sulfate.
METHODS AND OUTCOMES
We conducted a systematic overview, aiming to answer the following clinical question: What are the effects of magnesium sulfate for acute asthma? We searched: Medline, Embase, The Cochrane Library, and other important databases up to November 2014 (Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview).
RESULTS
At this update, searching of electronic databases retrieved 50 studies. After deduplication and removal of conference abstracts, 24 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 10 studies and the further review of 14 full publications. Of the 14 full articles evaluated, one systematic review was updated and one systematic review was added at this update. We performed a GRADE evaluation for five PICO combinations.
CONCLUSIONS
In this systematic overview, we categorised the efficacy for two comparisons based on information about the effectiveness and safety of magnesium sulfate (iv) versus placebo and magnesium sulfate (nebulised) plus short-acting beta2 agonists (inhaled) versus short-acting beta2 agonists (inhaled) alone.
Topics: Acute Disease; Administration, Inhalation; Adrenergic beta-2 Receptor Antagonists; Adult; Anti-Asthmatic Agents; Asthma; Humans; Magnesium Sulfate
PubMed: 26761432
DOI: No ID Found -
Journal of Dentistry Nov 2023There is limited scientific evidence regarding the medication-related osteonecrosis of the jaw (MRONJ) induced by regenerative therapy (RT) associated with dental... (Review)
Review
OBJECTIVES
There is limited scientific evidence regarding the medication-related osteonecrosis of the jaw (MRONJ) induced by regenerative therapy (RT) associated with dental implant treatment. Thus, the current scoping review systematically maps the MRONJ research induced by RTs in implant dentistry and recognizes the existing gaps in knowledge.
DATA
Original studies and reviews investigating the impact of RT on the development of MRONJ were included.
SOURCES
Two reviewers independently searched the MEDLINE-PubMed and Scopus databases according to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) extension for Scoping Review and included articles published in English up to March 31, 2023.
STUDY SELECTION
Eighteen articles that fulfilled the inclusion and exclusion criteria were included in this study. Ten mapping parameters for investigating the association of RTs with MRONJ development were examined and evaluated within the selected articles.
RESULTS
There was severely limited information regarding the procedures of RTs including; the grafting materials, surgical protocols, and success and failure rates. The RT associated with MRONJ cases was sinus floor augmentation in patients taking bisphosphonate and denosumab. Moreover, there were limited data on the implant treatment associated with RTs such as time of insertion, implant length and diameter, and loading protocol.
CONCLUSION
The current scoping review revealed that some specific RTs associated with other factors hold a potential risk of MRONJ occurrence. However, the scientific evidence is limited with many gaps. Further investigations are needed to establish an evidence-based clinical guideline for treating high-risk patients.
CLINICAL SIGNIFICANCE
Clinicians should cautiously assess the risk of MRONJ development during implant treatment planning for patients undertaking antiresorptive medications. The adverse outcome of RT procedures should not be underestimated and a complete explanation of the possible risks should be given to the patients.
Topics: Humans; Bisphosphonate-Associated Osteonecrosis of the Jaw; Bone Density Conservation Agents; Diphosphonates; Sinus Floor Augmentation
PubMed: 37708930
DOI: 10.1016/j.jdent.2023.104682 -
Frontiers in Psychiatry 2023Ketamine and psychedelics have abuse liability. They can also induce "transformative experiences" where individuals experience enhanced states of awareness. This... (Review)
Review
BACKGROUND
Ketamine and psychedelics have abuse liability. They can also induce "transformative experiences" where individuals experience enhanced states of awareness. This enhanced awareness can lead to changes in preexisting behavioral patterns which could be beneficial in the treatment of substance use disorders (SUDs). Preclinical and clinical studies suggest that ketamine and psychedelics may alter markers associated with synaptic density, and that these changes may underlie effects such as sensitization, conditioned place preference, drug self-administration, and verbal memory performance. In this scoping review, we examined studies that measured synaptic markers in animals and humans after exposure to ketamine and/or psychedelics.
METHODS
A systematic search was conducted following PRISMA guidelines, through PubMed, EBSCO, Scopus, and Web of Science, based on a published protocol (Open Science Framework, DOI: 10.17605/OSF.IO/43FQ9). Both and studies were included. Studies on the following synaptic markers were included: dendritic structural changes, PSD-95, synapsin-1, synaptophysin-1, synaptotagmin-1, and SV2A.
RESULTS
Eighty-four studies were included in the final analyses. Seventy-one studies examined synaptic markers following ketamine treatment, nine examined psychedelics, and four examined both. Psychedelics included psilocybin/psilocin, lysergic acid diethylamide, N,N-dimethyltryptamine, 2,5-dimethoxy-4-iodoamphetamine, and ibogaine/noribogaine. Mixed findings regarding synaptic changes in the hippocampus and prefrontal cortex (PFC) have been reported when ketamine was administered in a single dose under basal conditions. Similar mixed findings were seen under basal conditions in studies that used repeated administration of ketamine. However, studies that examined animals during stressful conditions found that a single dose of ketamine counteracted stress-related reductions in synaptic markers in the hippocampus and PFC. Repeated administration of ketamine also counteracted stress effects in the hippocampus. Psychedelics generally increased synaptic markers, but results were more consistently positive for certain agents.
CONCLUSION
Ketamine and psychedelics can increase synaptic markers under certain conditions. Heterogeneous findings may relate to methodological differences, agents administered (or different formulations of the same agent), sex, and type of markers. Future studies could address seemingly mixed results by using meta-analytical approaches or study designs that more fully consider individual differences.
PubMed: 37435405
DOI: 10.3389/fpsyt.2023.1197890