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Objectives: To define the validity of fecal blood as a marker for colorectal neoplasia in the screening setting and to compare yields by Hemoccult and HemoQuant fecal occult blood screening tests.Design: A multicenter masked comparison of fecal blood test results against structural colorectal evaluations and longitudinal follow-up, serving as criterion standards, in nonreferred subjects at risk for colorectal neoplasia.Setting: Communities, primary care centers, referral centers.Participants: Two groups: (1) 1217 patients aged at least 18 years undergoing routine structural surveillance evaluations following curative resection of a colorectal tumor and (2) 12312 relatives of colorectal cancer patients aged at least 50 years.Interventions: Blinded Hemoccult II and HemoQuant testing on three mailed-in stool samples per subject.Main Outcome Measure: Sensitivity of fecal blood tests for colorectal neoplasia.Results: In the postresection group, surveillance evaluations revealed 46 malignant colorectal neoplasms and 402 polyps. At matched specificity, sensitivity of either test for cancer was 26% (95% confidence interval, 13% to 39%). Hemoccult was positive in 21% of intraluminal recurrences, 33% of all new primary tumors, and 29% of Dukes A or B cancers; HemoQuant was elevated in 24%, 28%, and 29%, respectively. Sensitivity for polyps 1.0 cm or larger was 13% by Hemoccult and 11% by HemoQuant. In the group of relatives, estimated sensitivity for cancer at 1 to 3 years of follow-up was 25% to 33% by Hemoccult, not significantly different from the 29% to 43% by HemoQuant.Conclusions: Based on our observations in the screening setting, fecal blood appears to be a poor marker for colorectal neoplasia. Most cancers and the vast majority of polyps will be missed. Hemoccult and HemoQuant are similarly insensitive. [ABSTRACT FROM AUTHOR]

PURPOSE: The combination of a platinum compound and paclitaxel is a standard treatment for ovarian cancer. In this cooperative group trial, paclitaxel and carboplatin were combined in an outpatient schedule to determine the clinical benefit, toxicities, and effect on quality of life. PATIENTS AND METHODS: Women with International Federation of Gynecology and Obstetrics stage II to IV epithelial ovarian cancer with suboptimal residual disease (> 1 cm) were eligible. Paclitaxel, 150 mg/m2, was given over 3 hours, followed by carboplatin (area under the curve, 5). This was repeated every 4 weeks for six cycles. Quality of life was assessed using the Functional Assessment of Cancer Therapy-Ovarian Cancer scale. Fifty-nine patients were enrolled, 38 with measurable disease and 21 with evaluable disease. RESULTS: The response rate (complete response + partial response) was 72%. The progression-free interval for patients with measurable disease was 17.5 months and for patients with evaluable disease was 11.1 months. Median survivals were 30.1 months (measurable) and 25.7 months (evaluable). Toxicities were modest. Quality-of-life scores improved significantly during therapy. DISCUSSION: This regimen is ideal for most women with advanced ovarian cancer because it is convenient and well tolerated, with response and survival comparable to those of more aggressive regimens. Overall quality-of-life scores and physical well-being scores improved throughout this outpatient treatment regimen for most patients. [ABSTRACT FROM AUTHOR]

Background: The golden hour of trauma denotes the critical first hour after severe injury where timely medical response is crucial, although scientific support for this time frame is inconsistent. This study emphasizes optimizing trauma care by tailoring treatment to the specific injury rather than focusing solely on the speed of treatment. The aim is to document the need for improvement in prehospital trauma care, particularly by the use of blood and coagulation products., Methods: After a pilot study, a purpose-designed online questionnaire targeted at German physicians and rescue service personnel was utilized to collect their views on general trauma care and specifically on the use of blood and coagulation products in prehospital settings. It also assessed the appropriateness of nine specific blood and coagulation products via a 5-point Likert scale. The percentages for each item were calculated for both physicians (n = 110) and rescue service personnel (n = 142) separately as well as an overall score to delineate patterns of agreement or disagreement., Results: The study reached 9837 individuals, whereby 371 initially answered the questionnaire and 252 participants from Germany were finally included in the statistical analysis. The majority of both physicians (89.1%) and rescue service personnel (90.8%) agreed on the need to improve prehospital trauma care, particularly through the use of blood and coagulation products. Specifically, 60.9% of physicians and 83.8% of rescue personnel supported the prehospital administration of these products. Red blood cell concentrates and fibrinogen were notably endorsed, with 76.2% and 67.1% approval, respectively, for their potential to enhance survival in patients with significant blood loss; however, opinions varied on other blood products., Conclusion: The data demonstrated a readiness to change the trauma approach and confirmed that effective options are available. The utilization of certain products is supported by existing research, underlining the need for their practical implementation in preclinical settings. Here, the emphasis shifts from the isolated time components to the quality of care delivered in an optimized time interval. Ideally, timely and high-quality care should complement each other, leveraging all available therapeutic resources. This could lead to the development of a golden approach to trauma to optimize outcomes in trauma care., Competing Interests: Einhaltung ethischer Richtlinien. Interessenkonflikt: M.L. Bamberg, C. Grasshoff, J. Gerstner, M.F. Boos, M. Bentele, T. Viergutz, J. Fontana, P. Rosenberger und R. Wunderlich geben an, dass kein Interessenkonflikt besteht. Die ethische Genehmigung für die Studie wurde am 17.07.2023 unter der Projektnummer 338/2023BO2 von der Ethikkommission Tübingen erteilt. Alle Teilnehmenden, die sich bereit erklärten, durch Ausfüllen des Fragebogens an dieser Studie teilzunehmen, gaben ihre informierte Zustimmung., (© 2024. The Author(s).)

Background: Digitalization in disaster medicine holds significant potential to accelerate rescue operations and ultimately save lives. Mass casualty incidents demand rapid and accurate information management to coordinate effective responses. Currently, first responders manually record triage results on patient cards, and brief information is communicated to the command post via radio communication. Although this process is widely used in practice, it involves several time-consuming and error-prone tasks. To address these issues, we designed, implemented, and evaluated an app-based mobile triage system. This system allows users to document responder details, triage categories, injury patterns, GPS locations, and other important information, which can then be transmitted automatically to the incident commanders., Objective: This study aims to design and evaluate an app-based mobile system as a triage and coordination tool for emergency and disaster medicine, comparing its effectiveness with the conventional paper-based system., Methods: A total of 38 emergency medicine personnel participated in a within-subject experimental study, completing 2 triage sessions with 30 patient cards each: one session using the app-based mobile system and the other using the paper-based tool. The accuracy of the triages and the time taken for each session were measured. Additionally, we implemented the User Experience Questionnaire along with other items to assess participants' subjective ratings of the 2 triage tools., Results: Our 2 (triage tool) × 2 (tool order) mixed multivariate analysis of variance revealed a significant main effect for the triage tool (P<.001). Post hoc analyses indicated that participants were significantly faster (P<.001) and more accurate (P=.005) in assigning patients to the correct triage category when using the app-based mobile system compared with the paper-based tool. Additionally, analyses showed significantly better subjective ratings for the app-based mobile system compared with the paper-based tool, in terms of both school grading (P<.001) and across all 6 scales of the User Experience Questionnaire (all P<.001). Of the 38 participants, 36 (95%) preferred the app-based mobile system. There was no significant main effect for tool order (P=.24) or session order (P=.06) in our model., Conclusions: Our findings demonstrate that the app-based mobile system not only matches the performance of the conventional paper-based tool but may even surpass it in terms of efficiency and usability. This advancement could further enhance the potential of digitalization to optimize processes in disaster medicine, ultimately leading to the possibility of saving more lives., (©Martin Schmollinger, Jessica Gerstner, Eric Stricker, Alexander Muench, Benjamin Breckwoldt, Manuel Sigle, Peter Rosenberger, Robert Wunderlich. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 21.11.2024.)

Background: Disaster medicine is a component of the German medical education since 2003. Nevertheless, studies have shown some inconsistencies within the implementation of the national curriculum, and limits in the number of students trained over the years. Recently, the SARS-CoV-2 pandemic and other disasters have called attention to the importance of training medical students in disaster medicine on a coordinated basis. The aim of this study is to present and evaluate the disaster medicine and humanitarian assistance course, which was developed in the University of Tübingen, Germany., Methods: The University Clinic for Anesthesiology and Intensive Care Medicine in Tübingen expanded the existing curriculum of undergraduate disaster medicine training with fundamentals of humanitarian medicine, integrating distance learning, interactive teaching and simulation sessions in a 40 h course for third-, fourth- and fifth- year medical students. This prospective and cross-sectional study evaluates the Disaster Medicine and Humanitarian Assistance course carried out over five semesters during the period between 2018 and 2020. Three survey tools were used to assess participants' previous experiences and interest in the field of disaster medicine, to compare the subjective and objective level of knowledge before and after training, and to evaluate the course quality., Results: The total number of medical students attending the five courses was n = 102 of which n = 60 females (59%) and n = 42 males (41%). One hundred two students entered the mandatory knowledge assessment, with the rate of correct answers passing from 73.27% in the pre-test to 95.23% in the post-test (t [101] = 18.939, p < .001, d = 1.88). To determine the subjective perception of knowledge data were collected from 107 observations. Twenty-five did not complete the both questionnaires. Out of a remaining sample of 82 observations, the subjective perception of knowledge increased after the course (t [81] = 24.426, p < .001, d = 2.69), alongside with the interest in engaging in the field of disaster medicine (t [81] = 7.031, p < .001, d = .78). The 93.46% of the medical students (n = 100) graded the training received with an excellent overall score (1.01 out of 6)., Conclusion: The study indicates a significant increase in students' understanding of disaster medicine using both subjective and objective measurements, as well as an increase interest in the field of disaster medicine and humanitarian assistance. Whereas former studies showed insufficient objective knowledge regarding disaster medical practices as well as subjective insecurities about their skills and knowledge to deal with disaster scenarios, the presented course seems to overcome these deficiencies preparing future physicians with the fundamentals of analysis and response to disasters. The development and successful implementation of this course is a first step towards fulfilling disaster medicine education requirements, appearing to address the deficiencies documented in previous studies. A possible adaptation with virtual reality approaches could expand access to a larger audience. Further effort must be made to develop also international training programs, which should be a mandatory component of medical schools' curricula., (© 2021. The Author(s).)

Introduction: Crises, wars, and disasters are remarkably increasing across the world. Responders are frequently tackled with an ever-greater number of challenges, and undoubtedly, they are physically and mentally affected during and after their missions, during which posttraumatic stress disorder (PTSD) is considered high-risk. To the authors' knowledge, no studies have addressed which type of incident has the greatest influence to trigger stress, and consequently, to cause PTSD for the responders after their missions., Methods: A prospective longitudinal study was conducted with 69 participants of the "Safety and Security" course at the Federal Office for Civil Protection and Disaster Aid of the Federal Ministry of Interior Affairs (Berlin, Germany). The course is certified by the Hostile Environment Awareness Training (HEAT) guidelines of Europe's New Training Initiative for Civilian Crisis Management (ENTRi; Center for International Peace Operations; Berlin, Germany). Four incidents were evaluated: hostage-taking, carjacking, evacuation, and border-crossing. The participants completed the Positive and Negative Affect Schedule (PANAS) before and after each incident. For each incident, the delta of the PANAS scores was calculated. The differences between the described incidents, as well as the differences between novice and experienced responders, were evaluated., Results: The hostage-taking incident had the greatest influence on the participants' temper, followed by carjacking and evacuation. Ultimately, the border-crossing event had the least effect on the responders. Novices were more affected by hostage-taking than experienced responders; however, no significant difference had been demonstrated between novices and experienced responders for the other evaluated incidents., Conclusion: Different incidents have big psychological impacts on humanitarian responders, in which consequences vary from short-term effects to PTSD. Therefore, humanitarian responders should be selected very carefully. They should also have more specific preparation for their missions. Mental after-care should be obligatory. Further studies are needed to understand and avoid reasons for the development of PTSD or other potential problems of responders.

Unlabelled: HCV re-occurs after liver transplantation and increases mortality. Cyclosporine, but not tacrolimus, has potent antiviral effects against HCV replication in cell culture. To determine the conditions, if any, under which HCV is susceptible to cyclosporine in vivo, we selected for cyclosporine-resistant mutant HCV in vitro. The resulting mutations were mapped to x-ray crystallographic structures and sequence databases. Mutations selected by cyclosporine were clustered in the nonstructural (NS) proteins NS5A and NS5B. Different sets of mutations in NS5A, paired with the same 2 NS5B mutations, conferred different levels of cyclosporine resistance when engineered back into the HCV replicon. Mutations in NS5B are structurally consistent with a proposed model of regulation of RNA binding by cyclophilin B (CyPB). These mutations also highlight a natural polymorphism between different HCV genotypes that correlates with the variation in response to cyclosporine A (CsA) noted in some clinical trials. Replicons engineered to have mutations in only NS5A (P < or = 0.0001) or only NS5B (P = 0.002) suggest that while both NS5A or NS5B variants alter cyclosporine susceptibility, NS5A has the largest effect., Conclusion: Preexisting sequence variation could alter the effect of cyclosporine on HCV in vivo.

Gene expression profiling of suprachiasmatic nucleus, ventrolateral preoptic area and the lateral hypothalamus was used to identify genes regulated diurnally in the hypothalamus of Mus musculus. The putative transcription regulator, cysteine and histidine-rich domain-containing, zinc binding protein 1, which had not been previously described in brain, was found to cycle diurnally in hypothalamus and forebrain with peak levels of mRNA expression during the dark phase. mRNA for the brain-type fatty acid binding protein 7 was found to change rhythmically in hypothalamic and extra-hypothalamic brain regions reaching peak levels early in the light phase suggesting that lipid metabolism is under circadian regulation in astrocytes. Rhythmically expressed genes in suprachiasmatic nucleus identified here were compared with previous reports in a meta-analysis. Genes held in common included fabp7, and the period gene, Per2. Also identified were genes implicated in guanosine-mediated signaling pathways that included dexamethasone-induced ras-related protein one (dexras1), regulator of G-protein signaling (rgs) 16, and ras-like family member 11b. Northern blotting confirmed diurnal changes in mRNA expression in the hypothalamus for these genes. Ras-like family member 11b was examined in more detail using in situ hybridization and antiphase diurnal changes in expression in suprachiasmatic nucleus and arcuate nucleus were identified implicating the gene in circadian-related, guanosine-mediated signaling. The transcription transactivator protein, CBP/p300-interacting transactivators with glutamic acid/aspartic acid-rich carboxyl-terminal domain, which had not been previously identified in brain, was enriched in suprachiasmatic nucleus and discrete regions of the hypothalamus and forebrain. The potential regulatory role of CBP/p300-interacting transactivators with glutamic acid/aspartic acid-rich carboxyl-terminal domain in the transcription of genes like TGF-alpha implicates the protein in diurnal activity rhythms. These results demonstrate the ability of gene expression profiling to identify potential candidates important in circadian or homeostatic processes.

Between March 1992 and November 1994, 91 patients with stage III and IV ovarian carcinoma were enrolled in a randomized comparative study of cyclophosphamide 600 mg/m2 plus carboplatin 300 mg/m2 vs. cyclophosphamide 600 mg/m2 plus carboplatin 600 mg/m2, each regimen given monthly for six cycles. Patients on the intensive regimen also received 10 micrograms/kg of granulocyte macrophage colony stimulating factor (GM-CSF) (molgramostim) daily for 14 days following each chemotherapy treatment. The study was closed prematurely because of very poor case accrual following the preliminary announcement (in May 1993) that paclitaxel appeared superior to cyclophosphamide in the platinum-based treatment of ovarian cancer. More than 4 years after our last case entry, we analyzed the survival results for the 44 eligible patients who received the conventional dose of carboplatin and the 43 eligible patients receiving our intensified dose of carboplatin. More than 90% of the treated patients receiving the conventional dose regimen received at least 75% of the planned doses at each of the six treatment intervals, whereas the percentage of treated patients able to receive at least 75% of the assigned intensive dose regimen had declined from 95% in cycle 2 to 53% by cycle 6. Furthermore, although 32 patients received all six planned cycles of treatment in the conventional regimen group, only 15 received all six cycles of the intensified regimen. Patients receiving the intensive regimen had more fever, dermatitis, lethargy, musculoskeletal pain, and pulmonary complications than did the conventional dose patients. Median survival times for the two treatment groups were very similar (38.5 and 38.1 months, respectively, for the conventional and intensive regimens), and we saw no evidence that the distribution of survival times differed between the treatment regimens (p = 0.95).

Paclitaxel is an antimicrotubule agent that interferes with cell division. It has demonstrated promising single-agent activity against non-small-cell lung cancer. The purpose of this study was to evaluate the therapeutic effectiveness of paclitaxel in previously untreated patients with extensive stage small-cell lung cancer (SCLC). The study was designed as a two-stage phase II trial. All patients who entered received paclitaxel by intravenous infusion at a dose of 250 mg/m2 during 24 hours. Granulocyte colony stimulating factor was also provided to ameliorate neutropenia. Cycles were repeated at 21-day intervals. Patients who achieved a complete response received a maximum of 10 cycles of treatment, whereas those who achieved a partial response/regression continued treatment until progression or undue toxicity developed. Patients who progressed or maintained stable disease for six cycles were crossed over to cisplatin and etoposide. Forty-three patients entered the study and all were evaluable for analysis. Responses were observed in 23 (53%) of the patients. There was no significant difference in the response rates in patients with measurable or evaluable disease (13/23 versus 10/20, p = 0.76). At the time of analysis, 39 patients had progressed with a median time to progression of 95 days, and 39 patients had died with a median survival of 278 days. The 1-year achieved survival rate was 24%. Significant neutropenia (absolute neutrophil count <1,000/microl) occurred in 24 (56%) of the patients, but only 2 patients experienced severe infection (grade > or = 3), and there were no septic deaths. The results indicate that paclitaxel is active against SCLC. Myelosuppression was the main side effect in this patient population. Response duration was short (median = 3.4 months), which suggests that paclitaxel is not sufficient as a single agent. Further studies of paclitaxel in combination with other agents against SCLC are currently in progress within the North Central Cancer Treatment Group and other cancer treatment groups. Key Words: Paclitaxel-G-CSF-Small-cell lung cancer-North Central Cancer Treatment Group.

At present there is no established standard chemotherapy for advanced gastric cancer. Combination regimens have yielded response rates at times exceeding 50% but with no improvement in survival compared to single agents. This study examined the role of 5-fluorouracil and high-dose levamisole in a phase II setting using survival as the main endpoint. Patients with advanced carcinomas of the stomach or gastroesophageal junction were treated with 5-fluorouracil, 450 mg/m2 IV days 1 to 5, and levamisole, 100 mg/m2 orally three times daily on days 1 to 3, and 50 mg/m2 tid days 4 to 5 every 5 weeks. To allow more rapid accrual and to study a population that more accurately reflects the makeup of patients treated in clinical practice, patients with both measurable and nonmeasurable disease were entered in this study. Two of fifteen (13%) patients with measurable disease experienced a partial response to treatment. The adjusted 1-year survival rate for the 44 patients entered was 29.6%, which is similar to the historical 1-year survival of 30% observed in a group of nearly 400 patients treated in prior North Central Cancer Treatment Group studies. This regimen offers no improvement in therapeutic activity for advanced gastric cancer. This study design, however, allows rapid screening of phase II regimens in patients who would usually be candidates for phase III trials.

Purpose: Because small-cell lung cancer is a rapidly proliferating tumor, it was hypothesized that it may be more responsive to thoracic irradiation (TI) given twice-daily than once-daily. This hypothesis was tested in a phase III trial., Patients and Methods: Patients with limited-stage small-cell lung cancer were entered onto a phase III trial, and all patients initially received three cycles of etoposide (130 mg/m(2) x 3) and cisplatin (30 mg/m(2) x 3). Subsequently, patients who did not have progression to a distant site (other than brain) were randomized to twice-daily thoracic irradiation (TDTI) versus once-daily thoracic irradiation (ODTI) given concomitantly with two additional cycles of etoposide (100 mg/m(2) x 3) and cisplatin (30 mg/m(2) x 3). The irradiation doses were TDTI, 48 Gy in 32 fractions, with a 2.5-week break after the initial 24 Gy, and ODTI, 50.4 Gy in 28 fractions. After thoracic irradiation, the patients received a sixth cycle of etoposide/cisplatin, followed by prophylactic cranial irradiation (30 Gy/15 fractions) if they had a complete response., Results: Of 311 assessable patients enrolled in the trial, 262 underwent randomization to TDTI or ODTI. There were no differences between the two treatments with respect to local-only progression rates, overall progression rates, or overall survival. The patients who received TDTI had greater esophagitis (> or = grade 3) than those who received ODTI (12.3% v 5.3%; P =.05). Although patients received thoracic irradiation encompassing the postchemotherapy volumes, only seven of 90 local failures were out of the portal of irradiation., Conclusion: When TI is delayed until the fourth cycle of chemotherapy, TDTI does not result in improvement in local control or survival compared with ODTI.

The authors conducted a phase II study of somatostatin analogue in 18 patients with extensive stage small cell lung cancer (four with previous treatment, 14 without previous treatment). Patients received 2,000 mg subcutaneously thrice daily. They were required to have an Eastern Cooperative Oncology Group performance score of 0-2 and acceptable pretreatment biochemical parameters. No patient responded to treatment. The median time to progression was 44 days. The median survival was 106 days. Toxicity related to treatment consisted of mild diarrhea and anorexia. Somatostatin analogue is not active as a single agent in the treatment of extensive-stage small cell lung cancer.

Because of its unusual mechanism of action, docetaxel was selected for study in advanced soft tissue sarcomas of adults as part of a search for new active antisarcoma agents. Patients at least 18 years old with measurable histologically proven advanced nonosseous sarcomas were enrolled if they had ECOG performance status of < or = 2 and satisfactory leukocyte and platelet counts, and hepatic and renal function. Patients with Kaposi's sarcoma, mesothelioma, meningioma, embryonal rhabdomyosarcoma, and extraosseous Ewing's sarcoma were excluded, as were patients with brain or leptomeningeal metastases. Other specific contraindications to participation included other active cancer, previous or concurrent cancer chemotherapy or immunotherapy, and known allergy to the drug vehicle, polysorbate 80. Women of childbearing potential were required to have a negative pregnancy test. Following premedication with dexamethasone and diphenhydramine hydrochloride, docetaxel 100 mg/m2 as a concentrated solution containing 40 mg/ml in polysorbate 80 was infused over 1 h in 250 ml of either dextrose 5% in water or 0.9% saline. Treatment was repeated at 3-week intervals using standard definitions for objective responses. Up to two separate 25% toxicity directed dose reductions were permitted. Between May and December 1993, nine men and nine women registered (median age, 44 years). They received a total of 51 cycles of docetaxel (median, 2.5 cycles). Toxicity included moderate leukopenia (median first cycle nadir, 1.5 x 10(9)/L) but no significant thrombocytopenia. Alopecia, diarrhea, nausea, vomiting, and anorexia were common side effects. Fever, minor skin rashes, stomatitis, and edema were also observed. One drug-related death occurred in a neutropenic patient. One partial regression was observed (5.9%, 95% C.I. 0.15-28.7%) among the 17 eligible patients in a patient with metastatic uterine leiomyosarcoma.

The purification of oligonucleotides by ion-exchange displacement chromatography is demonstrated on the gram-scale. Using a 50 mmD x 100 mmL (203 ml) column operated in the displacement mode, 1.2 g of a 24mer phosphorothioate oligonucleotide was purified. Product yield for this separation was 70% (780 mg) at a purity of 96.4% and the mass balance recovery of all oligonucleotide was 97.5%. The displacement purification of four additional phosphorothioate oligonucleotides ranging in length from 18 to 25 bases is also demonstrated on the semi-preparative (10-50 mg) scale. All of these oligonucleotides were purified using similar displacement conditions and typical results were 60% yield at 96% purity. The displacement portion of these separations required <15 min and total cycle time including equilibration, feed loading and regeneration can be performed in under 30 min. These results seem to indicate that displacement chromatography may be amenable to generalizations in separation protocol that would greatly reduce the effort required to obtain an optimized purification scheme for moderately long oligonucleotides.