High-sensitive Troponin T assay for the diagnosis of acute myocardial infarction: An economic evaluation

__Abstract__ Background: Delayed diagnosis and treatment of Acute Myocardial Infarction (AMI) has a major adverse impact on prognosis in terms of both morbidity and mortality. Since conventional cardiac Troponin assays have a low sensitivity for diagnosing AMI in the first hours after myocardial necrosis, high-sensitive assays have been developed. The aim of this study was to assess the cost effectiveness of a high-sensitive Troponin T assay (hsTnT), alone or combined with the heart-type fatty acid-binding protein (H-FABP) assay in comparison with the conventional cardiac Troponin (cTnT) assay for the diagnosis of AMI in patients presenting to the hospital with chest pain.Methods: We performed a cost-utility analysis (quality adjusted life years-QALYs) and a cost effectiveness analysis (life years gained-LYGs) based on a decision analytic model, using a health care perspective in the Dutch context and a life time time-horizon. The robustness of model predictions was explored using one-way and probabilistic sensitivity analyses.Results: For a life time incremental cost of 30.70 Euros, use of hsTnT over conventional cTnT results in gain of 0.006 Life Years and 0.004 QALY. It should be noted here that hsTnT is a diagnostic intervention which costs only 4.39 Euros/test more than the cTnT test. The ICER generated with the use of hsTnT based diagnostic strategy comparing with the use of a cTnT-based strategy, is 4945 Euros per LYG and 7370 Euros per QALY. The hsTnT strategy has the highest probability of being cost effective at thresholds between 8000 and 20000 Euros per QALY. The combination of hsTnT and h-FABP strategy's probability of being cost effective remains lower than hsTnT at all willingness to pay thresholds.Conclusion: Our analysis suggests that hsTnT assay is a very cost effective diagnostic tool relative to conventional TnT assay. Combination of hsTnT and H-FABP does not offer any additional economic and health benefit over hsTnT test alone

Association of cytomegalovirus and other pathogens with frailty and diabetes mellitus, but not with cardiovascular disease and mortality in psycho-geriatric patients; a prospective cohort study

Background: Studies about associations of infections with herpes viruses and other pathogens, such as Chlamydia pneumoniae (CP) and Helicobacter pylori (HP) with cardiovascular disease (CVD), diabetes mellitus (DM), frailty and/or mortality are conflicting. Since high levels of antibodies against these pathogens occur in the elderly, the role of these pathogens in morbidity and mortality of vulnerable elderly was explored.Results: Blood samples of 295 community dwelling psycho-geriatric patients were tested for IgG antibodies to herpes simplex virus type 1 and 2, varicella zoster virus, Epstein Barr virus (EBV), cytomegalovirus (CMV), human herpes virus type 6 (HHV6), CP and HP. Frailty was defined with an easy-to-use previously described frailty risk score. Relative risks (RR) with 95% confidence intervals were calculated to evaluate associations between CVD, DM, frailty and pathogens. Pathogens as a predictor for subsequent mortality were tested using Kaplan Meier analyses and Cox proportional hazard models. The mean age was 78 (SD: 6.7) years, 20% died, 44% were defined as frail, 20% had DM and 49% had CVD. Presence of CMV antibody titers was associated with frailty, as shown by using both qualitative and quantitative tests, RR ratio 1.4 (95% CI: 1.003-2.16) and RR ratio 1.5 (95% CI: 1.06-2.30), respectively. High IgG antibody titers of HHV6 and EBV were associated with DM, RR ratio 3.3 (95% CI: 1.57-6.49). None of the single or combined pathogens were significantly associated with mortality and/or CVD.Conclusions: Prior CMV infection is associated with frailty, which could be in line with the concept that CMV might have an important role in immunosenescence, while high IgG titers of HHV6 and EBV are associated with DM. No association between a high pathogen burden and morbidity and/or mortality could be demonstrated

All that glisters is not gold: a comparison of electronic monitoring versus filled prescriptions – an observational study

BACKGROUND: Poor compliance with antihypertensive medication is assumed to be an important reason for unsatisfactory control of blood pressure. Poor compliance is difficult to detect. Each method of measuring compliance has its own strengths and weaknesses. The aim of the present study was to compare patient compliance with antihypertensive drugs as measured by two methods, electronic monitoring versus refill compliance. METHODS: 161 patients with a diagnosis of hypertension for at least a year prior to inclusion, and inadequate blood pressure control (systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 95 mmHg) despite the use of antihypertensive drugs, were included. Patients' pharmacy records from 12 months prior to inclusion were obtained. Refill compliance was calculated as the number of days for which the pills were prescribed divided by the total number of days in this period. After inclusion compliance was measured with an electronic monitor that records time and date of each opening of the pillbox. Agreement between both compliance measures was calculated using Spearman's correlation coefficient and Cohen's kappa coefficient. RESULTS: There was very little agreement between the two measures. Whereas refill compliance showed a large range of values, compliance as measured by electronic monitoring was high in almost all patients with estimates between 90% and 100%. Cohen's kappa coefficient was 0.005. CONCLUSION: While electronic monitoring is often considered to be the gold standard for compliance measurements, our results suggest that a short-term electronic monitoring period with the patient being aware of electronic monitoring is probably insufficient to obtain valid compliance data. We conclude that there is a strong need for more studies that explore the effect of electronic monitoring on patient's compliance

Black holes, gravitational waves and fundamental physics: a roadmap

The grand challenges of contemporary fundamental physics—dark matter, dark energy, vacuum energy, inflation and early universe cosmology, singularities and the hierarchy problem—all involve gravity as a key component. And of all gravitational phenomena, black holes stand out in their elegant simplicity, while harbouring some of the most remarkable predictions of General Relativity: event horizons, singularities and ergoregions. The hitherto invisible landscape of the gravitational Universe is being unveiled before our eyes: the historical direct detection of gravitational waves by the LIGO-Virgo collaboration marks the dawn of a new era of scientific exploration. Gravitational-wave astronomy will allow us to test models of black hole formation, growth and evolution, as well as models of gravitational-wave generation and propagation. It will provide evidence for event horizons and ergoregions, test the theory of General Relativity itself, and may reveal the existence of new fundamental fields. The synthesis of these results has the potential to radically reshape our understanding of the cosmos and of the laws of Nature. The purpose of this work is to present a concise, yet comprehensive overview of the state of the art in the relevant fields of research, summarize important open problems, and lay out a roadmap for future progress. This write-up is an initiative taken within the framework of the European Action on 'Black holes, Gravitational waves and Fundamental Physics'

Prophylactic Intravenous Hydration to Protect Renal Function From Intravascular Iodinated Contrast Material (AMACING): Long-term Results of a Prospective, Randomised, Controlled Trial

Background The aim of A MAastricht Contrast-Induced Nephropathy Guideline (AMACING) trial was to evaluate non-inferiority of no prophylaxis compared to guideline-recommended prophylaxis in preventing contrast induced nephropathy (CIN), and to explore the effect on long-term post-contrast adverse outcomes. The current paper presents the long-term results. Methods AMACING is a single-centre, randomised, parallel-group, open-label, phase 3, non-inferiority trial in patients with estimated glomerular filtration rate [eGFR] 30–59 mL/min/1.73 m2 combined with risk factors, undergoing elective procedures requiring intravenous or intra-arterial iodinated contrast material. Exclusion criteria were eGFR <30 mL/min/1.73 m2, dialysis, no referral for prophylaxis. The outcomes dialysis, mortality, and change in renal function at 1 year post-contrast were secondary outcomes of the trial. Subgroup analyses were performed based on pre-defined stratification risk factors. AMACING is registered with ClinicalTrials.gov: NCT02106234. Findings From 28,803 referrals, 1120 at-risk patients were identified. 660 consecutive patients agreed to participate and were randomly assigned (1:1) to no prophylaxis (n = 332) or standard prophylactic intravenous hydration (n = 328). Dialysis and mortality data were available for all patients. At 365 days post-contrast dialysis was recorded in two no prophylaxis (2/332, 0.60%), and two prophylaxis patients (2/328, 0.61%; p = 0.9909); mortality was recorded for 36/332 (10.84%) no prophylaxis, and 32/328 (9.76%) prophylaxis patients (p = 0.6490). The hazard ratio was 1.118 (no prophylaxis vs prophylaxis) for one-year risk of death (95% CI: 0.695 to 1.801, p = 0.6449). The differences in long-term changes in serum creatinine were small between groups, and gave no indication of a disadvantage for the no-prophylaxis group. Interpretation Assuming optimal contrast administration, not giving prophylaxis to elective patients with eGFR 30–59 mL/min/1.73 m2 is safe, even in the long-term

Optical coherence tomography for diagnosing recurrent or residual basal cell carcinoma after topical treatment:A diagnostic cohort study

Background: Recurrent/residual basal cell carcinoma (BCC) after topical treatment may not be visible during clinical and dermatoscopic examination (CDE). Optical coherence tomography (OCT) may detect these subclinical recurrences or residues. Objective: To compare the diagnostic accuracy of CDE with that of CDE combined with OCT (CDE-OCT) for detecting recurrent/residual BCC after topical treatment of superficial BCC. Methods: In this diagnostic cohort study, the suspicion level for recurrence or residue was recorded on a 5-point confidence scale. All patients with high suspicion of recurrence or residue based on CDE and/or CDE-OCT were referred for punch biopsy. Patients with a low suspicion on CDE and CDE-OCT were asked to (voluntarily) undergo a control biopsy. Histopathologic results of the biopsy were used for verification of CDE and CDE-OCT diagnoses (gold standard). Results: This study included 100 patients. A histopathologic recurrent/residual BCC was found in 20 patients. For recurrence or residue detection, sensitivity was 100% (20 of 20) for CDE-OCT and 60% (12 of 20) for CDE (P =.005) and specificity was 95% for CDE-OCT and 96.3% for CDE (P =.317). The area under the curve for CDE-OCT (0.98) was significantly higher than that for CDE (0.77) (P =.001). Limitations: Results are based on 2 OCT assessors. Conclusion: Compared with CDE alone, CDE-OCT results in a significantly higher ability to detect recurrent/residual BCCs after topical treatment

Preventieve intraveneuze hydratie ter voorkoming van contrastnefropathie helpt niet

DoelHet onderzoeken van de effectiviteit en kosteneffectiviteit van de geldende klinische richtlijnen, met name preventieve profylactische intraveneuze hydratie bij hoog-risicopatiënten, ter voorkoming van potentiële nierinsufficiëntie na intravasculair gebruik van jodiumhoudende contrastmiddelen (contrastnefropathie). Opzet Prospectief, gerandomiseerd, niet geblindeerd non-inferioriteitsonderzoek.  MethodeIn dit onderzoek werden hoog-risicopatiënten geïncludeerd die een electieve procedure met intravasculair contrastmiddel ondergingen en die werden doorverwezen voor preventieve intraveneuze hydratie. Hoog risico op contrastnefropathie was gedefinieerd als een eGFR 30-44 ml/min per 1,73 m2 of een eGFR 45-59 ml/min per 1,73m2 in combinatie met diabetes mellitus of ≥ 2 risicofactoren (leeftijd > 75 jaar, hart- en/of vaatlijden, gebruik van nefrotoxische medicatie, anemie). Patiënten die spoedinterventies moesten ondergaan, IC-patiënten, dialysepatienten en patiënten met een eGFR 25% of > 44 µmol/l, 2-6 dagen na contrasttoediening. De studie werd geregistreerd bij ClinicalTrials.gov (NCT02106234).  Resultaten In de periode 17 juni 2014-17 juli 2016 werden 28.803 electieve patiënten gescreend. 660 opeenvolgende hoog-risicopatiënten werden gerandomiseerd naar geen profylaxe (H-; n = 332) of standaard intraveneuze hydratie (H+; n = 328). De incidentie van contrastnefropathie was 2,6% in de H- groep versus 2,7% in de H+ groep (verschil: -0,10%; 95%-BI: -2,25-2,06). Het achterwege laten van profylaxe was in alle gevallen kostenbesparend. Er werd geen dialyse of aan het onderzoek gerelateerd overlijden geregistreerd binnen 35 dagen na contrasttoediening. De intraveneuze hydratie leidde bij 5,5% van de patiënten tot klinische complicaties.  Conclusie Geen profylaxe werd non-inferieur en kostenbesparend bevonden ten opzichte van standaard intraveneuze hydratie volgens geldende richtlijnen ter voorkoming van contrastnefropathie