Homeopathic pathogenetic trial of Plumbum metallicum: the complete 2000 trial with a synthesis of the original 1828 trial

Background: in a previous paper we reported the statistical analysis and other distribution data of a homeopathic pathogenetic trial (HPT) of Plumbum metallicum 30cH carried out by our group. However, at that time we did not report the resulting pure materia medica, i.e., the totality of symptoms elicited by the tested medicine on healthy volunteers. Aim: to communicate to the homeopathic community the full record of symptoms collected in our HPT of Plb. Methods: methods to collect and select symptoms have been reported in the previous paper. In synthesis were excluded all previous common symptoms of volunteers, even with slight differences, and selected only those that were really unknown, never seen, unusual or very strange for the prover. In this paper special emphasis was given to new symptoms as well as unusual or repeated dreams, while in the previous paper special emphasis was given to repeated and crossed symptoms. Results: symptoms are reported in their chronological order of appearance in each volunteer. 37 new symptoms were found, useful to update Homeopathic Repertories. It is also included a synthesis of the original HPT of Plb carried out in 1828 in order to make available the full experimental materia medica currently existing. Conclusions: the new HPT, besides widening the pathogenetic picture of Plb (skin and mucosae symptoms), also allowed us to give new and deeper meanings to some of the symptoms reported in the original trial, such as Anxiety, Activity, Depression, Slowness, Gastro-oesophageal problems, Colitis. The dreams complete the remedy image, mainly in work, religion and sexual themes. Up to the present time there is no peer-reviewed publication devoted to HPTs. For this reason, researchers are compelled to publish HPTs as private editions. This results in poor control of the quality of publications and a lack of standards on how to present the results of HPTs.

CPX-351 for Acute Myeloid Leukaemia: Real World Results Are Comparable to Trial Outcomes and Exceeds Them in Non-Adverse Risk Patients- a Multicentre Experience from West Midlands Hospitals on Behalf of West Midlands Research Consortium ( WMRC) UK

Patients with secondary AML or MDS derived AML have poor outcomes compared to de-novo AML. The benefits of intensive chemotherapy without anticipated transplant consolidation have been previously doubted. Outcomes in USA trial centres have not often been closely replicable in real world settings. From November 2018 CPX-351 has been available in the UK for secondary AML, therapy related AML, AML with MDS related Karyotype (AML-MRC) and licensed but not funded for AML with myelodysplastic related changes. Objectives Here we report our experience specifically on patient outcomes and toxicity across 5 Hospitals in West Midlands, UK Methods Patients receiving CPX 351 outcomes were evaluated retrospectively from 2018 to 2021. Baseline genetics, CPX 351 indications, patient's comorbidities, overall survival, remission status, number of cycles delivered, early mortality, reasons for early discontinuation, intensive care admission and time for neutrophil recovery (>0.5) was recorded. Time-to-event outcomes reported here are from a data cut on 01-06-21 Results In a total cohort of 57 patients baseline characteristics are shown on table 1 and compared with the original trial CPX-351 group. Median follow up was 376 days (range 21 to 1248 days). The mean age was 63, 17 patients were under 60, 31 males and 26 females. The most common indication for CPX-351 was AML with antecedent MDS/MPN 51% (N=29), therapy related 14% (N=8), MDS related karyotype (AML-MRC) 19% (N=11) and 16% (N=9) other patients. Mean Charleston co-morbidity score was 2.7 (range 0-6), 10.5% (N=6) had previous non myeloid malignancies, 8.7% (N=5) had prior ischaemic heart disease, only 3.5% (N=2) had ejection fractions under 50%. The most common mutations were TP53 21% (N=12), ASXL1 15.7% (N=9), TET2 15.7% (N=9), IDH2 10.5% (N=6), RUNX1 10.5% (N=6), SRSF2 7% (N=4), JAK2 3.5% (N=2), FLT3 5% (N=3), NPM1 5%(N=3) and IDH1 5% (N=3). MRC cytogenetic risk was adverse in 19 patients (33%), intermediate in 35 patients (61%) and favourable in 3 patients (5%). 30 patients (53%) had adverse European Leukaemia Network classification, 17 (30%) had intermediate and 10 (17%) had favourable. 30-day mortality was 3/57 (5%), 60-day mortality was 6 (10.5%) comparable to the 5.9% and 10.6% rates for the original trial. 9% or 5/57 patients were admitted to ITU with 2 survivors beyond 60 days. Neutropenic fever requiring antibiotics was 100% whereas only 5/57 (9%) had radiological evidence of fungal infection. Only one patient died from COVID 19. The mean time to neutrophil recovery was 35 days with a range of 12 to 84 days. 29 patients completed 1 cycle, 25 completed 2 cycles, only 3 completed 3 cycles. The reasons for stopping were death, refractory disease, drop in performance status, alternative chemotherapy chosen or moving to transplantation (39%). Composite remission rate including CRi was 61% 36/57, adverse ELN group demonstrated 50% 15/30, intermediate 76% 13/17 and favourable 80% 8/10. Mutated P53 was associated with a 50% 6/12 rate whereas in wild type P53 the remission rate was 60% 30/45. Overall median survival from diagnosis was 429 days [95% CI 274 to 788 days]. To compare with the original trial, we removed the under 60s and those with less than 1 year follow up, in this cohort of 30 patients the median survival was 289 days (9.5 months) with 95% CI of 255 to 476 days. P53 mutated patients had an estimated median survival of 257 days versus wild type p53 with 524 days hazard ratio of 2.418 (CI 1.077 to 5.248) with p value of 0.032. Median survival for ELN groups was 373 days (adverse), 413 days (intermediate) and not reached for favourable. Of the 36 patients who achieved a remission, 22 went on to receive an allogenic transplant with follow from 254 to 1248 days, median survival estimated 706 days (95% CI 429-not reached). Patients in remission who haven't received a transplant have a similar estimated survival of 788 days (305-not reached) pending longer follow up. Conclusion This is the first UK multicentre analysis to show comparable results to the landmark trial (median survival 9.5 months in equivalent cases). The improved overall remission rate 61% versus the 47% in the trial and the longer median survival 14 months versus 9.5 months in the trial is expected given the younger age and increase in favourable risk genetics. This study therefore supplies further data of CPX-351 efficacy in younger patients not included in the original studies and may now be used as a standard comparator arm. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Eye Outcomes in Veteran Affairs Diabetes Trial (VADT) After 17 Years

<b>Objective:</b> <p>The objective of this study was <a>to assess the long-term role of intensive glycemic control (INT) on accumulated eye procedures in patients with advanced diabetes compared with those receiving standard glycemic control (STD).</a></p> <p><b>Research design and Methodology:</b></p> <p>We compared the effect of treatment assignment on the accumulated number of eye procedures during the intervention period of Veteran Affairs Diabetes Trial (VADT) (2000-2008), median follow-up of 5.6 years), the interim VADT-Follow-up (2000-2013) and the full 17 years of VADT follow-up (2000-2017). We further analyzed data using various cardiovascular markers in 2 models; model I included total cholesterol, HDL-cholesterol (HDL-C), LDL -cholesterol (LDL-C), triglycerides, systolic and diastolic blood pressure, and BMI. Model II included the above covariates plus age and DR severity scores at baseline of the original trial. </p><p><b>Results:</b></p> <p>The final analysis of the data (detailed in Results section) showed a mild but nonsignificant increase in number of procedures, retinal or retinal plus cataract surgery during the three periods of the study (Table 3,4).</p> <p><b>Conclusions:</b></p> <p>We found no significant benefit of INT during the original trial period in eye related procedures such as various procedures for DR and cataract surgery during the 17 years follow up. Yet, after adjusting data for some known vascular markers, the increase in number of eye procedures in INT becomes more prevalent. This finding indicates that INT might not have a protective role on events that requires surgery in individual with advance DM.</p>

Eye Outcomes in Veteran Affairs Diabetes Trial (VADT) After 17 Years

<b>Objective:</b> <p>The objective of this study was <a>to assess the long-term role of intensive glycemic control (INT) on accumulated eye procedures in patients with advanced diabetes compared with those receiving standard glycemic control (STD).</a></p> <p><b>Research design and Methodology:</b></p> <p>We compared the effect of treatment assignment on the accumulated number of eye procedures during the intervention period of Veteran Affairs Diabetes Trial (VADT) (2000-2008), median follow-up of 5.6 years), the interim VADT-Follow-up (2000-2013) and the full 17 years of VADT follow-up (2000-2017). We further analyzed data using various cardiovascular markers in 2 models; model I included total cholesterol, HDL-cholesterol (HDL-C), LDL -cholesterol (LDL-C), triglycerides, systolic and diastolic blood pressure, and BMI. Model II included the above covariates plus age and DR severity scores at baseline of the original trial. </p><p><b>Results:</b></p> <p>The final analysis of the data (detailed in Results section) showed a mild but nonsignificant increase in number of procedures, retinal or retinal plus cataract surgery during the three periods of the study (Table 3,4).</p> <p><b>Conclusions:</b></p> <p>We found no significant benefit of INT during the original trial period in eye related procedures such as various procedures for DR and cataract surgery during the 17 years follow up. Yet, after adjusting data for some known vascular markers, the increase in number of eye procedures in INT becomes more prevalent. This finding indicates that INT might not have a protective role on events that requires surgery in individual with advance DM.</p>

Armageddon

Period: 1976–1986. A return to 1976 begins an account of a U.S. broadcast landmark: the demise of a TV network. Fouce’s lawsuit against SIN protracts when judges suspect violations of the foreign ownership rule making SIN an illegal firm. After ten years of proceedings, the FCC revokes SIN’s licenses and banishes Anselmo. The matter reverts to the original trial judge, Mariana Pfaelzer, who ends the lawsuit by persuading remaining SIN defendants to sell the firm. But, presiding over the sale, Pfaelzer affirms that, under the law, she cannot prevent the new owner from converting SIN from Spanish to English. On its pledge to preserve Spanish-language TV, Hallmark Cards becomes the new owner. Immediately, Hallmark is challenged. Needing to continue the network’s Televisa programming, Hallmark must pay Azcárraga’s huge fee. Then, the Reliance Insurance Company announces a rival network called “Telemundo.” Days before competition begins, Hallmark concludes a court-ordered reorganization by dissolving SIN and rechristening the network “Univision.”

Clinical outcome measures in SPMS trials: An analysis of the IMPACT and ASCEND original trial data sets

Background: Still too little is known about the natural history of clinical outcome measures beyond the Expanded Disability Status Scale (EDSS), such as the timed 25-foot walk (T25FW) and nine-hole peg test (9HPT) in secondary progressive multiple sclerosis (SPMS). Objective: To describe progression on the EDSS, T25FW, 9HPT, and their combinations. To investigate the association of the baseline characteristics age, sex, EDSS, T25FW, gadolinium-enhancing lesions, and relapse activity with EDSS and T25FW progression. Methods: Using original trial data from the placebo arms of the IMPACT and ASCEND randomized controlled trials, we describe disability progression (with and without 3- or 6-month confirmation). We investigated the association of selected baseline characteristics with EDSS and T25FW progression over 2 years using binary logistic regression. Results: T25FW was the single outcome measure with the largest proportion of patients progressing, followed by EDSS and 9HPT. EDSS and T25FW at baseline were associated with EDSS and T25FW progression in both data sets. Age and relapse activity were only mild and inconsistent predictors, while sex and gadolinium enhancement at baseline did not predict disability progression in either data set. Conclusion: Our analyses inform the selection of primary outcome measures as well as inclusion criteria for clinical trials in SPMS.

Mordet i Finderup Lade og det tabte Pergamentcodex – eller Jagten på den Forsvundne Skat

Svend Clausen: The Murder in Finderup Barn and the vanished Parchment Codex, or Raiders of the Lost Manuscript In 1286 the Danish King Erik Klipping was murdered under mysterious circumstances in a barn in Finderup, Jutland. This murder has become one of the most iconic events in Danish history and its mysteries remain unsolved. The following year some apparent perpetrators were proscribed. Most of these were powerful Danish noblemen and the Royal official Lord High Constable Stig became the most notorious of these. The sentence has been heavily debated.Already during the 1500s and early 1600s these events were described by contemporary Danish historians. Their versions of events have generally not been deemed important as it was believed that they had their knowledge solely from sources still available today.This article, however, shows that historians of this age actually did possess a now lost parchment manuscript that most likely contained the source material from the original trial following the murder. The existence of this so-called Constable Stig-manuscript has been forgotten until now, but its existence can actually be verified with certainty from manuscript lists from this age – most clearly in a manuscript list from 1595. The manuscript is also mentioned in handwritten notes by Anders Sørensen Vedel, one of the renowned historians of that age. In footnotes he made references to this manuscript, because he used its textual contents for his historical works.Apparently the Constable Stig-manuscript is also mentioned in 1608, maybe then for the last time, and at some point after this it was lost and forgotten about. Likely it burned in 1728 together with the rest of the university library. Sadly, none of its most likely important textual contents survives today. Even a debate in the 1950s regarding the source material for this murder ultimately failed to bring this lost manuscript into renewed focus.Even though its source material remains sadly lost, the existence itself of this manuscript is still important: First of all, the existence of such a manuscript shows that an actual trial must have been held in the aftermath of the murder. Even this has seemed somewhat unclear, because of the scarcity of the preserved source material. Finally, the existence of this manuscript forces us to begin looking at the works of these old historians in a different way. In the coming years it will be important to examine the preserved historical works and manuscripts of these historians thoroughly to reveal whether this can shed any new light upon any of the lost source material from the Constable Stig-manuscript.

Metallography of CB2 Steel Used for Cast Turbine Components

Steel CB2 developed in frame of the COST actions belongs to the most promising steel for production of cast turbine components working at ultra-supercritical steam conditions. VZÚ Plzeň has participated on assessment of original trial melt CB2 as well as on testing of samples coming from one of pilot valves produced of steel CB2 in full scale. Recently VZÚ Plzeň has cooperated with Doosan Škoda Power in development of weld processes of advanced power energy steels including steel CB2. This contribution deals with a comparison of properties of the steel CB2 produced by four various steelmakers from point of view of their microstructure in relation with their mechanical and creep resistant properties. Evaluation is focused on chemical heterogeneity, porosity, content of non-metallic inclusions, in particular on an occurrence of coarse NB, microstructure and substructure using methods of light and electron microscopy.