General practitioner\u27s knowledge regarding the diagnosis and drug therapy for acute myocardial infarction

OBJECTIVE: To assess the general practitioners (GP) knowledge regarding the diagnosis and initial drug therapy for acute myocardial infarction (AMI). METHODS: A questionnaire-based survey was conducted in randomly selected GPs of Karachi. Doctors working in community as GPs who were registered medical practitioners having a Bachelor of Medicine & Bachelor of Surgery degree were included in the study. Doctors working at tertiary care facilities or having a post graduate degree or post graduate training in a specialty other than family medicine were excluded from the study. RESULTS: A total of 186 GPs participated in our study. GPs who studied research journals were 2.33 times more likely to investigate serum cardiac troponins levels for the diagnosis of AMI compared to those who did not study research journals (P = 0.02). Twenty six percent of the GPs said that they would refer a patient with suspected AMI without treatment, while 76% said that they would consider some treatment prior to referral. Fifty eight percent of the GPs identified ST segment elevation myocardial infarction (STEMI) of \u3c 12 hours duration as an indication of thrombolysis while 28% identified posterior wall AMI as a thrombolytic indication. CONCLUSION: GPs, although adequately aware of the presenting features of AMI, were lacking in knowledge regarding the means for confirmation of diagnosis, initial drug therapy and were less likely to carry management steps in their practice

Women experiences of using external breast prosthesis after mastectomy.

Objective: The aim of this study was to identify the experiences of breast cancer patients using external breast prostheses (EBP) in the context of the Pakistani society. Methods: A qualitative descriptive exploratory design was used in the study. In-depth individual interviews were conducted with 15 postmastectomy women using EBP. A semi-structured interview guide with open-ended questions was used for the interviews. The analysis of the data was organized into four categories according to the study questions including reasons for using EBP, feeling about EBP, challenges for using EBP, and coping with lost breast. Each category was further divided into subcategories. Results: Women used EBP because they felt strange, incomplete, and embarrassed in front of other people, due to the asymmetrical shape of the chest after mastectomy. They faced several challenges with regard to obtaining and using the EBP. While EBP was used as an alternative of their lost breast, they experienced sadness and embarrassment. They found it challenging to take care of the EBP and were required to make changes in their lifestyle. However, they accepted living with their lost breast, either through rationalization, family support, or faith and prayers, which helped them to cope. Conclusions: The study findings have given insight into some real experiences of mastectomy patients. Mastectomy not only affects women\u27s physical health but also their psychological health, as a result of which they become reluctant to socialize. Using EBP can help them to improve their body image and body posture. Health-care providers\u27 support is very important to the families of the patients specifically where patients are very shy to openly seek information due to cultural constraints

In vitro and in vivo mRNA delivery using lipid-enveloped pHresponsive polymer nanoparticles

Biodegradable core−shell structured nanoparticles with a poly(β-amino ester) (PBAE) core enveloped by a phospholipid bilayer shell were developed for in vivo mRNA delivery with a view toward delivery of mRNA-based vaccines. The pH-responsive PBAE component was chosen to promote endosome disruption, while the lipid surface layer was selected to minimize toxicity of the polycation core. Messenger RNA was efficiently adsorbed via electrostatic interactions onto the surface of these net positively charged nanoparticles. In vitro, mRNA-loaded particle uptake by dendritic cells led to mRNA delivery into the cytosol with low cytotoxicity, followed by translation of the encoded protein in these difficult-to-transfect cells at a frequency of 30%. Particles loaded with mRNA administered intranasally (i.n.) in mice led to the expression of the reporter protein luciferase in vivo as soon as 6 h after administration, a time point when naked mRNA given i.n. showed no expression. At later time points, luciferase expression was detected in naked mRNA-treated mice, but this group showed a wide variation in levels of transfection, compared to particle-treated mice. This system may thus be promising for noninvasive delivery of mRNA-based vaccines.United States. Dept. of Defense (Institute for Soldier Nanotechnology, contract W911NF-07-D-0004)Ragon Institute of MGH, MIT and HarvardSingapore. Agency for Science, Technology and ResearchHoward Hughes Medical Institute (Investigator

Increasing Incidence of MDROs: An Emerging Global Concern

Introduction: With massive efflux of civilians from violence-stricken countries, the high rates of colonization with multidrug-resistant organisms (MDROs) amongst the refugees is an emerging global concern. Our report describes two Middle Eastern patients who suffered severe traumatic injuries in their home countries, subsequently developing chronic wounds. Upon arrival to the United States, the patients sought treatment in our institution for wound infection with MDRO. Materials and methods: Clinical data was collected from the patients’ charts. Identification and susceptibility testing were performed as part of routine identification/susceptibility test in the clinical microbiology laboratory. MICs performed by manual microbroth dilution according to Clinical and Laboratory Standards Institute (CLSI) guidelines.Time kill curves used to determine in vitro synergy of Pseudomonas aeruginosa isolate in various antibiotic combinations (½ x MIC meropenem plus ½ x MIC colistin, ½ x MIC meropenum plus ½ x MIC colistin plus ½ x MIC rifampin and ½ x MIC meropenem plus ½ x MIC ceftazidime/avibactam). Mueller Hinton II broth was used. Samples were serially diluted at 0, 4 and 24 hours and plated on TSA II agar. Time kill curves were constructed, plotting colony counts over time, with synergy being defined as ≥2-log10 decrease in CFU/ml between the combination and its most active constituent after 24h, the number of surviving organisms in the presence of combination must be ≥2 log10 CFU/ml below the starting inoculum. Results: Patient 1 came from Syria, and patient 2 from Yemen. Both patients’ wound infections were healthcare-associated, with underlying chronic osteomyelitis. Both had multiple risk factors for MDRO, including multiple prior surgeries and antibiotic courses. Patient 1 culture grew CRE Klebsiella and MDR Morganella, and later ESBL Escherichia coli. Patient 2 culture grew Pseudomonas aeruginosa sensitive only to colistin. Patient 1 was treated with ertapenem. Patient 2 received rifampin+meropenen+colistin, the only antibiotic combination demonstrating synergistic killing. Both patients required prolonged therapy, and on follow up were doing well. Conclusions: Colonization with MDRO amongst Middle Eastern immigrants is an alarming phenomenon.In vitro experiments with available antibacterial agents may assist in the choice of therapy for MDRO strains when conventional options are exhausted.https://scholarlycommons.henryford.com/merf2019basicsci/1001/thumbnail.jp

Systematic review on human resources for health interventions to improve maternal health outcomes: Evidence from low- and middle-income countries

There is a broad consensus and evidence that shows qualified, accessible, and responsive human resources for health (HRH) can make a major impact on the health of the populations. At the same time, there is widespread recognition that HRH crises particularly in low- and middle-income countries (LMICs) impede the achievement of better health outcomes/targets. In order to achieve the Sustainable Development Goals (SDGs), equitable access to a skilled and motivated health worker within a performing health system is need to be ensured. This review contributes to the vast pool of literature towards the assessment of HRH for maternal health and is focused on interventions delivered by skilled birth attendants (SBAs). Studies were included if (a) any HRH interventions in management system, policy, finance, education, partnership, and leadership were implemented; (b) these were related to SBA; (c) reported outcomes related to maternal health; (d) the studies were conducted in LMICs; and (e) studies were in English. Studies were excluded if traditional birth attendants and/or community health workers were trained. The review identified 25 studies which revealed reasons for poor maternal health outcomes in LMICs despite the efforts and policies implemented throughout these years. This review suggested an urgent and immediate need for formative evidence-based research on effective HRH interventions for improved maternal health outcomes. Other initiatives such as education and empowerment of women, alleviating poverty, establishing gender equality, and provision of infrastructure, equipment, drugs, and supplies are all integral components that are required to achieve SDGs by reducing maternal mortality and improving maternal health

Impact of service provision platforms on maternal and newborn health in conflict areas and their acceptability in Pakistan: a systematic review

Various models and strategies have been implemented over the years in different parts of the world to improve maternal and newborn health (MNH) in conflict affected areas. These strategies are based on specific needs and acceptability of local communities. This paper has undertaken a systematic review of global and local (Pakistan) information from conflict areas on platforms of health service provision in the last 10 years and information on acceptability from local stakeholders on effective models of service delivery; and drafted key recommendations for improving coverage of health services in conflict affected areas. The literature search revealed ten studies that described MNH service delivery platforms. The results from the systematic review showed that with utilisation of community outreach services, the greatest impacts were observed in skilled birth attendance and antenatal consultation rates. Facility level services, on the other hand, showed that labour room services for an internally displaced population (IDP) improved antenatal care coverage, contraceptive prevalence rate and maternal mortality. Consultative meetings and discussions conducted in Quetta and Peshawar (capitals of conflict affected provinces) with relevant stakeholders revealed that no systematic models of MNH service delivery, especially tailored for conflict areas, are available. During conflict, even previously available services and infrastructure suffered due to various barriers specific to times of conflict and unrest. A number of barriers that hinder MNH services were discussed. Suggestions for improving MNH services in conflict areas were also laid down by participants. The review identified some important steps that can be undertaken to mitigate the effects of conflict on MNH services, which include: improve provision and access to infrastructure and equipment; development and training of healthcare providers; and advocacy at different levels for free access to healthcare services and for the introduction of the programme model in existing healthcare system. The obligation is enormous, however, for a sustainable programme, it is important to work closely with both the IDP and host community, and collaborating with the government and non-government organisations

Early Short Course Corticosteroids in Hospitalized Patients with COVID-19

BACKGROUND: There is no proven antiviral or immunomodulatory therapy for COVID-19. The disease progression associated with the pro-inflammatory host response prompted us to examine the role of early corticosteroid therapy in patients with moderate to severe COVID-19. METHODS: We conducted a single pre-test, single post-test quasi-experiment in a multi-center health system in Michigan from March 12 to March 27, 2020. Adult patients with confirmed moderate to severe COVID were included. A protocol was implemented on March 20, 2020 using early, short-course, methylprednisolone 0.5 to 1 mg/kg/day divided in 2 intravenous doses for 3 days. Outcomes of standard of care (SOC) and early corticosteroid groups were evaluated, with a primary composite endpoint of escalation of care from ward to ICU, new requirement for mechanical ventilation, and mortality. All patients had at least 14 days of follow-up. RESULTS: We analyzed 213 eligible subjects, 81 (38%) and 132 (62%) in SOC and early corticosteroid groups, respectively.The composite endpoint occurred at a significantly lower rate in the early corticosteroid group (34.9% vs. 54.3%, p=0.005). This treatment effect was observed within each individual component of the composite endpoint. Significant reduction in median hospital length of stay was also observed in the early corticosteroid group (8 vs. 5 days, p \u3c 0.001). Multivariate regression analysis demonstrated an independent reduction in the composite endpoint at 14-days controlling for other factors (aOR: 0.41; 95% CI [0.22 - 0.77]). CONCLUSION: An early short course of methylprednisolone in patients with moderate to severe COVID-19 reduced escalation of care and improved clinical outcomes

Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017 : a systematic analysis for the Global Burden of Disease Study 2017

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk outcome pairs, and new data on risk exposure levels and risk outcome associations. Methods: We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017. Findings: In 2017,34.1 million (95% uncertainty interval [UI] 33.3-35.0) deaths and 121 billion (144-1.28) DALYs were attributable to GBD risk factors. Globally, 61.0% (59.6-62.4) of deaths and 48.3% (46.3-50.2) of DALYs were attributed to the GBD 2017 risk factors. When ranked by risk-attributable DALYs, high systolic blood pressure (SBP) was the leading risk factor, accounting for 10.4 million (9.39-11.5) deaths and 218 million (198-237) DALYs, followed by smoking (7.10 million [6.83-7.37] deaths and 182 million [173-193] DALYs), high fasting plasma glucose (6.53 million [5.23-8.23] deaths and 171 million [144-201] DALYs), high body-mass index (BMI; 4.72 million [2.99-6.70] deaths and 148 million [98.6-202] DALYs), and short gestation for birthweight (1.43 million [1.36-1.51] deaths and 139 million [131-147] DALYs). In total, risk-attributable DALYs declined by 4.9% (3.3-6.5) between 2007 and 2017. In the absence of demographic changes (ie, population growth and ageing), changes in risk exposure and risk-deleted DALYs would have led to a 23.5% decline in DALYs during that period. Conversely, in the absence of changes in risk exposure and risk-deleted DALYs, demographic changes would have led to an 18.6% increase in DALYs during that period. The ratios of observed risk exposure levels to exposure levels expected based on SDI (O/E ratios) increased globally for unsafe drinking water and household air pollution between 1990 and 2017. This result suggests that development is occurring more rapidly than are changes in the underlying risk structure in a population. Conversely, nearly universal declines in O/E ratios for smoking and alcohol use indicate that, for a given SDI, exposure to these risks is declining. In 2017, the leading Level 4 risk factor for age-standardised DALY rates was high SBP in four super-regions: central Europe, eastern Europe, and central Asia; north Africa and Middle East; south Asia; and southeast Asia, east Asia, and Oceania. The leading risk factor in the high-income super-region was smoking, in Latin America and Caribbean was high BMI, and in sub-Saharan Africa was unsafe sex. O/E ratios for unsafe sex in sub-Saharan Africa were notably high, and those for alcohol use in north Africa and the Middle East were notably low. Interpretation: By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning

Lebein, a snake venom disintegrin, induces apoptosis in human melanoma cells

© 2016 by the authors. This manuscript version is made available under the CC-BY 4.0 license http://creativecommons.org/licenses/by/4.0/ This document is the Published version of a Published Work that appeared in final form in Toxins. To access the final edited and published work see https://doi.org/10.3390/toxins8070206Melanoma, the most threatening form of skin cancer, has a very poor prognosis and is characterized by its very invasive and chemoresistant properties. Despite the recent promising news from the field of immunotherapy, there is an urgent need for new therapeutic approaches that are free of resistance mechanisms and side effects. Anti-neoplasic properties have been highlighted for different disintegrins from snake venom including Lebein; however, the exact effect of Lebein on melanoma has not yet been defined. In this study, we showed that Lebein blocks melanoma cell proliferation and induces a more differentiated phenotype with inhibition of extracellular signal-regulated kinase (ERK) phosphorylation and microphthalmia-associated transcription factor (MITF) overexpression. Melanoma cells became detached but were less invasive with upregulation of E-cadherin after Lebein exposure. Lebein induced a caspase-independent apoptotic program with apoptosis inducing factor (AIF), BCL-2-associated X protein (BAX) and Bim overexpression together with downregulation of B-cell lymphoma-2 (BCL-2). It generated a distinct response in reactive oxygen species (ROS) generation and p53 levels depending on the p53 cell line status (wild type or mutant). Therefore, we propose Lebein as a new candidate for development of potential therapies for melanoma