Infection Rates and Risk Factors for Infection Among Health Workers During Ebola and Marburg Virus Outbreaks: A Systematic Review.

Background: Infection in health workers (HWs) has characterized outbreaks of Ebola virus disease (EVD) and Marburg virus disease (MVD). We conducted a systematic review to investigate infection and mortality rates and common exposure risks in HWs in EVD and MVD outbreaks. Methods: We searched the EMBASE and PubMed databases to identify articles posted before 27 December 2017, with no language restrictions. Data on the number, frequency, and mortality of HW infection and exposure risks were extracted. Results: Ninety-four articles related to 22 outbreaks were included. HW infections composed 2%-100% of cases in EVD and 5%-50% of cases in MVD outbreaks. Among exposed HWs, 0.6%-92% developed EVD, and 1%-10% developed MVD. HW infection rates were consistent through outbreaks. The most common exposure risk situations were inadequate personal protective equipment and exposure to patients with unrecognized EVD/MVD. Similar risks were reported in past EVD/MVD outbreaks and in the recent outbreak in West Africa. Conclusions: Many outbreaks reported high proportions of infected HWs. Similar HW infection rates and exposure risk factors in both past and recent EVD and MVD outbreaks emphasize the need to improve the implementation of appropriate infection control measures consistently across all healthcare settings.

The Role of Nanotechnology in Understanding the Pathophysiology of Traumatic Brain Injury.

Recently, traumatic brain injury (TBI) has been a growing disorder due to frequent brain dysfunction. The Glasgow Coma Scale expresses TBI as classified as having mild, moderate, or severe brain effects, according to the effects on the brain. Brain receptors undergo various modifications in their pathology through chemical synaptic pathways, leading to depression, Alzheimer's, and Parkinson's disease. These brain disorders can be controlled using central receptors such as dopamine, glutamate, and γ-aminobutyric acid, which are clearly explained in this review. Furthermore, there are many complications in TBI's clinical trials and diagnostics, leading to insignificant treatment, causing permanent neuro-damage, physical disability, and even death. Bio-screening and conventional molecular-based therapies are inappropriate due to poor preclinical testing and delayed recovery. Hence, modern nanotechnology utilizing nanopulsed laser therapy and advanced nanoparticle insertion will be suitable for TBI's diagnostics and treatment. In recent days, nanotechnology has an important role in TBI control and provides a higher success rate than conventional therapies. This review highlights the pathophysiology of TBI by comprising the drawbacks of conventional techniques and supports suitable modern alternates for treating TBI.

Evaluation of guideline recommendations on oral medications for type 2 diabetes mellitus: a systematic review.

BACKGROUND: Clinical practice guidelines have an important role in guiding choices among the numerous medications available to treat type 2 diabetes mellitus, but little is known about their quality. PURPOSE: To assess whether guidelines on oral medications for type 2 diabetes are consistent with a systematic review of the current evidence and whether the consistency of the guidelines depends on the quality of guideline development. DATA SOURCES: MEDLINE, CINAHL, and guideline-specific databases were searched between July 2007 and August 2011, after the 2007 publication of a peer-reviewed systematic review on oral diabetes medications. STUDY SELECTION: Two reviewers independently screened citations to identify English-language guidelines on oral medications to treat type 2 diabetes that were applied in the United States, United Kingdom, and Canada. DATA EXTRACTION: Reviewers assessed whether the guidelines addressed and agreed with 7 evidence-based conclusions from the 2007 systematic review. Two reviewers independently rated guideline quality by using 2 domains from the Appraisal of Guidelines Research and Evaluation instrument. DATA SYNTHESIS: Of the 1000 screened citations, 11 guidelines met the inclusion criteria. Seven guidelines agreed with the conclusion that metformin is favored as the first-line agent. Ten guidelines agreed that thiazolidinediones are associated with higher rates of edema and congestive heart failure compared with other oral medications to treat type 2 diabetes. One guideline addressed no evidence-based conclusions, and 5 guidelines agreed with all 7 conclusions. The summary scores of the rigor of development (median, 28.6% [range, 16.7% to 100.0%]) and editorial independence (median, 75.0% [range, 8.3% to 100.0%]) domains varied greatly across guidelines. Guidelines that received higher quality scores contained more recommendations that were consistent with the evidence-based conclusions. LIMITATION: Only English-language guidelines targeting users in the United States, United Kingdom, and Canada that contained recommendations on oral medications were included. CONCLUSION: Not all practice guidelines on oral treatment of type 2 diabetes were consistent with available evidence from a systematic review. Guidelines judged to be of higher quality contained more recommendations consistent with evidence-based conclusions. The quality of guideline development processes varied substantially. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Healthcare workers, epidemic biological risks - recommendations based on the experience with COVID-19 and Ebolavirus.

Infectious disease outbreaks frequently cause illness and death among Healthcare Workers (HCWs). We compare strategies from recent, past and ongoing outbreak measures used to protect HCWs, including those facing additional challenges such as racial disparities, violence and stigmatization. Outbreaks and pandemics superimposed on countries with preexisting crises have also affected emergency response to these viral outbreaks. Strategies to protect HCWs include adherence to recommended infection prevention and control measures; new technology such as rapid point-of-care tests and remote monitoring; adopting national public health preparedness plans to ensure the supply and allocation of PPE, staff, and testing supplies; occupational health and mental health support services. Lessons learned from recent pandemics should be used by Infection Prevention and Control and Occupational Health staff to refine preparedness plans to protect HCWs better.

DANGER! Crisis Health Workers at Risk.

The occupational hazards of health workers (HWs) in standard work environments have been well defined in both the developed and developing world during routine working conditions. Less defined are the hazards to HWs during pandemics, epidemics, natural disasters, wars, conflicts, and other crises. How do crises affect the infrastructure of medical systems? What are the distinct needs of the patient population during crises? What are the peculiarities of the Crisis Health Worker (CHW)? What are the known CHWs' occupational risks? What are the protective factors? By means of a PubMed search, we synthesized the most relevant publications to try to answer these questions. Failures of healthcare infrastructure and institutions include CHW shortages, insufficient medical supplies, medications, transportation, poorly paid health workers, security concerns, and the absence of firm guidance in health policy. Healthcare needs affecting the patient population and CHWs include crisis-induced injury and illness, hazardous exposures, communicable diseases, mental healthcare, and continuity of care for pre-crisis medical conditions. CHWs' occupational hazards include supply deficiencies, infectious disease transmission, long working hours, staff shortages, financial reimbursements, mental fatigue, physical exhaustion, and inconsistent access to clean water, electricity, and Internet. CHWs suffer from injuries and illnesses that range from immediate, debilitating injuries to chronic, unforeseen effects like mental fatigue, physical exhaustion, anxiety, burnout, and even post-traumatic stress syndrome (PTSD). Protective factors include personal traits such as adaptability and resilience as well as skills learned through structured education and training. Success will be achieved by constructively collaborating with local authorities, local health workers, national military, foreign military, and aid organizations.

Cherubism with idiopathic gingival enlargement: A rare case report.

Cherubism is a congenital childhood disease of autosomal dominant inheritance. It is a benign, familial giant cell lesion characterized by gradually progressive painless swelling of the jaws. Idiopathic gingival enlargement is a rare condition and may be associated with some uncommon syndromes. This case report describes an 11-year-old patient with unusual clinical form of gingival enlargement, cherubic facial appearance. Clinical examination revealed the presence of the hyperplastic gingiva, which completely covered all teeth. The bilateral swelling of mandible and the appearance of the sclera beneath the iris suggested cherubism. The diagnosis was confirmed by histopathological examination, which revealed multinucleated giant cells. Computed tomography scan showed multiple osteolytic zones in the mandible. A full mouth gingivectomy was performed in four stages. Lesion healed successfully, and no recurrence observed after 1-year follow-up. There was a marked improvement in esthetics and function through the surgical excision of the overgrowth.

Comparative analysis of gingival crevicular fluid a disintegrin and metalloproteinase 8 levels in health and periodontal disease: A clinic-biochemical study.

AIM AND BACKGROUND: A disintegrin and metalloproteinase 8 (ADAM8) is a marker belonging to the class of ADAM family of metalloproteinase which is found to be involved in inflammation and bone resorption in periodontal disease by acting as osteoclast stimulating factor. In several systemic inflammatory diseases, elevated levels of ADAM8 are detected in human serum and other body fluids. Recently, ADAM8 was even detected in gingival crevicular fluid (GCF) of patients with periodontal diseases. Hence, the aim of the study was to estimate the levels of ADAM8 in GCF of healthy and chronic periodontitis subjects. MATERIALS AND METHODS: Periodontal examination and collection of GCF by the extracrevicular method was performed in 30 subjects selected randomly and categorized into two groups. Group I (healthy, n = 15) and Group II (chronic periodontitis, n = 15). ADAM8 levels in GCF were estimated by enzyme-linked immunosorbent assay. RESULTS: ADAM8 was detected in both Group I and II. Highest mean ADAM8 concentration was obtained for Group II, whereas the lowest concentration was seen in Group I. This suggests that ADAM8 levels increase proportionally with the progression of periodontal disease. There was a significant correlation between ADAM8 levels and clinical parameters in the study group. CONCLUSION: The results of our study indicate that the ADAM8 levels in GCF are positively associated with periodontal disease, which may provide a useful tool in monitoring its progression. Nevertheless, further longitudinal studies are required with larger sample sizes in which ADAM8 levels are progressively estimated and compared to baseline values.

LASER curettage as adjunct to SRP, compared to SRP alone, in patients with periodontitis and controlled type 2 diabetes mellitus: A comparative clinical study.

AIM: To compare the effect of scaling and root planning (SRP) alone, and laser curettage as an adjunct to SRP, on the clinical parameters of patients with periodontitis and controlled type 2 diabetes mellitus. MATERIALS AND METHODS: Ten patients were divided into two equal groups in a split-mouth design - Group I: SRP alone, Group II: SRP + laser curettage. The following clinical parameters were recorded: (i) Gingival index (ii) plaque index (iii) sulcular bleeding index (iv) probing depth (PD) and (v) clinical attachment level (CAL). SRP was done in one quadrant using Gracey curettes and in another quadrant SRP plus laser curettage was done. Three weeks after the therapy, the clinical parameters were recorded and the results were analyzed and the percentage of improvement were evaluated. RESULTS: The results of this study indicated that both SRP and SRP + laser curettage were efficient for reducing gingival inflammation and PD. Group II showed more reduction in PD and more gain in CAL than Group I. Mean reduction in PD was 20.22% in Group I and 26.76% in Group II. Mean CAL gain is 32.5% in Group II and 22.34% in Group I. CONCLUSION: In both the groups, gingival inflammation was reduced. When laser curettage was used as adjunct to SRP more reduction in PD and CAL was seen.

Use of case reports and the Adverse Event Reporting System in systematic reviews: overcoming barriers to assess the link between Crohn's disease medications and hepatosplenic T-cell lymphoma.

BACKGROUND: To identify demographic and clinical characteristics associated with cases of hepatosplenic T-cell lymphoma (HSTCL) in patients with Crohn's disease, and to assess strength of evidence for a causal relationship between medications and HSTCL in Crohn's disease. METHODS: We identified cases of HSTCL in Crohn's disease in studies included in a comparative effectiveness review of Crohn's disease medications, through a separate search of PubMed and Embase for published case reports, and from the Food and Drug Administration (FDA) Adverse Event Reporting System (AERS). We used three causality assessment tools to evaluate the relationship between medication exposure and HSTCL. RESULTS: We found 37 unique cases of HSTCL in patients with Crohn's disease. Six cases were unique to the published literature and nine were unique to AERS. Cases were typically young (<40 years of age) and male (86%). The most commonly reported medications were anti-metabolites (97%) and anti-tumor necrosis factor alpha (anti-TNFa) medications (76%). Dose and duration of therapy were not consistently reported. Use of aminosalicylates and corticosteroids were rarely reported, despite the high prevalence of these medications in routine treatment. Using the causality assessment tools, it could only be determined that anti-metabolite and anti-TNFa therapies were possible causes of HSTCL in Crohn's disease based on the data contained in the case reports. CONCLUSION: Systematic reviews that incorporate case reports of rare lethal events should search both published literature and AERS, but consideration should be given to the limitations of case reports. In this study, establishing a causative effect other than 'possible' between anti-metabolite or anti-TNFa therapies and HSTCL was not feasible because case reports lacked data required by the causality assessments, and because of the limited applicability of causality assessment tools for rare irreversible events. We recommend minimum reporting requirements for case reports to improve causality assessment and routine reporting of rare life-threatening events, including their absence, in clinical trials to help clinicians determine whether rare adverse events are causally related to a medication.

Heterologous immunity triggered by a single, latent virus in Mus musculus: combined costimulation- and adhesion- blockade decrease rejection.

The mechanisms underlying latent-virus-mediated heterologous immunity, and subsequent transplant rejection, especially in the setting of T cell costimulation blockade, remain undetermined. To address this, we have utilized MHV68 to develop a rodent model of latent virus-induced heterologous alloimmunity. MHV68 infection was correlated with multimodal immune deviation, which included increased secretion of CXCL9 and CXCL10, and with the expansion of a CD8(dim) T cell population. CD8(dim) T cells exhibited decreased expression of multiple costimulation molecules and increased expression of two adhesion molecules, LFA-1 and VLA-4. In the setting of MHV68 latency, recipients demonstrated accelerated costimulation blockade-resistant rejection of skin allografts compared to non-infected animals (MST 13.5 d in infected animals vs 22 d in non-infected animals, p<.0001). In contrast, the duration of graft acceptance was equivalent between non-infected and infected animals when treated with combined anti-LFA-1/anti-VLA-4 adhesion blockade (MST 24 d for non-infected and 27 d for infected, p = n.s.). The combination of CTLA-4-Ig/anti-CD154-based costimulation blockade+anti-LFA-1/anti-VLA-4-based adhesion blockade led to prolonged graft acceptance in both non-infected and infected cohorts (MST>100 d for both, p<.0001 versus costimulation blockade for either). While in the non-infected cohort, either CTLA-4-Ig or anti-CD154 alone could effectively pair with adhesion blockade to prolong allograft acceptance, in infected animals, the prolonged acceptance of skin grafts could only be recapitulated when anti-LFA-1 and anti-VLA-4 antibodies were combined with anti-CD154 (without CTLA-4-Ig, MST>100 d). Graft acceptance was significantly impaired when CTLA-4-Ig alone (no anti-CD154) was combined with adhesion blockade (MST 41 d). These results suggest that in the setting of MHV68 infection, synergy occurs predominantly between adhesion pathways and CD154-based costimulation, and that combined targeting of both pathways may be required to overcome the increased risk of rejection that occurs in the setting of latent-virus-mediated immune deviation.

Expansion of effector memory TCR Vbeta4+ CD8+ T cells is associated with latent infection-mediated resistance to transplantation tolerance.

Therapies that control largely T cell-dependent allograft rejection in humans also possess the undesirable effect of impairing T cell function, leaving transplant recipients susceptible to opportunistic viruses. Prime among these opportunists are the ubiquitous herpesviruses. To date, studies are lacking that address the effect of viruses that establish a true latent state on allograft tolerance or the effect of tolerance protocols on the immune control of latent viruses. By using a mixed chimerism-based tolerance-induction protocol, we found that mice undergoing latent infection with gammaHV68, a murine gamma-herpesvirus closely related to human gamma-herpesviruses such as EBV and Kaposi's sarcoma-associated herpesvirus, significantly resist tolerance to allografts. Limiting the degree of virus reactivation or innate immune response did not reconstitute chimerism in latently infected mice. However, gammaHV68-infected mice showed increased frequency of CD8+ T cell alloreactivity and, interestingly, expansion of virus-induced, alloreactive, "effector/effector memory" TCR Vbeta4+CD8+ T cells driven by the gammaHV68-M1 gene was associated with resistance to tolerance induction in studies using gammaHV68-M1 mutant virus. These results define the viral gene and immune cell types involved in latent infection-mediated resistance to allograft tolerance and underscore the influence of latent herpesviruses on allograft survival.