Association between high vancomycin minimum inhibitory concentration and clinical outcomes in patients with methicillin-resistant Staphylococcus aureus bacteraemia - A retrospective cohort study.

The purpose of this study is to determine the role of high (≥ 1.5 mg/L) vancomycin minimum inhibitory concentration (VMIC) in predicting clinical outcomes in patients with methicillin-resistant Staphylococcus aureus bacteraemia (MRSAB). A retrospective study was conducted at Mayo Clinic, Minnesota. Patients ≥ 18 years with a 3-month follow-up were included. Outcomes were defined as 30-day all-cause in-hospital mortality, median duration of bacteraemia, metastatic infectious complications, and relapse of MRSAB. A total of 475 patients with MRSAB were identified, and 93 (19.6%) of them had high VMIC isolates. Sixty-four percent of patients were male with a mean age of 69.0 years. Active solid organ malignancy and skin and soft tissue infection as source of MRSAB were associated with high VMIC, while septic arthritis as a complication was significantly associated with low VMIC on multivariate analysis. Eighty-one (17.1%) patients died within 30 days of hospitalization, with no significant difference in mortality rates between the two groups. In-hospital mortality, median duration of bacteraemia, and metastatic infectious complications were not significantly associated with high VMIC MRSAB.

Association between high vancomycin minimum inhibitory concentration and clinical outcomes in patients with methicillin-resistant Staphylococcus aureus bacteremia: a meta-analysis.

PURPOSE: To assess the relationship between high vancomycin minimum inhibitory concentrations (MIC), in patients with methicillin-resistant Staphylococcus aureus bacteremia (MRSAB), and both mortality and complicated bacteremia. METHODS: Embase, Medline, EBM, Scopus and Web of Science were searched for studies published from January 1st 2014 to February 29th 2020. "High" vancomycin MIC cut off was defined as ≥ 1.5 mg/L. Three referees independently reviewed studies that compared outcomes in patients with MRSAB stratified by vancomycin MIC. Subgroup analyses were performed for rates of mortality and complicated bacteremia. RESULTS: A total of 13 studies with 2089 patients were included. Overall, mortality was 27.7% and 23.3% in the high and low vancomycin MIC group, respectively. No significant difference was found between vancomycin MIC groups for overall mortality, in-hospital mortality, late mortality, persistent bacteremia, severe sepsis or septic shock, acute renal failure, septic emboli or endocarditis, and osteomyelitis or septic arthritis. Early mortality was significantly associated with low vancomycin MIC. Mortality in studies using broth microdilution method (BMD) and need for mechanical ventilation were significantly associated with high vancomycin MIC. CONCLUSION: Overall mortality and complicated bacteremia were not significantly associated with high vancomycin MICs in a patient with MRSAB. Randomized controlled trials to assess the utility of vancomycin MIC values in predicting mortality and other adverse clinical outcomes are warranted.

Impact of delayed device re-implantation on outcomes of patients with cardiovascular implantable electronic device related infective endocarditis.

BACKGROUND: Optimal timing of cardiovascular implantable electronic device (CIED) re-implantation following device removal due to infection is undefined. Multinational guidelines reflect this and include no specific recommendation for this timing, while others have recommended waiting at least 14 days in cases of CIED related infective endocarditis (CIED-IE). The current work seeks to clarify this issue. METHODS: We retrospectively reviewed institutional data at Mayo Clinic, Minnesota of patients aged ≥ 18 years who developed CIED-IE from January 1, 1991 to February 1, 2016. CIED-IE was defined as echocardiogram reported device lead or valvular vegetation. Regression analyses were used to relate the risk of clinical outcomes to the interval between CIED removal and re-implantation and the location of vegetations. RESULTS: A total of 109 patients met study inclusion criteria. A majority (68.8%) of patients were men and the median age was 68.0 years. Transoesophageal echocardiogram (TEE) was performed in 95.4% of patients, with valve vegetations detected in 33.9% (n = 37). Survival analysis comparing patients in whom device re-implantation was < 14 days vs. ≥14 days, and further categorized by those with and without valve vegetation, showed a significant difference (P = 0.028); patients with valve vegetation and reimplantation interval < 14 days had the lowest (58.7%) 12-month survival. When adjusted for valve vegetation, longer time interval for reimplantation trended toward increased hospital length of stay (P = 0.079). CONCLUSION: Our findings suggest that the recommended 14-day delay between CIED extraction and re-implantation in CIED-IE patients is associated with a survival benefit, but longer length of hospital stay following re-implantation.

Benzenedicarboxylic acid upregulates O48814 and Q9FJQ8 for improved nutritional contents of tomato and low risk of fungal attack.

BACKGROUND: Tomato is an important food item and a cocktail of phytonutrients. In the current study, metabolites from a non-pathogenic fungal species Penicillium oxalicum have been exploited to obtain nutritionally augmented tomato fruits from the plants to better withstand against Alternaria alternata infection. RESULTS: Initially, bioactivity-guided assay and chromatographic analyses identified the bioactive metabolites of P. oxalicum [benzenedicarboxylic acid (BDA) and benzimidazole]. Then, ≥3 times elevated quantities of vitamins and other nutritional elements (protein, fat, fibers, and carbohydrates) were achieved by the foliar application of BDA. The maximum increase (625.81%) was recorded in riboflavin contents; however, thiamine showed the second highest enhancement (542.86%). Plant metabolites analysis revealed that jasmonic acid contents were boosted 121.53% to significantly enhance guaiacyl lignin defenses along with the reduction in coumarin contents. The protein profile analysis explored three most actively responding protein species toward BDA applications, (i) palmitoyltransferase protein Q9FLM3; (ii) serine/threonine-protein kinase O48814; and (iii) E3 ubiquitin-protein ligase Q9FJQ8. The O48814 improved plant defenses; whereas, Q9FJQ8 protein was negatively regulating cysteine-type endopeptidase activity and assisted plant to resist schedule alterations. Tomato cultivar with more active innate metabolism was found to be more responsive toward BDA. Furthermore, the bioactive compounds were enriched by using the two-step extraction method of ethyl acetate and chloroform, respectively. CONCLUSION: Penicillium oxalicum a non-pathogenic fungal species, produced BDA, induced nutritional contents in tomato and protected it against Alternaria alternata. The current study is the first report on the bioactivity of BDA and benzimidazole concerning the nutritional enhancement and plant defense improvement. © 2019 Society of Chemical Industry.

Native Vertebral Osteomyelitis in Patients with Staphylococcus Aureus Bacteremia.

BACKGROUND: The purpose of the study was to assess the epidemiology, risk factors and outcomes of native vertebral osteomyelitis (NVO) in patients with Staphylococcus aureus bacteremia (SAB). METHODS: A retrospective institutional review was conducted at Mayo Clinic, Minnesota. Patients aged ≥18 years with SAB who developed NVO from January 1, 2006 to December 31, 2020 were included and 3-month follow-up data were abstracted. Data pertaining to patient demographics, risk factors and outcomes were recorded using REDCap. A 1:2 nested case-control analysis was performed, and controls were matched according to age, sex and year of SAB diagnosis. RESULTS: A total of 103 patients had NVO. A majority (60.2%) of patients was male, with a median age of 62.0 years. Thirty-one (30.1%) cases were caused by methicillin-resistant S. aureus (MRSA). The lumbar spine was most commonly (57.6%) and the most commonly reported comorbid conditions included diabetes mellitus (36.9%) and coronary artery disease (27.2%). Mortality at three-month follow-up was 18.6%. Nested case-control analysis revealed that injection drug use (IDU) and tobacco consumption were significant risk factors associated with NVO, while chronic hemodialysis and chronic liver disease (CLD) were associated with a decreased risk of NVO. CONCLUSIONS: Atherosclerotic vascular disease was prominent in our contemporary cohort with NVO in the setting of SAB. Diabetes mellitus, tobacco consumption, older age and male sex likely contributed to this profile. Because IDU was associated with NVO, an increased number of cases should be anticipated among patients with IDU given the ongoing opioid epidemic in the United States.

Effects of preconception care and periconception interventions on maternal nutritional status and birth outcomes in low- and middle-income countries: A systematic review.

Background: The preconception period is an ideal time to introduce interventions relating to nutrition and other lifestyle factors to ensure good pregnancy preparedness, and to promote health of mothers and babies. In adolescents, malnutrition and early pregnancy are the common challenges, particularly among those who live in low- and middle-income countries (LMIC) where 99% of all maternal and newborn deaths occur. These girls receive little or no attention until their first pregnancy and often the interventions after pregnancy are too late to revert any detrimental health risks that may have occurred due to malnutrition and early pregnancy. Objectives: To synthesise the evidence of the effectiveness of preconception care interventions relating to delayed age at first pregnancy, optimising inter-pregnancy intervals, periconception folic acid, and periconception iron-folic acid supplementation on maternal, pregnancy, birth and child outcomes. Search Methods: Numerous electronic databases (e.g., CINAHL, ERIC) and databases of selected development agencies or research firms were systematically searched for all available years up to July 2019. In addition, we searched the reference lists of relevant articles and reviews, and asked experts in the area about ongoing and unpublished studies. Selection Criteria: Primary studies, including large-scale programme evaluations that assessed the effectiveness of interventions using randomised controlled trials (RCTs) or quasi-experimental designs (natural experiments, controlled before-after studies, regression discontinuity designs, interrupted time series [ITS]), that targeted women of reproductive age (i.e., 10-49 years) during the pre- and periconceptional period in LMICs were included. Interventions were compared against no intervention, standard of care or placebo. Data Collection and Analysis: Two or more review authors independently reviewed searches, selected studies for inclusion or exclusion, extracted data and assessed risk of bias. We used random-effects model to conduct meta-analyses, given the diverse contexts, participants, and interventions, and separate meta-analyses for the same outcome was performed with different study designs (ITS, RCTs and controlled before after studies). For each comparison, the findings were descriptively summarised in text which included detailing the contextual factors (e.g., setting) to assess their impact on the implementation and effectiveness of each intervention. Main Results: We included a total of 43 studies; two of these were included in both delaying pregnancy and optimising interpregnancy intervals resulting in 26 studies for delaying the age at first pregnancy (14 RCTs, 12 quasi-experimental), four for optimising interpregnancy intervals (one RCT, three quasi-experimental), five on periconceptional folic acid supplementation (two RCTs, three quasi-experimental), and 10 on periconceptional iron-folic acid supplementation (nine RCTs, one quasi-experimental). Geographically, studies were predominantly conducted across Africa and Asia, with few studies from North and Central America and took place in a combination of settings including community, schools and clinical. The education on sexual health and contraception interventions to delay the age at first pregnancy may make little or no difference on risk of unintended pregnancy (risk ratio [RR], 0.42; 95% confidence internal [CI], 0.07-3.26; two studies, =490; random-effect; χ 2 p .009; I 2 = 85%; low certainty of evidence using GRADE assessment), however, it significantly improved the use of condom (ever) (RR, 1.54; 95% CI, 1.08-2.20; six studies, n = 1604; random-effect, heterogeneity: χ 2 p .004; I 2 = 71%). Education on sexual health and and provision of contraceptive along with involvement of male partneron optimising interpregnancy intervals probably makes little or no difference on the risk of unintended pregnancies when compared to education on sexual health only (RR, 0.32; 95% CI, 0.01-7.45; one study, n = 45; moderate certainty of evidence using GRADE assessments). However, education on sexual health and contraception intervention alone or with provision of contraceptive showed a significant improvement in the uptake of contraceptive method. We are uncertain whether periconceptional folic acid supplementation reduces the incidence of neural tube defects (NTDs) (RR, 0.53; 95% CI, 0.41-0.77; two studies, n = 248,056; random-effect; heterogeneity: χ 2 p .36; I 2 = 0%; very low certainty of evidence using GRADE assessment). We are uncertain whether preconception iron-folic acid supplementation reduces anaemia (RR, 0.66; 95% CI, 0.53-0.81; six studies; n = 3430, random-effect; heterogeneity: χ 2 p < .001; I 2 = 88%; very low certainty of evidence using GRADE assessment) even when supplemented weekly (RR, 0.70; 95% CI, 0.55-0.88; six studies; n = 2661; random-effect; heterogeneity: χ 2 p < .001; I 2 = 88%; very low certainty of evidence using GRADE assessments),and in school set-ups (RR, 0.66; 95% CI, 0.51-0.86; four studies; n = 3005; random-effect; heterogeneity: χ 2 p < .0001; I 2 = 87%; very low certainty of evidence using GRADE assessment). Data on adverse effects were reported on in five studies for iron-folic acid, with the main complaint relating to gastrointestinal side effects. The quality of evidence across the interventions of interest was variable (ranging from very low to moderate) which may be attributed to the different study designs included in this review. Concerning risk of bias, the most common concerns were related to blinding of participants and personnel (performance bias) and whether there were similar baseline characteristic across intervention and comparison groups. Authors' Conclusions: There is evidence that education on sexual health and contraception interventions can improve contraceptive use and knowledge related to sexual health, this review also provides further support for the use of folic acid in pregnancy to reduce NTDs, and notes that weekly regimes of IFA are most effective in reducing anaemia. However the certainty of the evidence was very low and therefore more robust trials and research is required, including ensuring consistency for reporting unplanned pregnancies, and further studies to determine which intervention settings (school, community, clinic) are most effective. Although this review demonstrates promising findings, more robust evidence from RCTs are required from LMICs to further support the evidence.

Temporal Trends of Infective Endocarditis in North America From 2000 to 2017-A Systematic Review.

BACKGROUND: The objective of this paper was to examine temporal changes of infective endocarditis (IE) incidence and epidemiology in North America. METHODS: A systematic review was conducted at Mayo Clinic, Rochester. Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus, and Web of Science were searched for studies published between January 1, 2000, and May 31, 2020. Four referees independently reviewed all studies, and those that reported a population-based incidence of IE in patients aged 18 years and older in North America were included. RESULTS: Of 8588 articles screened, 14 were included. Overall, IE incidence remained largely unchanged throughout the study period, except for 2 studies that demonstrated a rise in incidence after 2014. Five studies reported temporal trends of injection drug use (IDU) prevalence among IE patients with a notable increase in prevalence observed. Staphylococcus aureus was the most common pathogen in 7 of 9 studies that included microbiologic findings. In-patient mortality ranged from 3.7% to 14.4%, while the percentage of patients who underwent surgery ranged from 6.4% to 16.0%. CONCLUSIONS: The overall incidence of IE has remained stable among the 14 population-based investigations in North America identified in our systematic review. Standardization of study design for future population-based investigations has been highlighted for use in subsequent systematic reviews of IE.

Disparities in Cardiovascular Research Output and Disease Outcomes among High-, Middle- and Low-Income Countries - An Analysis of Global Cardiovascular Publications over the Last Decade (2008-2017).

Background: Cardiovascular disease (CVD) is the leading cause of death and disability worldwide. Health research is crucial to managing disease burden. Previous work has highlighted marked discrepancies in research output and disease burden between high-income countries (HICs) and low- and lower-middle-income countries (LI-LMICs) and there is little data to understand whether this gap has bridged in recent years. We conducted a global, country level bibliometric analysis of CVD publications with respect to trends in disease burden and county development indicators. Methods: A search filter with a precision and recall of 0.92 and 0.91 respectively was developed to extract cardiovascular publications from the Web of Science (WOS) for the years 2008-2017. Data for disease burden and country development indicators were extracted from the Global Burden of Disease and the World Bank database respectively. Results: Our search revealed 847,708 CVD publications for the period 2008-17, with a 43.4% increase over the decade. HICs contributed 81.1% of the global CVD research output and accounted for 8.1% and 8.5% of global CVD DALY losses deaths respectively. LI-LMICs contributed 2.8% of the total output and accounted for 59.5% and 57.1% global CVD DALY losses and death rates. Conclusions: A glaring disparity in research output and disease burden persists. While LI-LMICs contribute to the majority of DALYs and mortality from CVD globally, their contribution to research output remains the lowest. These data call on national health budgets and international funding support to allocate funds to strengthen research capacity and translational research to impact CVD burden in LI-LMICs.

Escalating incidence of infective endocarditis in Europe in the 21st century.

AIM: To provide a contemporary analysis of incidence trends of infective endocarditis (IE) with its changing epidemiology over the past two decades in Europe. METHODS: A systematic review was conducted at the Mayo Clinic, Rochester. Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus and Web of Science were searched for studies published between 1 January 2000 and 30 November 2020. All studies were independently reviewed by four referees and those that included a population-based incidence of IE in patients, irrespective of age, in Europe were included. Least squares regression was used to estimate pooled temporal trends in IE incidence. RESULTS: Of 9138 articles screened, 18 studies were included in the review. Elderly men predominated in all studies. IE incidence increased 4.1% per year (95% CI 1.8% to 6.4%) in the pooled regression analysis of eight studies that included comprehensive and consistent trends data. When trends data were weighted according to population size of individual countries, an increase in yearly incidence of 0.27 cases per 100 000 people was observed. Staphylococci and streptococci were the most common pathogens identified. The rate of surgical intervention ranged from 10.2% to 60.0%, and the rate of inpatient mortality ranged from 14.3% to 17.5%. In six studies that examined the rate of injection drug use, five of them reported a rate of less than 10%. CONCLUSION: Based on findings from our systematic review, IE incidence in Europe has doubled over the past two decades in Europe. Multiple factors are likely responsible for this striking increase. TRIAL REGISTERATION NUMBER: CRD42020191196.

Effects of Preconception Care and Periconception Interventions on Maternal Nutritional Status and Birth Outcomes in Low- and Middle-Income Countries: A Systematic Review.

Pregnancy in adolescence and malnutrition are common challenges in low- and middle-income countries (LMICs), and are associated with many complications and comorbidities. The preconception period is an ideal period for intervention as a preventative tactic for teenage pregnancy, and to increase micronutrient supplementation prior to conception. Over twenty databases and websites were searched and 45 randomized controlled trials (RCTs) or quasi-experimental interventions with intent to delay the age at first pregnancy (n = 26), to optimize inter-pregnancy intervals (n = 4), and supplementation of folic acid (n = 5) or a combination of iron and folic acid (n = 10) during the periconception period were included. The review found that educational interventions to delay the age at first pregnancy and optimizing inter-pregnancy intervals significantly improved the uptake of contraception use (RR = 1.71, 95% CI = 1.42-2.05; two studies, n = 911; I2 = 0%) and (RR = 2.25, 95% CI = 1.29-3.93; one study, n = 338), respectively. For periconceptional folic acid supplementation, the incidence of neural tube defects were reduced (RR = 0.53; 95% CI = 0.41-0.77; two studies, n = 248,056; I2 = 0%), and iron-folic acid supplementation improved the rates of anemia (RR = 0.66, 95% CI = 0.53-0.81; six studies; n = 3430, I2 = 88%), particularly when supplemented weekly and in a school setting. Notwithstanding the findings, more robust RCTs are required from LMICs to further support the evidence.

Value of Routine Preoperative Tests for Coagulation Before Elective Cranial Surgery. Results of an Institutional Audit and a Nationwide Survey of Neurosurgical Centers in Pakistan.

BACKGROUND: Routine preoperative blood testing has become a dogma. The general practice is to order preoperative workup as a knee-jerk response rather than individualize it for each patient. The fact that the bleeding brain tends to swell, which coupled with limited options for proximal control, packing, and overall hemostasis, leads to an overemphasis on the preoperative coagulation profile. MATERIAL AND METHODS: This is a retrospective review of the medical records of patients admitted at Aga Khan University Hospital from January 2010 to December 2015 for an elective craniotomy. The hospital registry was used to identify files for review. Data were collected on a predefined proforma. A nationwide survey was performed, and 30 neurosurgery centers were contacted across Pakistan to confirm the practice of preoperative workup. RESULTS: The survey revealed that all centers had a similar practice of preoperative workup. This included complete blood count, serum electrolytes, and coagulation profile, including prothrombin time, activated partial thromboplastin time (aPTT), and international normalized ratio (INR). A total of 1800 files were reviewed. Nine (0.5%) patients were found to have deranged clotting profile without any predictive history of clotting derangement; 56% were male and 44% were female. Median age was 32 years with an interquartile range of 27 years. Median aPTT was (40.8 with 20.8 IQR). Median INR was (1.59 with 0.48 IQR). Median blood loss was (400 with 50 IQR). No significant association between coagulation profile (aPTT, INR) and blood loss was found (P = 0.85, r = -0.07). CONCLUSIONS: We conclude that patients without a history of coagulopathy and normal physical examination do not require routine coagulation screening before elective craniotomy.

Mathematical modeling of cotton leaf curl virus with respect to environmental factors.

This study mathematically correlates incidence of cotton leaf curl virus (CLCuV), environmental factors (i.e., rainfall, humidity and temperature), and silverleaf whitefly population in agricultural system of Pakistan. It has been concluded that the disease is directly linked with rainfall and humidity. The third most influential factor in defining CLCuV incidence is the vector population, which is also strictly dependent upon monthly mean temperature of Pakistan. Developed mathematical interrelation is capable of predicting disease incidence of future months. Therefore, it will help agriculturists to control disease in agricultural areas of Pakistan. It is strongly advised on the basis of current research that vector population controlling practices should be immediately applied after detecting small elevations in mean monthly temperature.