Systematic Review of Nosocomial Waterborne Infections caused by Nontuberculous Mycobacteria

Background: Healthcare-acquired infections are an increasing priority for health care providers and policy makers. Water is an overlooked source of infectious microorganisms in health care facilities. Waterborne nontuberculous mycobacteria (NTM) are ubiquitous, especially in health care facility water systems, and are known to result in a variety of clinical diseases. Purpose: To contribute to an understanding of prevalence and disease burden, we conducted a systematic review to assess health care associated NTM infections from health care facility water systems. We document susceptible populations, modes of transmission, and the median attack rate. We aim to identify transmission risk factors and inform evidence-based policies for infection control and prevention. Methods: We searched Embase, Pubmed, Web of Science and clinicaltrials.gov without date restrictions. English language articles with original data on NTM waterborne infections in health care settings were included. Study Selection & Data Extraction: Randomized controlled trials, descriptive studies (case reports, case series), case-control studies, cohort studies, cross-sectional surveys, and quasiexperimental studies on nosocomial waterborne infections were included. Three investigators independently screened titles and abstracts for relevant articles, and one screened full-text articles. Data was extracted by one investigator, and a second confirmed accuracy for 10% of results. Results: We included 22 observational studies. Immunocompromised, post-surgical, and hemodialysis patients were commonly affected populations, and a range of exposure routes such as uncovered central venous catheters (CVCs), wound exposure, and contamination during surgical procedures was reported. The median attack rate was 12.1% (interquartile range, 11- 27.2). Conclusion: Waterborne NTM infection affects susceptible patients through common, preventable exposure routes. Effective prevention strategies will require both medical and environmental health expertise, and inter-professional cooperation will optimize these efforts. Additional high-quality studies using genotypic methods are also needed, especially in low- and middle-income countries.Master of Public Healt

Determinants of village doctors’ job satisfaction under China’s health sector reform: a cross-sectional mixed methods study

Background: To strengthen rural health workforce, the Chinese government has launched a series of policies to promote the job satisfaction of village doctors since the health sector reform. The purpose of this mixed-method study is to describe village doctors’ job satisfaction under the context of health sector reform and investigate the associated factors. Methods: Data was obtained from a survey of village doctors across three Chinese provinces in 2014. Using a multistage sampling process, quantitative data was collected from village doctors through the self-administered questionnaire and analyzed by multilevel logistic regression models. Qualitative data was collected through face-to-face semi-structured interviews on both village doctors and health managers. Theoretical coding was then conducted to analyze qualitative data. Results: Among the 1221 respondents, 48.6% felt satisfied with their job. Older village doctors with less of a workload and under high-level integrated management were more likely to feel satisfied with their job. Village doctors who earned the top level of monthly income felt more satisfied, while on the county level, those who lived in counties with the highest GDP felt less satisfied. However, enrollment in a pension plan showed no significant difference in regards to village doctors’ job satisfaction. Among 34 participants of qualitative interviews, most believed that age, income, and integrated management had a positive influence on the job satisfaction, while pension plan and basic public health care policies exhibited negative effects. Also, the increasing in availability of healthcare and health resources along with local economic development had negative effects on village doctors’ job satisfaction. Conclusion: Village doctors’ job satisfaction was quite low in regards to several determinants including age, income, workload, enrollment in a pension plan, integrated management, and county economic and medical availability development

Programmed cell death in host-symbiont associations, viewed through the Gene Ontology

Manipulation of programmed cell death (PCD) is central to many host microbe interactions. Both plant and animal cells use PCD as a powerful weapon against biotrophic pathogens, including viruses, which draw their nutrition from living tissue. Thus, diverse biotrophic pathogens have evolved many mechanisms to suppress programmed cell death, and mutualistic and commensal microbes may employ similar mechanisms. Necrotrophic pathogens derive their nutrition from dead tissue, and many produce toxins specifically to trigger programmed cell death in their hosts. Hemibiotrophic pathogens manipulate PCD in a most exquisite way, suppressing PCD during the biotrophic phase and stimulating it during the necrotrophic phase. This mini-review will summarize the mechanisms that have evolved in diverse microbes and hosts for controlling PCD and the Gene Ontology terms developed by the Plant-Associated Microbe Gene Ontology (PAMGO) Consortium for describing those mechanisms

Overcoming Redundancy: An RNAi Enhancer Screen for Morphogenesis Genes in Caenorhabditis elegans

Morphogenesis is an important component of animal development. Genetic redundancy has been proposed to be common among morphogenesis genes, posing a challenge to the genetic dissection of morphogenesis mechanisms. Genetic redundancy is more generally a challenge in biology, as large proportions of the genes in diverse organisms have no apparent loss of function phenotypes. Here, we present a screen designed to uncover redundant and partially redundant genes that function in an example of morphogenesis, gastrulation in Caenorhabditis elegans. We performed an RNA interference (RNAi) enhancer screen in a gastrulation-sensitized double-mutant background, targeting genes likely to be expressed in gastrulating cells or their neighbors. Secondary screening identified 16 new genes whose functions contribute to normal gastrulation in a nonsensitized background. We observed that for most new genes found, the closest known homologs were multiple other C. elegans genes, suggesting that some may have derived from rounds of recent gene duplication events. We predict that such genes are more likely than single copy genes to comprise redundant or partially redundant gene families. We explored this prediction for one gene that we identified and confirmed that this gene and five close relatives, which encode predicted substrate recognition subunits (SRSs) for a CUL-2 ubiquitin ligase, do indeed function partially redundantly with each other in gastrulation. Our results implicate new genes in C. elegans gastrulation, and they show that an RNAi-based enhancer screen in C. elegans can be used as an efficient means to identify important but redundant or partially redundant developmental genes

Cardiovascular risk burden, dementia risk and brain structural imaging markers:a study from UK Biobank

Background:Cardiovascular risk burden is associated with dementia risk and neurodegeneration-related brain structure, while the role of genetics and incident cardiovascular disease (CVD) remains unclear. Aims:To examine the association of overall cardiovascular risk burden with the risk of major dementia subtypes and volumes of related brain regions in a large sample, and to explore the role of genetics and CVD onset. Methods:A prospective study among 354 654 participants free of CVD and dementia (2006–2010, mean age 56.4 years) was conducted within the UK Biobank, with brain magnetic resonance imaging (MRI) measurement available for 15 104 participants since 2014. CVD risk burden was evaluated by the Framingham General Cardiovascular Risk Score (FGCRS). Dementia diagnosis was ascertained from inpatient and death register data. Results:Over a median 12.0-year follow-up, 3998 all-cause dementia cases were identified. Higher FGCRS was associated with increased all-cause dementia risk after adjusting for demographic, major lifestyle, clinical factors and the polygenic risk score (PRS) of Alzheimer’s disease. Comparing the high versus low tertile of FGCRS, the odds ratios (ORs) and 95% confidence intervals (CIs) were 1.26 (1.12 to 1.41) for all-cause dementia, 1.67 (1.33 to 2.09) for Alzheimer’s disease and 1.53 (1.07 to 2.16) for vascular dementia (all ptrend&lt;0.05). Incident stroke and coronary heart disease accounted for 14% (95% CI: 9% to 21%) of the association between FGCRS and all-cause dementia. Interactions were not detected for FGCRS and PRS on the risk of any dementia subtype. We observed an 83% (95% CI: 47% to 128%) higher all-cause dementia risk comparing the high–high versus low–low FGCRS–PRS category. For brain volumes, higher FGCRS was associated with greater log-transformed white matter hyperintensities, smaller cortical volume and smaller grey matter volume. Conclusions:Our findings suggest that the positive association of cardiovascular risk burden with dementia risk also applies to major dementia subtypes. The association of cardiovascular risk burden with all-cause dementia is largely independent of CVD onset and genetic predisposition to dementia.</p

Cardiovascular risk burden, dementia risk and brain structural imaging markers:a study from UK Biobank

Background:Cardiovascular risk burden is associated with dementia risk and neurodegeneration-related brain structure, while the role of genetics and incident cardiovascular disease (CVD) remains unclear. Aims:To examine the association of overall cardiovascular risk burden with the risk of major dementia subtypes and volumes of related brain regions in a large sample, and to explore the role of genetics and CVD onset. Methods:A prospective study among 354 654 participants free of CVD and dementia (2006–2010, mean age 56.4 years) was conducted within the UK Biobank, with brain magnetic resonance imaging (MRI) measurement available for 15 104 participants since 2014. CVD risk burden was evaluated by the Framingham General Cardiovascular Risk Score (FGCRS). Dementia diagnosis was ascertained from inpatient and death register data. Results:Over a median 12.0-year follow-up, 3998 all-cause dementia cases were identified. Higher FGCRS was associated with increased all-cause dementia risk after adjusting for demographic, major lifestyle, clinical factors and the polygenic risk score (PRS) of Alzheimer’s disease. Comparing the high versus low tertile of FGCRS, the odds ratios (ORs) and 95% confidence intervals (CIs) were 1.26 (1.12 to 1.41) for all-cause dementia, 1.67 (1.33 to 2.09) for Alzheimer’s disease and 1.53 (1.07 to 2.16) for vascular dementia (all ptrend&lt;0.05). Incident stroke and coronary heart disease accounted for 14% (95% CI: 9% to 21%) of the association between FGCRS and all-cause dementia. Interactions were not detected for FGCRS and PRS on the risk of any dementia subtype. We observed an 83% (95% CI: 47% to 128%) higher all-cause dementia risk comparing the high–high versus low–low FGCRS–PRS category. For brain volumes, higher FGCRS was associated with greater log-transformed white matter hyperintensities, smaller cortical volume and smaller grey matter volume. Conclusions:Our findings suggest that the positive association of cardiovascular risk burden with dementia risk also applies to major dementia subtypes. The association of cardiovascular risk burden with all-cause dementia is largely independent of CVD onset and genetic predisposition to dementia.</p

PCSK9 inhibitors and ezetimibe with or without statin therapy for cardiovascular risk reduction: a systematic review and network meta-analysis.

OBJECTIVE To compare the impact of ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors on cardiovascular outcomes in adults taking maximally tolerated statin therapy or who are statin intolerant. DESIGN Network meta-analysis. DATA SOURCES Medline, EMBASE, and Cochrane Library up to 31 December 2020. ELIGIBILITY CRITERIA FOR SELECTING STUDIES Randomised controlled trials of ezetimibe and PCSK9 inhibitors with ≥500 patients and follow-up of ≥6 months. MAIN OUTCOME MEASURES We performed frequentist fixed-effects network meta-analysis and GRADE (grading of recommendations, assessment, development, and evaluation) to assess certainty of evidence. Results included relative risks (RR) and absolute risks per 1000 patients treated for five years for non-fatal myocardial infarction (MI), non-fatal stroke, all-cause mortality, and cardiovascular mortality. We estimated absolute risk differences assuming constant RR (estimated from network meta-analysis) across different baseline therapies and cardiovascular risk thresholds; the PREDICT risk calculator estimated cardiovascular risk in primary and secondary prevention. Patients were categorised at low to very high cardiovascular risk. A guideline panel and systematic review authors established the minimal important differences (MID) of 12 per 1000 for MI and 10 per 1000 for stroke. RESULTS We identified 14 trials assessing ezetimibe and PCSK9 inhibitors among 83 660 adults using statins. Adding ezetimibe to statins reduced MI (RR 0.87 (95% confidence interval 0.80 to 0.94)) and stroke (RR 0.82 (0.71 to 0.96)) but not all-cause mortality (RR 0.99 (0.92 to 1.06)) or cardiovascular mortality (RR 0.97 (0.87 to 1.09)). Similarly, adding PCSK9 inhibitor to statins reduced MI (0.81 (0.76 to 0.87)) and stroke (0.74 (0.64 to 0.85)) but not all-cause (0.95 (0.87 to 1.03)) or cardiovascular mortality (0.95 (0.87 to 1.03)). Among adults with very high cardiovascular risk, adding PCSK9 inhibitor was likely to reduce MI (16 per 1000) and stroke (21 per 1000) (moderate to high certainty); whereas adding ezetimibe was likely to reduce stroke (14 per 1000), but the reduction of MI (11 per 1000) (moderate certainty) did not reach MID. Adding ezetimibe to PCSK9 inhibitor and statin may reduce stroke (11 per 1000), but the reduction of MI (9 per 1000) (low certainty) did not reach MID. Adding PCSK9 inhibitors to statins and ezetimibe may reduce MI (14 per 1000) and stroke (17 per 1000) (low certainty). Among adults with high cardiovascular risk, adding PCSK9 inhibitor probably reduced MI (12 per 1000) and stroke (16 per 1000) (moderate certainty); adding ezetimibe probably reduced stroke (11 per 1000), but the reduction in MI did not achieve MID (8 per 1000) (moderate certainty). Adding ezetimibe to PCSK9 inhibitor and statins did not reduce outcomes beyond MID, while adding PCSK9 inhibitor to ezetimibe and statins may reduce stroke (13 per 1000). These effects were consistent in statin-intolerant patients. Among moderate and low cardiovascular risk groups, adding PCSK9 inhibitor or ezetimibe to statins yielded little or no benefit for MI and stroke. CONCLUSIONS Ezetimibe or PCSK9 inhibitors may reduce non-fatal MI and stroke in adults at very high or high cardiovascular risk who are receiving maximally tolerated statin therapy or are statin-intolerant, but not in those with moderate and low cardiovascular risk

Triangle Interprofessional Partners for Prevention (TIPP): Students Collaborating to Improve Care for Superutilizer Patients

Background: • In the US, 5% of Medicaid patients account for nearly half of health care costs, but this spending does not improve patient outcomes. • Cost-effectiveness and value are an increasing focus in health care; therefore these so-called superutilizer (SU) patients are garnering increased national attention, through the initiatives of Camden Coalition. • Interdisciplinary care can improve care for patients, but medical education often neglects these interprofessional (IP) experiences. • Triangle Interprofessional Partners for Prevention (TIPP) was established with a way to improve SU patient care, decrease hospitalization costs, and promote IP education among students in health care fields. Objectives: 1. Develop sustainable processes to engage IP students in improving quality of health care. 2. Decrease unnecessary hospitalizations and Emergency Department visits for SU patients, lowering total hospital charges. 3. Increase opportunities for IP students to collaborate, fostering mutual understanding and respect. Methods: • An EMR-generated algorithm identified SU patients at UNC (>3 hospitalizations in 12 months). • IP teams of 2-3 social work, nursing, public health, and medicine students conducted home visits and appointments to identify root causes of hospitalizations. Teams worked closely with patients to address risk factors for readmission and coordinate care. • Students met weekly with IP faculty to discuss patient needs and progress. Examples of services provided to patients include: assistance with food insecurity and unstable housing, arranging a new primary care physician, facilitating application for financial assistance with medical bills. Results: • Recruitment is ongoing, but preliminary results for patients enrolled in 2016 are available. • Of the seven enrolled patients, pre-intervention average monthly inpatient charges ranged from $2,235 to$19,662 monthly. Pre-intervention average monthly outpatient charges ranged from $0 to$6,457. • Post-intervention, average monthly inpatient cost decreased in five of seven patients. For these patients, average monthly inpatient charges ranged from $0 to$50,267 and outpatient charges ranged from $85 to$5,290. Three of seven patients have not had any additional hospitalizations post-intervention. Five of seven patients had a decrease in average hospitalization rate. • Results last updated February 2017 Key Lessons for Dissemination: To support other programs who wish to adapt this model at their home institutions, we summarize these key lessons for implementation: o Identifying and Connecting with Patients • During the course of our program, we trialed models including inpatient, outpatient, and a mixed patient populations, balancing SU needs with logistical necessities. It was easiest for us to successfully make contact with hospitalized patients, thus we favor an inpatient population model. If we were unable to connect with hospitalized patients before discharge, we established initial contact with patients over the phone. • We initially experienced challenges identifying hospitalized patients and assigning available team members in real time. A team member with protected time to identify patients is ideal. o IP Education and Collaboration • The divergent schedules of IP students presented challenges in finding a consistent time to meet as a large team. We propose identifying a weekly IP half day set aside by all schools for IP activities. • Successful implementation of IP initiatives requires institutional buy-in and administrative support. Our enthusiastic and supportive IP faculty champions have been essential to the TIPP’s success. o Students as significant contributors to care • We believe this program is mutually beneficial to student and patient and demonstrates the students’ potential to directly improve patient care. • Students are low cost contributors to care. TIPP’s cost of implementation consists solely of faculty time contributed to meeting with students. o Sustainability • TIPP is currently run by faculty and student volunteers. As we continue to grow, incorporating students from other professional schools, and as UNC transitions to a Next Generation Accountable Care Organization, institutional buy-in will be key to future sustainability. Conclusion: • As high value care becomes an increasing focus, addressing these SU patients is an important strategy to improve the quality and efficiency of health care. • TIPP is a student-driven organization aiming to improve the quality and efficiency of SU patient care and promote IP education. • Students work in IP teams to address SU patients’ risk factors for rehospitalization. • IP educational opportunities are an important way to develop quality interdisciplinary care givers in the future. • Results from patients recruited last year demonstrate that five of seven enrolled patients had a decrease in average monthly inpatient cost and average hospitalization rate after enrollment in the TIPP program. • Patient recruitment is ongoing and as we continue to refine our processes, we hope to include additional IP students from the schools of pharmacy and physician assistants. • Students are an abundant, untapped resource in academic medical centers and a potentially significant contributor to improve the quality and efficiency of patient care

A systematic review of syphilis serological treatment outcomes in HIV-infected and HIV-uninfected persons: rethinking the significance of serological non-responsiveness and the serofast state after therapy

Abstract Background Syphilis remains a global public health threat and can lead to severe complications. In addition to resolution of clinical manifestations, a reduction in nontreponemal antibody titers after treatment is regarded as “proof of cure.” However, some patients manifest < 4-fold decline (“serological non-response”) or persistently positive nontreponemal titers despite an appropriate decline (“serofast”) that may represent treatment failure, reinfection, or a benign immune response. To delineate these treatment phenomena, we conducted a systematic review of the literature regarding serological outcomes and associated factors among HIV-infected and -uninfected subjects. Methods Six databases (PubMed, Embase, CINAHL, Web of Science, Scopus, and BIOSIS) were searched with no date restrictions. Relevant articles that evaluated serological treatment responses and correlates of serological cure (≥ four-fold decline in nontreponemal titers) were included. Results We identified 1693 reports in the literature, of which 20 studies met selection criteria. The median proportion of patients who had serological non-response was 12.1 % overall (interquartile range, 4.9–25.6), but varied depending on the time points after therapy. The serofast proportion could only be estimated from 2 studies, which ranged from 35.2–44.4 %. Serological cure was primarily associated with younger age, higher baseline nontreponemal titers, and earlier syphilis stage. The relationship between serological cure and HIV status was inconsistent; among HIV-infected patients, CD4 count and HIV viral load was not associated with serological cure. Conclusions Serological non-response and the serofast state are common syphilis treatment outcomes, highlighting the importance of determining the immunological and clinical significance of persistent nontreponemal antibody titers after therapy

Improving calculation, interpretation and communication of familial colorectal cancer risk: Protocol for a randomized controlled trial

Contains fulltext : 88114.pdf (publisher's version ) (Open Access)BACKGROUND: Individuals with multiple relatives with colorectal cancer (CRC) and/or a relative with early-onset CRC have an increased risk of developing CRC. They are eligible for preventive measures, such as surveillance by regular colonoscopy and/or genetic counselling. Currently, most at-risk individuals do not follow the indicated follow-up policy. In a new guideline on familial and hereditary CRC, clinicians have new tasks in calculating, interpreting, and communicating familial CRC risk. This will lead to better recognition of individuals at an increased familial CRC risk, enabling them to take effective preventive measures. This trial compares two implementation strategies (a common versus an intensive implementation strategy), focussing on clinicians' risk calculation, interpretation, and communication, as well as patients' uptake of the indicated follow-up policy. METHODS: A clustered randomized controlled trial including an effect, process, and cost evaluation will be conducted in eighteen hospitals. Nine hospitals in the control group will receive the common implementation strategy (i.e., dissemination of the guideline). In the intervention group, an intensive implementation strategy will be introduced. Clinicians will receive education and tools for risk calculation, interpretation, and communication. Patients will also receive these tools, in addition to patient decision aids. The effect evaluation includes assessment of the number of patients for whom risk calculation, interpretation, and communication is performed correctly, and the number of patients following the indicated follow-up policy. The actual exposure to the implementation strategies and users' experiences will be assessed in the process evaluation. In a cost evaluation, the costs of the implementation strategies will be determined. DISCUSSION: The results of this study will help determine the most effective method as well as the costs of improving the recognition of individuals at an increased familial CRC risk. It will provide insight into the experiences of both patients and clinicians with these strategies.The knowledge gathered in this study can be used to improve the recognition of familial and hereditary CRC at both the national and international level, and will serve as an example to improve care for patients and their relatives worldwide. Our results may also be useful in improving healthcare in other diseases. TRIAL REGISTRATION: ClinicalTrials.gov NCT00929097