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European Review For Medical and... Nov 2021The aim of the study is to investigate the efficacy of cell-based therapy in the surgical treatment of periodontal intrabony defects. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The aim of the study is to investigate the efficacy of cell-based therapy in the surgical treatment of periodontal intrabony defects.
MATERIALS AND METHODS
PRISMA guidelines were followed, and the study protocol was regis-tered in PROSPERO. Electronic and hand searches were carried out on electronic databases and major international journals of periodontology. All randomized clinical trials (RCTs) comparing cell-based therapies com-bined with surgery to surgery alone for the treatment of periodontal intrabony defects were considered. Quality assessment was performed using the Cochrane Risk of Bias Tool for randomized clinical trials (RoB 2). Quantitative evaluation of data was performed by meta-analysis.
RESULTS
Five hundred twenty-eight records were initially screened and 5 RCTs fulfilling the eligibility criteria were included. Periodontal ligament stem cells, dental pulp stem cells, periosteum-derived stem cells, gingival fibroblasts and their associated stem cells were used in combination with different surgical techniques to treat intrabony periodontal defects. Meta-analysis showed a statistically signif-icant effect in favor of cell-based groups for clinical attachment level gain (p=0.004), with a difference in means of 1.7 mm (95% CI 0.5; 2.9). This was replicated for intrabony defect depth reduction (p=0.006), with a difference in means of 1.3 (95% CI 0.4; 2.3).
CONCLUSIONS
Cell-based therapies have been positively applied for the surgical treatment of intrabony periodontal defects with promising results. However, the results obtained should be interpreted with caution due to the low number of available RCTs, the study design heterogeneity, and the limited extension of the follow-up.
Topics: Cell- and Tissue-Based Therapy; Humans; Periodontal Diseases; Randomized Controlled Trials as Topic
PubMed: 34787862
DOI: 10.26355/eurrev_202111_27102 -
BMC Medical Research Methodology Nov 2021Major adverse cardiovascular events (MACE) are increasingly used as composite outcomes in randomized controlled trials (RCTs) and observational studies. However, it is...
BACKGROUND
Major adverse cardiovascular events (MACE) are increasingly used as composite outcomes in randomized controlled trials (RCTs) and observational studies. However, it is unclear how observational studies most commonly define MACE in the literature when using administrative data.
METHODS
We identified peer-reviewed articles published in MEDLINE and EMBASE between January 1, 2010 to October 9, 2020. Studies utilizing administrative data to assess the MACE composite outcome using International Classification of Diseases 9th or 10th Revision diagnosis codes were included. Reviews, abstracts, and studies not providing outcome code definitions were excluded. Data extracted included data source, timeframe, MACE components, code definitions, code positions, and outcome validation.
RESULTS
A total of 920 articles were screened, 412 were retained for full-text review, and 58 were included. Only 8.6% (n = 5/58) matched the traditional three-point MACE RCT definition of acute myocardial infarction (AMI), stroke, or cardiovascular death. None matched four-point (+unstable angina) or five-point MACE (+unstable angina and heart failure). The most common MACE components were: AMI and stroke, 15.5% (n = 9/58); AMI, stroke, and all-cause death, 13.8% (n = 8/58); and AMI, stroke and cardiovascular death 8.6% (n = 5/58). Further, 67% (n = 39/58) did not validate outcomes or cite validation studies. Additionally, 70.7% (n = 41/58) did not report code positions of endpoints, 20.7% (n = 12/58) used the primary position, and 8.6% (n = 5/58) used any position.
CONCLUSIONS
Components of MACE endpoints and diagnostic codes used varied widely across observational studies. Variability in the MACE definitions used and information reported across observational studies prohibit the comparison, replication, and aggregation of findings. Studies should transparently report the administrative codes used and code positions, as well as utilize validated outcome definitions when possible.
Topics: Cardiovascular Diseases; Heart Failure; Humans; Myocardial Infarction; Stroke
PubMed: 34742250
DOI: 10.1186/s12874-021-01440-5 -
Journal of Public Health Management and...Continuous quality improvement (CQI) has become prominent in public health settings; yet, little consolidated guidance exists for building CQI capacity of...
CONTEXT
Continuous quality improvement (CQI) has become prominent in public health settings; yet, little consolidated guidance exists for building CQI capacity of community-based organizations.
OBJECTIVE
To synthesize relevant literature to identify guiding principles and core components critical to building the capacity of organizations to adopt and use CQI.
DESIGN
We employed a systematic review approach to assess guiding principles and core components for CQI capacity-building as outlined in the literature.
ELIGIBILITY CRITERIA
Studies meeting the following criteria were eligible for review: (1) empirical, peer-reviewed journal article, evaluation study, review, or systematic review; (2) published in 2010 or later; and (3) capacity-building activities were described in enough detail to be replicable. Studies not including human subjects, published in a language other than English, or for which full text was not available were excluded.
STUDY SELECTION
The initial return of records included 6557 articles, of which 1455 were duplicates. The research team single-screened titles and abstracts of 5102 studies, resulting in the exclusion of 4842 studies. Two hundred sixty-two studies were double-screened during full-text review, yielding a final sample of 61 studies from which data were extracted.
MAIN OUTCOME MEASURES
Outcome measures of interest were operationalized descriptions of guiding principles and core components of the CQI capacity-building approach.
RESULTS
Results yielded articles from medical education, health care, and public health settings. Findings included guiding principles and core components of CQI capacity-building identified in current practice, as well as infrastructural and contextual elements needed to build CQI capacity.
CONCLUSIONS
This consolidation of guiding principles and core components for CQI capacity-building is valuable for public health and related workforces. Despite the uneven distribution of articles from health care, medical education, and public health settings, our findings can be used to guide public health organizations in building CQI capacity in a well-informed, systematic manner.
Topics: Capacity Building; Delivery of Health Care; Humans; Public Health; Quality Improvement
PubMed: 34520447
DOI: 10.1097/PHH.0000000000001412 -
Journal of Geriatric Psychiatry and... Jul 2022Alzheimer's disease (AD) is a complex neurodegenerative disorder and the most prevalent cause of dementia. In spite of the urgent need for more effective AD drug therapy...
IMPORTANCE
Alzheimer's disease (AD) is a complex neurodegenerative disorder and the most prevalent cause of dementia. In spite of the urgent need for more effective AD drug therapy strategies, evidence of the efficacy of combination therapy with existing drugs remains unclear.
OBJECTIVE
To assess the efficacy of combined drug therapy on cognition and progress in patients with AD in comparison to single agent drug therapy.
METHODS
The electronic databases MEDLINE and EMBASE were systematically searched to identify relevant publications. Only randomized controlled clinical trials were included, but no limits were applied to language or time published. Data were extracted from May 27th until December 29th, 2020.
RESULTS
Three trials found that a combination of ChEI with additional memantine provides a slight benefit for patients with moderate to severe AD over ChEI monotherapy and placebo. However, a further 4 trials could not replicate this effect. One trial reported benefits of add-on in donepezil-treated patients with moderate AD (using a formula containing Gingko and other antioxidants) compared to donepezil with placebo. A further trial found no significant effect of combining EGb 761® and donepezil in patients with probable AD over donepezil with placebo. Approaches with idalopirdine, atorvastatin or vitamin supplementation in combination with ChEI have not proven effective and have not been retried since. Fluoxetine and ST101 have shown partial benefits in combination with ChEI over ChEI monotherapy and placebo. However, these effects must be replicated by further research.
CONCLUSION
Additional memantine in combination with ChEI might be of slight benefit in patients with moderate to severe AD, but evidence is ambiguous. Longer trials are needed. No major cognitive benefit is missed, if solely appropriate ChEI monotherapy is initiated.
Topics: Alzheimer Disease; Cholinesterase Inhibitors; Donepezil; Drug Therapy, Combination; Humans; Indans; Memantine; Piperidines
PubMed: 34476990
DOI: 10.1177/08919887211044746 -
Palliative Medicine Dec 2021Palliative care is advocated for older people with frailty and multimorbidity in the community. However, how to best deliver it is unclear.
Timely short-term specialized palliative care service intervention for older people with frailty and their family carers in primary care: Development and modelling of the frailty+ intervention using theory of change.
BACKGROUND
Palliative care is advocated for older people with frailty and multimorbidity in the community. However, how to best deliver it is unclear.
AIM
To develop and model an intervention of short-term specialized palliative care that is initiated timely based on complex care needs and integrated with primary care for older people with frailty and their family, detailing the intervention components, outcomes and preconditions needed for implementation, using a novel theoretical approach.
DESIGN
Observational study informed by the UK MRC guidance for complex interventions integrated with a Theory of Change (i.e. hypothetical causal pathway to impact) approach. We synthesized evidence from a systematic review, semi-structured interviews, group discussions and Theory of Change workshops.
SETTING
Primary care in Flanders, Belgium.
RESULTS
We identified patient and family carer-related long-term outcomes and preconditions to achieve them for example, service providers are willing and able to deliver the intervention. The intervention components included implementation components, for example, training for service providers, and a core component, that is, provision of timely short-term specialized palliative care by a specialized palliative home care nurse. The latter includes: short-term service delivery; collaborative and integrative working within primary care; delivery of holistic needs- and capacity-based care; person-centred and family-focussed; and goal-oriented pro-active care.
CONCLUSIONS
The Theory of Change approach allowed us to identify multiple intervention components targeting different stakeholders to achieve the desired outcomes. It also facilitated a detailed description of the intervention which aims to increase replicability and effective comparisons with other interventions.
Topics: Aged; Belgium; Caregivers; Frailty; Humans; Observational Studies as Topic; Palliative Care; Primary Health Care
PubMed: 34423701
DOI: 10.1177/02692163211040187 -
Frontiers in Immunology 2021CD4 T-cell depletion is pathognomonic for AIDS in both HIV and simian immunodeficiency virus (SIV) infections. It occurs early, is massive at mucosal sites, and is not...
CD4 T-cell depletion is pathognomonic for AIDS in both HIV and simian immunodeficiency virus (SIV) infections. It occurs early, is massive at mucosal sites, and is not entirely reverted by antiretroviral therapy (ART), particularly if initiated when T-cell functions are compromised. HIV/SIV infect and kill activated CCR5-expressing memory and effector CD4 T-cells from the intestinal lamina propria. Acute CD4 T-cell depletion is substantial in progressive, nonprogressive and controlled infections. Clinical outcome is predicted by the mucosal CD4 T-cell recovery during chronic infection, with no recovery occurring in rapid progressors, and partial, transient recovery, the degree of which depends on the virus control, in normal and long-term progressors. The nonprogressive infection of African nonhuman primate SIV hosts is characterized by partial mucosal CD4 T-cell restoration, despite high viral replication. Complete, albeit very slow, recovery of mucosal CD4+ T-cells occurs in controllers. Early ART does not prevent acute mucosal CD4 T-cell depletion, yet it greatly improves their restoration, sometimes to preinfection levels. Comparative studies of the different models of SIV infection support a critical role of immune activation/inflammation (IA/INFL), in addition to viral replication, in CD4 T-cell depletion, with immune restoration occurring only when these parameters are kept at bay. CD4 T-cell depletion is persistent, and the recovery is very slow, even when both the virus and IA/INFL are completely controlled. Nevertheless, partial mucosal CD4 T-cell recovery is sufficient for a healthy life in natural hosts. Cell death and loss of CD4 T-cell subsets critical for gut health contribute to mucosal inflammation and enteropathy, which weaken the mucosal barrier, leading to microbial translocation, a major driver of IA/INFL. In turn, IA/INFL trigger CD4 T-cells to become either viral targets or apoptotic, fueling their loss. CD4 T-cell depletion also drives opportunistic infections, cancers, and comorbidities. It is thus critical to preserve CD4 T cells (through early ART) during HIV/SIV infection. Even in early-treated subjects, residual IA/INFL can persist, preventing/delaying CD4 T-cell restoration. New therapeutic strategies limiting mucosal pathology, microbial translocation and IA/INFL, to improve CD4 T-cell recovery and the overall HIV prognosis are needed, and SIV models are extensively used to this goal.
Topics: Animals; Bacterial Translocation; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Gastrointestinal Microbiome; HIV; HIV Infections; Haplorhini; Host-Pathogen Interactions; Humans; Immunity, Mucosal; Immunocompromised Host; Inflammation Mediators; Intestinal Mucosa; Phenotype; Simian Acquired Immunodeficiency Syndrome; Simian Immunodeficiency Virus; Time Factors
PubMed: 34367156
DOI: 10.3389/fimmu.2021.695674 -
The Cochrane Database of Systematic... Aug 2021Remdesivir is an antiviral medicine with properties to inhibit viral replication of SARS-CoV-2. Positive results from early studies attracted media attention and led to...
BACKGROUND
Remdesivir is an antiviral medicine with properties to inhibit viral replication of SARS-CoV-2. Positive results from early studies attracted media attention and led to emergency use authorisation of remdesivir in COVID-19. A thorough understanding of the current evidence regarding the effects of remdesivir as a treatment for SARS-CoV-2 infection based on randomised controlled trials (RCTs) is required.
OBJECTIVES
To assess the effects of remdesivir compared to placebo or standard care alone on clinical outcomes in hospitalised patients with SARS-CoV-2 infection, and to maintain the currency of the evidence using a living systematic review approach.
SEARCH METHODS
We searched the Cochrane COVID-19 Study Register (which comprises the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, and medRxiv) as well as Web of Science (Science Citation Index Expanded and Emerging Sources Citation Index) and WHO COVID-19 Global literature on coronavirus disease to identify completed and ongoing studies without language restrictions. We conducted the searches on 16 April 2021.
SELECTION CRITERIA
We followed standard Cochrane methodology. We included RCTs evaluating remdesivir for the treatment of SARS-CoV-2 infection in hospitalised adults compared to placebo or standard care alone irrespective of disease severity, gender, ethnicity, or setting. We excluded studies that evaluated remdesivir for the treatment of other coronavirus diseases.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methodology. To assess risk of bias in included studies, we used the Cochrane RoB 2 tool for RCTs. We rated the certainty of evidence using the GRADE approach for outcomes that were reported according to our prioritised categories: all-cause mortality at up to day 28, duration to liberation from invasive mechanical ventilation, duration to liberation from supplemental oxygen, new need for mechanical ventilation (high-flow oxygen or non-invasive or invasive mechanical ventilation), new need for invasive mechanical ventilation, new need for non-invasive mechanical ventilation or high-flow oxygen, new need for oxygen by mask or nasal prongs, quality of life, adverse events (any grade), and serious adverse events.
MAIN RESULTS
We included five RCTs with 7452 participants diagnosed with SARS-CoV-2 infection and a mean age of 59 years, of whom 3886 participants were randomised to receive remdesivir. Most participants required low-flow oxygen (n=4409) or mechanical ventilation (n=1025) at baseline. We identified two ongoing studies, one was suspended due to a lack of COVID-19 patients to recruit. Risk of bias was considered to be of some concerns or high risk for clinical status and safety outcomes because participants who had died did not contribute information to these outcomes. Without adjustment, this leads to an uncertain amount of missing values and the potential for bias due to missing data. Effects of remdesivir in hospitalised individuals Remdesivir probably makes little or no difference to all-cause mortality at up to day 28 (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.81 to 1.06; risk difference (RD) 8 fewer per 1000, 95% CI 21 fewer to 7 more; 4 studies, 7142 participants; moderate-certainty evidence). Considering the initial severity of condition, only one study showed a beneficial effect of remdesivir in patients who received low-flow oxygen at baseline (RR 0.32, 95% CI 0.15 to 0.66, 435 participants), but conflicting results exists from another study, and we were unable to validly assess this observations due to limited availability of comparable data. Remdesivir may have little or no effect on the duration to liberation from invasive mechanical ventilation (2 studies, 1298 participants, data not pooled, low-certainty evidence). We are uncertain whether remdesivir increases or decreases the chance of clinical improvement in terms of duration to liberation from supplemental oxygen at up to day 28 (3 studies, 1691 participants, data not pooled, very low-certainty evidence). We are very uncertain whether remdesivir decreases or increases the risk of clinical worsening in terms of new need for mechanical ventilation at up to day 28 (high-flow oxygen or non-invasive ventilation or invasive mechanical ventilation) (RR 0.78, 95% CI 0.48 to 1.24; RD 29 fewer per 1000, 95% CI 68 fewer to 32 more; 3 studies, 6696 participants; very low-certainty evidence); new need for non-invasive mechanical ventilation or high-flow oxygen (RR 0.70, 95% CI 0.51 to 0.98; RD 72 fewer per 1000, 95% CI 118 fewer to 5 fewer; 1 study, 573 participants; very low-certainty evidence); and new need for oxygen by mask or nasal prongs (RR 0.81, 95% CI 0.54 to 1.22; RD 84 fewer per 1000, 95% CI 204 fewer to 98 more; 1 study, 138 participants; very low-certainty evidence). The evidence suggests that remdesivir may decrease the risk of clinical worsening in terms of new need for invasive mechanical ventilation (67 fewer participants amongst 1000 participants; RR 0.56, 95% CI 0.41 to 0.77; 2 studies, 1159 participants; low-certainty evidence). None of the included studies reported quality of life. Remdesivir probably decreases the serious adverse events rate at up to 28 days (RR 0.75, 95% CI 0.63 to 0.90; RD 63 fewer per 1000, 95% CI 94 fewer to 25 fewer; 3 studies, 1674 participants; moderate-certainty evidence). We are very uncertain whether remdesivir increases or decreases adverse events rate (any grade) (RR 1.05, 95% CI 0.86 to 1.27; RD 29 more per 1000, 95% CI 82 fewer to 158 more; 3 studies, 1674 participants; very low-certainty evidence).
AUTHORS' CONCLUSIONS
Based on the currently available evidence, we are moderately certain that remdesivir probably has little or no effect on all-cause mortality at up to day 28 in hospitalised adults with SARS-CoV-2 infection. We are uncertain about the effects of remdesivir on clinical improvement and worsening. There were insufficient data available to validly examine the effect of remdesivir on mortality in subgroups depending on the extent of respiratory support at baseline. Future studies should provide additional data on efficacy and safety of remdesivir for defined core outcomes in COVID-19 research, especially for different population subgroups. This could allow us to draw more reliable conclusions on the potential benefits and harms of remdesivir in future updates of this review. Due to the living approach of this work, we will update the review periodically.
Topics: Adenosine Monophosphate; Alanine; Antiviral Agents; Bias; COVID-19; Cause of Death; Confidence Intervals; Disease Progression; Humans; Middle Aged; Oxygen; Randomized Controlled Trials as Topic; Respiration, Artificial; SARS-CoV-2; Ventilator Weaning; COVID-19 Drug Treatment
PubMed: 34350582
DOI: 10.1002/14651858.CD014962 -
Cancer Chemotherapy and Pharmacology Nov 2021Melphalan is a bifunctional alkylating agent that elicits its cytotoxic activity by rapidly forming an initial DNA monoadduct, which then produces an inter-strand...
PURPOSE
Melphalan is a bifunctional alkylating agent that elicits its cytotoxic activity by rapidly forming an initial DNA monoadduct, which then produces an inter-strand crosslink. Most studies exploring the role of inherited differences in DNA repair and melphalan outcomes focus on inter-strand crosslink repair, however, monoadduct repair likely plays a key role since it minimises the ultimate production of these crosslinks. The purpose of this systematic review was to assess evidence of an association between variation in monoadduct repair pathways and melphalan response.
METHODS
A literature search was undertaken using Medline, Embase, Scopus and PubMed databases. Duplicates were removed and only full-text articles were included. To be included for critique in this systematic review, articles were assessed for relevance using strict inclusion/exclusion criteria.
RESULTS
Fourteen studies were identified that involved patients treated with melphalan, however, in 3, only a minority of the cohort received melphalan. Across the remaining 11 studies, 61 genes/proteins in DNA monoadduct repair pathways were assessed. Both germline SNP (CDKN1A, ERCC1, ERCC2, ERCC4, ERCC6, EXO1, MLH1, MNAT1, MUTYH, PARP4, PCNA, POLE, POLR1G, RAD23B, RFC1, RFC3, RPA1, RPA3, TREX1, UNG, XPC, XRCC1) and somatic expression (CDKN1A, PARP1, PCNA, MGMT, RECQL, RFC5) were associated with melphalan outcomes in ≥ 1 study.
CONCLUSION
It appears that inherited germline differences in monoadduct repair genes may be a risk factor for poor outcomes. However, the diversity of study design, patient cohorts, genes assessed and lack of replication, preclude any meta-analysis. Further prospective studies are required to validate these findings.
Topics: Antineoplastic Agents, Alkylating; DNA Adducts; DNA Repair; Gene Expression Regulation, Neoplastic; Humans; Melphalan; Neoplasms; Pharmacogenomic Variants; Progression-Free Survival; Treatment Outcome
PubMed: 34347127
DOI: 10.1007/s00280-021-04340-z -
Sensors (Basel, Switzerland) Jul 2021This article performs a Systematic Review of studies to answer the question: What are the researches related to the learning process with (Serious) Business Games using... (Review)
Review
This article performs a Systematic Review of studies to answer the question: What are the researches related to the learning process with (Serious) Business Games using data collection techniques with Electroencephalogram or Eye tracking signals? The PRISMA declaration method was used to guide the search and inclusion of works related to the elaboration of this study. The 19 references resulting from the critical evaluation initially point to a gap in investigations into using these devices to monitor serious games for learning in organizational environments. An approximation with equivalent sensing studies in serious games for the contribution of skills and competencies indicates that continuous monitoring measures, such as mental state and eye fixation, proved to identify the players' attention levels effectively. Also, these studies showed effectiveness in the flow at different moments of the task, motivating and justifying the replication of these studies as a source of insights for the optimized design of business learning tools. This study is the first systematic review and consolidates the existing literature on user experience analysis of business simulation games supported by human-computer interfaces.
Topics: Computers; Humans; Psychotherapy; User-Computer Interface; Video Games
PubMed: 34300549
DOI: 10.3390/s21144810 -
Sleep & Breathing = Schlaf & Atmung Jun 2022Obstructive sleep apnea (OSA) is the most common pathologic sleep disorder with an estimated prevalence in the USA of up to 25% of adult males. With military aviation... (Review)
Review
PURPOSE
Obstructive sleep apnea (OSA) is the most common pathologic sleep disorder with an estimated prevalence in the USA of up to 25% of adult males. With military aviation being heavily comprised of adult men, the impact of OSA on flying operations is concerning as OSA is disqualifying for all flying classes in the US Air Force. In order to minimize the impact of OSA on operations, early identification of at-risk patients is critical in disease management. Individuals could be identified for whom regular polysomnography testing may reveal OSA while mild or sub-clinical, at which point treatment may be initiated in order to promote continued medical qualification for duty and career retention.
METHODS
We performed a keyword search of PubMed, EMBASE, and Google Scholar along with searches in the NHGRI/EBI GWAS Catalogue and the Atlas of GWAS Summary Statistics. We included primary research from candidate gene, GWAS, and meta-analyses. We also included other review articles in our search to confirm interpretations and implications of any genetic associations with OSA. Only studies related to OSA susceptibility or risk were included.
RESULTS
We identified 134 publications reporting or reviewing genetic associations with OSA risk. These papers reported 301 variants, of which 195 were unique and 33 were replicated in at least two papers. With respect to the strength of association, 43 variants exhibited odds ratios greater than 2. Finally, there were 84 null results reported, 51 of which were in conflict with reported associations.
CONCLUSION
There is ample evidence in the literature to confirm that genetics provide an important contribution to OSA development. The high number of strongly associated variants suggests that a polygenic risk model could be created with high predictive value for prognostic screening.
Topics: Adult; Aerospace Medicine; Aviation; Genetic Predisposition to Disease; Humans; Male; Military Personnel; Sleep; Sleep Apnea, Obstructive
PubMed: 34231084
DOI: 10.1007/s11325-021-02427-8