We explore energy densities of the magnetic fields and relativistic electrons in the M87 jet. Since the radio core at the jet base is identical to the optically thick surface against synchrotron ...self-absorption (SSA), the observing frequency is identical to the SSA turnover frequency. As a first step, we assume the radio core has a simple uniform sphere geometry. Using the observed angular size of the radio core measured by the Very Long Baseline Array at 43 GHz, we estimate the energy densities of magnetic fields (U sub(B)) and relativistic electrons (U sub(e)) on the basis of the standard SSA formula. Imposing the condition that the Poynting power and kinetic power of relativistic electrons should be smaller than the total power of the jet, we find that (1) the allowed range of the magnetic field strength (B sub(tot)) is 1 G < or =, slant B sub(tot) < or =, slant 15G and that (2) 1 x 10 super(-5) < or =, slant U sub(e)/U sub(B) < or =, slant 6 x 10 super(2) holds. The uncertainty of U sub(e)/U sub(B) comes from the strong dependence on the angular size of the radio core and the minimum Lorentz factor of non-thermal electrons (gamma sub(e, min)) in the core. It is still unsettled whether resultant energetics are consistent with either the magnetohydrodynamic jet or the kinetic power dominated jet even on the ~10 Schwarzschild radii scale.
Empirical evidence suggests that lack of blinding may be associated with biased estimates of treatment benefit in randomized controlled trials, but the influence on medication-related harms is not ...well-recognized. We aimed to investigate the association between blinding and clinical trial estimates of medication-related harms.
We searched PubMed from January 1, 2015, till January 1, 2020, for systematic reviews with meta-analyses of medication-related harms. Eligible meta-analyses must have contained trials both with and without blinding. Potential covariates that may confound effect estimates were addressed by restricting trials within the comparison or by hierarchical analysis of harmonized groups of meta-analyses (therefore harmonizing drug type, control, dosage, and registration status) across eligible meta-analyses. The weighted hierarchical linear regression was then used to estimate the differences in harm estimates (odds ratio, OR) between trials that lacked blinding and those that were blinded. The results were reported as the ratio of OR (ROR) with its 95% confidence interval (CI).
We identified 629 meta-analyses of harms with 10,069 trials. We estimated a weighted average ROR of 0.68 (95% CI: 0.53 to 0.88, P < 0.01) among 82 trials in 20 meta-analyses where blinding of participants was lacking. With regard to lack of blinding of healthcare providers or outcomes assessors, the RORs were 0.68 (95% CI: 0.53 to 0.87, P < 0.01 from 81 trials in 22 meta-analyses) and 1.00 (95% CI: 0.94 to 1.07, P = 0.94 from 858 trials among 155 meta-analyses) respectively. Sensitivity analyses indicate that these findings are applicable to both objective and subjective outcomes.
Lack of blinding of participants and health care providers in randomized controlled trials may underestimate medication-related harms. Adequate blinding in randomized trials, when feasible, may help safeguard against potential bias in estimating the effects of harms.
We introduce a quality-effects approach that combines evidence from a series of trials comparing 2 interventions. This approach incorporates the heterogeneity of effects in the analysis of the ...overall interventional efficacy. However, unlike the random-effects model based on observed between-trial heterogeneity, we suggest adjustment based on measured methodological heterogeneity between studies. We propose a simple noniterative procedure for computing the combined effect size under this model and suggest that this could represent a more convincing alternative to the random effects model.
Annually more than 100,000 Japanese encephalitis (JE) cases and 25,000 deaths worldwide are caused by JE virus infection. More than 15 JE vaccines are currently in use worldwide. It is unknown ...whether any of the vaccines is superior to the others in terms of immunogenicity and safety.
Four databases were systematically searched for randomised controlled trials that compared two or more types of JE vaccines. Vaccines were classified into four classes: inactivated mouse brain-derived (oldest class), inactivated Vero cell, live chimeric, and live attenuated. Network meta-analysis was used to generate mixed effect estimates against inactivated mouse brain-derived vaccines for seroconversion, and against placebo for adverse event (AE) and severe adverse event (SAE).
23 studies (38,496 participants) were included. All newer vaccine classes had better immunogenicity, the difference was statistically significant for inactivated Vero cell (OR = 2.98; 95 %CI: 1.02–8.65) and live chimeric (OR = 5.93; 95 %CI: 1.73–20.32) vaccines. Inactivated mouse-derived vaccines had the highest odds for AEs (OR = 2.27; 95 %CI: 1.59–3.23), the odds of AE of newer vaccines was not different to placebo. There was no difference in SAEs across vaccine classes.
All newer JE vaccines have comparable safety profiles, live chimeric and inactivated Vero cell vaccines are the most immunogenic among the newer vaccine classes.
Monitoring of left ventricular ejection fraction (LVEF) is the current standard for detection of trastuzumab-induced cardiotoxicity; however, time-to-diagnosis and cost of assessment are suboptimal ...in women with early-stage breast cancer. We assessed the utility of B-type natriuretic peptide (BNP), high-sensitivity C-reactive protein (hs-CRP), and cardiac troponin I (cTnI) as serum biomarkers for early detection of trastuzumab-induced cardiotoxicity. Fifty-four women with human epidermal growth factor receptor 2 (HER2)-positive early-stage breast cancer were prospectively enrolled, and the relationship between elevated serum BNP, hs-CRP, and cTnI levels and clinically significant decreases in LVEF was examined. LVEF was monitored at 3–4 month intervals during trastuzumab treatment. Laboratory testing for candidate biomarkers was repeated every 3 weeks with each cycle of trastuzumab. Trastuzumab-induced cardiotoxicity was defined as a decrease in LVEF of ≥15 % or to a value below 50 %. A clinically significant decrease in LVEF was observed in 28.6 % of women. Abnormal hs-CRP (≥3 mg/L) predicted decreased LVEF with a sensitivity of 92.9 % (95 % CI 66.1–99.8) and specificity of 45.7 % (95 % CI 28.8–63.4), and subjects with normal hs-CRP levels (<3 mg/L) have 94.1 % negative predictive 94.1 % (95 % CI 70.3–99.9) suggesting that normal hs-CRP levels may be associated with low future risk for decreased LVEF; however, no association with BNP or cTnI was observed. A false positive would have a relatively low associated cost in breast cancer patients undergoing adjuvant trastuzumab therapy and would indicate continuation of routine observation during treatment through traditional means. The maximum hs-CRP value was observed a median of 78 days prior to detection of cardiotoxicity by decreased LVEF, and those with normal levels were at lower risk for cardiotoxicity. Regular monitoring of hs-CRP holds promise as a biomarker for identifying women with early-stage breast cancer at low risk for asymptomatic trastuzumab-induced cardiotoxicity. To our knowledge, this is the first study documenting the utility of a less expensive, reproducible, easily obtainable biomarker with rapid results for evaluating cardiotoxicity related to trastuzumab therapy.
COVID-19 pandemic has created an extreme pressure on the global healthcare services. Fast, reliable, and early clinical assessment of the severity of the disease can help in allocating and ...prioritizing resources to reduce mortality. In order to study the important blood biomarkers for predicting disease mortality, a retrospective study was conducted on a dataset made public by Yan et al. in
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of 375 COVID-19 positive patients admitted to Tongji Hospital (China) from January 10 to February 18, 2020. Demographic and clinical characteristics and patient outcomes were investigated using machine learning tools to identify key biomarkers to predict the mortality of individual patient. A nomogram was developed for predicting the mortality risk among COVID-19 patients. Lactate dehydrogenase, neutrophils (%), lymphocyte (%), high-sensitivity C-reactive protein, and age (LNLCA)—acquired at hospital admission—were identified as key predictors of death by multi-tree XGBoost model. The area under curve (AUC) of the nomogram for the derivation and validation cohort were 0.961 and 0.991, respectively. An integrated score (LNLCA) was calculated with the corresponding death probability. COVID-19 patients were divided into three subgroups: low-, moderate-, and high-risk groups using LNLCA cutoff values of 10.4 and 12.65 with the death probability less than 5%, 5–50%, and above 50%, respectively. The prognostic model, nomogram, and LNLCA score can help in early detection of high mortality risk of COVID-19 patients, which will help doctors to improve the management of patient stratification.
All neuronal networks are modulated by multiple neuropeptides and biogenic amines. Yet, few studies investigate how different modulators interact to regulate network activity. Here we explored the ...state-dependent functional interactions between three excitatory neuromodulators acting on neurokinin1 (NK1), alpha1 noradrenergic (alpha1 NE), and 5-HT2 serotonin receptors within the pre-Bötzinger complex (pre-BötC), an area critical for the generation of breathing. In anesthetized, in vivo mice, the reliance on endogenous NK1 activation depended on spontaneous breathing frequency and the modulatory state of the animal. Endogenous NK1 activation had no significant respiratory effect when stimulating raphe magnus and/or locus ceruleus, but became critical when alpha1 NE and 5-HT2 receptors were pharmacologically blocked. The dependence of the centrally generated respiratory rhythm on NK1 activation was blunted in the presence of alpha1 NE and 5-HT2 agonists as demonstrated in slices containing the pre-BötC. We conclude that a modulator's action is determined by the concurrent modulation and interaction with other neuromodulators. Deficiencies in one neuromodulator are immediately compensated by the action of other neuromodulators. This interplay could play a role in the state dependency of certain breathing disorders.
Background. The global increase in type 2 diabetes (T2D) poses a significant public health challenge worldwide. Due to the chronic and complex nature of the disease, management does not depend on ...pharmacotherapy alone; rather, a comprehensive medical and self-management plan is required. Diabetes Self-Management Education programs should address diabetes-specific behaviors and be grounded in patients’ perceptions of their disease and its consequences. Aim. The study aims to understand perceptions of diabetes self-management (DSM) among persons of different nationalities with T2D living in Qatar. Method. A phenomenological qualitative study was implemented using four focus group interviews using Triandis Interpersonal Behavior Model to understand factors influencing DSM perceptions and behaviors. Therefore, deductive content analysis was used, also inductive content analysis used to find new emerging themes. Twenty-nine participants with T2D of 12 different nationalities were recruited. Results. Content analyses revealed that participants were mainly motivated to manage their diabetes by fear of future health complications—and the resulting impact on their families—triggered by witnessing these complications on other family members and friends. Factors that influenced DSM included cultural factors such as food content and holidays’ customs, weather conditions, psychological distress, and social factors such as lack of family support. Furthermore, access to healthy food, number of working hours and time, and cost of DSM supplies were found to be among the barriers to DSM. Conclusion. Understanding and considering patients’ perspectives is a core component of culturally competent and evidence-based DSM programs, and it should be considered in any DSM program.
Schistosomiasis is a widespread public health concern in the poorest regions of the world. The principal control strategy is regular praziquantel administration to school-aged children in endemic ...areas. With calls for the elimination of schistosomiasis as a public health problem, expanding praziquantel delivery to all community members has been advocated. This systematic review and meta-analysis compares the impact of community-wide and child-targeted praziquantel distribution on schistosomiasis prevalence and intensity in school-aged children.
We searched MEDLINE, Embase and Web of Science to identify papers that reported schistosome prevalence before and after praziquantel administration, either to children only or to all community members. Extracted data included Schistosoma species, drug administration strategy, number of treatment rounds, follow-up interval and prevalence and intensity before and after treatment. We used inverse variance weighted generalised linear models to examine the impact of mass versus targeted drug administration on prevalence reduction, and weighted boxplots to examine the impact on infection intensity reduction. This study is registered with PROSPERO, number CRD42018095377. In total, 34 articles were eligible for systematic review and 28 for meta-analysis. Schistosoma mansoni was reported in 20 studies; Schistosoma haematobium in 19 studies, and Schistosoma japonicum in two studies. Results of generalised linear models showed no detectable difference between mass and targeted treatment strategies on prevalence reduction in school-aged children for S. mansoni (odds ratio 0.47, 95%CI 0.13-1.68, p = 0.227) and S. haematobium (0.41, 95%CI 0.06-3.03, p = 0.358). Box plots also showed no apparent differences in intensity reduction between the two treatment strategies.
The results of this meta-analysis do not support the hypothesis that community-wide treatment is more effective than targeted treatment at reducing schistosomiasis infections in children. This may be due to the relatively small number of included studies, insufficient treatment coverage, persistent infection hotspots and unmeasured confounders. Further field-based studies comparing mass and targeted treatment are required.
Clostridium difficile infection (CDI) has been extensively described in healthcare settings; however, risk factors associated with community-acquired (CA) CDI remain uncertain. This study aimed to ...synthesize the current evidence for an association between commonly prescribed medications and comorbidities with CA-CDI.
A systematic search was conducted in 5 electronic databases for epidemiologic studies that examined the association between the presence of comorbidities and exposure to medications with the risk of CA-CDI. Pooled odds ratios were estimated using 3 meta-analytic methods. Subgroup analyses by location of studies and by life stages were conducted.
Twelve publications (n=56,776 patients) met inclusion criteria. Antimicrobial (odds ratio, 6.18; 95% CI, 3.80-10.04) and corticosteroid (1.81; 1.15-2.84) exposure were associated with increased risk of CA-CDI. Among the comorbidities, inflammatory bowel disease (odds ratio, 3.72; 95% CI, 1.52-9.12), renal failure (2.64; 1.23-5.68), hematologic cancer (1.75; 1.02-5.68), and diabetes mellitus (1.15; 1.05-1.27) were associated with CA-CDI. By location, antimicrobial exposure was associated with a higher risk of CA-CDI in the United States, whereas proton-pump inhibitor exposure was associated with a higher risk in Europe. By life stages, the risk of CA-CDI associated with antimicrobial exposure greatly increased in adults older than 65 years.
Antimicrobial exposure was the strongest risk factor associated with CA-CDI. Further studies are required to investigate the risk of CA-CDI associated with medications commonly prescribed in the community. Patients with diarrhea who have inflammatory bowel disease, renal failure, hematologic cancer, or diabetes are appropriate populations for interventional studies of screening.
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