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IntroductionObservational studies are valuable for investigating correlations between patient-reported treatment outcomes. In this study, we report a secondary analysis of a published pharmacy-based observational (patient-centered “real-world” outcomes) study on experiences reported by patients who treated their headache with an over-the-counter analgesic.MethodsA pharmacy-based exploratory survey was conducted in German community pharmacies. Patients buying a fixed-dose analgesic combination product (400 mg ibuprofen + 100 mg caffeine; IbuCaff) to treat their headache were offered a questionnaire that contained—among others—questions about time to onset of pain relief (OPR), assessment of time to onset of pain relief (AOPR), assessment of efficacy and tolerability, and pain intensity 2 h after intake. A correlation analysis of the data was performed. Moreover, perceived treatment effects compared to other acute headache medications used in the past were collected.ResultsThe correlation between OPR and AOPR was high (Spearman rank correlation r = 0.594, p < 0.0001). Headache patients assessed the onset of analgesic action within 15 min as “very fast” and within 30 min as “fast”. The other readouts were correlated as well [assessment of efficacy and % pain intensity difference (%PID) at 2 h: r = 0.487; OPR/AOPR and %PID at 2 h: r = 0.295/0.318; OPR/AOPR and assessment of tolerability: r = 0.206/0.397; OPR/AOPR and assessment of efficacy: r = 0.406/0.594; assessment of efficacy and assessment of tolerability: r = 0.608; p < 0.0001 for all correlations]. Compared to previous treatments, most patients (>89%) assessed the speed of analgesic action, efficacy, and tolerability of IbuCaff as equal to or better than for the previous treatment.DiscussionHeadache patients assessed the onset of analgesia within 15 min as “very fast” and within 30 min as “fast”. Efficacy assessments for acute headache medication appear to be highly correlated.

Background High‐sensitivity cardiac troponin (hs‐cTn)‐based diagnostic algorithms are recommended for the management of patients with suspected myocardial infarction (MI) without ST elevation. Although mirroring different phases of myocardial injury, falling and rising troponin patterns (FPs and RPs, respectively) are equally considered by most algorithms. We aimed to compare the performance of diagnostic protocols for RPs and FPs, separately. Methods and Results We pooled 2 prospective cohorts of patients with suspected MI and stratified patients to stable, FP, and RP during serial sampling separately for hs‐cTnI and hs‐cTnT and applied the European Society of Cardiology 0/1‐ and 0/3‐hour algorithms comparing the positive predictive values to rule in MI. Overall, 3523 patients were included in the hs‐cTnI study population. The positive predictive value for patients with an FP was significantly reduced compared with patients with an RP (0/1‐hour: FP, 53.3% [95% CI, 45.0–61.4] versus RP, 76.9 [95% CI, 71.6–81.7]; 0/3‐hour: FP, 56.9% [95% CI, 42.2–70.7] versus RP, 78.1% [95% CI, 74.0–81.8]). The proportion of patients in the observe zone was larger in the FP using 0/1‐hour (31.3% versus 55.8%) and 0/3‐hour (14.6% versus 38.6%) algorithms. Alternative cutoffs did not improve algorithm performances. Compared with stable hs‐cTn, the risk for death or MI was highest in those with an FP (adjusted hazard ratio [HR], hs‐cTnI 2.3 [95% CI, 1.7–3.2]; RP adjusted HR, hs‐cTnI 1.8 [95% CI, 1.4–2.4]). Findings were similar for hs‐cTnT tested in 3647 patients overall. Conclusions The positive predictive value to rule in MI by the European Society of Cardiology 0/1‐ and 0/3‐hour algorithms is significantly lower in patients with FP than RP. These are at highest risk for incident death or MI. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02355457, NCT03227159.

Background As only a small proportion of patients with chest pain suffers from myocardial infarction (MI), safe rule-out of MI is of immense importance. Recently an ultrasensitive microphone performing diastolic heart sound analysis (CADScorSystem) for rule-out of coronary artery disease (CAD) has emerged. In this explorational study, we aimed to evaluate the feasibility of the CADScorSystem for diagnosis of MI in the setting of a large emergency department.Methods Patients presenting to the emergency department with suspected MI were included. Acoustic heart sound analysis was performed in all patients and automated CAD-score values were calculated via a device-embedded algorithm, which also requires inclusion of three clinical variables: age, sex and presence of hypertension. Patients additionally received serial high-sensitive troponin T measurement measurements to assess the final diagnosis according to third Universal Definition of Myocardial Infarction applying the European Society of Cardiology 0 hour/3 hours algorithm. Diagnostic parameters for MI, considering different CAD-score cut-offs, were computed.Results Of 167 patients, CAD-scores were available in 61.1%. A total of eight patients were diagnosed with MI. At a cut-off value of

The Earth’s atmosphere near both the geographic and magnetic equators and at altitudes between 120 and 200 km is called the low-latitude valley region (LLVR) and is among the least understood regions of the ionosphere/thermosphere due to its complex interplay of neutral dynamics, electrodynamics, and photochemistry. Radar studies of the region have revealed puzzling daytime echoes scattered from between 130 and 170 km in altitude. The echoes are quasi-periodic and are observed in solar-zenith-angle dependent layers. Populations with two distinct types of spectral features are observed. A number of radars have shown scattering cross-sections with different seasonal and probing-frequency dependencies. The sources and configurations of the so-called 150-km echoes and the related irregularities have been long-standing riddles for which some solutions are finally starting to emerge as will be described in this review paper. Although the 150-km echoes were discovered in the early 1960s, their practical significance and implications were not broadly recognized until the early 1990s, and no compelling explanations of their generation mechanisms and observed features emerged until about a decade ago. Now, more rapid progress is being made thanks to a multi-disciplinary team effort described here and recent developments in kinetic simulations and theory: 18 of 27 riddles to be described in this paper stand solved (and a few more partially solved) at this point in time. The source of the irregularities is no longer a puzzle as compelling evidence has emerged from simulations and theory, presented since 2016 that they are being caused by photoelectrons driving an upper hybrid plasma instability process. Another resolved riddle concerns the persistent gaps observed between the 150-km scattering layers—we now understand that they are likely to be the result of enhanced thermal Landau damping of the upper hybrid instability process at upper hybrid frequencies matching the harmonics of the electron gyrofrequency. The remaining unsolved riddles, e.g., minute-scale variability, multi-frequency dependence, to name a few, are still being explored observationally and theoretically—they are most likely unidentified consequences of interplay between plasma physics, photochemistry, and lower atmospheric dynamic processes governing the LLVR.

Background: While cardiac-specific troponin (cTn) allows for rapid diagnosis of acute type 1 myocardial infarction (T1MI), its performance to differentiate acute myocardial injury (AI) or type 2 myocardial infarction (T2MI) is limited. The objective was to combine biomarkers to improve discrimination of different myocardial infarction (MI) aetiologies. Methods: We determined levels of cardiac troponin T and I (cTnT, cTnI), cardiac myosin-binding protein C (cMyBP-C), NT-proBNP and ten miRNAs, known to be associated with cardiac pathology in a total of n = 495 serial plasma samples at three time points (on admission, after 1 h and 3 h) from 57 NSTEMI (non-ST-elevation myocardial infarction), 18 AI, and 31 STEMI patients, as defined by fourth universal definition of MI (UDMI4) and 59 control individuals. We then applied linear mixed effects model to compare the kinetics of all molecules in these MI sub-types. Results: Established (cTnT, cTnI) and novel (cMyBP-C) cardiac necrosis markers failed in differentiating T1MI vs T2MI at early time points. All cardiac necrosis markers were higher in T1MI than in T2MI at 3 h after admission. Muscle-enriched miRNAs (miR-1 and miR-133a) were correlated with cardiac necrosis protein markers and did not offer better discrimination. Established cardiac strain marker NT-proBNP differentiated AI and T1MI at all time points but failed to discriminate T2MI from T1MI. However, the combination of NT-proBNP and cTnT along with age returned an overall AUC of 0.76 [95 % CI 0.67–0.84] for differentiating T1MI, T2MI and AI. Conclusions: Rather than using single biomarkers of myocardial necrosis, a combination of clinical biomarkers for cardiac necrosis (troponin) and cardiac strain (NT-proBNP) might aid in differentiating T1MI, T2MI and AI.

Abstract Background The prevalence of obesity in childhood is increasing worldwide and may be affected by genetic factors and the lifestyle (exercise, nutrition behavior) of expectant parents. Lifestyle factors affect adipokines, namely leptin, resistin, and adiponectin as well as cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), which are involved in the regulation of maternal metabolic homeostasis, glucose metabolism, and the development of insulin resistance, metabolic syndrome, gestational diabetes mellitus, and hypertension. However, studies focusing on the effect of exercise or a combination of parental exercise and nutrition on the above-mentioned markers in newborns (venous cord blood) and especially on the long-term development of infants’ weight gain are lacking. The study will investigate the effects of a multimodal intervention (regular exercise, diet) on parental and childhood adipocytokines (leptin, resistin, adiponectin, TNF-α, IL-6, BDNF). The effect of a lifestyle-related change in “fetal environmental conditions” on the long-term weight development of the child up to the age of two will also be assessed. Methods/design A randomized multi-center controlled trial will be conducted in Germany, comparing supervised aerobic and resistance training 2x/week (13th to 36th weeks of gestation) and nutritional counseling (6th to 36th weeks of gestation) during pregnancy with usual care. Thirty women (pre-pregnancy Body Mass Index ≥25 kg/m2, 6th–10th week of gestation) will be included in each group. Maternal anthropometric and physical measurements as well as blood sampling will occur at the 6th–10th, 13th–14th, 21st-24th, and 36th week of gestation, at delivery as well as 8 weeks and 24 months postpartum. Neonatal measurements and umbilical blood sampling will be performed at birth. Maternal and infants’ weight development will be assessed every 6 months till 24 months postpartum. A difference in childhood BMI of 1 kg/m2 at the age of two years between both groups will be assumed. A power size of 80% using a significance level of 0.05 and an effect size of 1.0 is presumed. Discussion A better understanding of how lifestyle-related changes in the fetal environment might influence infants’ outcome after two years of life could have a profound impact on the prevention and development of infants’ obesity. Trial registration The trial is registered at the German Clinical Trial Register ( DRKS00007702 ); Registered on 10th of August 2016; retrospectively registered https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00007702

BackgroundAfter an acute myocardial infarction (MI), repeated measurement of cardiac biomarkers is commonly performed, although not recommended in current guidelines. There is only limited data on the kinetics of troponin in this phase. For high-sensitivity cardiac troponin T (hs-cTnT), but not high-sensitivity cardiac troponin I (hs-cTnI), late increases in terms of a second peak have been described. Their impact on the prognosis of patients with MI remains unclear.MethodsWe included 2,305 patients presenting to the emergency department with symptoms suggestive of MI. Five hundred and seven were diagnosed with MI. Hs-cTnT, creatine kinase (CK) and the MB fraction of CK (CK-MB) were measured at admission, after 1 and 3 h and thereafter as indicated by the treating physician. A mixed-model approach was applied for modeling the biomarker kinetics. All patients were followed up to assess a composite endpoint of mortality, recurrent MI, revascularization and rehospitalization and to investigate the effect of a second hs-cTnT peak on prognosis.ResultsOut of 507 patients with MI, 192 had a sufficient amount of hs-cTnT measurements after the index MI. In 111 (57.8%) patients a second hs-cTnT peak was found after 4.48 days. For CK and CK-MB a second peak could not be identified. Regarding the composite endpoint there was no significant difference between patients with and without a second hs-cTnT peak.ConclusionIn our analyses, a second peak of hs-cTnT after an acute MI was common, but not associated with poorer outcome. Thus, the clinical value of hs-cTnT for monitoring myocardial ischemia might be limited in this phase and other biomarkers might be more suitable.Trial Registration:www.ClinicalTrials.gov, identifier: NCT02355457, Date of registration: February 4, 2015.