The significance of surgically modifying soft tissue phenotype around fixed dental prostheses: An American Academy of Periodontology best evidence review

BackgroundThis systematic review endeavored to investigate the effect of soft tissue phenotype modification therapy (PhMT- s) at sites with a tooth or an implant supported fixed dental prosthesis.MethodsA comprehensive literature search was conducted by two independent examiners to identify relevant studies reporting differences in clinical, esthetic, or radiographic outcomes of interest between sites underwent PhMT- s and sites that remained untreated. Risk of bias assessment was calculated for all included studies. Meta- analyses involving endpoints of interest were performed when feasible.ResultsNo controlled studies pertaining to tooth sites were identified. A total of six articles reporting on the outcomes of buccal soft tissue phenotype modification around implants were selected, of which, five were included in the meta- analyses. Quantitative analyses showed a weighted mean difference (WMD) of 0.98 mm (95% CI = 0.25 to 1.72 mm, P = 0.009) for change of tissue thickness; a WMD of - 4.87% (95% CI = - 34.27 to 24.53%, P = 0.75) for bleeding on probing (BOP); a WMD of 0.36 mm (95% CI = 0.12 to 0.59 mm, P = 0.003) for mucosal recession (MR); a WMD of 0.13 mm (95% CI = - 0.11 to 0.36 mm, P = 0.30 for probing depth (PD); a WMD of 1.08 (95% CI = - 0.39 to 2.55, P = 0.15) for pink esthetic score (PES), and a WMD of 0.40 mm (95% CI = - 0.34 to 1.14 mm, P = 0.28) for marginal bone loss (MBL).ConclusionsSurgical modification of peri- implant soft tissue phenotype via PhMT- s may decrease the amount of MR. Future clinical trials are needed to warrant the clinical benefits of modifying soft tissue phenotype around tooth- supported restorations.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154660/1/jper10458-sup-0006-figureS1F.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154660/2/jper10458_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154660/3/jper10458-sup-0001-figureS1A.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154660/4/jper10458-sup-0005-figureS1E.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154660/5/jper10458-sup-0004-figureS1D.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154660/6/jper10458-sup-0003-figureS1C.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154660/7/jper10458-sup-0002-figureS1B.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154660/8/jper10458.pd

Altered Development of NKT Cells, γδ T Cells, CD8 T Cells and NK Cells in a PLZF Deficient Patient

In mice, the transcription factor, PLZF, controls the development of effector functions in invariant NKT cells and a subset of NKT cell-like, γδ T cells. Here, we show that in human lymphocytes, in addition to invariant NKT cells, PLZF was also expressed in a large percentage of CD8+ and CD4+ T cells. Furthermore, PLZF was also found to be expressed in all γδ T cells and in all NK cells. Importantly, we show that in a donor lacking functional PLZF, all of these various lymphocyte populations were altered. Therefore, in contrast to mice, PLZF appears to control the development and/or function of a wide variety of human lymphocytes that represent more than 10% of the total PBMCs. Interestingly, the PLZF-expressing CD8+ T cell population was found to be expanded in the peripheral blood of patients with metastatic melanoma but was greatly diminished in patients with autoimmune disease

Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015.

BACKGROUND: Healthy life expectancy (HALE) and disability-adjusted life-years (DALYs) provide summary measures of health across geographies and time that can inform assessments of epidemiological patterns and health system performance, help to prioritise investments in research and development, and monitor progress toward the Sustainable Development Goals (SDGs). We aimed to provide updated HALE and DALYs for geographies worldwide and evaluate how disease burden changes with development. METHODS: We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015. We calculated DALYs by summing years of life lost (YLLs) and years of life lived with disability (YLDs) for each geography, age group, sex, and year. We estimated HALE using the Sullivan method, which draws from age-specific death rates and YLDs per capita. We then assessed how observed levels of DALYs and HALE differed from expected trends calculated with the Socio-demographic Index (SDI), a composite indicator constructed from measures of income per capita, average years of schooling, and total fertility rate. FINDINGS: Total global DALYs remained largely unchanged from 1990 to 2015, with decreases in communicable, neonatal, maternal, and nutritional (Group 1) disease DALYs offset by increased DALYs due to non-communicable diseases (NCDs). Much of this epidemiological transition was caused by changes in population growth and ageing, but it was accelerated by widespread improvements in SDI that also correlated strongly with the increasing importance of NCDs. Both total DALYs and age-standardised DALY rates due to most Group 1 causes significantly decreased by 2015, and although total burden climbed for the majority of NCDs, age-standardised DALY rates due to NCDs declined. Nonetheless, age-standardised DALY rates due to several high-burden NCDs (including osteoarthritis, drug use disorders, depression, diabetes, congenital birth defects, and skin, oral, and sense organ diseases) either increased or remained unchanged, leading to increases in their relative ranking in many geographies. From 2005 to 2015, HALE at birth increased by an average of 2·9 years (95% uncertainty interval 2·9-3·0) for men and 3·5 years (3·4-3·7) for women, while HALE at age 65 years improved by 0·85 years (0·78-0·92) and 1·2 years (1·1-1·3), respectively. Rising SDI was associated with consistently higher HALE and a somewhat smaller proportion of life spent with functional health loss; however, rising SDI was related to increases in total disability. Many countries and territories in central America and eastern sub-Saharan Africa had increasingly lower rates of disease burden than expected given their SDI. At the same time, a subset of geographies recorded a growing gap between observed and expected levels of DALYs, a trend driven mainly by rising burden due to war, interpersonal violence, and various NCDs. INTERPRETATION: Health is improving globally, but this means more populations are spending more time with functional health loss, an absolute expansion of morbidity. The proportion of life spent in ill health decreases somewhat with increasing SDI, a relative compression of morbidity, which supports continued efforts to elevate personal income, improve education, and limit fertility. Our analysis of DALYs and HALE and their relationship to SDI represents a robust framework on which to benchmark geography-specific health performance and SDG progress. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform financial and research investments, prevention efforts, health policies, and health system improvement initiatives for all countries along the development continuum. FUNDING: Bill & Melinda Gates Foundation

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

Forouzanfar MH, Afshin A, Alexander LT, et al. Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. LANCET. 2016;388(10053):1659-1724.Background The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors-the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57.8% (95% CI 56.6-58.8) of global deaths and 41.2% (39.8-42.8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211.8 million [192.7 million to 231.1 million] global DALYs), smoking (148.6 million [134.2 million to 163.1 million]), high fasting plasma glucose (143.1 million [125.1 million to 163.5 million]), high BMI (120.1 million [83.8 million to 158.4 million]), childhood undernutrition (113.3 million [103.9 million to 123.4 million]), ambient particulate matter (103.1 million [90.8 million to 115.1 million]), high total cholesterol (88.7 million [74.6 million to 105.7 million]), household air pollution (85.6 million [66.7 million to 106.1 million]), alcohol use (85.0 million [77.2 million to 93.0 million]), and diets high in sodium (83.0 million [49.3 million to 127.5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Copyright (C) The Author(s). Published by Elsevier Ltd

The effects of microbiome-targeted therapy on cognitive impairment and postoperative cognitive dysfunction-A systematic review.

BACKGROUND: The gut-brain axis involves bidirectional communication between the gut-microbiota and central nervous system. This study aimed to investigate whether probiotics and/or prebiotics, known as Microbiome-targeted Therapies (MTTs), improve cognition and prevent postoperative cognitive dysfunction (POCD). METHODS: Relevant animal and human studies were identified using a systematic database search (PubMed, EMBASE, Cochrane Library, and Web of Science), focusing on the effects of MTTs on inflammation, perioperative and non-perioperative cognitive impairment. Screening and data extraction were conducted by two independent reviewers. The Risk of bias was assessed using the SYRCLEs risk of bias tool for animal studies. The revised Cochrane risk of bias tool (RoB 2) was used for human studies. RESULTS: A total of 24 articles were selected; 16 of these involved animal studies, and 8 described studies in humans. In these papers, the use of MTTs consistently resulted in decreased inflammation in perioperative and non-perioperative settings. Out of 16 animal studies, 5 studies (2 associated with delirium and 3 studies related to POCD) were conducted in a perioperative setting. MTTs improved perioperative cognitive behavior and reduced inflammation in all 5 animal studies. Eleven animal studies were conducted in a non-perioperative setting. In all of these studies, MTTs showed improvement in learning and memory function. MTTs showed a positive effect on levels of pro-inflammatory cytokines and biomarkers related to cognitive function. Among the 8 human studies, only one study examined the effects of perioperative MTTs on cognitive function. This study showed a reduced incidence of POCD along with improved cognitive function. Of the remaining 7 studies, 6 suggested that MTTs improved behavioral test results and cognition in non-perioperative environments. One study failed to show any significant differences in memory, biomarkers of inflammation, or oxidative factors. CONCLUSION: In the studies we examined, most showed that MTTs decrease inflammation by down-regulating inflammatory cytokines and oxidative stress in both perioperative and non-perioperative settings. In general, MTTs also seem to have a positive effect on cognition through neural, immune, endocrine, and metabolic pathways. However, these effects have not yet resulted in a consensus regarding preventative strategies or treatments. Based on these current research results, MTTs could be a potential new preventative strategy for cognitive impairment after surgery

Experiences of transgender and gender diverse patients in emergency psychiatric settings: A scoping review.

OBJECTIVE: This scoping review aims to characterize what is known about transgender and gender diverse (TGD) individuals in emergency psychiatric settings and identify what gaps persist in this literature. METHODS: A search of 4 electronic databases (PubMed, Web of Science, GenderWatch, and PsycINFO) was used for data collection. Included were studies that looked at TGD individuals presenting to a psychiatric emergency department (ED) or ED with a primary mental health concern. Study screening progress was documented in a Preferred Reporting Items for Systematic reviews and Meta-Analyses flow chart. A total of 232 titles and abstracts were screened, 38 full texts were evaluated for eligibility, and 10 studies were included. RESULTS: The studies reviewed identified mental health vulnerabilities unique to the TGD population, including service denial in health care settings, gender dysphoria, increased rates of non-suicidal self-injury, and in some studies an increase in suicidality. Societal inequities, including the risk of discrimination and residential instability, were also revealed. A subset of the studies identified best practices in caring for this population, including the use of non-judgmental, affirmative, and inclusive language, and on a structural level creating emergency environments that are confidential, inclusive, and therapeutic for these individuals. CONCLUSIONS: There is limited information on TGD individuals in emergency psychiatric settings, and thus it is difficult to form strong conclusions. However, the current evidence available suggests possible inequities in this population. Three major themes with regards to TGD individuals in emergency psychiatric settings were identified: mental health vulnerabilities, societal inequities, and best practices in caring for this population. Overall, there is a scarcity of literature in this field, and further research on the experiences of this population is needed to inform clinical practice

Association of tooth loss with morbidity and mortality by diabetes status in older adults: a systematic review.

ObjectiveThis systematic review assesses the association of tooth loss (TL), as the exposure, with morbidity and mortality by diabetes mellitus (DM) status, as the outcome, in older adults.BackgroundIndividuals with DM have higher prevalence of severe TL and increased risk of developing morbidities and mortality. No systematic review has evaluated the association between TL with morbidity and mortality by DM status.Material and methodsComprehensive searches used multiple publication databases containing reports published between 01/01/2000 and 04/21/2021. Two authors independently evaluated included studies for quality and risk of bias using the Critical Appraisal Skills Programme (CASP) checklist for cohort and Center for Evidence-Based Medicine (CEBM) critical appraisal sheet for cross-sectional studies, while a third author arbitrated decisions to resolve disagreements.ResultsThirteen studies met the inclusion criteria: eight cross-sectional and five cohort. Qualitative review of the included studies indicated TL is associated with increased incidence and prevalence of DM. TL is also associated with DM-related morbidities including greater prevalence of heart disease, diabetic retinopathy, metabolic syndrome; poorer health-related quality of life; poorer survival of participants with chronic kidney disease; and increased medical expenditure. Overall, the quality of the evidence reviewed was medium, as per the Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence.Conclusions/practical implicationsThis review found significant associations of TL with prevalence and incidence of DM and adverse DM-related outcomes. An interprofessional team-care approach that includes an oral health component could benefit the prevention and management of DM

Earlier initiation of palliative care in the disease trajectory of people living with dementia: a scoping review protocol

Introduction While the need for palliative care for people living with dementia has widely been recognised, they continue to be a disadvantaged group when it comes to timely initiation, and controversies remain regarding appropriate timing, or what elements constitute high quality palliative care early in the disease trajectory. To date, no literature review has summarised this debate or offered insights. The aim of this scoping review is to provide a general overview of research regarding palliative care in mild or moderate dementia, to identify existing controversies, and to examine what are key components of palliative care in dementia, specifically when initiated earlier in the disease trajectory.Methods and analysis Consistent with recent guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews, we carried out a search for academic literature in PubMed, CINAHL, EMBASE, Cochrane Library, PsycINFO, Web of Science; on 5 November 2019 and an updated search on 2 February 2021. We will include studies with different study designs published in English over the last decade that focused on palliative care in early stages of dementia. We will include models targeting at least one outcome domain of palliative care (physical, psychological, social or spiritual) and advance care planning, and will exclude hospice models with limited prognosis similar to the requirements in the USA. We will report study characteristics and quality. We aim to apply narrative synthesis techniques to develop a theoretical model of how, for whom and why palliative care can be relevant in early stages of dementia, and what are facilitators and barriers. We anticipate to also describe if and how the concept of (early) palliative care in dementia changed across time and studies.Ethics and dissemination No ethical review required. Results will identify research gaps and lay out basic principles for conceptualising palliative care in early stages of dementia

Experiences of transgender and gender diverse patients in emergency psychiatric settings: A scoping review

Abstract Objective This scoping review aims to characterize what is known about transgender and gender diverse (TGD) individuals in emergency psychiatric settings and identify what gaps persist in this literature. Methods A search of 4 electronic databases (PubMed, Web of Science, GenderWatch, and PsycINFO) was used for data collection. Included were studies that looked at TGD individuals presenting to a psychiatric emergency department (ED) or ED with a primary mental health concern. Study screening progress was documented in a Preferred Reporting Items for Systematic reviews and Meta‐Analyses flow chart. A total of 232 titles and abstracts were screened, 38 full texts were evaluated for eligibility, and 10 studies were included. Results The studies reviewed identified mental health vulnerabilities unique to the TGD population, including service denial in health care settings, gender dysphoria, increased rates of non‐suicidal self‐injury, and in some studies an increase in suicidality. Societal inequities, including the risk of discrimination and residential instability, were also revealed. A subset of the studies identified best practices in caring for this population, including the use of non‐judgmental, affirmative, and inclusive language, and on a structural level creating emergency environments that are confidential, inclusive, and therapeutic for these individuals. Conclusions There is limited information on TGD individuals in emergency psychiatric settings, and thus it is difficult to form strong conclusions. However, the current evidence available suggests possible inequities in this population. Three major themes with regards to TGD individuals in emergency psychiatric settings were identified: mental health vulnerabilities, societal inequities, and best practices in caring for this population. Overall, there is a scarcity of literature in this field, and further research on the experiences of this population is needed to inform clinical practice

Survival outcomes in pediatric recurrent high-grade glioma: results of a 20-year systematic review and meta-analysis.

Recurrent pediatric high-grade glioma is a leading cause of cancer-related death in children. We report results of a systematic review and meta-analysis investigating survival outcome in pediatric patients with recurrent high-grade glioma over the last 20 years. MEDLINE/PubMed, EMBASE, Web of Science and Cochrane Review databases were searched for relevant studies reporting on survival outcomes for pediatric patients with recurrent high-grade glioma treated between 1996 and 2016. Progression-free survival (PFS) and overall survival (OS) were calculated cumulatively over all studies, by therapy subgroup, and by decade of treatment. Random effects models were used to control for heterogeneity as measured by the I2 statistic. A total of 17 studies across 4 treatment strategies were included. Eleven investigated traditional chemotherapy, 1 investigated targeted therapy, 3 investigated immunotherapy, and 2 investigated radiotherapy. A total of 129 patients were included with a median age of 10.0 years. Cumulative PFS was 3.5 months (95% CI 2.1-5.0). Cumulative OS was 5.6 months (95% CI 3.9-7.3). OS was 4.0 months (95% CI 1.9-6.1) using traditional chemotherapy, 9.3 months using targeted therapies (95% CI 5.4-13), 6.9 months using immunotherapy (95% CI 2.1-12), and 14 months using reirradiation (95% CI 2.8-25). OS between 1996 and 2006 was 4.2 months (95% CI 2.1-6.2) compared to 8.5 months (95% CI 5.6-11) after 2006. Pediatric patients with recurrent high-grade glioma suffer from poor PFS and OS, regardless of therapy. There may be a trend towards improved OS in the last decade