Nevin Manimala

Microb Drug Resist. 2021 Mar 15. doi: 10.1089/mdr.2020.0350. Online ahead of print.

ABSTRACT

Aims: Several in vitro and in vivo studies demonstrated that adding a β-lactam to vancomycin (VAN) or daptomycin (DAP) can provide synergy against methicillin-resistant Staphylococcus aureus (MRSA). However, the results from clinical studies were controversial. The objective of this systematic review and meta-analysis was to compare the efficacy and safety of using VAN or DAP plus a β-lactam (combination therapy) and using VAN or DAP alone (monotherapy) in MRSA bloodstream infections. Methods: We included randomized controlled trials and observational studies evaluating whether combination therapy can improve clinical and microbiological outcomes and safety compared to monotherapy with VAN or DAP in MRSA-related bacteremia. Results: Literature search identified 3 randomized clinical trials and 10 observational studies involving at least 1,796 patients. There were no significant associations between the combination therapy and risk of mortality within 30 days (risk ratios [RRs], 1.10, 95% confidence interval [CI], 0.82-1.46), in-hospital mortality (RR, 0.59, 95% CI, 0.31-1.13) and mortality within 60-90 days (RR, 0.91, 95% CI, 0.64-1.29). There was also no evidence that there was a difference in length of hospital stay between the combination therapy and monotherapy (mean difference, -0.41 days, 95% CI, -3.41 to 2.59). However, compared with monotherapy, combination therapy seemed to have a shorter duration of bacteremia(mean difference, -1.06 days, 95% CI, -1.53 to -0.60), a lower risk of persistent bacteremia (RR, 0.63, 95% CI, 0.51-0.79) and a lower risk of bacteremia recurrence within 60-90 days (RR, 0.61, 95% CI, 0.40-0.92). There were no statistically significant differences in the total number of adverse events, including acute kidney injury (AKI) (RR, 1.52, 95% CI, 0.84-2.73), thrombocytopenia (RR, 1.13, 95% CI, 0.74-1.73), and diarrhea (RR, 1.36, 95% CI, 0.70-2.65), between patients with combination therapy and monotherapy. In subgroup analysis, when the analysis was limited to the studies comparing using DAP plus ceftaroline with monotherapy, we found that the former had a lower risk of mortality within 30 days. In addition, a subgroup analysis limited to randomized clinical trials showed that the combination therapy was associated with a higher risk of AKI compared with using VAN or DAP alone. Conclusions: Although adding a β-lactam to standard therapy seemed to experience a higher clearance compared with monotherapy in patients with MRSA bacteremia, the combination therapy did not increase survival benefits. Based on the available evidence, the combination therapy was not supported as the routine management of MRSA-related bacteremia, and both its harms and benefits should be taken into account.

PMID:33728980 | DOI:10.1089/mdr.2020.0350

J Comp Eff Res. 2021 Mar 17. doi: 10.2217/cer-2020-0275. Online ahead of print.

ABSTRACT

Aim: To evaluate the effectiveness and safety of anti-TNF drugs for ankylosing spondylitis. Materials & methods: A prospective cohort study was performed at a pharmacy in the Brazilian Public Health System. Effectiveness by Bath Ankylosing Spondylitis Disease Activity Index, functionality by Health Assessment Questionnaire Disability Index, quality of life by European Quality of Life Five-Dimensions and safety was assessed at 6 and 12 months of follow-up. Results: About 160 patients started the treatment with adalimumab, etanercept or infliximab. There was a statistically significant improvement in disease activity, functionality and quality of life at 6 and 12 months (p < 0.05). Conclusion: This real-world study has shown that anti-TNF drugs are effective and well tolerated for ankylosing spondylitis patients.

PMID:33728937 | DOI:10.2217/cer-2020-0275

J Am Heart Assoc. 2021 Mar 17:e019216. doi: 10.1161/JAHA.120.019216. Online ahead of print.

ABSTRACT

Background Perioperative blood glucose level has shown an association with postoperative outcomes. We compared the incidences of myocardial injury after noncardiac surgery (MINS) and 30-day mortality, according to preoperative blood glucose and hemoglobin A1c (HbA1c) levels. Methods and Results The patients were divided according to blood glucose level within 1 day before surgery. The hyperglycemia group was defined with fasting glucose >140 mg/dL or random glucose >180 mg/dL. In addition, we compared the outcomes according to HbA1c >6.5% among patients with available HbA1c within 3 months before surgery. The primary outcome was MINS, and 30-day mortality was also compared. A total of 12 304 patients were enrolled and divided into 2 groups: 8324 (67.7%) in the normal group and 3980 (32.3%) in the hyperglycemia group. After adjustment with inverse probability of weighting, the hyperglycemia group exhibited significantly higher incidences of MINS and 30-day mortality (18.7% versus 27.6%; odds ratio, 1.29; 95% CI, 1.18-1.42; P<0.001; and 2.0% versus 5.1%; hazard ratio, 2.00; 95% CI, 1.61-2.49; P<0.001, respectively). In contrast to blood glucose, HbA1c was not associated with MINS or 30-day mortality. Conclusions Preoperative hyperglycemia was associated with MINS and 30-day mortality, whereas HbA1c was not. Immediate glucose control may be more crucial than long-term glucose control in patients undergoing noncardiac surgery. Registration URL: https://www.cris.nih.go.kr; Unique identifier: KCT0004244.

PMID:33728934 | DOI:10.1161/JAHA.120.019216

J Am Heart Assoc. 2021 Mar 17:e015292. doi: 10.1161/JAHA.119.015292. Online ahead of print.

ABSTRACT

Background Small intestinal bacterial overgrowth (SIBO) is a common pathological condition of intestinal microbiota. The prevalence of SIBO and its prognostic value in patients with heart failure (HF) are unknown. Methods and Results A total of 287 patients tested for SIBO using lactulose hydrogen-methane breath test were evaluated. At least 1 of the following criteria fulfilled was SIBO positive: patients with fasting hydrogen level ≥20 parts per million (ppm) or a ≥20 ppm rise in hydrogen by 90 minutes were diagnosed with SIBO (H₂) positive; and patients with methane levels ≥10 ppm at any test point were diagnosed with SIBO (CH₄) positive. The association between SIBO and the composite of cardiovascular death and HF rehospitalization was investigated. In 287 consecutive patients with HF, 128 (45%) were positive for SIBO. Our result showed SIBO increased the risk of HF rehospitalization in patients with HF with reduced ejection fraction (P<0.001), and the risk of cardiovascular death in patients with HF with preserved EF (P=0.011). SIBO was an independent risk factor of primary end point in patients with HF (hazard ratio [HR], 2.13; 95% CI; 1.26-3.58; P=0.005). In addition, SIBO (CH₄) showed a prognostic value on adverse outcomes (HR, 2.35; 95% CI, 1.38-4.02; P<0.001), whereas the association between SIBO (H₂) and outcomes was not statistically significant. Conclusions There was high prevalence of SIBO in patients with HF, and SIBO was independently associated with poor outcomes. Proactive treatment for SIBO may provide extra benefit for patients with HF.

PMID:33728933 | DOI:10.1161/JAHA.119.015292

J Chem Theory Comput. 2021 Mar 17. doi: 10.1021/acs.jctc.0c01151. Online ahead of print.

ABSTRACT

A variety of enhanced statistical and numerical methods are now routinely used to extract important thermodynamic and kinetic information from the vast amount of complex, high-dimensional data obtained from molecular simulations. For the characterization of kinetic properties, Markov state models, in which the long-time statistical dynamics of a system is approximated by a Markov chain on a discrete partition of configuration space, have seen widespread use in recent years. However, obtaining kinetic properties for molecular systems with high energy barriers remains challenging as often enhanced sampling techniques are required with biased simulations to observe the relevant rare events. Particularly, the calculation of diffusion coefficients remains elusive from biased molecular simulation data. Here, we propose a novel method that can calculate multidimensional position-dependent diffusion coefficients equally from either biased or unbiased simulations using the same formalism. Our method builds on Markov state model analysis and the Kramers-Moyal expansion. We demonstrate the validity of our formalism using one- and two-dimensional analytic potentials and also apply it to data from explicit solvent molecular dynamics simulations, including the water-mediated conformations of alanine dipeptide and umbrella sampling simulations of drug transport across a lipid bilayer. Importantly, the developed algorithm presents significant improvement compared to standard methods when the transport of solute across three-dimensional heterogeneous porous media is studied, for example, the prediction of membrane permeation of drug molecules.

PMID:33728916 | DOI:10.1021/acs.jctc.0c01151

Health Rep. 2021 Mar 17;32(3):3-16. doi: 10.25318/82-003-x202100300001-eng.

ABSTRACT

BACKGROUND: Prescription medications are used throughout the life course, including among children and youth. Prescribing practices may be influenced by emerging medical conditions, the availability of new medications, changing clinical practices, and evolving knowledge of the safety and effectiveness of medications. The Canadian Health Measures Survey (CHMS) provides national-level information to help monitor the use of prescribed medications in the population.

DATA AND METHODS: Based on data from the CHMS (2012 to 2017), this article describes prescription medication use in the past month among those aged 3 to 19 years. Information on up to 45 prescription medications was recorded and classified according to Health Canada’s Anatomical Therapeutic Chemical classification. Frequencies and bivariate analyses examined medication use by sociodemographic and health-related factors. The most common medication classes were identified for each age group.

RESULTS: An estimated 23% of Canadian children and youth (1.5 million) had used at least one prescription medication in the past month and 9% had used two or more prescription medications.Prescription medication use was more common among those who reported lower levels of general and mental health, as well as among those with asthma (51%), a mood disorder (71%), attention deficit disorder (60%) or a learning disability (43%). Medications for the respiratory and nervous systems were among those most commonly prescribed. Of youth aged 14 years or older, 4% had misused prescription medications for non-medicinal purposes, for the experience, for the feeling they cause or to get high.

DISCUSSION: Prescription medication use among children and youth is common in Canada. It is associated with lower levels of self-reported health and the presence of chronic conditions. The estimates provide a benchmark to help monitor prescription drug use in Canada.

PMID:33728887 | DOI:10.25318/82-003-x202100300001-eng

Monaldi Arch Chest Dis. 2021 Mar 16. doi: 10.4081/monaldi.2021.1758. Online ahead of print.

ABSTRACT

Coronavirus disease (COVID-19) may predispose patients to pulmonary embolism (PE), despite standard thromboprophylaxis. Our retrospective study aimed to report the prevalence of PE in patients with COVID-19 and severe respiratory failure (SRF) treated with intermediate- to full-dose enoxaparin. We analyzed data from patients with COVID-19 pneumonia and SRF admitted to our Respiratory Intensive Care Unit (RICU) from February 27 to April 20, 2020. All patients received at least intermediate-dose enoxaparin (40 mg twice daily). Computed tomography pulmonary angiography (CTPA) was used to detect PE. Ninety-two patients with COVID-19 pneumonia and SRF were admitted to our RICU. Twenty-two patients underwent CTPA (24 %), 11 of whom had PEs (12%). We hypothesize that the enoxaparin treatment may be responsible for the lower prevalence of PE as compared to previous reports of similar patients, even if our report had several limitations, mainly the small sample size.

PMID:33728885 | DOI:10.4081/monaldi.2021.1758

NPJ Digit Med. 2021 Mar 16;4(1):51. doi: 10.1038/s41746-021-00420-9.

ABSTRACT

The true risk of a COVID-19 resurgence as states reopen businesses is unknown. In this paper, we used anonymized cell-phone data to quantify the potential risk of COVID-19 transmission in business establishments by building a Business Risk Index that measures transmission risk over time. The index was built using two metrics, visits per square foot and the average duration of visits, to account for both density of visits and length of time visitors linger in the business. We analyzed trends in traffic patterns to 1,272,260 businesses across eight states from January 2020 to June 2020. We found that potentially risky traffic behaviors at businesses decreased by 30% by April. Since the end of April, the risk index has been increasing as states reopen. There are some notable differences in trends across states and industries. Finally, we showed that the time series of the average Business Risk Index is useful for forecasting future COVID-19 cases at the county-level (P < 0.001). We found that an increase in a county’s average Business Risk Index is associated with an increase in positive COVID-19 cases in 1 week (IRR: 1.16, 95% CI: (1.1-1.26)). Our risk index provides a way for policymakers and hospital decision-makers to monitor the potential risk of COVID-19 transmission from businesses based on the frequency and density of visits to businesses. This can serve as an important metric as states monitor and evaluate their reopening strategies.

PMID:33727636 | DOI:10.1038/s41746-021-00420-9

Sci Rep. 2021 Mar 16;11(1):6084. doi: 10.1038/s41598-021-85692-7.

ABSTRACT

Oestradiol, an important hormone in follicular development and endometrial receptivity, is closely related to clinical outcomes of fresh in vitro fertilization-embryo transfer (IVF-ET) cycles. A supraphysiologic E2 level is inevitable during controlled ovarian hyper-stimulation (COH), and its effect on the outcome of IVF-ET is controversial. The aim of this retrospective study is to evaluate the association between elevated serum oestradiol (E2) levels on the day of human chorionic gonadotrophin (hCG) administration and neonatal birthweight after IVF-ET cycles. The data of 3659 infertile patients with fresh IVF-ET cycles were analysed retrospectively between August 2009 and February 2017 in First Hospital of Zhengzhou University. Patients were categorized by serum E2 levels on the day of hCG administration into six groups: group 1 (serum E₂ levels ≤ 1000 pg/mL, n = 230), group 2 (serum E2 levels between 1001 and 2000 pg/mL, n = 524), group 3 (serum E₂ levels between 2001 and 3000 pg/mL, n = 783), group 4 (serum E₂ levels between 3001 and 4000 pg/mL, n = 721), group 5 (serum E2 levels between 4001 and 5000 pg/mL, n = 548 ), and group 6 (serum E2 levels > 5000 pg/mL, n = 852). Univariate linear regression was used to evaluate the independent correlation between each factor and outcome index. Multiple logistic regression was used to adjust for confounding factors. The LBW rates were as follows: 3.0% (group 1), 2.9% (group 2), 1.9% (group 3), 2.9% (group 4), 2.9% (group 5), and 2.0% (group 6) (P = 0.629), respectively. There were no statistically significant differences in the incidences of neonatal LBW among the six groups. We did not detect an association between peak serum E2 level during ovarian stimulation and neonatal birthweight after IVF-ET. The results of this retrospective cohort study showed that serum E2 peak levels during ovarian stimulation were not associated with birth weight during IVF cycles. In addition, no association was found between higher E2 levels and increased LBW risk. Our observations suggest that the hyper-oestrogenic milieu during COS does not seem to have adverse effects on the birthweight of offspring after IVF. Although this study provides some reference, the obstetric-related factors were not included due to historical reasons. The impact of the high estrogen environment during COS on the birth weight of IVF offspring still needs future research.

PMID:33727635 | DOI:10.1038/s41598-021-85692-7

Int J Obes (Lond). 2021 Mar 16. doi: 10.1038/s41366-021-00799-1. Online ahead of print.

ABSTRACT

BACKGROUND/OBJECTIVE: Exercise may reduce the risk of breast cancer through adiposity changes, but the dose-response effects of exercise volume on adiposity markers are unknown in postmenopausal women. We aimed to compare the dose-response effects of prescribed aerobic exercise volume on adiposity outcomes.

PARTICIPANTS/METHODS: Data from the Alberta Physical Activity and Breast Cancer Prevention (ALPHA) and Breast Cancer and Exercise Trial in Alberta (BETA) were pooled for this analysis (N = 720). These were 12-month randomized controlled trials, where participants were randomized to 225 min/week (mid-volume) of aerobic exercise versus usual inactive lifestyle (ALPHA), or 150 min/week (low-volume) versus 300 min/week (high-volume) (BETA). Fat mass and fat-free mass were measured using DXA and intra-abdominal and subcutaneous fat area were assessed with computed tomography.

RESULTS: After 12 months of aerobic exercise, increasing exercise volumes from no exercise/control to 300 min/week resulted in statistically significant reductions in BMI, weight, fat mass, fat percentage, intra-abdominal and subcutaneous fat area (P < 0.001). Compared with controls, fat mass loss was -1.13, -1.98 and -2.09 kg in the low-, mid- and high-volume groups, respectively. Similarly, weight loss was -1.47, -1.83, -2.21 kg in the low-, mid- and high-volume groups, respectively, compared to controls, and intra-abdominal fat area loss was -7.44, -15.56 and -8.76 cm² in the low-, mid- and high-volume groups, respectively, compared to controls. No evidence for a dose-response effect on fat-free mass was noted.

CONCLUSION: A dose-response effect of exercise volume on adiposity markers was noted, however, the differences in adiposity markers were smaller when comparing 225 min/week to 300 min/week of exercise. Given the strong positive associations between obesity and postmenopausal breast cancer risk, this study provides evidence on the importance of exercise volume as part of the exercise prescription to reduce adiposity and, ultimately, postmenopausal breast cancer risk.

PMID:33727632 | DOI:10.1038/s41366-021-00799-1