Nonclinical evaluation of immunological safety in Göttingen Minipigs: The CONFIRM initiative.

There is a growing need to consider non-rodent species for the immunological safety evaluation of drug candidates. The EU Framework-6 RETHINK Project demonstrated that the Göttingen Minipig is a relevant animal model for regulatory toxicology studies. Extensive knowledge on the immune system of domestic pigs is available and fewer differences from humans have been identified as compared to other species, such as mice or non-human primates. Minipig data are too scarce to allow for claiming full immunological comparability with domestic pigs. Another gap limiting minipig use for immunological safety evaluation is the lack of a qualified and validated database. However, available data lend support to the use of minipigs. The need for a COllaborative Network For Immunological safety Research in Minipigs (the CONFIRM Initiative) was obvious. It is intended to trigger immunological safety research in Göttingen Minipigs, to assist and synergize fundamental, translational and regulatory investigative efforts relevant to the immunological safety evaluation of pharmaceuticals and biologics, and to spread current knowledge and new findings to the scientific and regulatory toxicology community.

Crambescin C1 Exerts a Cytoprotective Effect on HepG2 Cells through Metallothionein Induction.

The Mediterranean marine sponge Crambe crambe is the source of two families of guanidine alkaloids known as crambescins and crambescidins. Some of the biological effects of crambescidins have been previously reported while crambescins have undergone little study. Taking this into account, we performed comparative transcriptome analysis to examine the effect of crambescin-C1 (CC1) on human tumor hepatocarcinoma cells HepG2 followed by validation experiments to confirm its predicted biological activities. We report herein that, while crambescin-A1 has a minor effect on these cells, CC1 protects them against oxidative injury by means of metallothionein induction even at low concentrations. Additionally, at high doses, CC1 arrests the HepG2 cell cycle in G0/G1 and thus inhibits tumor cell proliferation. The findings presented here provide the first detailed approach regarding the different effects of crambescins on tumor cells and provide a basis for future studies on other possible cellular mechanisms related to these bioactivities.

Prospective cohort study: whether or not patients benefit from participation itself in randomized-controlled trials (SELECT BC ECO).

The randomized-controlled trial is widely accepted as a clinical trial to decide a standard therapy. It remains to be concluded whether or not patients benefit from participation itself in a randomized-controlled trial. This study was aimed at comparing prognoses between trial participants and participation-refusers. Concerned randomized trials are 'selection of effective chemotherapy for breast cancer' (SELECT BC) and its successor trial, SELECT BC-CONFIRM. Study subjects are all of metastatic breast cancer patients who are requested by their doctors to participate in these two trials. This trial is a hitherto exceptional prospective study and is suitable to clarify the effects of participation per se in such a trial on prognosis when compared with previous two studies.

Analysis of different standards for life support technology in manned submersible.

Life support technology is one of the most critical technologies in manned submersibles, acting for the pilots of the submersible and thus directly affecting its underwater safety. Due to its importance, many countries and international organizations have proposed standards and specifications for life support technology. This paper presents an overview of the life support technology of manned submersibles, comparing the standards proposed for it. Furthermore, it analyzes the specific data of oxygen supply and carbon dioxide absorption, both of which are critical aspects of life support technology in each standard, and identifies the data that is widely acknowledged and recognized as the basis for establishing ISO standard 22252:2020). Finally, ISO standard data such as oxygen and carbon dioxide concentration are further confirmed by the environmental parameters of manned submersibles such as the Fendouzhe.

Model-based learn and confirm: designing effective treatment regimens against multidrug resistant Gram-negative pathogens.

Over the last decade, there has been a growing appreciation for the use of in vitro and in vivo infection models to generate robust and informative nonclinical PK/PD data to accelerate the clinical translation of treatment regimens. The objective of this study was to develop a model-based "learn and confirm" approach to help with the design of combination regimens using in vitro infection models to optimise the clinical utility of existing antibiotics. Static concentration time-kill studies were used to evaluate the PD activity of polymyxin B (PMB) and meropenem against two carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates; BAA2146 (PMB-susceptible) and BRKP67 (PMB-resistant). A mechanism-based model (MBM) was developed to quantify the joint activity of PMB and meropenem. In silico simulations were used to predict the time-course of bacterial killing using clinically-relevant PK exposure profiles. The predictive accuracy of the model was further evaluated by validating the model predictions using a one-compartment PK/PD in vitro dynamic infection model (IVDIM). The MBM captured the reduction in bacterial burden and regrowth well in both the BAA2146 and BRKP67 isolate (R2 = 0.900 and 0.940, respectively). The bacterial killing and regrowth predicted by the MBM were consistent with observations in the IVDIM: sustained activity against BAA2146 and complete regrowth of the BRKP67 isolate. Differences observed in PD activity suggest that additional dose optimisation might be beneficial in PMB-resistant isolates. The model-based approach presented here demonstrates the utility of the MBM as a translational tool from static to dynamic in vitro systems to effectively perform model-informed drug optimisation.

Chronic non-bacterial osteomyelitis (CNO) in childhood and adolescence - a disease with many faces. / Die Chronische Nicht Bakterielle Osteomyelitis (CNO) im Kindes- und Jugendalter ­ eine Erkrankung mit vielen Gesichtern.

BACKGROUND: Chronic non-bacterial osteomyelitis (CNO) is a chronic inflammatory skeletal disease that affects particularly children and adolescents and is often diagnosed with a delay. With whole-body MRI, early diagnosis of this disease is possible in many cases. Since children and adolescents frequently present with non-specific complaints for outpatient radiological diagnosis, every radiologist should have basic knowledge of this complex clinical picture. MATERIALS: In this review the basics and current findings regarding the disease are discussed. Unusual courses are also presented. RESULTS AND CONCLUSION: With knowledge of the radiographic and MR tomographic characteristics of the mostly multifocal bone lesions, the diagnosis of CNO can be reliably made in many cases. In particular, the early use of whole-body MRI plays an important role. Thus, therapeutic delays and resulting complications and the number of unnecessary biopsies for diagnosis can be reduced.

Reducing bias in secondary data analysis via an Explore and Confirm Analysis Workflow (ECAW): a proposal and survey of observational researchers.

Background. Although preregistration can reduce researcher bias and increase transparency in primary research settings, it is less applicable to secondary data analysis. An alternative method that affords additional protection from researcher bias, which cannot be gained from conventional forms of preregistration alone, is an Explore and Confirm Analysis Workflow (ECAW). In this workflow, a data management organization initially provides access to only a subset of their dataset to researchers who request it. The researchers then prepare an analysis script based on the subset of data, upload the analysis script to a registry, and then receive access to the full dataset. ECAWs aim to achieve similar goals to preregistration, but make access to the full dataset contingent on compliance. The present survey aimed to garner information from the research community where ECAWs could be applied-employing the Avon Longitudinal Study of Parents and Children (ALSPAC) as a case example. Methods. We emailed a Web-based survey to researchers who had previously applied for access to ALSPAC's transgenerational observational dataset. Results. We received 103 responses, for a 9% response rate. The results suggest that-at least among our sample of respondents-ECAWs hold the potential to serve their intended purpose and appear relatively acceptable. For example, only 10% of respondents disagreed that ALSPAC should run a study on ECAWs (versus 55% who agreed). However, as many as 26% of respondents agreed that they would be less willing to use ALSPAC data if they were required to use an ECAW (versus 45% who disagreed). Conclusion. Our data and findings provide information for organizations and individuals interested in implementing ECAWs and related interventions. Preregistration. https://osf.io/g2fw5 Deviations from the preregistration are outlined in electronic supplementary material A.

Responder analysis for improvement in 6-min walk test with ferric carboxymaltose in patients with heart failure with reduced ejection fraction and iron deficiency.

AIM: Improving functional capacity is a key goal in heart failure (HF). This pooled analysis of FAIR-HF and CONFIRM-HF assessed the likelihood of improvement or deterioration in 6-min walk test (6MWT) among iron-deficient patients with chronic HF with reduced ejection fraction (HFrEF) receiving ferric carboxymaltose (FCM). METHODS AND RESULTS: Data for 760 patients (FCM: n = 454; placebo: n = 306) were analysed. The proportions of patients receiving FCM or placebo who had ≥20, ≥30, and ≥40 m improvements or ≥10 m deterioration in 6MWT at 12 and 24 weeks were assessed. Patients receiving FCM experienced a mean (standard deviation) 31.1 (62.3) m improvement in 6MWT versus 0.1 (77.1) m improvement for placebo at week 12 (difference in mean changes 26.8 [16.6-37.0]). At week 12, the odds [95% confidence interval] of 6MWT improvements of ≥20 m (odds ratio 2.16 [1.57-2.96]; p < 0.0001), ≥30 m (2.00 [1.44-2.78]; p < 0.0001), and ≥40 m (2.29 [1.60-3.27]; p < 0.0001) were greater with FCM versus placebo, while the odds of a deterioration ≥10 m were reduced with FCM versus placebo (0.55 [0.38-0.80]; p = 0.0019). Among patients who experienced 6MWT improvements of ≥20, ≥30, or ≥40 m with FCM at week 12, more than 80% sustained this improvement at week 24. CONCLUSION: Ferric carboxymaltose resulted in a significantly higher likelihood of improvement and a reduced likelihood of deterioration in 6MWT versus placebo among iron-deficient patients with HF. Of the patients experiencing clinically significant improvements at week 12, the majority sustained this improvement at week 24. These results are supportive of FCM to improve exercise capacity in HF.

Tsunami of immunotherapy reaches mesothelioma.

Malignant pleural mesothelioma (MPM) is the most common type of malignant mesothelioma. It is a rare tumor linked to asbestos exposure and is associated with a poor prognosis. Until very recently, patients with advanced or unresectable disease had limited treatment options, primarily based on doublet chemotherapy with cisplatin and pemetrexed. In 2020 and 2021, after more than a decade with no major advances or new drugs, two phase III clinical trials published results positioning immunotherapy as a promising option for the first- and second-line treatment of MPM. Immunotherapy has revolutionized the treatment of many cancers and is also showing encouraging results in malignant mesothelioma. Both immune checkpoint inhibition and dual cytotoxic T-lymphocyte-associated antigen 4 and programmed death-ligand 1 pathway blockade resulted in significantly improved overall survival in randomized phase III trials. In the CheckMate 743 trial, first-line therapy with nivolumab plus ipilimumab outperformed standard chemotherapy, while in the CONFIRM trial, nivolumab outperformed placebo in patients previously treated with chemotherapy. These two trials represent a major milestone in the treatment of MPM and are set to position immunotherapy as a viable alternative for treatment-naïve patients and patients with progressive disease after chemotherapy.

Impact of alternative strategies to improve the pool of blood donation by off-hour donation: A pilot study and its future prospects.

BACKGROUND: The escalating need for blood component due to increasing accidents and surgeries are always challenging for blood banks and hospitals. In this fast and busy world, collecting blood from a healthy and voluntary donor is quite challenging due to time constraints. Many blood donors who wish to donate blood were unable to go to the blood bank because of simultaneous operational timings of the blood bank and office hours of the donors. We dealt with this concern by extending the donation hours and also started collecting blood on the weekends following LAARC (Listen, Acknowledge, Assess, Respond, Confirm) methodology as a pilot project for improving blood donor convenience and satisfaction at the blood bank. METHODOLOGY: It was a prospective observational pilot study conducted at the government tertiary care institute in the Department of Transfusion Medicine from December 2018 to June 2019. All blood donations were made as per the guidelines laid down by the Drug and Cosmetic Act. The donation timings were divided as office-hour donations (8 am to 5 pm on weekdays) and off-hours donations (5 pm to 8 pm, weekends and holidays). RESULTS: In this pilot project, over 7 months out of a total of 1,591 donations, 664 donations (41.73%) were done during the off-hours. The donor experiences were pleasing, and they felt extra cared due to the convenient donation timings. CONCLUSIONS: Increasing the donation base needs more donor-friendly timings for the pleasant donation experience without hampering their work. More extensive studies should be conducted to include such strategies for increasing voluntary blood donation.

Removal of ammonia nitrogen from water by mesoporous carbon electrode-based membrane capacitance deionization.

The removal of ammonia nitrogen from wastewater is always a focus in current water treatment. In this study, a combination of mesoporous carbon electrode and selective ion exchange membrane was used to assemble a membrane capacitor deionization system (MCDI). The optimal process parameters were determined as follows: the plate spacing was 1 mm, the voltage was 1.2 V, and the flow rate was 23.8 mL/min. Under the optimal conditions, the removal efficiency of ammonia nitrogen can reach more than 80%. The quasi-first order kinetics and Langmuir adsorption isotherm model can well describe the adsorption process of MCDI. The nature of physical adsorption between ammonia nitrogen cations and mesoporous carbon electrode was demonstrated by the calculation of activation energy and thermodynamic parameters. Moreover, 1500 mg/L NH4Cl, NaNO2, and NaNO3 solutions were tested respectively. The results showed that the removal efficiencies of NH4+, NO2-, and NO3- were 82.33%, 90.96%, and 97.73% respectively, indicating that MCDI is feasible to removal different forms of inorganic nitrogen from water.

Telemedicine in paediatric otorhinolaryngology: Lessons learnt from remote encounters during the Covid19 pandemic and implications for future practice.

INTRODUCTION: Covid19 has necessitated new methods of conducting outpatient consultations. At our institute, patient-facing paediatric ENT appointments were replaced with telemedical consultations. METHOD: We performed a prospective analysis of the outcomes following telephone consultations with parents and describe our experience of remote consulting during a pandemic, and the possibilities for future applications of telemedicine in paediatric ENT. RESULTS: 215 patients were appropriately referred to the paediatric ENT clinic, 65% of these patients were deemed suitable for remote telephone consultation. Following a telephone call, 50% did not need further ENT clinic management, most commonly due to being listed for surgery (20%) or discharged (18%). The treating consultant assessed 81% of phone consultations as being effective. When given the choice, patients reported that 29% would choose a telephone consultation whilst 43% preferred a face to face consultation. CONCLUSION: Our experience has shown that there are areas of paediatric ENT that can be streamlined effectively by substituting face to face consultations with telephone consultations. However, prospective evaluation of these remote contacts suggest that telephone consultations are not a panacea and cannot be indiscriminately applied to all. Instead, the strategies to take forwards into a post Covid19 practice are vetting of referrals, individualised treatment plans, and giving patients a choice.

Implantable loop recorders for cardiac dysrhythmia monitoring.

Incorporation of technological advances in healthcare delivery has played a foundational role in development of modern healthcare. With the use of wireless transmission in conjunction with digitization of electrocardiography, continuous monitoring strategies have redefined our approach to dysrhythmia. These devices show promising results in evolving implantable loop recorder technology. In this review, we summarize the history of remote monitoring, indications for loop recorders, devices available, evidence for specific devices and anticipated studies.

Implantable cardiac monitors to detect atrial fibrillation after cryptogenic stroke: a systematic review and economic evaluation.

BACKGROUND: Cryptogenic stroke is a stroke for which no cause is identified after standard diagnostic tests. Long-term implantable cardiac monitors may be better at diagnosing atrial fibrillation and provide an opportunity to reduce the risk of stroke recurrence with anticoagulants. OBJECTIVES: The objectives were to assess the diagnostic test accuracy, clinical effectiveness and cost-effectiveness of three implantable monitors [BioMonitor 2-AF™ (Biotronik SE & Co. KG, Berlin, Germany), Confirm Rx™ (Abbott Laboratories, Lake Bluff, IL, USA) and Reveal LINQ™ (Medtronic plc, Minneapolis, MN, USA)] in patients who have had a cryptogenic stroke and for whom no atrial fibrillation is detected after 24 hours of external electrocardiographic monitoring. DATA SOURCES: MEDLINE, EMBASE, The Cochrane Library, Database of Abstracts of Reviews of Effects and Health Technology Assessment databases were searched from inception until September 2018. REVIEW METHODS: A systematic review was undertaken. Two reviewers agreed on studies for inclusion and performed quality assessment using the Cochrane Risk of Bias 2.0 tool. Results were discussed narratively because there were insufficient data for synthesis. A two-stage de novo economic model was developed: (1) a short-term patient flow model to identify cryptogenic stroke patients who have had atrial fibrillation detected and been prescribed anticoagulation treatment (rather than remaining on antiplatelet treatment) and (2) a long-term Markov model that captured the lifetime costs and benefits of patients on either anticoagulation or antiplatelet treatment. RESULTS: One randomised controlled trial, Cryptogenic Stroke and underlying Atrial Fibrillation (CRYSTAL-AF) (Sanna T, Diener HC, Passman RS, Di Lazzaro V, Bernstein RA, Morillo CA, et al. Cryptogenic stroke and underlying atrial fibrillation. N Engl J Med 2014;370:2478-86), was identified, and no diagnostic test accuracy study was identified. The CRYSTAL-AF trial compared the Reveal™ XT (a Reveal LINQ predecessor) (Medtronic plc) monitor with standard of care monitoring. Twenty-six single-arm observational studies for the Reveal devices were also identified. The only data for BioMonitor 2-AF or Confirm Rx were from mixed population studies supplied by the companies. Atrial fibrillation detection in the CRYSTAL-AF trial was higher with the Reveal XT than with standard monitoring at all time points. By 36 months, atrial fibrillation was detected in 19% of patients with an implantable cardiac monitor and in 2.3% of patients receiving conventional follow-up. The 26 observational studies demonstrated that, even in a cryptogenic stroke population, atrial fibrillation detection rates are highly variable and most cases are asymptomatic; therefore, they probably would not have been picked up without an implantable cardiac monitor. Device-related adverse events, such as pain and infection, were low in all studies. The de novo economic model produced incremental cost effectiveness ratios comparing implantable cardiac monitors with standard of care monitoring to detect atrial fibrillation in cryptogenic stroke patients based on data for the Reveal XT device, which can be related to Reveal LINQ. The BioMonitor 2-AF and Confirm RX were included in the analysis by making a strong assumption of equivalence with Reveal LINQ. The results indicate that implantable cardiac monitors could be considered cost-effective at a £20,000-30,000 threshold. When each device is compared incrementally, BioMonitor 2-AF dominates Reveal LINQ and Confirm RX. LIMITATIONS: The cost-effectiveness analysis for implantable cardiac monitors is based on a strong assumption of clinical equivalence and should be interpreted with caution. CONCLUSIONS: All three implantable cardiac monitors could be considered cost-effective at a £20,000-30,000 threshold, compared with standard of care monitoring, for cryptogenic stroke patients with no atrial fibrillation detected after 24 hours of external electrocardiographic monitoring; however, further clinical studies are required to confirm their efficacy in cryptogenic stroke patients. STUDY REGISTRATION: This study is registered as PROSPERO CRD42018109216. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 5. See the NIHR Journals Library website for further project information.

An abnormal heart rhythm (atrial fibrillation) is an important cause of stroke. Clots form in the heart, break off, pass into blood vessels in the head and block the blood supply to parts of the brain. This is important to diagnose because atrial fibrillation can be treated with blood-thinning drugs, which can prevent further stroke. For this reason, all patients with stroke are tested for atrial fibrillation. Unfortunately, the standard tests, which include 24 hours of outpatient external heart monitoring, may miss the condition. Implantable cardiac monitors, which are small devices placed beneath the skin of the chest that can monitor the heart for up to 4 years, may be better than the standard tests. This study compared three different implantable cardiac monitors [BioMonitor 2-AF™ (Biotronik SE & Co. KG, Berlin, Germany), Confirm Rx™ (Abbott Laboratories, Lake Bluff, IL, USA) and Reveal LINQ™ (Medtronic plc, Minneapolis, MN, USA)] to determine how effective they are at detecting atrial fibrillation in people who have had a cryptogenic stroke (a stroke for which no cause is identified), whether or not they are better than standard monitoring and whether or not they offer good value for money. No evidence was found that directly compared the three implantable monitors in cryptogenic stroke patients. The limited evidence found suggested that all three monitors had few side effects; only one monitor (Reveal LINQ) had evidence that it was better than standard monitoring. By 36 months, 19% of patients had atrial fibrillation detected by Reveal LINQ compared with only 2.3% with conventional monitoring. There was insufficient information for the other monitors. Overall, implantable monitors offer value for money when compared with standard monitoring for people who have had a cryptogenic stroke and for whom atrial fibrillation has not been detected with standard tests.

Structural and socio-cultural barriers to accessing mental healthcare among Syrian refugees and asylum seekers in Switzerland.

Background: Due to their experiences of major stressful life events, including post-displacement stressors, refugees and asylum seekers are vulnerable to developing mental health problems. Yet, despite the availability of specialized mental health services in Western European host countries, refugees and asylum seekers display low mental healthcare utilization. Objective: The aim of this study was to explore structural and socio-cultural barriers to accessing mental healthcare among Syrian refugees and asylum seekers in Switzerland. Method: In this qualitative study, key-informant (KI) interviews with Syrian refugees and asylum seekers, Swiss healthcare providers and other stakeholders (e.g. refugee coordinators or leaders) were conducted in the German-speaking part of Switzerland. Participants were recruited using snowball sampling. Interviews were audiotaped and transcribed, and then analysed using thematic analysis, combining deductive and inductive coding. Results: Findings show that Syrian refugees and asylum seekers face multiple structural and socio-cultural barriers, with socio-cultural barriers being perceived as more pronounced. Syrian key informants, healthcare providers, and other stakeholders identified language, gatekeeper-associated problems, lack of resources, lack of awareness, fear of stigma and a mismatch between the local health system and perceived needs of Syrian refugees and asylum seekers as key barriers to accessing care. Conclusions: The results show that for Syrian refugees and asylum seekers in Switzerland several barriers exist. This is in line with previous findings. A possible solution for the current situation might be to increase the agility of the service system in general and to improve the willingness to embrace innovative paths, rather than adapting mental healthcare services regarding single barriers and needs of a new target population.

Revista Europea de PsicotraumatologíaAntecedentes: Debido a sus experiencias de eventos vitales estresantes mayores, incluidos los estresores posteriores al desplazamiento, los refugiados y solicitantes de asilo son vulnerables a desarrollar problemas de salud mental. Sin embargo, a pesar de la disponibilidad de servicios especializados de salud mental en los países hospedadores de Europa occidental, los refugiados y los solicitantes de asilo muestran una baja utilización de cuidados salud mental.Objetivo: El objetivo de este estudio fue explorar las barreras estructurales y socioculturales para acceder a cuidados de salud mental para refugiados y solicitantes de asilo sirios, en Suiza.Método: En este estudio cualitativo, se realizaron entrevistas informante-clave (IC) con refugiados y solicitantes de asilo sirios, proveedores de cuidados de salud suizos y otros grupos de interes (por ejemplo, coordinadores o líderes de refugiados) en la parte de habla alemana de Suiza. Los participantes fueron reclutados mediante muestreo de bola de nieve. Las entrevistas fueron grabadas en audio y transcritas, y luego analizadas mediante análisis temático, combinando codificación deductiva e inductiva.Resultados: Los resultados muestran que los refugiados y solicitantes de asilo sirios, enfrentan múltiples barreras estructurales y socioculturales, siendo las socio-culturales percibidas como más pronunciadas. Los informantes-clave sirios, los proveedores de cuidados de salud y otras grupos de interes, identificaron el idioma, problemas asociados con la puerta de entrada a las instituciones, falta de recursos, falta de conciencia, miedo al estigma y discordancia entre el sistema de salud local y las necesidades percibidas de los sirios refugiados y solicitantes de asilo como barreras clave para acceder a la atención.Conclusiones: Los resultados muestran que para los refugiados y solicitantes de asilo sirios en Suiza existen varias barreras. Esto está en línea con hallazgos previos. Una posible solución para la situación actual podría ser aumentar la agilidad del sistema de servicios en general y mejorar la disposición a adoptar caminos innovadores, en lugar de adaptar los servicios de salud mental con respecto a las barreras y necesidades individuales de una nueva población objetivo.

Higher sense of coherence is associated with better mental and physical health in emergency medical services: results from investigations on the revised sense of coherence scale (SOC-R) in rescue workers.

As rescue workers are regularly confronted with potentially traumatising on-duty events, they have an increased risk to develop trauma-related mental and physical health impairments, including post-traumatic, depressive, and somatic symptoms. For this high-risk group, it could be of particular importance to experience their occupational burden as manageable, meaningful, and coherent. This mindset - called sense of coherence - may be a potential resilience factor against the development of mental and physical health problems. In a cross-sectional cohort of 102 rescue workers (Mdn(QD)age = 26.0 (8.5), age range: 18-61), including 36 women, we investigated whether higher values on the Revised Sense of Coherence Scale (SOC-R) predicted lower post-traumatic, depressive, and somatic symptoms. In addition, we evaluated the factor structure of the SOC-R using confirmatory factor analyses. Linear regressions indicated that higher SOC-R, but particularly manageability scores were associated with less post-traumatic (ß = -.31, p = .009), depressive (ß = -.44, p < .001), and somatic symptoms (ß = -.36, p = .002). Furthermore, we found that all symptom scores significantly increased with occupational and private-life trauma exposure. The SOC-R's factor structure was replicated, comprising the three subscales manageability, reflection, and balance. However, the SOC-R's convergent factor validity was rather low in the present sample. Taken together, a high sense of coherence, and in particular a high manageability conviction, was observed as resilience factors for high-risk groups that are frequently exposed to potentially traumatic events. Future studies might investigate whether strengthening the sense of coherence could be one building block in an effective prevention program for maintaining long-term health in risk groups.

Debido a que los trabajadores de rescate se enfrentan regularmente con eventos laborales potencialmente traumatizantes, presentan un mayor riesgo de desarrollar trastornos mentales y físicos relacionados con el trauma, incluyendo síntomas postraumáticos, depresivos y somáticos. Para este grupo de alto riesgo sería importante el experimentar su trabajo como manejable, significativo y coherente. Esta perspectiva ­llamada sentido de coherencia­ podría ser un factor potencial de resiliencia en contra del desarrollo de problemas mentales y físicos. En una cohorte transversal con 102 trabajadores de rescate (Mdn(QD)edad = 26.0 (8.5), rango de edad: 18-61), de los cuáles 36 eran mujeres, investigamos si los valores más altos en la Escala del Sentido de Coherencia Revisada (SOC-R) predijeron menos síntomas postraumáticos, depresivos y somáticos. Además, evaluamos la estructura factorial del SOC-R mediante análisis factoriales confirmatorios. Las regresiones lineales indicaron que las puntuaciones más altas del SOC-R, pero particularmente la capacidad de menejabilidad, se asociaron con menos síntomas postraumáticos (ß = −.31, p = .009), depresivos (ß = −.44, p <.001) y somáticos (ß = −.36, p = .002). Además, encontramos que a mayor la exposición con traumas laborales y privados los puntajes de estos síntomas aumentaron significativamente. La estructura factorial del SOC-R se replicó con sus tres subescalas manejabilidad, reflexión y equilibrio. Sin embargo, la validez del factor convergente del SOC-R era menor en la presente muestra. En general, se observó que un alto sentido de coherencia y, en particular una alta manejabilidad, funcionan como factores de resiliencia en grupos de alto riesgo que con frecuencia están expuestos a eventos potencialmente traumáticos. Estudios futuros deberían investigar si el fortalecimiento del sentido de coherencia podría ser un componente básico en un programa de prevención eficaz para mantener la salud a largo plazo en grupos de riesgo.

Statistical Interactions in a Clinical Trial.

New statisticians entering industry tend to "test statistical interactions" whenever there is a need. However, in many real-world applications, especially in clinical development of new drugs, most interactions need to be estimated, instead of tested. In this manuscript, the distinction between hypothesis testing and estimation will be articulated, and the use of statistical interactions in clinical development programs will be discussed. According to ICH E-9, the treatment by subgroup interaction should not be included in the prespecified primary statistical analysis model. The reasons behind this ICH E-9 recommendation are also clarified in this manuscript.